Spatial patterns of microbial diversity and activity in an aged creosote-contaminated site

Restoration of polluted sites via in situ bioremediation relies heavily on the indigenous microbes and their activities. Spatial heterogeneity of microbial populations, contaminants and soil chemical parameters on such sites is a major hurdle in optimizing and implementing an appropriate bioremediation regime. We performed a grid-based sampling of an aged creosote-contaminated site followed by geostatistical modelling to illustrate the spatial patterns of microbial diversity and activity and to relate these patterns to the distribution of pollutants. Spatial distribution of bacterial groups unveiled patterns of niche differentiation regulated by patchy distribution of pollutants and an east-to-west pH gradient at the studied site. Proteobacteria clearly dominated in the hot spots of creosote pollution, whereas the abundance of Actinobacteria, TM7 and Planctomycetes was considerably reduced from the hot spots. The pH preferences of proteobacterial groups dominating in pollution could be recognized by examining the order and family-level responses. Acidobacterial classes came across as generalists in hydrocarbon pollution whose spatial distribution seemed to be regulated solely by the pH gradient. Although the community evenness decreased in the heavily polluted zones, basal respiration and fluorescein diacetate hydrolysis rates were higher, indicating the adaptation of specific indigenous microbial populations to hydrocarbon pollution. Combining the information from the kriged maps of microbial and soil chemistry data provided a comprehensive understanding of the long-term impacts of creosote pollution on the subsurface microbial communities. This study also highlighted the prospect of interpreting taxa-specific spatial patterns and applying them as indicators or proxies for monitoring polluted sites

Alzheimer's disease-associated P460L variant of EphA1 dysregulates receptor activity and blood-brain barrier function

INTRODUCTION: Genome-wide association studies link susceptibility to late-onset Alzheimer's disease (LOAD) with EphA1. Sequencing identified a non-synonymous substitution P460L as a LOAD risk variant. Other Ephs regulate vascular permeability and immune cell recruitment. We hypothesized that P460L dysregulates EphA1 receptor activity and impacts neuroinflammation. METHODS: EphA1/P460L receptor activity was assayed in isogenic Human Embryonic Kidney (HEK) cells. Soluble EphA1/P460L (sEphA1/sP460L) reverse signaling in brain endothelial cells was assessed by T-cell recruitment and barrier function assays. RESULTS: EphA1 and P460L were expressed in HEK cells, but membrane and soluble P460L were significantly reduced. Ligand engagement induced Y781 phosphorylation of EphA1 but not P460L. sEphA1 primed brain endothelial cells for increased T-cell recruitment; however, sP460L was less effective. sEphA1 decreased the integrity of the brain endothelial barrier, while sP460L had no effect. DISCUSSION: These findings suggest that P460L alters EphA1-dependent forward and reverse signaling, which may impact blood-brain barrier function in LOAD. Highlights: EphA1-dependent reverse signaling controls recruitment of T cells by brain endothelial cells. EphA1-dependent reverse signaling remodels brain endothelial cell contacts. LOAD-associated P460L variant of EphA1 shows reduced membrane expression and reduced ligand responses. LOAD-associated P460L variant of EphA1 fails to reverse signal to brain endothelial cells.Neuroscience and Mental Health Research Institute (NMHRI), Cardiff University and Sir Geraint Evans Cardiovascular Fund, Cardiff University (grant to A.A. and A.J.R.), L.E.T. by UK Dementia Research Institute, Cardiff University, O.R.M. by School of Medicine, Cardiff University, S.S. and C.L.T. by Eli Lilly (grant to J.W. and A.A.), and C.C. by School of Cellular and Molecular Medicine, University of Bristol. The Bioflux 200 was funded by the Leukemia Research Appeal for Wales, and iBright 1500 was funded by the Ser Cymru II programme (grant CU209 to V.K. and Manon Pritch, which was partially funded by Cardiff University and the European Regional Development Fund through the Welsh Government (Grant CU209 to V.K. and Manon Pritchard)

The phenotype associated with a large deletion on MECP2

Multiplex ligation-dependent Probe Amplification (MLPA) has become available for the detection of a large deletion on the MECP2 gene allowing genetic confirmation of previously unconfirmed cases of clinical Rett syndrome. This study describes the phenotype of those with a large deletion and compares with those with other pathogenic MECP2 mutations. Individuals were ascertained from the Australian Rett Syndrome and InterRett databases with data sourced from family and clinician questionnaires, and two case studies were constructed from the longitudinal Australian data. Regression and survival analysis were used to compare severity and age of onset of symptoms in those with and without a large deletion. Data were available for 974 individuals including 51 with a large deletion and ages ranged from 1 year 4 months to 49 years (median 9 years). Those with a large deletion were more severely affected than those with other mutation types. Specifically, individuals with large deletions were less likely to have learned to walk (OR 0.42, 95% CI: 0.22–0.79, P=0.007) and to be currently walking (OR 0.53, 95% CI: 0.26–1.10, P=0.089), and were at higher odds of being in the most severe category of gross motor function (OR 1.84, 95% CI: 0.98–3.48, P=0.057) and epilepsy (OR 2.72, 95% CI: 1.38–5.37, P=0.004). They also developed epilepsy, scoliosis, hand stereotypies and abnormal breathing patterns at an earlier age. We have described the disorder profile associated with a large deletion from the largest sample to date and have found that the phenotype is severe with motor skills particularly affected

A Systematic Literature Review of Sport and Physical Activity Participation in Culturally and Linguistically Diverse (CALD) Migrant Populations

Culturally and linguistically diverse (CALD) migrants face significant health risks as they adapt to new cultures. These risks are exacerbated by their limited participation in preventative behaviours such as sports and physical activity. The review aimed to identify studies that examined the correlates of sport and physical activity participation in migrants. The systematic review identified 72 papers, including 6 interventions, 18 qualitative and 48 quantitative studies. The 44 identified correlates highlight the complexities involved in working with migrants. The correlates were grouped in four themes using the social ecological model; acculturation, demographic, psychosocial and environmental/organisational. The social ecological model identified general correlates such as social support and safety. However, there were unique correlates relating to individuals who are facing cultural changes such as acculturation and language. Overall, there is a lack of contextualisation of CALD migrants’ sport and physical activity experiences because many studies fail to consider acculturation comprehensively. Initially titled: A review of sport and physical activity in culturally and linguistically diverse migrant

Quantifying Tertiary Lymphoid Structure-Associated Genes in Formalin-Fixed Paraffin-Embedded Breast Cancer Tissues.

Tertiary lymphoid structures (TLS) have been detected in several types of human solid tumors. These structures are thought to regulate local adaptive immune responses that can promote or antagonize tumor progression. Despite positive prognostic values associated with a TLS presence in several studies, discrepancies still exist. TLS are structurally organized entities composed of varying numbers of multiple cell types making their assessment in tumor tissues, particularly biopsies, challenging. Immunohistochemical staining of TLS-related cell populations is the most frequently used method for identifying and scoring them; however, TLS-related gene expression has also been explored. The protocols described are detailed to allow the user to quantify TLS-related gene expression on formalin-fixed paraffin-embedded human breast tumor tissues.info:eu-repo/semantics/publishe

Untreated Reproductive Morbidities among Ever Married Women of Slums of Rajkot City, Gujarat: The Role of Class, Distance, Provider Attitudes, and Perceived Quality of Care

It is a common problem in India for women in the reproductive age group to suffer from reproductive illnesses and not seek care. This paper is an attempt to assess untreated reproductive morbidities and to study factors affecting treatment-seeking behavior among ever married women of urban slums. We selected 1,046 women of the reproductive age group (15–49 years) using two-stage cluster sampling for a community-based, cross-sectional study. From this sample, 593 responses reporting reproductive morbidity were analyzed for treatment-seeking behavior and its correlates. Information was collected on demographics, socioeconomic status, self-reported reproductive morbidity, and treatment-seeking patterns, along with reasons for not utilizing available health services, all using a pretested, structured interview schedule. Univariate and multivariate analyses were done in SPSS 15.0. In our sample, 57% of women had at least one reproductive morbidity; of these, only one third sought health care. Women belonging to the Scheduled Castes/Scheduled Tribes caste group (OR = 3.92, 95% CI 1.44–10.64), at a distance of more than 2 km from a health facility (OR = 2.67, 95% CI 1.28–5.58), and whose duration of illness was more than 1 year (OR = 14.44, 95% CI 3.66–56.87) accessed fewer reproductive health services compared to their counterparts. The present study found that a lower sense of need, the cost of care, and societal barriers were the reasons for not seeking care. Providers’ poor attitudes, poor quality of services, and long waiting times were found to be the reasons for not utilizing health facilities. The determinants for accessing reproductive health care were resources available at the household level, social factors, the availability of services, and behaviors related to health. Government facilities remained underutilized