Dysregulation of endothelial cell connexin-43 localisation in response to doxorubicin

Introduction: Anthracyclines, such as doxorubicin, remain an important class of chemotherapeutic agent however their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity. Whilst most studies have focused on cardiomyocyte impairment, circulating doxorubicin has been shown to impact human microvascular responses to doxorubicin in coronary vessels.1 Studies show increased endothelial cell permeability resulting in increased paracellular permeability due to damage to the integrity of cell-cell junctions.2 Strategies to maintain vessel integrity and prevent endothelial cell dysregulation could represent a novel therapeutic opportunity to limit the toxic effects of doxorubicin. The aim of this project was to assess the impact of doxorubicin upon endothelial gap junction proteins, in particular connexin-43 (Cx43)

Busy Streets Theory: The Effects of Communityâ engaged Greening on Violence

Lack of maintenance on vacant neighborhood lots is associated with higher levels of depression, anxiety, and stress for nearby residents. Overgrown grasses and dense brush provide hiding spots for criminals and space to conduct illicit activities. This study builds upon previous research by investigating greening programs that engage community members to conduct routine maintenance on vacant lots within their neighborhoods. The Clean & Green program is a communityâ based solution that facilitates residentâ driven routine maintenance of vacant lots in a midsized, Midwestern city. We use mixed effects regression to compare assault and violent crime counts on streets where vacant lot(s) are maintained by community members (N = 216) versus streets where vacant lots were left alone (N = 446) over a 5â year timeframe (2009â 2013). Street segments with vacant lots maintained through the Clean & Green program had nearly 40% fewer assaults and violent crimes than street segments with vacant, abandoned lots, which held across 4 years with a large sample and efforts to test counterfactual explanations. Communityâ engaged greening programs may not only provide a solution to vacant lot maintenance, but also work as a crime prevention or reduction strategy. Engaging the community to maintain vacant lots in their neighborhood reduces costs and may increase the sustainability of the program.HighlightsBlighted and abandoned properties generate substantial costs and risk for postindustrial cities.Communityâ engaged maintenance of properties can reduce blight and increase social cohesion.We compare levels of crime on streets with â greenedâ versus unmaintained vacant lots.Community greened lots may reduce blight and crime at lower cost to cities and build social capital.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146412/1/ajcp12270_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146412/2/ajcp12270.pd

Atlantic deep water formation occurs primarily in the Iceland Basin and Irminger Sea by local buoyancy forcing

The Atlantic Meridional Overturning Circulation (AMOC), a key mechanism in the climate system, delivers warm and salty waters from the subtropical gyre to the subpolar gyre and Nordic Seas, where they are transformed into denser waters flowing southward in the lower AMOC limb. The prevailing hypothesis is that dense waters formed in the Labrador and Nordic Seas are the sources for the AMOC lower limb. However, recent observations reveal that convection in the Labrador Sea contributes minimally to the total overturning of the subpolar gyre. In this study, we show that the AMOC is instead primarily composed of waters formed in the Nordic Seas and Irminger and Iceland basins. A first direct estimate of heat and freshwater fluxes over these basins demonstrates that buoyancy forcing during the winter months can almost wholly account for the dense waters of the subpolar North Atlantic that are exported as part of the AMOC

Role of air–sea fluxes and ocean surface density in the production of deep waters in the eastern subpolar gyre of the North Atlantic

Wintertime convection in the North Atlantic Ocean is a key component of the global climate as it produces dense waters at high latitudes that flow equatorward as part of the Atlantic Meridional Overturning Circulation (AMOC). Recent work has highlighted the dominant role of the Irminger and Iceland basins in the production of North Atlantic Deep Water. Dense water formation in these basins is mainly explained by buoyancy forcing that transforms surface waters to the deep waters of the AMOC lower limb. Air–sea fluxes and the ocean surface density field are both key determinants of the buoyancy-driven transformation. We analyze these contributions to the transformation in order to better understand the connection between atmospheric forcing and the densification of surface water. More precisely, we study the impact of air–sea fluxes and the ocean surface density field on the transformation of subpolar mode water (SPMW) in the Iceland Basin, a water mass that “pre-conditions” dense water formation downstream. Analyses using 40 years of observations (1980–2019) reveal that the variance in SPMW transformation is mainly influenced by the variance in density at the ocean surface. This surface density is set by a combination of advection, wind-driven upwelling and surface fluxes. Our study shows that the latter explains ∼ 30 % of the variance in outcrop area as expressed by the surface area between the outcropped SPMW isopycnals. The key role of the surface density in SPMW transformation partly explains the unusually large SPMW transformation in winter 2014–2015 over the Iceland Basin

Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences

Non-invasive measurement of metabolic rates in wild, free-living birds using doubly labelled water

Please read abstract in the article.DST-NRF Centre of Excellence at the FitzPatrick Institute for African Ornithology; National Research Foundation of South Africa, Grant/Award Number: 110506; Universities of Cambridge and Zurich; MAVA Foundation, ERC, Grant/Award Number: 294494; University of Pretoria; The Oppenheimer Memorial Trust, Grant/Award Number: OMT 20747/01http://wileyonlinelibrary.com/journal/fechj2020Mammal Research InstituteZoology and Entomolog

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Open Data Privacy

Cities today collect and store a wide range of data that may contain sensitive information about residents. As cities embrace open data initiatives, more of this information is released to the public. While opening data has many important benefits, sharing data comes with inherent risks to individual privacy: released data can reveal information about individuals that would otherwise not be public knowledge. The goal of this document is to take a first step toward codifying responsible privacy-protective approaches and processes that could be adopted by cities and other groups that are publicly releasing data

Preliminary Test Results for Stability and Control Characteristics of a Generic T-Tail Transport Airplane at High Angle of Attack

Tests of a generic T-tail transport airplane, in flaps-up configuration, were conducted using two wind tunnels, a water tunnel, and computational fluid dynamics. Static force and moment testing, forced oscillation testing and dye flow visualization test techniques were used. The purpose of the testing was to obtain stability and control characteristics for development of a research flight simulator aerodynamic database. The purpose of that database was for assessment of aerodynamic model fidelity requirements to train airline pilots to recognize and recover from full stall conditions. Preliminary results, at initial stall conditions, include: an unstable stall pitch break, and near-neutral roll damping. Preliminary results, at deep stall conditions, include: a potential static longitudinal trim condition at approximately 35 degrees angle of attack, large aerodynamic asymmetries, and localized unstable dynamic stability