Mycobacterial infection-induced miR-206 inhibits protective neutrophil recruitment via the CXCL12/CXCR4 signalling axis

Pathogenic mycobacteria actively dysregulate protective host immune signalling pathways during infection to drive the formation of permissive granuloma microenvironments. Dynamic regulation of host microRNA (miRNA) expression is a conserved feature of mycobacterial infections across host-pathogen pairings. Here we examine the role of miR-206 in the zebrafish model of Mycobacterium marinum infection, which allows investigation of the early stages of granuloma formation. We find miR-206 is upregulated following infection by pathogenic M. marinum and that antagomir-mediated knockdown of miR-206 is protective against infection. We observed striking upregulation of cxcl12a and cxcr4b in infected miR-206 knockdown zebrafish embryos and live imaging revealed enhanced recruitment of neutrophils to sites of infection. We used CRISPR/Cas9-mediated knockdown of cxcl12a and cxcr4b expression and AMD3100 inhibition of Cxcr4 to show that the enhanced neutrophil response and reduced bacterial burden caused by miR-206 knockdown was dependent on the Cxcl12/Cxcr4 signalling axis. Together, our data illustrate a pathway through which pathogenic mycobacteria induce host miR-206 expression to suppress Cxcl12/Cxcr4 signalling and prevent protective neutrophil recruitment to granulomas

Predictors of Employee Involvement in a Worksite Health Promotion Program

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67001/2/10.1177_109019819001700404.pd

Purification and Immunophenotypic Characterization of Human CD19+CD24hiCD38hi and CD19+CD24hiCD27+ B Cells.

Regulatory B cells (Bregs) have immunosuppressive capacity, primarily via the production of IL-10. IL-10 expression and immunosuppression have been described in a number of human B cell subsets, two of which include the CD19+CD24hiCD38hi and CD19+CD24hiCD27+ populations. In this chapter, we describe how to identify and isolate these subsets from peripheral blood B cells via flow cytometry. We also explain how to expand Bregs in culture and how to identify them based on intracellular expression of IL-10

Acceptability of novel lifelogging technology to determine context of sedentary behaviour in older adults

<strong>Objective:</strong> Lifelogging, using body worn sensors (activity monitors and time lapse photography) has the potential to shed light on the context of sedentary behaviour. The objectives of this study were to examine the acceptability, to older adults, of using lifelogging technology and indicate its usefulness for understanding behaviour.<strong> </strong><strong>Method:</strong> 6 older adults (4 males, mean age: 68yrs) wore the equipment (ActivPAL^TM and Vicon Revue^TM/SenseCam^TM) for 7 consecutive days during free-living activity. The older adults’ perception of the lifelogging technology was assessed through semi-structured interviews, including a brief questionnaire (Likert scale), and reference to the researcher&#39;s diary. <strong>Results:</strong> Older adults in this study found the equipment acceptable to wear and it did not interfere with privacy, safety or create reactivity, but they reported problems with the actual technical functioning of the camera. <strong>Conclusion:</strong> This combination of sensors has good potential to provide lifelogging information on the context of sedentary behaviour

Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Trends over 5 Decades in U.S. Occupation-Related Physical Activity and Their Associations with Obesity

BACKGROUND: The true causes of the obesity epidemic are not well understood and there are few longitudinal population-based data published examining this issue. The objective of this analysis was to examine trends in occupational physical activity during the past 5 decades and explore how these trends relate to concurrent changes in body weight in the U.S. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of energy expenditure for occupations in U.S. private industry since 1960 using data from the U.S. Bureau of Labor Statistics. Mean body weight was derived from the U.S. National Health and Nutrition Examination Surveys (NHANES). In the early 1960's almost half the jobs in private industry in the U.S. required at least moderate intensity physical activity whereas now less than 20% demand this level of energy expenditure. Since 1960 the estimated mean daily energy expenditure due to work related physical activity has dropped by more than 100 calories in both women and men. Energy balance model predicted weights based on change in occupation-related daily energy expenditure since 1960 for each NHANES examination period closely matched the actual change in weight for 40-50 year old men and women. For example from 1960-62 to 2003-06 we estimated that the occupation-related daily energy expenditure decreased by 142 calories in men. Given a baseline weight of 76.9 kg in 1960-02, we estimated that a 142 calories reduction would result in an increase in mean weight to 89.7 kg, which closely matched the mean NHANES weight of 91.8 kg in 2003-06. The results were similar for women. CONCLUSION: Over the last 50 years in the U.S. we estimate that daily occupation-related energy expenditure has decreased by more than 100 calories, and this reduction in energy expenditure accounts for a significant portion of the increase in mean U.S. body weights for women and men

Structural and biochemical characterization of the exopolysaccharide deacetylase Agd3 required for Aspergillus fumigatus biofilm formation

The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Deletion of a gene encoding a putative deacetylase, Agd3, leads to defects in GAG deacetylation, biofilm formation, and virulence. Here, we show that Agd3 deacetylates GAG in a metal-dependent manner, and is the founding member of carbohydrate esterase family CE18. The active site is formed by four catalytic motifs that are essential for activity. The structure of Agd3 includes an elongated substrate-binding cleft formed by a carbohydrate binding module (CBM) that is the founding member of CBM family 87. Agd3 homologues are encoded in previously unidentified putative bacterial exopolysaccharide biosynthetic operons and in other fungal genomes. The exopolysaccharide galactosaminogalactan (GAG) is an important virulence factor of the fungal pathogen Aspergillus fumigatus. Here, the authors study an A. fumigatus enzyme that deacetylates GAG in a metal-dependent manner and constitutes a founding member of a new carbohydrate esterase family.Bio-organic Synthesi

Relationships Between Cardiorespiratory Fitness, Physical Activity, and Psychosocial Variables in Overweight and Obese Breast Cancer Survivors

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Breast cancer survivors not only experience distressing physical symptoms associated with treatments, but also are faced with psychosocial challenges. Despite growing scientific evidence that physical activity (PA) may mitigate psychosocial distress experienced by women treated for breast cancer, the literature is equivocal. Purpose This study investigated the relationships between cardiorespiratory fitness (CRF), PA, and psychosocial factors in breast cancer survivors. Method Data involving overweight or obese breast cancer survivors (N=260) were examined. CRF was determined by a submaximal graded exercise test. PA, depressive symptoms, total fatigue, and global self-esteem were assessed with selfreport measures. Pearson&apos;s correlations were conducted to determine associations among CRF, PA, depressive symptoms, total fatigue, and global self-esteem. Multiple regression models, with age and body mass index as covariates, were performed using continuous levels for CRF and PA. Results Bivariate correlations suggested that CRF and PA were unrelated to the psychosocial variables. One of the regression models identified a marginally significant (P=0.06) inverse association between depressive symptoms and PA. Conclusion CRF and PA were not associated with psychosocial factors in this sample of breast cancer survivors. However

DNA methylation in Friedreich ataxia silences expression of frataxin isoform E

Supplementary Information: https://static-content.springer.com/esm/art%3A10.1038%2Fs41598-022-09002-5/MediaObjects/41598_2022_9002_MOESM1_ESM.pdfCopyright © The Author(s) 2022. Epigenetic silencing in Friedreich ataxia (FRDA), induced by an expanded GAA triplet-repeat in intron 1 of the FXN gene, results in deficiency of the mitochondrial protein, frataxin. A lesser known extramitochondrial isoform of frataxin detected in erythrocytes, frataxin-E, is encoded via an alternate transcript (FXN-E) originating in intron 1 that lacks a mitochondrial targeting sequence. We show that FXN-E is deficient in FRDA, including in patient-derived cell lines, iPS-derived proprioceptive neurons, and tissues from a humanized mouse model. In a series of FRDA patients, deficiency of frataxin-E protein correlated with the length of the expanded GAA triplet-repeat, and with repeat-induced DNA hypermethylation that occurs in close proximity to the intronic origin of FXN-E. CRISPR-induced epimodification to mimic DNA hypermethylation seen in FRDA reproduced FXN-E transcriptional deficiency. Deficiency of frataxin E is a consequence of FRDA-specific epigenetic silencing, and therapeutic strategies may need to address this deficiency.National Institutes of Health [R01 NS072418; P30 ES013508; U01 NS114143; Muscular Dystrophy Association [MDA604011; Friedreich Ataxia Research Alliance; CureFA Foundation

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities