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"Wilkinson, G"
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The spirit level : why equality is better for everyone
It is common knowledge that, in rich societies, the poor have worse health and suffer more from almost every social problem. This book explains why inequality is the most serious problem societies face today.
Income Inequality and Social Dysfunction
Population health tends to be better in societies where income is more equally distributed. Recent evidence suggests that many other social problems, including mental illness, violence, imprisonment, lack of trust, teenage births, obesity, drug abuse, and poor educational performance of schoolchildren, are also more common in more unequal societies. Differences in the prevalence of ill health and social problems between more and less equal societies seem to be large and to extend to the vast majority of the population. Rather than referencing all the literature, this paper attempts to show which interpretations of these relationships are consistent with the research evidence. After discussing their more important and illuminating characteristics, we conclude that these relationships are likely to reflect a sensitivity of health and social problems to the scale of social stratification and status competition, underpinned by societal differences in material inequality.
Journal Article
Rethinking global governance
\"Once celebrated as an answer to the myriad ills of the post-Cold War era, global governance is now in trouble. Written by two of the leading scholars in the field, Rethinking Global Governance provides an antidote to simplistic usage and an authoritative yet readable attempt to grasp the governance of our globe--past, present, and future\"-- Provided by publisher.
Book
High-resolution human cytomegalovirus transcriptome
Deep sequencing was used to bring high resolution to the human cytomegalovirus (HCMV) transcriptome at the stage when infectious virion production is under way, and major findings were confirmed by extensive experimentation using conventional techniques. The majority (65.1%) of polyadenylated viral RNA transcription is committed to producing four noncoding transcripts (RNA2.7, RNA1.2, RNA4.9, and RNA5.0) that do not substantially overlap designated protein-coding regions. Additional noncoding RNAs that are transcribed antisense to protein-coding regions map throughout the genome and account for 8.7% of transcription from these regions. RNA splicing is more common than recognized previously, which was evidenced by the identification of 229 potential donor and 132 acceptor sites, and it affects 58 protein-coding genes. The great majority (94) of 96 splice junctions most abundantly represented in the deep-sequencing data was confirmed by RT-PCR or RACE or supported by involvement in alternative splicing. Alternative splicing is frequent and particularly evident in four genes (RL8A, UL74A, UL124, and UL150A) that are transcribed by splicing from any one of many upstream exons. The analysis also resulted in the annotation of four previously unrecognized protein-coding regions (RL8A, RL9A, UL150A, and US33A), and expression of the UL150A protein was shown in the context of HCMV infection. The overall conclusion, that HCMV transcription is complex and multifaceted, has implications for the potential sophistication of virus functionality during infection. The study also illustrates the key contribution that deep sequencing can make to the genomics of nuclear DNA viruses.
Journal Article
كتاب التاريخ
\"كتاب التاريخ هو رحلة رائعة عبر الأحداث الأكثر أهمية في التاريخ والأفكار الكبيرة وراء كل واحدة، من فجر الحضارة إلى الثقافة التي تسير بخطى البرق اليوم. تستكشف مائة مقالة واضحة تمامًا قانون حمورابي، وعصر النهضة، والثورة الأمريكية، والحرب العالمية الثانية، وأكثر من ذلك بكثير، لإحضار الأحداث وموضوعات التاريخ إلى الحياة. تشرح أفكار DK الرئيسية الحائزة على جوائز في كتاب السيرة الذاتية والأفكار الكبيرة. يقدم القادة والمفكرون والمحاربون الرئيسيون، من يوليوس قيصر إلى باراك أوباما، نظرة ثاقبة لحياتهم ومزيد من الأفكار التاريخية حول هذه الحلقات المتغيرة للعالم. يجعل كتاب التاريخ أكثر من 4000 سنة من التاريخ متاحًا ويوفر التنوير حول القوى التي شكلت العالم كما نعرفه اليوم، للطلاب وهواة التاريخ على حد سواء.
The Role of Immunometabolism in the Pathogenesis of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder in which pathogenic abnormalities within both the innate and adaptive immune response have been described. In order to activated, proliferate and maintain this immunological response a drastic upregulation in energy metabolism is required. Recently, a greater understanding of these changes in cellular bioenergetics have provided new insight into the links between immune response and the pathogenesis of a number of diseases, ranging from cancer to diabetes and multiple sclerosis. In this review, we highlight the latest understanding of the role of immunometabolism in SLE with particular focus on the role of abnormal mitochondrial function, lipid metabolism, and mTOR signaling in the immunological phenomenon observed in the SLE. We also consider what implications this has for future therapeutic options in the management of the disease in future.
Journal Article
Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis
ObjectivesTo define the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM).MethodsRNA-sequencing was performed on CD4+, CD8+, CD14+ and CD19+ cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, on-treatment n=11) and age/sex-matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC). Mitochondrial morphology and superoxide were assessed by fluorescence microscopy, cellular metabolism by 13C glucose uptake assays, and oxidised mitochondrial DNA (oxmtDNA) content by dot-blot. Healthy-control PBMC and JDM pretreatment PBMC were cultured with IFN-α, oxmtDNA, cGAS-inhibitor, TLR-9 antagonist and/or n-acetyl cysteine (NAC). IFN-stimulated gene (ISGs) expression was measured by qPCR. Total numbers of patient and controls for functional experiments, JDM n=82, total CHC n=35.ResultsDysregulated mitochondrial-associated gene expression correlated with increased ISG expression in JDM CD14+ monocytes. Altered mitochondrial-associated gene expression was paralleled by altered mitochondrial biology, including ‘megamitochondria’, cellular metabolism and a decrease in gene expression of superoxide dismutase (SOD)1. This was associated with enhanced production of oxidised mitochondrial (oxmt)DNA. OxmtDNA induced ISG expression in healthy PBMC, which was blocked by targeting oxidative stress and intracellular nucleic acid sensing pathways. Complementary experiments showed that, under in vitro experimental conditions, targeting these pathways via the antioxidant drug NAC, TLR9 antagonist and to a lesser extent cGAS-inhibitor, suppressed ISG expression in pretreatment JDM PBMC.ConclusionsThese results describe a novel pathway where altered mitochondrial biology in JDM CD14+ monocytes lead to oxmtDNA production and stimulates ISG expression. Targeting this pathway has therapeutical potential in JDM and other IFN type 1-driven autoimmune diseases.
Journal Article
Regulation of AUXIN RESPONSE FACTOR condensation and nucleo-cytoplasmic partitioning
Auxin critically regulates plant growth and development. Auxin-driven transcriptional responses are mediated through the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. ARF protein condensation attenuates ARF activity, resulting in dramatic shifts in the auxin transcriptional landscape. Here, we perform a forward genetics screen for ARF hypercondensation, identifying an F-box protein, which we named AUXIN RESPONSE FACTOR F-BOX1 (AFF1). Functional characterization of SCF
AFF1
revealed that this E3 ubiquitin ligase directly interacts with ARF19 and ARF7 to regulate their accumulation, condensation, and nucleo-cytoplasmic partitioning. Mutants defective in
AFF1
display attenuated auxin responsiveness, and developmental defects, suggesting that SCF
AFF1
-mediated regulation of ARF protein drives aspects of auxin response and plant development.
Auxin-driven transcriptional responses are mediated by ARF transcription factors. Here the authors characterize an F-box protein, AFF1, that regulates the accumulation, condensation, and nucleo-cytoplasmic partitioning of ARF19 and ARF7.
Journal Article