Molecular patterns of evolutionary changes throughout the whole nervous system of multiple nematode species.

One avenue to better understand brain evolution is to map molecular patterns of evolutionary changes in neuronal cell types across entire nervous systems of distantly related species. Generating whole-animal single-cell transcriptomes of three nematode species from the genus, we observed a remarkable stability of neuronal cell type identities over more than 45 million years of evolution. Conserved patterns of combinatorial expression of homeodomain transcription factors are among the best classifiers of homologous neuron classes.

Selfish conflict underlies RNA-mediated parent-of-origin effects.

Genomic imprinting-the non-equivalence of maternal and paternal genomes-is a critical process that has evolved independently in many plant and mammalian species. According to kinship theory, imprinting is the inevitable consequence of conflictive selective forces acting on differentially expressed parental alleles. Yet, how these epigenetic differences evolve in the first place is poorly understood.

Kawasaki Disease Before and During the COVID-19 Pandemic: A Nationwide Population-based Study in the United States.

Background: A decrease in the incidence of Kawasaki disease during the COVID-19 pandemic has been reported globally. Yet, previous US studies utilized patient populations of limited size and geographic scope, leaving a knowledge gap regarding the national trend. Employing a large sample size will increase the generalizability of the results and allow for more detailed analyses.

Pumping iron: A multi-omics analysis of two extremophilic algae reveals iron economy management.

Marine algae are responsible for half of the world's primary productivity, but this critical carbon sink is often constrained by insufficient iron. One species of marine algae, , is remarkable for its ability to maintain photosynthesis and thrive in low-iron environments. A related species, Bardawil, shares this attribute but is an extremophile found in hypersaline environments.

Island-specific evolution of a sex-primed autosome in a sexual planarian.

The sexual strain of the planarian Schmidtea mediterranea, indigenous to Tunisia and several Mediterranean islands, is a hermaphrodite. Here we isolate individual chromosomes and use sequencing, Hi-C and linkage mapping to assemble a chromosome-scale genome reference. The linkage map reveals an extremely low rate of recombination on chromosome 1.

Diabetes mellitus in dialysis and renal transplantation.

Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate.

Whole-organism eQTL mapping at cellular resolution with single-cell sequencing.

Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode that uses single-cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment.

A meta-analysis of level I evidence comparing tenotomy vs tenodesis in the management of long head of biceps pathology.

Background: The ideal surgical treatment of long head of biceps pathology is unclear. This review evaluates Level I studies comparing tenotomy and tenodesis for the management of long head of biceps pathology.

Methods: Medline, EMBASE, and the Cochrane Library databases were searched from database inception though April 17, 2020.

Ubiquitous Selfish Toxin-Antidote Elements in Caenorhabditis Species.

Toxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but very few examples are known in animals. Here, we report the discovery of maternal-effect TAs in both C.

Alerting on mortality among patients discharged from the emergency department: a machine learning model.

Objectives: Physicians continuously make tough decisions when discharging patients. Alerting on poor outcomes may help in this decision. This study evaluates a machine learning model for predicting 30-day mortality in emergency department (ED) discharged patients.

Toxin-Antidote Elements Across the Tree of Life.

In life's constant battle for survival, it takes one to kill but two to conquer. Toxin-antitoxin or toxin-antidote (TA) elements are genetic dyads that cheat the laws of inheritance to guarantee their transmission to the next generation. This seemingly simple genetic arrangement-a toxin linked to its antidote-is capable of quickly spreading and persisting in natural populations.

Three-dimensional virtual refocusing of fluorescence microscopy images using deep learning.

We demonstrate that a deep neural network can be trained to virtually refocus a two-dimensional fluorescence image onto user-defined three-dimensional (3D) surfaces within the sample. Using this method, termed Deep-Z, we imaged the neuronal activity of a Caenorhabditis elegans worm in 3D using a time sequence of fluorescence images acquired at a single focal plane, digitally increasing the depth-of-field by 20-fold without any axial scanning, additional hardware or a trade-off of imaging resolution and speed. Furthermore, we demonstrate that this approach can correct for sample drift, tilt and other aberrations, all digitally performed after the acquisition of a single fluorescence image.

Fast genetic mapping of complex traits in C. elegans using millions of individuals in bulk.

Genetic studies of complex traits in animals have been hindered by the need to generate, maintain, and phenotype large panels of recombinant lines. We developed a new method, C. elegans eXtreme Quantitative Trait Locus (ceX-QTL) mapping, that overcomes this obstacle via bulk selection on millions of unique recombinant individuals.

Are we losing future talent? A national survey of UK medical student interest and perceptions of cardiothoracic surgery.

Objectives: Cardiothoracic surgery appears to have become a significantly less popular career option among UK medical graduates. This study aimed to elucidate the current levels of interest in pursuing a career in cardiothoracic surgery among surgically orientated UK medical students and to determine the factors underlying this decision.

Methods: An online cross-sectional survey generated using the LimeSurvey was distributed to the surgical societies of all 32 UK medical schools.

A genetic signature of the evolution of loss of flight in the Galapagos cormorant.

We have a limited understanding of the genetic and molecular basis of evolutionary changes in the size and proportion of limbs. We studied wing and pectoral skeleton reduction leading to flightlessness in the Galapagos cormorant (). We sequenced and de novo assembled the genomes of four cormorant species and applied a predictive and comparative genomics approach to find candidate variants that may have contributed to the evolution of flightlessness.

A maternal-effect selfish genetic element in .

Selfish genetic elements spread in natural populations and have an important role in genome evolution. We discovered a selfish element causing embryonic lethality in crosses between wild strains of the nematode The element is made up of , a maternal-effect toxin that kills developing embryos, and , its zygotically expressed antidote. has long been considered essential for pharynx development on the basis of its mutant phenotype, but this phenotype arises from a loss of suppression of toxicity.

Varying Intolerance of Gene Pathways to Mutational Classes Explain Genetic Convergence across Neuropsychiatric Disorders.

Genetic susceptibility to intellectual disability (ID), autism spectrum disorder (ASD), and schizophrenia (SCZ) often arises from mutations in the same genes, suggesting that they share common mechanisms. We studied genes with de novo mutations in the three disorders and genes implicated in SCZ by genome-wide association study (GWAS). Using biological annotations and brain gene expression, we show that mutation class explains enrichment patterns more than specific disorder.

Discovering Single Nucleotide Polymorphisms Regulating Human Gene Expression Using Allele Specific Expression from RNA-seq Data.

The study of the genetics of gene expression is of considerable importance to understanding the nature of common, complex diseases. The most widely applied approach to identifying relationships between genetic variation and gene expression is the expression quantitative trait loci (eQTL) approach. Here, we increased the computational power of eQTL with an alternative and complementary approach based on analyzing allele specific expression (ASE).

Imputing Phenotypes for Genome-wide Association Studies.

Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be insufficient to achieve the desired statistical power. The phenotype of interest is often difficult to collect, whereas surrogate phenotypes or related phenotypes are easier to collect and have already been collected in very large samples.

Oncogenes create a unique landscape of fragile sites.

Recurrent genomic instability in cancer is attributed to positive selection and/or the sensitivity of specific genomic regions to breakage. Among these regions are fragile sites (FSs), genomic regions sensitive to replication stress conditions induced by the DNA polymerase inhibitor aphidicolin. However, the basis for the majority of cancer genomic instability hotspots remains unclear.

Transcriptional dynamics in colorectal carcinogenesis: new insights into the role of c-Myc and miR17 in benign to cancer transformation.

Colorectal cancer develops in a sequential, evolutionary process, leading to a heterogenic tumor. Comprehensive molecular studies of colorectal cancer have been previously performed; still, the process of carcinogenesis is not fully understood. We utilized gene expression patterns from 94 samples including normal, adenoma, and adenocarcinoma colon biopsies and performed a coexpression network analysis to determine gene expression trajectories of 8,000 genes across carcinogenesis.

Chromatin regulators, phenotypic robustness, and autism risk.

Though extensively characterized clinically, the causes of autism spectrum disorder (ASD) remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD.

Allelic expression analysis in the brain suggests a role for heterogeneous insults affecting epigenetic processes in autism spectrum disorders.

Monoallelic expression, including genomic imprinting, X-chromosome inactivation and random monoallelic expression of autosomal genes are epigenetic phenomena. Genes that are expressed in a monoallelic way may be more vulnerable to genetic or epigenetic mutations. Thus, comprehensive exploration of monoallelic expression in human brains may shed light on complex brain disorders.