Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Elsevier  (1,429,804)
Collection
  • 1
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters B 294 (1992), S. 466-478 
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters B 317 (1993), S. 474-484 
    ISSN: 0370-2693
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    facet.materialart.
    Unknown
    New York, NY : Elsevier
    Keywords: Biochemistry ; Enzymes
    Notes: This is a series title, single volumes see link below.
    ISSN: 1557-7988
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Unknown
    Edinburgh : Elsevier
    Call number: ALLG-BERUF-Q180:084(7)
    Notes: For online access to this volume please contact the library staff in room D124 (phone 3661, e-mail: http://www.dkfz.de/de/zbib/mitarbeiter/kontakt/fernleihe.php)
    Pages: vi, 213 p.
    Edition: 7th ed.
    ISBN: 9780702074936
    Signatur Availability
    ALLG-BERUF-Q180:084(7) available
    BibTip Others were also interested in ...
  • 5
    Unknown
    Amsterdam : Elsevier
    Call number: QZ200:575(3)/3
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 605 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
    Signatur Availability
    QZ200:575(3)/3 available
    BibTip Others were also interested in ...
  • 6
    Unknown
    Amsterdam : Elsevier
    Call number: QZ200:575(3)/2
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 577 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
    Signatur Availability
    QZ200:575(3)/2 available
    BibTip Others were also interested in ...
  • 7
    Unknown
    München : Elsevier
    Call number: QZ269:204(3)
    Keywords: Neoplasms / radiotherapy ; Radiotherapy
    Pages: xxviii, 419 p. : ill.
    Edition: 3. Aufl.
    ISBN: 9783437232923
    Signatur Availability
    QZ269:204(3) available
    BibTip Others were also interested in ...
  • 8
    Unknown
    Amsterdam : Elsevier
    Call number: QZ200:575(3)/1
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 585 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
    Signatur Availability
    QZ200:575(3)/1 available
    BibTip Others were also interested in ...
  • 9
    Call number: QZ269:203(3)
    Keywords: Radiation Oncology / methods ; Neoplasms / radiotherapy
    Pages: xxviii, 713 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128141281
    Signatur Availability
    QZ269:203(3) available
    BibTip Others were also interested in ...
  • 10
    Unknown
    München : Elsevier
    Call number: WN180:10(5)
    Pages: ix, 141 p. : ill.
    Edition: 5. Aufl.
    ISBN: 9783437422973
    Signatur Availability
    WN180:10(5) available
    BibTip Others were also interested in ...
  • 11
    Publication Date: 2018-05-05
    Description: Publication date: Available online 3 May 2018 Source: Neuron Author(s): Padhraig Gormley, Mitja I. Kurki, Marjo Eveliina Hiekkala, Kumar Veerapen, Paavo Häppölä, Adele A. Mitchell, Dennis Lal, Priit Palta, Ida Surakka, Mari Anneli Kaunisto, Eija Hämäläinen, Salli Vepsäläinen, Hannele Havanka, Hanna Harno, Matti Ilmavirta, Markku Nissilä, Erkki Säkö, Marja-Liisa Sumelahti, Jarmo Liukkonen, Matti Sillanpää, Liisa Metsähonkala, Seppo Koskinen, Terho Lehtimäki, Olli Raitakari, Minna Männikkö, Caroline Ran, Andrea Carmine Belin, Pekka Jousilahti, Verneri Anttila, Veikko Salomaa, Ville Artto, Markus Färkkilä, Heiko Runz, Mark J. Daly, Benjamin M. Neale, Samuli Ripatti, Mikko Kallela, Maija Wessman, Aarno Palotie Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71–1.81, p = 1.7 × 10 −109 ) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25–1.38, p = 7.2 × 10 −17 ). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine. Teaser Gormley et al. use polygenic risk scores to show that common variation, captured by genome-wide association studies, in combination contributes to the aggregation of migraine in families. The results may have similar implications for other complex traits in general.
    Print ISSN: 0896-6273
    Electronic ISSN: 1097-4199
    Topics: Biology , Medicine
    Published by Elsevier on behalf of Cell Press.
    Signatur Availability
    BibTip Others were also interested in ...
  • 12
    Publication Date: 2018-05-05
    Description: Publication date: Available online 3 May 2018 Source: Neuron Author(s): Chengbo Meng, Jingheng Zhou, Amy Papaneri, Teja Peddada, Karen Xu, Guohong Cui To achieve simultaneous measurement of multiple cellular events in molecularly defined groups of neurons in vivo , we designed a spectrometer-based fiber photometry system that allows for spectral unmixing of multiple fluorescence signals recorded from deep brain structures in behaving animals. Using green and red Ca 2+ indicators differentially expressed in striatal direct- and indirect-pathway neurons, we were able to simultaneously monitor the neural activity in these two pathways in freely moving animals. We found that the activities were highly synchronized between the direct and indirect pathways within one hemisphere and were desynchronized between the two hemispheres. We further analyzed the relationship between the movement patterns and the magnitude of activation in direct- and indirect-pathway neurons and found that the striatal direct and indirect pathways coordinately control the dynamics and fate of movement. Teaser Using a new method for simultaneous multi-color fluorescence measurements, Meng et al. show that neural activities are synchronized between two parallel striatal pathways, and the magnitude of activation in these two pathways coordinately determines the dynamics and fate of movement.
    Print ISSN: 0896-6273
    Electronic ISSN: 1097-4199
    Topics: Biology , Medicine
    Published by Elsevier on behalf of Cell Press.
    Signatur Availability
    BibTip Others were also interested in ...
  • 13
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Louis Marcellin, Pierre Delorme, Marie Pierre Bonnet, Gilles Grange, Gilles Kayem, Vassilis Tsatsaris, François Goffinet Background Abnormally invasive placentation is the leading cause of obstetric hysterectomy and can cause poor to disastrous maternal outcomes. Most previous studies of peripartum management and maternal morbidity have included variable proportions of severe and less severe cases. Objective The aim of this study was to compare maternal morbidity from placenta percreta and accreta. Study design This retrospective study at a referral center in Paris includes all women with abnormally invasive placentation from 2003 to 2017. Placenta percreta and accreta were diagnosed histologically or clinically. When placenta percreta was suspected before birth, a conservative approach leaving the placenta in situ was proposed because of the intraoperative risk of cesarean delivery. When placenta accreta was suspected, parents were offered a choice of a conservative approach or an attempt to remove the placenta, to be followed in case of failure by hysterectomy. Maternal outcomes were compared between women with placenta percreta and those with placenta accreta/increta. The primary outcome measure was a composite criterion of severe acute maternal morbidity including at least one of the following: hysterectomy during cesarean delivery, delayed hysterectomy, transfusion of ≥ 10 units of packed red blood cells, septic shock, acute kidney injury, cardiovascular failure, maternal transfer to intensive care, or death. Results Of the 156 women included, 51 had placenta percreta and 105 placenta accreta. Abnormally invasive placentation was suspected antenatally nearly four times more frequently in the percreta than the accreta group (96.1% (49/51) vs. 25.7% (27/105), P 〈0.01). Among the 76 women with antenatally suspected abnormally invasive placentation (48.7%), the rate of antenatal decisions for conservative management was higher in the percreta than the accreta group (100% (49/49) vs. 40.7% (11/27), P 〈0.01). The composite maternal morbidity rate was significantly higher in the percreta than the accreta group (86.3% (44/51) vs. 28/105 (26.7%), P 〈0.001). A secondary analysis restricted to women with an abnormally invasive placentation diameter > 6 cm showed similar results (86.0% (43/50) vs. 48.7% (19/38), P 〈0.01). The rate of hysterectomy during cesareans was significantly higher in the percreta than the accreta group (52.9% (27/51) vs. 20.9% (22/105), P 〈 0.01) as was the total hysterectomy rate (43/51 (84.3%) vs. 23.8% (25/105), P 〈0.01). Conclusion Severe maternal morbidity is much more frequent in women with placenta percreta than with placenta accreta, despite multidisciplinary planning, management in a referral center, and better antenatal suspicion.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 14
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Azhar Jabareen, Manal Suleman, Aya Abu-Jaafar, Mahmoud Huleihel HTLV-1 and HIV-1 are retroviruses involved in different human diseases. However, following infection, these viruses inter into a latent state. Tax and Tat are regarded as trans-activators of HTLV-1 and HIV-1 respectively. As it known, during the latent state the infected cells contain low Tax and Tat protein levels, so the activation of these viruses must be independent of these proteins. Here we focus on exploring the mechanism of activation of these viruses by 12-O-tetradecanoylphorbol-13-acetate (TPA), which is a potent activator of protein kinase C (PKC) and considered as a stress-inducing agent. Our results showed that short exposure to TPA considerably stimulated only the HIV-1 LTR expression, while long exposure stimulated only the HTLV-1 LTR and that their activation is agonized or antagonized by PKC respectively. It was found that TPA induced interaction between the transcriptional factors Sp1 and P53 producing Sp1-p53 complex which strongly interacted with c-Jun only after short exposure to TPA. In addition, TPA treatment highly induced the expression of CREB which attached to the Sp1-p53 complex mainly after a long exposure to TPA. A strong binding of sp1, p53 and CREB proteins with HTLV-1 LTR and strong binding of NF-κB with HIV-1 LTR were observed after long (24 h) and short (6 h) exposures to TPA respectively by Chip assay. These results support the possibility that sp1, p53 and CREB are involved in the TPA induced HTLV-1 LTR expression while TPA activation of HIV-1 LTR seems to be dependent on PKC activity through the NF-κB pathway.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 15
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: Analytical Biochemistry Author(s): Marie K. Schwinn, Trish Hoang, Xiaofeng Yang, Xiansi Zhao, Jingya Ma, Ping Li, Keith V. Wood, William D. Mallender, Michael E. Bembenek, Zhong-Hua Yan Neddylation is a posttranslational modification that regulates protein stability, activity, and subcellular localization. Here, we describe a new tool for exploring the neddylation cycle of cullin1 (Cul1) directly in a cellular context. This assay utilizes the NanoLuc ® Binary Technology (NanoBiT) to monitor the covalent neddylation status of Cul1. A stable clonal cell line derived from HEK293 was developed that expressed a C-terminus LgBiT tagged-Cul1 and N-terminus SmBiT tagged-Nedd8. Using this cell line, we screened inhibitors that are known to disrupt Nedd8 biology and demonstrated that both inhibitors of Nedd8-activating enzyme (NAE) and Constitutive photomorphogenesis 9 signalosome (CSN) complex produce concentration and time dependent signal decreases and increases, respectively. The kinetics of both responses could be monitored in real time and demonstrated that modulation of the Nedd8 pathway occurs rapidly. Further characterization of the cellular components of this cell line was performed in order to quantify the various levels of Cul1, Nedd8 and NAE and determined to be near endogenous levels. There was no difference between control and stably transfected cell lines in viability studies of NAE and CSN inhibitors. Taken together, these results suggest that the NanoBiT assay can be used to monitor Cul1 neddylation specifically and in real time.
    Print ISSN: 0003-2697
    Electronic ISSN: 1096-0309
    Topics: Biology , Chemistry and Pharmacology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 16
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Folabomi A. Oladosu, Frank. F. Tu, Saaniya Farhan, Ellen F. Garrison, Nicole D. Steiner, Genevieve E. Roth, Kevin M. Hellman Background Dysmenorrhea is a pervasive pain condition that affects 20-50% of reproductive-aged women. Distension of a visceral organ, such as the uterus, could elicit a viscero-motor reflex resulting in involuntary skeletal muscle activity and referred pain. Although referred abdominal pain mechanisms can contribute to visceral pain, the role of abdominal muscle activity has not yet been investigated within the context of menstrual pain. Objective The goal of this study is to determine if involuntary abdominal muscle activity precedes spontaneous episodes of menstrual cramping pain in dysmenorrheic women and if naproxen administration affects abdominal muscle activity. Study Design Abdominal electromyography activity was recorded from women with severe dysmenorrheic (n=38) and healthy controls (n=10) during menses. Simultaneously, pain was measured in real-time using a squeeze-bulb or visual analog rheostat. Ninety minutes after naproxen administration, abdominal electromyography activity and menstrual pain were re-assessed. As an additional control, women were also recorded off-menses and data were analyzed in relation to random bulb squeezes. Since it is unknown whether mechanisms of menstrual cramps are different in primary or secondary dysmenorrhea/chronic pelvic pain, the relationship between medical history and abdominal muscle activity was examined. To further examine differences in nociceptive mechanisms, pressure pain thresholds were also measured to evaluate changes in widespread pain sensitivity. Results Abdominal muscle activity related to random-bulb squeezing was rarely observed in healthy controls on menses (0.9 ±0.6 episodes / hour) and in dysmenorrhea participants off menses (2.3 ± 0.6 episodes / hour). In dysmenorrheic participants during menses, abdominal muscle activity was frequently associated with bulb-squeezing indicative of menstrual cramping pain (10.8 ± 3.0 episodes / hour; p 〈0.004). Whereas 45% (17/38) of the women with dysmenorrhea had episodes of abdominal muscle activity associated pain, only 13% (5/38) had episodes after naproxen ( p = 0.011). Women with the abdominal muscle activity-associated pain were less likely to have a diagnosis for secondary dysmenorrhea or chronic pelvic pain (2/17) than women without this pain phenotype (10/21; p = 0.034). Similarly, women with the abdominal muscle activity-associated pain phenotype had less non-menstrual pain days/month (0.6 ± 0.5) than women without the phenotype (12.4 ± 0.3; p = 0.002). Women with abdominal muscle activity-associated pain had pressure pain thresholds (22.4 ± 3.0 N) comparable to healthy controls (22.2 ± 3.0 N; p = 0.967). In contrast, women without abdominal muscle activity-associated pain had lower pressure pain thresholds (16.1 ± 1.9 N; p = 0.039). Conclusions Abdominal muscle activity may contribute to cramping pain in primary dysmenorrhea, but is resolvable with naproxen. Dysmenorrheic patients without cramp-associated abdominal muscle activity exhibit widespread pain sensitivity (lower pressure pain thresholds) and are more likely to also have a chronic pain diagnosis, suggesting their cramps are linked to changes in central pain processes. This preliminary study suggests new tools to phenotype menstrual pain and supports the hypothesis that multiple distinct mechanisms may contribute to dysmenorrhea.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 17
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Farhan Chowdhury, Sultan Doğanay, Benjamin J. Leslie, Rishi Singh, Kshitij Amar, Bhavana Talluri, Seongjin Park, Ning Wang, Taekjip Ha Recently, a robust mechanical method has been established to isolate a small subpopulation of highly tumorigenic tumor repopulating cells (TRCs) from parental melanoma cells. In order to characterize the molecular and mechanical properties of TRCs, we utilized the tension gauge tether (TGT) single-molecule platform and investigated force requirements during early cell spreading events. TRCs required the peak single molecular tension of around 40 pN through integrins for initial adhesion like the parental control cells, but unlike the control cells, they did not spread and formed very few mature focal adhesions (FAs). Single molecule resolution RNA quantification of three Rho GTPases showed that downregulation of Cdc42 , but not Rac1 , is responsible for the unusual biophysical features of TRCs and that a threshold level of Cdc42 transcripts per unit cell area is required to initiate cell spreading. Cdc42 overexpression rescued TRC spreading through FA formation and restored the sensitivity to tension cues such that TRCs, like parental control cells, increase cell spreading with increasing single-molecular tension cues. Our single molecule studies identified an unusual biophysical feature of suppressed spreading of TRCs that may enable us to distinguish TRC population from a pool of heterogeneous tumor cell population.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 18
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Eva Källberg, Sahar Tahvili, Fredrik Ivars, Tomas Leanderson We show here that increased S100A8 and S100A9 protein expression is induced in spleen of animals with active inflammation or with inoculated tumors. In tumor bearing animals an increased expression was also detected in the lung. To further analyze the induced proteins, we performed chemical cross-linking followed by Western blotting. We observed in protein extracts from spleen that both S100A8/S100A9 heterodimers as well as S100A9 homodimers were formed, both after tumor and inflammatory challenge. The cellular source for S100A9 homodimers were CD11b + GR1 + cells. S100A9 homodimers were also secreted into the extracellular space. Lastly, in the spleen from normal and tumor bearing animals cells expressing relatively higher levels of S100A9 compared to S100A8 could be observed by immunohistochemistry. Taken together, these data show that the biologically potent dimeric form of S100A9 is induced in vivo in situations of tumor burden or inflammatory challenge.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 19
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Christie L. Walker, Audrey A. Merriam, Eric O. Ohuma, Manjiri K. Dighe, Michael Gale, Lakshmi Rajagopal, Aris T. Papageorghiou, Cynthia Gyamfi-Bannerman, Kristina M. Adams Waldorf Background Zika virus (ZIKV) is a mosquito-transmitted flavivirus, which can induce fetal brain injury and growth restriction following maternal infection during pregnancy. Prenatal diagnosis of ZIKV-associated fetal injury in the absence of microcephaly is challenging due to an incomplete understanding of how maternal ZIKV infection affects fetal growth and the use of different sonographic reference standards around the world. We hypothesized that skeletal growth is unaffected by ZIKV infection and that the femur length can represent an internal standard to detect growth deceleration of the fetal head and/or abdomen by ultrasound. Objective To determine if maternal ZIKV infection is associated with a femur-sparing pattern of intrauterine growth restriction (IUGR) through analysis of fetal biometric measures and/or body ratios using the INTERGROWTH-21 st Project (IG-21) and World Health Organization Fetal Growth Chart (WHO-FGC) sonographic references. Study Design Pregnant women diagnosed with a possible recent ZIKV infection at Columbia University Medical Center after traveling to an endemic area were retrospectively identified and included if a fetal ultrasound was performed. Data was collected regarding ZIKV testing, fetal biometry, pregnancy and neonatal outcomes. The IG-21 and WHO-FGC sonographic standards were applied to obtain Z-scores and/or percentiles for fetal head, abdominal circumference (HC, AC) and femur length (FL) specific for each gestational week. A novel IG-21 standard was also developed to generate Z-scores for fetal body ratios with respect to femur length (HC:FL, AC:FL). Data was then grouped within clinically relevant gestational age strata (〈24 weeks, 24-27 6/7, 28-33 6/7, >34 weeks) to analyze time-dependent effects of ZIKV infection on fetal size. Statistical analysis was performed using Wilcoxon signed-rank test on paired data, comparing either AC or HC to FL. Results A total of 56 pregnant women were included in the study with laboratory evidence of a confirmed or possible recent ZIKV infection. Based on the CDC definition for microcephaly after congenital ZIKV exposure, microcephaly was diagnosed in 5% (3/56) by both the IG-21 and WHO-FGC standards (HC Z-score ≤ -2 or ≤ 2.3%). Using IG-21, IUGR was diagnosed in 18% of pregnancies (10/56; AC Z-score ≤-1.3, 〈10%). Analysis of fetal size using the last ultrasound scan for all subjects revealed a significantly abnormal skewing of fetal biometrics with a smaller AC versus FL by either IG-21 or WHO-FGC (p〈0.001 for both). A difference in distribution of fetal AC compared to FL was first apparent in the 24-27 6/7 week strata (IG-21, p=0.002; WHO-FGC, p=0.001). A significantly smaller HC compared to FL was also observed by IG-21 as early as the 28-33 6/7 week strata (IG-21, p=0.007). Overall, a femur-sparing pattern of growth restriction was detected in 52% of pregnancies with either an HC:FL or AC:FL fetal body ratio less than the 10 th percentile (IG-21 Z-score ≤-1.3). Conclusions An unusual femur-sparing pattern of fetal growth restriction was detected in the majority of fetuses with congenital ZIKV exposure. Fetal body ratios may represent a more sensitive ultrasound biomarker to detect viral injury in nonmicrocephalic fetuses that could impart long-term risk for complications of congenital ZIKV infection.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 20
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Wenyi Wang, Jian Wang, Meiling Yan, Jiechun Jiang, Ailin Bian Aims diabetes mellitus is one of the most common metabolic diseases worldwide characterized by insulin resistance and pancreatic β cell dysfunction. miRNA plays an important role in DM. In previous studies, miRNA-92a could function as targets for innovative precision medicines to reduce T1D islet autoimmunity. However, the relationship between miRNA-92a and pancreatic β cell dysfunction remains unknown. The aim of the study was to investigate the role of miRNA-92a in pancreatic β cell dysfunction. Methods Apoptosis, proliferation, insulin secretion and cell survival rate were detected to evaluate the function of miRNA-92a. Results we found that miRNA-92a could inhibit apoptosis induced by high-glucose environment and increase the insulin secretion and proliferation. Moreover, we identify the KLF2 as direct target of miRNA-92a, suggesting that miRNA-92a may function through regulating KLF2. Conclusion Altogether, we verified the function and mechanism of miRNA-92a and provide evidence that miRNA-92a may serve a potential candidate for the clinical treatment for DM.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 21
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Juan Wei, Guannan Chen, Xuan Shi, Huanping Zhou, Meiyun Liu, Yuanli Chen, Di Feng, Pengcheng Zhang, Lingmin Wu, Xin Lv The transcription factor nuclear factor E2-related factor 2 (Nrf2) is known to control the expression of antioxidant response elements and cytoprotective genes and modulate inflammatory response, helping to ameliorate damage in many diseases. Exactly how Nrf2 regulates innate inflammatory homeostasis remains unclear. In this study, we provide in vitro and in vivo evidence that Nrf2 plays a crucial role in macrophage polarization and acute respiratory distress syndrome (ARDS). We conducted in vitro experiments using a mouse alveolar macrophage cell line as well as primary cultures of macrophages in which cells were exposed to lipopolysaccharide (LPS) or interferon-γ in order to mimic ARDS, in the presence or absence of the Nrf2 activator tert-butylhydroquinone (tBHQ). Using siRNA-mediated Nrf2 knockdown, we showed that Nrf2 inhibited the inflammatory response by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization. At the same time, tBHQ activated Nrf2-mediated inhibition of the p65 nuclear factor-κB pathway and activation of peroxisome proliferator-activated receptor-γ, which play important roles in regulating macrophage polarization. We also conducted in vivo experiments in which mice were given tBHQ with or without intratracheal LPS, then their survival was monitored, lung injury was assessed using histology, and levels of pro- and anti-inflammatory cytokines were assayed in the lungs and serum. Activation of Nrf2 with tBHQ dramatically reduced LPS-induced mortality and lung injury, down-regulated pro-inflammatory mediators and up-regulated anti-inflammatory mediators. These results suggest that Nrf2 can help prevent ARDS progression by promoting M2 polarization of macrophages. Interfering with Nrf2 may be an effective strategy for reprogramming macrophage polarization in order to treat ARDS.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 22
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Masateru Magotani, Aya Nakamura, Haruka Ikegami, Saori Kunii, Yuji Mishina, Koichi Morimoto, Satoshi Kishigami Transgenic animals provide attractive systems for the production of valuable recombinant proteins. Previous studies indicate that milk is a suitable source of secreted recombinant proteins. In the current study, we examine whether excrement can be another source of recombinant proteins by using transgenic mice ubiquitously-expressing green fluorescent protein (GFP) as a model. We found that the surface of excrement from GFP-transgenic mice was fluorescent, and the supernatant after centrifugation of an excrement suspension was rich in undegraded, actively fluorescing GFP. GFP was successfully purified from stool as a fluorescent 27 kDa protein by using a common procedure. Finally, we observed that the fluorescence of digested materials began in the ileum and persisted throughout the remainder of the digestive tract. Our results demonstrate that excrement, which is produced daily regardless of the sex or age of the animal, may be another feasible source of recombinant proteins. The preparation method is simple, economical, and noninvasive.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 23
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Marta Panella, Nicola Mosca, Armando Di Palo, Nicoletta Potenza, Aniello Russo MicroRNA-125a exhibits an antiproliferative activity and is downregulated in several types of tumors, including hepatocellular carcinoma where it targets sirtuin-7, matrix metalloproteinase-11, and c-Raf. Another target of miR-125a is Lin28, a pluripotency factor that is generally undetectable in differentiated cells but is often upregulated/reactivated in tumors where it acts as an oncogenic factor promoting cell proliferation and tumor progression. In this study we show that downregulation of Lin28b by miR-125a partially accounts for its antiproliferative activity toward hepatocellular carcinoma cells. We also found that Lin28b is able to bind a conserved GGAG motif of pre-miR-125a and to inhibit its maturation in hepatocellular carcinoma cells. Reciprocal inhibition between miR-125a and Lin28b reasonably generates a positive feedback loop where reactivation of Lin-28b inhibits the expression of both miR-125a and let-7, reinforcing its own expression and leading to a marked overexpression of the mitogenic targets of the two miRNAs. On the other hand, perturbation of these circuits by overexpression of miR-125a suppresses Lin28b leading to a decreased cell proliferation. Overall, these data support a tumor suppressive role for miR-125a and contribute to the elucidation of its molecular targets.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 24
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Yuezhen Ma, Yanni Liu, Huihui Hou, Yanfen Yao, Hua Meng MiR-150 is involved into some pathological processes, such as tumorigenesis and autoimmune diseases. However, little is known about the involvement of miR-150 in human sepsis. In this study, plasma miR-150 level had a diagnostic and independent prognostic value in patients with sepsis, and negatively correlated with renal dysfunction and 28-day survival as well as plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). MiR-150 expression was also significantly decreased in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice with sepsis after lipopolysaccharides (LPS) treatment. In-vitro, miR-150 over-expression protected HUVECs from LPS-induced apoptosis and the expressions of nuclear factor-κB1 (NF-κB1), IL-6, TNF-α, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Furthermore, NF-κB1 was identified as a direct target of miR-150. Restored NF-κB1 expression antagonized the protective effects of miR-150, while suppression of NF-κB1 enhanced these protective effects. Our findings indicate miR-150 predicts survival in patients with sepsis and inhibits LPS-induced inflammatory factors and apoptosis by targeting NF-κB1 in human umbilical vein endothelial cells. Thus, miR-150 may be a useful biomarker or target in the diagnosis, prognosis and treatment of patients with sepsis.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 25
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: Biochemical Pharmacology Author(s): Sushma Chaturvedi, Robert M. Hoffman, Joseph R. Bertino Normal cells can synthesize sufficient methionine for growth requirements from homocysteine and 5-methyltetrahydrofolate and vitamin B12. However, many cancer-cell types require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) deficiency is associated with methionine dependence in cancer cells, there are other causes for tumors to require exogenous methionine. In this review we describe studies that show restricting methionine to certain cancers by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics is a promising antitumor strategy. The basis for methionine dependence in tumor cells is also briefly reviewed . Graphical abstract
    Print ISSN: 0006-2952
    Electronic ISSN: 1873-2968
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 26
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Ning Han, Zhaotao Wang, Guoqi Wang, Jun Yu, Chen Chen, Huiyong Huang, Ruxiang Xu In this study, we established an in vitro hypoxic system driven by a self-regulated chemical reaction that proved effective for cell culture. The hypoxic device was modified from a 1.5 L polypropylene preservation box normally employed for food storage. Pyrogallic acid, sodium hydroxide, and sodium carbonate were dissolved in water and injected into the box. Sodium dihydrogen phosphate solution was injected into the box after 15 min. We measured the concentrations of oxygen and carbon dioxide in the box to determine viability of the hypoxic system. It maintained low levels of oxygen less than 0.2% and stabilizing levels of carbon dioxide at 5% for at least 96 h. Therefore, this device sustained a stable hypoxic environment that may be applicable for cell culture and in vitro studies of hypoxia.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 27
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Wen Zhong, Zonghong Li, Maoge Zhou, Tao Xu, You Wang DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1. These DDX1-targeted alternative splicing genes are mainly associated with calcium ion binding, high voltage-gated calcium channel, and transmembrane transporter. Functionally, silencing DDX1 impairs calcium influx and insulin secretion in the pancreatic β cells. These results reveal an important role for DDX1 in the regulation of gene alternative splicing and insulin secretion in pancreatic β cells.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 28
    Publication Date: 2018-05-07
    Description: Publication date: August 2018 Source: Biomaterials, Volume 173 Author(s): Tomoki Takashina, Takayoshi Koyama, Satoshi Nohara, Masakatsu Hasegawa, Akira Ishiguro, Kenta Iijima, Jun Lu, Mari Shimura, Tadashi Okamura, Tetsushi Sakuma, Takashi Yamamoto, Yukihito Ishizaka Cellular reprogramming is a promising technology in regenerative medicine, but most studies have been performed by using expression vectors. For future clinical applications, it is necessary to establish a system in which cell engineering can be manipulated without any risk of damaging the genome. Here, we identified a cell-penetrating peptide composed of 10 amino acids (RIFIHFRIGC) with nuclear trafficking activity and found that it was significantly more potent than a Tat-derived peptide or polyarginine peptide (R11). We named the peptide “nuclear trafficking peptide” (NTP) and applied it to a protein-based artificial transcription factor (NTP-ATF), which was composed of a transcription activator-like effector and transcription domain (VP64). An NTP-ATF designed to the proximal promoter region of the microRNA-302/367 cluster efficiently induced endogenous RNA expression at an extremely low concentration (0.25 nM), and repetitive treatment of mouse embryonic fibroblasts with NTP-ATF generated induced pluripotent stem-like cells, which gave chimeric mice. Together with the observation that recombinant NTP-ATF protein did not induce any apparent cytotoxicity, we propose that NTP-ATF is a promising system for cellular reprogramming applicable to regenerative medicine.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 29
    Publication Date: 2018-05-07
    Description: Publication date: August 2018 Source: Biomaterials, Volume 173 Author(s): Di Zhang, Feng Feng, Qilong Li, Xiuyu Wang, Li Yao Nanomaterials-based photodynamic therapy (PDT) has been used to treat malignant cells. However, the intrinsic impact of nanomaterials-based PDT on mechanical properties of intractable tumor cells is not well understood. Herein, we demonstrated that the mechanical forces of Taxol-resistant tumor cells were decreased by nanopurpurin-based PDT destructing extracellular matrix (ECM), increasing therapy sensitivity and repressing tumor metastasis. Combining FIRMS and general confocal microscope, we observed that the disruption of ECM by photodynamic reaction of P18-nanoconfined liposome ( P18⊂L ) induced a decrease of adhesion force and biomechanical properties of Taxol-resistant cells through the attenuation of actomyosin-based contractility thereby inhibiting cell migration and metastasis in vivo. Moreover, the destroyed ECM by P18⊂L PDT increased the therapy sensitivity. A clearer understanding of the effect of nanopurpurin-based PDT on mechanical properties and behaviors of intractable tumor cells will provide new and important basis for developing new therapeutic strategies.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 30
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Jing Wang, Lucy K. Shewell, Adrienne W. Paton, James C. Paton, Christopher J. Day, Michael P. Jennings The B subunit of the subtilase cytotoxin (SubB) recognises N -glycolylneuraminic acid (Neu5Gc) containing glycans, the most prominent form of aberrant glycosylation in human cancers. We have previously engineered SubB by construction of a SubB ΔS106/ΔT107 mutant (SubB2M) for greater specificity and enhanced recognition of Neu5Gc containing glycans. In this study, we further explore the utility of SubB2M as a Neu5Gc lectin by showing its improved specificity and recognition for Neu5Gc containing glycans over the wild-type SubB protein and an anti-Neu5Gc IgY antibody in a N -acetylneuraminic acid (Neu5Ac)/Neu5Gc glycan array and by surface plasmon resonance. Far-western blot analysis showed that SubB2M preferentially binds to bovine serum glycoproteins over human serum glycoproteins. SubB2M was also able to detect Neu5Gc containing bovine glycoproteins spiked into normal human serum with greater sensitivity than the wild-type SubB and the anti-Neu5Gc IgY antibody. These results suggest that SubB2M will be a useful tool for the testing of serum and other bodily fluids for cancer diagnosis and prognosis.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 31
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Author(s): Alexandra Vasilyeva, Lyubov' Yurina, Maria Indeykina, Anna Bychkova, Anna Bugrova, Marina Biryukova, Alexey Kononikhin, Evgene Nikolaev, Mark Rosenfeld Plasma fibrin-stabilizing factor (pFXIII) is a heterotetrameric proenzyme composed of two catalytic A subunits (FXIII-A 2 ) and two inhibitory/carrier B subunits (FXIII-B 2 ). The main function of the protein is the formation of cross-links between the polypeptide chains of the fibrin clot. The conversion of pFXIII into the enzymatic form FXIII-A 2 * is a multistage process. Like many other blood plasma proteins, pFXIII is an oxidant-susceptible target. The influence of distinct sites susceptible to oxidation-mediated modifications on the changes in the structural-functional characteristics of the protein remains fully unexplored. For the first time, a set of the oxidation sites within FXIII-A 2 under ozone-induced oxidation of pFXIII at different stages of its activation have been identified by mass spectrometry, and the extent as well as the chemical nature of these modifications have been explored. It was shown that the set of amino acid residues susceptible to oxidative attack and the degree of oxidation of these residues in FXIII-A 2 of non-activated pFXIII, pFXIII activated by Ca 2+ and fully activated pFXIII treated with thrombin and Ca 2+ significantly differ. The obtained data enable one to postulate that in the process of the proenzyme conversion into FXIII-A 2 *, new earlier-unexposed amino acid residues become available for the oxidizer while some of the initially surface-exhibited residues are buried within the protein globule. Graphical abstract
    Print ISSN: 1570-9639
    Electronic ISSN: 1878-1454
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 32
    Publication Date: 2018-05-07
    Description: Publication date: July 2018 Source: Biomaterials, Volume 171 Author(s): Si-Yong Qin, Yin-Jia Cheng, Qi Lei, Ai-Qing Zhang, Xian-Zheng Zhang The clinical outcomes of conventional mono-chemotherapy of cancers are usually far from satisfactory due to some issues such as tumor heterogeneity and resistance to chemotherapeutic drugs. With the increasing knowledge of molecular signal pathways and pathological mechanisms involved in the initiation and progression of cancers, collaborative strategies have been elaborated to optimize therapeutic outcomes. This review surveys the most recent advances in combination therapy including combination chemotherapy, chemotherapy plus gene therapy, chemotherapy plus phototherapy, as well as chemotherapy plus immunotherapy. Additionally, chemotherapy-involved multiple therapy that merges various therapeutic modalities is also presented. We try to elicit the rationales of applying these combinational formulations for cancer chemotherapy, which might provide new guidelines for high-performance cancer treatments. Graphical abstract
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 33
    Publication Date: 2018-05-07
    Description: Publication date: July 2018 Source: Biomaterials, Volume 171 Author(s): Ferdinand Wagner, Boris M. Holzapfel, Jacqui A. McGovern, Abbas Shafiee, Jeremy G. Baldwin, Laure C. Martine, Christoph A. Lahr, Felix M. Wunner, Thor Friis, Onur Bas, Melanie Boxberg, Peter M. Prodinger, Ali Shokoohmand, Davide Moi, Roberta Mazzieri, Daniela Loessner, Dietmar W. Hutmacher Background Existing preclinical murine models often fail to predict effects of anti-cancer drugs. In order to minimize interspecies-differences between murine hosts and human bone tumors of in vivo xenograft platforms, we tissue-engineered a novel orthotopic humanized bone model. Methods Orthotopic humanized tissue engineered bone constructs (ohTEBC) were fabricated by 3D printing of medical-grade polycaprolactone scaffolds, which were seeded with human osteoblasts and embedded within polyethylene glycol-based hydrogels containing human umbilical vein endothelial cells (HUVECs). Constructs were then implanted at the femur of NOD- scid and NSG mice. NSG mice were then bone marrow transplanted with human CD34  +  cells. Human osteosarcoma (OS) growth was induced within the ohTEBCs by direct injection of Luc-SAOS-2 cells. Tissues were harvested for bone matrix and marrow morphology analysis as well as tumor biology investigations. Tumor marker expression was analyzed in the humanized OS and correlated with the expression in 68 OS patients utilizing tissue micro arrays (TMA). Results After harvesting the femurs micro computed tomography and immunohistochemical staining showed an organ, which had all features of human bone. Around the original mouse femur new bone trabeculae have formed surrounded by a bone cortex. Staining for human specific (hs) collagen type-I (hs Col-I) showed human extracellular bone matrix production. The presence of nuclei staining positive for human nuclear mitotic apparatus protein 1 (hs NuMa) proved the osteocytes residing within the bone matrix were of human origin. Flow cytometry verified the presence of human hematopoietic cells. After injection of Luc-SAOS-2 cells a primary tumor and lung metastasis developed. After euthanization histological analysis showed pathognomic features of osteoblastic OS. Furthermore, the tumor utilized the previously implanted HUVECS for angiogenesis. Tumor marker expression was similar to human patients. Moreover, the recently discovered musculoskeletal gene C12orf29 was expressed in the most common subtypes of OS patient samples. Conclusion OhTEBCs represent a suitable orthotopic microenvironment for humanized OS growth and offers a new translational direction, as the femur is the most common location of OS. The newly developed and validated preclinical model allows controlled and predictive marker studies of primary bone tumors and other bone malignancies.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 34
    Publication Date: 2018-05-07
    Description: Publication date: July 2018 Source: Biomaterials, Volume 171 Author(s): Ling Li, Shuo Hu, Xiaoyuan Chen In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome editing systems have become one of the most robust platforms in basic biomedical research and therapeutic applications. To date, efficient in vivo delivery of the CRISPR/Cas9 system to the targeted cells remains a challenge. Although viral vectors have been widely used in the delivery of the CRISPR/Cas9 system in vitro and in vivo , their fundamental shortcomings, such as the risk of carcinogenesis, limited insertion size, immune responses and difficulty in large-scale production, severely limit their further applications. Alternative non-viral delivery systems for CRISPR/Cas9 are urgently needed. With the rapid development of non-viral vectors, lipid- or polymer-based nanocarriers have shown great potential for CRISPR/Cas9 delivery. In this review, we analyze the pros and cons of delivering CRISPR/Cas9 systems in the form of plasmid, mRNA, or protein and then discuss the limitations and challenges of CRISPR/Cas9-based genome editing. Furthermore, current non-viral vectors that have been applied for CRISPR/Cas9 delivery in vitro and in vivo are outlined in details. Finally, critical obstacles for non-viral delivery of CRISPR/Cas9 system are highlighted and promising strategies to overcome these barriers are proposed.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 35
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics Author(s): Salman Shahid, Ashish Kabra, Surbhi Mundra, Ravi Kant Pal, Sarita Tripathi, Anupam Jain, Ashish Arora Background Bacterial peptidyl-tRNA hydrolase (Pth) is an essential enzyme that alleviates tRNA starvation by recycling prematurely dissociated peptidyl-tRNAs. The specificity of Pth for N-blocked-aminoacyl-tRNA has been proposed to be contingent upon conserved residue N14 forming a hydrogen bond with the carbonyl of the first peptide bond in the substrate. M71 is involved in forming a conserved hydrogen bond with N14. Other interactions facilitating this recognition are not known. Methods The structure, dynamics, and stability of the M71A mutant of Pth from Vibrio cholerae (VcPth) were characterized by X-ray crystallography, NMR spectroscopy, MD simulations and DSC. Results Crystal structure of M71A mutant was determined. In the structure, the dimer interface is formed by the insertion of six C-terminal residues of one molecule into the active site of another molecule. The side-chain amide of N14 was hydrogen bonded to the carbonyl of the last peptide bond formed between residues A196 and E197, and also to A71. The CSP profile of mutation was similar to that observed for the N14D mutant. M71A mutation lowered the thermal stability of the protein. Conclusion Our results indicate that the interactions of M71 with N14 and H24 play an important role in optimal positioning of their side-chains relative to the peptidyl-tRNA substrate. Overall, these interactions of M71 are important for the activity, stability, and compactness of the protein. Significance The work presented provides original and new structural and dynamics information that significantly enhances our understanding of the network of interactions that govern this enzyme's activity and selectivity.
    Print ISSN: 1570-9639
    Electronic ISSN: 1878-1454
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 36
    Publication Date: 2018-05-07
    Description: Publication date: 7 June 2018 Source: Biochemical and Biophysical Research Communications, Volume 500, Issue 3 Author(s): Shanshan Li, Xiaorui Lou, Yueyang Xu, Xiaozhen Teng, Shiyou Che, Ruihua Liu, Mark Bartlam The C5 pathway in bacteria is responsible for the synthesis of 5-aminolevulinic acid, which forms the core skeleton of cofactors required for metabolism. One of the key actors in this pathway is a pyridoxamine-5′-phosphate (PMP)/pyridoxal-5′-phosphate (PLP) dependent enzyme called glutamate-1-semialdehyde aminomutase (GSAM). In this study, we crystallized the expression product of the uncharacterized pa4088 gene from the opportunistic pathogen Pseudomonas aeruginosa PAO1. The resulting high-resolution structure confirms it to be a member of the GSAM family. Continuous electron density indicates the presence of a PLP cofactor with a Schiff base linkage between the PLP cofactor and the ε-amino group of Lys286. A crystal structure of a K286A mutant in complex with PMP is also reported. As GSAM enzymes are not present in mammalian cells, this work provides a starting point for the investigation of GSAM as a target for drug development against P. aeruginosa infection.
    Print ISSN: 0006-291X
    Electronic ISSN: 1090-2104
    Topics: Biology , Chemistry and Pharmacology , Physics
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 37
    Publication Date: 2018-05-07
    Description: Publication date: August 2018 Source: Biomaterials, Volume 173 Author(s): Sadegh Davoudi, Chih-Ying Chin, Michael J. Cooke, Roger Y. Tam, Molly S. Shoichet, Penney M. Gilbert Adult skeletal muscle tissue harbors the capacity for self-repair due to the presence of tissue resident muscle stem cells (MuSCs). Advances in the area of prospective MuSC isolation demonstrated the potential of cell transplantation therapy as a regenerative medicine strategy to restore strength and long-term regenerative capacity to aged, injured, or diseased skeletal muscle tissue. However, cell loss during ejection, limits to post-injection proliferation, and poor donor cell dispersion distal to the injection site are amongst hurdles to overcome to maximize MuSC transplant impact. Here, we assess a physical blend of hyaluronan and methylcellulose (HAMC) as a bioactive, shear thinning hydrogel cell delivery system to improve MuSC transplantation efficiency. Using in vivo transplantation studies, we found that the HAMC delivery system results in a >45% increase in the number of donor-derived fibers as compared to saline delivery. We demonstrate that increases in donor-derived fibers when using HAMC are attributed to increased MuSC proliferation via a CD44-independent mechanism, preventing injected cell active clearance, and supporting in vivo expansion by delaying differentiation. Furthermore, we observed a significant improvement in donor fiber dispersion when MuSCs were delivered in HAMC. Our study results suggest that HAMC is a promising muscle stem cell delivery vehicle.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 38
    Publication Date: 2018-05-07
    Description: Publication date: July 2018 Source: Biomaterials, Volume 171 Author(s): Chiara Stüdle, Queralt Vallmajó-Martín, Alexander Haumer, Julien Guerrero, Matteo Centola, Arne Mehrkens, Dirk J. Schaefer, Martin Ehrbar, Andrea Barbero, Ivan Martin Despite the various reported approaches to generate osteochondral composites by combination of different cell types and materials, engineering of templates with the capacity to autonomously and orderly develop into cartilage-bone bi-layered structures remains an open challenge. Here, we hypothesized that the embedding of cells inducible to endochondral ossification (i.e. bone marrow derived mesenchymal stromal cells, BMSCs) and of cells capable of robust and stable chondrogenesis (i.e. nasal chondrocytes, NCs) adjacent to each other in bi-layered hydrogels would develop directly in vivo into osteochondral tissues. Poly(ethylene glycol) (PEG) hydrogels were functionalized with TGFβ3 or BMP-2, enzymatically polymerized encapsulating human BMSCs, combined with a hydrogel layer containing human NCs and ectopically implanted in nude mice without pre-culture. The BMSC-loaded layers reproducibly underwent endochondral ossification and generated ossicles containing bone and marrow. The NC-loaded layers formed cartilage tissues, which (under the influence of BMP-2 but not of TGFβ3 from the neighbouring layer) remained phenotypically stable. The proposed strategy, resulting in orderly connected osteochondral composites, should be further assessed for the repair of osteoarticular defects and will be useful to model developmental processes leading to cartilage-bone interfaces.
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 39
    Publication Date: 2018-05-07
    Description: Publication date: August 2018 Source: Cancer Genetics, Volumes 224–225 Author(s): Yanisa Rattanapan, Veerawat Korkiatsakul, Adcharee Kongruang, Takol Chareonsirisuthigul, Budsaba Rerkamnuaychoke, Anna Wongkularb, Sarikapan Wilailak DNA methylation is one of the epigenetic mechanisms associated with gene expression and plays a key role as in activation and deactivation of oncogenes and tumor suppressor genes, respectively. This study employed DNA methylation array to identify methylated genes which are highly correlated with various phenotypes of epithelial ovarian cancer (EOC) in Thai patients and to quantify promoter CpG-island methylation of candidate genes. Tissues from patients with serous and non-serous EOC showed significantly higher promoter methylation of EGFL7 and RASSF1 compared to benign cases. These results indicate the potential of investigating promoter CpG-island methylation of cancer-associated genes as biomarkers of disease progression and even possibly of early detection.
    Print ISSN: 2210-7762
    Electronic ISSN: 1873-4456
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 40
    Publication Date: 2018-05-07
    Description: Publication date: June 2018 Source: Current Opinion in Genetics & Development, Volume 50 Author(s): Katharine R Owen Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic causes of beta-cell dysfunction and diabetes arising in children and young adults. Making an accurate diagnosis of MODY is important for establishing the correct management. Recent advances in our understanding of human sequence variation, through data collated in resources such as the Exome Aggregation Consortium have refined guidelines for assessment of rare genetic variants. This will allow a more precise aetiological diagnosis in childhood and young adult diabetes. No major new monogenic causes of diabetes outside the neonatal period have been identified in recent years, but the allelic spectrum of disease phenotype associated with known genes continues to expand. Improving uptake of genetic testing by defining who should be tested is an area of active research. A population based study found that 6.5% of children who have negative beta-cell antibodies at diagnosis have rare functional variants in MODY genes. Defining the high risk groups in adults with diabetes is more difficult, but online decision aids will assist clinicians in selecting who to refer for testing.
    Print ISSN: 0959-437X
    Electronic ISSN: 1879-0380
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 41
    Publication Date: 2018-05-07
    Description: Publication date: August 2018 Source: Current Opinion in Immunology, Volume 53 Author(s): Giulietta Saletti, Thomas Gerlach, Guus F Rimmelzwaan Currently used inactivated influenza vaccines aim at the induction of virus-neutralizing antibodies directed to the variable head domain of the viral hemagglutinin. Although these vaccines are effective against antigenically matching virus strains, they offer little protection against antigenically distinct drift variants or potentially pandemic viruses of alternative subtypes. In the last decades, the threat of novel influenza pandemics has sparked research efforts to develop vaccines that induce more broadly protective immunity. Here, we discuss the immune responses induced by conventional ‘tailor-made’ inactivated and live influenza vaccines and novel ‘one fits all’ candidate vaccines able to induce cross-reactive virus-specific antibody and T cell responses and to afford protection to a wider range of influenza viruses.
    Print ISSN: 0952-7915
    Electronic ISSN: 1879-0372
    Topics: Biology , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 42
    Publication Date: 2018-05-07
    Description: Publication date: June 2018 Source: Current Opinion in Immunology, Volume 52 Author(s): Rachel N Cotton, Adam Shahine, Jamie Rossjohn, D Branch Moody Peptide and lipid antigens are presented to T cells when bound to MHC or CD1 proteins, respectively. The general paradigm of T cell antigen recognition is that T cell receptors (TCRs) co-recognize an epitope comprised of the antigen and antigen presenting molecule. Here we review the latest studies in which T cells operate outside the co-recognition paradigm: TCRs can broadly contact CD1 itself, but not the carried lipid. The essential structural feature in these new mechanisms is a large ‘antigen free’ zone on the outer surface of certain antigen presenting molecules. Whereas peptides dominate the exposed surface of MHC-peptide complexes, all human CD1 proteins have a closed, antigen-free surface, which is known as the A′ roof. These new structural models help to interpret recent biological studies of CD1 autoreactive T cells in vivo , which have now been broadly observed in studies on TCR-transgenic mice, healthy humans and patients with autoimmune disease. Graphical abstract
    Print ISSN: 0952-7915
    Electronic ISSN: 1879-0372
    Topics: Biology , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 43
    Publication Date: 2018-05-07
    Description: Publication date: October 2018 Source: Cytokine, Volume 110 Author(s): Reena Kumari, Sandeep Kumar, Mohammad Kaleem Ahmad, Rajeev Singh, Shashi Kant Kumar, Akshayaya Pradhan, Sharad Chandra, Sudhir Kumar Background Tumor necrosis factor-alpha (TNF-α) are considered as a pro inflammatory and interleukin-10 (IL-10) anti inflammatory have been shown to predict the risk of incident of coronary artery disease (CAD). The polymorphism at promoter of TNF-α and IL-10 has been shown to increase transcriptional activity of the gene and play a important role in patho physiology of CAD. Aim of present study is to examine the impact of the TNF-α and IL-10 variant allele on various markers of the CAD and to study its relation with circulating TNF-α and IL-10 levels. Methods The −308 G/A & −238 G/A of TNF-α and −1082 G/A & −819 C/T of IL-10 gene polymorphism has been studied in 301 diagnosed CAD subjects (Age 51.50 ± 9.28; BMI 25.30 ± 3.58) and 305 healthy controls (Age 51.57 ± 9.50; BMI 24.06 ± 7.26). These polymorphism of TNF-α and IL-10 were detected by real time PCR by using Taqman SNP genotyping assay. Furthermore serum TNF-alpha and IL-10 levels were also measured by ELISA. Results Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls ( p  > 0.05). On allele contrast, significant association with susceptibility to CAD was detected with polymorphisms in TNF-α -308 G/A, that variant genotype GA + AA (dominant model) (p = 0.030: OR = 1.61: 95% CI = 1.06–2.44) and variant allele (A) (p = 0.006: OR = 1.71: 95% CI = 1.17–2.51) of TNF-α 308 G/A gene was significant highly observed in the cases as compared to control group. Furthermore, variant genotype CT + TT (dominant model) (p = 0.004: OR = 1.62: 95% CI = 1.17–2.24) and variant allele (T) (p 〈 0.001: OR = 1.49: 95% CI = 1.17–1.89) of IL-10 −819 C/T gene was significant highly observed in the cases as compared to control group. Conclusion Our results suggest that the TNF-α G-308A polymorphism independently associated with DBP, cholesterol, triglyceride, LDL, TNF-α and IL-10 levels which may be leads to the development of coronary artery disease of North Indians. Graphical abstract
    Print ISSN: 1043-4666
    Electronic ISSN: 1096-0023
    Topics: Biology , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 44
    facet.materialart.
    Unknown
    Elsevier
    Publication Date: 2018-05-07
    Description: Publication date: April 2018 Source: Current Opinion in Immunology, Volume 51
    Print ISSN: 0952-7915
    Electronic ISSN: 1879-0372
    Topics: Biology , Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 45
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: European Journal of Cancer Author(s): Therese M-L. Andersson, Gerda Engholm, Eero Pukkala, Magnus Stenbeck, Laufey Tryggvadottir, Hans Storm, Elisabete Weiderpass Background Alcohol consumption is an important and preventable cause of cancer. The aim of this study was to quantify the proportion of the cancer burden in the Nordic countries linked to alcohol and estimate the potential for cancer prevention by changes in alcohol consumption. Methods Using the Prevent macro-simulation model, the number of cancer cases in the Nordic countries over a 30-year period (2016–2045) was modelled for six sites, under different scenarios of changing alcohol consumption, and compared to the projected number of cases if constant alcohol consumption prevailed. The studied sites were colorectal, post-menopausal breast, oral cavity and pharynx, liver, larynx as well as oesophageal squamous cell carcinoma. The alcohol consumption was based on the categories of non-drinkers/occasional drinkers, light drinkers (〈=12.5 g alcohol per day), moderate drinkers (>12.5 and ≤ 50 g/day) and heavy drinkers (>50 g/day). Results About 83,000 cancer cases could be avoided in the Nordic countries in a 30-year period if alcohol consumption was entirely eliminated, which is 5.5% of the expected number of cases for the six alcohol-related cancer types. With a 50% reduction in the proportion with moderate alcohol consumption by year 2025, 21,500 cancer cases could be avoided. The number of avoidable cases was highest for post-menopausal breast and colorectal cancer, but the percentage was highest for oesophageal squamous cell carcinoma. Conclusion The results from this study can be used to understand the potential impact and significance of primary prevention programmes targeted towards reducing the alcohol consumption in the Nordic countries.
    Print ISSN: 0959-8049
    Electronic ISSN: 1879-0852
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 46
    Publication Date: 2018-05-07
    Description: Publication date: June 2018 Source: European Journal of Cancer, Volume 96 Author(s): Chu Matsuda, Megumi Ishiguro, Satoshi Teramukai, Yoshiki Kajiwara, Shoichi Fujii, Yusuke Kinugasa, Yoshihiko Nakamoto, Masanori Kotake, Yoshiyuki Sakamoto, Kiyotaka Kurachi, Atsuyuki Maeda, Koji Komori, Naohiro Tomita, Yasuhiro Shimada, Keiichi Takahashi, Kenjiro Kotake, Masahiko Watanabe, Hidetaka Mochizuki, Yoko Nakagawa, Kenichi Sugihara Background Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafur–uracil (UFT) to surgery alone for stage II colon cancer. Methods Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500–600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. Results A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75–1.10; p = 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgery-alone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65–1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66–1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. Conclusions Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. Trial registration ClinicalTrials. Gov. # NCT00392899 .
    Print ISSN: 0959-8049
    Electronic ISSN: 1879-0852
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 47
    Publication Date: 2018-05-07
    Description: Publication date: June 2018 Source: European Journal of Cancer, Volume 96 Author(s): N. Nabieva, T. Fehm, L. Häberle, J. de Waal, M. Rezai, B. Baier, G. Baake, H.-C. Kolberg, M. Guggenberger, M. Warm, N. Harbeck, R. Wuerstlein, J.-U. Deuker, P. Dall, B. Richter, G. Wachsmann, C. Brucker, J.W. Siebers, M. Popovic, T. Kuhn, C. Wolf, H.-W. Vollert, G.-P. Breitbach, W. Janni, R. Landthaler, A. Kohls, D. Rezek, T. Noesselt, G. Fischer, S. Henschen, T. Praetz, V. Heyl, T. Kühn, T. Krauss, C. Thomssen, A. Hohn, H. Tesch, C. Mundhenke, A. Hein, C.C. Hack, K. Schmidt, E. Belleville, S.Y. Brucker, S. Kümmel, M.W. Beckmann, D. Wallwiener, P. Hadji, P.A. Fasching Background Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Patients and methods Post-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Results Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84). Conclusions These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. Clinical Trials Number CFEM345DDE19.
    Print ISSN: 0959-8049
    Electronic ISSN: 1879-0852
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 48
    Publication Date: 2018-05-07
    Description: Publication date: Available online 3 May 2018 Source: European Journal of Cancer Author(s): Giorgio Minotti
    Print ISSN: 0959-8049
    Electronic ISSN: 1879-0852
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 49
    facet.materialart.
    Unknown
    Elsevier
    In: Gene
    Publication Date: 2018-05-07
    Description: Publication date: 30 July 2018 Source: Gene, Volume 665 Author(s): Weibo Liu, Haifeng Wei, Zhengyu Gao, Guanghui Chen, Yujie Liu, Xin Gao, Guangjian Bai, Shaohui He, Tielong Liu, Wei Xu, Xinghai Yang, Jian Jiao, Jianru Xiao Background Lung cancer leads to the largest number of cancer-related deaths worldwide and is usually accompanied with metastasis which is the primary cause of those death and correlated with poor prognosis. However, the mechanism of lung cancer metastasis is still lack of definition. Methods We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of Kras G12D and inactivation of P53 in mouse lungs by analyzing GSE40222 about the differentially expressed genes (DEGs), pathways and hub genes. And human lung AD databases are used to verify the conversed changes of identified key gene and then followed functional studies are performed to explore the functions of key gene. Results We identified 165 genes differentially expressed in lung AD metastasis compared to primary AD. Pathway analysis identified 649 GO biological processes and 8 KEGG pathways, such as ECM-receptor interaction. Biological network interaction identified the hub genes during lung adenocarcinoma metastasis, such as the up-regulated COL5A1 , a novel gene in AD metastasis. We found it's also increased in human AD and advanced stage. Knockdown of COL5A1 in human AD metastatic cells inhibited cell growth and invasion, and induced cell apoptosis. Notably, higher expression of COL5A1 was observed in the lung AD patients with recurrence and short survive. Conclusion By analyzing mouse lung AD and its metastases, we identified the potential key genes and pathways regulating lung AD metastasis, such as COL5A1 . The following analysis of COL5A1 in human AD database and cells explores its functions, holding the implications of target therapy in AD metastasis and also providing more clues for future studies.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 50
    Publication Date: 2018-05-07
    Description: Publication date: 30 July 2018 Source: Gene, Volume 665 Author(s): Pingyang Wang, Simin Bi, Weiyang Wei, Zhiyong Qiu, Dingguo Xia, Xingjia Shen, Qiaoling Zhao Aldose reductase (AR) is a rate-limiting enzyme in the polyol pathway and is also the key enzyme involved in diabetic complications. The silkworm purple quail-like mutant ( q-l p ) exhibits pigmented dots on its epidermis. The q-l p mutant also shows developmental abnormalities and decreased vitality. In this study, fat bodies from the q-l p mutant and the wildtype 932VR strain were subjected to two-dimensional gel electrophoresis (2-DE) analysis, and the Bombyx mori AR ( BmAR ) protein was found to be significantly downregulated in the q-l p mutant. The expression of BmAR at the mRNA level was also significantly downregulated, as verified through quantitative reverse transcription PCR (qRT-PCR). Knockdown of the expression of BmAR via RNAi resulted in a reduction of silkworm weight. The sorbitol level in q-l p was significantly lower than in the wildtype. These results suggested that the BmAR gene is closely related to the development of the q-l p mutant. Investigation of the cause of BmAR downregulation in the q-l p mutant could contribute to revealing the function of AR in insects and offers a new method of identifying AR inhibitors for the treatment of diabetic complications.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 51
    Publication Date: 2018-05-07
    Description: Publication date: 30 July 2018 Source: Gene, Volume 665 Author(s): Ke-Yi Ma, Shu-Fang Zhang, Si-Si Wang, Gao-Feng Qiu As an essential mediator in the Gonadotropin-releasing hormone (GnRH) signaling pathway, GnRH receptor (GnRHR) coupled to GnRH, plays an important role in activating the downstream pathway after stimulating a series of cascades to regulate reproduction. To detect the existence of GnRHR and potential GnRH signaling pathway, we cloned and characterized GnRHR in the Chinese mitten crab, Eriocheir sinensis (named EsGnRHR ). The full-length EsGnRHR cDNA is 2038 bp in length, including an open reading frame (ORF) of 1566 bp, a 57 bp 5′-untranslated region (5′-UTR) and a 415 bp 3′-UTR. Prediction of transmembrane domains in protein sequence revealed that the EsGnRHR protein contained seven hydrophobic transmembrane regions (TMs). Reverse transcription PCR revealed that EsGnRHR was mainly expressed in the thoracic nerve group and ovary, and weakly distributed in the testis and brain. In situ hybridization further demonstrated that EsGnRHR mRNA was localized at the protocerebrum and deutocerebrum. In the ovary and testis, the hybridization signal was dominantly at the earlier developmental stages. The signal was mainly localized in the cytoplasm cell in the ovary, and in the epithelium cell in the testis. During the different stages of gonadal development, EsGnRHR displayed increasing trends in both female and male when analyzed by quantitative real-time PCR, suggesting that EsGnRHR was involved in controlling gonadal development. Our study provides important information for further research on the molecular mechanisms underlying crab development.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 52
    Publication Date: 2018-05-07
    Description: Publication date: 15 July 2018 Source: Gene, Volume 663 Author(s): Hanting Liu, Haixia Zhu, Weihong Shi, Yadi Lin, Gaoxiang Ma, Guoquan Tao, Weida Gong, Qinghong Zhao, Mulong Du, Meilin Wang, Haiyan Chu, Zhengdong Zhang Objective We explored the association between single nucleotide polymorphisms (SNPs) rs207454 and rs494852 located in xanthine dehydrogenase ( XDH ) and gastric cancer (GC) survival. Methods A total of 940 patients with gastric cancer were enrolled and genotyped using TaqMan allelic discrimination method. The Kaplan–Meier test and log-rank examine were used to assess the effect of genetic variation. Results Patients carrying rs207454 CC genotype had a longer survival time than those with the AA genotype ( P  = 0.042). The similar association was detected in the recessive model ( P  = 0.017). We conducted expression quantitative trait loci (eQTL) analysis and found that gastric cancer patients carrying rs207454 CC genotype had significant lower XDH levels than those with AA/AC genotype, suggesting that rs207454 polymorphism effected the expression of XDH . Additionally, the Kaplan-Meier curves showed that gastric cancer patients with high expression of XDH had remarkably poor survival outcome than those with low expression (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.29–1.82). Conclusions Genetic variants in XDH were associated with the survival of gastric cancer and may act as prognostic markers for individual suffered from gastric cancer.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 53
    Publication Date: 2018-05-07
    Description: Publication date: 30 July 2018 Source: Gene, Volume 665 Author(s): Huiyu Wang, Xia Ye, Jidong Li, Bin Tan, Peng Chen, Jun Cheng, Wei Wang, Xianbo Zheng, Jiancan Feng Background Jujube witches' broom (JWB), caused by a phytoplasma, devastates jujube tree ( Ziziphus jujuba ) growth and production in Asia. Although host responses to phytoplasmas are studied at the phenotypic, physiological, biochemical and molecular levels, it remains unclear how a host plant responds at the molecular level during the primary stage of infection. Methods To understand the response of the jujube tree to JWB infection, leaves were sampled at different times during the phytoplasma infection. Transcriptomic analyses at six stages were performed to reveal how phytoplasma infection affects Chinese jujube gene expression through the determination of the key differentially expressed genes (DEGs), and their related pathways. Quantitative real-time PCR was applied to validate 10 differentially expressed genes at different JWB phytoplasma infection stages. Results A total of 25,067 unigenes were mapped to jujube genome reference sequences. In the first infection stage (0–2 weeks after grafting (WAG), a total of 582 jujube genes were differentially regulated but no visible symptoms appeared. Quite a few DEGs related to abscisic acid (ABA) and cytokinin (CTK) were down-regulated, while some related to jasmonic acid (JA) and salicylic acid (SA) were up-regulated, Genes related to plant-pathogen interaction were also differentially expressed. In the second infection stage (37–39WAG), witches' broom symptoms were visible, and a total of 4373 DEGs were identified. Genes involved in biosynthesis and signal transduction of ABA, brassinosteroid (BR), CTK, ethylene (ET), and auxin (IAA), GA, JA and SA, plant-pathogen interaction, flavonoid biosynthesis genes were significantly regulated, suggesting that jujube trees activated defense factors related to SA, JA, ABA and secondary metabolites to defend against phytoplasma infection. By the third infection stage (48–52WAG), serious symptoms occurred and 3386 DEGs were identified. Most DEGs involved in biosynthesis and signal transduction of JA, SA and GA were up-regulated, while those relating to ABA were down-regulated. Genes involved in plant-pathogen interaction were up- or down-regulated, while phenylpropanoid and flavonoid biosynthesis genes were significantly up-regulated. Meanwhile, DEGs involved in photosynthesis, chlorophyll and peroxisome biosynthesis, and carbohydrate metabolism were down-regulated. These results suggested that phytoplasma infection had completely destroyed jujube trees' defense system and had disturbed chlorophyll synthesis and photosynthetic activity in the infected leaves at the late stage, resulting in yellow leaves and other JWB symptoms. Discussion The results in this report suggested that phytohormone biosynthesis and signal transduction, photosynthesis, and secondary metabolism all played important roles in the battle between colonization and defense in the interaction between Ca . Phytoplasma ziziphi and jujube.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 54
    Publication Date: 2018-05-07
    Description: Publication date: 30 July 2018 Source: Gene, Volume 665 Author(s): Da Huo, Xiao Jiang, Xiaofen Wu, Chunhua Ren, Zonghe Yu, Jinshang Liu, Hongmei Li, Yao Ruan, Jing Wen, Ting Chen, Chaoqun Hu Trehalases are a group of enzymes that catalyse the conversion of trehalose to glucose, and they are observed in most organisms. In this study, the first echinoderm trehalase, designated Hl-Tre, was identified from a tropical sea cucumber, Holothuria leucospilota . The full-length cDNA of H. leucospilota trehalase ( Hl-Tre ) is 2461 bp in length with an open reading frame (ORF) of 1788 bp that encodes a 595-amino-acid protein with a deduced molecular weight of 67.95 KDa. The Hl-Tre protein contains a signal peptide at the N-terminal and a functional trehalase domain, which includes the signature motifs 1 and 2. The mRNA expression of Hl-Tre was ubiquitously detected in all selected tissues, with the highest level being detected in the intestine. By in situ hybridization (ISH), the positive Hl-Tre signals were observed in the brush borders of the intestinal mucosa. In embryonic and larval stages, the transcript levels of Hl-Tre decreased during embryonic development and increased after the pentactula stage. After a challenge of starvation, the intestinal Hl-Tre mRNA levels were observed to be first decreased and partially recovered thereafter. Overall, our study provided the first evidence for trehalase in echinoderms and showed that this enzyme was potentially linked to a trehalose metabolic pathway in sea cucumbers.
    Print ISSN: 0378-1119
    Electronic ISSN: 1879-0038
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 55
    Publication Date: 2018-05-07
    Description: Publication date: 1 August 2018 Source: NeuroImage, Volume 176 Author(s): Pierpaolo Croce, Filippo Zappasodi, Sara Spadone, Paolo Capotosto Different electrophysiological (EEG) correlates may provide specific important assessment of the period that anticipates an imperative stimulus. Previous study of our group showed that a local (i.e. parietal) anticipatory EEG marker (i.e. the event related de-synchronization of the alpha rhythms; ERD) is selectively affected when transcranial magnetic stimulation (TMS) is delivered over crucial nodes belonging to well-known human networks involved in different cognitive domains. Here, we investigated whether such distinction is also present in the whole brain activity as seen through the pre-stimulus microstate's topography, representing a global and reference-free measure of the neural activity. First, when subjects received a pseudo-stimulation (sham), we found two distinct pre-stimulus topographies during perceptual or memory task, respectively. Second, we reported that, during the visuo-spatial attention task, stimulation of left intraparietal sulcus (IPS), but not left angular gyrus (AG), significantly modifies the topography observed in the Sham condition. Conversely, stimulation of AG, but not IPS, changes the topography observed in the Sham condition during a semantic memory task. These findings provide the first causal evidence for the task and region specificity of the pre-stimulus EEG microstates, thus proposing this EEG index as of particular interest for the assessment of the period that precedes a predictable event.
    Print ISSN: 1053-8119
    Electronic ISSN: 1095-9572
    Topics: Medicine , Psychology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 56
    facet.materialart.
    Unknown
    Elsevier
    In: Lancet
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: The Lancet Author(s): Johanna A A G Damen, Lotty Hooft, Karel G M Moons
    Print ISSN: 0140-6736
    Electronic ISSN: 1474-547X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 57
    Publication Date: 2018-05-07
    Description: Publication date: 14 August 2018 Source: Journal of Theoretical Biology, Volume 451 Author(s): Ragna M. Eide, Andrew L. Krause, Nabil T. Fadai, Robert A. Van Gorder We examine the role of the travel time of a predator along a spatial network on predator-prey population interactions, where the predator is able to partially or fully sustain itself on a resource subsidy. The impact of access to food resources on the stability and behaviour of the predator-prey-subsidy system is investigated, with a primary focus on how incorporating travel time changes the dynamics. The population interactions are modelled by a system of delay differential equations, where travel time is incorporated as discrete delay in the network diffusion term in order to model time taken to migrate between spatial regions. The model is motivated by the Arctic ecosystem, where the Arctic fox consumes both hunted lemming and scavenged seal carcass. The fox travels out on sea ice, in addition to quadrennially migrating over substantial distances. We model the spatial predator-prey-subsidy dynamics through a “stepping-stone” approach. We find that a temporal delay alone does not push species into extinction, but rather may stabilize or destabilize coexistence equilibria. We are able to show that delay can stabilize quasi-periodic or chaotic dynamics, and conclude that the incorporation of dispersal delay has a regularizing effect on dynamics, suggesting that dispersal delay can be proposed as a solution to the paradox of enrichment.
    Print ISSN: 0022-5193
    Electronic ISSN: 1095-8541
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 58
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: The Lancet Author(s): Romana Pylypchuk, Sue Wells, Andrew Kerr, Katrina Poppe, Tania Riddell, Matire Harwood, Dan Exeter, Suneela Mehta, Corina Grey, Billy P Wu, Patricia Metcalf, Jim Warren, Jeff Harrison, Roger Marshall, Rod Jackson Background Most cardiovascular disease risk prediction equations in use today were derived from cohorts established last century and with participants at higher risk but less socioeconomically and ethnically diverse than patients they are now applied to. We recruited a nationally representative cohort in New Zealand to develop equations relevant to patients in contemporary primary care and compared the performance of these new equations to equations that are recommended in the USA. Methods The PREDICT study automatically recruits participants in routine primary care when general practitioners in New Zealand use PREDICT software to assess their patients' risk profiles for cardiovascular disease, which are prospectively linked to national ICD-coded hospitalisation and mortality databases. The study population included male and female patients in primary care who had no prior cardiovascular disease, renal disease, or congestive heart failure. New equations predicting total cardiovascular disease risk were developed using Cox regression models, which included clinical predictors plus an area-based deprivation index and self-identified ethnicity. Calibration and discrimination performance of the equations were assessed and compared with 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCEs). The additional predictors included in new PREDICT equations were also appended to the PCEs to determine whether they were independent predictors in the equations from the USA. Findings Outcome events were derived for 401 752 people aged 30–74 years at the time of their first PREDICT risk assessment between Aug 27, 2002, and Oct 12, 2015, representing about 90% of the eligible population. The mean follow-up was 4·2 years, and a third of participants were followed for 5 years or more. 15 386 (4%) people had cardiovascular disease events (1507 [10%] were fatal, and 8549 [56%] met the PCEs definition of hard atherosclerotic cardiovascular disease) during 1 685 521 person-years follow-up. The median 5-year risk of total cardiovascular disease events predicted by the new equations was 2·3% in women and 3·2% in men. Multivariable adjusted risk increased by about 10% per quintile of socioeconomic deprivation. Māori, Pacific, and Indian patients were at 13–48% higher risk of cardiovascular disease than Europeans, and Chinese or other Asians were at 25–33% lower risk of cardiovascular disease than Europeans. The PCEs overestimated of hard atherosclerotic cardiovascular disease by about 40% in men and by 60% in women, and the additional predictors in the new equations were also independent predictors in the PCEs. The new equations were significantly better than PCEs on all performance metrics. Interpretation We constructed a large prospective cohort study representing typical patients in primary care in New Zealand who were recommended for cardiovascular disease risk assessment. Most patients are now at low risk of cardiovascular disease, which explains why the PCEs based mainly on old cohorts substantially overestimate risk. Although the PCEs and many other equations will need to be recalibrated to mitigate overtreatment of the healthy majority, they also need new predictors that include measures of socioeconomic deprivation and multiple ethnicities to identify vulnerable high-risk subpopulations that might otherwise be undertreated. Funding Health Research Council of New Zealand, Heart Foundation of New Zealand, and Healthier Lives National Science Challenge.
    Print ISSN: 0140-6736
    Electronic ISSN: 1474-547X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 59
    facet.materialart.
    Unknown
    Elsevier
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: The Lancet Oncology Author(s): David M Ross
    Print ISSN: 1470-2045
    Electronic ISSN: 1474-5488
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 60
    Publication Date: 2018-05-07
    Description: Publication date: 14 August 2018 Source: Journal of Theoretical Biology, Volume 451 Author(s): Travis Monk A principal problem of evolutionary graph theory is to find the probability that an initial mutant population will fix on a graph, i.e. that the mutants will eventually replace the indigenous population. This problem is particularly difficult when the dimensionality of a graph is high. Martingales can yield compact and exact expressions for the fixation probability of an evolutionary graph. Crucially, the tractability of martingales does not necessarily depend on the dimensionality of a graph. We will use martingales to obtain the exact fixation probability of graphs with high dimensionality, specifically k-partite graphs (or ‘circular flows’) and megastars (or ‘superstars’). To do so, we require that the edges of the graph permit mutants to reproduce in one direction and indigenous in the other. The resultant expressions for fixation probabilities explicitly show their dependence on the parameters that describe the graph structure, and on the starting position(s) of the initial mutant population. In particular, we will investigate the effect of funneling on the fixation probability of k-partite graphs, as well as the effect of placing an initial mutant in different partitions. These are the first exact and explicit results reported for the fixation probability of evolutionary graphs with dimensionality greater than 2, that are valid over all parameter space. It might be possible to extend these results to obtain fixation probabilities of high-dimensional evolutionary graphs with undirected or directed connections. Martingales are a formidable theoretical tool that can solve fundamental problems in evolutionary graph theory, often within a few lines of straightforward mathematics. Graphical abstract
    Print ISSN: 0022-5193
    Electronic ISSN: 1095-8541
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 61
    Publication Date: 2018-05-07
    Description: Publication date: Available online 30 April 2018 Source: Seminars in Cancer Biology Author(s): Shuai Jiang, Zhi Yang, Shouyin Di, Wei Hu, Zhiqiang Ma, Fulin Chen, Yang Yang Forkhead box O (FOXO) family has recently been highlighted as important transcriptional regulators associated with many diverse carcinomas. Although redundant functionality between FOXO family members with cancer is known, regulatory ability of FOXO4 for tumorigenesis and tumor metastasis is still on the way. FOXO4 significantly regulates cell cycle, resists oxidative stress, and responses to hypoxia. FOXO4 alteration is closely linked to the progression of human cancer. In this review, we introduce the regulation of FOXO4 in physiological and pathological conditions. Particularly, the pathophysiological processes and molecular pathways regulated by FOXO4 in the development and progression of cancer are also summarized. Moreover, whether FOXO4 acts as a tumor-suppressor or pro-tumoral factor in tumors and the potential directions of future FOXO4 research are discussed. The information reviewed here may assist in the experimental design and increase the potential of FOXO4 as a therapeutic target for cancer.
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 62
    Publication Date: 2018-05-07
    Description: Publication date: Available online 23 April 2018 Source: Seminars in Cancer Biology Author(s): Bi Ning Zhang, Andrés Bueno Venegas, Ian D. Hickson, Wai Kit Chu Genome instability and cell cycle dysregulation are commonly associated with cancer. DNA replication stress driven by oncogene activation during tumorigenesis is now well established as a source of genome instability. Replication stress generates DNA damage not only during S phase, but also in the subsequent mitosis, where it impacts adversely on chromosome segregation. Some regions of the genome seem particularly sensitive to replication stress-induced instability; most notably, chromosome fragile sites. In this article, we review some of the important issues that have emerged in recent years concerning DNA replication stress and fragile site expression, as well as how chromosome instability is minimized by a family of ring-shaped protein complexes known as SMC proteins. Understanding how replication stress impacts on S phase and mitosis in cancer should provide opportunities for the development of novel and tumour-specific treatments.
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 63
    Publication Date: 2018-05-07
    Description: Publication date: Available online 21 April 2018 Source: Seminars in Cancer Biology Author(s): Chong T. Luo, Ming O. Li The evolutionally conserved forkhead box O (Foxo) family of transcription factors is pivotal in the control of nutrient sensing and stress responses. Recent studies have revealed that the Foxo proteins have been rewired to regulate highly specialized T cell activities. Here, we review the latest advances in the understanding of how Foxo transcription factors control T cell biology, including T cell trafficking, naive T cell homeostasis, effector and memory responses, as well as the differentiation and function of regulatory T cells. We also discuss the emerging evidence on Foxo-mediated regulation in antitumor immunity. Future work will further explore how the Foxo-dependent programs in T cells can be exploited for cancer immunotherapy.
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 64
    facet.materialart.
    Unknown
    Elsevier
    Publication Date: 2018-05-07
    Description: Publication date: Available online 16 April 2018 Source: Seminars in Cancer Biology Author(s): Tianzuo Zhan, Niklas Rindtorff, Johannes Betge, Matthias P. Ebert, Michael Boutros CRISPR/Cas9 has become a powerful method for making changes to the genome of many organisms. First discovered in bacteria as part of an adaptive immune system, CRISPR/Cas9 and modified versions have found a widespread use to engineer genomes and to activate or to repress the expression of genes. As such, CRISPR/Cas9 promises to accelerate cancer research by providing an efficient technology to dissect mechanisms of tumorigenesis, identify targets for drug development, and possibly arm cells for cell-based therapies. Here, we review current applications of the CRISPR/Cas9 technology for cancer research and therapy. We describe novel Cas9 variants and how they are used in functional genomics to discover novel cancer-specific vulnerabilities. Furthermore, we highlight the impact of CRISPR/Cas9 in generating organoid and mouse models of cancer. Finally, we provide an overview of the first clinical trials that apply CRISPR/Cas9 as a therapeutic approach against cancer.
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 65
    facet.materialart.
    Unknown
    Elsevier
    Publication Date: 2018-05-07
    Description: Publication date: April 2018 Source: Seminars in Cancer Biology, Volume 49
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 66
    Publication Date: 2018-05-07
    Description: Publication date: June 2018 Source: Data in Brief, Volume 18 Author(s): Chinyerem Adeniji, Olufemi Adeyeye, Oluwole Iyiola, Maxwell Olokundun, Deborah Motilewa, Stephen Ibidunni, Mosunmola Akinbode In today’s business environment, organizations must continually and constantly reinvent themselves to stay relevant because they conduct operations in workplaces that are characterized by steady competition and erratic change. Most studies show that organizational improvement cannot occur without strategic changes directed to yield a difference in performance. Thus, improving performance requires the consideration of change-related policies and individuals’ dispositions relevant to change. Strategic change as perceived by many authors requires qualitative changes and not simple continuous and usual changes. Strategic change must be aligned to the mission, and purpose of an organization. Employees’ attitudes towards change strongly relates to their attitudes about their employer and changes at their organization because organizations continually commence new programs of organizational change, these ongoing and seemingly endless efforts put a lot of burden not only on organizations but also on individuals. Researchers highlight the challenges to strategic change as; poor organizational management and culture, increased technology installation, organizational structure, strong competition and employee issues. Attitudes toward strategic change are the feelings employees have toward different internal policies of the organization. Many investigations suggest that it is reasonable to expect employees to react to strategic change efforts since the process of change involves going from the known to the unknown. Consequently, it can be a very unpleasant experience for employees thus this article presents data in this regard.
    Print ISSN: 2352-3409
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 67
    facet.materialart.
    Unknown
    Elsevier
    Publication Date: 2018-05-07
    Description: Publication date: 15 June 2018 Source: Developmental Biology, Volume 438, Issue 2
    Print ISSN: 0012-1606
    Electronic ISSN: 1095-564X
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 68
    Publication Date: 2018-05-07
    Description: Publication date: Available online 5 May 2018 Source: DNA Repair Author(s): Marcus C. Parrish, Isaac A. Chaim, Zachary D. Nagel, Steven R. Tannenbaum, Leona D. Samson, Bevin P. Engelward Nitric oxide, a reactive nitrogen species released by lymphocytes during inflammation, has been shown to react with DNA, proteins, and cells. Protein S-nitrosation, the process by which nitric oxide reacts with cysteine residues on proteins, has been found to modulate DNA repair. However, relatively little is known about the role of S-nitrosation in the context of repair of alkylation damage by the base excision repair pathway (BER). BER of DNA exposed to a methylating agent, such as methylmethane sulfonate (MMS), is initiated by the Alkyladenine DNA Glycosylase (AAG), which removes damaged bases. Here, we analyzed the effects of the transnitrosating peptide S-nitrosoglutathione (GSNO) on the repair of methylated bases. Through the use of the CometChip, a high-throughput version of the comet assay that measures DNA strand breaks, we observed an AAG-dependent increase in BER intermediates in GSNO-exposed mouse embryonic fibroblasts after MMS challenge. Through the use of the Fluorescence-based Multiplexed Host Cell Reactivation Assay (FM-HCR), a high-throughput assay used to measure DNA repair capacity, GSNO exposure was found to alter the activities of BER proteins and reduce overall BER capacity. Furthermore, cells exposed to both GSNO and MMS displayed reduced viability. Given that unrepaired BER intermediates are toxic, these results suggest that the altered activities of BER proteins following GSNO exposure induces an increase in BER intermediates that leads to increased cell death. Taken together, this study shows the detrimental effects of S-nitrosation on the BER pathway and reveals the deleterious impact of altered BER capacity under conditions of co-exposure to an alkylating agent.
    Print ISSN: 1568-7864
    Electronic ISSN: 1568-7856
    Topics: Biology
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 69
    facet.materialart.
    Unknown
    Elsevier
    In: Urology
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: Urology Author(s): Dima Raskolnikov, John L. Gore
    Print ISSN: 0090-4295
    Electronic ISSN: 1527-9995
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 70
    facet.materialart.
    Unknown
    Elsevier
    In: Urology
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: Urology Author(s): Amy N. Luckenbaugh, Tudor Borza
    Print ISSN: 0090-4295
    Electronic ISSN: 1527-9995
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 71
    Publication Date: 2018-05-07
    Description: Publication date: 24 May 2018 Source: Vaccine, Volume 36, Issue 22 Author(s): Laura M. Fischer, Michael W. Wolff, Udo Reichl The continuously increasing demand for potent and safe vaccines and the intensifying economic pressure on health care systems underlines the need for further optimization of vaccine manufacturing. Here, we focus on downstream processing of human influenza vaccines, investigating the purification of serum-free cell culture-derived influenza virus (A/PR/8/34 H1N1) using continuous chromatography. Therefore, quaternary amine anion exchange monoliths (CIM® QA) were characterized for their capacity to capture virus particles from animal cells cultivated in different media and their ability to separate virions from contaminating host cell proteins and DNA. The continuous chromatography was implemented as simulated moving bed chromatography (SMB) in a three zone open loop configuration with a detached high salt zone for regeneration. SMBs exploiting 10% and 50% of the monoliths’ dynamic binding capacity, respectively, allowed the depletion of >98% of the DNA and >52% of the total protein. Based on the hemagglutination assay (HA assay), the virus yield was higher at 10% capacity use (89% vs. 45%). Both SMB separations resulted in a ratio of total protein to hemagglutinin antigen (based on single radial diffusion assay, SRID assay) below the required levels for manufacturing of human vaccines (less than 100 µg of protein per virus strain per dose). The level of contaminating DNA was five-times lower for the 10% loading, but still exceeded the required limit for human vaccines. A subsequent Benzonase® treatment step, however, reduced the DNA contamination below 10 ng per dose. Coupled to continuous cultivations for virus propagation, the establishment of integrated processes for fully continuous production of vaccines seems to be feasible.
    Print ISSN: 0264-410X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 72
    Publication Date: 2018-05-07
    Description: Publication date: Available online 4 May 2018 Source: Urology Author(s): Klaus Eredics, David Wachabauer, Florian Röthlin, Stephan Madersbacher, Ingrid Schauer Objective To assess long-term re-operation rates and mortality after transurethral resection of the prostate (TURP) and open prostatectomy (PE) as therapy for lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE). Methods Analysis of a nation-wide data base of all patients who underwent TURP/open PE 2002-2006 and who were followed for 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision) and death were calculated. Data were provided by the Austrian Public Health Institute. This series was compared to a previously published almost equally sized nation-wide cohort that underwent surgery 1992-1996 in Austria. Results Between 2002 and 2006 a total of 21.674 patients underwent TURP (n=20.388) or open PE (n=1.286). At 8yrs, the re-TURP rate after primary TURP was 8.3% versus 4.3% after open PE. The re-TURP rate was higher in the 80+ cohort. The overall endourological re-intervention rate at 8yrs was 12.7% for TURP and 8.8% for open PE. Re-intervention rates did not improve as compared to the 1992-1996 series. The 30days in-hospital mortality rate was 0.1% for TURP and 0.2% for open PE. Mortality rates improved by approximately 20% as compared to the 1992-1996 series. Conclusions In Austria TURPs rates remained stable between 1992 and 2006, paralleled by a 50% decline of open PE. Within a decade, mortality rates declined by 20%, yet re-intervention rates remained unchanged.
    Print ISSN: 0090-4295
    Electronic ISSN: 1527-9995
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 73
    Publication Date: 2018-05-07
    Description: Publication date: 24 May 2018 Source: Vaccine, Volume 36, Issue 22 Author(s): Rohiverth Guarecuco, Jennifer Lu, Kevin J. McHugh, James J. Norman, Lavanya S. Thapa, Emily Lydon, Robert Langer, Ana Jaklenec The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40 years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters. Sixteen poly(lactic-co-glycolic acid) (PLGA) microsphere formulations containing bovine serum albumin (BSA) as a model vaccine antigen were screened in vitro to determine their respective release kinetics. Three formulations that exhibited desirable pulsatile release profiles were then selected for studying immunogenicity in mice. Two low-dose microsphere formulations induced peak anti-BSA IgG antibody titers of 13.9 ± 1.3 and 13.7 ± 2.2 log 2 compared to 15.5 ± 1.5 log 2 for a series of three bolus injections delivered at 0, 4, and 8 weeks with an equivalent cumulative dose. Similarly, high-dose formulations induced peak antibody titers that were 16.1 ± 2.1 log 2 compared to 17.7 ± 2.2 log 2 for controls. All three microparticle formulations studied in vivo induced peak antibody titers that were statistically similar to bolus controls. These results suggest that pulsatile antigen release from polymeric microparticles is a promising approach for single-injection vaccination, which could potentially reduce the logistical burden associated with immunization in the developing world.
    Print ISSN: 0264-410X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 74
    facet.materialart.
    Unknown
    Elsevier
    In: Vaccine
    Publication Date: 2018-05-07
    Description: Publication date: 24 May 2018 Source: Vaccine, Volume 36, Issue 22
    Print ISSN: 0264-410X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 75
    Publication Date: 2018-05-07
    Description: Publication date: 24 May 2018 Source: Vaccine, Volume 36, Issue 22 Author(s): Jian Yan, Matthew P. Morrow, Jaemi S. Chu, Trina Racine, Charles C. Reed, Amir S. Khan, Kate E. Broderick, J. Joseph Kim, Gary P. Kobinger, Niranjan Y. Sardesai, David B. Weiner Despite the routine development and distribution of seasonal influenza vaccines, influenza remains an important pathogen contributing to significant human morbidity as well as mortality each year. The seasonal variability of influenza creates a significant issue for vaccine development of seasonal strains that can afford protection from infection or disease based on serotype matching. It is appreciated that the globular head of the HA antigen contained in the vaccines generates antibodies that result in HAI activity that are a major correlates of the protection against a particular strain. Due to seasonal genetic changes in the HA protein, however, new vaccine strains are needed to be developed continually to match the new HA antigen of that seasons virus. A distinct advantage in seasonal vaccine development would be if a small group of antigens could be developed that could span many seasons without needed to be replaced due to this genetic drift. Here we report on a synthetic microconsensus approach that relies on a small collection of 4 synthetic H1HA DNA antigens which together induce broad protective HAI immunity spanning decades of H1 influenza viruses in mice, guinea pigs and non-human primates. The protective HAI titers induced by microconsensus immunogens are fully functional in vivo as immunized ferrets were completely protected from A/Mexico/InDRE4487/2009 virus infection and morbidity associated with lethal challenge. These results are encouraging that a limited easy-to-formulate collection of invariant antigens can be developed which can span seasonal vaccine changes allowing for continued immune protection.
    Print ISSN: 0264-410X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...
  • 76
    Publication Date: 2018-05-07
    Description: Publication date: 24 May 2018 Source: Vaccine, Volume 36, Issue 22 Author(s): D.V. Lopez-Guerrero, N. Arias, L. Gutierrez-Xicotencatl, L. Chihu-Amparan, A. González, A. Pedroza-Saavedra, G. Rosas-Salgado, J.C. Villegas-Garcia, O. Badillo-Godinez, G. Fernandez, S. Lopez, F. Esquivel-Guadarrama VP2/VP6 virus like particles (VLPs) are very effective in inducing protection against the rotavirus infection in animal models. Individually, VP6 can also induce protection. However, there is no information about the immunogenicity of VP2. The aim of this work was to evaluate the efficacy of DNA vaccines codifying for VP2 or VP6, alone or combined, to induce protection against the rotavirus infection. Murine rotavirus VP2 and VP6 genes were cloned into the pcDNA3 vector. Adult BALB/c mice were inoculated three times by intramuscular (i.m.) injections with 100 or 200 µg of pcDNA3-VP2 or pcDNA3-VP6 alone or co-administered with 100 µg of pcDNA3-VP2/100 µg of pcDNA3-VP6. Two weeks after the last inoculation, mice were challenged with the wild type murine rotavirus strain epizootic diarrhea of infant mice (EDIM wt ). We found that both plasmids, pcDNA3-VP2 and pcDNA3-VP6, were able to induce rotavirus-specific serum antibodies, but not intestinal rotavirus-specific IgA; only 200 µg of pcDNA3-VP6 induced 35% protection against the infection. A similar level of protection was found when mice were co-administered with 100 µg of pcDNA3-VP2/100 µg of pcDNA3-VP6 (1:1 ratio). However, the best protection (up to 58%) occurred when mice were inoculated with 10 µg of pcDNA3-VP2/100 µg of pcDNA3-VP6 (1:10 ratio). These results indicate that the DNA plasmid expressing VP6 is a better vaccine candidate that the one expressing VP2. However, when co-expressed, VP2 potentiates the immunogenicity and protective efficacy of VP6.
    Print ISSN: 0264-410X
    Topics: Medicine
    Published by Elsevier
    Signatur Availability
    BibTip Others were also interested in ...