Decreasing body size is associated with reduced calving probability in critically endangered North Atlantic right whales

Funding: This work was supported by the Office of Naval Research (grant nos. N000142012697 and N000142112096) and the Strategic Environmental Research and Development Program (grant nos. RC20-1097, RC20-7188 and RC21-3091). Photogrammetry was supported by NOAA grant no. NA14OAR4320158 to Woods Hole Oceanographic Institution, and by NOAA's Southwest Fisheries Science Center.Body size is key to many life-history processes, including reproduction. Across species, climate change and other stressors have caused reductions in the body size to which animals can grow, called asymptotic size, with consequences for demography. A reduction in mean asymptotic length was documented for critically endangered North Atlantic right whales, in parallel with declines in health and vital rates resulting from human activities and environmental changes. Here, we tested whether smaller body size was associated with lower reproductive output, using a state-space model for individual health, survival and reproduction that quantifies the mechanistic links between these processes. Body size (as represented by the cube of length) was strongly associated with a female's calving probability at each reproductive opportunity. This relationship explained 62% of the variation in calving among reproductive females, along with their decreasing health (20%). The effects of decreasing mean body size on reproductive performance are another concerning indication of the worsening prospects for this species and many others affected by environmental change, requiring a focus of conservation and management interventions on improving conditions that affect reproduction as well as reducing mortality.Peer reviewe

Hybrid bioactive hydrogels containing single-walled carbon nanotubes covalently integrated via strain-promoted azide-alkyne cycloaddition

A non-photochemical and metal-free orthogonal route for the covalent incorporation of single-walled carbon nanotubes into a κ-carrageenan-based bioactive hydrogel scaffold is reported. The characterization of materials was carried out by usual analytical techniques and hybrid biohydrogels were evaluated for in vitro cytotoxicity on HeLa cell lines. The results revealed a significant antiproliferative effect instead of additional cytotoxicity with respect to native hydrogels.Peer reviewe

Correction: Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings.

[This corrects the article DOI: 10.5334/gh.823.]

A rev1–vpu polymorphism unique to HIV-1 subtype A and C strains impairs envelope glycoprotein expression from rev–vpu–env cassettes and reduces virion infectivity in pseudotyping assays

Functional studies of HIV-1 envelope glycoproteins (Envs) commonly include the generation of pseudoviruses, which are produced by co-transfection of rev-vpu-env cassettes with an env-deficient provirus. Here, we describe six Env constructs from transmitted/founder HIV-1 that were defective in the pseudotyping assay, although two produced infectious virions when expressed from their cognate proviruses. All of these constructs exhibited an unusual gene arrangement in which the first exon of rev (rev1) and vpu were in the same reading frame without an intervening stop codon. Disruption of the rev1-vpu fusion gene by frameshift mutation, stop codon, or abrogation of the rev initiation codon restored pseudovirion infectivity. Introduction of the fusion gene into wildtype Env cassettes severely compromised their function. The defect was not due to altered env and rev transcription or a dominant negative effect of the expressed fusion protein, but seemed to be caused by inefficient translation at the env initiation codon. Although the rev1-vpu polymorphism affects Env expression only in vitro, it can cause problems in studies requiring Env complementation, such as analyses of co-receptor usage and neutralization properties, since 3% of subtype A, 20% of subtype C and 5% of CRF01_A/E viruses encode the fusion gene. A solution is to eliminate the rev initiation codon when amplifying rev-vpu-env cassettes since this increases Env expression irrespective of the presence of the polymorphism

Management of Cardiovascular Disease Patients With Confirmed or Suspected COVID-19 in Limited Resource Settings

In this paper, we provide recommendations on the management of cardiovascular disease (CVD) among patients with confirmed or suspected coronavirus disease (COVID-19) to facilitate the decision making of healthcare professionals in low resource settings. The emergence of novel coronavirus disease, also known as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has presented an unprecedented global challenge for the healthcare community. The ability of SARS-CoV-2 to get transmitted during the asymptomatic phase and its high infectivity have led to the rapid transmission of COVID-19 beyond geographic regions, leading to a pandemic. There is concern that COVID-19 is cardiotropic, and it interacts with the cardiovascular system on multiple levels. Individuals with established CVD are more susceptible to severe COVID-19. Through a consensus approach involving an international group this WHF statement summarizes the links between cardiovascular disease and COVID-19 and present some practical recommendations for the management of hypertension and diabetes, acute coronary syndrome, heart failure, rheumatic heart disease, Chagas disease, and myocardial injury for patients with COVID-19 in low-resource settings. This document is not a clinical guideline and it is not intended to replace national clinical guidelines or recommendations. Given the rapidly growing burden posed by COVID-19 illness and the associated severe prognostic implication of CVD involvement, further research is required to understand the potential mechanisms linking COVID-19 and CVD, clinical presentation, and outcomes of various cardiovascular manifestations in COVID-19 patients

Identification and Characterization of Nucleolin as a COUP-TFII Coactivator of Retinoic Acid Receptor β Transcription in Breast Cancer Cells

The orphan nuclear receptor COUP-TFII plays an undefined role in breast cancer. Previously we reported lower COUP-TFII expression in tamoxifen/endocrine-resistant versus sensitive breast cancer cell lines. The identification of COUP-TFII-interacting proteins will help to elucidate its mechanism of action as a transcriptional regulator in breast cancer.FLAG-affinity purification and multidimensional protein identification technology (MudPIT) identified nucleolin among the proteins interacting with COUP-TFII in MCF-7 tamoxifen-sensitive breast cancer cells. Interaction of COUP-TFII and nucleolin was confirmed by coimmunoprecipitation of endogenous proteins in MCF-7 and T47D breast cancer cells. In vitro studies revealed that COUP-TFII interacts with the C-terminal arginine-glycine repeat (RGG) domain of nucleolin. Functional interaction between COUP-TFII and nucleolin was indicated by studies showing that siRNA knockdown of nucleolin and an oligonucleotide aptamer that targets nucleolin, AS1411, inhibited endogenous COUP-TFII-stimulated RARB2 expression in MCF-7 and T47D cells. Chromatin immunoprecipitation revealed COUP-TFII occupancy of the RARB2 promoter was increased by all-trans retinoic acid (atRA). RARβ2 regulated gene RRIG1 was increased by atRA and COUP-TFII transfection and inhibited by siCOUP-TFII. Immunohistochemical staining of breast tumor microarrays showed nuclear COUP-TFII and nucleolin staining was correlated in invasive ductal carcinomas. COUP-TFII staining correlated with ERα, SRC-1, AIB1, Pea3, MMP2, and phospho-Src and was reduced with increased tumor grade.Our data indicate that nucleolin plays a coregulatory role in transcriptional regulation of the tumor suppressor RARB2 by COUP-TFII

Establishing outcome measures in early knee osteoarthritis

The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting