Basal Signalling Through Death Receptor 5 and Caspase 3 Activates p38 Kinase To Regulate Serum Response Factor (SRF)-Mediated Myod Transcription

We have previously reported that stable expression of a dominant negative Death Receptor 5 (dnDR5) in skeletal myoblasts results in decreased basal caspase activity and decreased mRNA and protein expression of the muscle regulatory transcription factor MyoD in growth medium (GM), resulting in inhibited differentation when myoblasts are then cultured in differentiation media (DM). Further, this decreased level of MyoD mRNA was not a consequence of altered message stability, but rather correlated with decreased acetylation of histones in the distal regulatory region (DRR) of the MyoD extended promoter known to control MyoD transcription. As serum response factor (SRF) is the transcription factor known to be responsible for basal MyoD expression in GM, we compared the level of SRF binding to the non-canonical serum response element (SRE) within the DRR in parental and dnDR5 expressing myoblasts. Herein, we report that stable expression of dnDR5 resulted in decreased levels of serum response factor (SRF) binding to the CArG box in the SRE of the DRR. Total SRF expression levels were not affected, but phosphorylation indicative of SRF activation was impaired. This decreased SRF phosphorylation correlated with decreased phosphorylation-induced activation of p38 kinase. Moreover, the aforementioned signaling events affected by expression of dnDR5 could be appropriately recapitulated using either a pharmacological inhibitor of caspase 3 or p38 kinase. Thus, our results have established a signaling pathway from DR5 through caspases to p38 kinase activation, to SRF activation and the basal expression of MyoD

Sheep Updates 2007 - part 3

This session covers seven papers from different authors: PROFITABILITY 1. Benchmarking demonstrates both the potential and realised productivity gains in the sheep and wool industry, Andrew Ritchie, Edward Riggall and James Hall, ICON Agriculture, Darkan 2. Improving sheep genetics will increase farm profitability, Gus Rose, Johan Greeff Department of Agriculture and Food Western Australia, John Young Farming Systems Analysis Service, WA 3. Meat, Merinos and making money in WA Pastoral Zone, M. Alchin, M. Young and T. Johnson, Department of Agriculture and Food Western Australia, GRAZING 4. Nitrogen - farmers\u27 friend or foe? John Lucy and Martin Staines, Department of Agriculture and Food Western Australia 5. Drought proofing grazing systems - a case study from Binnu 2006/7, Tim Wiley & Rob Grima, Department of Agriculture & Food Western Australia 6. Minimising \u27Esperance Storm\u27 livestock losses, Sandra Prosser and Matt Ryan, Department of Agriculture and Food Western Australia 7. Sub-tropical grasses in WA - what is their potential? Geoff Moore, Tony Albertsen, Department of Agriculture & Food Western Australia, Phil Barrett-Lennard, Evergreen Farming, George Woolston, John Titterington, Department of Agriculture and Food Western Australia, Sarah Knight, Irwin-Mingenew Group, Brianna Peake, Liebe Group, Buntine, W

Food Insecurity Prevalence Across Diverse Sites During COVID-19: A Year of Comprehensive Data

Key Findings NFACT includes 18 study sites in 15 states as well as a national poll, collectively representing a sample size of more than 26,000 people. Some sites have implemented multiple survey rounds, here we report results from 22 separate surveys conducted during the year since the COVID-19 pandemic began in March 2020. 18 out of 19 surveys in 14 sites with data for before and since the pandemic began found an increase in food insecurity since the start of the COVID-19 pandemic as compared to before the pandemic. In nearly all surveys (18/19) that measured food insecurity both before and during the pandemic, more Black, Indigenous, and People of Color (BIPOC) were classified as food insecure during the pandemic as compared to before it began. Prevalence of food insecurity for BIPOC respondents was higher than the overall population in the majority of surveys (19/20) sampling a general population. In almost all surveys (21/22), the prevalence of food insecurity for households with children was higher than the overall prevalence of food insecurity. Food insecurity prevalence was higher for households experiencing a negative job impact during the pandemic (i.e. job loss, furlough, reduction in hours) in nearly all surveys and study sites (21/22). Food insecurity prevalence in most sites was significantly higher before COVID-19 than estimates from that time period. Reporting a percent change between pre and during COVID-19 prevalence may provide additional information about the rate of change in food insecurity since the start of the pandemic, which absolute prevalence of food insecurity may not capture. Results highlight consistent trends in food insecurity outcomes since the start of the COVID-19 pandemic, across diverse study sites, methodological approaches, and time

Cultivating Connections: A Housing & Economic Development Implementation Strategy for the Mechanicsville Neighborhood of Atlanta

The future of Mechanicsville has been laid out in several previous plans, but they have resulted in little additional development for the neighborhood. Rather than creating another plan, the goal of this studio was to provide an implementation framework for community level development strategies. They are based on best practices observed in other communities, both in the City of Atlanta and around the United States as well as key input from Mechanicsville stakeholders. A key goal of the studio was to create a collection of practical ideas and recommendations which can be taken and applied by the Mechanicsville community, developers, and the City

Using golf carts as a transportation mode: Who does it?

Golf carts are rising in popularity among older adults, not only for use on the course but also for traveling short distances. Studies focus on the increasing incidence of related injuries, giving limited attention to identifying who uses golf carts as a transportation mode. Using data from a survey of Floridians aged 50 and older conducted between December 2020 and April 2021 (n = 4199), we conducted OLS regression to examine factors predicting the frequency of golf cart use. We examine six sets of predictors: sociodemographics, health, self-perceptions of aging, social relationships, transportation experiences, and built environment. More frequent use is associated with being younger, male, and married or partnered, reporting less loneliness and older age identities, walking and biking more frequently, and interacting more often with friends – but less often with family members. It also is associated with living in an inland rather than coastal county and one with lower golf cart injury rates. Our findings indicate that predictors of more frequent golf cart use differ from those associated with transitioning from driving, suggesting that greater golf cart use is not part of this process. Our results instead allude to the possible role of golf carts in enhancing middle-aged and older adults’ friendships and well-being

Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles

Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC) exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO) and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively) in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS) was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut’s ability to perform complex tasks during extended missions in deep space. Keywords: Human neural stem cells, Oxidative stress, Charged particle, Space radiatio

Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles.

Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC) exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO) and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively) in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS) was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut's ability to perform complex tasks during extended missions in deep space

3D surface analysis of hippocampal microvasculature in the irradiated brain.

Cranial irradiation used to control CNS malignancies can also disrupt the vasculature and impair neurotransmission and cognition. Here we describe two distinct methodologies for quantifying early and late radiation injury in CNS microvasculature. Intravascular fluorescently labeled lectin was used to visualize microvessels in the brain of the irradiated mouse 2 days post exposure and RECA-1 immunostaining was similarly used to visualize microvessels in the brain of the irradiated rat 1-month post exposure. Confocal microscopy, image deconvolution and 3-dimensional rendering methods were used to define vascular structure in a ∼4 × 10(7) μm(3) defined region of the brain. Quantitative analysis of these 3D images revealed that irradiation caused significant short- and long-term reductions in capillary density, diameter and volume. In mice, irradiation reduced mean vessel volume from 2,250 to 1,470 μm(3) and mean vessel diameter from 5.0 to 4.5 μm, resulting in significant reductions of 34% and 10%, in the hippocampus respectively. The number of vessel branch points and area was also found to also drop significantly in mice 2 days after irradiation. For rats, immunostaining revealed a significant, three-fold drop in capillary density 1 month after exposure compared to controls. Such radiation-induced disruption of the CNS microvasculature may be contributory if not causal to any number of neurocognitive side effects that manifest in cancer patients following cranial radiotherapy. This study demonstrates the utility of two distinct methodologies for quantifying these important adverse effects of radiotherapy. Environ. Mol. Mutagen. 57:341-349, 2016. © 2016 Wiley Periodicals, Inc