Deciphering metal-induced oxidative damages on glycated albumin structure and function

Background: Metal ions such as copper or zinc are involved in the development of neurodegenerative pathologies and metabolic diseases such as diabetes mellitus. Albumin structure and functions are impaired following metal- and glucose-mediated oxidative alterations. The aim of this study was to elucidate effects of Cu(II) and Zn(II) ions on glucose-induced modifications in albumin by focusing on glycation, aggregation, oxidation and functional aspects. Methods: Aggregation and conformational changes in albumin were monitored by spectroscopy, fluorescence and microscopy techniques. Biochemical assays such as carbonyl, thiol groups, albumin-bound Cu, fructosamine and amine group measurements were used. Cellular assays were used to gain functional information concerning antioxidant activity of oxidized albumins. Results: Both metals promoted inhibition of albumin glycation associated with an enhanced aggregation and oxidation process. Metal ions gave rise to the formation of β-amyloid type aggregates in albumin exhibiting impaired antioxidant properties and toxic activity to murine microglia cells (BV2). The differential efficiency of both metal ions to inhibit albumin glycation, to promote aggregation and to affect cellular physiology is compared. Conclusions and general significance: Considering the key role of oxidized protein in pathology complications, glycation-mediated and metal ion-induced impairment of albumin properties might be important parameters to be followed and fought. © 2013 Elsevier B.V

Capacity building to reduce maternal and neonatal morbidity and mortality

In sub-Saharan Africa midwifery educators are in short supply and opportunities to pursue advanced education are severely restricted. Postgraduate programmes that encourage critical thinking and strategic planning in midwifery education, practice, management and research are required to empower midwives to lead their profession. A unique user-led distance learning programme was developed by adopting a participatory approach to developing a curriculum for a Masters in Midwifery and Women's Health. Midwives from the East Central and South Africa (ECSA) region and the UK participated along with a representative from the Commonwealth Secretariat and International Confederation of Midwives (ICM). The curriculum was based on shared goals but adaptable to cultural and local context. Brainstorming sessions, informal workshops and formal consensus methods were used to reach decisions regarding modules and subsequent content. This article describes the process of developing a shared curriculum, the challenges faced in working across and within regions, and participants’ views of contributing to the end product. </jats:p

Youth and Caregiver Physical Activity and Sedentary Time: HCHS/SOL Youth

We examined associations between youth and caregiver moderate/vigorous physical activity (MVPA) and sedentary (SED) time, using accelerometery, in the Hispanic Community Health Study/Study of Latino Youth (HCHS/SOL) Youth

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins

Atmospheric gas absorption knowledge in the submillimeter: Modeling, field measurements, and uncertainty quantification

Members of the atmospheric and astronomical science communities met to review the current state of the art of the submillimeter spectral region. Knowledge of gas spectroscopy is still questionable at these frequencies but is important to fully exploit upcoming meteorological satellite measurements

Particulate air pollution and chronic ischemic heart disease in the eastern United States: a county level ecological study using satellite aerosol data

<p>Abstract</p> <p>Background</p> <p>There are several known factors that cause ischemic heart disease. However, the part played by air pollution still remains something of a mystery. Recent attention has focused on the chronic effect of particulate matter on heart disease. Satellite-derived aerosol optical depth (AOD) was found to be correlated with <it>PM</it>_2.5in the eastern US. The objective of this study was to examine if there is an association between aerosol air pollution as indicated by AOD and chronic ischemic heart disease (CIHD) in the eastern US.</p> <p>Methods</p> <p>An ecological geographic study method was employed. Race and age standardized mortality rate (SMR) of CIHD was computed for each of the 2306 counties for the time period 2003–2004. A mean AOD raster grid for the same period was derived from Moderate Resolution Imaging Spectrometer (MODIS) aerosol data and the average AOD was calculated for each county. A bivariate Moran's I scatter plot, a map of local indicator of spatial association (LISA) clusters, and three regression models (ordinary least square, spatial lag, and spatial error) were used to analyze the relationship between AOD and CIHD SMR.</p> <p>Results</p> <p>The global Moran's I value is 0.2673 (<it>p </it>= 0.001), indicating an overall positive spatial correlation of CIHD SMR and AOD. The entire study area is dominated by spatial clusters of AOD against SMR (high AOD and high SMR in the east, and low AOD and low SMR in the west) (permutations = 999, <it>p </it>= 0.05). Of the three regression models, the spatial error model achieved the best fit (R²= 0.28). The effect of AOD is positive and significant (beta = 0.7774, p = 0.01).</p> <p>Conclusion</p> <p>Aerosol particle pollution has adverse effect on CIHD mortality risk in the eastern US. High risk of CIHD mortality was found in areas with elevated levels of outdoor aerosol air pollution as indicated by satellite derived AOD. The evidence of the association would support targeting of policy interventions on such areas to reduce air pollution levels. Remote sensing AOD data could be used as an alternative health-related indictor of air quality.</p

Lysophosphatidate Induces Chemo-Resistance by Releasing Breast Cancer Cells from Taxol-Induced Mitotic Arrest

Taxol is a microtubule stabilizing agent that arrests cells in mitosis leading to cell death. Taxol is widely used to treat breast cancer, but resistance occurs in 25-69% of patients and it is vital to understand how Taxol resistance develops to improve chemotherapy. The effects of chemotherapeutic agents are overcome by survival signals that cancer cells receive. We focused our studies on autotaxin, which is a secreted protein that increases tumor growth, aggressiveness, angiogenesis and metastasis. We discovered that autotaxin strongly antagonizes the Taxol-induced killing of breast cancer and melanoma cells by converting the abundant extra-cellular lipid, lysophosphatidylcholine, into lysophosphatidate. This lipid stimulates specific G-protein coupled receptors that activate survival signals.In this study we determined the basis of these antagonistic actions of lysophosphatidate towards Taxol-induced G2/M arrest and cell death using cultured breast cancer cells. Lysophosphatidate does not antagonize Taxol action in MCF-7 cells by increasing Taxol metabolism or its expulsion through multi-drug resistance transporters. Lysophosphatidate does not lower the percentage of cells accumulating in G2/M by decreasing exit from S-phase or selective stimulation of cell death in G2/M. Instead, LPA had an unexpected and remarkable action in enabling MCF-7 and MDA-MB-468 cells, which had been arrested in G2/M by Taxol, to normalize spindle structure and divide, thus avoiding cell death. This action involves displacement of Taxol from the tubulin polymer fraction, which based on inhibitor studies, depends on activation of LPA receptors and phosphatidylinositol 3-kinase.This work demonstrates a previously unknown consequence of lysophosphatidate action that explains why autotaxin and lysophosphatidate protect against Taxol-induced cell death and promote resistance to the action of this important therapeutic agent

Attitudes and Preferences Towards Exercise Training in Individuals with Alcohol Use Disorders in a Residential Treatment Setting

Alcohol use disorders (AUD) are a major public health concern due to their association with several acute and chronic health conditions. Exercise training offers a myriad of physical and mental health benefits, and may be a promising adjunct intervention for those in AUD treatment. The purpose of this study was to explore the possible role of exercise training as a treatment strategy by examining the attitudes, beliefs, and preferences of individuals entering residential AUD treatment. Surveys were administered to eligible individuals with AUD within 2days of intake to one of two residential treatment centers. The survey asked respondents about their attitudes, beliefs, and preferences towards exercise training as a part of their residential treatment. Respondents were in favor of receiving exercise counseling as part of their treatment (70.6%), in a face-to-face format (90.0%), and from an exercise counselor at the treatment center (55.5%). The top reported benefits included: improved health, feeling good about oneself, and feeling more confident. The most commonly reported barriers to exercise training included transportation issues, lack of motivation, knowledge, and proper equipment, and cost. Our study supports previous work in individuals with substance abuse disorders and suggests that exercise training would be widely accepted as a part of residential treatment for AUD. This study also identified several strategies that can be used to individualize exercise training programs to better meet the needs of AUD patients and maximize their participation in future interventions. •Survey on exercise attitudes and beliefs in individuals with alcohol use disorders.•Conducted in a diverse, lower income population in residential treatment centers.•Exercise training as a part of residential treatment appears to be well received.•Participants reported few barriers and multiple benefits to exercise training.•Exercise training programs should be individualized to patients' preferences

Mental Health Among LGBTQ Cannabis Users During the COVID-19 Pandemic: Analysis of the COVID-19 Cannabis Health Study

The purpose of this study is to compare the responses of lesbian, gay, bisexual. transgender, and queer or questioning (LGBTQ) cannabis consumers and their non-LGBTQ counterparts on anxiety, depression, substance use, and coronavirus disease 2019 (COVID-19) coping and stress during the pandemic. Data from an Internet survey of cannabis users during the COVID-19 pandemic were analyzed (N = 2,319). Approximately 18% of the sample identified as LGBTQ. Bivariate analyses were used to examine the relationship between LGBTQ identity and symptoms of anxiety and depression, substance use, and pandemic-related coping strategies and stressors. Logistic regression models were used to evaluate the association between pandemic stressors and coping strategies with LGBTQ identity, while adjusting for sex, age, and race and ethnicity. Differences in the proportion of medicinal cannabis use among LGBTQ respondents (74.6%) and non-LGBTQ respondents (75.3%) were insignificant. LGBTQ cannabis users were more likely to report COVID-19-related stressors and coping behaviors, including increased alcohol use. After adjustment for covariates, LGBTQ cannabis users were more likely to report symptoms of depression and anxiety than non-LGBTQ cannabis users. These results show that compared to their cisgender heterosexual counterparts, LGBTQ cannabis users are experiencing more problematic mental health outcomes during the COVID-19 pandemic