Abstract
The PathoSystems Resource Integration Center (PATRIC) is the bacterial Bioinformatics Resource Center funded by the National Institute of Allergy and Infectious Diseases ...(https://www.patricbrc.org). PATRIC supports bioinformatic analyses of all bacteria with a special emphasis on pathogens, offering a rich comparative analysis environment that provides users with access to over 250 000 uniformly annotated and publicly available genomes with curated metadata. PATRIC offers web-based visualization and comparative analysis tools, a private workspace in which users can analyze their own data in the context of the public collections, services that streamline complex bioinformatic workflows and command-line tools for bulk data analysis. Over the past several years, as genomic and other omics-related experiments have become more cost-effective and widespread, we have observed considerable growth in the usage of and demand for easy-to-use, publicly available bioinformatic tools and services. Here we report the recent updates to the PATRIC resource, including new web-based comparative analysis tools, eight new services and the release of a command-line interface to access, query and analyze data.
If Black communities are to participate in Covid-19 trials, clinicians, investigators, and pharmaceutical companies must provide convincing evidence — sufficient to overcome the extensive historical ...evidence to the contrary — that they are, in fact, trustworthy.
The National Institute of Allergy and Infectious Diseases (NIAID) established the Bioinformatics Resource Center (BRC) program to assist researchers with analyzing the growing body of genome sequence ...and other omics-related data. In this report, we describe the merger of the PAThosystems Resource Integration Center (PATRIC), the Influenza Research Database (IRD) and the Virus Pathogen Database and Analysis Resource (ViPR) BRCs to form the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) https://www.bv-brc.org/. The combined BV-BRC leverages the functionality of the bacterial and viral resources to provide a unified data model, enhanced web-based visualization and analysis tools, bioinformatics services, and a powerful suite of command line tools that benefit the bacterial and viral research communities.
Adults with type 2 diabetes and CKD were assigned to receive bardoxolone methyl at a dose of 25 mg, 75 mg, or 150 mg once daily or placebo. Drug treatment was associated with improved estimated GFR, ...a finding that persisted throughout the 52-week treatment period.
Diabetes mellitus is a major cause of chronic kidney disease (CKD) worldwide.
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The complications of CKD (e.g., cardiovascular disease and death) occur before kidney failure develops and are independent of known risk factors (i.e., hypertension and proteinuria).
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Although CKD progression is slowed by the use of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs), in many patients, the condition progresses to kidney failure.
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CKD in patients with diabetes is associated with chronic inflammation and oxidative stress.
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Effects of these processes result in glomerular endothelial dysfunction and mesangial-cell contraction and, with time, glomerular fibrosis and mesangial expansion. These . . .
Abstract
Background
Major advances in selection progress for cattle have been made following the introduction of genomic tools over the past 10–12 years. These tools depend upon the Bos taurus ...reference genome (UMD3.1.1), which was created using now-outdated technologies and is hindered by a variety of deficiencies and inaccuracies.
Results
We present the new reference genome for cattle, ARS-UCD1.2, based on the same animal as the original to facilitate transfer and interpretation of results obtained from the earlier version, but applying a combination of modern technologies in a de novo assembly to increase continuity, accuracy, and completeness. The assembly includes 2.7 Gb and is >250× more continuous than the original assembly, with contig N50 >25 Mb and L50 of 32. We also greatly expanded supporting RNA-based data for annotation that identifies 30,396 total genes (21,039 protein coding). The new reference assembly is accessible in annotated form for public use.
Conclusions
We demonstrate that improved continuity of assembled sequence warrants the adoption of ARS-UCD1.2 as the new cattle reference genome and that increased assembly accuracy will benefit future research on this species.
Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to ...Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.
Five or more circulating tumor cells (CTCs) per 7.5 mL of blood predicts for poorer progression-free survival (PFS) in patients with metastatic breast cancer (MBC). We conducted a prospective study ...to demonstrate that CTC results correlate strongly with radiographic disease progression at the time of and in advance of imaging.
Serial CTC levels were obtained in patients starting a new treatment regimen for progressive, radiographically measurable MBC. Peripheral blood was collected for CTC enumeration at baseline and at 3- to 4-week intervals. Clinical outcomes were based on radiographic studies performed in 9- to 12-week intervals.
Sixty-eight patients were evaluable for the CTC-imaging correlations, and 74 patients were evaluable for the PFS analysis. Median follow-up was 13.3 months. A statistically significant correlation was demonstrated between CTC levels and radiographic disease progression in patients receiving chemotherapy or endocrine therapy. This correlation applied to CTC results obtained at the time of imaging (odds ratio OR, 6.3), 3 to 5 weeks before imaging (OR, 3.1), and 7 to 9 weeks before imaging (OR, 4.9). Results from analyses stratified by type of therapy remained statistically significant. Shorter PFS was observed for patients with five or more CTCs at 3 to 5 weeks and at 7 to 9 weeks after the start of treatment.
We provide, to our knowledge, the first evidence of a strong correlation between CTC results and radiographic disease progression in patients receiving chemotherapy or endocrine therapy for MBC. These findings support the role of CTC enumeration as an adjunct to standard methods of monitoring disease status in MBC.
The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, ...produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)--a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among HELICONIUS: Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with λmax = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate.
Objective: Many studies document efficacy of cognitive behavioral therapy (CBT) for chronic pain, but few studies have examined potential treatment mechanisms. In analyses of data from a controlled ...trial, we examined whether changes in attitudes toward adopting a pain self-management approach-CBT-specific mechanisms-and quality of working alliance and patient expectations-general mechanisms-early in treatment were related to later-treatment changes in outcomes. Method: Our sample was composed of 94 adults (primarily White; mean age: 55.3 years, SD = 11.7; 23% female) who participated in enhanced or standard CBT, and completed measures of attitudes toward self-management (mechanisms), pain intensity, pain interference, depressive symptoms and goal accomplishment (outcomes) at pretreatment, 4- and 8-week assessments, and posttreatment. Working alliance was measured at 4 and 8 weeks, and patient expectations at 3 weeks. Results: Because the CBT conditions produced comparable improvements, we combined them. Precontemplation and action attitudes toward pain self-management showed significant quadratic trends over assessments such that 67% and 94.1% (respectively) of total pre-post changes occurred in the first 4 weeks. Outcomes showed only significant linear trends. Cross-lagged regressions revealed that pretreatment-to-4-week changes in action attitudes and 4-week levels of working alliance were related significantly with 4-week-to-posttreatment changes in pain intensity and interference but not vice versa and that 3-week patient expectations were related to 4-week-to-posttreatment changes in interference. Analyses in which mechanism factors were entered simultaneously revealed nonsignificant unique effects on outcomes. Conclusions: Adopting an action attitude early in treatment may represent a specific CBT mechanism but with effects held largely in common with 2 general mechanisms.
Our objective was to perform a systematic review and meta-analysis of the research literature assessing the effect of caffeine ingestion on maximal voluntary contraction (MVC) strength and muscular ...endurance.
Thirty-four relevant studies between 1939 and 2008 were included in the meta-analyses of caffeine's effects on MVC strength (n = 27 studies) and muscular endurance (n = 23 studies). Effect sizes (ES) were calculated as the standardized mean difference and meta-analyses were completed using a random-effects model.
Overall, caffeine ingestion was found to result in a small beneficial effect on MVC strength (overall ES = 0.19, P = 0.0003). However, caffeine appears to improve MVC strength primarily in the knee extensors (i.e., by approximately 7%, ES = 0.37) and not in other muscle groups such as the forearm or the knee flexors. In an attempt to offer a physiological mechanism behind caffeine's ability to improve MVC strength, a meta-analysis was run on ES from nine studies that measured percent muscle activation during MVC in trials comparing caffeine versus placebo; the overall ES (0.67) was highly significant (P = 0.00008) and of moderate to large size, thus implicating an effect of caffeine on the CNS. Caffeine ingestion was also found to exert a small beneficial effect on muscular endurance (overall ES = 0.28, P = 0.00005). However, it appears caffeine improves muscular endurance only when it is assessed using open (i.e., by approximately 18%, ES = 0.37) and not fixed end point tests.
Overall, caffeine ingestion improves MVC strength and muscular endurance. The effect on strength appears exclusively in the knee extensors, and the effect on muscular endurance appears only detectable with open end point tests.
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