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Institution

University of New Mexico

EducationAlbuquerque, New Mexico, United States
About: University of New Mexico is a education organization based out in Albuquerque, New Mexico, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 28870 authors who have published 64767 publications receiving 2578371 citations. The organization is also known as: UNM & Universitatis Novus Mexico.


Papers
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Journal ArticleDOI
TL;DR: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population, and immune-related AEs were manageable and generally reversible with corticosteroids.

480 citations

Journal ArticleDOI
TL;DR: Recent studies indicate that the inhibition of cytokine induced increase in intestinal TJ permeability has an important protective effect against intestinal mucosal damage and development of intestinal inflammation.
Abstract: Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta?IL-1beta?, and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-beta are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an important physiological and pathological effect on intestinal tight junction (TJ) barrier. Consistent with their known pro-inflammatory activities, pro-inflammatory cytokines cause a disturbance in intestinal TJ barrier, allowing increased tissue penetration of luminal antigens. Recent studies indicate that the inhibition of cytokine induced increase in intestinal TJ permeability has an important protective effect against intestinal mucosal damage and development of intestinal inflammation. In this review, the effects of various pro-inflammatory and anti-inflammatory cytokines on intestinal TJ barrier and the progress into the mechanisms that mediate the cytokine modulation of intestinal TJ barrier are reviewed.

480 citations

Journal ArticleDOI
TL;DR: It is shown that the world of Reals is significantly under-sampled as the MW of compounds increases, which supports the design and screening of 'reduced complexity' (leadlike) compound libraries, preferably with synthetic handles available for rapid chemical iteration and detected as interesting by careful screening or biophysical assays.

478 citations

Journal ArticleDOI
TL;DR: The human–chimpanzee split is dated to at least 7–8 million years and the population split between Neanderthals and modern humans to 400,000–800,000 y ago, which suggests that molecular divergence dates may not be in conflict with the attribution of 6- to 7-million-y-old fossils to the human lineage and 400,,000-Y-old bones to the Neanderthal lineage.
Abstract: Fossils and molecular data are two independent sources of information that should in principle provide consistent inferences of when evolutionary lineages diverged. Here we use an alternative approach to genetic inference of species split times in recent human and ape evolution that is independent of the fossil record. We first use genetic parentage information on a large number of wild chimpanzees and mountain gorillas to directly infer their average generation times. We then compare these generation time estimates with those of humans and apply recent estimates of the human mutation rate per generation to derive estimates of split times of great apes and humans that are independent of fossil calibration. We date the human–chimpanzee split to at least 7–8 million years and the population split between Neanderthals and modern humans to 400,000–800,000 y ago. This suggests that molecular divergence dates may not be in conflict with the attribution of 6- to 7-million-y-old fossils to the human lineage and 400,000-y-old fossils to the Neanderthal lineage.

477 citations

Journal ArticleDOI
TL;DR: Only polygenic mutation-selection balance seems consistent with the data on mental disorder prevalence rates, fitness costs, the likely rarity of susceptibility alleles, and the increased risks of mental disorders with brain trauma, inbreeding, and paternal age.
Abstract: Given that natural selection is so powerful at optimizing complex adaptations, why does it seem unable to eliminate genes (susceptibility alleles) that predispose to common, harmful, heritable mental disorders, such as schizophrenia or bipolar disorder? We assess three leading explanations for this apparent paradox from evolutionary genetic theory: (1) ancestral neutrality (susceptibility alleles were not harmful among ancestors), (2) balancing selection (susceptibility alleles sometimes increased fitness), and (3) polygenic mutation-selection balance (mental disorders reflect the inevitable mutational load on the thousands of genes underlying human behavior). The first two explanations are commonly assumed in psychiatric genetics and Darwinian psychiatry, while mutation-selection has often been discounted. All three models can explain persistent genetic variance in some traits under some conditions, but the first two have serious problems in explaining human mental disorders. Ancestral neutrality fails to explain low mental disorder frequencies and requires implausibly small selection coefficients against mental disorders given the data on the reproductive costs and impairment of mental disorders. Balancing selection (including spatio-temporal variation in selection, heterozygote advantage, antagonistic pleiotropy, and frequency-dependent selection) tends to favor environmentally contingent adaptations (which would show no heritability) or high-frequency alleles (which psychiatric genetics would have already found). Only polygenic mutation-selection balance seems consistent with the data on mental disorder prevalence rates, fitness costs, the likely rarity of susceptibility alleles, and the increased risks of mental disorders with brain trauma, inbreeding, and paternal age. This evolutionary genetic framework for mental disorders has wide-ranging implications for psychology, psychiatry, behavior genetics, molecular genetics, and evolutionary approaches to studying human behavior.

477 citations


Authors

Showing all 29120 results

NameH-indexPapersCitations
Bruce S. McEwen2151163200638
David Miller2032573204840
Jing Wang1844046202769
Paul M. Thompson1832271146736
David A. Weitz1781038114182
David R. Williams1782034138789
John A. Rogers1771341127390
George F. Koob171935112521
John D. Minna169951106363
Carlos Bustamante161770106053
Lewis L. Lanier15955486677
Joseph Wang158128298799
John E. Morley154137797021
Fabian Walter14699983016
Michael F. Holick145767107937
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202390
2022595
20213,060
20203,048
20192,779
20182,729