Widespread genetic heterogeneity of human ribosomal RNA genes

Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling and used high-coverage whole-genome sequencing (WGS) data from the 1000 Genomes Project to analyze variants in 2504 individuals from 26 populations. We identified a total of 3791 variant positions. The variants positioned nonrandomly on the rRNA gene. Invariant regions included the promoter, early 5 ' ETS, most of 18S, 5.8S, ITS1, and large areas of the intragenic spacer. A total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants were located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. Several variants were validated based on RNA-seq analyses. Population analyses showed remarkable ancestry-linked genetic variance and the presence of both high penetrance and frequent variants in the 5 ' ETS, ITS2, and 28S regions segregating according to the continental populations. These findings provide a genetic view of rRNA gene array heterogeneity and raise the need to functionally assess how the 28S rRNA variants affect ribosome functions.Peer reviewe

Avian primordial germ cells are bipotent for male or female gametogenesis

In birds, males are the homogametic sex (ZZ) and females are the heterogametic sex (ZW). Here, we investigate the role of chromosomal sex and germ cell competition on avian germ cell differentiation. We recently developed genetically sterile layer cockerels and hens for use as surrogate hosts for primordial germ cell (PGC) transplantation. Using in vitro propagated and cryopreserved PGCs from a pedigree Silkie broiler breed, we now demonstrate that sterile surrogate layer hosts injected with same sex PGCs have normal fertility and produced pure breed Silkie broiler offspring when directly mated to each other in Sire Dam Surrogate mating. We found that female sterile hosts carrying chromosomally male (ZZ) PGCs formed functional oocytes and eggs, which gave rise to 100% male offspring after fertilization. Unexpectedly, we also observed that chromosomally female (ZW) PGCs carried by male sterile hosts formed functional spermatozoa and produced viable offspring. These findings demonstrate that avian PGCs are not sexually restricted for functional gamete formation and provide new insights for the cryopreservation of poultry and other bird species using diploid stage germ cells

The Dilemma of the Dilated Main Pancreatic Duct in the Distal Pancreatic Remnant After Proximal Pancreatectomy for IPMN

Objective(s) A dilated main pancreatic duct in the distal remnant after proximal pancreatectomy for intraductal papillary mucinous neoplasms (IPMN) poses a diagnostic dilemma. We sought to determine parameters predictive of remnant main-duct IPMN and malignancy during surveillance. Methods Three hundred seventeen patients underwent proximal pancreatectomy for IPMN (Indiana University, 1991–2016). Main-duct dilation included those ≥ 5 mm or “dilated” on radiographic reports. Statistics compared groups using Student’s T/Mann-Whitney U tests for continuous variables or chi-square/Fisher’s exact test for categorical variables with P < 0.05 considered significant. Results High-grade/invasive IPMN or adenocarcinoma at proximal pancreatectomy predicted malignant outcomes (100.0% malignant outcomes; P < 0.001) in remnant surveillance. Low/moderate-grade lesions revealed benign outcomes at last surveillance regardless of duct diameter. Twenty of 21 patients undergoing distal remnant reoperation had a dilated main duct. Seven had main-duct IPMN on remnant pathology; these patients had greater mean maximum main-duct diameter prior to reoperation (9.5 vs 6.2 mm, P = 0.072), but this did not reach statistical significance. Several features showed high sensitivity/specificity for remnant main-duct IPMN. Conclusions Remnant main-duct dilation after proximal pancreatectomy for IPMN remains a diagnostic dilemma. Several parameters show a promise in accurately diagnosing main-duct IPMN in the remnant

Local adaptation and archaic introgression shape global diversity at human structural variant loci.

Large genomic insertions and deletions are a potent source of functional variation, but are challenging to resolve with short-read sequencing, limiting knowledge of the role of such structural variants (SVs) in human evolution. Here, we used a graph-based method to genotype long-read-discovered SVs in short-read data from diverse human genomes. We then applied an admixture-aware method to identify 220 SVs exhibiting extreme patterns of frequency differentiation - a signature of local adaptation. The top two variants traced to the immunoglobulin heavy chain locus, tagging a haplotype that swept to near fixation in certain southeast Asian populations, but is rare in other global populations. Further investigation revealed evidence that the haplotype traces to gene flow from Neanderthals, corroborating the role of immune-related genes as prominent targets of adaptive introgression. Our study demonstrates how recent technical advances can help resolve signatures of key evolutionary events that remained obscured within technically challenging regions of the genome

Overfishing Drives Over One-Third of All Sharks and Rays Toward a Global Extinction Crisis

The scale and drivers of marine biodiversity loss are being revealed by the International Union for Conservation of Nature (IUCN) Red List assessment process. We present the first global reassessment of 1,199 species in Class Chondrichthyes-sharks, rays, and chimeras. The first global assessment (in 2014) concluded that one-quarter (24%) of species were threatened. Now, 391 (32.6%) species are threatened with extinction. When this percentage of threat is applied to Data Deficient species, more than one-third (37.5%) of chondrichthyans are estimated to be threatened, with much of this change resulting from new information. Three species are Critically Endangered (Possibly Extinct), representing possibly the first global marine fish extinctions due to overfishing. Consequently, the chondrichthyan extinction rate is potentially 25 extinctions per million species years, comparable to that of terrestrial vertebrates. Overfishing is the universal threat affecting all 391 threatened species and is the sole threat for 67.3% of species and interacts with three other threats for the remaining third: loss and degradation of habitat (31.2% of threatened species), climate change (10.2%), and pollution (6.9%). Species are disproportionately threatened in tropical and subtropical coastal waters. Science-based limits on fishing, effective marine protected areas, and approaches that reduce or eliminate fishing mortality are urgently needed to minimize mortality of threatened species and ensure sustainable catch and trade of others. Immediate action is essential to prevent further extinctions and protect the potential for food security and ecosystem functions provided by this iconic lineage of predators

Overdose Prevention and Naloxone Prescription for Opioid Users in San Francisco

Opiate overdose is a significant cause of mortality among injection drug users (IDUs) in the United States (US). Opiate overdose can be reversed by administering naloxone, an opiate antagonist. Among IDUs, prevalence of witnessing overdose events is high, and the provision of take-home naloxone to IDUs can be an important intervention to reduce the number of overdose fatalities. The Drug Overdose Prevention and Education (DOPE) Project was the first naloxone prescription program (NPP) established in partnership with a county health department (San Francisco Department of Public Health), and is one of the longest running NPPs in the USA. From September 2003 to December 2009, 1,942 individuals were trained and prescribed naloxone through the DOPE Project, of whom 24% returned to receive a naloxone refill, and 11% reported using naloxone during an overdose event. Of 399 overdose events where naloxone was used, participants reported that 89% were reversed. In addition, 83% of participants who reported overdose reversal attributed the reversal to their administration of naloxone, and fewer than 1% reported serious adverse effects. Findings from the DOPE Project add to a growing body of research that suggests that IDUs at high risk of witnessing overdose events are willing to be trained on overdose response strategies and use take-home naloxone during overdose events to prevent deaths

“Still good life”: On the value of reuse and distributive labor in “depleted” rural Maine

This article explores the production of wealth through distributive labor in Maine\u27s secondhand economy. While reuse is often associated with economic disadvantage, our research complicates that perspective. The labor required to reclaim, repair, redistribute, and reuse secondhand goods provides much more than a means of living in places left behind by international capitalism, but the value generated by this work is persistently discounted by dominant economic logics. On the basis of semistructured interviews, participant observation, and statewide surveys with reuse market participants in Maine, we find that the relational value of reuse, produced through caring, flexible, distributive labor, is especially significant. We argue that paying attention to the practices, politics, and value of distribution is critical for understanding wealth in communities perceived to have been left behind by global capitalist systems, particularly as wage labor opportunities and natural resources grow increasingly scarce

Characterization of regulatory T cells in urban newborns

© 2009 Ly et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The Confidence Database

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects