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  • American Institute of Physics (AIP)  (154,286)
  • Public Library of Science (PLoS)  (10,492)
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  • 1
    Publication Date: 2018-05-19
    Description: by Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian Background The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the characteristics of these combinations in vivo . Methodology/Principal findings Working with the hookworm Ancylostoma ceylanicum -hamster infection system, we establish a laboratory paradigm for studying anti-nematode combinations in vivo using Cry5B and the nicotinic acetylcholine receptor (nAChR) agonists tribendimidine and pyrantel pamoate. We demonstrate that Cry5B strongly synergizes in vivo with both tribendimidine and pyrantel at specific dose ratios against hookworm infections. For example, whereas 1 mg/kg Cry5B and 1 mg/kg tribendimidine individually resulted in only a 0%-6% reduction in hookworm burdens, the combination of the two resulted in a 41% reduction (P = 0.020). Furthermore, when mixed at synergistic ratios, these combinations eradicate hookworm infections at doses where the individual doses do not. Using cyathostomin nematode parasites of horses, we find based on inhibitory concentration 50% values that a strongylid parasite population doubly resistant to nAChR agonists and benzimidazoles is more susceptible or “hypersusceptible” to Cry5B than a cyathostomin population not resistant to nAChR agonists, consistent with previous Caenhorhabditis elegans results. Conclusions/Significance Our study provides a powerful means by which anthelmintic combination therapies can be examined in vivo in the laboratory. In addition, we demonstrate that Cry5B and nAChR agonists have excellent combinatorial properties—Cry5B combined with nAChR agonists gives rise to potent cures that are predicted to be recalcitrant to the development of parasite resistance. These drug combinations highlight bright spots in new anthelmintic development for human and veterinary animal intestinal nematode infections.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 2
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-19
    Description: by Jinming Du Global cooperation is urgently needed to prevent risks of world-wide extreme events and disasters for sustainable development. In human societies, however, there exists bias toward interacting with partners with similar characteristics, but not contributing globally. We study how complex interactive behaviors evolve under risks through proposing a threshold public goods game model. In the model, individuals either play games with participants who own the same phenotype, or contribute to the collective target of global public goods. We further introduce an insurance compensation mechanism into the model to probe the evolution of global cooperation. It is found that the introduction of the insurance remarkably promotes the emergence of global cooperative behavior and inhibits the tendency to play games only with individuals of the same phenotype. Besides, contrary to models without insurance, global cooperation is strengthened with the increase of imitation intensities. In addition, high risk and high threshold are in favor of global cooperation.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 3
    Publication Date: 2018-05-19
    Description: by Jennifer Yourkavitch, Kristen Hassmiller Lich, Valerie L. Flax, Elialilia S. Okello, John Kadzandira, Anne Ruhweza Katahoire, Alister C. Munthali, James C. Thomas Retention in care remains an important issue for prevention of mother-to-child transmission (PMTCT) programs according to WHO guidelines, formerly called the “Option B+” approach. The objective of this study was to examine how poverty, gender, and health system factors interact to influence women’s participation in PMTCT services. We used qualitative research, literature, and hypothesized variable connections to diagram causes and effects in causal loop models. We found that many factors, including antiretroviral therapy (ART) use, service design and quality, stigma, disclosure, spouse/partner influence, decision-making autonomy, and knowledge about PMTCT, influence psychosocial health, which in turn affects women’s participation in PMTCT services. Thus, interventions to improve psychosocial health need to address many factors to be successful. We also found that the design of PMTCT services, a modifiable factor, is important because it affects several other factors. We identified 66 feedback loops that may contribute to policy resistance—that is, a policy’s failure to have its intended effect. Our findings point to the need for a multipronged intervention to encourage women’s continued participation in PMTCT services and for longitudinal research to quantify and test our causal loop model.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 4
    Publication Date: 2018-05-19
    Description: by Maria Ivanova, Bea De Cupere, Jonathan Ethier, Elena Marinova The Old World farming system arose in the semi-arid Mediterranean environments of southwest Asia. Pioneer farmers settling the interior of the Balkans by the early sixth millennium BC were among the first to introduce southwest Asian-style cultivation and herding into areas with increasingly continental temperate conditions. Previous research has shown that the bioarchaeological assemblages from early farming sites in southeast Europe vary in their proportions of plant and animal taxa, but the relationship between taxonomic variation and climate has remained poorly understood. To uncover associations between multiple species and environmental factors simultaneously, we explored a dataset including altitude, five bioclimatic and 30 bioarchaeological variables (plant and animal taxa) for 57 of the earliest farming sites in southeast Europe using Canonical Correspondence Analysis (CCA). An extension of correspondence analysis, CCA is widely used in applied ecology to answer similar questions of species-environment relationships, but has not been previously applied in prehistoric archaeology to explore taxonomic and climatic variables in conjunction. The analyses reveal that the changes in plant and animal exploitation which occurred with the northward dispersal of farmers, crops and livestock correlate with south-north climate gradients, and emphasize the importance of adaptations in the animal domain for the initial establishment of farming beyond the Mediterranean areas.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 5
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-19
    Description: by Bedilu Alamirie Ejigu, Eshetu Wencheko, Kiros Berhane Anaemia is a condition in which the haemoglobin concentration falls below an established cut-off value due to a decrease in the number and size of red blood cells. The current study aimed (i) to assess the spatial pattern and (ii) to identify determinants related to anaemia using the third Ethiopian demographic health survey. To achieve these objectives, this study took into account the sampling weight and the clustered nature of the data. As a result, multilevel modeling has been used in the statistical analysis. The analysis included complete cases from 15,909 females, and 13,903 males. Among all subjects who agreed for hemeoglobin test, 5.22% males, and 16.60% females were anemic. In both binary and ordinal outcome modeling approaches, educational level, age, wealth index, BMI and HIV status were found to be significant predictors of anaemia prevalence. Furthermore, this study applied spatial methods to generate maps at regional level which could be useful for policy makers where great efforts should be concentrated to reduce the prevalence of anaemia. As revealed by Moran’s I test, significant spatial autocorrelation were noted across clusters. The risk of anaemia was found to vary across different regions, and higher prevalences were observed in Somali and Affar regions.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 6
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-19
    Description: by Waqas Haque, Abu Minhajuddin, Arjun Gupta, Deepak Agrawal Background Almost all medical journals now require authors to publicly disclose conflicts of interests (COI). The same standard and scrutiny is rarely employed for the editors of the journals although COI may affect editorial decisions. Methods We conducted a retrospective observational study to determine the prevalence and magnitude of financial relationships among editors of 60 influential US medical journals (10 each for internal medicine and five subspecialties: cardiology, gastroenterology, neurology, dermatology and allergy & immunology). Open Payments database was reviewed to determine the percentage of physician editors receiving payments and the nature and amount of these payments. Findings 703 unique physician editors were included in our analysis. 320/703 (46%) received 8659 general payments totaling $8,120,562. The median number of payments per editor was 9 (IQR 3–26) and the median amount per payment was $91 (IQR $21–441). The median total payment received by each editor in one year was $4,364 (IQR $319–23,143). 152 (48%) editors received payments more than $5,000 in a year, a threshold considered significant by the National Institutes of Health. COI policies for editors were available for 34/60 (57%) journals but only 7/34 (21%) publicly reported the disclosures and only 2 (3.%) reported the dollar amount received. Interpretation A significant number of editors of internal medicine and subspecialty medical journals have financial COI and very few are publicly disclosed. Specialty journal editors have more COI compared to general medicine journal editors. Current policies for disclosing COI for editors are inconsistent and do not comply with the recommended standards.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 7
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-19
    Description: by David D. J. Taylor, Alexander H. Slocum, Andrew J. Whittle Intermittent water supplies (IWS) deliver piped water to one billion people; this water is often microbially contaminated. Contaminants that accumulate while IWS are depressurized are flushed into customers’ homes when these systems become pressurized. In addition, during the steady-state phase of IWS, contaminants from higher-pressure sources (e.g., sewers) may continue to intrude where pipe pressure is low. To guide the operation and improvement of IWS, this paper proposes an analytic model relating supply pressure, supply duration, leakage, and the volume of intruded, potentially-contaminated, fluids present during flushing and steady-state. The proposed model suggests that increasing the supply duration may improve water quality during the flushing phase, but decrease the subsequent steady-state water quality. As such, regulators and academics should take more care in reporting if water quality samples are taken during flushing or steady-state operational conditions. Pipe leakage increases with increased supply pressure and/or duration. We propose using an equivalent orifice area (EOA) to quantify pipe quality. This provides a more stable metric for regulators and utilities tracking pipe repairs. Finally, we show that the volume of intruded fluid decreases in proportion to reductions in EOA. The proposed relationships are applied to self-reported performance indicators for IWS serving 108 million people described in the IBNET database and in the Benchmarking and Data Book of Water Utilities in India. This application shows that current high-pressure, continuous water supply targets will require extensive EOA reductions. For example, in order to achieve national targets, utilities in India will need to reduce their EOA by a median of at least 90%.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 8
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-19
    Description: by Dora Posfai, Kayla Sylvester, Anupama Reddy, Jack G. Ganley, Johannes Wirth, Quinlan E. Cullen, Tushar Dave, Nobutaka Kato, Sandeep S. Dave, Emily R. Derbyshire Within the liver a single Plasmodium parasite transforms into thousands of blood-infective forms to cause malaria. Here, we use RNA-sequencing to identify host genes that are upregulated upon Plasmodium berghei infection of hepatocytes with the hypothesis that host pathways are hijacked to benefit parasite development. We found that expression of aquaporin-3 (AQP3), a water and glycerol channel, is significantly induced in Plasmodium- infected hepatocytes compared to uninfected cells. This aquaglyceroporin localizes to the parasitophorous vacuole membrane, the compartmental interface between the host and pathogen, with a temporal pattern that correlates with the parasite’s expansion in the liver. Depletion or elimination of host AQP3 expression significantly reduces P . berghei parasite burden during the liver stage and chemical disruption by a known AQP3 inhibitor, auphen, reduces P . falciparum asexual blood stage and P . berghei liver stage parasite load. Further use of this inhibitor as a chemical probe suggests that AQP3-mediated nutrient transport is an important function for parasite development. This study reveals a previously unknown potential route for host-dependent nutrient acquisition by Plasmodium which was discovered by mapping the transcriptional changes that occur in hepatocytes throughout P . berghei infection. The dataset reported may be leveraged to identify additional host factors that are essential for Plasmodium liver stage infection and highlights Plasmodium’s dependence on host factors within hepatocytes.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 9
    Publication Date: 2018-05-19
    Description: by Benjamin Hommel, Liliane Mukaremera, Radames J. B. Cordero, Carolina Coelho, Christopher A. Desjardins, Aude Sturny-Leclère, Guilhem Janbon, John R. Perfect, James A. Fraser, Arturo Casadevall, Christina A. Cuomo, Françoise Dromer, Kirsten Nielsen, Alexandre Alanio The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection, producing both typical size 5 to 7 μm cells and large titan cells (〉 10 μm and up to 100 μm). We found and optimized in vitro conditions that produce titan cells in order to identify the ancestry of titan cells, the environmental determinants, and the key gene regulators of titan cell formation. Titan cells generated in vitro harbor the main characteristics of titan cells produced in vivo including their large cell size (〉10 μm), polyploidy with a single nucleus, large vacuole, dense capsule, and thick cell wall. Here we show titan cells derived from the enlargement of progenitor cells in the population independent of yeast growth rate. Change in the incubation medium, hypoxia, nutrient starvation and low pH were the main factors that trigger titan cell formation, while quorum sensing factors like the initial inoculum concentration, pantothenic acid, and the quorum sensing peptide Qsp1p also impacted titan cell formation. Inhibition of ergosterol, protein and nucleic acid biosynthesis altered titan cell formation, as did serum, phospholipids and anti-capsular antibodies in our settings. We explored genetic factors important for titan cell formation using three approaches. Using H99-derivative strains with natural genetic differences, we showed that titan cell formation was dependent on LMP1 and SGF29 genes. By screening a gene deletion collection, we also confirmed that GPR4/5-RIM101 , and CAC1 genes were required to generate titan cells and that the PKR1 , TSP2 , USV101 genes negatively regulated titan cell formation. Furthermore, analysis of spontaneous Pkr1 loss-of-function clinical isolates confirmed the important role of the Pkr1 protein as a negative regulator of titan cell formation. Through development of a standardized and robust in vitro assay, our results provide new insights into titan cell biogenesis with the identification of multiple important factors/pathways.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 10
    Publication Date: 2018-05-30
    Description: by Thomas Hart, Ngoc Thien Thu Nguyen, Nancy A. Nowak, Fuming Zhang, Robert J. Linhardt, Maria Diuk-Wasser, Sanjay Ram, Peter Kraiczy, Yi-Pin Lin Borrelia burgdorferi sensu lato ( Bbsl ), the causative agent of Lyme disease, establishes an initial infection in the host’s skin following a tick bite, and then disseminates to distant organs, leading to multisystem manifestations. Tick-to-vertebrate host transmission requires that Bbsl survives during blood feeding. Complement is an important innate host defense in blood and interstitial fluid. Bbsl produces a polymorphic surface protein, CspA, that binds to a complement regulator, Factor H (FH) to block complement activation in vitro . However, the role that CspA plays in the Bbsl enzootic cycle remains unclear. In this study, we demonstrated that different CspA variants promote spirochete binding to FH to inactivate complement and promote serum resistance in a host-specific manner. Utilizing a tick-to-mouse transmission model, we observed that a cspA -knockout B . burgdorferi is eliminated from nymphal ticks in the first 24 hours of feeding and is unable to be transmitted to naïve mice. Conversely, ectopically producing CspA derived from B . burgdorferi or B . afzelii , but not B . garinii in a cspA -knockout strain restored spirochete survival in fed nymphs and tick-to-mouse transmission. Furthermore, a CspA point mutant, CspA-L246D that was defective in FH-binding, failed to survive in fed nymphs and at the inoculation site or bloodstream in mice. We also allowed those spirochete-infected nymphs to feed on C3 -/- mice that lacked functional complement. The cspA -knockout B . burgdorferi or this mutant strain complemented with cspA variants or cspA-L246D was found at similar levels as wild type B . burgdorferi in the fed nymphs and mouse tissues. These novel findings suggest that the FH-binding activity of CspA protects spirochetes from complement-mediated killing in fed nymphal ticks, which ultimately allows Bbsl transmission to mammalian hosts.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 11
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-30
    Description: by Preeti Jaggi, Asuncion Mejias, Zhaohui Xu, Han Yin, Melissa Moore-Clingenpeel, Bennett Smith, Jane C. Burns, Adriana H. Tremoulet, Alejandro Jordan-Villegas, Damien Chaussabel, Karen Texter, Virginia Pascual, Octavio Ramilo Background Early identification of children with Kawasaki Disease (KD) is key for timely initiation of intravenous immunoglobulin (IVIG) therapy. However, the diagnosis of the disease remains challenging, especially in children with an incomplete presentation (inKD). Moreover, we currently lack objective tools for identification of non-response (NR) to IVIG. Methods Children with KD were enrolled and samples obtained before IVIG treatment and sequentially at 24 h and 4–6 weeks post-IVIG in a subset of patients. We also enrolled children with other febrile illnesses [adenovirus (AdV); group A streptococcus (GAS)] and healthy controls (HC) for comparative analyses. Blood transcriptional profiles were analyzed to define: a) the cKD and inKD biosignature, b) compare the KD signature with other febrile illnesses and, c) identify biomarkers predictive of clinical outcomes. Results We identified a cKD biosignature (n = 39; HC, n = 16) that was validated in two additional cohorts of children with cKD (n = 37; HC, n = 20) and inKD (n = 13; HC, n = 8) and was characterized by overexpression of inflammation, platelets, apoptosis and neutrophil genes, and underexpression of T and NK cell genes. Classifier genes discriminated KD from adenovirus with higher sensitivity and specificity (92% and 100%, respectively) than for GAS (75% and 87%, respectively). We identified a genomic score (MDTH) that was higher at baseline in IVIG-NR [median 12,290 vs. 5,572 in responders, p = 0.009] and independently predicted IVIG-NR. Conclusion A reproducible biosignature from KD patients was identified, and was similar in children with cKD and inKD. A genomic score allowed early identification of children at higher risk for non-response to IVIG.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 12
    Publication Date: 2018-05-31
    Description: by Ahmed A. Saleh, Ali H. El-Far, Mervat A. Abdel-Latif, Mohamed A. Emam, Rania Ghanem, Hatem S. Abd El-Hamid Diminishing the cost of broiler chicken diet is a critical issue in the poultry industry. Numerous studies were performed to achieve this pivotal objective by diet supplementation with alternative feed additives. In the current study, low-energy broiler rations were supplemented with different commercial multienzyme formulations to minimize the cost, and increase the digestibility and absorption of the digested macronutrients. Cobb Avian 48 broiler chicks (mixed sex, 1-d-old, n = 3120) were randomly allocated into six groups, and each group was subdivided into four replicates (130 birds per replicate). The birds were randomly allocated into a control group fed basal diet (CB); control group fed low-energy diet (CL); and birds fed low-energy diets supplemented with different enzyme formulations. The enzyme formulations used were Xylam 500 ® (CLX group), Hemicell ® (CLH group), Avizyme ® (CLA group), and Megazyme ® (CLM group,) following the doses recommended by the manufacturers. The growth performance of CLA and CLH group birds was significantly improved when compared with CL. In comparison with CB, Avizyme ® significantly ( p 〈 0.001) increased the intestinal PEPT1 , GLUT2 , ACC , and IL-2 expression; PEPT1 facilitates the absorption of micronutrients. In conclusion, exogenous multienzyme complexes may be included in the low-energy diet to enhance the performance of broiler chickens (Avizyme ® ˃ Hemicell ® ˃ Megazyme ® ), and reduce the diet cost by up-regulating the expression of intestinal nutrient transporter genes, and improving the immunity and serum biochemical parameters of broiler chickens.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 13
    Publication Date: 2018-05-31
    Description: by Edgar Kigozi, George W. Kasule, Kenneth Musisi, Deus Lukoye, Samuel Kyobe, Fred Ashaba Katabazi, Eddie M. Wampande, Moses L. Joloba, David Patrick Kateete Background Accurate diagnosis of tuberculosis, especially by using rapid molecular assays, can reduce transmission of drug resistant tuberculosis in communities. However, the frequency of resistance conferring mutations varies with geographic location of Mycobacterium tuberculosis , and this affects the efficiency of rapid molecular assays in detecting resistance. This has created need for characterizing drug resistant isolates from different settings to investigate frequencies of resistance conferring mutations. Here, we describe the prevalence and patterns of rifampicin- and isoniazid- resistance conferring mutations in isolates from Uganda, which could be useful in the management of MDR-TB patients in Uganda and other countries in sub-Saharan Africa. Results Ninety seven M . tuberculosis isolates were characterized, of which 38 were MDR, seven rifampicin-resistant, 12 isoniazid-mono-resistant, and 40 susceptible to rifampicin and isoniazid. Sequence analysis of the rpoB rifampicin-resistance determining region ( rpoB /RRDR) revealed mutations in six codons: 588, 531, 526, 516, 513, and 511, of which Ser531Leu was the most frequent (40%, 18/45). Overall, the three mutations (Ser531Leu, His526Tyr, Asp516Tyr) frequently associated with rifampicin-resistance occurred in 76% of the rifampicin resistant isolates while 18% (8/45) of the rifampicin-resistant isolates lacked mutations in rpoB /RRDR. Furthermore, sequence analysis of katG and inhA gene promoter revealed mainly the Ser315Thr (76%, 38/50) and C(-15)T (8%, 4/50) mutations, respectively. These two mutations combined, which are frequently associated with isoniazid-resistance, occurred in 88% of the isoniazid resistant isolates. However, 20% (10/50) of the isoniazid-resistant isolates lacked mutations both in katG and inhA gene promoter. The sensitivity of sequence analysis of rpoB /RRDR for rifampicin-resistance via detection of high confidence mutations (Ser531Leu, His526Tyr, Asp516Tyr) was 81%, while it was 77% for analysis of katG and inhA gene promoter to detect isoniazid-resistance via detection of high confidence mutations (Ser315Thr, C(-15)T, T(-8)C). Furthermore, considering the circulating TB genotypes in Uganda, the isoniazid-resistance conferring mutations were more frequent in M . tuberculosis lineage 4/sub-lineage Uganda, perhaps explaining why this genotype is weakly associated with MDR-TB. Conclusion Sequence analysis of rpoB /RRDR, katG and inhA gene promoter is useful in detecting rifampicin/isoniazid resistant M . tuberculosis isolates in Uganda however, about ≤20% of the resistant isolates lack known resistance-conferring mutations hence rapid molecular assays may not detect them as resistant.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 14
    Publication Date: 2018-05-31
    Description: by Kwan-Il Kim, Ji Hee Jun, Hyunjung Baek, Jae-Hyo Kim, Beom-Joon Lee, Hee-Jae Jung Background Radiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored. Objective The aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy. Methods We searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results Twenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45–0.63, I 2 = 8%) and the incidence of severe radiation pneumonitis ( n = 903; RR 0.22, 95% CI 0.11–0.41, I 2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05–8.18, I 2 = 82%). Conclusion There is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach, further rigorously designed large scale trials are warranted.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 15
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-31
    Description: by Murat C. Kalem, Evgeny S. Gerasimov, Pamela K. Vu, Sara L. Zimmer The insect-transmitted protozoan parasite Trypanosoma cruzi experiences changes in nutrient availability and rate of flux through different metabolic pathways across its life cycle. The species encompasses much genetic diversity of both the nuclear and mitochondrial genomes among isolated strains. The genetic or expression variation of both genomes are likely to impact metabolic responses to environmental stimuli, and even steady state metabolic function, among strains. To begin formal characterization these differences, we compared aspects of metabolism between genetically similar strains CL Brener and Tulahuen with less similar Esmeraldo and Sylvio X10 strains in a culture environment. Epimastigotes of all strains took up glucose at similar rates. However, the degree of medium acidification that could be observed when glucose was absent from the medium varied by strain, indicating potential differences in excreted metabolic byproducts. Our main focus was differences related to electron transport chain function. We observed differences in ATP-coupled respiration and maximal respiratory capacity, mitochondrial membrane potential, and mitochondrial morphology between strains, despite the fact that abundances of two nuclear-encoded proteins of the electron transport chain are similar between strains. RNA sequencing reveals strain-specific differences in abundances of mRNAs encoding proteins of the respiratory chain but also other metabolic processes. From these differences in metabolism and mitochondrial phenotypes we have generated tentative models for the differential metabolic fluxes or differences in gene expression that may underlie these results.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 16
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-31
    Description: by Gaëtan Merlhiot, Martial Mermillod, Jean-Luc Le Pennec, Frédéric Dutheil, Laurie Mondillon In cases of impending natural disasters, most events are uncertain and emotionally relevant, both critical factors for decision-making. Moreover, for exposed individuals, the sensitivity to the framing of the consequences (gain or loss) and the moral judgments they have to perform (e.g., evacuate or help an injured person) constitute two central effects that have never been examined in the same context of decision-making. In a framed decision-making task with moral dilemma, we investigated whether uncertainty (i.e., unpredictably of events) and a threatening context would influence the framing effect (actions framed in loss are avoided in comparison to the ones framed in gain) and the personal intention effect (unintentional actions are more morally acceptable in comparison to intentional actions) on the perceived moral acceptability of taking action. Considering the impact of uncertainty and fear on the processes underlying these effects, we assumed that these emotions would lead to the negation of the two effects. Our results indicate that the exposure to uncertain events leads to the negation of the framing effect, but does not influence the moral acceptability and the effect of personal intention. We discuss our results in the light of dual-process models (i.e. systematic vs . heuristic), appraisal theories, and neurocognitive aspects. These elements highlight the importance of providing solutions to cope with uncertainty, both for scientists and local populations exposed to natural hazards.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 17
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    Public Library of Science (PLoS)
    Publication Date: 2018-05-31
    Description: by Bernt Lindtjørn, Demissew Mitike, Zillo Zidda, Yaliso Yaya Previous studies from South Ethiopia have shown that interventions that focus on intrapartum care substantially reduce maternal mortality and there is a need to operationalize health packages that could reduce stillbirths. The aim of this paper is to evaluate if a programme that aimed to improve maternal health, and mainly focusing on strengthening intrapartum care, also would reduce the number of stillbirths, and to estimate if there are other indicators that explains high stillbirth rates. Our study used a “continuum of care” approach and focussed on providing essential antenatal and obstetric services in communities through health extension workers, at antenatal and health facility services. In this follow up study, which includes the same 38.312 births registered by community health workers, shows that interventions focusing on improved intrapartum care can also reduce stillbirths (by 46%; from 14.5 to 7.8 per 1000 births). Other risk factors for stillbirths are mainly related to complications during delivery and illnesses during pregnancy. We show that focusing on Comprehensive Emergency Obstetric Care and antenatal services reduces stillbirths. However, the study also underlines that illnesses during pregnancy and complications during delivery still represent the main risk factors for stillbirths. This indicates that obstetric care need still to be strengthened, should include the continuum of care from home to the health facility, make care accessible to all, and reduce delays.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 18
    Publication Date: 2018-05-31
    Description: by Hong-Wei Wang, Hua-Ning Shi, Jia Cheng, Fang Xie, Yu-Kun Luo, Jie Tang Purpose The first aim of this study was to analyze the relationships between liver stiffness measurement, hepatic venous pressure and liver fibrosis. The second aim was to demonstrate the utility of real-time shear wave elastography for evaluation of Budd-Chiari syndrome patients before and after balloon hepatic venous angioplasty. Materials and methods A total of 32 patients with Budd-Chiari syndrome slated for successful balloon angioplasty met the inclusion and exclusion criteria. Shear wave elastography was used to generate dynamic liver stiffness measurement 2 days before angioplasty and 2 days, 3 months, and 6 months after angioplasty. Hepatic venous pressures were measured during balloon angioplasty. Correlations among liver stiffness, hepatic venous pressure, and fibrosis were assessed. Result Mean liver stiffness was 35.17 ± 10.60 kPa, 20.15 ± 5.47 kPa, 15.36 ± 4.34 kPa and 15.68 ± 5.58 kPa at baseline and 2 days, 3 months, and 6 months after angioplasty, respectively. Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P 〈 0.001); liver stiffness measured at 6 months after angioplasty was not significantly different from that measured at 3 months after angioplasty (P = 0.636). Analysis of liver stiffness measurement and hepatic venous pressure before balloon angioplasty yielded a coefficient of correlation r = 0.701 (P 〈 0.001). Before and 2d after angioplasty, liver stiffness measurement did not correlated with fibrosis (r = − 0.170, P = 0.22), (r = 0.223, P = 0.220), respectively, while the LSM difference before and 2 days after angioplasty negatively correlated with stiffness severity (r = − 0.502, P = 0.003). Liver stiffness measured at 2 days and 3 months after angioplasty was significantly decreased (P 〈 0.001), remaining stable at 3 months, though still in the cirrhotic range. Conclusions The liver stiffness of Budd-Chiari syndrome patients, measured by shear wave elastography, decreased considerably after hepatic venous recanalization, and significantly correlated with hepatic venous pressure though not with degree of fibrosis. Shear wave elastography may be effective in monitoring short- and long-term treatment outcomes in Budd-Chiari syndrome.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 19
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    Publication Date: 2018-05-31
    Description: by Cristina Faralla, Effie E. Bastounis, Fabian E. Ortega, Samuel H. Light, Gabrielle Rizzuto, Salvatorre Nocadello, Wayne F. Anderson, Jennifer R. Robbins, Julie A. Theriot, Anna I. Bakardjiev During pregnancy, the placenta protects the fetus against the maternal immune response, as well as bacterial and viral pathogens. Bacterial pathogens that have evolved specific mechanisms of breaching this barrier, such as Listeria monocytogenes , present a unique opportunity for learning how the placenta carries out its protective function. We previously identified the L . monocytogenes protein Internalin P (InlP) as a secreted virulence factor critical for placental infection. Here, we show that InlP, but not the highly similar L . monocytogenes internalin Lmo2027, binds to human afadin (encoded by AF-6 ), a protein associated with cell-cell junctions. A crystal structure of InlP reveals several unique features, including an extended leucine-rich repeat (LRR) domain with a distinctive Ca 2+ -binding site. Despite afadin’s involvement in the formation of cell-cell junctions, MDCK epithelial cells expressing InlP displayed a decrease in the magnitude of the traction stresses they could exert on deformable substrates, similar to the decrease in traction exhibited by AF-6 knock-out MDCK cells. L . monocytogenes ΔinlP mutants were deficient in their ability to form actin-rich protrusions from the basal face of polarized epithelial monolayers, a necessary step in the crossing of such monolayers (transcytosis). A similar phenotype was observed for bacteria expressing an internal in-frame deletion in inlP ( inlP Δ LRR5) that specifically disrupts its interaction with afadin. However, afadin deletion in the host cells did not rescue the transcytosis defect. We conclude that secreted InlP targets cytosolic afadin to specifically promote L . monocytogenes transcytosis across the basal face of epithelial monolayers, which may contribute to the crossing of the basement membrane during placental infection.
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  • 20
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    Publication Date: 2018-05-31
    Description: by Jiayang He, Nicola K. Beck, Alexandra L. Kossik, Jiawei Zhang, Edmund Seto, John Scott Meschke, Igor Novosselov Bioaerosol sampling and identification are vital for the assessment and control of airborne pathogens, allergens, and toxins. In-situ analysis of chemical and biological particulate matter can significantly reduce the costs associated with sample preservation, transport, and analysis. The analysis of conventional filters is challenging, due to dilute samples in large collection regions. A low-cost cartridge for collection and analysis of aerosols is developed for use in epidemiological studies and personal exposure assessments. The cartridge collects aerosol samples in a micro-well which reduces particles losses due to the bounce and does not require any coating. The confined particle collection area (d well ~1.4 mm) allows reducing the elution volume for subsequent analysis. The performance of the cartridge is validated in laboratory studies using aerosolized bacterial spores ( Bacillus subtilis ). Colony forming unit analysis is used for bacterial spore enumeration. Cartridge collection efficiency is evaluated by comparison with the reference filters and found to be consistent with tested flow rates. Sample recovery for the pipette elution is ~80%. Due to the high density of the collected sample, the cartridge is compatible with in-situ spectroscopic analysis and sample elution into the 10–20 μl liquid volume providing a significant increase in sample concentration for subsequent analysis.
    Electronic ISSN: 1932-6203
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  • 21
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    Publication Date: 2018-05-31
    Description: by Seulggie Choi, Jin A. Choi, Jin Woo Kwon, Sang Min Park, Donghyun Jee Objectives Although determining the quality of life among glaucoma patients has important clinical and public health implications, the utility value of glaucoma patients has not yet been determined in Korea. Methods The Korean National Health and Nutrition Examination Survey database was used to identify 833 glaucoma patients based on ophthalmologic examinations. The adjusted mean utility values, calculated by EuroQol-5D (EQ-5D-3L), of glaucoma patients according to patient demographics and measures of glaucoma severity were determined using multivariate linear regression analysis. Results The mean utility value of glaucoma patients was 0.8968. Patients aged 70 years or more had significantly lower utility value (0.86, p value 0.005) compared to those aged less than 50 years (0.96). Patients within the lowest quartile of income had a utility value of 0.87, compared to a utility value of 0.96 for those within the highest quartile ( p value 0.001). Patients who were not married had lower utility value (0.87) compared to married patients (0.93). Patients within the lowest quartile of worse eye frequency doubling technology (FDT) score had lower utility value (0.88) compared to those within the highest quartile (0.94). Finally, bilateral vision loss patients had significantly lower utility value (0.83, p value 0.013) compared to patients without vision loss (0.92). Conclusion The present study assessed utility values of Korean glaucoma patients. The quality of life determined by EQ-5D-3L in Korean glaucoma patients was higher compared to those in other countries. Patient demographics as well as measures of disease severity were important factors in determining the quality of life within glaucoma patients.
    Electronic ISSN: 1932-6203
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  • 22
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    Publication Date: 2018-06-01
    Description: by Lubomir Tomaska, Jozef Nosek
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 23
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    Publication Date: 2018-06-01
    Description: by Imran Mohammad, Kari Nousiainen, Santosh D. Bhosale, Inna Starskaia, Robert Moulder, Anne Rokka, Fang Cheng, Ponnuswamy Mohanasundaram, John E. Eriksson, David R. Goodlett, Harri Lähdesmäki, Zhi Chen The transcriptional network and protein regulators that govern T helper 17 (Th17) cell differentiation have been studied extensively using advanced genomic approaches. For a better understanding of these biological processes, we have moved a step forward, from gene- to protein-level characterization of Th17 cells. Mass spectrometry–based label-free quantitative (LFQ) proteomics analysis were made of in vitro differentiated murine Th17 and induced regulatory T (iTreg) cells. More than 4,000 proteins, covering almost all subcellular compartments, were detected. Quantitative comparison of the protein expression profiles resulted in the identification of proteins specifically expressed in the Th17 and iTreg cells. Importantly, our combined analysis of proteome and gene expression data revealed protein expression changes that were not associated with changes at the transcriptional level. Our dataset provides a valuable resource, with new insights into the proteomic characteristics of Th17 and iTreg cells, which may prove useful in developing treatment of autoimmune diseases and developing tumor immunotherapy.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 24
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    Publication Date: 2018-06-01
    Description: by Paul D. Donovan, Linda M. Holland, Lisa Lombardi, Aisling Y. Coughlan, Desmond G. Higgins, Kenneth H. Wolfe, Geraldine Butler Riboswitches are non-coding RNA molecules that regulate gene expression by binding to specific ligands. They are primarily found in bacteria. However, one riboswitch type, the thiamin pyrophosphate (TPP) riboswitch, has also been described in some plants, marine protists and fungi. We find that riboswitches are widespread in the budding yeasts (Saccharomycotina), and they are most common in homologs of DUR31 , originally described as a spermidine transporter. We show that DUR31 (an ortholog of N . crassa gene NCU01977) encodes a thiamin transporter in Candida species. Using an RFP/riboswitch expression system, we show that the functional elements of the riboswitch are contained within the native intron of DUR31 from Candida parapsilosis , and that the riboswitch regulates splicing in a thiamin-dependent manner when RFP is constitutively expressed. The DUR31 gene has been lost from Saccharomyces , and may have been displaced by an alternative thiamin transporter. TPP riboswitches are also present in other putative transporters in yeasts and filamentous fungi. However, they are rare in thiamin biosynthesis genes THI4 and THI5 in the Saccharomycotina, and have been lost from all genes in the sequenced species in the family Saccharomycetaceae, including S . cerevisiae .
    Print ISSN: 1553-7390
    Electronic ISSN: 1553-7404
    Topics: Biology
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  • 25
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    Publication Date: 2018-06-01
    Description: by Raquel Burger-Calderon, Karla Gonzalez, Sergio Ojeda, José Victor Zambrana, Nery Sanchez, Cristhiam Cerpas Cruz, Harold Suazo Laguna, Fausto Bustos, Miguel Plazaola, Brenda Lopez Mercado, Douglas Elizondo, Sonia Arguello, Jairo Carey Monterrey, Andrea Nuñez, Josefina Coloma, Jesse J. Waggoner, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris Zika virus (ZIKV) infection recently caused major epidemics in the Americas and is linked to congenital birth defects and Guillain-Barré Syndrome. A pilot study of ZIKV infection in Nicaraguan households was conducted from August 31 to October 21, 2016, in Managua, Nicaragua. We enrolled 33 laboratory-confirmed Zika index cases and their household members (109 contacts) and followed them on days 3–4, 6–7, 9–10, and 21, collecting serum/plasma, urine, and saliva specimens along with clinical, demographic, and socio-economic status information. Collected samples were processed by rRT-PCR to determine viral load (VL) and duration of detectable ZIKV RNA in human bodily fluids. At enrollment, 11 (10%) contacts were ZIKV rRT-PCR-positive and 23 (21%) were positive by IgM antibodies; 3 incident cases were detected during the study period. Twenty of 33 (61%) index households had contacts with ZIKV infection, with an average of 1.9 (range 1–6) positive contacts per household, and in 60% of these households, ≥50% of the members were positive for ZIKV infection. Analysis of clinical information allowed us to estimate the symptomatic to asymptomatic (S:A) ratio of 14:23 (1:1.6) among the contacts, finding 62% of the infections to be asymptomatic. The maximum number of days during which ZIKV RNA was detected was 7 days post-symptom onset in saliva and serum/plasma and 22 days in urine. Overall, VL levels in serum/plasma, saliva, and urine specimens were comparable, with means of 5.6, 5.3 and 4.5 log 10 copies/ml respectively, with serum attaining the highest VL peak at 8.1 log 10 copies/ml. Detecting ZIKV RNA in saliva over a similar time-period and level as in serum/plasma indicates that saliva could potentially serve as a more accessible diagnostic sample. Finding the majority of infections to be asymptomatic emphasizes the importance of silent ZIKV transmission and helps inform public health interventions in the region and globally.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 26
    Publication Date: 2018-06-01
    Description: by Sarah K. White, Carla Mavian, Maha A. Elbadry, Valery Madsen Beau De Rochars, Taylor Paisie, Taina Telisma, Marco Salemi, John A. Lednicky, J. Glenn Morris Jr. In the context of recent arbovirus epidemics, questions about the frequency of simultaneous infection of patients with different arbovirus species have been raised. In 2014, a major Chikungunya virus (CHIKV) epidemic impacted the Caribbean and South America. As part of ongoing screening of schoolchildren presenting with acute undifferentiated febrile illness in rural Haiti, we used RT-PCR to identify CHIKV infections in 82 of 100 children with this diagnosis during May—August 2014. Among these, eight were infected with a second arbovirus: six with Zika virus (ZIKV), one with Dengue virus serotype 2, and one with Mayaro virus (MAYV). These dual infections were only detected following culture of the specimen, suggesting low viral loads of the co-infecting species. Phylogenetic analyses indicated that the ZIKV and MAYV strains differ from those detected later in 2014 and 2015, respectively. Moreover, CHIKV and ZIKV strains from co-infected patients clustered monophyletically in their respective phylogeny, and clock calibration traced back the common ancestor of each clade to an overlapping timeframe of introduction of these arboviruses onto the island.
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  • 27
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    Publication Date: 2018-06-01
    Description: by Getachew Ferede, Moges Tiruneh, Ebba Abate, Yitayih Wondimeneh, Demekech Damtie, Endalamaw Gadisa, Rawleigh Howe, Abraham Aseffa, Belay Tessema Background Dengue is one of the most serious and rapidly spreading arboviral diseases in the world. Despite many acute febrile illnesses in Ethiopia, the burden of illness due to dengue in the country is largely unknown. Thus, the present study aimed to provide the first baseline data on seroprevalence and associated risk factors of dengue virus (DENV) infection in the country. Methods A cross-sectional study of febrile patients who were visiting Metema and Humera hospitals in Northwest Ethiopia from March 2016 to May 2017 was conducted. Blood samples were collected from each participant and serum samples were separated and tested for IgM and IgG antibodies against DENV infection by enzyme-linked immunosorbent assay (ELISA). Risk factors associated with the prevalence of anti-DENV antibodies were tested using logistic regression analysis. Results Of the 600 samples tested, the overall seroprevalence against DENV infection was 33.3%, while the seroprevalence by the study area was 40% in Metema and 27.5% in Humera. The overall prevalence of IgM and IgG antibodies against DENV infection was 19% and 21% respectively. Of these, 6.7% were positive for both IgM and IgG antibodies. Residence and occupational status were significantly associated with the prevalence of anti-DENV IgM seropositivity and anti-DENV IgM-/G+serostatus. The seasonal variation was significantly associated with the prevalence of anti-DENV IgM but not with anti-DENV IgM-/G+serostatus. The prevalence of anti-DENV IgM-/G+serostatus was significantly higher in Metema than Humera. High prevalence of anti-DENV IgM seropositivity was found in the summer and spring, with a peak in the month of August. The presence of uncovered water either indoor or outdoor and lack of mosquito net use was identified as risk factors for DENV infection. Conclusions These findings provide the preliminary data on seroprevalence and associated risk factors of DENV infection in the country. The presence of antibodies against DENV infection indicates dengue as one of the causes of undifferentiated febrile illnesses in the study areas. This suggests that prevention and control measures should be designed considering the risk factors identified by this study. Furthermore, we recommend a large-scale study to include DENV infection in the differential diagnosis of all febrile illnesses in Ethiopia.
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  • 28
    Publication Date: 2018-06-01
    Description: by Shiao-Pieng Lee, Chen-Yu Kao, Shun-Cheng Chang, Yi-Lin Chiu, Yen-Ju Chen, Ming-Hsing G. Chen, Chun-Chia Chang, Yu-Wen Lin, Chien-Ping Chiang, Jehng- Kang Wang, Chen-Yong Lin, Michael D. Johnson
    Electronic ISSN: 1932-6203
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  • 29
    Publication Date: 2018-06-01
    Description: by Shuai Zhou, Jingsong Zhang, Fuying Ma, Chuanhong Tang, Qingjiu Tang, Xiaoyu Zhang Ganoderma lucidum is a medicinal mushroom that is well known for its ability to enhance human health, and products made from this fungus have been highly profitable. The substrate-degrading ability of G . lucidum could be related to its growth. CAZy proteins were more abundant in its genome than in the other white rot fungi models. Among these CAZy proteins, changes in lignocellulolytic enzymes during growth have not been well studied. Using genomic, transcriptomic and secretomic analyses, this study focuses on the lignocellulolytic enzymes of G . lucidum strain G0119 to determine which of these degradative enzymes contribute to its growth. From the genome sequencing data, genes belonging to CAZy protein families, especially genes involved in lignocellulose degradation, were investigated. The gene expression, protein abundance and enzymatic activity of lignocellulolytic enzymes in mycelia over a growth cycle were analysed. The overall expression cellulase was higher than that of hemicellulase and lignin-modifying enzymes, particularly during the development of fruiting bodies. The cellulase and hemicellulase abundances and activities increased after the fruiting bodies matured, when basidiospores were produced in massive quantities till the end of the growth cycle. Additionally, the protein abundances of the lignin-modifying enzymes and the expression of their corresponding genes, including laccases and lignin-degrading heme peroxidases, were highest when the mycelia fully spread in the compost bag. Type I cellobiohydrolase was observed to be the most abundant extracellular lignocellulolytic enzyme produced by the G . lucidum strain G0119. The AA2 family haem peroxidases were the dominant lignin-modifying enzyme expressed during the mycelial growth phase, and several laccases might play roles during the formation of the primordium. This study provides insight into the changes in the lignocellulose degradation ability of G . lucidum during its growth and will facilitate the discovery of new approaches to accelerate the growth of G . lucidum in culture.
    Electronic ISSN: 1932-6203
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  • 30
    Publication Date: 2018-06-01
    Description: by Li Li, Yong Cheng, Scott Emrich, Jeffrey Schorey Endothelial cells play an essential role in regulating an immune response through promoting leukocyte adhesion and cell migration and production of cytokines such as TNFα. Regulation of endothelial cell immune function is tightly regulated and recent studies suggest that extracellular vesicles (EVs) are prominently involved in this process. However, the importance of EVs in regulating endothelial activation in the context of a bacterial infection is poorly understood. To begin addressing this knowledge gap we characterized the endothelial cell response to EVs released from Mycobacterium tuberculosis ( Mtb ) infected macrophages. Our result showed increased macrophage migration through the monolayer when endothelial cells were pretreated with EVs isolated from Mtb -infected macrophages. Transcriptome analysis showed a significant upregulation of genes involved in cell adhesion and the inflammatory process in endothelial cells treated with EVs. These results were validated by quantitative PCR and flow cytometry. Pathway analysis of these differentially expressed genes indicated that several immune response-related pathways were up-regulated. Endothelial cells were also treated with EVs isolated from the serum of Mtb -infected mice. Interestingly, EVs isolated 14 days but not 7 or 21 days post-infection showed a similar ability to induce endothelial cell activation suggesting a change in EV function during the course of an Mtb infection. Immunofluorescence microscopy result indicated that NF-κB and the Type 1 interferon pathways were involved in endothelial activation by EVs. In summary, our data suggest that EVs can activate endothelial cells and thus may play an important role in modulating host immune responses during an Mtb infection.
    Electronic ISSN: 1932-6203
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  • 31
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    Publication Date: 2018-06-01
    Description: by Henrique Pereira Neiva, Luís Brandão Faíl, Mikel Izquierdo, Mário C. Marques, Daniel A. Marinho The main purpose of the present study was to verify the effects of a 12-week water aerobics program in a real-life context on health indicators and physical fitness in adults and older adults. Fifteen volunteers (58.80 ± 14.32 years old) were part of an experimental group (Exercise), and eight volunteers (59.00 ± 12.26 years old) were part of the control group (Control). The Exercise performed 45 min of water aerobics twice a week for 12 weeks; no physical exercise was permitted for the Control during the same period. The evaluations were performed the week before (pre-training) and after the training program (post-training). The primary outcomes were the strength and cardiorespiratory fitness variables and the secondary outcomes included body anthropometry, lipid profile and blood pressure. Adjusted analysis for age and baseline values showed no differences between Exercise and Control in post-training moment. However, there was a moderated tendency for increased explosive strength of the upper limbs (η p 2 = 0.17), reduced body fat (η p 2 = 0.17), reduced systolic blood pressure (η p 2 = 0.14) and triglycerides (η p 2 = 0.19) in Exercise. Within groups changes showed that the training program caused an increase mainly in explosive strength in the upper limbs (0.26 m, 95% CI, 0.03, 0.49; ES = 0.63) In addition, there was a significant decrease in fat mass (-0.89%, 95% CI, -1.74, -0.03; ES = 0.61) and in the systolic blood pressure (-0.83 mmHg, -1.46, -0.19; ES = 0.71). Nonetheless, no significant changes were observed for the lipid profile. These results suggest that 12 weeks of water aerobics performed twice a week in a real-life context seem to benefit the explosive strength, body composition, and blood pressure of adults and older adults but is insufficient to alter cardiorespiratory fitness and lipid profiles.
    Electronic ISSN: 1932-6203
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  • 32
    Publication Date: 2018-06-01
    Description: by Nahed O. ElHassan, Shasha Bai, Neal Gibson, Greg Holland, James M. Robbins, Jeffrey R. Kaiser Background The relative influence of prematurity vs. maternal social factors (socioeconomic status and education level) on academic performance has rarely been examined. Objective To examine the impact of prematurity and maternal social factors on academic performance from 3 rd through 8 th grade. Methods We conducted a retrospective cohort study of infants born in 1998 at the University of Arkansas for Medical Sciences. The study sample included 58 extremely low gestational age newborns (ELGANs, 23‒
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  • 33
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    Publication Date: 2018-06-01
    Description: by Daniel R. Ram, Cordelia Manickam, Brady Hueber, Hannah L. Itell, Sallie R. Permar, Valerie Varner, R. Keith Reeves Natural killer (NK) cells classically typify the nonspecific effector arm of the innate immune system, but have recently been shown to possess memory-like properties against multiple viral infections, most notably CMV. Expression of the activating receptor NKG2C is elevated on human NK cells in response to infection with CMV as well as HIV, and may delineate cells with memory and memory-like functions. A better understanding of how NKG2C+ NK cells specifically respond to these pathogens could be significantly advanced using nonhuman primate (NHP) models but, to date, it has not been possible to distinguish NKG2C from its inhibitory counterpart, NKG2A, in NHP because of unfaithful antibody cross-reactivity. Using novel RNA-based flow cytometry, we identify for the first time true memory NKG2C+ NK cells in NHP by gene expression (KLRC2), and show that these cells have elevated frequencies and diversify their functional repertoire specifically in response to rhCMV and SIV infections.
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  • 34
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    Publication Date: 2018-06-01
    Description: by Samuel Bevet, Meredith T. Niles, Lizzy Pope A mixed-methods approach was used to evaluate and improve the “late-night dining” options in a university dining hall. Surveys assessed student desires for late-night offerings, and evaluated students’ habits and motivations during late-night dining. Two interventions were implemented to see if students could be “nudged” into different choice patterns. In the first, a “veggie-heavy” entrée was added at the beginning of the entrée line, so that students would substitute an entrée containing vegetables for the alternatives. In the second, a snack-food bar was set up to cater to students who didn’t want to stand in the long entrée line, and preferred a snack. Data on food choice was collected during the interventions. Survey responses showed significant differences in the reasons females and males utilized late-night dining (p
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  • 35
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    Publication Date: 2018-06-01
    Description: by Yang Sun Park, Kyung Koh, Hyun Joon Kwon, Okjin Lee, Jae Kun Shim Human central nervous system (CNS) undergoes neurological changes during the aging process, leading to declines in hand and finger functions. Previous studies have shown that the CNS can independently process multi-finger force control and moment of force control. However, if both force and moment control are simultaneously imposed by motor task constraints, the CNS needs to resolve competing interests of generating negative and positive covariances between fingers, respectively, which causes “ conflict of interest or COI” . Here, we investigated how aging affects the CNS’s abilities to solve COI through a new experimental paradigm. Both elderly and young subjects performed a constant force production task using index and middle fingers under two conditions, multi-finger pressing with no COI and with COI . We found that the elderly increased variance of a virtual finger (VF: an imagined finger producing the same mechanical effect as both fingers together) in time-to-time basis (i.e. online control), while increasing covariance between individual fingers (IF) forces in trial-to-trial basis (i.e. offline control) with COI than no COI . Aging affects the CNS’s abilities to solve COI by deteriorating VF actions in online control and IF actions in offline control.
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  • 36
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    Publication Date: 2018-06-01
    Description: by Masato Yuasa, Masanori Saito, Cesar Molina, Stephanie N. Moore-Lotridge, Michael A. Benvenuti, Nicholas A. Mignemi, Atsushi Okawa, Toshitaka Yoshii, Herbert S. Schwartz, Jeffry S. Nyman, Jonathan G. Schoenecker Immediately following a fracture, a fibrin laden hematoma is formed to prevent bleeding and infection. Subsequently, the organized removal of fibrin, via the protease plasmin, is essential to permit fracture repair through angiogenesis and ossification. Yet, when plasmin activity is lost, the depletion of fibrin alone is insufficient to fully restore fracture repair, suggesting the existence of additional plasmin targets important for fracture repair. Previously, activated matrix metalloproteinase 9 (MMP-9) was demonstrated to function in fracture repair by promoting angiogenesis. Given that MMP-9 is a defined plasmin target, it was hypothesized that pro-MMP-9, following plasmin activation, promotes fracture repair. This hypothesis was tested in a fixed murine femur fracture model with serial assessment of fracture healing. Contrary to previous findings, a complete loss of MMP-9 failed to affect fracture healing and union through 28 days post injury. Therefore, these results demonstrated that MMP-9 is dispensable for timely fracture union and cartilage transition to bone in fixed femur fractures. Pro-MMP-9 is therefore not a significant target of plasmin in fracture repair and future studies assessing additional plasmin targets associated with angiogenesis are warranted.
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  • 37
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    Publication Date: 2018-06-01
    Description: by Lauren C. Aguado, Benjamin tenOever
    Print ISSN: 1553-7366
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  • 38
    Publication Date: 2018-06-01
    Description: by Jake Jianjun Wen, Yuhui Whitney Yin, Nisha Jain Garg Chagasic cardiomyopathy is caused by Trypanosoma cruzi infection. Poly(ADP-ribose) polymerase 1 (PARP1) is known for its function in nuclear DNA repair. In this study, we have employed genetic deletion and chemical inhibition approaches to determine the role of PARP1 in maintaining mtDNA dependent mitochondrial function in Chagas disease. Our data show that expression of PARP1 and protein PARylation were increased by 〉2-fold and 〉16-fold, respectively, in the cytosolic, nuclear, and mitochondrial fractions of the human cardiac myocytes and the myocardium of wildtype (WT) mice chronically infected with T . cruzi . The nuclear and cytosolic PARP1/PAR did not interfere with the transcription and translation of the components of the mtDNA replisome machinery in infected cardiomyocytes and chagasic murine myocardium. However, PARP1 binding to Polymerase γ and mtDNA in mitochondria were increased, and associated with a loss in mtDNA content, mtDNA-encoded gene expression, and oxidative phosphorylation (OXPHOS) capacity, and an increase in mitochondrial ROS production in cells and heart of WT mice infected with T . cruzi . Subsequently, an increase in oxidative stress, and cardiac collagen deposition, and a decline in LV function was noted in chagasic mice. Genetic deletion of PARP1 or treatment with selective inhibitor of PARP1 (PJ34) improved the mtDNA content, mitochondrial function, and oxidant/antioxidant balance in human cardiomyocytes and chronically infected mice. Further, PARP1 inhibition was beneficial in preserving the cardiac structure and left ventricular function in chagasic mice. We conclude that PARP1 overexpression is associated with a decline in Pol γ-dependent maintenance of mtDNA content, mtDNA-encoded gene expression, and mitochondrial respiratory function, and subsequently contributes to an increase in mtROS and oxidative stress in chagasic myocardium. Inhibition of mitochondrial PARP1/PAR offers a novel therapy in preserving the mitochondrial and LV function in chronic Chagas disease.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 39
    Publication Date: 2018-06-02
    Description: by Tao He, Xavier Mortensen, Ping Wang, Ning Tian
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 40
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-02
    Description: by Caitlin C. Murphy, Amit G. Singal In this month's Editorial Caitlin C. Murphy and Amit Singal discuss the increasing incidence of early-onset colorectal cancer in patients under the age of 50.
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
    Topics: Medicine
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  • 41
    Publication Date: 2018-06-02
    Description: by Seiichi Mawatari, Kohei Oda, Kazuaki Tabu, Sho Ijuin, Kotaro Kumagai, Kunio Fujisaki, Masafumi Hashiguchi, Yukiko Inada, Hirofumi Uto, Yasunari Hiramine, Takeshi Kure, Takeshi Hori, Oki Taniyama, Ai Kasai, Tsutomu Tamai, Akihiro Moriuchi, Akio Ido Objective The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs). Methods Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed. Results Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naïve and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and γ-glutamyltranspeptidase were associated with virologic failure. In the naïve patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%). Conclusions Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 42
    Publication Date: 2018-06-02
    Description: by Mufaro Kanyangarara, Neff Walker, Ties Boerma Background Syphilis in pregnancy is an under-recognized public health problem, especially in sub-Saharan Africa which accounts for over 60% of the global burden of syphilis. If left untreated, more than half of maternal syphilis cases will result in adverse pregnancy outcomes including stillbirth and fetal loss, neonatal death, prematurity or low birth weight, and neonatal infections. Achieving universal coverage of antenatal syphilis screening and treatment has been the focus of the global campaign for the elimination of mother-to-child transmission of syphilis. However, little is known about the availability of antenatal syphilis screening and treatment across sub-Saharan Africa. The objective of this study was to estimate the ‘likelihood of appropriate care’ for antenatal syphilis screening and treatment by analyzing health facility surveys and household surveys conducted from 2010 to 2015 in 12 sub-Saharan African countries. Methods In this secondary data analysis, we linked indicators of health facility readiness to provide antenatal syphilis detection and treatment from Service Provision Assessments (SPAs) and Service Availability and Readiness Assessments (SARAs) to indicators of ANC use from the Demographic and Health Surveys (DHS) to compute estimates of the ‘likelihood of appropriate care’. Results Based on data from 5,593 health facilities that reported offering antenatal care (ANC) services, the availability of syphilis detection and treatment in ANC facilities ranged from 2% to 83%. The availability of syphilis detection and treatment was substantially lower in ANC facilities in West Africa compared to the other sub-regions. Levels of ANC attendance were high (median 94.9%), but only 27% of ANC attendees initiated care at less than 4 months gestation. We estimated that about one in twelve pregnant women received ANC early (
    Electronic ISSN: 1932-6203
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  • 43
    Publication Date: 2018-06-02
    Description: by Hyojin Kim, Hyun Jung Kwon, Soo Young Park, Youngmi Park, Eunhyang Park, Jin-Haeng Chung In this study, we present the clinicopathological features associated with PD-L1 protein and mRNA expression in a large Asian cohort of patients with non-small cell lung cancer (NSCLC) and assessed the prognostic implications of PD-L1 expression, particularly in early stage NSCLC. We retrospectively analyzed 687 NSCLC specimens (476 adenocarcinoma and 211 squamous cell carcinoma) using tissue microarray. PD-L1 immunohistochemistry (IHC) was performed using Dako 22C3 pharmDx assay and PDL1 mRNA was measured using RNA in situ hybridization (RISH). The overall prevalence of PD-L1 protein expression was 25.2% in tumor cells and PDL1 mRNA expression was 11.9%. There was a strong positive correlation between PD-L1 IHC and RISH results (Spearman’s rho = 0.6, p
    Electronic ISSN: 1932-6203
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  • 44
    Publication Date: 2018-06-02
    Description: by Yuan Li, Wenyun Jia, Guohua Lei, Dan Zhao, Guirong Wang, Shibing Qin Background Both osteoarticular tuberculosis (OA-TB) and inflammatory arthritis can lead to osteoarticular structural damage. These conditions exhibit similar symptoms, physical signs, and imaging features. Rapidly and accurately diagnosing OA-TB in patients with inflammatory arthritis presents a challenge to clinicians. Xpert MTB/RIF (Xpert) has been endorsed by the World Health Organization (WHO) as a rapid diagnostic tool for diagnosis of pulmonary and extrapulmonary TB. This study was designed to investigate diagnostic efficiency of Xpert for OA-TB in patients with inflammatory arthritis in China. Methods A total of 83 consecutive patients with inflammatory arthritis and suspected OA-TB were enrolled prospectively from June 2014 to May 2018. Demographic, clinical, and biological data were recorded. Xpert assay, smear microscopy examination (smear), BACTEC MGIT 960 (MGIT 960), pathological examination, and T-SPOT.TB test were performed for each patient who received operations. Diagnostic efficiency of Xpert was evaluated based on a composite reference standard (CRS). Results A total of 49 out of 83 patients with inflammatory arthritis and suspected OA-TB received operations, and 49 specimens were obtained during operations. According to CRS, 36 out of 49 patients with inflammatory arthritis were diagnosed with OA-TB, and 13 were not affected by the condition. Sensitivity of Xpert assay, smear, MGIT 960, pathological examination, and T-SPOT.TB test reached 66.70% (24/36), 25.00% (9/36), 30.55% (11/36), 47.22% (17/36), and 80.55% (29/36), respectively. Specificity of Xpert assay, smear, MGIT 960, and pathological examination was all 100% (13/13). Specificity of T-SPOT.TB test was 53.84% (7/13). Sensitivity of Xpert was higher than that of smear, MGIT 960 and pathological examination, but the sensitivity of Xpert was lower than that of T-SPOT.TB. Sensitivity of Xpert was statistically different from that of smear and MGIT 960 ( P
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  • 45
    Publication Date: 2018-06-02
    Description: by Jiaxing Zhang, Yi Liang, Yuan Ai, Xiaosi Li, Juan Xie, Youping Li, Wenyi Zheng, Rui He Purpose In absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP). Methods We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication. Results Nine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [ Risk Ratio(RR) = 0.59, 95% Confidence Interval(CI) : 0.24–1.45], the incidence of adverse events ( RR = 0.98, 95% CI : 0.79–1.21), durable response ( RR = 0.47, 95% CI : 0.08–2.81), the incidence of overall bleeding ( RR = 1.15, 95% CI : 0.52–2.57) and clinically significant bleeding ( RR = 1.09, 95% CI : 0.37–3.24), and the proportion of patients receiving rescue treatment ( RR = 0.95, 95% CI : 0.47–1.90) were similar between eltrombopag and romiplostim. Conclusions Eltrombopag and romiplostim might be equivalent in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs. Registration PROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: CRD42017068661).
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 46
    Publication Date: 2018-06-02
    Description: by Maryam Noordadi, Faramarz Mehrnejad, Reza H. Sajedi, Majid Jafari, Bijan Ranjbar In this study, we report a detailed experimental, binding free energy calculation and molecular dynamics (MD) simulation investigation of the interactions of carboxylic-functionalized multi-walled carbon nanotubes (COOH-f-MWCNTs) with porcine trypsin (pTry). The enzyme exhibits decreased thermostability at 330K in the presence of COOH-f-MWCNTs. Furthermore, the activity of pTry also decreases in the presence of COOH-f-MWCNTs. The restricted diffusion of the substrate to the active site of the enzyme was observed in the experiment. The MD simulation analysis suggested that this could be because of the blocking of the S1 pocket of pTry, which plays a vital role in the substrate selectivity. The intrinsic fluorescence of pTry is quenched with increase in the COOH-f-MWCNTs concentration. Circular dichroism (CD) and UV–visible absorption spectroscopies indicate the ability of COOH-f-MWCNTs to experience conformational change in the native structure of the enzyme. The binding free energy calculations also show that electrostatics, π-cation, and π-π stacking interactions play important roles in the binding of the carboxylated CNTs with pTry. The MD simulation results demonstrated that the carboxylated CNTs adsorb to the enzyme stronger than the CNT without the–COOH groups. Our observations can provide an example of the nanoscale toxicity of COOH-f-MWCNTs for proteins, which is a critical issue for in vivo application of COOH-f-MWCNTs.
    Electronic ISSN: 1932-6203
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  • 47
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-02
    Description: by Rafael Rios, Carmen Pineda, Ignacio Lopez, Juan Muñoz-Castañeda, Mariano Rodriguez, Escolastico Aguilera-Tejero, Ana I. Raya This study was designed to evaluate the influence of phosphorus (P) restriction on the deleterious effects of high fat diets on mineral metabolism. Twenty-four rats were allotted to 3 groups (n = 8 each) that were fed different diets for 7 months. Rats in group 1 were fed normal fat-normal P (0.6%) diet (NF-NP), rats in group 2 were fed high fat- normal P diet (HF-NP) and rats in group 3 were fed high fat-low P (0.2%) diet (HF-LP). Blood, urine and tissues were collected at the end of the experiments. When compared with the control group (NF-NP), rats fed HF diets showed increases in body weight, and in plasma concentrations of triglycerides and leptin, and decreased plasma calcitriol concentrations. In rats fed HF-NP plasma fibroblast growth factor 23 (FGF23) was higher (279.6±39.4 pg/ml vs 160.6±25.0 pg/ml, p = 0.018) and renal klotho (ratio klotho/GAPDH) was lower (0.75±0.06 vs 1.06±0.08, p
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  • 48
    Publication Date: 2018-06-05
    Description: by Jewel Gausman, Iván Mejía-Guevara, S. V. Subramanian, Fahad Razak
    Print ISSN: 1549-1277
    Electronic ISSN: 1549-1676
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  • 49
    Publication Date: 2018-06-05
    Description: by Xiaoru Xue, Chuan Xue, Min Tang Recent experiments showed that engineered Escherichia coli colonies grow and self-organize into periodic stripes with high and low cell densities in semi-solid agar. The stripes develop sequentially behind a radially propagating colony front, similar to the formation of many other periodic patterns in nature. These bacteria were created by genetically coupling the intracellular chemotaxis pathway of wild-type cells with a quorum sensing module through the protein CheZ. In this paper, we develop multiscale models to investigate how this intracellular pathway affects stripe formation. We first develop a detailed hybrid model that treats each cell as an individual particle and incorporates intracellular signaling via an internal ODE system. To overcome the computational cost of the hybrid model caused by the large number of cells involved, we next derive a mean-field PDE model from the hybrid model using asymptotic analysis. We show that this analysis is justified by the tight agreement between the PDE model and the hybrid model in 1D simulations. Numerical simulations of the PDE model in 2D with radial symmetry agree with experimental data semi-quantitatively. Finally, we use the PDE model to make a number of testable predictions on how the stripe patterns depend on cell-level parameters, including cell speed, cell doubling time and the turnover rate of intracellular CheZ.
    Print ISSN: 1553-734X
    Electronic ISSN: 1553-7358
    Topics: Biology , Computer Science
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  • 50
    Publication Date: 2018-06-05
    Description: by Izabela Maurício de Rezende, Lívia Sacchetto, Érica Munhoz de Mello, Pedro Augusto Alves, Felipe Campos de Melo Iani, Talita Émile Ribeiro Adelino, Myrian Morato Duarte, Ana Luísa Furtado Cury, André Felipe Leal Bernardes, Tayrine Araujo Santos, Leonardo Soares Pereira, Maria Rita Teixeira Dutra, Dario Brock Ramalho, Benoit de Thoisy, Erna Geessien Kroon, Giliane de Souza Trindade, Betânia Paiva Drumond Background Yellow fever (YF) is endemic in the Brazilian Amazon Basin, and sporadic outbreaks take place outside the endemic area in Brazil. Since 2016, YF epidemics have been occurring in Southeast Brazil, with more than 1,900 human cases and more than 1,600 epizooties of non-human primates (NHPs) reported until April 2018. Previous studies have demonstrated that Yellow fever virus (YFV) causing outbreaks in 2017 formed a monophyletic group. Methodology/Principal findings Aiming to decipher the origin of the YFV responsible for the recent epidemics, we obtained nucleotide sequences of YFV detected in humans (n = 6) and NHPs (n = 10) from Minas Gerais state during 2017–2018. Next, we performed evolutionary analyses and discussed the results in the light of epidemiological records (official numbers of YFV cases at each Brazilian Federative unit, reported by the Brazilian Ministry of Health). Nucleotide sequences of YFV from Southeast Brazil from 2016 to 2018 were highly conserved and formed a monophyletic lineage (BR-YFV_2016/18) within the genotype South America I. Different clusters were observed within lineage YFV-BR_2016/18, one containing the majority of isolates (from humans and NHPs), indicating the sylvatic transmission of YFV. We also detected a cluster characterized by two synapomorphies (amino acid substitutions) that contained YFV only associated with NHP what should be further investigated. The topology of lineage BR-YFV_2016/18 was congruent with epidemiological and temporal patterns of the ongoing epidemic. YFV isolates detected in 2016, in São Paulo state were located in the most basal position of the lineage, followed by the isolates from Minas Gerais and Espírito Santo obtained in 2017 and 2018. The most recent common ancestor of the lineage BR-YFV_2016/18 dated to 2015 (95% credible intervals = 2014–2016), in a period that was coincident with the reemergence of YFV in the Midwest region of Brazil. Conclusions The results demonstrated a single introduction of YFV in the Southeast region and the silent viral circulation before the onset of the outbreaks in 2016. Evolutionary analyses combined with epidemiological records supported the idea that BR-YFV_2016/18 was probably introduced from the Midwest into the Southeast region, possibly in São Paulo state. The persistence of YFV in the Southeast region, causing epidemics from 2016 to 2018, suggests that this region presents suitable ecological and climatic conditions for YFV maintenance during the epidemic and interepidemic seasons. This fact poses risks for the establishing of YF enzootic cycles and epidemics, outside the Amazon Basin in Brazil. YF surveillance and studies of viral dynamics deserve particular attention, especially in Midwest, Southeast and neighbor regions which are the main areas historically associated with YF outbreaks outside the Amazon Basin. YFV persistence in Southeast Brazil should be carefully considered in the context of public health, especially for public health decision-makers and researchers.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
    Topics: Medicine
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  • 51
    Publication Date: 2018-06-05
    Description: by Julien Riou, Chiara Poletto, Pierre-Yves Boëlle Model-based epidemiological assessment is useful to support decision-making at the beginning of an emerging Aedes -transmitted outbreak. However, early forecasts are generally unreliable as little information is available in the first few incidence data points. Here, we show how past Aedes -transmitted epidemics help improve these predictions. The approach was applied to the 2015–2017 Zika virus epidemics in three islands of the French West Indies, with historical data including other Aedes -transmitted diseases (Chikungunya and Zika) in the same and other locations. Hierarchical models were used to build informative a priori distributions on the reproduction ratio and the reporting rates. The accuracy and sharpness of forecasts improved substantially when these a priori distributions were used in models for prediction. For example, early forecasts of final epidemic size obtained without historical information were 3.3 times too high on average (range: 0.2 to 5.8) with respect to the eventual size, but were far closer (1.1 times the real value on average, range: 0.4 to 1.5) using information on past CHIKV epidemics in the same places. Likewise, the 97.5% upper bound for maximal incidence was 15.3 times (range: 2.0 to 63.1) the actual peak incidence, and became much sharper at 2.4 times (range: 1.3 to 3.9) the actual peak incidence with informative a priori distributions. Improvements were more limited for the date of peak incidence and the total duration of the epidemic. The framework can adapt to all forecasting models at the early stages of emerging Aedes -transmitted outbreaks.
    Print ISSN: 1935-2727
    Electronic ISSN: 1935-2735
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  • 52
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-05
    Description: by George Stratigopoulos, Maria Caterina De Rosa, Charles A. LeDuc, Rudolph L. Leibel, Claudia A. Doege Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 (Cas9) has become the tool of choice for genome editing. Despite the fact that it has evolved as a highly efficient means to edit/replace coding sequence, CRISPR/Cas9 efficiency for “clean” editing of non-coding DNA remains low. We set out to introduce a single base-pair substitution in two intronic SNPs at the FTO locus without altering nearby non-coding sequence. Substitution efficiency increased up to 10-fold by treatment of human embryonic stem cells (ESC) with non-toxic levels of DMSO (1%) before CRISPR/Cas9 delivery. Treatment with DMSO did not result in CRISPR/Cas9 off-target effects or compromise the chromosomal stability of the ESC. Twenty-four hour treatment of human ESC with DMSO before CRISPR/Cas9 delivery may prove a simple means to increase editing efficiency of non-coding DNA without incorporation of undesirable mutations.
    Electronic ISSN: 1932-6203
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  • 53
    Publication Date: 2018-06-05
    Description: by Shang-Yi Lin, Hung-Pin Tu, Tun-Chieh Chen, Mei-Chiou Shen, Yi-Wen Chiu, Yen-Hsu Chen, Po-Liang Lu Objectives Methicillin-resistant Staphylococcus aureus (MRSA) infections in the hemodialysis (HD) population are epidemiologically classified as healthcare-associated infections. The data about the clinical impact and bacterial characteristics of hospital-onset (HO)- and community-onset (CO)-MRSA in HD patients are scarce. The current study analyzed the difference in the clinical and molecular characteristics of HO-MRSA and CO-MRSA. Methods We performed a retrospective review and molecular analysis of clinical isolates from 106 HD patients with MRSA bacteremia from 2009 to 2014. CA genotypes were defined as isolates carrying the SCC mec type IV or V, and HA genotypes were defined as isolates harboring SCC mec type I, II, or III. Results CO-MRSA infections occurred in 76 patients, and 30 patients had HO-MRSA infections. There was no significant difference in the treatment failure rates between patients with CO-MRSA infections and those with HO-MRSA infections. CA genotypes were associated with less treatment failure (odds ratio [OR]: 0.18; 95% confidence interval [95% CI], 0.07–0.49; p = 0.001). For isolates with a vancomycin minimum inhibitory concentration (MIC) 〈 1.5 mg/L, the multivariate analysis revealed that HA genotypes and cuffed tunneled catheter use were associated with treatment failure. For isolates with a vancomycin MIC ≥1.5 mg/L, the only risk factor for treatment failure was a higher Pitt score (OR: 1.76; 95% CI, 1.02–3.05; p = 0.043). Conclusion CA genotypes, but not the epidemiological classification of CO-MRSA, impacted the clinical outcome of MRSA bacteremia in the HD population.
    Electronic ISSN: 1932-6203
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  • 54
    Publication Date: 2018-06-05
    Description: by Pratchaya Pramoj Na Ayutthaya, Chanpen Chanchao, Surasak Chunsrivirot Honey from the European honeybee, Apis mellifera , is produced by α-glucosidases (HBGases) and is widely used in food, pharmaceutical, and cosmetic industries. Categorized by their substrate specificities, HBGases have three isoforms: HBGase I, II and III. Previous experimental investigations showed that wild-type HBGase III from Apis mellifera (WT) preferred sucrose to maltose as a substrate, while the Y227H mutant (MT) preferred maltose to sucrose. This mutant can potentially be used for malt hydrolysis because it can efficiently hydrolyze maltose. In this work, to elucidate important factors contributing to substrate specificity of this enzyme and gain insight into how the Y227H mutation causes substrate specificity change, WT and MT homology models were constructed, and sucrose/maltose was docked into active sites of the WT and MT. AMBER14 was employed to perform three independent molecular dynamics runs for these four complexes. Based on the relative binding free energies calculated by the MM-GBSA method, sucrose is better than maltose for WT binding, while maltose is better than sucrose for MT binding. These rankings support the experimentally observed substrate specificity that WT preferred sucrose to maltose as a substrate, while MT preferred maltose to sucrose, suggesting the importance of binding affinity for substrate specificity. We also found that the Y227H mutation caused changes in the proximities between the atoms necessary for sucrose/maltose hydrolysis that may affect enzyme efficiency in the hydrolysis of sucrose/maltose. Moreover, the per-residue binding free energy decomposition results show that Y227/H227 may be a key residue for preference binding of sucrose/maltose in the WT/MT active site. Our study provides important and novel insight into the binding of sucrose/maltose in the active site of Apis mellifera HBGase III and into how the Y227H mutation leads to the substrate specificity change at the molecular level. This knowledge could be beneficial in the design of this enzyme for increased production of desired products.
    Electronic ISSN: 1932-6203
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  • 55
    Publication Date: 2018-06-05
    Description: by Jennifer Spohrs, Julia E. Bosch, Lisa Dommes, Petra Beschoner, Julia C. Stingl, Franziska Geiser, Katharina Schneider, Jörg Breitfeld, Roberto Viviani Functional imaging studies of affective disorders have demonstrated abnormal activity in the amygdala in response to emotionally salient stimuli. Since in other studies this response has been shown to habituate during the scanning session, it is not clear if it may be of use in monitoring disease progression or remission, or in monitoring the effects of therapy, as habituation may confound normalisation of response. We investigated here amygdala activation in healthy participants exposed to displays of emotional facial expressions in a sample of N = 31 individuals assessed twice in an interval of three weeks. At this interval no habituation could be detected, suggesting the validity of this imaging assay in repeated assessments of amygdalar reactivity. However, the fusiform gyrus and the inferior frontal lobes showed decreases in activations that may be related to the role of these areas in encoding visual and emotional aspects of the stimuli.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 56
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-05
    Description: by Ewa Forma, Paweł Jóźwiak, Piotr Ciesielski, Agnieszka Zaczek, Katarzyna Starska, Magdalena Bryś, Anna Krześlak Enhancer of zest homolog 2 (EZH2) is a histone methyltransferase which plays a crucial role in cancer progression by regulation of genes involved in cellular processes such as proliferation, invasion and self-renewal. Activity and biological function of EZH2 are regulated by posttranslational modifications. It is suggested that EZH2 stability may be regulated by O-GlcNAc transferase (OGT), which is an enzyme catalyzing the addition of GlcNAc moieties to target proteins. In this study, we determined the impact of OGT on expression of EZH2 target genes FOXA1 and FOXC1 , that are involved in breast cancer progression. The results of chromatin immunoprecipitation experiments showed that both EZH2 and OGT are targeted to the promoter regions of FOXA1 and FOXC1 and knockdown of EZH2 or OGT affects expression of studied genes in breast non-malignant (MCF10A) and cancer cells (MCF7, T47D and MDA-MB-231). The results showed that OGT silencing affects EZH2 binding to FOXC1 promoter but the effect is cell-context dependent. Despite the slight decrease in EZH2 protein level in cells with OGT depletion, EZH2 binding to FOXC1 was increased. Moreover, OGT binding to promoter regions of FOXA1 and FOXC1 was increased in cells with knockdown of EZH2. Increased expression of FOXA1 and FOXC1 in cells with OGT deregulation was associated with increased acetylation level of histone H3. The results suggest that OGT is involved in regulation of FOXA1 and FOXC1 expression but its role is not associated with regulation of EZH2 protein stability.
    Electronic ISSN: 1932-6203
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  • 57
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    Publication Date: 2018-06-05
    Description: by Md Akter Hussain, Alauddin Bhuiyan, Chi D. Luu, R. Theodore Smith, Robyn H. Guymer, Hiroshi Ishikawa, Joel S. Schuman, Kotagiri Ramamohanarao In this paper, we propose a novel classification model for automatically identifying individuals with age-related macular degeneration (AMD) or Diabetic Macular Edema (DME) using retinal features from Spectral Domain Optical Coherence Tomography (SD-OCT) images. Our classification method uses retinal features such as the thickness of the retina and the thickness of the individual retinal layers, and the volume of the pathologies such as drusen and hyper-reflective intra-retinal spots. We extract automatically, ten clinically important retinal features by segmenting individual SD-OCT images for classification purposes. The effectiveness of the extracted features is evaluated using several classification methods such as Random Forrest on 251 (59 normal, 177 AMD and 15 DME) subjects. We have performed 15-fold cross-validation tests for three phenotypes; DME, AMD and normal cases using these data sets and achieved accuracy of more than 95% on each data set with the classification method using Random Forrest. When we trained the system as a two-class problem of normal and eye with pathology, using the Random Forrest classifier, we obtained an accuracy of more than 96%. The area under the receiver operating characteristic curve (AUC) finds a value of 0.99 for each dataset. We have also shown the performance of four state-of-the-methods for classification the eye participants and found that our proposed method showed the best accuracy.
    Electronic ISSN: 1932-6203
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  • 58
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-05
    Description: by Milena Ilic, Sandra Grujicic Sipetic, Branko Ristic, Irena Ilic Background Although epidemiological evidence for the beneficial effect of low alcohol consumption on myocardial infarction is strong, the impact of heavy drinking episodes is less clear. Objectives The aim of this study was to investigate a possible association between the risk for acute myocardial infarction occurrence and alcohol consumption. Methods Our hospital-based case-control study comprised 374 participants (187 newly diagnosed patients with myocardial infarction and 187 controls, individually matched by gender, age, and place of residence). This study was performed in Kragujevac (a city in Serbia) during 2010. Logistic regression analysis was used to determine odds ratio (OR) with 95% confidence intervals (95% CI). Results The history of alcohol consumption in patients with acute myocardial infarction and their controls did not differ significantly: the percentage of those that were consuming alcohol was slightly higher in cases (54.5%) than in controls (50.3%). The habit of binge drinking during the previous 12 months was significantly more common in cases (25.1%) than in controls (12.8%): adjusted OR = 2.2 (95%CI = 1.2–4.2, p = 0.017), p for trend = 0.015. Analysis of binge drinking by age, gender and place of residence revealed that the increase in risk for acute myocardial infarction was associated with older age (adjusted OR = 5.1, 95%CI = 1.7–15.1, p for trend = 0.010), male gender (adjusted OR = 2.3, 95%CI = 1.1–5.2, p for trend = 0.028) and rural place of residence (adjusted OR = 4.8, 95%CI = 1.3–18.5, p for trend = 0.033). Conclusion Our results suggest that binge drinking is associated with twice the risk for myocardial infarction compared to not drinking. Since consumption of alcohol is very common in the Serbian population, the effect of binge drinking on myocardial infarction should be considered an important public health issue.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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  • 59
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    Publication Date: 2018-06-05
    Description: by Ambrin Sarwar, Günter Brader, Erika Corretto, Gajendar Aleti, Muhammad Abaidullah, Angela Sessitsch, Fauzia Yusuf Hafeez Bacillus spp. produce a broad spectrum of lipopeptide biosurfactants, among which surfactin, iturin and fengycin are widely studied families. The goals of this study were to characterize the biosurfactant activity of Bacillus spp. and to investigate their motility and biofilm formation capabilities. In addition, we extracted lipopeptides from these bacteria to assess their antifungal activities and analyzed these products by mass spectrometry (MS). B . amyloliquefaciens FZB42, Bacillus sp. NH 217 and B . subtilis NH-100 exhibited excellent biosurfactant and surface spreading activities, whereas B . atrophaeus 176s and Paenibacillus polymyxa C1225 showed moderate activity, and B . subtilis 168 showed no activity. Strains FZB42, NH-100, NH-217, 176s and CC125 exhibited excellent biofilm formation capabilities. Lipopeptide extracts displayed good antifungal activity against various phytopathogens and their associated diseases, such as Fusarium moniliforme (rice bakanae disease), Fusarium oxysporum (root rot), Fusarium solani (root rot) and Trichoderma atroviride (ear rot and root rot). Lipopeptide extracts of these strains also showed hemolytic activity, demonstrating their strong potential to produce surfactants. LCMS-ESI analyses identified the presence of surfactin, iturin and fengycin in the extracts of Bacillus strains. Thus, the strains assayed in this study show potential as biocontrol agents against various Fusarium and Trichoderma species.
    Electronic ISSN: 1932-6203
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  • 60
    Publication Date: 2018-06-05
    Description: by Wei Liu, Qin Li, Hui Li, Jia Li, Hai-Jun Wang, Bin Li To examine the 20-year trends in the combined prevalence of overweight and obesity among children aged 0–6 years between 1995 and 2015 in Harbin, China, we selected altogether 49,553 children aged 0–6 years old by using a multistage stratified cluster sampling methods in Harbin, one provincial capital city in northeast China in 1995, 2005 and 2015. Height and weight information of the children were collected. We used the child growth standards of World Health Organization to calculate the Z-scores for body mass index (BMI). Cut-offs recommended by World Health Organization and International Obesity Task Force were used to define overweight and obesity for each children. We found there is no difference between boys’ BMI and girls’ among newborns in each survey point (p〉0.05), but in older age groups, the BMI of boys was higher than that of girls (p
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  • 61
    Publication Date: 2018-06-05
    Description: by Lone Kirkeby, Poul Frost, Torben Bæk Hansen, Susanne Wulff Svendsen Objectives We aimed to determine the prognosis after early MRI on clinical suspicion of scaphoid fracture, hypothesising that MRI pathology is associated with more disability and that MRI pathology and high occupational mechanical hand-arm exposures are associated with slower return to work (RTW). Methods We conducted a follow-up study of a cohort of 469 patients, who were scanned in the period 2006 to 2010. The respondents constituted our cohort for disability analysis and the subset that was in the labour market at the time of the trauma constituted our sub-cohort for RTW analysis. Questionnaires included disability scores, job title, and lifestyle factors. Job titles were linked with a job exposure matrix to estimate occupational exposures. Register information was obtained on time until RTW. We used logistic regression analysis of disability and Cox regression analysis of time until RTW. Results The proportion that responded was 53% (249/469) for the disability analysis and 59% (125/212) for the RTW analysis. The mean age at follow up was 43.5 years, the mean time since trauma was 4.8 years, 53% had injury of the dominant hand, and 54% had MRI pathology. Men constituted 43% of the cohort and 56% of the sub-cohort. MRI pathology was not associated with more disability [e.g., for a 'Disabilities of the Arm Shoulder and Hand'-score ≥20 the odds ratio was 0.58 (95% confidence interval 0.26–1.17)]. Patients without MRI pathology and with low occupational exposures were off work for an average of four weeks. Patients with MRI pathology or high occupational exposures were off work for twice as long time. Conclusion MRI pathology was not associated with more disability. For patients, who were in the labour market at the time of the trauma, MRI pathology and high occupational mechanical hand-arm exposures were associated with slower RTW.
    Electronic ISSN: 1932-6203
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  • 62
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    Publication Date: 2018-06-05
    Description: by Lin Yang, Ai Koyanagi, Lee Smith, Liang Hu, Graham A. Colditz, Adetunji T. Toriola, Guillermo Felipe López Sánchez, Davy Vancampfort, Mark Hamer, Brendon Stubbs, Thomas Waldhör Background We evaluated the associations of handgrip strength and cognitive function in cancer survivors ≥ 60 years old using data from the National Health and Nutrition Examination Survey (NHANES). Methods Data in two waves of NHANES (2011–2014) were aggregated. Handgrip strength in kilogram (kg) was defined as the maximum value achieved using either hand. Two cognitive function tests were conducted among adults 60 years and older. The Animal Fluency Test (AFT) examines categorical verbal fluency (a component of executive function), and the Digital Symbol Substitution test (DSST) assesses processing speed, sustained attention, and working memory. Survey analysis procedures were used to account for the complex sampling design of the NHANES. Multiple linear regression models were used to estimate associations of handgrip strength with cognitive test scores, adjusting for confounders (age, gender, race/ethnicity, education, marital status, smoking status, depressive symptoms and leisure time physical activity). Results Among 383 cancer survivors (58.5% women, mean age = 70.9 years, mean BMI = 29.3 kg/m 2 ), prevalent cancer types were breast (22.9%), prostate (16.4%), colon (6.9%) and cervix (6.2%). In women, each increase in kg of handgrip strength was associated with 0.20 (95% CI: 0.08 to 0.33) higher score on AFT and 0.83 (95% CI: 0.30 to 1.35) higher score on DSST. In men, we observed an inverted U-shape association where cognitive function peaked at handgrip strength of 40–42 kg. Conclusions Handgrip strength, a modifiable factor, appears to be associated with aspects of cognitive functions in cancer survivors. Prospective studies are needed to address their causal relationship.
    Electronic ISSN: 1932-6203
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  • 63
    Publication Date: 2018-06-05
    Description: by Tuan T. Tran, Alvaro L. Pérez-Quintero, Issa Wonni, Sara C. D. Carpenter, Yanhua Yu, Li Wang, Jan E. Leach, Valérie Verdier, Sébastien Cunnac, Adam J. Bogdanove, Ralf Koebnik, Mathilde Hutin, Boris Szurek Most Xanthomonas species translocate Transcription Activator-Like (TAL) effectors into plant cells where they function like plant transcription factors via a programmable DNA-binding domain. Characterized strains of rice pathogenic X . oryzae pv. oryzae harbor 9–16 different tal effector genes, but the function of only a few of them has been decoded. Using sequencing of entire genomes, we first performed comparative analyses of the complete repertoires of TAL effectors, herein referred to as TALomes, in three Xoo strains forming an African genetic lineage different from Asian Xoo . A phylogenetic analysis of the three TALomes combined with in silico predictions of TAL effector targets showed that African Xoo TALomes are highly conserved, genetically distant from Asian ones, and closely related to TAL effectors from the bacterial leaf streak pathogen Xanthomonas oryzae pv. oryzicola ( Xoc ). Nine clusters of TAL effectors could be identified among the three TALomes, including three showing higher levels of variation in their repeat variable diresidues (RVDs). Detailed analyses of these groups revealed recombination events as a possible source of variation among TAL effector genes. Next, to address contribution to virulence, nine TAL effector genes from the Malian Xoo strain MAI1 and four allelic variants from the Burkinabe Xoo strain BAI3, thus representing most of the TAL effector diversity in African Xoo strains, were expressed in the TAL effector-deficient X . oryzae strain X11-5A for gain-of-function assays. Inoculation of the susceptible rice variety Azucena lead to the discovery of three TAL effectors promoting virulence, including two TAL effectors previously reported to target the susceptibility ( S ) gene OsSWEET14 and a novel major virulence contributor, TalB. RNA profiling experiments in rice and in silico prediction of EBEs were carried out to identify candidate targets of TalB, revealing OsTFX1 , a bZIP transcription factor previously identified as a bacterial blight S gene, and OsERF#123 , which encodes a subgroup IXc AP2/ERF transcription factor. Use of designer TAL effectors demonstrated that induction of either gene resulted in greater susceptibility to strain X11-5A. The induction of OsERF#123 by BAI3Δ1, a talB knockout derivative of BAI3, carrying these designer TAL effectors increased virulence of BAI3Δ1, validating OsERF#123 as a new, bacterial blight S gene.
    Print ISSN: 1553-7366
    Electronic ISSN: 1553-7374
    Topics: Medicine
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  • 64
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    Publication Date: 2018-06-05
    Description: by Shannon K. Esher, Kyla S. Ost, Maria A. Kohlbrenner, Kaila M. Pianalto, Calla L. Telzrow, Althea Campuzano, Connie B. Nichols, Carol Munro, Floyd L. Wormley Jr., J. Andrew Alspaugh The human fungal pathogen, Cryptococcus neoformans , dramatically alters its cell wall, both in size and composition, upon entering the host. This cell wall remodeling is essential for host immune avoidance by this pathogen. In a genetic screen for mutants with changes in their cell wall, we identified a novel protein, Mar1, that controls cell wall organization and immune evasion. Through phenotypic studies of a loss-of-function strain, we have demonstrated that the mar1Δ mutant has an aberrant cell surface and a defect in polysaccharide capsule attachment, resulting in attenuated virulence. Furthermore, the mar1Δ mutant displays increased staining for exposed cell wall chitin and chitosan when the cells are grown in host-like tissue culture conditions. However, HPLC analysis of whole cell walls and RT-PCR analysis of cell wall synthase genes demonstrated that this increased chitin exposure is likely due to decreased levels of glucans and mannans in the outer cell wall layers. We observed that the Mar1 protein differentially localizes to cellular membranes in a condition dependent manner, and we have further shown that the mar1Δ mutant displays defects in intracellular trafficking, resulting in a mislocalization of the β-glucan synthase catalytic subunit, Fks1. These cell surface changes influence the host-pathogen interaction, resulting in increased macrophage activation to microbial challenge in vitro . We established that several host innate immune signaling proteins are required for the observed macrophage activation, including the Card9 and MyD88 adaptor proteins, as well as the Dectin-1 and TLR2 pattern recognition receptors. These studies explore novel mechanisms by which a microbial pathogen regulates its cell surface in response to the host, as well as how dysregulation of this adaptive response leads to defective immune avoidance.
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  • 65
    Publication Date: 2018-06-05
    Description: by Maria Albertina Romaniuk, Alberto Carlos Frasch, Alejandro Cassola Trypanosomes, protozoan parasites of medical importance, essentially rely on post-transcriptional mechanisms to regulate gene expression in insect vectors and vertebrate hosts. RNA binding proteins (RBPs) that associate to the 3’-UTR of mature mRNAs are thought to orchestrate master developmental programs for these processes to happen. Yet, the molecular mechanisms by which differentiation occurs remain largely unexplored in these human pathogens. Here, we show that ectopic inducible expression of the RBP TcUBP1 promotes the beginning of the differentiation process from non-infective epimastigotes to infective metacyclic trypomastigotes in Trypanosoma cruzi . In early-log epimastigotes TcUBP1 promoted a drop-like phenotype, which is characterized by the presence of metacyclogenesis hallmarks, namely repositioning of the kinetoplast, the expression of an infective-stage virulence factor such as trans -sialidase, increased resistance to lysis by human complement and growth arrest. Furthermore, TcUBP1-ectopic expression in non-infective late-log epimastigotes promoted full development into metacyclic trypomastigotes. TcUBP1-derived metacyclic trypomastigotes were infective in cultured cells, and developed normally into amastigotes in the cytoplasm. By artificial in vivo tethering of TcUBP1 to the 3’ untranslated region of a reporter mRNA we were able to determine that translation of the reporter was reduced by 8-fold, while its mRNA abundance was not significantly compromised. Inducible ectopic expression of TcUBP1 confirmed its role as a translational repressor, revealing significant reduction in the translation rate of multiple proteins, a reduction of polysomes, and promoting the formation of mRNA granules. Expression of TcUBP1 truncated forms revealed the requirement of both N and C-terminal glutamine-rich low complexity sequences for the development of the drop-like phenotype in early-log epimastigotes. We propose that a rise in TcUBP1 levels, in synchrony with nutritional deficiency, can promote the differentiation of T . cruzi epimastigotes into infective metacyclic trypomastigotes.
    Print ISSN: 1553-7366
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  • 66
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    Publication Date: 2018-06-06
    Description: by Kazutaka Maeda, Jun Kunimatsu, Okihide Hikosaka Choosing valuable objects and rewarding actions is critical for survival. While such choices must be made in a way that suits the animal’s circumstances, the neural mechanisms underlying such context-appropriate behavior are unclear. To address this question, we devised a context-dependent reward-seeking task for macaque monkeys. Each trial started with the appearance of one of many visual scenes containing two or more objects, and the monkey had to choose the good object by saccade to get a reward. These scenes were categorized into two dimensions of emotional context: dangerous versus safe and rich versus poor. We found that many amygdala neurons were more strongly activated by dangerous scenes, by rich scenes, or by both. Furthermore, saccades to target objects occurred more quickly in dangerous than in safe scenes and were also quicker in rich than in poor scenes. Thus, amygdala neuronal activity and saccadic reaction times were negatively correlated in each monkey. These results suggest that amygdala neurons facilitate targeting saccades predictably based on aspects of emotional context, as is necessary for goal-directed and social behavior.
    Print ISSN: 1544-9173
    Electronic ISSN: 1545-7885
    Topics: Biology
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  • 67
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-06
    Description: by The PLOS ONE Editors
    Electronic ISSN: 1932-6203
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  • 68
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    Publication Date: 2018-06-06
    Description: by Fabian Wunderlich, Daniel Memmert Betting odds are frequently found to outperform mathematical models in sports related forecasting tasks, however the factors contributing to betting odds are not fully traceable and in contrast to rating-based forecasts no straightforward measure of team-specific quality is deducible from the betting odds. The present study investigates the approach of combining the methods of mathematical models and the information included in betting odds. A soccer forecasting model based on the well-known ELO rating system and taking advantage of betting odds as a source of information is presented. Data from almost 15.000 soccer matches (seasons 2007/2008 until 2016/2017) are used, including both domestic matches (English Premier League, German Bundesliga, Spanish Primera Division and Italian Serie A) and international matches (UEFA Champions League, UEFA Europe League). The novel betting odds based ELO model is shown to outperform classic ELO models, thus demonstrating that betting odds prior to a match contain more relevant information than the result of the match itself. It is shown how the novel model can help to gain valuable insights into the quality of soccer teams and its development over time, thus having a practical benefit in performance analysis. Moreover, it is argued that network based approaches might help in further improving rating and forecasting methods.
    Electronic ISSN: 1932-6203
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  • 69
    Publication Date: 2018-06-06
    Description: by Jian Huang, Qisheng Han, Junjian Li Ectomycorrhizal (ECM) fungal propagule bank could facilitate the regeneration and plantation of seedlings in disturbed area. In this study, Masson pine ( Pinus massoniana ) seedlings were used to bait the ECM fungal propagule bank buried in the soils collected from a manganese (Mn) mine wasteland and a non-polluted area in China. After 6-month growth, we found the seedlings grown in the Mn mine soil (Mn:3200 mg kg -1 ) did not display any toxicity symptoms. Based on morphotyping and ITS-PCR sequencing, we identified a total of 16 ECM fungal OTUs (operative taxonomic units) at 97% similarity threshold, among which 11 OTUs were recovered in the Mn mine soils and 14 in the non-polluted soil. Two soil types shared 9 OTUs and both of them were dominated by a Tylospora sp. Based on those soil propagule banks in Masson pine forests reported in previous, we speculated that some Atheliaceae species may be preferred in the soil propagule bank of some pine species, such as Masson pine. In addition, NMDS ordination displayed geographical position effects on soil propagule banks in five Masson pine forest from three sites at regional scale. In conclusion, Masson pine ECM seedlings could grow well in the Mn wasteland as a suitable tree species used for reforestation application in Mn mineland, in addition, Mn pollution did not alter the dominant ECM fungal species in the soil propagule banks.
    Electronic ISSN: 1932-6203
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  • 70
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    Publication Date: 2018-06-06
    Description: by Paula von Spreckelsen, Klaske A. Glashouwer, Elise C. Bennik, Ineke Wessel, Peter J. de Jong Consistent with the view that disgust might be involved in persistent body dissatisfaction, there is preliminary evidence showing a positive correlation between measures of negative body image and indices of both trait disgust and self-directed disgust. In two correlational studies among undergraduates ( N = 577 and N = 346, respectively) we aimed at replicating and extending these findings by testing a series of critical relationships, which follow from our hypotheses that 1) trait disgust propensity would increase the risk of developing a negative body image by increasing the likelihood of feeling self-disgust, and 2) trait disgust sensitivity would heighten the impact of self-disgust on the development of persistent negative body appraisals. Replicating previous research, both studies showed that negative body image was positively related to self-disgust, disgust propensity and disgust sensitivity. Mediation analyses showed that, in line with our model, self-disgust partly accounted for the association between disgust propensity and negative body image. Although disgust sensitivity showed an independent relationship with body image, disgust sensitivity did not moderate the association between self-disgust and negative body image. All in all, findings are consistent with the view that self-disgust-induced avoidance may contribute to persistent negative body appraisals.
    Electronic ISSN: 1932-6203
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  • 71
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    Publication Date: 2018-06-06
    Description: by Sebsibe Tadesse, Fikre Enqueselassie, Seifu Hagos Introduction Spatial targeting is advocated as an effective method that contributes for achieving tuberculosis control in high-burden countries. However, there is a paucity of studies clarifying the spatial nature of the disease in these countries. This study aims to identify the location, size and risk of purely spatial and space-time clusters for high occurrence of tuberculosis in Gurage Zone, Southern Ethiopia during 2007 to 2016. Materials and methods A total of 15,805 patient data that were retrieved from unit TB registers were included in the final analyses. The spatial and space-time cluster analyses were performed using the global Moran’s I , Getis-Ord Gi* and Kulldorff’s scan statistics. Results Eleven purely spatial and three space-time clusters were detected ( P 〈 0.001).The clusters were concentrated in border areas of the Gurage Zone. There were considerable spatial variations in the risk of tuberculosis by year during the study period. Conclusions This study showed that tuberculosis clusters were mainly concentrated at border areas of the Gurage Zone during the study period, suggesting that there has been sustained transmission of the disease within these locations. The findings may help intensify the implementation of tuberculosis control activities in these locations. Further study is warranted to explore the roles of various ecological factors on the observed spatial distribution of tuberculosis.
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  • 72
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    Publication Date: 2018-06-06
    Description: by Fuqiang Zhao, Marie A. Holahan, Xiaohai Wang, Jason M. Uslaner, Andrea K. Houghton, Jeffrey L. Evelhoch, Christopher T. Winkelmann, Catherine D. G. Hines Studies in rodents show that olfactory processing in the principal neurons of olfactory bulb (OB) and piriform cortex (PC) is controlled by local inhibitory interneurons, and glutamate NMDA receptor plays a role in this inhibitory control. It is not clear if findings from studies in rodents translate to olfactory processing in nonhuman primates (NHPs). In this study, the effect of the glutamate NMDA receptor antagonist MK801 on odorant-induced olfactory responses in the OB and PC of anesthetized NHPs (rhesus monkeys) was investigated by cerebral blood volume (CBV) fMRI. Isoamyl-acetate was used as the odor stimulant. For each NHP, sixty fMRI measurements were made during a 4-h period, with each 4-min measurement consisting of a 1-min baseline period, a 1-min odor stimulation period, and a 2-min recovery period. MK801 (0.3 mg/kg) was intravenously delivered 1 hour after starting fMRI. Before MK801 injection, olfactory fMRI activations were observed only in the OB, not in the PC. After MK801 injection, olfactory fMRI activations in the OB increased, and robust olfactory fMRI activations were observed in the PC. The data indicate that MK801 enhances the olfactory responses in both the OB and PC. The enhancement effects of MK801 are most likely from its blockage of NMDA receptors on local inhibitory interneurons and the attenuation of the inhibition onto principal neurons. This study suggests that the mechanism of local inhibitory control of principal neurons in the OB and PC derived from studies in rodents translates to NHPs.
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  • 73
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    Publication Date: 2018-06-06
    Description: by Marco Fiorentino, Fadi A. Tohme, Shu Wang, Raghavan Murugan, Derek C. Angus, John A. Kellum Background Several studies have shown that long-term survival after acute kidney injury (AKI) is reduced even if there is clinical recovery. However, we recently reported that in septic shock patients those that recover from AKI have survival similar to patients without AKI. Here, we studied a cohort with less severe sepsis to examine the effects of AKI on longer-term survival as a function of recovery by discharge. Methods We analyzed patients with community-acquired pneumonia from the Genetic and Inflammatory Markers of Sepsis (GenIMS) cohort. We included patients who developed AKI (KDIGO stages 2–3) and defined renal recovery as alive at hospital discharge with return of SCr to within 150% of baseline without dialysis. Our primary outcome was survival up to 3 years analyzed using Gray’s model. Results Of the 1742 patients who survived to hospital discharge, stage 2–3 AKI occurred in 262 (15%), of which 111 (42.4%) recovered. Compared to recovered patients, patients without recovery were older (75 ±14 vs 69 ±15 years, p
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  • 74
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    Publication Date: 2018-06-06
    Description: by Mari N. Willeman, Sarah E. Mennenga, Ashley L. Siniard, Jason J. Corneveaux, Matt De Both, Lauren T. Hewitt, Candy W. S. Tsang, Jason Caselli, B. Blair Braden, Heather A. Bimonte-Nelson, Matthew J. Huentelman Enzastaurin is a Protein Kinase C-β selective inhibitor that was developed to treat cancers. Protein Kinase C-β is an important enzyme for a variety of neuronal functions; in particular, previous rodent studies have reported deficits in spatial and fear-conditioned learning and memory with lower levels of Protein Kinase C-β. Due to Enzastaurin’s mechanism of action, the present study investigated the consequences of Enzastaurin exposure on learning and memory in 12-month-old Fischer-344 male rats. Rats were treated daily with subcutaneous injections of either vehicle or Enzastaurin, and behaviorally tested using the spatial reference memory Morris Water Maze. Rats treated with Enzastaurin exhibited decreased overnight retention and poorer performance on the latter testing day, indicating a mild, but significant, memory impairment. There were no differences during the probe trial indicating that all animals were able to spatially localize the platform to the proper quadrant by the end of testing. RNA isolated from the hippocampus was analyzed using Next Generation Sequencing (Illumina). No statistically significant transcriptional differences were noted. Our findings suggest that acute Enzastaurin treatment can impair hippocampal-based learning and memory performance, with no effects on transcription in the hippocampus. We propose that care should be taken in future clinical trials that utilize Protein Kinase C-ß inhibitors, to monitor for possible cognitive effects, future research should examine if these effects are fully reversible.
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  • 75
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    Publication Date: 2018-06-06
    Description: by Xiaoli Wang, Liang Li, Xing Wei, Yuanyuan Wang, Hui Zhang, Ao Shi, Tao Liu, Xiaodi Yang, Qiang Fang Trichinella spiralis mainly dwells in the muscle tissue of its host and is the main causative agent of trichinellosis in humans. Nitric oxide (NO), an important intracellular signaling molecule that may restrict pathogen growth in infected hosts, has been known for its anti-pathogenic activity, including resistance to T . spiralis . Herein, we applied label-free analysis to investigate the effect of sodium nitroprusside (SNP, a NO donor compound) on the proteome of T . spiralis muscle larvae (ML), followed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway cluster analyses. Of the 1,476 proteins detected in the ML, 121 proteins showed differential expression, including 50 significantly upregulated and 71 downregulated proteins. The functions of the 108 annotated proteins were primarily related to signal transduction, transcription/translation, material metabolism, protein synthesis/assembly/degradation, and stress/defense/antioxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) assay verified that FRMD5 and CUT-1 gene expression levels were significantly increased, while COX2 gene expression level was significantly decreased. GO annotation and KEGG pathway analyses showed that the majority of differentially expressed proteins were mainly involved in the molecular function of the catalytic activity, biological process of the immune system process, metabolic process, cellular component organization, biological adhesion, and cellular component of the macromolecular complex. Our results demonstrate the first comprehensive protein expression profile of the ML in response to NO stress and provide novel references for understanding the potential mechanism underlying the effects of NO on trichinellosis.
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  • 76
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-06
    Description: by Tatsuya Hayashi, William N. Krebs, Megumi Saito-Kato, Yoshihiro Tanimura Fossil evidence indicates that modern assemblages of temperate nonmarine planktonic diatoms began near the middle/late Miocene boundary when the genus Actinocyclus , an important constituent of lacustrine planktonic diatom assemblages during the early to middle Miocene, was replaced by genera of the family Stephanodiscaceae. This floral turnover has been confirmed in many regions of the world, except eastern Asia where taxonomic data about early and middle Miocene planktonic diatom assemblages have until recently been scarce. Our analysis of Lower and Middle Miocene lacustrine diatomaceous rocks in Japan confirms that species of nonmarine Actinocyclus were important constituents of lake phytoplankton there as well. The appearance of nonmarine Actinocyclus species near the beginning of the Miocene may have resulted from the introduction of euryhaline species into lacustrine environments during a highstand of sea level at that time. Similarly, it is possible that species of Stephanodiscaceae evolved from marine thalassiosiroid ancestors that invaded high latitude lacustrine environments during multiple Paleogene highstands, resulting in a polyphyletic origin of the family. The turnover from nonmarine Actinocyclus to Stephanodiscaceae genera near the middle/late Miocene boundary may be linked to a contemporaneous increase in silica concentrations in lakes caused by active volcanism, increased weathering of silicate rocks due to orogeny, and the expansion of C 4 grasslands. This turnover may also have been influenced by enhanced seasonal environmental changes in the euphotic zone caused by the initiation of monsoon conditions and a worldwide increase in meridional temperature gradients during the late Miocene. Morphological characteristics of Stephanodiscaceae genera, such as strutted processes and small size, suggest their species were better adapted to seasonal environmental changes than nonmarine species of Actinocyclus because of their superiority in floating and drifting capabilities and possibly metabolism, intrinsic growth rate, and reproductivity. As climates deteriorated during the late Miocene, Stephanodiscaceae species may have spread from high latitudes to temperate lakes where they diversified, ultimately displacing Actinocyclus .
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Public Library of Science (PLoS)
    Publication Date: 2018-06-06
    Description: by Iain J. Staniland, Norman Ratcliffe, Philip N. Trathan, Jaume Forcada Leopard seals are an important Antarctic apex predator that can affect marine ecosystems through local predation. Here we report on the successful use of micro geolocation logging sensor tags to track the movements, and activity, of four leopard seals for trips of between 142–446 days including one individual in two separate years. Whilst the sample size is small the results represent an advance in our limited knowledge of leopard seals. We show the longest periods of tracking of leopard seals’ migratory behaviour between the pack ice, close to the Antarctic continent, and the sub-Antarctic island of South Georgia. It appears that these tracked animals migrate in a directed manner towards Bird Island and, during their residency, use this as a central place for foraging trips as well as exploiting the local penguin and seal populations. Movements to the South Orkney Islands were also recorded, similar to those observed in other predators in the region including the krill fishery. Analysis of habitat associations, taking into account location errors, indicated the tracked seals had an affinity for shallow shelf water and regions of sea ice. Wet and dry sensors revealed that seals hauled out for between 22 and 31% of the time with maximum of 74 hours and a median of between 9 and 11 hours. The longest period a seal remained in the water was between 13 and 25 days. Fitting GAMMs showed that haul out rates changed throughout the year with the highest values occurring during the summer which has implications for visual surveys. Peak haul out occurred around midday for the months between October and April but was more evenly spread across the day between May and September. The seals’ movements between, and behaviour within, areas important to breeding populations of birds and other seals, coupled with the dynamics of the region’s fisheries, shows an understanding of leopard seal ecology is vital in the management of the Southern Ocean resources.
    Electronic ISSN: 1932-6203
    Topics: Medicine , Natural Sciences in General
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    Publication Date: 2018-06-06
    Description: by Zahra Hosseininejad, Mehdi Sharif, Shahabeddin Sarvi, Afsaneh Amouei, Seyed Abdollah Hosseini, Tooran Nayeri Chegeni, Davood Anvari, Reza Saberi, Shaban Gohardehi, Azadeh Mizani, Mitra Sadeghi, Ahmad Daryani Background Toxoplasmosis is a cosmopolitan infection caused by an intracellular obligatory protozoan, Toxoplasma gondii . Infection to this parasite in immunocompetent patients is usually asymptomatic, but today it is believed that the infection can be a risk factor for a variety of diseases, including rheumatoid arthritis (RA). RA is an autoimmune disease and the most common type of inflammatory arthritis that is a major cause of disability. The aim of this systematic review and meta-analysis was to address the association between RA and toxoplasmosis in light of the available research. Methods Based on the keywords, a systematic search of eight databases was conducted to retrieve the relevant English-language articles. Then, the studies were screened based on the inclusion and exclusion criteria. The random effect model was used to calculate the odds ratio (OR) using forest plot with 95% confidence interval (CI). Results Overall, 4168 Individual, extracted from 9 articles were included for systematic review evaluation, with 1369 RA patients (46% positive toxoplasmosis) and 2799 individuals as controls (21% positive toxoplasmosis). Then, eight articles (10 datasets) were used for meta-analysis (1244 rheumatoid arthritis patients and 2799 controls). By random effect model, the combined OR was 3.30 (95% CI: 2.05 to 5.30) with P 〈 0.0001. Conclusion Although toxoplasmosis could be considered as a potential risk factor for rheumatoid arthritis, more a