Intriguing effects of selection intensity on the evolution of prosocial behaviors.

In many models of evolving populations, genetic drift has an outsized role relative to natural selection, or vice versa. While there are many scenarios in which one of these two assumptions is reasonable, intermediate balances between these forces are also biologically relevant. In this study, we consider some natural axioms for modeling intermediate selection intensities, and we explore how to quantify the long-term evolutionary dynamics of such a process. To illustrate the sensitivity of evolutionary dynamics to drift and selection, we show that there can be a "sweet spot" for the balance of these two forces, with sufficient noise for rare mutants to become established and sufficient selection to spread. This balance allows prosocial traits to evolve in evolutionary models that were previously thought to be unconducive to the emergence and spread of altruistic behaviors. Furthermore, the effects of selection intensity on long-run evolutionary outcomes in these settings, such as when there is global competition for reproduction, can be highly non-monotonic. Although intermediate selection intensities (neither weak nor strong) are notoriously difficult to study analytically, they are often biologically relevant; and the results we report suggest that they can elicit novel and rich dynamics in the evolution of prosocial behaviors.

Subcongenic analysis of a quantitative trait locus affecting body weight and glucose metabolism in zinc transporter 7 (znt7)-knockout mice.

BACKGROUND: A genome-wide mapping study using male F2 zinc transporter 7-knockout mice (znt7-KO) and their wild type littermates in a mixed 129P1/ReJ (129P1) and C57BL/6J (B6) background identified a quantitative trait locus (QTL) on chromosome 7, which had a synergistic effect on body weight gain and fat deposit with the znt7-null mutation. RESULTS: The genetic segment for body weight on mouse chromosome 7 was investigated by newly created subcongenic znt7-KO mouse strains carrying different lengths of genomic segments of chromosome 7 from the 129P1 donor strain in the B6 background. We mapped the sub-QTL for body weight in the proximal region of the previously mapped QTL, ranging from 47.4 to 64.4 megabases (Mb) on chromosome 7. The 129P1 donor allele conferred lower body weight gain and better glucose handling during intraperitoneal glucose challenge than the B6 allele control. We identified four candidate genes, including Htatip2, E030018B13Rik, Nipa1, and Atp10a, in this sub-QTL using quantitative RT-PCR and cSNP detection (single nucleotide polymorphisms in the protein coding region). CONCLUSIONS: This study dissected the genetic determinates of body weight and glucose metabolism in znt7-KO mice. The study demonstrated that a 17-Mb long 129P1 genomic region on mouse chromosome 7 conferred weight reduction and improved glucose tolerance in znt7-KO male mice. Among the four candidate genes identified, Htatip2 is the most likely candidate gene involved in the control of body weight based on its function in regulation of lipid metabolism. The candidate genes discovered in this study lay a foundation for future studies of their roles in development of metabolic diseases, such as obesity and type 2 diabetes.

Epigenetic clock and methylation studies in vervet monkeys.

DNA methylation-based biomarkers of aging have been developed for many mammals but not yet for the vervet monkey (Chlorocebus sabaeus), which is a valuable non-human primate model for biomedical studies. We generated novel DNA methylation data from vervet cerebral cortex, blood, and liver using highly conserved mammalian CpGs represented on a custom array (HorvathMammalMethylChip40). We present six DNA methylation-based estimators of age: vervet multi-tissue epigenetic clock and tissue-specific clocks for brain cortex, blood, and liver. In addition, we developed two dual species clocks (human-vervet clocks) for measuring chronological age and relative age, respectively. Relative age was defined as ratio of chronological age to maximum lifespan to address the species differences in maximum lifespan. The high accuracy of the human-vervet clocks demonstrates that epigenetic aging processes are evolutionary conserved in primates. When applying these vervet clocks to tissue samples from another primate species, rhesus macaque, we observed high age correlations but strong offsets. We characterized CpGs that correlate significantly with age in the vervet. CpG probes that gain methylation with age across tissues were located near the targets of Polycomb proteins SUZ12 and EED and genes possessing the trimethylated H3K27 mark in their promoters. The epigenetic clocks are expected to be useful for anti-aging studies in vervets.

Cell recovery comparison between plasma depletion/reduction- and red cell reduction-processing of umbilical cord blood.

BACKGROUND AIMS: Limited cell dose has hampered the use of cord blood transplantation (CBT) in adults. One method of minimizing nucleated cell loss in cord blood (CB) processing is to deplete or reduce plasma but not red blood cells - plasma depletion/reduction (PDR). METHODS: The nucleated cell loss of PDR was studied, and determined to be less than 0.1% in the discarded supernatant plasma fraction in validation experiments. After testing and archival sampling, the median nucleated cell recovery for PDR processing was 90%, and median CD34(+) cell recovery 88%. In a CB bank inventory of 12 339 products with both pre- and post-processing total nucleated cells (TNC), PDR processing resulted in median post-processing TNC recoveries of 90.0% after testing and archival samples removal. Using the same 10 CB units divided into two halves, we compared directly the recovery of PDR against hydroxyethyl starch red cell reduction (RCR) for TNC, CD34(+) cells and colony-forming units (CFU-GM, CFU-E, CFU-GEMM and total CFU) after parallel processing. We also compared the loss of very small embryonic-like stem cells (VSEL). RESULTS: We demonstrated significantly higher recoveries using PDR for TNC (124%), CD34(+) cells (121%), CFU-GM (225%), CFU-GEMM (201%), total CFU (186%) and VSEL (187%). The proportion of high TNC products was compared between 10 912 PDR and 38 819 RCR CB products and found to be 200% higher for products that had TNC ≥150 × 10(7) (P = 0.0001) for the PDR inventory. CONCLUSIONS: Our data indicate that PDR processing of CB provides a significantly more efficient usage of this valuable and scarce resource.

Quantitative proteomics analysis by isobaric tags for relative and absolute quantitation identified Lumican as a potential marker for acute aortic dissection.

Acute aortic dissection (AAD) is a serious vascular disease. Currently the diagnosis relies on clinical and radiological means whereas serum biomarkers are lacking. The purpose of this study was to identify potential serum biomarkers for AAD using isobaric tags for relative and absolute quantitation (iTRAQ) approach. A total of 120 serum samples were collected from three groups: AAD patients (n = 60), patients with acute myocardial infarction (AMI, n = 30), and healthy volunteers (n = 30), whereas the first 10 samples from each group were used for iTRAQ analysis. Using iTRAQ approach, a total of 174 proteins were identified as significantly different between AAD patients and healthy subjects. Among them, forty-six proteins increased more than twofold, full-scale analysis using serum sample for the entire 120 subjects demonstrated that Lumican level was significantly increased relative to control and AMI samples. Further, Lumican level correlated with time from onset to admission in AAD but not AMI samples. Using iTRAQ approach, our study showed that Lumican may be a potential AAD-related serum marker that may assist the diagnosis of AAD.

Management of centrally located hepatocellular carcinoma: Update 2016.

Centrally located hepatocellular carcinoma (HCC) is sited in the central part of the liver and adjacent to main hepatic vascular structures. This special location is associated with an increase in the difficulty of surgery, aggregation of the recurrence disease, and greater challenge in disease management. This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies, surgical approaches and recurrence prevention methods. To improve patient survival, a multi-disciplinary modality is greatly needed throughout the whole treatment period.

Zebrafish in the wild: a review of natural history and new notes from the field.

The zebrafish, Danio rerio, has emerged as a major model organism for biomedical research, yet little is known about its natural history. We review the literature pertaining to the geographic range, biotic and abiotic habitats, and life cycle of the zebrafish. We also report our own field study to document several aspects of zebrafish natural history across sites in northeast India. We found zebrafish particularly abundant in silt-bottomed, well-vegetated pools and rice paddies adjacent to slow moving streams at a range of elevations. We further identified co-occurring fishes likely to be zebrafish competitors and predators. Finally, we present observations that indicate substantial habitat degradation and loss, and suggest guidelines for documenting and preserving natural zebrafish populations.