Gene network effects on brain microstructure and intellectual performance identified in 472 twins

A major challenge in neuroscience is finding which genes affect brain integrity, connectivity, and intellectual function. Discovering influential genes holds vast promise for neuroscience, but typical genome-wide searches assess approximately one million genetic variants one-by-one, leading to intractable false positive rates, even with vast samples of subjects. Even more intractable is the question of which genes interact and how they work together to affect brain connectivity. Here, we report a novel approach that discovers which genes contribute to brain wiring and fiber integrity at all pairs of points in a brain scan. We studied genetic correlations between thousands of points in human brain images from 472 twins and their nontwin siblings (mean age: 23.7 ± 2.1 SD years; 193 male/279 female). We combined clustering with genome-wide scanning to find brain systems with common genetic determination. We then filtered the image in a new way to boost power to find causal genes. Using network analysis, we found a network of genes that affect brain wiring in healthy young adults. Our new strategy makes it computationally more tractable to discover genes that affect brain integrity. The gene network showed small-world and scale-free topologies, suggesting efficiency in genetic interactions and resilience to network disruption. Genetic variants at hubs of the network influence intellectual performance by modulating associations between performance intelligence quotient and the integrity of major white matter tracts, such as the callosal genu and splenium, cingulum, optic radiations, and the superior longitudinal fasciculus

Pain in people living with HIV and its association with healthcare resource use, well-being and functional status

Objective: We describe the prevalence of pain and its associations with healthcare resource utilisation and quality-of-life. Design: The POPPY Study recruited three cohorts: older PLWH (≥50 years, n = 699), younger demographically/lifestyle similar PLWH (<50 years, n = 374) and older demographically/lifestyle similar HIV-negative (≥50 years, n = 304) people from April 2013-February 2016. Methods: Current pain and pain-related healthcare use was collected via a self-reported questionnaire. Logistic regression assessed between-group differences in the prevalence of pain in the past month and current pain after controlling for potential confounders. Associations between current pain and healthcare resource use, reported joint problems, depressive symptoms, quality-of-life and functional status were assessed in PLWH using Mann-Whitney U and Chi-squared tests. Results: Pain in the past month was reported by 473/676 (70.0%) older PLWH, 224/357 (62.7%) younger PLWH and 188/295 (63.7%) older HIV-negative controls (p = 0.03), with current pain reported in 330 (48.8%), 134 (37.5%) and 116 (39.3%), respectively (p = 0.0007). Older PLWH were more likely to experience current pain, even after adjustment for confounders. Of those with pain in the past month, 56/412 (13.6%) had missed days of work or study due to pain, and 520 (59%) had seen a doctor about their pain. PLWH experiencing current painhad more depressive symptoms, poorer quality-of-life on all domains, and greater functional impairment, regardless of age group. Conclusions: Even in the effective ART era, pain remains common in PLWH and has a major impact on quality-of-life and associated healthcare and societal costs. Interventions are required to assist clinicians and PLWH to proactively manage pain

Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2.

Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1790-9)

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

Antarctic Relic Microbial Mat Community Revealed by Metagenomics and Metatranscriptomics

Buried upslope from the modern lakes in the McMurdo Dry Valleys of Antarctica are relict lake deposits embedded in valley walls. Within these relict deposits, ancient microbial mats, or paleomats, have been preserved under extremely arid and cold conditions since the receding of larger paleolakes thousands of years ago, and now serve as a sheltered niche for microbes in a highly challenging oligotrophic environment. To explore whether paleomats could be repositories for ancient lake cells or were later colonized by soil microbes, determine what types of metabolic pathways might be present, analyze potential gene expression, and explore whether the cells are in a vegetative or dormant state, we collected paleomat samples from ancient lake facies on the northern slopes of Lake Vanda in Wright Valley in December 2016. Using a gentle lysis technique optimized to preserve longer molecules, combined with a polyenzymatic treatment to maximize yields from different cell types, we isolated high-molecular weight DNA and RNA from ancient paleomat samples. Community composition analysis suggests that the paleomat community may retain a population of indigenous mat cells that may flourish once more favorable conditions are met. In addition to harboring a diverse microbial community, paleomats appear to host heterotrophs in surrounding soils utilizing the deposits as a carbon source. Whole genome long-read PacBio sequencing of native DNA and Illumina metagenomic sequencing of size-sorted DNA (&gt;2,500 nt) indicated possible cell viability, with mat community composed of bacterial taxa. Metagenome assemblies identified genes with predicted roles in nitrogen cycling and complex carbohydrate degradation, and we identified key metabolic pathways such as stress response, DNA repair, and sporulation. Metatranscriptomic data revealed that the most abundant transcripts code for products involved in genetic information processing pathways, particularly translation, DNA replication, and DNA repair. Our results lend new insight into the functional ecology of paleomat deposits, with implications for our understanding of cell biology, Antarctic microbiology and biogeography, and the limits of life in extremely harsh environments

The Effect of Locally Delivered Controlledâ Release Doxycycline or Scaling and Root Planing on Periodontal Maintenance Patients Over 9 Months

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142157/1/jper0022.pd

Association of lung function, chest radiographs and clinical features in infants with cystic fibrosis

The optimal strategy for monitoring cystic fibrosis (CF) lung disease in infancy remains unclear