Molecular signatures of natural selection for polymorphic genes of the human dopaminergic and serotonergic systems: A review

A large body of research has examined the behavioral and mental health consequences of polymorphisms in genes of the dopaminergic and serotonergic systems. Along with this, there has been considerable interest in the possibility that these polymorphisms have developed and/or been maintained due to the action of natural selection. Episodes of natural selection on a gene are expected to leave molecular “footprints” in the DNA sequences of the gene and adjacent genomic regions. Here we review the research literature investigating molecular signals of selection for genes of the dopaminergic and serotonergic systems. The gene SLC6A4, which codes for a serotonin transport protein, was the one gene for which there was consistent support from multiple studies for a selective episode. Positive selection on SLC6A4 appears to have been initiated ∼ 20–25,000 years ago in east Asia and possibly in Europe. There are scattered reports of molecular signals of selection for other neurotransmitter genes, but these have generally failed at replication across studies. In spite of speculation in the literature about selection on these genes, current evidence from population genomic analyses supports selectively neutral processes, such as genetic drift and population dynamics, as the principal drivers of recent evolution in dopaminergic and serotonergic genes other than SLC6A4

Agents of Bioterrorism: Curriculum and Pedagogy in an Online Masters Program

The Agents of Bioterrorism course (BSBD 640, University of Maryland University College) is a graduate level course created in response to an elevated need for scientists working in the field of medical countermeasures to biological and chemical weapons in the years following 9/11. Students read and evaluate assigned current primary literature articles investigating medical countermeasures at each stage of development. In addition, students learn concepts of risk assessment, comparing and ranking several agents of terror. Student learning is assessed through a variety of assignments. A term paper focuses on a lesser known weapon of terror, with students recommending the best countermeasure in development and delivering a risk assessment comparing their agent to other major weapons of terror discussed throughout the semester. Similarly, a group project on an assigned major weapon of terror (anthrax, plague, smallpox, vesicants, or nerve agent) focuses more heavily on evaluating primary literature and concluding which countermeasure(s) in development are the best. Students complete the course with a fundamental understanding of the mechanism of action of many biological agents, information literacy for the medical literature available at PubMed and the primary scientific literature, and a basic understanding of the role of the government in biodefense research. This paper describes the pedagogical approaches used to teach this course and how they might be adopted for other courses

An Integrated Approach to Diabetes Prevention: Anthropology, Public Health, and Community Engagement

Diabetes is an enormous public health problem with particular concern within Hispanic communities and among individuals with low wealth. However, attempts to expand the public health paradigm to include social determinants of health rarely include analysis of social and contextual factors considered outside the purview of health research. As a result, conceptualization of the dynamics of diabetes health disparities remains shallow. We argue that using a holistic anthropological lens has the potential to offer insights regarding the nature of the interface between broader social determinants, health outcomes and health disparity. In a primarily Hispanic, immigrant community in Albuquerque, New Mexico, we conducted a mixed methods study that integrates an anthropological lens with a community engaged research design. Our data from focus groups, interviews, a survey and blood sampling demonstrate the need to conceptualize social determinants more broadly, more affectively and more dynamically than often considered. These results highlight a need to include, in addition to individual - level factors that are traditionally the focus of public health and more innovative structural factors that are currently in vogue, an in - depth, qualitative exploration of local context, social environment, and culture, and their interactions and intersectionality, as key factors when considering how to achieve change. The discussion presented here offers a model for culturally situated and contextually relevant scientific research. This model achieves the objectives and goals of both public health and anthropology while providing valuable insights and mechanisms for addressing health disparity such as that which exists in relation to diabetes among Hispanic immigrants in New Mexico. Such an approach has implications for how research projects are designed and conceptualizing social determinants more broadly. The discussion presented provides insights with relevance for both disciplines

Fly\u27n\u27don\u27t Build: What We Learned From Our Study of Development Projects in Nepal

Everest. Sherpas. The world’s only nonquadrilateral flag. The country? Nepal, of course. The nine Avondale College of Higher Education students who visited June 17 - July 15 learned much more about this landlocked nation, though. Rough roads ran beside raging rapids. Patriarchy and entrenched poverty. The caste system, the influence of climate change both impacting a vulnerable but proud people fighting for a better life. The trip served as the practical component of one of our international poverty and development studies units. We’d previously completed other units in the course and prepared extensively throughout first semester for the trip. During our month in Nepal, we traversed 19 of its 75 districts to visit 15 villages, all beneficiaries of Adventist Development and Relief Agency (ADRA) projects

Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families

BACKGROUND: Recent studies have indicated that quantitative autistic traits (QATs) of parents reflect inherited liabilities that may index background genetic risk for clinical autism spectrum disorder (ASD) in their offspring. Moreover, preferential mating for QATs has been observed as a potential factor in concentrating autistic liabilities in some families across generations. Heretofore, intergenerational studies of QATs have focused almost exclusively on Caucasian populations—the present study explored these phenomena in a well-characterized Hispanic population. METHODS: The present study examined QAT scores in siblings and parents of 83 Hispanic probands meeting research diagnostic criteria for ASD, and 64 non-ASD controls, using the Social Responsiveness Scale-2 (SRS-2). Ancestry of the probands was characterized by genotype, using information from 541,929 single nucleotide polymorphic markers. RESULTS: In families of Hispanic children with an ASD diagnosis, the pattern of quantitative trait correlations observed between ASD-affected children and their first-degree relatives (ICCs on the order of 0.20), between unaffected first-degree relatives in ASD-affected families (sibling/mother ICC = 0.36; sibling/father ICC = 0.53), and between spouses (mother/father ICC = 0.48) were in keeping with the influence of transmitted background genetic risk and strong preferential mating for variation in quantitative autistic trait burden. Results from analysis of ancestry-informative genetic markers among probands in this sample were consistent with that from other Hispanic populations. CONCLUSIONS: Quantitative autistic traits represent measurable indices of inherited liability to ASD in Hispanic families. The accumulation of autistic traits occurs within generations, between spouses, and across generations, among Hispanic families affected by ASD. The occurrence of preferential mating for QATs—the magnitude of which may vary across cultures—constitutes a mechanism by which background genetic liability for ASD can accumulate in a given family in successive generations

Middle School Math Acceleration and Equitable Access to 8th Grade Algebra: Evidence from the Wake County Public School System

School districts across the country have struggled to increase the proportion of students taking algebra by 8th grade, thought to be an important milestone on the pathway to college preparedness. We highlight key features of a research collaboration between the Wake County Public School System and Harvard University that have enabled investigation of one such effort to solve this problem. In 2010, the district began assigning middle school students to accelerated math coursework leading to 8th grade algebra on the basis of a clearly defined measured of prior academic skill. We document two important facts. First, use of this new rule greatly reduced the relationship between course assignment and student factors such as income and race while increasing the relationship between course assignment and academic skill. Second, using a regression discontinuity analytic strategy, we show that the assignment rule had strong impacts on the fraction of students on track to complete algebra by 8th grade. Students placed in accelerated math were exposed to higher-skilled peers but larger class sizes. We describe future plans for assessing impacts on achievement and high school course-taking outcomes.Other Research Uni

Insights into the Evolution of Cotton Diploids and Polyploids from Whole-Genome Re-sequencing

Understanding the composition, evolution, and function of the Gossypium hirsutum (cotton) genome is complicated by the joint presence of two genomes in its nucleus (AT and DT genomes). These two genomes were derived from progenitor A-genome and D-genome diploids involved in ancestral allopolyploidization. To better understand the allopolyploid genome, we re-sequenced the genomes of extant diploid relatives that contain the A1 (Gossypium herbaceum), A2 (Gossypium arboreum), or D5 (Gossypium raimondii) genomes. We conducted a comparative analysis using deep re-sequencing of multiple accessions of each diploid species and identified 24 million SNPs between the A-diploid and D-diploid genomes. These analyses facilitated the construction of a robust index of conserved SNPs between the A-genomes and D-genomes at all detected polymorphic loci. This index is widely applicable for read mapping efforts of other diploid and allopolyploid Gossypium accessions. Further analysis also revealed locations of putative duplications and deletions in the A-genome relative to the D-genome reference sequence. The approximately 25,400 deleted regions included more than 50% deletion of 978 genes, including many involved with starch synthesis. In the polyploid genome, we also detected 1,472 conversion events between homoeologous chromosomes, including events that overlapped 113 genes. Continued characterization of the Gossypium genomes will further enhance our ability to manipulate fiber and agronomic production of cotton

Genome-wide analysis of the omega-3 fatty acid desaturase gene family in Gossypium

Background The majority of commercial cotton varieties planted worldwide are derived from Gossypium hirsutum, which is a naturally occurring allotetraploid produced by interspecific hybridization of A- and D-genome diploid progenitor species. While most cotton species are adapted to warm, semi-arid tropical and subtropical regions, and thus perform well in these geographical areas, cotton seedlings are sensitive to cold temperature, which can significantly reduce crop yields. One of the common biochemical responses of plants to cold temperatures is an increase in omega-3 fatty acids, which protects cellular function by maintaining membrane integrity. The purpose of our study was to identify and characterize the omega-3 fatty acid desaturase (FAD) gene family in G. hirsutum, with an emphasis on identifying omega-3 FADs involved in cold temperature adaptation. Results Eleven omega-3 FAD genes were identified in G. hirsutum, and characterization of the gene family in extant A and D diploid species (G. herbaceum and G. raimondii, respectively) allowed for unambiguous genome assignment of all homoeologs in tetraploid G. hirsutum. The omega-3 FAD family of cotton includes five distinct genes, two of which encode endoplasmic reticulum-type enzymes (FAD3-1 and FAD3-2) and three that encode chloroplast-type enzymes (FAD7/8-1, FAD7/8-2, and FAD7/8-3). The FAD3-2 gene was duplicated in the A genome progenitor species after the evolutionary split from the D progenitor, but before the interspecific hybridization event that gave rise to modern tetraploid cotton. RNA-seq analysis revealed conserved, gene-specific expression patterns in various organs and cell types and semi-quantitative RT-PCR further revealed that FAD7/8-1 was specifically induced during cold temperature treatment of G. hirsutum seedlings. Conclusions The omega-3 FAD gene family in cotton was characterized at the genome-wide level in three species, showing relatively ancient establishment of the gene family prior to the split of A and D diploid progenitor species. The FAD genes are differentially expressed in various organs and cell types, including fiber, and expression of the FAD7/8-1 gene was induced by cold temperature. Collectively, these data define the genetic and functional genomic properties of this important gene family in cotton and provide a foundation for future efforts to improve cotton abiotic stress tolerance through molecular breeding approaches

Cosmological Constraints from the Clustering of the Sloan Digital Sky Survey DR7 Luminous Red Galaxies

We present the power spectrum of the reconstructed halo density field derived from a sample of Luminous Red Galaxies (LRGs) from the Sloan Digital Sky Survey Seventh Data Release (DR7). The halo power spectrum has a direct connection to the underlying dark matter power for k <= 0.2 h/Mpc, well into the quasi-linear regime. This enables us to use a factor of ~8 more modes in the cosmological analysis than an analysis with kmax = 0.1 h/Mpc, as was adopted in the SDSS team analysis of the DR4 LRG sample (Tegmark et al. 2006). The observed halo power spectrum for 0.02 < k < 0.2 h/Mpc is well-fit by our model: chi^2 = 39.6 for 40 degrees of freedom for the best fit LCDM model. We find \Omega_m h^2 * (n_s/0.96)^0.13 = 0.141^{+0.009}_{-0.012} for a power law primordial power spectrum with spectral index n_s and \Omega_b h^2 = 0.02265 fixed, consistent with CMB measurements. The halo power spectrum also constrains the ratio of the comoving sound horizon at the baryon-drag epoch to an effective distance to z=0.35: r_s/D_V(0.35) = 0.1097^{+0.0039}_{-0.0042}. Combining the halo power spectrum measurement with the WMAP 5 year results, for the flat LCDM model we find \Omega_m = 0.289 +/- 0.019 and H_0 = 69.4 +/- 1.6 km/s/Mpc. Allowing for massive neutrinos in LCDM, we find \sum m_{\nu} < 0.62 eV at the 95% confidence level. If we instead consider the effective number of relativistic species Neff as a free parameter, we find Neff = 4.8^{+1.8}_{-1.7}. Combining also with the Kowalski et al. (2008) supernova sample, we find \Omega_{tot} = 1.011 +/- 0.009 and w = -0.99 +/- 0.11 for an open cosmology with constant dark energy equation of state w.Comment: 26 pages, 19 figures, submitted to MNRAS. The power spectrum and a module to calculate the likelihoods is publicly available at http://lambda.gsfc.nasa.gov/toolbox/lrgdr/ . v2 fixes abstract formatting issu

Environmental Stimulation Chamber for Nanosatellite Functional Testing

The goal of this project is to develop a nanosatellite thermal testing chamber for the Robotic Systems Laboratory at Santa Clara University. The nanosatellite industry has thrived in recent years and continues to grow at the level of universities and small businesses. To meet this demand, the team designed and built a testing bed capable of achieving environmental conditions adequate for testing nanosatellite hardware as a low-cost and low-maintenance alternative to more expensive and robust systems. Furthermore, the design can be fully manufactured and assembled at the university or small business level with inexpensive, sustainable, and commercially available components. The final product will save money and decrease energy consumption while fully realizing the thermal testing needs for nanosatellite communication hardware