The Year in Thoracic Anesthesia: Selected Highlights from 2022.

This article reviews research highlights in the field of thoracic anesthesia. The highlights of this year included new developments in the preoperative assessment and prehabilitation of patients requiring thoracic surgery, updates on the use of devices for one-lung ventilation (OLV) in adults and children, updates on the anesthetic and postoperative management of these patients, including protective OLV ventilation, the use of opioid-sparing techniques and regional anesthesia, and outcomes using enhanced recovery after surgery, as well as the use of expanding indications for extracorporeal membrane oxygenation, specialized anesthetic techniques for airway surgery, and nonintubated video-assisted thoracic surgery.

Environmental Association Identifies Candidates for Tolerance to Low Temperature and Drought.

Barley (Hordeum vulgare ssp. vulgare) is cultivated from the equator to the Arctic Circle. The wild progenitor species, Hordeum vulgare ssp. spontaneum, occupies a relatively narrow latitudinal range (∼30 - 40° N) primarily at low elevation (< 1,500 m). Adaptation to the range of cultivation has occurred over ∼8,000 years. The genetic basis of adaptation is amenable to study through environmental association. An advantage of environmental association in a well-characterized crop is that many loci that contribute to climatic adaptation and abiotic stress tolerance have already been identified. This provides the opportunity to determine if environmental association approaches effectively identify these loci of large effect. Using published genotyping from 7,864 SNPs in 803 barley landraces, we examined allele frequency differentiation across multiple partitions of the data and mixed model associations relative to bioclimatic variables. Using newly generated resequencing data from a subset of these landraces, we tested for linkage disequilibrium (LD) between SNPs queried in genotyping and SNPs in neighboring loci. Six loci previously reported to contribute to adaptive differences in flowering time and abiotic stress in barley and six loci previously identified in other plant species were identified in our analyses. In many cases, patterns of LD are consistent with the causative variant occurring in the immediate vicinity of the queried SNP. The identification of barley orthologs to well-characterized genes may provide a new understanding of the nature of adaptive variation and could permit a more targeted use of potentially adaptive variants in barley breeding and germplasm improvement.

Comparative Genomics Approaches Accurately Predict Deleterious Variants in Plants.

Recent advances in genome resequencing have led to increased interest in prediction of the functional consequences of genetic variants. Variants at phylogenetically conserved sites are of particular interest, because they are more likely than variants at phylogenetically variable sites to have deleterious effects on fitness and contribute to phenotypic variation. Numerous comparative genomic approaches have been developed to predict deleterious variants, but the approaches are nearly always assessed based on their ability to identify known disease-causing mutations in humans. Determining the accuracy of deleterious variant predictions in nonhuman species is important to understanding evolution, domestication, and potentially to improving crop quality and yield. To examine our ability to predict deleterious variants in plants we generated a curated database of 2,910 Arabidopsis thaliana mutants with known phenotypes. We evaluated seven approaches and found that while all performed well, their relative ranking differed from prior benchmarks in humans. We conclude that deleterious mutations can be reliably predicted in A. thaliana and likely other plant species, but that the relative performance of various approaches does not necessarily translate from one species to another.

angsd-wrapper: utilities for analysing next-generation sequencing data.

High-throughput sequencing has changed many aspects of population genetics, molecular ecology and related fields, affecting both experimental design and data analysis. The software package angsd allows users to perform a number of population genetic analyses on high-throughput sequencing data. angsd uses probabilistic approaches which can directly make use of genotype likelihoods; thus, SNP calling is not required for comparative analyses. This takes advantage of all the sequencing data and produces more accurate results for samples with low sequencing depth. Here, we present angsd-wrapper, a set of wrapper scripts that provides a user-friendly interface for running angsd and visualizing results. angsd-wrapper supports multiple types of analyses including estimates of nucleotide sequence diversity neutrality tests, principal component analysis, estimation of admixture proportions for individual samples and calculation of statistics that quantify recent introgression. angsd-wrapper also provides interactive graphing of angsd results to enhance data exploration. We demonstrate the usefulness of angsd-wrapper by analysing resequencing data from populations of wild and domesticated Zea. angsd-wrapper is freely available from https://github.com/mojaveazure/angsd-wrapper.

The Role of Deleterious Substitutions in Crop Genomes.

Populations continually incur new mutations with fitness effects ranging from lethal to adaptive. While the distribution of fitness effects of new mutations is not directly observable, many mutations likely either have no effect on organismal fitness or are deleterious. Historically, it has been hypothesized that a population may carry many mildly deleterious variants as segregating variation, which reduces the mean absolute fitness of the population. Recent advances in sequencing technology and sequence conservation-based metrics for inferring the functional effect of a variant permit examination of the persistence of deleterious variants in populations. The issue of segregating deleterious variation is particularly important for crop improvement, because the demographic history of domestication and breeding allows deleterious variants to persist and reach moderate frequency, potentially reducing crop productivity. In this study, we use exome resequencing of 15 barley accessions and genome resequencing of 8 soybean accessions to investigate the prevalence of deleterious single nucleotide polymorphisms (SNPs) in the protein-coding regions of the genomes of two crops. We conclude that individual cultivars carry hundreds of deleterious SNPs on average, and that nonsense variants make up a minority of deleterious SNPs. Our approach identifies known phenotype-altering variants as deleterious more frequently than the genome-wide average, suggesting that putatively deleterious variants are likely to affect phenotypic variation. We also report the implementation of a SNP annotation tool BAD_Mutations that makes use of a likelihood ratio test based on alignment of all currently publicly available Angiosperm genomes.

Molecular characterization of uterine fibroids and its implication for underlying mechanisms of pathogenesis.

OBJECTIVE: To identify genes involved in fibroid development by performing global expression profiling on tissues of normal myometrium and uterine leiomyoma origin using Affymetrix HG-U133A GeneChip microarrays. DESIGN: Whole-genome analysis of mRNA levels in leiomyoma and normal myometrium tissue samples. SETTING: University research laboratory. PATIENT(S): Eight patients of varying age and race undergoing surgery for symptomatic fibroids. INTERVENTION(S): After tissue collection of five tumors and five normals from human pathological specimens, labeled cRNA was generated and hybridized to the oligonucleotide-composed arrays. MAIN OUTCOME MEASURE(S): Quantification of transcript expression levels in uterine fibroids relative to normal myometrium. RESULT(S): Model-based expression analysis revealed that of the 22,500 transcripts represented on the arrays, 226 genes were found to be dysregulated by a > or =1.5-fold change between leiomyoma and normal myometrium. Moreover, our research identified many dysregulated apoptosis-related genes, of particular interest was TRAIL and Ask1, and also found numerous differentially expressed proliferation genes, including TGFB1, PDGFC, and two dual specificity phosphatases. CONCLUSION(S): These results indicate that these genes may play a significant role in the development of leiomyomas from normal uterine tissue. We hypothesize that the deregulation of apoptotic and proliferative processes is pivotal to fibroid development.