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The repeated adaptation of oceanic threespine sticklebacks to fresh water has made it a premier organism to study parallel evolution. These small fish have multiple distinct ecotypes that display a wide range of diverse phenotypic traits. Ecotypes are easily crossed in the laboratory, and families are large and develop quickly enough for quantitative trait locus analyses, positioning the threespine stickleback as a versatile model organism to address a wide range of biological questions. Extensive genomic resources, including linkage maps, a high-quality reference genome, and developmental genetics tools have led to insights into the genomic basis of adaptation and the identification of genomic changes controlling traits in vertebrates. Recently, threespine sticklebacks have been used as a model system to identify the genomic basis of highly complex traits, such as behavior and host-microbiome and host-parasite interactions. We review the latest findings and new avenues of research that have led the threespine stickleback to be considered a supermodel of evolutionary genomics. selleck chemical Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 22 is August 2021. Please see http//www.annualreviews.org/page/journal/pubdates for revised estimates.

Establishing research capacity in low- and middle-income countries (LMICs) is key for improving the outcomes of patients with hematologic diseases globally. Few studies have analyzed the contributions of LMICs to global hematology. The American Society of Hematology Meeting (ASH) is the largest international academic event where peer-reviewed contributions in our field are presented.

In this cross-sectional analysis, all abstracts accepted to ASH 2018 selected for a poster or oral presentation were reviewed. Those that had a contributing author from an LMIC were identified. The proportion of LMIC abstracts across categories was analyzed. Country of origin, high-income country participation, the presence of a conflict of interest (COI), and sponsorship were determined.

From 4,871 abstracts reviewed, 506 had a contributing author from an LMIC (10.4%), with 277 (54.7%) contributions in partnership with a high-income country. LMIC-independent contributions corresponded to 19 of 1,026 oral abstracts (1.9%) anational collaboration, with clinical, multicenter studies predominating and COI disclosures a frequent and unexpected feature, reflecting the instrumental nature of LMIC participation and a lack of independent, robust, locally developed hematology research.Histone deacetylase inhibitors, such as valproic acid (VPA), have important clinical therapeutic and cellular reprogramming applications. They induce chromatin re-organization that is associated with altered cellular morphology. However, there is a lack of comprehensive characterization of VPA-induced changes of nuclear size and shape. Here, we quantify 3D nuclear morphology of primary human astrocyte cells treated with VPA over time (hence, 4D). We compared volumetric and surface-based representations and identified seven features that jointly discriminate between normal and treated cells with 85% accuracy on day 7. From day 3, treated nuclei were more elongated and flattened and then continued to morphologically diverge from controls over time, becoming larger and more irregular. On day 7, most of the size and shape descriptors demonstrated significant differences between treated and untreated cells, including a 24% increase in volume and 6% reduction in extent (shape regularity) for treated nuclei. Overall, we show that 4D morphometry can capture how chromatin re-organization modulates the size and shape of the nucleus over time. These nuclear structural alterations may serve as a biomarker for histone (de-)acetylation events and provide insights into mechanisms of astrocytes-to-neurons reprogramming.

Patients with Diffuse Large B-cell Lymphoma (DLBCL) in need of immediate therapy are largely under-represented in clinical trials. The diagnosis-to-treatment interval (DTI) has recently been described as a metric to quantify such patient selection bias, with short DTI being associated with adverse risk factors and inferior outcomes. Here, we characterized the relationships between DTI, circulating tumor DNA (ctDNA), conventional risk factors, and clinical outcomes, with the goal of defining objective disease metrics contributing to selection bias.

We evaluated pretreatment ctDNA levels in 267 patients with DLBCL treated across multiple centers in Europe and the United States using Cancer Personalized Profiling by Deep Sequencing. Pretreatment ctDNA levels were correlated with DTI, total metabolic tumor volumes (TMTVs), the International Prognostic Index (IPI), and outcome.

Short DTI was associated with advanced-stage disease (

.001) and higher IPI (

.001). We also found an inverse correlation betweesing pretreatment ctDNA levels. Pretreatment ctDNA levels therefore have utility for quantifying and guarding against selection biases in prospective DLBCL clinical trials.Chromosome instability (CIN) is a major hallmark of cancer cells and believed to drive tumor progression. Several cellular defects including weak centromeric cohesion are proposed to promote CIN, but the molecular mechanisms underlying these defects are poorly understood. In a screening for SET protein levels in various cancer cell lines, we found that most of the cancer cells exhibit higher SET protein levels than nontransformed cells, including RPE-1. Cancer cells with elevated SET often show weak centromeric cohesion, revealed by MG132-induced cohesion fatigue. Partial SET knockdown largely strengthens centromeric cohesion in cancer cells without increasing overall phosphatase 2A (PP2A) activity. Pharmacologically increased PP2A activity in these cancer cells barely ameliorates centromeric cohesion. These results suggest that compromised PP2A activity, a common phenomenon in cancer cells, may not be responsible for weak centromeric cohesion. Furthermore, centromeric cohesion in cancer cells can be strengthened by ectopic Sgo1 overexpression and weakened by SET WT, not by Sgo1-binding-deficient mutants. Altogether, these findings demonstrate that SET overexpression contributes to impaired centromeric cohesion in cancer cells and illustrate misregulated SET-Sgo1 pathway as an underlying mechanism.