Human ​gephyrin is encompassed within giant functional noncoding yin–yang sequences

Gephyrin is a highly conserved gene that is vital for the organization of proteins at inhibitory receptors, molybdenum cofactor biosynthesis and other diverse functions. Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases. Here we report a remarkable yin–yang haplotype pattern encompassing gephyrin. Yin–yang haplotypes arise when a stretch of DNA evolves to present two disparate forms that bear differing states for nucleotide variations along their lengths. The gephyrin yin–yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution. Several independent lines of evidence indicate strong positive selection on the region and suggest these high-frequency haplotypes represent two distinct functional mechanisms. This discovery holds potential to deepen our understanding of variable human-specific regulation of gephyrin while providing clues for rapid evolutionary events and allelic migrations buried within human history

INTERDEPENDENT INFRASTRUCTURE RESILIENCE IN THE U.S. VIRGIN ISLANDS: PRELIMINARY ASSESSMENT

Prepared for: Federal Emergency Management AgencyThe U.S. Virgin Islands (USVI) is a territory comprised of three main islands—Saint Croix, Saint John, and Saint Thomas—and a number of smaller surrounding islands, located in the Leeward Islands of the Lesser Antilles approximately 40 miles east of Puerto Rico and over 1,100 miles from Miami, Florida. In September 2017, two Category-5 hurricanes made landfall within a two-week period and collectively devastated the homes, businesses, and infrastructure throughout the Territory.This technical report (1) explains the structure, function, and tensions associated with energy, water, transportation, and communication infrastructure that were chronic problems prior to the hurricanes; (2) documents hurricane response, recovery, and mitigation activities for these infrastructure systems after the hurricanes; and (3) provides concrete approaches to overcome potential barriers to resilience (where they exist) and open questions for research (where they do not yet exist).Federal Emergency Management AgencyFederal Emergency Management AgencyApproved for public release; distribution is unlimited

The role of landscape and history on the genetic structure of peripheral populations of the Near Eastern fire salamander, Salamandra infraimmaculata, in Northern Israel

Genetic studies on core versus peripheral populations have yielded many patterns. This diversity in genetic patterns may reflect diversity in the meaning of peripheral populations as defined by geography, gene flow patterns, historical effects, and ecological conditions. Populations at the lower latitude periphery of a species' range are of particular concern because they may be at increased risk for extinction due to global climate change. In this work we aim to understand the impact of landscape and ecological factors on different geographical types of peripheral populations with respect to levels of genetic diversity and patterns of local population differentiation. We examined three geographical types of peripheral populations of the endangered salamander, Salamandra infraimmaculata, in Northern Israel, in the southernmost periphery of the genus Salamandra, by analyzing the variability in 15 microsatellite loci from 32 sites. Our results showed that: (1) genetic diversity decreases towards the geographical periphery of the species' range; (2) genetic diversity in geographically disjunct peripheral areas is low compared to the core or peripheral populations that are contiguous to the core and most likely affected by a founder effect; (3) ecologically marginal conditions enhance population subdivision. The patterns we found lead to the conclusion that genetic diversity is influenced by a combination of geographical, historical, and ecological factors. These complex patterns should be addressed when prioritizing areas for conservation.Peer reviewe

Latitudinal clines of the human vitamin D receptor and skin color genes

The well-documented latitudinal clines of genes affecting human skin color presumably arise from the need for protection from intense ultraviolet radiation (UVR) vs. the need to use UVR for vitamin D synthesis. Sampling 751 subjects from a broad range of latitudes and skin colors, we investigated possible multilocus correlated adaptation of skin color genes with the vitamin D receptor gene (VDR), using a vector correlation metric and network method called BlocBuster. We discovered two multilocus networks involving VDR promoter and skin color genes that display strong latitudinal clines as multilocus networks, even though many of their single gene components do not. Considered one by one, the VDR components of these networks show diverse patterns: no cline, a weak declining latitudinal cline outside of Africa, and a strong in- vs. out-of-Africa frequency pattern. We confirmed these results with independent data from HapMap. Standard linkage disequilibrium analyses did not detect these networks. We applied BlocBuster across the entire genome, showing that our networks are significant outliers for interchromosomal disequilibrium that overlap with environmental variation relevant to the genes\u27 functions. These results suggest that these multilocus correlations most likely arose from a combination of parallel selective responses to a common environmental variable and coadaptation, given the known Mendelian epistasis among VDR and the skin color genes

The Druze: A Population Genetic Refugium of the Near East

BACKGROUND: Phylogenetic mitochondrial DNA haplogroups are highly partitioned across global geographic regions. A unique exception is the X haplogroup, which has a widespread global distribution without major regions of distinct localization. PRINCIPAL FINDINGS: We have examined mitochondrial DNA sequence variation together with Y-chromosome-based haplogroup structure among the Druze, a religious minority with a unique socio-demographic history residing in the Near East. We observed a striking overall pattern of heterogeneous parental origins, consistent with Druze oral tradition, together with both a high frequency and a high diversity of the mitochondrial DNA (mtDNA) X haplogroup within a confined regional subpopulation. Furthermore demographic modeling indicated low migration rates with nearby populations. CONCLUSIONS: These findings were enabled through the use of a paternal kindred based sampling approach, and suggest that the Galilee Druze represent a population isolate, and that the combination of a high frequency and diversity of the mtDNA X haplogroup signifies a phylogenetic refugium, providing a sample snapshot of the genetic landscape of the Near East prior to the modern age

A Review of Interventions to Reduce Mechanical Restraint and Seclusion among Adult Psychiatric Inpatients

Objective: This review examines nature and effectiveness of interventions to reduce the use of mechanical restraint and seclusion among adult psychiatric inpatients. Method: Electronic searches were conducted to locate post-1960 empirical studies of restraint and seclusion reduction in English. A total of 36 studies were identified, mostly from the USA. Analysis was conducted using a structured data extraction tool. Results: The majority of studies reported reduced levels or mechanical restraint and/or seclusion, but the standard of evidence was poor. There were no randomised trials. Most were retrospective studies of official records before and after the intervention was introduced, with varying follow-up periods. The interventions were diverse, but tended to include one or more of the following: new restraint and/or seclusion policies, staffing changes, staff training, review procedures and crisis management initiatives. The research was unable to address which of these elements was most effective. There was also evidence that some improved outcomes were achieved by substituting restraint or seclusion for each other or for alternatives forms of containment (medication in particular). Nurses’ attitudes, skills and approach to patient care were absent from the literature. Conclusions: Interventions probably can reduce the use of restraint and seclusion, but better designed research is required to demonstrate their effectiveness conclusively. More attention should also be paid to understanding how interventions work, particularly from the perspective of nursing staff. This is essential to the successful implementation of restraint and seclusion interventions across different psychiatric settings and treatment populations

Sixty Years of Modern Human Origins in the American Anthropological Association

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65197/1/aa.2003.105.1.89.pd

Neolithic Mitochondrial Haplogroup H Genomes and the Genetic Origins of Europeans

Haplogroup H dominates present-day Western European mitochondrial DNA variability (\u3e40%), yet was less common (~19%) among Early Neolithic farmers (~5450 BC) and virtually absent in Mesolithic hunter-gatherers. Here we investigate this major component of the maternal population history of modern Europeans and sequence 39 complete haplogroup H mitochondrial genomes from ancient human remains. We then compare this ‘real-time’ genetic data with cultural changes taking place between the Early Neolithic (~5450 BC) and Bronze Age (~2200 BC) in Central Europe. Our results reveal that the current diversity and distribution of haplogroup H were largely established by the Mid Neolithic (~4000 BC), but with substantial genetic contributions from subsequent pan-European cultures such as the Bell Beakers expanding out of Iberia in the Late Neolithic (~2800 BC). Dated haplogroup H genomes allow us to reconstruct the recent evolutionary history of haplogroup H and reveal a mutation rate 45% higher than current estimates for human mitochondria

Long-Range Autocorrelations of CpG Islands in the Human Genome

In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI) in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb) and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local) feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes