The Drosophila transcriptional network is structured by microbiota.

BACKGROUND: Resident microorganisms (microbiota) have far-reaching effects on the biology of their animal hosts, with major consequences for the host's health and fitness. A full understanding of microbiota-dependent gene regulation requires analysis of the overall architecture of the host transcriptome, by identifying suites of genes that are expressed synchronously. In this study, we investigated the impact of the microbiota on gene coexpression in Drosophila. RESULTS: Our transcriptomic analysis, of 17 lines representative of the global genetic diversity of Drosophila, yielded a total of 11 transcriptional modules of co-expressed genes. For seven of these modules, the strength of the transcriptional network (defined as gene-gene coexpression) differed significantly between flies bearing a defined gut microbiota (gnotobiotic flies) and flies reared under microbiologically sterile conditions (axenic flies). Furthermore, gene coexpression was uniformly stronger in these microbiota-dependent modules than in both the microbiota-independent modules in gnotobiotic flies and all modules in axenic flies, indicating that the presence of the microbiota directs gene regulation in a subset of the transcriptome. The genes constituting the microbiota-dependent transcriptional modules include regulators of growth, metabolism and neurophysiology, previously implicated in mediating phenotypic effects of microbiota on Drosophila phenotype. Together these results provide the first evidence that the microbiota enhances the coexpression of specific and functionally-related genes relative to the animal's intrinsic baseline level of coexpression. CONCLUSIONS: Our system-wide analysis demonstrates that the presence of microbiota enhances gene coexpression, thereby structuring the transcriptional network in the animal host. This finding has potentially major implications for understanding of the mechanisms by which microbiota affect host health and fitness, and the ways in which hosts and their resident microbiota coevolve

Smoking and Multiple Sclerosis: An Updated Meta-Analysis

Background: Multiple sclerosis (MS) is a leading cause of disability in young adults. Susceptibility to MS is determined by environmental exposure on the background of genetic risk factors. A previous meta-analysis suggested that smoking was an important risk factor for MS but many other studies have been published since then.Methods/Principal Findings: We performed a Medline search to identify articles published that investigated MS risk following cigarette smoking. A total of 14 articles were included in this study. This represented data on 3,052 cases and 457,619 controls. We analysed these studies in both a conservative (limiting our analysis to only those where smoking behaviour was described prior to disease onset) and non-conservative manner. Our results show that smoking is associated with MS susceptibility (conservative: risk ratio (RR) 1.48, 95% confidence interval (CI) 1.35-1.63, p<10(-15); non-conservative: RR 1.52, 95% CI 1.39-1.66, p<10(-19)). We also analysed 4 studies reporting risk of secondary progression in MS and found that this fell just short of statistical significance with considerable heterogeneity (RR 1.88, 95% CI 0.98-3.61, p = 0.06).Discussion: Our results demonstrate that cigarette smoking is important in determining MS susceptibility but the effect on the progression of disease is less certain. Further work is needed to understand the mechanism behind this association and how smoking integrates with other established risk factors

Past, present and future—sample environments for materials research studies in scattering and spectroscopy; a UK perspective

Small angle x-ray scattering and x-ray absorption fine structure are two techniques that have been employed at synchrotron sources ever since their inception. Over the course of the development of the techniques, the introduction of sample environments for added value experiments has grown dramatically. This article reviews past successes, current developments and an exploration of future possibilities for these two x-ray techniques with an emphasis on the developments in the United Kingdom between 1980–2020

Receptor-targeted, magneto-mechanical stimulation of osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Mechanical cues are employed to promote stem cell differentiation and functional tissue formation in tissue engineering and regenerative medicine. We have developed a Magnetic Force Bioreactor (MFB) that delivers highly targeted local forces to cells at a pico-newton level, utilizing magnetic micro- and nano-particles to target cell surface receptors. In this study, we investigated the effects of magnetically targeting and actuating specific two mechanical-sensitive cell membrane receptors-platelet-derived growth factor receptor α (PDGFRα) and integrin ανβ3. It was found that a higher mineral-to-matrix ratio was obtained after three weeks of magneto-mechanical stimulation coupled with osteogenic medium culture by initially targeting PDGFRα compared with targeting integrin ανβ3 and non-treated controls. Moreover, different initiation sites caused a differentiated response profile when using a 2-day-lagged magneto-mechanical stimulation over culture periods of 7 and 12 days). However, both resulted in statistically higher osteogenic marker genes expression compared with immediate magneto-mechanical stimulation. These results provide insights into important parameters for designing appropriate protocols for ex vivo induced bone formation via magneto-mechanical actuation

Bone health in Parkinson's disease: a systematic review and meta-analysis

AJN: Travel support from the National Institute of Health Research for presentations at MDS Congresses and Association of British Neurologists Meetings; grants from Parkinson’s UK Innovation Grant (K-1006), Parkinson’s UK Career Development Award (F-1201), National Institute of Health Research Academic Clinical Fellowship, Élan/Prothena Pharmaceuticals and GE Healthcare. KMD: beneficiary of a Reta Lila Weston Scholarship and received a Parkinson’s UK Innovation Grant (K-1010

Bone health in Parkinson's disease: A systematic review and meta-analysis

Objective: Parkinson's disease (PD) and osteoporosis are chronic diseases associated with increasing age. Single studies have reported associations between them and the major consequence, namely, increased risk of fractures. The aim of this systematic review and meta-analysis was to evaluate the relationship of PD with osteoporosis, bone mineral density (BMD) and fracture risk. Methods: A literature search was undertaken on 4 September 2012 using multiple indexing databases and relevant search terms. Articles were screened for suitability and data extracted where studies met inclusion criteria and were of sufficient quality. Data were combined using standard meta-analysis methods. Results: 23 studies were used in the final analysis. PD patients were at higher risk of osteoporosis (OR 2.61; 95% CI 1.69 to 4.03) compared with healthy controls. Male patients had a lower risk for osteoporosis and osteopenia than female patients (OR 0.45; 95% CI 0.29 to 0.68). PD patients had lower hip, lumbar spine and femoral neck BMD levels compared with healthy controls; mean difference, -0.08, 95% CI -0.13 to -0.02 for femoral neck; -0.09, 95% CI -0.15 to -0.03 for lumbar spine; and -0.05, 95% CI -0.07 to -0.03 for total hip. PD patients were also at increased risk of fractures (OR 2.28; 95% CI 1.83 to 2.83). Conclusions: This systematic review and meta-analysis demonstrate that PD patients are at higher risk for both osteoporosis and osteopenia compared with healthy controls, and that female patients are at greater risk than male patients. Patients with PD also have lower BMD and are at increased risk of fractures. © 2014 by the BMJ Publishing Group Ltd

Influence of dopant metal ions on the formation of cordierite using combined SAXS/WAXS and EXAFS/WAXS techniques

Time-resolved combined scattering and spectroscopic techniques were used to understand in detail the formation of cordierite ceramic from two sources, (a) zeolite B and (b) cordierite glass systems. Time-resolved in situ combined EXAFS/XRD (at the Zn K-edge) investigation of the zinc oxide mixed zeolite B reveal that a series of transformations occur before the formation of cordierite ceramic. In particular the study revealed that addition of small amounts of zinc oxide promote the transformation of cordierite, through the formation of ZnAl2O4, at lower temperatures compared to the system without zinc oxide. Using in situ time-resolved SAXS/WAXS technique chromium doped in the cordierite glass system was investigated which revealed that, in addition to the formation of phase pure cordierite phase some amount of MgCr2O4 spinel phase are also produced

Safety Implications of High-Field MRI: Actuation of Endogenous Magnetic Iron Oxides in the Human Body

Background: Magnetic Resonance Imaging scanners have become ubiquitous in hospitals and high-field systems (greater than 3 Tesla) are becoming increasingly common. In light of recent European Union moves to limit high-field exposure for those working with MRI scanners, we have evaluated the potential for detrimental cellular effects via nanomagnetic actuation of endogenous iron oxides in the body.Methodology: Theoretical models and experimental data on the composition and magnetic properties of endogenous iron oxides in human tissue were used to analyze the forces on iron oxide particles.Principal Finding and Conclusions: Results show that, even at 9.4 Tesla, forces on these particles are unlikely to disrupt normal cellular function via nanomagnetic actuation

Lower lymphocyte count is associated with increased risk of Parkinson's disease

Objectives: Patients with established Parkinson’s disease (PD) display differences in peripheral blood biomarkers of immune function, including leukocyte differential counts, compared to controls. These differences may be useful biomarkers to predict PD and shed light on pathogenesis. We sought to identify whether peripheral immune dysregulation was associated with increased risk of subsequent PD diagnosis. Methods: We examined the relationship between incident PD and baseline differential leukocyte count and other blood markers of acute inflammation in UK Biobank, a longitudinal cohort with >500 000 participants. We used a range of sensitivity analyses and Mendelian randomization (MR) to further explore the nature of associations. Results: After excluding individuals with comorbidities which could influence biomarkers of inflammation, 465 incident PD cases and 312,125 controls remained. Lower lymphocyte count was associated with increased risk of subsequent PD diagnosis (per 1‐SD decrease in lymphocyte count OR 1.18, 95% CI 1.07‐1.32, padjusted=0.01). There was some evidence that reductions in eosinophil and monocyte counts and CRP were associated with increased PD risk, as was higher neutrophil count. Only the association between lower lymphocyte count and increased PD risk remained robust to sensitivity analyses. MR suggested that the effect of lower lymphocyte count on PD risk may be causal (per 1‐SD decrease in lymphocyte count; ORMR 1.09, 95% CI 1.01‐1.18, p=0.02). Interpretation: We provide converging evidence from observational analyses in UKB and MR that lower lymphocyte count is associated with an increased risk of subsequent PD

Wolbachia Induces Male-Specific Mortality in the Mosquito Culex pipiens (LIN Strain)

Background: Wolbachia are maternally inherited endosymbionts that infect a diverse range of invertebrates, including insects, arachnids, crustaceans and filarial nematodes. Wolbachia are responsible for causing diverse reproductive alterations in their invertebrate hosts that maximize their transmission to the next generation. Evolutionary theory suggests that due to maternal inheritance, Wolbachia should evolve toward mutualism in infected females, but strict maternal inheritance means there is no corresponding force to select for Wolbachia strains that are mutualistic in males. Methodology/Principal findings: Using cohort life-table analysis, we demonstrate that in the mosquito Culex pipiens (LIN strain), Wolbachia-infected females show no fitness costs due to infection. However, Wolbachia induces up to a 30% reduction in male lifespan. Conclusions/significance: These results indicate that the Wolbachia infection of the Culex pipiens LIN strain is virulent in a sex-specific manner. Under laboratory situations where mosquitoes generally mate at young ages, Wolbachia strains that reduce male survival could evolve by drift because increased mortality in older males is not a significant selective force