Aims/hypothesis
Increasing evidence suggests that environmental factors changing the normal colonisation pattern in the gut strongly influence the risk of developing autoimmune diabetes. The aim of ...this study was to investigate, both during infancy and adulthood, whether treatment with vancomycin, a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes.
Methods
Accordingly, one group of mice received vancomycin from birth until weaning (day 28), while another group received vancomycin from 8 weeks of age until onset of diabetes. Pyrosequencing of the gut microbiota and flow cytometry of intestinal immune cells was used to investigate the effect of vancomycin treatment.
Results
At the end of the study, the cumulative diabetes incidence was found to be significantly lower for the neonatally treated group compared with the untreated group, whereas the insulitis score and blood glucose levels were significantly lower for the mice treated as adults compared with the other groups. Mucosal inflammation was investigated by intracellular cytokine staining of the small intestinal lymphocytes, which displayed an increase in cluster of differentiation (CD)4
+
T cells producing pro-inflammatory cytokines in the neonatally treated mice. Furthermore, bacteriological examination of the gut microbiota composition by pyrosequencing revealed that vancomycin depleted many major genera of Gram-positive and Gram-negative microbes while, interestingly, one single species,
Akkermansia muciniphila
, became dominant.
Conclusions/interpretation
The early postnatal period is a critical time for microbial protection from type 1 diabetes and it is suggested that the mucolytic bacterium
A. muciniphila
plays a protective role in autoimmune diabetes development, particularly during infancy.
INTRODUCTIONThe International Physical Activity Questionnaire (IPAQ) is one of the most widely used questionnaires to assess physical activity (PA). Validation studies for the IPAQ have been ...executed, but still there is a need for studies comparing absolute values between IPAQ and accelerometer in large population studies.
PURPOSETo compare PA and sedentary time from the self-administered, short version of the IPAQ with data from ActiGraph accelerometer in a large national sample.
METHODSA total of 1751 adults (19–84 yr) wore an accelerometer (ActiGraph GT1M) for seven consecutive days and completed the IPAQ–Short Form. Sedentary time, total PA, and time spent in moderate to vigorous activity were compared in relation to sex, age, and education.
RESULTSMen and women reported, on average, 131 min·d (SE = 4 min·d) less sedentary time compared with the accelerometer measurements. The difference between self-reported and measured sedentary time and vigorous-intensity PA was greatest among men with a lower education level and for men 65 yr and older. Although men reported 47% more moderate to vigorous physical activity (MVPA) compared with women, there were no differences between sexes in accelerometer-determined MVPA. Accelerometer-determined moderate PA was reduced from 110 to 42 min·d (62%) when analyzed in blocks of 10 min (P < 0.0001) compared with 1-min blocks. The main correlation coefficients between self-reported variables and accelerometer measures of physical activity were between 0.20 and 0.46.
CONCLUSIONSThe participants report through IPAQ–Short Form more vigorous PA and less sedentary time compared with the accelerometer. The difference between self-reported and accelerometer-measured MVPA increased with higher activity and intensity levels. Associations between the methods were affected by sex, age, and education, but not body mass index.
Beyond the smallest organisms, animals rely on tubes to transport cells, oxygen, nutrients, waste products, and a great variety of secretions. The cardiovascular system, lungs, gastrointestinal and ...genitourinary tracts, as well as major exocrine glands, are all composed of tubes. Paradoxically, despite their ubiquitous importance, most existing devices designed to study tubes are relatively complex to manufacture and/or utilize. The present work describes a simple method for generating tubes in vitro using nothing more than a low-cost 3D printer along with general lab supplies. The technology is termed "TruD", an acronym for true dimensional. Using this technology, it is readily feasible to cast tubes embedded in ECM with easy access to the lumen. The design is modular to permit more complex tube arrangements and to sustain flow. Importantly, by virtue of its simplicity, TruD technology enables typical molecular cell biology experiments where multiple conditions are assayed in replicate.
Delivery mode has been associated with long-term changes in gut microbiota composition and more recently also with changes in the immune system. This has further been suggested to link Cesarean ...section (C-section) with an increased risk for development of immune-mediated diseases such as type 1 diabetes. In this study, we demonstrate that both C-section and cross-fostering with a genetically distinct strain influence the gut microbiota composition and immune key markers in mice. Gut microbiota profiling by denaturing gradient gel electrophoresis and 454/FLX-based 16S rRNA gene amplicon sequencing revealed that mice born by C-section had a distinct bacterial profile at weaning characterized by higher abundance of Bacteroides and Lachnospiraceae, and less Rikenellaceae and Ruminococcus. No clustering according to delivery method as determined by principal component analysis of denaturing gradient gel electrophoresis profiles was evident in adult mice. However, the adult C-section-born mice had lower proportions of Foxp3(+) regulatory T cells, tolerogenic CD103(+) dendritic cells, and less Il10 gene expression in mesenteric lymph nodes and spleens. This demonstrates long-term systemic effect on the regulatory immune system that was also evident in NOD mice, a model of type 1 diabetes, born by C-section. However, no effect of delivery mode was seen on diabetes incidence or insulitis development. In conclusion, the first exposure to microorganisms seems to be crucial for the early life gut microbiota and priming of regulatory immune system in mice, and mode of delivery strongly influences this.
The high platinum loadings required to compensate for the slow kinetics of the oxygen reduction reaction (ORR) impede the widespread uptake of low-temperature fuel cells in automotive vehicles. We ...have studied the ORR on eight platinum (Pt)–lanthanide and Pt-alkaline earth electrodes, Pt₅M, where M is lanthanum, cerium, samarium, gadolinium, terbium, dysprosium, thulium, or calcium. The materials are among the most active polycrystalline Pt-based catalysts reported, presenting activity enhancement by a factor of 3 to 6 over Pt. The active phase consists of a Pt overlayer formed by acid leaching. The ORR activity versus the bulk lattice parameter follows a high peaked "volcano" relation. We demonstrate how the lanthanide contraction can be used to control strain effects and tune the activity, stability, and reactivity of these materials.
To test the hypothesis that lower extremity progressive resistance training (PRT) can improve muscle strength and functional capacity in patients with multiple sclerosis (MS) and to evaluate whether ...the improvements are maintained after the trial.
The present study was a 2-arm, 12-week, randomized controlled trial including a poststudy follow-up period of 12 weeks. Thirty-eight moderately impaired patients with MS were randomized to a PRT exercise group (n = 19) or a control group (n = 19). The exercise group completed a biweekly 12-week lower extremity PRT program and was afterward encouraged to continue training. After the trial, the control group completed the PRT intervention. Both groups were tested before and after 12 weeks of the trial and at 24 weeks (follow-up), where isometric muscle strength of the knee extensors (KE MVC) and functional capacity (FS; combined score of 4 tests) were evaluated.
KE MVC and FS improved after 12 weeks of PRT in the exercise group (KE MVC: 15.7% 95% confidence interval 4.3-27.0, FS: 21.5% 95% confidence interval 17.0-26.1; p < 0.05), and the improvements were better than in the control group (p < 0.05). The improvements of KE and FS in the exercise group persisted at follow-up after 24 weeks. Also, the exercise effects were reproduced in the control group during the 12-week posttrial PRT period.
Twelve weeks of intense progressive resistance training of the lower extremities leads to improvements of muscle strength and functional capacity in patients with multiple sclerosis, the effects persisting after 12 weeks of self-guided physical activity.
The present study provides level III evidence supporting the hypothesis that lower extremity progressive resistance training can improve muscle strength and functional capacity in patients with multiple sclerosis.
Two bacterial isolates from the Barents Sea, both belonging to the genus
, were found to yield extracts with anti-bacterial bioactivity. Mass spectrometry guided dereplication and purification of the ...active extracts lead to the isolation of the same active principle in both extracts. The structure of the bioactive compound was identified via mass spectrometry and nuclear resonance spectroscopy and it turned out to be the known lipopeptide Lipid 430. We discovered and determined its previously unknown anti-bacterial activity against
and revealed a cytotoxic effect against the A2058 human melanoma cell line at significantly lower concentrations compared to its anti-bacterial concentration. Flow cytometry and microscopy investigations of the cytotoxicity against the melanoma cell line indicated that Lipid 430 did not cause immediate cell lysis. The experiments with melanoma cells suggest that the compound functions trough more complex pathways than acting as a simple detergent.
A number of human diseases such as obesity and diabetes are associated with changes or imbalances in the gut microbiota (GM). Laboratory mice are commonly used as experimental models for such ...disorders. The introduction and dynamic development of next generation sequencing techniques have enabled detailed mapping of the GM of both humans and animal models. Nevertheless there is still a significant knowledge gap regarding the human and mouse common GM core and thus the applicability of the latter as an animal model. The aim of the present study was to identify inter- and intra-individual differences and similarities between the GM composition of particular mouse strains and humans.
A total of 1509428 high quality tag-encoded partial 16S rRNA gene sequences determined using 454/FLX Titanium (Roche) pyro-sequencing reflecting the GM composition of 32 human samples from 16 individuals and 88 mouse samples from three laboratory mouse strains commonly used in diabetes research were analyzed using Principal Coordinate Analysis (PCoA), nonparametric multivariate analysis of similarity (ANOSIM) and alpha diversity measures. A reliable cutoff threshold for low abundant taxa estimated on the basis of the present study is recommended for similar trials.
Distinctive quantitative differences in the relative abundance of most taxonomic groups between the examined categories were found. All investigated mouse strains clustered separately, but with a range of shared features when compared to the human GM. However, both mouse fecal, caecal and human fecal samples shared to a large extent not only representatives of the same phyla, but also a substantial fraction of common genera, where the number of shared genera increased with sequencing depth. In conclusion, the GM of mice and humans is quantitatively different (in terms of abundance of specific phyla and species) but share a large qualitatively similar core.
AbstractObjectiveTo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause ...mortality.DesignSystematic review and harmonised meta-analysis.Data sourcesPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.Eligibility criteriaProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.Data extraction and analysisGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.Main outcome measureAll cause mortality.Results39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).ConclusionHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.Systematic review registrationPROSPERO CRD42018091808.
Stress has profound influence on the gastro-intestinal tract, the immune system and the behavior of the animal. In this study, the correlation between gut microbiota composition determined by ...Denaturing Grade Gel Electrophoresis (DGGE) and tag-encoded 16S rRNA gene amplicon pyrosequencing (454/FLX) and behavior in the Tripletest (Elevated Plus Maze, Light/Dark Box, and Open Field combined), the Tail Suspension Test, and Burrowing in 28 female BALB/c mice exposed to two weeks of grid floor induced stress was investigated. Cytokine and glucose levels were measured at baseline, during and after exposure to grid floor. Stressing the mice clearly changed the cecal microbiota as determined by both DGGE and pyrosequencing. Odoribacter, Alistipes and an unclassified genus from the Coriobacteriaceae family increased significantly in the grid floor housed mice. Compared to baseline, the mice exposed to grid floor housing changed the amount of time spent in the Elevated Plus Maze, in the Light/Dark Box, and burrowing behavior. The grid floor housed mice had significantly longer immobility duration in the Tail Suspension Test and increased their number of immobility episodes from baseline. Significant correlations were found between GM composition and IL-1α, IFN-γ, closed arm entries of Elevated Plus Maze, total time in Elevated Plus Maze, time spent in Light/Dark Box, and time spent in the inner zone of the Open Field as well as total time in the Open Field. Significant correlations were found to the levels of Firmicutes, e.g. various species of Ruminococccaceae and Lachnospiraceae. No significant difference was found for the evaluated cytokines, except an overall decrease in levels from baseline to end. A significant lower level of blood glucose was found in the grid floor housed mice, whereas the HbA1c level was significantly higher. It is concluded that grid floor housing changes the GM composition, which seems to influence certain anxiety-related parameters.
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