Intrusive History and Petrogenesis of the Ash Mountain Complex, Sierra Nevada Batholith, California (USA)

The Ash Mountain Complex (AMC) in the western Sierra Nevada batholith (SNB; California, USA) is an exposure of six compositionally diverse intrusive lithologies with clear crosscutting relationships that permit a focused investigation of magma source characteristics and the relative roles of petrogenetic processes on the evolution of the system. We use new field observations, zircon U-Pb dates, major and trace element data, and Sr-Nd-Pb isotopic data to develop a model that can be applied to similar SNB intrusive suites. Stage 1 units, emplaced ca. 105 Ma, consist of two gabbros, a gabbrodiorite, and a granite. Stage 2 and stage 3 units were emplaced ca. 104 Ma and ca. 103 Ma, respectively, and are granites. We suggest that stage 1 gabbroids were derived by partial melting of lithospheric mantle, whereas coeval felsic magmas were derived by partial melting of a mafic, juvenile crustal source. Stage 2 and stage 3 granitoids were derived from similar sources that generated stage 1 granitoids, but there was greater input from evolved crust. Fractionation and/or assimilation played only a minor role in system evolution. Past studies of SNB magmas have come to conflicting conclusions about the petrogenesis of intermediate magmas that dominate the batholith; we hypothesize that mafic and felsic end members of the AMC could represent end members in mixing processes that generate these magmas. The timing of emplacement of the AMC coincides with a transition of magmatic style in the SNB, from smaller volume magmatic suites with mixed mantle and crustal sources to larger volume magmatic suites derived from greater proportions of crust

Disentangling a group of lensed submm galaxies at z∼ 2.9

MS0451.6−0305 is a rich galaxy cluster whose strong lensing is particularly prominent at submm wavelengths. We combine new Submillimetre Common-User Bolometer Array (SCUBA)-2 data with imaging from Herschel Spectral and Photometric Imaging Receiver (SPIRE) and PACS and Hubble Space Telescope in order to try to understand the nature of the sources being lensed. In the region of the ‘giant submm arc', we uncover seven multiply imaged galaxies (up from the previously known four), of which six are found to be at a redshift of z∼2.9, and possibly constitute an interacting system. Using a novel forward-modelling approach, we are able to simultaneously deblend and fit spectral energy distributions to the individual galaxies that contribute to the giant submm arc, constraining their dust temperatures, far-infrared luminosities, and star formation rates (SFRs). The submm arc first identified by SCUBA can now be seen to be composed of at least five distinct sources, four of these within a galaxy group at z∼2.9. Only a handful of lensed galaxy groups at this redshift are expected on the sky, and thus this is a unique opportunity for studying such systems in detail. The total unlensed luminosity for this galaxy group is (3.1±0.3)×1012 L⊙, which gives an unlensed SFR of (450±50) M⊙yr−1. This finding suggests that submm source multiplicity, due to physically associated groupings as opposed to chance alignment, extends to fainter flux densities than previously discovered. Many of these systems may also host optical companions undetected in the submm, as is the case her

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder

Management of infantile hemangiomas during the COVID pandemic

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided

NuMA Overexpression in Epithelial Ovarian Cancer

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon

Nck2 promotes human melanoma cell proliferation, migration and invasion in vitro and primary melanoma-derived tumor growth in vivo

<p>Abstract</p> <p>Background</p> <p>Nck1 and Nck2 adaptor proteins are involved in signaling pathways mediating proliferation, cytoskeleton organization and integrated stress response. Overexpression of Nck1 in fibroblasts has been shown to be oncogenic. Through the years this concept has been challenged and the consensus is now that overexpression of either Nck cooperates with strong oncogenes to transform cells. Therefore, variations in Nck expression levels in transformed cells could endorse cancer progression.</p> <p>Methods</p> <p>Expression of Nck1 and Nck2 proteins in various cancer cell lines at different stages of progression were analyzed by western blots. We created human primary melanoma cell lines overexpressing GFP-Nck2 and investigated their ability to proliferate along with metastatic characteristics such as migration and invasion. By western blot analysis, we compared levels of proteins phosphorylated on tyrosine as well as cadherins and integrins in human melanoma cells overexpressing or not Nck2. Finally, in mice we assessed tumor growth rate of human melanoma cells expressing increasing levels of Nck2.</p> <p>Results</p> <p>We found that expression of Nck2 is consistently increased in various metastatic cancer cell lines compared with primary counterparts. Particularly, we observed significant higher levels of Nck2 protein and mRNA, as opposed to no change in Nck1, in human metastatic melanoma cell lines compared with non-metastatic melanoma and normal melanocytes. We demonstrated the involvement of Nck2 in proliferation, migration and invasion in human melanoma cells. Moreover, we discovered that Nck2 overexpression in human primary melanoma cells correlates with higher levels of proteins phosphorylated on tyrosine residues, assembly of Nck2-dependent pY-proteins-containing molecular complexes and downregulation of cadherins and integrins. Importantly, we uncovered that injection of Nck2-overexpressing human primary melanoma cells into mice increases melanoma-derived tumor growth rate.</p> <p>Conclusions</p> <p>Collectively, our data indicate that Nck2 effectively influences human melanoma phenotype progression. At the molecular level, we propose that Nck2 in human primary melanoma promotes the formation of molecular complexes regulating proliferation and actin cytoskeleton dynamics by modulating kinases or phosphatases activities that results in increased levels of proteins phosphorylated on tyrosine residues. This study provides new insights regarding cancer progression that could impact on the therapeutic strategies targeting cancer.</p

Lipopolysaccharides Impair Insulin Gene Expression in Isolated Islets of Langerhans via Toll-Like Receptor-4 and NF-κB Signalling

BACKGROUND:Type 2 diabetes is characterized by pancreatic β-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that the signalling cascade activated by lipopolysaccharides (LPS) binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets. METHODOLOGY/PRINCIPAL FINDINGS:A 24-h exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of pancreas-duodenum homebox-1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Accordingly, LPS exposure also decreased glucose-induced insulin secretion. LPS repression of insulin, PDX-1 and MafA expression, as well as its inhibition of insulin secretion, were not observed in islets from TLR4-deficient mice. LPS inhibition of β-cell gene expression in rat islets was prevented by inhibition of the NF-κB pathway, but not the p38 mitogen-activated protein kinase (p38 MAPK) pathway. CONCLUSIONS/SIGNIFICANCE:Our findings demonstrate that LPS inhibit β-cell gene expression in a TLR4-dependent manner and via NF-κB signaling in pancreatic islets, suggesting a novel mechanism by which the gut microbiota might affect pancreatic β-cell function