Origin, migration pathways, and paleoenvironmental significance of Holocene ostracod records from the northeastern Black Sea shelf

Micropaleontological studies of the Black Sea, including ostracod records, have suggested that early Holocene salinity values were between ~5 and 10 practical salinity units (psu), contrasting with present values of 18–22 psu. However, more precise paleoenvironmental reconstructions based on ostracod assemblages require additional information related to their modern ecological affinities. This study uses modern species information collected from samples with living fauna to interpret the fossil Holocene assemblages of two sediment cores, Ak-2575 and Ak-521, collected from the northeastern outer shelf of the Black Sea. A total of 37 ostracod species are recorded in the fossil assemblages, with 2 related to freshwater/oligohaline environments, 23 from Caspian-type environments, and 12 from environments similar to the Mediterranean. Three distinct assemblage zones are identified from the Caspian type dominating in the early Holocene up to 7.4 cal ka BP, a mixed assemblage of Caspian type and Mediterranean type from 7.4 to 6.8 cal ka BP, and a progressive dominance of Mediterranean species from 6.8 cal ka BP. It is very likely that the dominant control of ostracod species occurrence during the period up to ~6.8 cal ka BP is salinity. A range of factors including temperature, biotope, and sedimentation rates influenced the species distribution over the last 6.8 cal ka BP

Effect of arsenic-phosphorus interaction on arsenic-induced oxidative stress in chickpea plants

Arsenic-induced oxidative stress in chickpea was investigated under glasshouse conditions in response to application of arsenic and phosphorus. Three levels of arsenic (0, 30 and 60 mg kg−1) and four levels of P (50, 100, 200, and 400 mg kg−1) were applied to soil-grown plants. Increasing levels of both arsenic and P significantly increased arsenic concentrations in the plants. Shoot growth was reduced with increased arsenic supply regardless of applied P levels. Applied arsenic induced oxidative stress in the plants, and the concentrations of H2O2 and lipid peroxidation were increased. Activity of superoxide dismutase (SOD) and concentrations of non-enzymatic antioxidants decreased in these plants, but activities of catalase (CAT) and ascorbate peroxidase (APX) were significantly increased under arsenic phytotoxicity. Increased supply of P decreased activities of CAT and APX, and decreased concentrations of non-enzymatic antioxidants, but the high-P plants had lowered lipid peroxidation. It can be concluded that P increased uptake of arsenic from the soil, probably by making it more available, but although plant growth was inhibited by arsenic the P may have partially protected the membranes from arsenic-induced oxidative stress

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia

Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival. Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32–91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1–9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008. Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value. Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients’ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient’s quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents

A Genomewide Functional Network for the Laboratory Mouse

Establishing a functional network is invaluable to our understanding of gene function, pathways, and systems-level properties of an organism and can be a powerful resource in directing targeted experiments. In this study, we present a functional network for the laboratory mouse based on a Bayesian integration of diverse genetic and functional genomic data. The resulting network includes probabilistic functional linkages among 20,581 protein-coding genes. We show that this network can accurately predict novel functional assignments and network components and present experimental evidence for predictions related to Nanog homeobox (Nanog), a critical gene in mouse embryonic stem cell pluripotency. An analysis of the global topology of the mouse functional network reveals multiple biologically relevant systems-level features of the mouse proteome. Specifically, we identify the clustering coefficient as a critical characteristic of central modulators that affect diverse pathways as well as genes associated with different phenotype traits and diseases. In addition, a cross-species comparison of functional interactomes on a genomic scale revealed distinct functional characteristics of conserved neighborhoods as compared to subnetworks specific to higher organisms. Thus, our global functional network for the laboratory mouse provides the community with a key resource for discovering protein functions and novel pathway components as well as a tool for exploring systems-level topological and evolutionary features of cellular interactomes. To facilitate exploration of this network by the biomedical research community, we illustrate its application in function and disease gene discovery through an interactive, Web-based, publicly available interface at http://mouseNET.princeton.edu

SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs). With sub-diffraction, three-dimensional, optical imaging, we visualised nsP3-positive structures with variable density and morphology, including high-density rod-like structures, large spherical granules, and small, low-density structures. Next, we confirmed the utility of the SNAP tag for studying protein turnover by pulse-chase labelling. We also revealed an association of nsP3 with cellular lipid droplets and examined the spatial relationships between nsP3 and the non-structural protein 1 (nsP1). Together, our study provides a sensitive, specific, and versatile system for fundamental research into the individual functions of a viral non-structural protein during infection with a medically important arthropod-borne virus (arbovirus)

A Hierarchical Taxonomy of Psychopathology Can Transform Mental Health Research

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is based on empirical patterns of co-occurrence among psychological symptoms. We highlight key ways in which this framework can advance mental-health research, and we provide some heuristics for using HiTOP to test theories of psychopathology. We then review emerging evidence that supports the value of a hierarchical, dimensional model of mental illness across diverse research areas in psychological science. These new data suggest that the HiTOP system has the potential to accelerate and improve research on mental-health problems as well as efforts to more effectively assess, prevent, and treat mental illness

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit