Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Abstract: Large-scale genome-wide association studies (GWAS) have likely uncovered all common variants at the GWAS significance level. Additional variants within the suggestive range (0.0001〉 P 〉 5x10(-8)) are, however, still of interest for identifying causal associations. This analysis aimed to apply novel variant prioritization approaches to identify additional lung cancer variants that may not reach the GWAS level. Effects were combined across studies with a total of 33456 controls and 6756 adenocarcinoma (AC; 13 studies), 5061 squamous cell carcinoma (SCC; 12 studies) and 2216 small cell lung cancer cases (9 studies). Based on prior information such as variant physical properties and functional significance, we applied stratified false discovery rates, hierarchical modeling and Bayesian false discovery probabilities for variant prioritization. We conducted a fine mapping analysis as validation of our methods by examining top-ranking novel variants in six independent populations with a total of 3128 cases and 2966 controls. Three novel loci in the suggestive range were identified based on our Bayesian framework analyses: KCNIP4 at 4p15.2 (rs6448050, P = 4.6x10(-7)) and MTMR2 at 11q21 (rs10501831, P = 3.1x10(-6)) with SCC, as well as GAREM at 18q12.1 (rs11662168, P = 3.4x10(-7)) with AC. Use of our prioritization methods validated two of the top three loci associated with SCC (P = 1.05x10(-4) for KCNIP4, represented by rs9799795) and AC (P = 2.16x10(-4) for GAREM, represented by rs3786309) in the independent fine mapping populations. This study highlights the utility of using prior functional data for sequence variants in prioritization analyses to search for robust signals in the suggestive range.
    Type of Publication: Journal article published
    PubMed ID: 26363033
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2013-07-03
    Description: All bactericidal antibiotics were recently proposed to kill by inducing reactive oxygen species (ROS) production, causing destabilization of iron-sulfur (Fe-S) clusters and generating Fenton chemistry. We find that the ROS response is dispensable upon treatment with bactericidal antibiotics. Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative machinery, SUF, cannot efficiently mature respiratory complexes I and II, resulting in impendence of the proton motive force (PMF), which is required for bactericidal aminoglycoside uptake. Similarly, during iron limitation, cells become intrinsically resistant to aminoglycosides by switching from ISC to SUF and down-regulating both respiratory complexes. We conclude that Fe-S proteins promote aminoglycoside killing by enabling their uptake.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ezraty, Benjamin -- Vergnes, Alexandra -- Banzhaf, Manuel -- Duverger, Yohann -- Huguenot, Allison -- Brochado, Ana Rita -- Su, Shu-Yi -- Espinosa, Leon -- Loiseau, Laurent -- Py, Beatrice -- Typas, Athanasios -- Barras, Frederic -- New York, N.Y. -- Science. 2013 Jun 28;340(6140):1583-7. doi: 10.1126/science.1238328.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Chimie Bacterienne, Aix-Marseille Universite, CNRS, UMR 7283, Institut de Microbiologie de la Mediterranee, 31 Chemin Joseph Aiguier, 13009 Marseille France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23812717" target="_blank"〉PubMed〈/a〉
    Keywords: Aminoglycosides/*metabolism/*pharmacology ; Ampicillin/metabolism/pharmacology ; Anti-Bacterial Agents/*metabolism/*pharmacology ; Carrier Proteins/genetics/*metabolism ; Drug Resistance, Bacterial/*genetics ; Electron Transport Complex I/metabolism ; Electron Transport Complex II/metabolism ; Escherichia coli/drug effects/metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Gentamicins/metabolism/pharmacology ; Iron/metabolism ; Iron-Sulfur Proteins/genetics/*metabolism ; Reactive Oxygen Species/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2018-05-01
    Description: The Journal of Organic Chemistry DOI: 10.1021/acs.joc.8b00142
    Print ISSN: 0022-3263
    Electronic ISSN: 1520-6904
    Topics: Chemistry and Pharmacology
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2018-07-10
    Description: Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury with various origins. HLA-DQA1 , -DQB1 , and -DRB1 have been associated with development of tubulointerstitial nephritis and uveitis (TINU) syndrome in case reports and small case series, but information about HLA genetic susceptibility to drug hypersensitivity–related ATIN (D-ATIN) or other types of ATIN is limited. In this article, we genotyped 154 patients with ATIN of different causes and 200 healthy controls at HLA-DQA1 , -DQB1 , and - DRB1 loci. We found that there was no difference between patients with D-ATIN and TINU in the carrier’s frequency of HLA-DQA1 , -DQB1 , or -DRB1 . Patients with Sjogren’s syndrome–ATIN and IgG4-related ATIN presented a different pattern of tested HLA alleles. HLA-DQA1*0104 ( p value corrected by false discovery rate method [ Pc ] = 4.72 x 10 –22 , odds ratio [OR] = 13.81), -DQB1*0503 ( Pc = 1.95 x 10 –14 , OR = 9.51), and -DRB1*1405 ( Pc = 8.06 x 10 –19 , OR = 12.80) were significant risk alleles for the occurrence of D-ATIN and TINU. There were no significant associations between tested HLA alleles and ATIN induced by other causes. Patients with D-ATIN/TINU carrying HLA-DQA1*0104 / DQB1*0503 / DRB1*1405 had higher peak serum creatinine and more severe renal tubulointerstitial inflammatory impairment. They also had significantly higher levels of tubular HLA-DR and HLA-DQ expression, which were correlated with the numbers of interstitial CD4 + T lymphocytes ( r = 0.975, p 〈 0.001 and r = 0.832, p = 0.005, respectively) and monocytes/macrophages ( r = 0.721, p = 0.004 and r = 0.615, p = 0.02, respectively). In conclusion, patients with D-ATIN or TINU have genetic susceptibility in HLA - DQA1 , - DQB1 , and - DRB1 alleles. HLA-DQA1*0104/DQB1*0503/DRB1*1405 serves as a significant risk haplotype for development of D-ATIN and TINU, which might facilitate renal tubulointerstitial inflammation by enhancing Ag-presenting capacity of renal tubular cells.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-11-29
    Description: We engineered a microneedle patch integrated with cardiac stromal cells (MN-CSCs) for therapeutic heart regeneration after acute myocardial infarction (MI). To perform cell-based heart regeneration, cells are currently delivered to the heart via direct muscle injection, intravascular infusion, or transplantation of epicardial patches. The first two approaches suffer from poor cell retention, while epicardial patches integrate slowly with host myocardium. Here, we used polymeric MNs to create "channels" between host myocardium and therapeutic CSCs. These channels allow regenerative factors secreted by CSCs to be released into the injured myocardium to promote heart repair. In the rat MI model study, the application of the MN-CSC patch effectively augmented cardiac functions and enhanced angiomyogenesis. In the porcine MI model study, MN-CSC patch application was nontoxic and resulted in cardiac function protection. The MN system represents an innovative approach delivering therapeutic cells for heart regeneration.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Publication Date: 2012-11-23
    Description: Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Su, Chih-Ying -- Menuz, Karen -- Reisert, Johannes -- Carlson, John R -- DC009613/DC/NIDCD NIH HHS/ -- F32 DC011242/DC/NIDCD NIH HHS/ -- F32DC011242/DC/NIDCD NIH HHS/ -- R01 DC004729/DC/NIDCD NIH HHS/ -- R01 DC009613/DC/NIDCD NIH HHS/ -- R01 DC011697/DC/NIDCD NIH HHS/ -- England -- Nature. 2012 Dec 6;492(7427):66-71. doi: 10.1038/nature11712. Epub 2012 Nov 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23172146" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles gambiae/drug effects/physiology ; Carbon Dioxide/pharmacology ; Dose-Response Relationship, Drug ; Drosophila melanogaster/cytology/drug effects/physiology ; Female ; Neural Inhibition/drug effects/*physiology ; Olfactory Pathways/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*metabolism ; Sensilla/cytology/drug effects/innervation/physiology ; Smell/drug effects/physiology ; *Synapses ; Synaptic Transmission/drug effects
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2016-04-14
    Description: Volcanic eruptions transfer huge amounts of gas to the atmosphere. In particular, the sulfur released during large silicic explosive eruptions can induce global cooling. A fundamental goal in volcanology, therefore, is to assess the potential for eruption of the large volumes of crystal-poor, silicic magma that are stored at shallow depths in the crust, and to obtain theoretical bounds for the amount of volatiles that can be released during these eruptions. It is puzzling that highly evolved, crystal-poor silicic magmas are more likely to generate volcanic rocks than plutonic rocks. This observation suggests that such magmas are more prone to erupting than are their crystal-rich counterparts. Moreover, well studied examples of largely crystal-poor eruptions (for example, Katmai, Taupo and Minoan) often exhibit a release of sulfur that is 10 to 20 times higher than the amount of sulfur estimated to be stored in the melt. Here we argue that these two observations rest on how the magmatic volatile phase (MVP) behaves as it rises buoyantly in zoned magma reservoirs. By investigating the fluid dynamics that controls the transport of the MVP in crystal-rich and crystal-poor magmas, we show how the interplay between capillary stresses and the viscosity contrast between the MVP and the host melt results in a counterintuitive dynamics, whereby the MVP tends to migrate efficiently in crystal-rich parts of a magma reservoir and accumulate in crystal-poor regions. The accumulation of low-density bubbles of MVP in crystal-poor magmas has implications for the eruptive potential of such magmas, and is the likely source of the excess sulfur released during explosive eruptions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Parmigiani, A -- Faroughi, S -- Huber, C -- Bachmann, O -- Su, Y -- England -- Nature. 2016 Apr 28;532(7600):492-5. doi: 10.1038/nature17401. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Geochemistry and Petrology, ETH Zurich, Zurich 8092, Switzerland. ; School of Earth and Atmospheric Sciences, Georgia Institute of Technology, Georgia 30332, USA. ; School of Civil and Environmental Engineering, Georgia Institute of Technology, Georgia 30332, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074507" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2018-11-02
    Description: Tumor metastatic relapse is the primary cause for cancer-associated mortality. Metastatic relapse is believed to arise from quantities of tumor cells that are below detectable thresholds, which are able to resist radio/chemotherapy by obtaining a dormant state and hiding in certain organs, i.e., tumor reservoirs. The thymus, a central T-cell immune organ, has been suggested to be a premetastatic tumor reservoir for B-lymphoma cells. However, it remains unknown whether the thymus is able to harbor nonlymphoid solid tumor cells, and whether chemotherapy can thoroughly eliminate cancer cells in the thymus. If chemotherapy is not able to eliminate these cells in the thymus, then what processes allow for this? Melanoma cell–inoculated and genotoxic doxorubicin-treated mouse model systems were used to determine that the thymus, particularly the atrophied thymus, was able to harbor blood stream–circulating melanoma cells. In addition, a chemotherapy-induced DNA-damage response triggered p53 activation in nonmalignant thymic cells, which in turn resulted in thymocyte death and thymic epithelial cell senescence to develop an inflammatory thymic microenvironment. This inflammatory condition induced thymic-harbored minimal tumor cells to acquire a chemoresistant state. Implications: Here, the thymus serves as a premetastatic reservoir for nonlymphoid solid tumor cells during chemotherapy, which could be a novel target of minimal residual disease in antitumor therapy, thus preventing tumor metastatic relapse. Mol Cancer Res; 16(11); 1652–64. ©2018 AACR .
    Print ISSN: 1541-7786
    Electronic ISSN: 1557-3125
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2018-07-06
    Description: The crystallization problem is an outstanding challenge in the chemistry of porous covalent organic frameworks (COFs). Their structural characterization has been limited to modeling and solutions based on powder x-ray or electron diffraction data. Single crystals of COFs amenable to x-ray diffraction characterization have not been reported. Here, we developed a general procedure to grow large single crystals of three-dimensional imine-based COFs (COF-300, hydrated form of COF-300, COF-303, LZU-79, and LZU-111). The high quality of the crystals allowed collection of single-crystal x-ray diffraction data of up to 0.83-angstrom resolution, leading to unambiguous solution and precise anisotropic refinement. Characteristics such as degree of interpenetration, arrangement of water guests, the reversed imine connectivity, linker disorder, and uncommon topology were deciphered with atomic precision—aspects impossible to determine without single crystals.
    Keywords: Chemistry, Materials Science
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Publication Date: 2018-08-01
    Description: Organic Letters DOI: 10.1021/acs.orglett.8b02045
    Print ISSN: 1523-7060
    Electronic ISSN: 1523-7052
    Topics: Chemistry and Pharmacology
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...