HNF1B variants associate with promoter methylation and regulate gene networks activated in prostate and ovarian cancer.

Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues. This tumor-suppressor activity is lost when HNF1B is silenced by promoter methylation in the progression to PC. Epigenetic inactivation of HNF1B in ovarian cancer also associates with known risk SNPs, with a similar impact on EMT. This represents one of the first comprehensive studies into the pleiotropic role of a GWAS-associated transcription factor across distinct cancer types, and is the first to describe a conserved role for a multi-cancer genetic risk factor

Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ

Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response

Investigating the Effect of Galaxy Interactions on the Enhancement of Active Galactic Nuclei at 0.5 < z < 3.0

Galaxy interactions and mergers are thought to play an important role in the evolution of galaxies. Studies in the nearby universe show a higher AGN fraction in interacting and merging galaxies than their isolated counterparts, indicating that such interactions are important contributors to black hole growth. To investigate the evolution of this role at higher redshifts, we have compiled the largest known sample of major spectroscopic galaxy pairs (2381 with $\Delta V <5000$ km s$^{-1}$) at $0.5<z<3.0$ from observations in the COSMOS and CANDELS surveys. We identify X-ray and IR AGN among this kinematic pair sample, a visually identified sample of mergers and interactions, and a mass-, redshift-, and environment-matched control sample for each in order to calculate AGN fractions and the level of AGN enhancement as a function of relative velocity, redshift, and X-ray luminosity. While we see a slight increase in AGN fraction with decreasing projected separation, overall, we find no significant enhancement relative to the control sample at any separation. In the closest projected separation bin ($<25$ kpc, $\Delta V <1000$ km s$^{-1}$), we find enhancements of a factor of 0.94$^{+0.21}_{-0.16}$ and 1.00$^{+0.58}_{-0.31}$ for X-ray and IR-selected AGN, respectively. While we conclude that galaxy interactions do not significantly enhance AGN activity on average over $0.5<z<3.0$ at these separations, given the errors and the small sample size at the closest projected separations, our results would be consistent with the presence of low-level AGN enhancement

Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

To identify knowledge gaps regarding new-onset agitation and impulsivity prior to onset of cognitive impairment or dementia the International Society to Advance Alzheimer's Research and Treatment Neuropsychiatric Syndromes (NPS) Professional Interest Area conducted a scoping review. Extending a series of reviews exploring the pre-dementia risk syndrome Mild Behavioral Impairment (MBI), we focused on late-onset agitation and impulsivity (the MBI impulse dyscontrol domain) and risk of incident cognitive decline and dementia. This scoping review of agitation and impulsivity pre-dementia syndromes summarizes the current biomedical literature in terms of epidemiology, diagnosis and measurement, neurobiology, neuroimaging, biomarkers, course and prognosis, treatment, and ongoing clinical trials. Validations for pre-dementia scales such as the MBI Checklist, and incorporation into longitudinal and intervention trials, are needed to better understand impulse dyscontrol as a risk factor for mild cognitive impairment and dementia.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Daniel Bateman receives support from the Indiana University Richard M. Fairbanks Chair of Aging Research, the Indiana University Cornelius and Yvonne Pettinga Chair of Medicine, and funding from the National Institute on Aging (NIA) grants K23AG059914 and P30AF10133. Sascha Gill receives funding from a University of Calgary Graduate Student Research Award. Sophie Hu receives funding from a Cana dian Institute of Health Research (CIHR) Master’s Research Award. Erin Foster: none. Myuri Ruthirakuhan receives funding from a CIHR Doctoral Research Award. Allis Sellek receives funding from Alzheimer Foundation of Costa Rica. Moyra Mortby receives support from the Australian National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) Dementia Research Development Fellowship #1102028. Veronika Matušková receives support from MH CZ – DRO, Motol University Hospital, Prague, Czech Republic 00064203 and Czech Ministry of Health grant 16-27611A. Kok Pin Ng: none. Rawan Tarawneh receives support from the Ohio State University Chronic Brain Injury Discovery Themes. Yvonne Freund-Levi:none. Sanjeev Kumar receives research support from Brain and Behavior Foundation, National institute on Ageing, BrightFocus Foundation, Brain Canada, Canadian Institute of Health Research, Centre for Ageing and Brain Health Innovation, Weston Brain Institute, and Centre for Mental Health and Addiction Foundation and University of Toronto. Serge Gauthier receives support from the CIHR, Weston, and the National Institutes of Health (NIH). Paul Rosenberg receives funding from the National Institute on Aging (NIA) grants R01AG049872 and R01 AG054771. Fabricio Ferreira de Oliveira has a grant from FAPESP - The State of São Paulo Research Foundation (grant #2015/10109-5). Devangere Devanand: none. Clive Ballard: none. Zahinoor Ismail has received funding from Alzheimer’s Society of Calgary via the Hotchkiss Brain Institute.published version, accepted version (12 month embargo), submitted versio

Geometric effects of sustainable auxetic structures integrating the particle swarm optimization and finite element method

The development of new materials based on industrial wastes has been the focus of much research for a sustainable world. The growing demand for tyres has been every year exacerbating environmental problems due to indiscriminate disposal in the nature, making a potentially harmful waste to public health. The incorporation of rubber particles from scrap tyres into polymeric composites has achieved high toughness and moderate mechanical properties. This work investigates the geometric effects (thickness, width and internal cell angle) of auxetic structures made of recycled rubber composites based on experimental and numerical data. The response surface models integrated with the swarm intelligence and finite element analysis were proposed in order to obtain a range of solutions that provides useful information to the user during the selection of geometric parameters for reentrant cells. The results revealed the cell thickness ranges from 39-40 mm and 5.98-6 mm, and the cell angle range from -0.01 to -0.06º maximize the ultimate strength. The same parameters were able to optimize the modulus of elasticity of rubber auxetic structures, excepting for the angle factor which must be set between -30º and 27.7º. The optimal Poisson's ratio was found when the cell angle ranged from -30º to -28.5º, cell width ranged from 5-5.6 mm and 2 mm in thickness

Plant defences mediate interactions between herbivory and the direct foliar uptake of atmospheric reactive nitrogen

Reactive nitrogen from human sources (e.g., nitrogen dioxide, NO2) is taken up by plant roots following deposition to soils, but can also be assimilated by leaves directly from the atmosphere. Leaf uptake should alter plant metabolism and overall nitrogen balance and indirectly influence plant consumers; however, these consequences remain poorly understood. Here we show that direct foliar assimilation of NO2 increases levels of nitrogen-based defensive metabolites in leaves and reduces herbivore consumption and growth. These results suggest that atmospheric reactive nitrogen could have cascading negative effects on communities of herbivorous insects. We further show that herbivory induces a decrease in foliar uptake, indicating that consumers could limit the ability of vegetation to act as a sink for nitrogen pollutants (e.g., smog from mobile emissions). Our study suggests that the interactions of foliar uptake, plant defence and herbivory could have significant implications for understanding the environmental consequences of reactive nitrogen

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021