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201.
Michael J. Overman Jiexin Zhang Scott Kopetz Michael Davies Jiang Zhi-Qin Katherine Stemke-Hale Petra Rümmele Christian Pilarsky Robert Grützmann Stanley Hamilton Rosa Hwang James L. Abbruzzese Gauri Varadhachary Bradley Broom Huamin Wang 《PloS one》2013,8(6)
Background
Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, bile duct, and duodenum by gene expression analysis.Methods
We analyzed 32 fresh-frozen resected, untreated periampullary adenocarcinomas (8 pancreatic, 2 extrahepatic biliary, 8 duodenal, and 14 ampullary) using the Affymetrix U133 Plus 2.0 genome array. Unsupervised and supervised hierarchical clustering identified two subtypes of ampullary carcinomas that were molecularly and histologically characterized.Results
Hierarchical clustering of periampullary carcinomas segregated ampullary carcinomas into two subgroups, which were distinctly different from pancreatic carcinomas. Non-pancreatic periampullary adenocarcinomas were segregated into two subgroups with differing prognoses: 5 year RFS (77% vs. 0%, p = 0.007) and 5 year OS (100% vs. 35%, p = 0.005). Unsupervised clustering analysis of the 14 ampullary samples also identified two subgroups: a good prognosis intestinal-like subgroup and a poor prognosis biliary-like subgroup with 5 year OS of 70% vs. 28%, P = 0.09. Expression of CK7+/CK20- but not CDX-2 correlated with these two subgroups. Activation of the AKT and MAPK pathways were both increased in the poor prognostic biliary-like subgroup. In an independent 80 patient ampullary validation dataset only histological subtype (intestinal vs. pancreaticobiliary) was significantly associated with OS in both univariate (p = 0.006) and multivariate analysis (P = 0.04).Conclusions
Gene expression analysis discriminated pancreatic adenocarcinomas from other periampullary carcinomas and identified two prognostically relevant subgroups of ampullary adenocarcinomas. Histological subtype was an independent prognostic factor in ampullary adenocarcinomas. 相似文献202.
Larson Boundenga Boris Makanga Benjamin Ollomo Aude Gilabert Virginie Rougeron Bertrand Mve-Ondo Céline Arnathau Patrick Durand Nancy Diamella Moukodoum Alain-Prince Okouga Lucresse Delicat-Loembet Lauriane Yacka-Mouele Nil Rahola Eric Leroy Cheikh Tidiane BA Francois Renaud Franck Prugnolle Christophe Paupy 《PloS one》2016,11(2)
Re-examination, using molecular tools, of the diversity of haemosporidian parasites (among which the agents of human malaria are the best known) has generally led to rearrangements of traditional classifications. In this study, we explored the diversity of haemosporidian parasites infecting vertebrate species (particularly mammals, birds and reptiles) living in the forests of Gabon (Central Africa), by analyzing a collection of 492 bushmeat samples. We found that samples from five mammalian species (four duiker and one pangolin species), one bird and one turtle species were infected by haemosporidian parasites. In duikers (from which most of the infected specimens were obtained), we demonstrated the existence of at least two distinct parasite lineages related to Polychromophilus species (i.e., bat haemosporidian parasites) and to sauropsid Plasmodium (from birds and lizards). Molecular screening of sylvatic mosquitoes captured during a longitudinal survey revealed the presence of these haemosporidian parasite lineages also in several Anopheles species, suggesting a potential role in their transmission. Our results show that, differently from what was previously thought, several independent clades of haemosporidian parasites (family Plasmodiidae) infect mammals and are transmitted by anopheline mosquitoes. 相似文献
203.
Matthew J. O’Brien Ji Young Lee Mercedes R. Carnethon Ronald T. Ackermann Maria C. Vargas Andrew Hamilton Nivedita Mohanty Sarah S. Rittner Jessica N. Park Amro Hassan David R. Buchanan Lei Liu Joseph Feinglass 《PLoS medicine》2016,13(7)
BackgroundIn 2015, the United States Preventive Services Task Force (USPSTF) recommended targeted screening for prediabetes and diabetes (dysglycemia) in adults who are aged 40 to 70 y old and overweight or obese. Given increasing prevalence of dysglycemia at younger ages and lower body weight, particularly among racial/ethnic minorities, we sought to determine whether the current screening criteria may fail to identify some high-risk population subgroups.ConclusionsTargeted diabetes screening based on new USPSTF criteria may detect approximately half of adult community health center patients with undiagnosed dysglycemia and proportionately fewer racial/ethnic minorities than whites. Future research is needed to estimate the performance of these screening criteria in population-based samples. 相似文献
204.
Michael E. Hall Tina E. Brinkley Haroon Chughtai Timothy M. Morgan Craig A. Hamilton Jennifer H. Jordan R. Brandon Stacey Sandra Soots W. Gregory Hundley 《PloS one》2016,11(1)
Background
Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women.Methods
Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress.Results
We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress.Conclusions
Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men. 相似文献205.
Claire E Naylor Claire Bagnéris Paul G DeCaen Altin Sula Antonella Scaglione David E Clapham BA Wallace 《The EMBO journal》2016,35(8):820-830
Voltage‐gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na+ ≈ Li+ ≫ K+, Ca2+, Mg2+) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones. 相似文献
206.
Genetic and paleomodelling evidence of the population expansion of the cattle egret Bubulcus ibis in Africa during the climatic oscillations of the Late Pleistocene
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Carlos Congrains Antônio F. Carvalho Elder A. Miranda Graeme S. Cumming Dominic A. W. Henry Shiiwua A. Manu Jacinta Abalaka Cristiano D. Rocha Moussa S. Diop Joãozinho Sá Hamilton Monteiro Lars H. Holbech Francis Gbogbo Silvia N. Del Lama 《Journal of avian biology》2016,47(6):846-857
Increasing aridity during glacial periods produced the retraction of forests and the expansion of arid and semi‐arid environments in Africa, with consequences for birds. Cattle egret Bubulcus ibis is a dispersive species that prefers semi‐arid environments and requires proximity to bodies of water. We expected that climatic oscillations led to the expansion of the range of the cattle egret during arid periods, such as the Last Maximum Glacial (LGM) and contraction of distribution during the Last Interglacial (LIG) period, resulting in contact of populations previously isolated. We investigated this hypothesis by evaluating the genetic structure and population history of 15 cattle egret breeding colonies located in west and South Africa using the mitochondrial DNA (mtDNA) control region, mtDNA ATPase 8 and 6, and an intron of nuclear gene transforming growth factor‐beta 2. Occurrence data and bioclimatic information were used to generate ecological niche models of three periods (present, LGM and LIG). We used the genetic and paleomodelling data to assess the responses of the cattle egret from Africa to the climatic oscillations during the late Pleistocene. Genetic data revealed low levels of genetic differentiation, signs of isolation‐by‐distance, as well as recent increases in effective population size that started during the LGM. The observed low genetic structure may be explained by recent colonization events due to the demographic expansion following the last glacial period and by dispersal capacity of this species. The paleomodels corroborated the expansion during the LGM, and a more restricted potential distribution during the LIG. Our findinds supports the hypothesis that the species range of the cattle egret expanded during arid periods and contracted during wet periods. 相似文献
207.
Michael A. Hardigan Emily Crisovan John P. Hamilton Jeongwoon Kim Parker Laimbeer Courtney P. Leisner Norma C. Manrique-Carpintero Linsey Newton Gina M. Pham Brieanne Vaillancourt Xueming Yang Zixian Zeng David S. Douches Jiming Jiang Richard E. Veilleux C. Robin Buell 《The Plant cell》2016,28(2):388-405
208.
209.
Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma
Vaishnavi Nathan Peter A. Johansson Jane M. Palmer Madeleine Howlie Hayley R. Hamilton Karin Wadt Gran Jnsson Kelly M. Brooks Antonia L. Pritchard Nicholas K. Hayward 《Pigment cell & melanoma research》2019,32(6):854-863
Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next‐generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four‐case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM. 相似文献