Sleep disturbance as a moderator of the association between physical activity and later pain onset among American adults aged 50 and over : evidence from the Health and Retirement Study

Funding DW is supported by a Foundation Fellowship Versus Arthritis (Award Number: 21742). Contributors DW, HG, LMS, TJB, AK and GLD were involved in study conception and design, and advised on the statistical analysis plan and interpretation of the data. HG compiled the dataset and DW performed the statistical analysis. DW drafted the manuscript. HG, LMS, TJB, AK and GLD reviewed the manuscript, provided amendments and approved the final version. DW, HG and GLD had full access to study data and take responsibility for its accuracy and the integrity of the analysis. Data availability statement Data are available in a public, open access repository. The dataset used for this study was generated from data products publicly released by the Health and Retirement Study (HRS): https://hrs.isr.umich.edu. The HRS is sponsored by the National Institute on Ageing (grant number NIA U01AG009740).Peer reviewedPublisher PD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Neuroprotective Diets Are Associated with Better Cognitive Function: The Health and Retirement Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138278/1/jgs14922.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138278/2/jgs14922_am.pd

Neuroprotective Diets Are Associated with Better Cognitive Function: The Health and Retirement Study

ObjectivesTo evaluate the association between the Mediterranean diet (MedDiet) and the Mediterranean-DASH diet Intervention for Neurodegeneration Delay (MIND diet) and cognition in a nationally representative population of older U.S. adults.DesignPopulation-based cross-sectional study.SettingHealth and Retirement Study.ParticipantsCommunity-dwelling older adults (N = 5,907; mean age 67.8 ± 10.8).MeasurementsAdherence to dietary patterns was determined from food frequency questionnaires using criteria determined a priori to generate diet scores for the MedDiet (range 0-55) and MIND diet (range 0-15). Cognitive performance was measured using a composite test score of global cognitive function (range 0-27). Linear regression was used to compare cognitive performance according to tertiles of dietary pattern. Logistic regression was used to examine the association between dietary patterns and clinically significant cognitive impairment. Models were adjusted for age, sex, race, educational attainment, and other health and lifestyle covariates.ResultsParticipants with mid (odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.71-1.02, P = .08) and high (OR 0.65, 95% CI = 0.52-0.81, P < .001) MedDiet scores were less likely to have poor cognitive performance than those with low scores in fully adjusted models. Results for the MIND diet were similar. Higher scores in each dietary pattern were independently associated with significantly better cognitive function (P < .001) in a dose-response manner (P trend  < .001).ConclusionIn a large nationally representative population of older adults, greater adherence to the MedDiet and MIND diet was independently associated with better cognitive function and lower risk of cognitive impairment. Clinical trials are required to elucidate the role of dietary patterns in cognitive aging

[P2–546]: Neuroprotective Dietary Patterns Are Associated With Better Cognitive Performance In Older U.S. Adults: The Health And Retirement Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152706/1/alzjjalz2017061204.pd

Insights into social insects from the genome of the honeybee Apis mellifera

Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement

The Somatic Genomic Landscape of Chromophobe Renal Cell Carcinoma

We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutationsclose5