Determinants of a transcriptionally competent environment at the GM-CSF promoter

Granulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells, but not B cells, in response to immune signals. GM-CSF gene activation in response to T-cell stimulation requires remodelling of chromatin associated with the gene promoter, and these changes do not occur in B cells. While the CpG methylation status of the murine GM-CSF promoter shows no correlation with the ability of the gene to respond to activation, we find that the basal chromatin environment of the gene promoter influences its ability to respond to immune signals. In unstimulated T cells but not B cells, the GM-CSF promoter is selectively marked by enrichment of histone acetylation, and association of the chromatin-remodelling protein BRG1. BRG1 is removed from the promoter upon activation concomitant with histone depletion and BRG1 is required for efficient chromatin remodelling and transcription. Increasing histone acetylation at the promoter in T cells is paralleled by increased BRG1 recruitment, resulting in more rapid chromatin remodelling, and an associated increase in GM-CSF mRNA levels. Furthermore, increasing histone acetylation in B cells removes the block in chromatin remodelling and transcriptional activation of the GM-CSF gene. These data are consistent with a model in which histone hyperacetylation and BRG1 enrichment at the GM-CSF promoter, generate a chromatin environment competent to respond to immune signals resulting in gene activation

How to achieve resilience as an older widower: turning points or gradual change?

ABSTRACT The paper draws together two conceptualisations of resilience in bereavement and widowhood that were developed b

Effects of Community Exercise Therapy on Metabolic, Brain, Physical, and Cognitive Function Following Stroke : A Randomized Controlled Pilot Trial

© The Author(s) 2014.Peer reviewedPostprintPostprin

Characterization of Staphylococcus aureus isolates from raw milk sources in Victoria, Australia

Background Highly pathogenic strains of Staphylococcus aureus can cause disease in both humans and animals. In animal species, including ruminants, S. aureus may cause severe or sub-clinical mastitis. Dairy animals with mastitis frequently shed S. aureus into the milk supply which can lead to food poisoning in humans. The aim of this study was to use genotypic and immunological methods to characterize S. aureus isolates from milk-related samples collected from 7 dairy farms across Victoria. Results A total of 30 S. aureus isolates were collected from milk and milk filter samples from 3 bovine, 3 caprine and 1 ovine dairy farms across Victoria, Australia. Pulsed Field Gel Electrophoresis (PFGE) identified 11 distinct pulsotypes among isolates; all caprine and ovine isolates shared greater than 80 % similarity regardless of source. Conversely, bovine isolates showed higher diversity. Multi-Locus Sequence Typing (MLST) identified 5 different sequence types (STs) among bovine isolates, associated with human or ruminant lineages. All caprine and ovine isolates were ST133, or a single allele variant of ST133. Two new novel STs were identified among isolates in this study (ST3183 and ST3184). With the exception of these 2 new STs, eBURST analysis predicted all other STs to be founding members of their associated clonal complexes (CCs). Analysis of genetic markers revealed a diverse range of classical staphylococcal enterotoxins (SE) among isolates, with 11 different SEs identified among bovine isolates, compared with just 2 among caprine and ovine isolates. None of the isolates contained mecA, or were resistant to oxacillin. The only antibiotic resistance identified was that of a single isolate resistant to penicillin; this isolate also contained the penicillin resistance gene blaZ. Production of SE was observed at 16 °C and/or 37 °C in milk, however no SE production was detected at 12 °C. Conclusion Although this study characterized a limited number of isolates, bovine-associated isolates showed higher genetic diversity than their caprine or ovine counterparts. This was also reflected in a more diverse SE repertoire among bovine isolates. Very little antibiotic resistance was identified among isolates in this study. These results suggest maintaining the milk cold chain will minimise any risk from SE production and highlights the need to prevent temperature abuse

Andromeda's Parachute: A Bright Quadruply Lensed Quasar at z=2.377

We present Keck Cosmic Web Imager spectroscopy of the four putative images of the lensed quasar candidate J014709+463037 recently discovered by Berghea et al. (2017). The data verify the source as a quadruply lensed, broad absorption-line quasar having z_S = 2.377 +/- 0.007. We detect intervening absorption in the FeII 2586, 2600, MgII 2796, 2803, and/or CIV 1548, 1550 transitions in eight foreground systems, three of which have redshifts consistent with the photometric-redshift estimate reported for the lensing galaxy (z_L ~ 0.57). By virtue of their positions on the sky, the source images probe these absorbers over transverse physical scales of ~0.3-21 kpc, permitting assessment of the variation in metal-line equivalent width W_r as a function of sight-line separation. We measure differences in W_r,2796 of <40% across all sight-line pairs subtending 7-21 kpc, suggestive of a high degree of spatial coherence for MgII-absorbing material. W_r,2600 is observed to vary by >50% over the same scales across the majority of sight-line pairs, while CIV absorption exhibits a wide range in W_r,1548 differences of ~5-80% within transverse distances less than ~3 kpc. J014709+463037 is one of only a handful of z > 2 quadruply lensed systems for which all four source images are very bright (r = 15.4-17.7 mag) and are easily separated in ground-based seeing conditions. As such, it is an ideal candidate for higher-resolution spectroscopy probing the spatial variation in the kinematic structure and physical state of intervening absorbers.Comment: Submitted to ApJL. 9 pages, 3 figures. Uses aastex61 forma

GM-CSF promoter chromatin remodelling and gene transcription display distinct signal and transcription factor requirements

Granulocyte-macrophage colony stimulating factor (GM-CSF) plays a key role in myeloid cell function and is rapidly and transiently expressed in T cells in response to immune or inflammatory stimuli. Induction of GM-CSF gene expression is accompanied by changes in chromatin structure across the proximal promoter region of the gene. We show that the promoter remodelling and subsequent gene transcription occurs with distinct signal and transcription factor requirements. Activation of the protein kinase C (PKC) signalling pathway is sufficient to induce changes in chromatin structure across the promoter, but both the PKC and calcium signalling pathways are required for efficient gene transcription. Although NFAT transcription factors contribute to GM-CSF gene transcription, they are not required for promoter remodelling. However, the presence of the nuclear factor-κB transcription factor, c-Rel, in the nucleus is strongly correlated with and required for the events of chromatin remodelling

The Compassionate Communities Connectors model for end-of-life care : a community and health service partnership in Western Australia

Background: There is an international drive towards increasing provision of community-led models of social and practical support for people living with advanced illness. Aim: This feasibility project aims to develop, implement and evaluate a model of community volunteers, identified as Compassionate Communities Connectors, to support people living with advanced life limiting illnesses/palliative care needs. The aims also include the development and evaluation of a training programme for volunteers and assessment of the feasibility, acceptability and preliminary effectiveness of this model of care. Methods: The approach seeks to map and mobilise people’s personal networks of care through the Connectors enlisting Caring Helpers (community volunteers). Up to 10 Connectors will be trained to work with at least 30 families selected by the palliative care service as requiring support. The primary outcome is the effect of the intervention on social connectedness. Secondary outcomes are the intervention’s effect on unplanned hospital utilisation, caregiver support needs, advance care plans and satisfaction with intervention for patients/carers, volunteers and service providers. Conclusion: It is expected that this intervention will enhance patient, carer and family social, psychological and practical support and reduce the need for dying people to be admitted to a hospital

CCN Data Interpretation Under Dynamic Operation Conditions

We have developed a new numerical model for the non-steadystate operation of the Droplet Measurement Technologies (DMT) Cloud Condensation Nuclei (CCN) counter. The model simulates the Scanning Flow CCN Analysis (SFCA) instrument mode, where a wide supersaturation range is continuously scanned by cycling the flowrate over 20–120 s. Model accuracy is verified using a broad set of data which include ammonium sulfate calibration data (under conditions of low CCN concentration) and airborne measurements where either the instrument pressure was not controlled or where exceptionally high CCN loadings were observed. It is shown here for the first time that small pressure and flow fluctuations can have a disproportionately large effect on the instrument supersaturation due to localized compressive/expansive heating and cooling. The model shows that, for fast scan times, these effects can explain the observed shape of the SFCA supersaturation-flow calibration curve and transients in the outlet droplet sizes. The extent of supersaturation depletion from the presence of CCN during SFCA operation is also examined; we found that depletion effects can be neglected below 4000 cm−3 for CCN number

Interventions to prevent obesity in school-aged children 6-18 years: An update of a Cochrane systematic review and meta-analysis including studies from 2015–2021

Background Childhood obesity remains a global public health priority due to the enormous burden it generates. Recent surveillance data suggests there has been a sharp increase in the prevalence of childhood obesity during the COVID-19 pandemic. The Cochrane review of childhood obesity prevention interventions (0–18 years) updated to 2015 is the most rigorous and comprehensive review of randomised controlled trials (RCTs) on this topic. A burgeoning number of high quality studies have been published since that are yet to be synthesised. Methods An update of the Cochrane systematic review was conducted to include RCT studies in school-aged children (6-18 years) published to 30 June 2021 that assessed effectiveness on child weight (PROSPERO registration: CRD42020218928). Available cost-effectiveness and adverse effect data were extracted. Intervention effects on body mass index (BMI) were synthesised in random effects meta-analyses by setting (school, after-school program, community, home), and meta-regression examined the association of study characteristics with intervention effect. Findings Meta-analysis of 140 of 195 included studies (183,063 participants) found a very small positive effect on body mass index for school-based studies (SMD –0·03, 95%CI –0·06,–0·01; trials = 93; participants = 131,443; moderate certainty evidence) but not after-school programs, community or home-based studies. Subgroup analysis by age (6–12 years; 13–18 years) found no differential effects in any setting. Meta-regression found no associations between study characteristics (including setting, income level) and intervention effect. Ten of 53 studies assessing adverse effects reported presence of an adverse event. Insufficient data was available to draw conclusions on cost-effectiveness. Interpretation This updated synthesis of obesity prevention interventions for children aged 6–18 years, found a small beneficial impact on child BMI for school-based obesity prevention interventions. A more comprehensive assessment of interventions is required to identify mechanisms of effective interventions to inform future obesity prevention public health policy, which may be particularly salient in for COVID-19 recovery planning. Funding This research was funded by the National Health and Medical Research Council (NHMRC), Australia (Application No APP1153479)