Voluntary Exercise Reduces Alzheimer’s-like Pathology After Inflammation in Mice

Current global statistics estimate that 44.4 million people are afflicted with dementia, and that 50%-75% of these patients suffer from Alzheimer’s disease (AD; Prince et al. 2013). AD, a progressive disorder categorized by neuronal and behavioral deterioration, is the 6th leading cause of death in America (Alz facts and figure 2012). One hallmark pathology of AD is the presence of amyloid-beta (Aβ) in the brain, which can limit cell-to-cell communication, leading to cognitive deficits, and neuronal cell death. Although the exact origins of this disease still remain unknown, one possible catalyst of AD pathology is inflammation. Our lab has previously shown that 7 consecutive peripheral injections of a bacterial mimetic led to systemic inflammation, increased levels of Ab in the brain, and cognitive dysfunction (Kahn et al., 2012; Weintraub et al., 2013). Currently there are very few effective treatments that diminish AD symptomology. One documented way to decrease inflammation without the use of pharmaceuticals is through regular physical exercise (Cho et al., 2003; Cotman & Berchtold, 2002; Cotman et al., 2007). The present study tested the hypothesis that voluntary exercise would decrease the level of brain Ab following inflammation. Interestingly, we found that two weeks of voluntary wheel running after inflammation led to a reduction of Ab when compared to sedentary recovery. These results indicate that exercise may be an effective modality to reduce AD-like pathology, and that these effects appear to be facilitated by higher versus lower levels of exercise, as measured by total distance run

PVLSI (Pioneer Valley Life Sciences Institute) Posters - 2019

PVLSI (Pioneer Valley Life Sciences Institute) Posters - 2019https://scholarlycommons.libraryinfo.bhs.org/research_education/1014/thumbnail.jp

The Importance of Socio-Economic Versus Environmental Risk Factors for Reported Dengue Cases in Java, Indonesia

Background: Dengue is a major mosquito-borne viral disease and an important public health problem. Identifying which factors are important determinants in the risk of dengue infection is critical in supporting and guiding preventive measures. In South-East Asia, half of all reported fatal infections are recorded in Indonesia, yet little is known about the epidemiology of dengue in this country. Methodology/Principal findings: Hospital-reported dengue cases in Banyumas regency, Central Java were examined to build Bayesian spatial and spatio-temporal models assessing the influence of climatic, demographic and socio-economic factors on the risk of dengue infection. A socio-economic factor linking employment type and economic status was the most influential on the risk of dengue infection in the Regency. Other factors such as access to healthcare facilities and night-time temperature were also found to be associated with higher risk of reported dengue infection but had limited explanatory power. Conclusions/Significance: Our data suggest that dengue infections are triggered by indoor transmission events linked to socio-economic factors (employment type, economic status). Preventive measures in this area should therefore target also specific environments such as schools and work areas to attempt and reduce dengue burden in this community. Although our analysis did not account for factors such as variations in immunity which need further investigation, this study can advise preventive measures in areas with similar patterns of reported dengue cases and environmen

Comparative structural and functional analysis of Bunyavirus and Arenavirus cap-snatching Endonucleases

Segmented negative strand RNA viruses of the arena-, bunya- and orthomyxovirus families uniquely carry out viral mRNA transcription by the cap-snatching mechanism. This involves cleavage of host mRNAs close to their capped 5′ end by an endonuclease (EN) domain located in the N-terminal region of the viral polymerase. We present the structure of the cap-snatching EN of Hantaan virus, a bunyavirus belonging to hantavirus genus. Hantaan EN has an active site configuration, including a metal co-ordinating histidine, and nuclease activity similar to the previously reported La Crosse virus and Influenza virus ENs (orthobunyavirus and orthomyxovirus respectively), but is more active in cleaving a double stranded RNA substrate. In contrast, Lassa arenavirus EN has only acidic metal co-ordinating residues. We present three high resolution structures of Lassa virus EN with different bound ion configurations and show in comparative biophysical and biochemical experiments with Hantaan, La Crosse and influenza ENs that the isolated Lassa EN is essentially inactive. The results are discussed in the light of EN activation mechanisms revealed by recent structures of full-length influenza virus polymerase

What is ‘anti’ about anti-reaches? Reference frames selectively affect reaction times and endpoint variability

Reach movement planning involves the representation of spatial target information in different reference frames. Neurons at parietal and premotor stages of the cortical sensorimotor system represent target information in eye- or hand-centered reference frames, respectively. How the different neuronal representations affect behavioral parameters of motor planning and control, i.e. which stage of neural representation is relevant for which aspect of behavior, is not obvious from the physiology. Here, we test with a behavioral experiment if different kinematic movement parameters are affected to a different degree by either an eye- or hand-reference frame. We used a generalized anti-reach task to test the influence of stimulus-response compatibility (SRC) in eye- and hand-reference frames on reach reaction times, movement times, and endpoint variability. While in a standard anti-reach task, the SRC is identical in the eye- and hand-reference frames, we could separate SRC for the two reference frames. We found that reaction times were influenced by the SRC in eye- and hand-reference frame. In contrast, movement times were only influenced by the SRC in hand-reference frame, and endpoint variability was only influenced by the SRC in eye-reference frame. Since movement time and endpoint variability are the result of planning and control processes, while reaction times are consequences of only the planning process, we suggest that SRC effects on reaction times are highly suited to investigate reference frames of movement planning, and that eye- and hand-reference frames have distinct effects on different phases of motor action and different kinematic movement parameters

Efficacy and cost-effectiveness of a web-based and mobile stress-management intervention for employees: design of a randomized controlled trial

Background: Work-related stress is associated with a variety of mental and emotional problems and can lead to substantial economic costs due to lost productivity, absenteeism or the inability to work. There is a considerable amount of evidence on the effectiveness of traditional face-to-face stress-management interventions for employees; however, they are often costly, time-consuming, and characterized by a high access threshold. Web-based interventions may overcome some of these problems yet the evidence in this field is scarce. This paper describes the protocol for a study that will examine the efficacy and cost-effectiveness of a web-based guided stress-management training which is based on problem solving and emotion regulation and aimed at reducing stress in adult employees. Methods. The study will target stressed employees aged 18 and older. A randomized controlled trial (RCT) design will be applied. Based on a power calculation of d=.35 (1-β of 80%, α =.05), 264 participants will be recruited and randomly assigned to either the intervention group or a six-month waitlist control group. Inclusion criteria include an elevated stress level (Cohen's Perceived Stress Scale-10 ≥ 22) and current employment. Exclusion criteria include risk of suicide or previously diagnosed psychosis or dissociative symptoms. The primary outcome will be perceived stress, and secondary outcomes include depression and anxiety. Data will be collected at baseline and seven weeks and six months after randomization. An extended follow up at 12 months is planned for the intervention group. Moreover, a cost-effectiveness analysis will be conducted from a societal perspective and will include both direct and indirect health care costs. Data will be analyzed on an intention-to-treat basis and per protocol. Discussion. The substantial negative consequences of work-related stress emphasize the necessity for effective stress-management trainings. If the proposed internet intervention proves to be (cost-) effective, a preventative, economical stress-management tool will be conceivable. The strengths and limitations of the present study are discussed. Trial registration. German Register of Clinical Studies (DRKS): DRKS00004749. © 2013 Heber et al.; licensee BioMed Central Ltd

Large-scale genome sequencing of mycorrhizal fungi provides insights into the early evolution of symbiotic traits

Mycorrhizal fungi are mutualists that play crucial roles in nutrient acquisition in terrestrial ecosystems. Mycorrhizal symbioses arose repeatedly across multiple lineages of Mucoromycotina, Ascomycota, and Basidiomycota. Considerable variation exists in the capacity of mycorrhizal fungi to acquire carbon from soil organic matter. Here, we present a combined analysis of 135 fungal genomes from 73 saprotrophic, endophytic and pathogenic species, and 62 mycorrhizal species, including 29 new mycorrhizal genomes. This study samples ecologically dominant fungal guilds for which there were previously no symbiotic genomes available, including ectomycorrhizal Russulales, Thelephorales and Cantharellales. Our analyses show that transitions from saprotrophy to symbiosis involve (1) widespread losses of degrading enzymes acting on lignin and cellulose, (2) co-option of genes present in saprotrophic ancestors to fulfill new symbiotic functions, (3) diversification of novel, lineage-specific symbiosis-induced genes, (4) proliferation of transposable elements and (5) divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild. Mycorrhizal symbioses have evolved repeatedly in diverse fungal lineages. A large phylogenomic analysis sheds light on genomic changes associated with transitions from saprotrophy to symbiosis, including divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

National trends in total cholesterol obscure heterogeneous changes in HDL and non-HDL cholesterol and total-to-HDL cholesterol ratio : a pooled analysis of 458 population-based studies in Asian and Western countries

Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and nonHDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since similar to 1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at similar to 0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as similar to 0.7 per decade in Swiss men (equivalent to similar to 26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.Peer reviewe

The image biomarker standardization initiative: Standardized convolutional filters for reproducible radiomics and enhanced clinical insights

Standardizing convolutional filters that enhance specific structures and patterns in medical imaging enables reproducible radiomics analyses, improving consistency and reliability for enhanced clinical insights. Filters are commonly used to enhance specific structures and patterns in images, such as vessels or peritumoral regions, to enable clinical insights beyond the visible image using radiomics. However, their lack of standardization restricts reproducibility and clinical translation of radiomics decision support tools. In this special report, teams of researchers who developed radiomics software participated in a three-phase study (September 2020 to December 2022) to establish a standardized set of filters. The first two phases focused on finding reference filtered images and reference feature values for commonly used convolutional filters: mean, Laplacian of Gaussian, Laws and Gabor kernels, separable and nonseparable wavelets (including decomposed forms), and Riesz transformations. In the first phase, 15 teams used digital phantoms to establish 33 reference filtered images of 36 filter configurations. In phase 2, 11 teams used a chest CT image to derive reference values for 323 of 396 features computed from filtered images using 22 filter and image processing configurations. Reference filtered images and feature values for Riesz transformations were not established. Reproducibility of standardized convolutional filters was validated on a public data set of multimodal imaging (CT, fluorodeoxyglucose PET, and T1-weighted MRI) in 51 patients with soft-tissue sarcoma. At validation, reproducibility of 486 features computed from filtered images using nine configurations × three imaging modalities was assessed using the lower bounds of 95% CIs of intraclass correlation coefficients. Out of 486 features, 458 were found to be reproducible across nine teams with lower bounds of 95% CIs of intraclass correlation coefficients greater than 0.75. In conclusion, eight filter types were standardized with reference filtered images and reference feature values for verifying and calibrating radiomics software packages. A web-based tool is available for compliance checking