Bacterial genospecies that are not ecologically coherent : population genomics of Rhizobium leguminosarum

Biological species may remain distinct because of genetic isolation or ecological adaptation, but these two aspects do not always coincide. To establish the nature of the species boundary within a local bacterial population, we characterized a sympatric population of the bacterium Rhizobium leguminosarum by genomic sequencing of 72 isolates. Although all strains have 16S rRNA typical of R. leguminosarum, they fall into five genospecies by the criterion of average nucleotide identity (ANI). Many genes, on plasmids as well as the chromosome, support this division: recombination of core genes has been largely within genospecies. Nevertheless, variation in ecological properties, including symbiotic host range and carbon-source utilization, cuts across these genospecies, so that none of these phenotypes is diagnostic of genospecies. This phenotypic variation is conferred by mobile genes. The genospecies meet the Mayr criteria for biological species in respect of their core genes, but do not correspond to coherent ecological groups, so periodic selection may not be effective in purging variation within them. The population structure is incompatible with traditional 'polyphasic taxonomy' that requires bacterial species to have both phylogenetic coherence and distinctive phenotypes. More generally, genomics has revealed that many bacterial species share adaptive modules by horizontal gene transfer, and we envisage a more consistent taxonomic framework that explicitly recognizes this. Significant phenotypes should be recognized as 'biovars' within species that are defined by core gene phylogeny

Using geographically weighted regression to explore the spatially heterogeneous spread of bovine tuberculosis in England and Wales

An understanding of the factors that affect the spread of endemic bovine tuberculosis (bTB) is critical for the development of measures to stop and reverse this spread. Analyses of spatial data need to account for the inherent spatial heterogeneity within the data, or else spatial autocorrelation can lead to an overestimate of the significance of variables. This study used three methods of analysis—least-squares linear regression with a spatial autocorrelation term, geographically weighted regression (GWR) and boosted regression tree (BRT) analysis—to identify the factors that influence the spread of endemic bTB at a local level in England and Wales. The linear regression and GWR methods demonstrated the importance of accounting for spatial differences in risk factors for bTB, and showed some consistency in the identification of certain factors related to flooding, disease history and the presence of multiple genotypes of bTB. This is the first attempt to explore the factors associated with the spread of endemic bTB in England and Wales using GWR. This technique improves on least-squares linear regression approaches by identifying regional differences in the factors associated with bTB spread. However, interpretation of these complex regional differences is difficult and the approach does not lend itself to predictive models which are likely to be of more value to policy makers. Methods such as BRT may be more suited to such a task. Here we have demonstrated that GWR and BRT can produce comparable outputs

On the brain structure heterogeneity of autism: Parsing out acquisition site effects with significance-weighted principal component analysis.

Neuroimaging studies have reported structural and physiological differences that could help understand the causes and development of Autism Spectrum Disorder (ASD). Many of them rely on multisite designs, with the recruitment of larger samples increasing statistical power. However, recent large-scale studies have put some findings into question, considering the results to be strongly dependent on the database used, and demonstrating the substantial heterogeneity within this clinically defined category. One major source of variance may be the acquisition of the data in multiple centres. In this work we analysed the differences found in the multisite, multi-modal neuroimaging database from the UK Medical Research Council Autism Imaging Multicentre Study (MRC AIMS) in terms of both diagnosis and acquisition sites. Since the dissimilarities between sites were higher than between diagnostic groups, we developed a technique called Significance Weighted Principal Component Analysis (SWPCA) to reduce the undesired intensity variance due to acquisition site and to increase the statistical power in detecting group differences. After eliminating site-related variance, statistically significant group differences were found, including Broca's area and the temporo-parietal junction. However, discriminative power was not sufficient to classify diagnostic groups, yielding accuracies results close to random. Our work supports recent claims that ASD is a highly heterogeneous condition that is difficult to globally characterize by neuroimaging, and therefore different (and more homogenous) subgroups should be defined to obtain a deeper understanding of ASD. Hum Brain Mapp 38:1208-1223, 2017. © 2016 Wiley Periodicals, Inc.Contract grant sponsor: UK Medical Research Council AIMS network; Contract grant number: G0400061; Contract grant sponsors: “Vicerrectorado de Relaciones Internacionales de la Universidad de Granada” and CEI BioTic Granada; Contract grant: “Convocatoria de Movilidad Internacional de Estudiantes de Doctorado Curso 2013/2014”; Contract grant sponsor: MINECO/ FEDER; Contract grant numbers: TEC2012-34306 and TEC2015- 64718-R; Contract grant sponsor: Consejeria de Economia, Innovacion, Ciencia y Empleo (Junta de Andalucia, Spain); Contract grant numbers: P09-TIC-4530 and P11-TIC-710

Identifying the Profile of Helicobacter pylori-Negative Gastric Cancers: A Case-Only Analysis within the Stomach Cancer Pooling (StoP) Project

Background: The prevalence of Helicobacter pylori-negative gastric cancer (HpNGC) can be as low as 1%, when infection is assessed using more sensitive tests or considering the presence of gastric atrophy. HpNGC may share a high-risk profile contributing to the occurrence of cancer in the absence of infection. We estimated the proportion of HpNGC, using different criteria to define infection status, and compared HpNGC and positive cases regarding gastric cancer risk factors. Methods: Cases from 12 studies from the Stomach cancer Pooling (StoP) Project providing data on H. pylori infection status determined by serologic test were included. HpNGC was reclassified as positive (eight studies) when cases presented CagA markers (four studies), gastric atrophy (six studies), or advanced stage at diagnosis (three studies), and were compared with positive cases. A two-stage approach (random-effects models) was used to pool study-specific prevalence and adjusted odds ratios (OR). Results: Among non-cardia cases, the pooled prevalence of HpNGC was 22.4% (n = 166/853) and decreased to 7.0% (n = 55) when considering CagA status; estimates for all criteria were 21.8% (n = 276/1, 325) and 6.6% (n = 97), respectively. HpNGC had a family history of gastric cancer more often [OR = 2.18; 95% confidence interval (CI), 1.03-4.61] and were current smokers (OR = 2.16; 95% CI, 0.52-9.02). Conclusion: This study found a low prevalence of HpNGC, who are more likely to have a family history of gastric cancer in first-degree relatives. Impact: Our results support that H. pylori infection is present in most non-cardia gastric cancers, and suggest that HpNGC may have distinct patterns of exposure to other risk factors.S. Morais, B. Peleteiro, N. Araújo, and N. Lunet received national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020). S. Morais received funding under the scope of the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI-01-0145-FEDER-032358; ref. PTDC/SAU-EPI/32358/2017) funded by FEDER through the Operational Program Competitiveness and Internationalization, and national funding from FCT, and the EPIunit – Junior Research – Prog Financing (UIDP/04750/2020). N. Araújo received an individual grant (SFRH/BD/119390/2016) funded by FCT and the ‘Programa Operacional Capital Humano’ (POCH/FSE). C. La Vecchia received funding from the Italian Association for Cancer Research (AIRC, investigator grant no. 21378). All authors received support from the European Cancer Prevention (ECP) Organization for project meetings. All authors thank all MCC-Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, University of León, ibs. Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and cols). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact

Oligodendrocyte differentiation from adult multipotent stem cells is modulated by glutamate

We used multipotent stem cells (MSCs) derived from the young rat subventricular zone (SVZ) to study the effects of glutamate in oligodendrocyte maturation. Glutamate stimulated oligodendrocyte differentiation from SVZ-derived MSCs through the activation of specific N-methyl--aspartate (NMDA) receptor subunits. The effect of glutamate and NMDA on oligodendrocyte differentiation was evident in both the number of newly generated oligodendrocytes and their morphology. In addition, the levels of NMDAR1 and NMDAR2A protein increased during differentiation, whereas NMDAR2B and NMDAR3 protein levels decreased, suggesting differential expression of NMDA receptor subunits during maturation. Microfluorimetry showed that the activation of NMDA receptors during oligodendrocyte differentiation elevated cytosolic calcium levels and promoted myelination in cocultures with neurons. Moreover, we observed that stimulation of MSCs by NMDA receptors induced the generation of reactive oxygen species (ROS), which were negatively modulated by the NADPH inhibitor apocynin, and that the levels of ROS correlated with the degree of differentiation. Taken together, these findings suggest that ROS generated by NADPH oxidase by the activation of NMDA receptors promotes the maturation of oligodendrocytes and favors myelination

Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of Case‐Control Studies of the Stop Consortium

Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 case‐control studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83–0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77–0.94) and non‐cardia GC (OR = 0.87, 95% CI = 0.81–0.94), and for diffuse (OR = 0.79, 95% CI = 0.69–0.89) and intestinal type (OR = 0.88, 95% CI = 0.79–0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This study was supported by the Fondazione AIRC per la Ricerca sul Cancro, Project no. 21378 (Investigator Grant). The Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit; UIDB/04750/2020) and the Laboratório para a Investigação Integrativa e Translacional em Saúde Populacional (ITR; LA/P/0064/2020) were funded by the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education). SM was supported by the project “NEON‐PC—Neuro‐oncological complications of prostate cancer: longitudinal study of cognitive decline” (POCI‐01‐0145‐FEDER‐032358; ref. PTDC/SAU‐EPI/32358/2017), which is funded by FEDER through the Operational Programme competitiveness and Internationalization, and national funding from FCT and the EPIUnit—Junior Research—Prog Financing (UIDP/04750/2020). The authors thank the European Cancer Prevention (ECP) Organization for providing support for the StoP Project meetings and all MCC‐Spain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, ibs.Granada, Instituto Salud Pública de Navarra, FISABIO, Murcia Regional Health Authority and cols)

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

Technology for monitoring everyday prosthesis use : a systematic review

Abstract: Background: Understanding how prostheses are used in everyday life is central to the design, provision and evaluation of prosthetic devices and associated services. This paper reviews the scientific literature on methodologies and technologies that have been used to assess the daily use of both upper- and lower-limb prostheses. It discusses the types of studies that have been undertaken, the technologies used to monitor physical activity, the benefits of monitoring daily living and the barriers to long-term monitoring, with particular focus on low-resource settings. Methods: A systematic literature search was conducted in PubMed, Web of Science, Scopus, CINAHL and EMBASE of studies that monitored the activity of prosthesis users during daily-living. Results: Sixty lower-limb studies and 9 upper-limb studies were identified for inclusion in the review. The first studies in the lower-limb field date from the 1990s and the number has increased steadily since the early 2000s. In contrast, the studies in the upper-limb field have only begun to emerge over the past few years. The early lower-limb studies focused on the development or validation of actimeters, algorithms and/or scores for activity classification. However, most of the recent lower-limb studies used activity monitoring to compare prosthetic components. The lower-limb studies mainly used step-counts as their only measure of activity, focusing on the amount of activity, not the type and quality of movements. In comparison, the small number of upper-limb studies were fairly evenly spread between development of algorithms, comparison of everyday activity to clinical scores, and comparison of different prosthesis user populations. Most upper-limb papers reported the degree of symmetry in activity levels between the arm with the prosthesis and the intact arm. Conclusions: Activity monitoring technology used in conjunction with clinical scores and user feedback, offers significant insights into how prostheses are used and whether they meet the user’s requirements. However, the cost, limited battery-life and lack of availability in many countries mean that using sensors to understand the daily use of prostheses and the types of activity being performed has not yet become a feasible standard clinical practice. This review provides recommendations for the research and clinical communities to advance this area for the benefit of prosthesis users

Association of Cholinergic Basal Forebrain Volume and Functional Connectivity with Markers of Inflammatory Response in the Alzheimer's Disease Spectrum

BACKGROUND: Inflammation has been described as a key pathogenic event in Alzheimer's disease (AD), downstream of amyloid and tau pathology. Preclinical and clinical data suggest that the cholinergic basal forebrain may moderate inflammatory response to different pathologies. OBJECTIVE: To study the association of cholinergic basal forebrain volume and functional connectivity with measures of neuroinflammation in people from the AD spectrum. METHODS: We studied 261 cases from the DELCODE cohort, including people with subjective cognitive decline, mild cognitive impairment, AD dementia, first degree relatives, and healthy controls. Using Bayesian ANCOVA, we tested associations of MRI indices of cholinergic basal forebrain volume and functional connectivity with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglia activation, and serum levels of complement C3. Using Bayesian elastic net regression, we determined associations between basal forebrain measures and a large inflammation marker panel from CSF and serum. RESULTS: We found anecdotal to moderate evidence in favor of the absence of an effect of basal forebrain volume and functional connectivity on CSF sTREM2 and serum C3 levels both in Aβ42/ptau-positive and negative cases. Bayesian elastic net regression identified several CSF and serum markers of inflammation that were associated with basal forebrain volume and functional connectivity. The effect sizes were moderate to small. CONCLUSION: Our data-driven analyses generate the hypothesis that cholinergic basal forebrain may be involved in the neuroinflammation response to Aβ42 and phospho-tau pathology in people from the AD spectrum. This hypothesis needs to be tested in independent samples