Dark-matter-deficient dwarf galaxies form via tidal stripping of dark matter in interactions with massive companions

Copyright 2021 The Author(s). Published by Oxford University Press on behalf of Royal Astronomical Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.In the standard Lambda-CDM paradigm, dwarf galaxies are expected to be dark-matter-rich, as baryonic feedback is thought to quickly drive gas out of their shallow potential wells and quench star formation at early epochs. Recent observations of local dwarfs with extremely low dark matter content appear to contradict this picture, potentially bringing the validity of the standard model into question. We use NewHorizon, a high-resolution cosmological simulation, to demonstrate that sustained stripping of dark matter, in tidal interactions between a massive galaxy and a dwarf satellite, naturally produces dwarfs that are dark-matter-deficient, even though their initial dark matter fractions are normal. The process of dark matter stripping is responsible for the large scatter in the halo-to-stellar mass relation in the dwarf regime. The degree of stripping is driven by the closeness of the orbit of the dwarf around its massive companion and, in extreme cases, produces dwarfs with halo-to-stellar mass ratios as low as unity, consistent with the findings of recent observational studies. ~30 per cent of dwarfs show some deviation from normal dark matter fractions due to dark matter stripping, with 10 per cent showing high levels of dark matter deficiency (Mhalo/M*<10). Given their close orbits, a significant fraction of dark-matter-deficient dwarfs merge with their massive companions (e.g. ~70 per cent merge over timescales of ~3.5 Gyrs), with the dark-matter-deficient population being constantly replenished by new interactions between dwarfs and massive companions. The creation of these galaxies is, therefore, a natural by-product of galaxy evolution and their existence is not in tension with the standard paradigm.Peer reviewedFinal Published versio

Irresponsiveness of two retinoblastoma cases to conservative therapy correlates with up- regulation of hERG1 channels and of the VEGF-A pathway

<p>Abstract</p> <p>Background</p> <p>Treatment strategies for Retinoblastoma (RB), the most common primary intraocular tumor in children, have evolved over the past few decades and chemoreduction is currently the most popular treatment strategy. Despite success, systemic chemotherapeutic treatment has relevant toxicity, especially in the pediatric population. Antiangiogenic therapy has thus been proposed as a valuable alternative for pediatric malignancies, in particolar RB. Indeed, it has been shown that vessel density correlates with both local invasive growth and presence of metastases in RB, suggesting that angiogenesis could play a pivotal role for both local and systemic invasive growth in RB. We present here two cases of sporadic, bilateral RB that did not benefit from the conservative treatment and we provide evidence that the VEGF-A pathway is significantly up-regulated in both RB cases along with an over expression of hERG1 K⁺channels.</p> <p>Case presentation</p> <p>Two patients showed a sporadic, bilateral RB, classified at Stage II of the Reese-Elsworth Classification. Neither of them got benefits from conservative treatment, and the two eyes were enucleated. In samples from both RB cases we studied the VEGF-A pathway: VEGF-A showed high levels in the vitreous, the <it>vegf-a, flt-1, kdr</it>, and <it>hif1-α </it>transcripts were over-expressed. Moreover, both the transcripts and proteins of the hERG1 K⁺channels turned out to be up-regulated in the two RB cases compared to the non cancerous retinal tissue.</p> <p>Conclusions</p> <p>We provide evidence that the VEGF-A pathway is up-regulated in two particular aggressive cases of bilateral RB, which did not experience any benefit from conservative treatment, showing the overexpression of the <it>vegf-a</it>, <it>flt-1</it>, <it>kdr </it>and <it>hif1-α </it>transcripts and the high secretion of VEGF-A. Moreover we also show for the first time that the <it>herg1 </it>gene transcripts and protein are over expressed in RB, as occurs in several aggressive tumors. These results further stress the relevance of the VEGF-A pathway in RB and the correlation with hERG1, making aggressive and recurrent RB cases good candidates for antiangiogenesis therapies based on the targeting of VEGF-A.</p

Depression and physical activity in a sample of nigerian adolescents: levels, relationships and predictors

<p>Abstract</p> <p>Background</p> <p>Physical inactivity is related to many morbidities but the evidence of its link with depression in adolescents needs further investigation in view of the existing conflicting reports.</p> <p>Methods</p> <p>The data for this cross-sectional study were collected from 1,100 Nigerian adolescents aged 12-17 years. Depressive symptomatology and physical activity were assessed using the Children's Depression Inventory (CDI) and the Physical Activity Questionnaire-Adolescent version (PAQ-A) respectively. Independent t tests, Pearson's Moment Correlation and Multi-level logistic regression analyses for individual and school area influences were carried out on the data at p < 0.05.</p> <p>Results</p> <p>The mean age of the participants was 15.20 ± 1.435 years. The prevalence of mild to moderate depression was 23.8%, definite depression was 5.7% and low physical activity was 53.8%. More severe depressive symptoms were linked with lower levels of physical activity (r = -0.82, p < 0.001) and moderate physical activity was linked with reduced risk of depressive symptoms (OR = 0.42, 95% CI = 0.29-0.71). The odds of having depressive symptoms were higher in older adolescents (OR = 2.16, 95% CI = 1.81-3.44) and in females (OR = 2.92, 95% CI = 1.82-3.54). Females had a higher risk of low physical activity than male adolescents (OR = 2.91, 95% CI = 1.51-4.26). Being in Senior Secondary class three was a significant predictor of depressive symptoms (OR = 3.4, 95% CI = 2.55-4.37) and low physical activity.</p> <p>Conclusions</p> <p>A sizable burden of depression and low physical activity existed among the studied adolescents and these were linked to both individual and school factors. Future studies should examine the effects of physical activity among clinical samples of adolescents with depression.</p

Antiangiogenic Activity of 2-Deoxy-D-Glucose

During tumor angiogenesis, endothelial cells (ECs) are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO) N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR), which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay). Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETA)T(AG) transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies conference

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized here

Geographical Distribution and Risk Association of Human Papillomavirus Genotype 52–Variant Lineages

Human papillomavirus (HPV) genotype 52 is commonly found in Asian cases of cervical cancer but is rare elsewhere. Analysis of 611 isolates collected worldwide revealed a remarkable geographical distribution, with lineage B predominating in Asia (89.0% vs 0%–5.5% ; Pcorrected &lt; .001), whereas lineage A predominated in Africa, the Americas, and Europe. We propose that the name “Asian lineage” be used to denote lineage B, to signify this feature. Preliminary analysis suggested a higher disease risk for lineage B, although ethnogeographical confounders could not be excluded. Further studies are warranted to verify whether the reported high attribution of disease to HPV52 in Asia is due to the high prevalence of lineage B

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized her