In Silico Synchronization of Cellular Populations Through Expression Data Deconvolution

Cellular populations are typically heterogenous collections of cells at different points in their respective cell cycles, each with a cell cycle time that varies from individual to individual. As a result, true single-cell behavior, particularly that which is cell-cycle--dependent, is often obscured in population-level (averaged) measurements. We have developed a simple deconvolution method that can be used to remove the effects of asynchronous variability from population-level time-series data. In this paper, we summarize some recent progress in the development and application of our approach, and provide technical updates that result in increased biological fidelity. We also explore several preliminary validation results and discuss several ongoing applications that highlight the method's usefulness for estimating parameters in differential equation models of single-cell gene regulation.Comment: accepted for the 48th ACM/IEEE Design Automation Conferenc

Androgen Receptor and Vasopressin Receptor (AVPR1a) Genetic Polymorphisms are not associated with Marital Status or Fertility among Ariaal Men of Northern Kenya

A growing body of scholarship implicates testosterone and vasopressin in male reproductive behavior, including in humans. Since hormones exert their effects through their respective receptors, an open question has been whether genetic polymorphisms in the androgen receptor and vasopressin 1a receptor (AVPR1a) impact human male social behavior. Here, we sought to test for associations between polymorphisms in the coding region of the androgen receptor and promoter region of AVPR1a in relation to marital status and fertility among pastoralist Ariaal men of northern Kenya. None of the three polymorphisms were related to marital status (single, monogamously married, polygynously married) or fertility (number of current living children). We discuss these null findings in light of existing data

Obesity, Attention Deficit-Hyperactivity Disorder and the Dopaminergic Reward System

The obesity epidemic has focused attention on obesity’s health consequences beyond cardio-vascular disease and diabetes. To evaluate the potential consequences of obesity for Attention Deficit-Hyperactivity Disorder (ADHD), we surveyed the literature. Current findings link both obesity and ADHD to the dopamine system and implicate dopamine genes in body weight, eating, and ADHD. Detailed consideration suggests that dopaminergic changes in the prefrontal cortex among individuals with the ADHD subtype Attention Deficit Disorder (ADD) may increase their risk for obesity. Thus, individuals and populations with a high prevalence of hyperdopaminergic genes may experience higher rates of obesity in the presence of abundant food. From an evolutionary perspective, alterations in the dopamine system appear to effect a wide range of behavioral phenotypes. We suggest that recent evolutionary changes in the dopamine receptor genes selected to increase cognitive and behavioral flexibility may now be associated with attention problems and increased food consumption in an obesogenic environment

NPS Researchers Advance Infrastructure Resilience Plans for the U.S. Virgin Islands

Energy Academic Group (EAG) New

Practical Applications of Woods’ Four Resilience Concepts

Energy Academic Group (EAG) New

Resilience Corner: The Four Horsemen of Infrastructure Vulnerability

Energy Academic Group (EAG) New

Early Postoperative Outcomes and Medication Cost Savings after Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Type 2 Diabetes

Background. We investigated the effect of laparoscopic sleeve gastrectomy (LSG) on morbidly obese diabetics and examined the short-term impact of LSG on diabetic medication cost. Methods. A prospective database of consecutive bariatric patients was reviewed. Morbidly obese patients with type 2 diabetes who underwent LSG were included in the study. Age, gender, body mass index (BMI), diabetic medication use, glucose, insulin, and HbA1c levels were documented preoperatively, and at 2 weeks, 2 months, 6 months, and 12 months postoperatively. Insulin resistance was estimated using the homeostatic model assessment (HOMA). Use and cost of diabetic medications were followed. Results. Of 178 patients, 22 were diabetics who underwent LSG. Diabetes remission was observed in 62% of patients within 2 months and in 75% of patients within 12 months. HOMA-IR improved after only two weeks following surgery (16.5 versus 6.6, P < 0.001). Average number of diabetic medications decreased from 2.2 to <1, within 2 weeks after surgery; corresponding to a diabetes medication cost savings of 80%, 91%, 99%, and 99.7% after 2 weeks, 2 months, 6 months, and 12 months, respectively. Conclusion. Morbidly obese patients with diabetes who undergo LSG have high rates of diabetes remission early after surgery. This translates to a significant medication cost savings

Assortative human pair-bonding for partner ancestry and allelic variation of the dopamine receptor D4 (DRD4) gene

The 7R allele of the dopamine receptor D4 gene has been associated with attention-deficit hyperactivity disorder and risk taking. On the cross-population scale, 7R allele frequencies have been shown to be higher in populations with more of a history of long-term migrations. It has also been shown that the 7R allele is associated with individuals having multiple-ancestries. Here we conduct a replication of this latter finding with two independent samples. Measures of subjects&#x2019; ancestry are used to examine past reproductive bonds. The individuals&#x2019; history of inter-racial/ancestral dating and their feelings about this are also assessed. Tentative support for an association between multiple ancestries and the 7R allele were found. These results are dependent upon the method of questioning subjects about their ancestries. Inter-racial dating and feelings about inter-racial pairing were not related to the presence of the 7R allele. This might be accounted for by secular trends that might have substantively altered the decision-making process employed when considering relationships with individuals from different groups. This study provides continued support for the 7R allele playing a role in migration and/or mate choice patterns. However, replications and extensions of this study are needed and must carefully consider how ancestry/race is assessed

Dopamine receptor genetic polymorphisms and body composition in undernourished pastoralists: An exploration of nutrition indices among nomadic and recently settled Ariaal men of northern Kenya

<p>Abstract</p> <p>Background</p> <p>Minor alleles of the human dopamine receptor polymorphisms, DRD2/TaqI A and DRD4/48 bp, are related to decreased functioning and/or numbers of their respective receptors and have been shown to be correlated with body mass, height and food craving. In addition, the 7R minor allele of the DRD4 gene is at a higher frequency in nomadic compared to sedentary populations. Here we examine polymorphisms in the DRD2 and DRD4 genes with respect to body mass index (BMI) and height among men in two populations of Ariaal pastoralists, one recently settled (n = 87) and the other still nomadic (n = 65). The Ariaal live in northern Kenya, are chronically undernourished and are divided socially among age-sets.</p> <p>Results</p> <p>Frequencies of the DRD4/7R and DRD2/A1 alleles were 19.4% and 28.2%, respectively and did not differ between the nomadic and settled populations. BMI was higher in those with one or two DRD4/7R alleles in the nomadic population, but lower among the settled. Post-hoc analysis suggests that the DRD4 differences in BMI were due primarily to differences in fat free body mass. Height was unrelated to either DRD2/TaqI A or DRD4/48 bp genotypes.</p> <p>Conclusion</p> <p>Our results indicate that the DRD4/7R allele may be more advantageous among nomadic than settled Ariaal men. This result suggests that a selective advantage mediated through behaviour may be responsible for the higher frequency of the 7R alleles in nomadic relative to sedentary populations around the world. In contrast to previous work, we did not find an association between DRD2 genotypes and height. Our results support the idea that human phenotypic expression of genotypes should be rigorously evaluated in diverse environments and genetic backgrounds.</p