Neonatal obstructive nephropathy induces necroptosis and necroinflammation

Urinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1 alpha, INF-gamma, TNF-alpha) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy

Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.

Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases

Gender differences in the associations between age trends of social media interaction and well-being among 10-15 year olds in the UK

Background Adolescents are among the highest consumers of social media while research has shown that their well-being decreases with age. The temporal relationship between social media interaction and well-being is not well established. The aim of this study was to examine whether the changes in social media interaction and two well-being measures are related across ages using parallel growth models. Methods Data come from five waves of the youth questionnaire, 10-15 years, of the Understanding Society, the UK Household Longitudinal Study (pooled n =9859). Social media interaction was assessed through daily frequency of chatting on social websites. Well-being was measured by happiness with six domains of life and the Strengths and Difficulties Questionnaire. Results Findings suggest gender differences in the relationship between interacting on social media and well-being. There were significant correlations between interacting on social media and well-being intercepts and between social media interaction and well-being slopes among females. Additionally higher social media interaction at age 10 was associated with declines in well-being thereafter for females, but not for males. Results were similar for both measures of well-being. Conclusions High levels of social media interaction in early adolescence have implications for well-being in later adolescence, particularly for females. The lack of an association among males suggests other factors might be associated with their reduction in well-being with age. These findings contribute to the debate on causality and may inform future policy and interventions

Communications Biophysics

Contains research objectives and summary of research on thirteen research projects split into four section.National Institutes of Health (Grant 1 RO1 NS10737-01)National Institutes of Health (Grant 1 ROI NS10916-01)National Institutes of Health (Grant 5 RO1 NS11000-02)National Institutes of Health (Grant 1 RO1 NS11153-01)Harvard M.I.T. Rehabilitation Engineering CenterU. S. Department of Health, Education, and Welfare, Grant 23-P-55854National Institutes of Health (Grant 1 RO1 NS11680-01)Norlin Music, Inc.Clarence J. LeBel FundNational Institutes of Health (Grant 1 RO1 NS11080-01A1)National Institutes of Health (Grant 5 TO1 GM01555-08)M.I.T. Health Sciences FundBoston City Hospital Purchase Order 1176-05-21335-C

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Artwork by Yvonne Singer

Yvonne Singer, The Freud Text, 1998. The Freud Text This print using a selection of Freud's writing is an excerpted from the installation, The Veiled Room that was conceived for and exhibited in Weimar, Germany in 1998. My work was an investigation of the intersection of personal and political histories