Characterisation of microvesicles released from cells constitutively and upon stimulation

Constitutively released microvesicles (cMVs) are released as a part of normal cell physiology and this is summarised in Fig. 1 (1). However stimulated microvesicles (sMVs) are released as a result of a number of possible stress factors (2, 3). We found sMVs to be released in higher numbers than cMVs, typically ten-fold higher numbers, in the same time frame, and where the stress factor was a pharmacological agent, the microvesiculation was an attempt to release this chemical stress factor. Using a mass sensing technique, the sMVs were released over a 15 min period after stimulation. Using sizing beads on a flow cytometer and by transmission electron microscopy the cMVs were typically smaller (less than 300 nm in diameter) than sMVs (300-500 nm in diameter). However cMVs were found to carry more protein. By contrast, phosphatidylserine expression was greater on the larger sMVs, which also more effectively inhibited complement-mediated lysis.Peer reviewedFinal Accepted Versio

Managing without Authority: Records Managers in Interorganizational Contexts

Information professionals are taking on new roles in modern organizations. Specifically, these professionals are tasked with gaining coworkers’ compliance with information communication and management policies. However, they often lack the formal authority of traditional managers. We report on preliminary findings from a qualitative study of records managers, focusing on the interpersonal skills they use to achieve compliance.ye

Effects of acute and chronic exercise on immunological parameters in the elderly aged: can physical activity counteract the effects of aging?

Immunosenescence is characterized by deterioration of the immune system caused by aging which induces changes to innate and adaptive immunity. Immunosenescence affects function and phenotype of immune cells, such as expression and function of receptors for immune cells which contributes to loss of immune function (chemotaxis, intracellular killing). Moreover, these alterations decrease the response to pathogens, which leads to several age-related diseases including cardiovascular disease, Alzheimer's disease, and diabetes in older individuals. Furthermore, increased risk of autoimmune disease and chronic infection is increased with an aging immune system, which is characterized by a pro-inflammatory environment, ultimately leading to accelerated biological aging. During the last century, sedentarism rose dramatically, with a concomitant increase in certain type of cancers (such as breast cancer, colon, or prostate cancer), and autoimmune disease. Numerous studies on physical activity and immunity, with focus on special populations (i.e., people with diabetes, HIV patients) demonstrate that chronic exercise enhances immunity. However, the majority of previous work has focused on either a pathological population or healthy young adults whilst research in elderly populations is scarce. Research conducted to date has primarily focused on aerobic and resistance exercise training and its effect on immunity. This review focuses on the potential for exercise training to affect the aging immune system. The concept is that some lifestyle strategies such as high-intensity exercise training may prevent disease through the attenuation of immunosenescence. In this context, we take a top-down approach and review the effect of exercise and training on immunological parameters in elderly at rest and during exercise in humans, and how they respond to different modes of training. We highlight the impact of these different exercise modes on immunological parameters, such as cytokine and lymphocyte concentration in elderly individuals

Sex Differences and Psychological Stress: Responses to the COVID-19 Pandemic in China

BACKGROUND: About 83,000 COVID-19 patients were confirmed in China up to May 2020. Amid the well-documented threats to physical health, the effects of this public health crisis - and the varied efforts to contain its spread - have altered individuals\u27 normal daily functioning. These impacts on social, psychological, and emotional well-being remain relatively unexplored - in particular, the ways in which Chinese men and women experience and respond to potential behavioral stressors. Our study investigated sex differences in psychological stress, emotional reactions, and behavioral responses to COVID-19 and related threats among Chinese residents. METHODS: In late February (2020), an anonymous online questionnaire was disseminated via WeChat, a popular social media platform in China. The cross-sectional study utilized a non-probabilistic snowball or convenience sampling of residents from various provinces and regions of China. Basic demographic characteristics (e.g., age and gender) - along with residential living arrangements and conditions - were measured along with psychological stress and emotional responses to the COVID-19 pandemic. RESULTS: Three thousand eighty-eight questionnaires were returned: 1749 females (56.6%) and 1339 males (43.4%). The mean stress level,as measured by a visual analog scale, was 3.4 (SD = 2.4) - but differed significantly by sex. Besides sex, factors positively associated with stress included: age (\u3c 45 years), employment (unsteady income, unemployed), risk of infection (exposureto COVID-19, completed medical observation), difficulties encountered (diseases, work/study, financial, mental), and related behaviors (higher desire for COVID-19 knowledge, more time concerning on the COVID-19 outbreak). Protective factors included frequent contact with colleagues, calmness of mood comparing with the pre-pandemic, and psychological resilience. Males and females also differed significantly in adapting to current living/working, conditions, responding to run a fever, and needing psychological support services. CONCLUSIONS: The self-reported stress of Chinese residents related to the COVID-19 pandemic was significantly related to sex, age, employment, resilience and coping styles. Future responses to such public health threats may wish to provide sex- and/or age-appropriate supports for psychological health and emotional well-being to those at greatest risk of experiencing stress

Isolation and characterization of extracellular vesicles and future directions in diagnosis and therapy

Extracellular vesicles (EVs) are a unique and heterogeneous class of lipid bilayer nanoparticles secreted by most cells. EVs are regarded as important mediators of intercellular communication in both prokaryotic and eukaryotic cells due to their ability to transfer proteins, lipids and nucleic acids to recipient cells. In addition to their physiological role, EVs are recognized as modulators in pathological processes such as cancer, infectious diseases, and neurodegenerative disorders, providing new potential targets for diagnosis and therapeutic intervention. For a complete understanding of EVs as a universal cellular biological system and its translational applications, optimal techniques for their isolation and characterization are required. Here, we review recent progress in those techniques, from isolation methods to characterization techniques. With interest in therapeutic applications of EVs growing, we address fundamental points of EV‐related cell biology, such as cellular uptake mechanisms and their biodistribution in tissues as well as challenges to their application as drug carriers or biomarkers for less invasive diagnosis or as immunogens.This article is categorized under: Diagnostic Tools > BiosensingTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Diseas

CHILD: a new tool for detecting low-abundance insertions and deletions in standard sequence traces

Several methods have been proposed for detecting insertion/deletions (indels) from chromatograms generated by Sanger sequencing. However, most such methods are unsuitable when the mutated and normal variants occur at unequal ratios, such as is expected to be the case in cancer, with organellar DNA or with alternatively spliced RNAs. In addition, the current methods do not provide robust estimates of the statistical confidence of their results, and the sensitivity of this approach has not been rigorously evaluated. Here, we present CHILD, a tool specifically designed for indel detection in mixtures where one variant is rare. CHILD makes use of standard sequence alignment statistics to evaluate the significance of the results. The sensitivity of CHILD was tested by sequencing controlled mixtures of deleted and undeleted plasmids at various ratios. Our results indicate that CHILD can identify deleted molecules present as just 5% of the mixture. Notably, the results were plasmid/primer-specific; for some primers and/or plasmids, the deleted molecule was only detected when it comprised 10% or more of the mixture. The false positive rate was estimated to be lower than 0.4%. CHILD was implemented as a user-oriented web site, providing a sensitive and experimentally validated method for the detection of rare indel-carrying molecules in common Sanger sequence reads

The Met Office Unified Model Global Atmosphere 6.0/6.1 and JULES Global Land 6.0/6.1 configurations

We describe Global Atmosphere 6.0 and Global Land 6.0: the latest science configurations of the Met Office Unified Model and JULES land surface model developed for use across all timescales. Global Atmosphere 6.0 includes the ENDGame dynamical core, which significantly increases mid-latitude variability improving a known model bias. Alongside developments of the model’s physical parametrisations, ENDGame also increases variability in the tropics, which leads to an improved representation of tropical cyclones and other tropical phenomena. Further developments of the atmospheric and land surface parametrisations improve other aspects of model performance, including the forecasting of surface weather phenomena. We also describe Global Atmosphere 6.1 and Global Land 6.1, which include a small number of long-standing differences from our main trunk configurations that we continue to require for operational global weather prediction. Since July 2014, GA6.1/GL6.1 has been used by the Met Office for operational global NWP, whilst GA6.0/GL6.0 was implemented in its remaining global prediction systems over the following year

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer

DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6x10-5) and rs2155388 in CHEK1 (p=3.1x10-6), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes