Dropping off the edge 2015: persistent communal disadvantage in Australia

This report shows that complex and entrenched disadvantage is experienced by a small but persistent number of locations in each state and territory across Australia. Foreword In 2007, Jesuit Social Services and Catholic Social Services Australia commissioned ground-breaking research into place-based disadvantage across the nation. The resulting report, Dropping off the edge, built on previous work that Jesuit Social Services had engaged Professor Tony Vinson to undertake on its behalf and quickly became a critical resource for governments, service providers and communities attempting to address the challenge of entrenched and often complex geographical disadvantage. That report received over 284 scholarly citations and supported the establishment of the Australian Social Inclusion Board – a body charged with identifying long-term strategies to end poverty in Australia. Since the publication of Dropping off the edge, our organisations have received many requests to update the findings and produce a new report tracking the wellbeing of communities in Australia over the intervening time. Sadly, the current report drives home the enormous challenge that lies in front of our policy makers and service providers, as many communities identified as disadvantaged in 2007 once again head the list in each state and territory. As a society we cannot, and should not, turn away from the challenge of persistent and entrenched locational disadvantage, no matter how difficult it may be to solve the problem. We call on government, community and business to come together to work alongside these communities to ensure long term sustainable change. We hold hope that the young people and future generations in these communities will have a better outlook and life opportunities than is currently available to them. It is our belief that every Australian should have access to the opportunities in life that will enable them to flourish – to complete their education, to get a job, to access safe and affordable housing, to raise their children in safe communities and to see the next generation thrive. Jesuit Social Services and Catholic Social Services Australia are indebted to the dedication and perseverance of Professor Tony Vinson in leading this important research and analysis over the past 15 years. Julie Edwards Chief Executive Officer Jesuit Social Services Marcelle Mogg Chief Executive Officer Catholic Social Services Australi

Geochemical evolution of the Critical Zone across variable time scales informs concentration-discharge relationships: Jemez River Basin Critical Zone Observatory

This study investigates the influence of water, carbon, and energy fluxes on solute production and transport through the Jemez Critical Zone (CZ) and impacts on C-Q relationships over variable spatial and temporal scales. Chemical depletion-enrichment profiles of soils, combined with regolith thickness and groundwater data indicate the importance to stream hydrochemistry of incongruent dissolution of silicate minerals during deep bedrock weathering, which is primarily limited by water fluxes, in this highly fractured, young volcanic terrain. Under high flow conditions (e.g., spring snowmelt), wetting of soil and regolith surfaces and presence of organic acids promote mineral dissolution and provide a constant supply of base cations, Si, and DIC to soil water and groundwater. Mixing of waters from different hydrochemical reservoirs in the near stream environment during “wet” periods leads to the chemostatic behavior of DIC, base cations, and Si in stream flow. Metals transported by organic matter complexation (i.e., Ge, Al) and/or colloids (i.e., Al) during periods of soil saturation and lateral connectivity to the stream display a positive relationship with Q. Variable Si-Q relationships, under all but the highest flow conditions, can be explained by nonconservative transport and precipitation of clay minerals, which influences long versus short-term Si weathering fluxes. By combining measurements of the CZ obtained across different spatial and temporal scales, we were able to constrain weathering processes in different hydrological reservoirs that may be flushed to the stream during hydrologic events, thereby informing C-Q relationships

Melanocortin receptor accessory proteins in adrenal disease and obesity.

Melanocortin receptor accessory proteins (MRAPs) are regulators of the melanocortin receptor family. MRAP is an essential accessory factor for the functional expression of the MC2R/ACTH receptor. The importance of MRAP in adrenal gland physiology is demonstrated by the clinical condition familial glucocorticoid deficiency type 2. The role of its paralog melanocortin-2-receptor accessory protein 2 (MRAP2), which is predominantly expressed in the hypothalamus including the paraventricular nucleus, has recently been linked to mammalian obesity. Whole body deletion and targeted brain specific deletion of the Mrap2 gene result in severe obesity in mice. Interestingly, Mrap2 complete knockout (KO) mice have increased body weight without detectable changes to food intake or energy expenditure. Rare heterozygous variants of MRAP2 have been found in humans with severe, early-onset obesity. In vitro data have shown that Mrap2 interaction with the melanocortin-4-receptor (Mc4r) affects receptor signaling. However, the mechanism by which Mrap2 regulates body weight in vivo is not fully understood and differences between the phenotypes of Mrap2 and Mc4r KO mice may point toward Mc4r independent mechanisms

Tools for interpretation of wastewater SARS-CoV-2 temporal and spatial trends demonstrated with data collected in the San Francisco Bay Area

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be integrated with COVID-19 case data to inform timely pandemic response. However, more research is needed to apply and develop systematic methods to interpret the true SARS-CoV-2 signal from noise introduced in wastewater samples (e.g., from sewer conditions, sampling and extraction methods, etc.). In this study, raw wastewater was collected weekly from five sewersheds and one residential facility. The concentrations of SARS-CoV-2 in wastewater samples were compared to geocoded COVID-19 clinical testing data. SARS-CoV-2 was reliably detected (95% positivity) in frozen wastewater samples when reported daily new COVID-19 cases were 2.4 or more per 100,000 people. To adjust for variation in sample fecal content, four normalization biomarkers were evaluated: crAssphage, pepper mild mottle virus, Bacteroides ribosomal RNA (rRNA), and human 18S rRNA. Of these, crAssphage displayed the least spatial and temporal variability. Both unnormalized SARS-CoV-2 RNA signal and signal normalized to crAssphage had positive and significant correlation with clinical testing data (Kendall's Tau-b (τ)=0.43 and 0.38, respectively), but no normalization biomarker strengthened the correlation with clinical testing data. Locational dependencies and the date associated with testing data impacted the lead time of wastewater for clinical trends, and no lead time was observed when the sample collection date (versus the result date) was used for both wastewater and clinical testing data. This study supports that trends in wastewater surveillance data reflect trends in COVID-19 disease occurrence and presents tools that could be applied to make wastewater signal more interpretable and comparable across studies

Electron cryo-microscopy reveals mechanism of action of propranolol on artificial membranes.

The pharmacological activity of several amphiphilic drugs is often related to their ability to interact with biological membranes. Propranolol is an efficient multidrug resistance (MDR) modulator; it is a nonselective beta-blocker and is thought to reduce hypertension by decreasing the cardiac frequency and thus blood pressure. It is used in drug delivery studies in order to treat systemic hypertension. We are interested in the interaction of propranolol with artificial membranes, as liposomes of controllable size are used as biocompatible and protective structures to encapsulate labile molecules, such as proteins, nucleic acids or drugs, for pharmaceutical, cosmetic or chemical applications. We present here a study of the interaction of propranolol, a cationic surfactant, with pure egg phosphatidylcholine (EPC) vesicles. The gradual transition from liposome to micelle of EPC vesicles in the presence of propranolol was monitored by time-resolved electron cryo-microscopy (cryo-EM) under different experimental conditions. The liposome-drug interaction was studied with varying drug/lipid (D/L) ratios and different stages were captured by direct thin-film vitrification. The time-series cryo-EM data clearly illustrate the mechanism of action of propranolol on the liposome structure: the drug disrupts the lipid bilayer by perturbing the local organization of the phospholipids. This is followed by the formation of thread-like micelles, also called worm-like micelles (WLM), and ends with the formation of spherical (globular) micelles. The overall reaction is slow, with the process taking almost two hours to be completed. The effect of a monovalent salt was also investigated by repeating the lipid-surfactant interaction experiments in the presence of KCl as an additive to the lipid/drug suspension. When KCl was added in the presence of propranolol the overall reaction was the same but with slower kinetics, suggesting that this monovalent salt affects the general lipid-to-micelle transition by stabilizing the membrane, presumably by binding to the carbonyl chains of the phosphatidylcholine