Designing Chromatin Substrates for Structural and Functional Analysis of Regulatory Complexes

The processes behind cellular differentiation and the maintenance of cellular identity are both thought to be regulated by chromatin modification. Furthering our understanding of these mechanisms could offer invaluable insights into both cancer and development. This study will focus on a specific group of proteins called polycomb repressive complexes, which help to control gene expression through the modifications they exert on chromatin. Polycomb group proteins consist of three families: PRC1 which deposits ubiquitin on H2AK119, PRC2 which mono-, di-, and tri-methylates H3K27, and PR-DUB which acts as a proofreading mechanism, removing misplaced ubiquitin on H2A. The exact mechanism by which PRC1, an E3 ubiquitin ligase, is recruited to and activated on chromatin is poorly understood. To better understand how PRC1 acts on chromatin, chromatin substrates were designed and assembled for experimental analysis. All four histones making up the histone octamer, as well as modified histones capable of crosslinking with ubiquitin, were cloned, expressed, and purified using a wide variety of biochemical techniques. This was used to form the nucleosome core particle which can undergo functional and structural assays in conjunction with PRC1-RYBP. This PRC1-RYBP was found to be active, capable of binding to CpG rich nucleosome sequences and modifying chromatin by ubiquitinating H2A. Preliminary tests that explored the interaction of PRC1-RYBP with the nucleosome found that PRC1-RYBP had a higher affinity for the nucleosome modified with ubiquitin on H2A than for the wild-type nucleosome. This affinity is higher than previously thought, binding much more tightly than other E3 ligases. More work involving PRC1, including additional activity and binding assays along with negative stain and cryo-EM structural analysis will continue to be carried out in the future, providing a deeper look into the critical role that PRCs play in controlling gene expression.&nbsp;</p

Investigating Radiation Damage in the Zircon (U-Th)/He Thermochronometer with Raman Spectroscopy

Radiation damage has a strong influence on He diffusion kinetics and the temperature sensitivity of (U-Th)/He thermochronometers. Understanding these effects is critical for the accurate interpretation of (U-Th)/He datasets and can lead to more detailed thermal history reconstructions. This information is particularly important for settings with protracted thermal histories, such as the Kaapvaal Craton, where U and Th-rich minerals have accumulated significant radiation damage. Models for how radiation damage influences He diffusion kinetics have been published for apatite (Flowers et al., 2009) and zircon (Guenthner et al., 2013). However, the kinetic model for zircon is less calibrated at the higher damage end of the spectrum. Negative date-effective uranium (eU) correlations in zircon from the Kaapvaal Craton suggest the variable influence of radiation damage on the data. I used Raman spectroscopy to quantitatively and qualitatively characterize the variable magnitudes of radiation damage in this zircon suite. Our measurements of Raman Spectra full width at half maximum (FWHM) show a range of closure temperatures spanning ~50 ºC. This variation can explain the presence of negative date-eU correlations. Furthermore, our research showed that Raman spectroscopy could characterize zonation in radiation damage

COVID-19 infection and cardiometabolic complications: short- and long-term treatment and management considerations

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Effects of robotic-assisted gait training on the central vascular health of individuals with spinal cord injury: A pilot study.

Objective: To investigate the effect of a short-term, robotic-assisted (exoskeleton) gait training (RGT) program on central and peripheral hemodynamic measures in patients with spinal cord injury (SCI). Design: Parallel group, non-randomized trial with before (baseline) and after (follow-up) assessments. Setting: Single-center, community-based neuro-physiotherapy practice. Participants: Twelve individuals with SCI (ASI A to C). Interventions: Participants completed either a 5-day RGT program plus physiotherapy (n = 6), or a usual care physiotherapy only program (control group; n = 6). The RGT program consisted of daily 60-min physiotherapy and 90-min of RGT. Outcome measures were measured before and after the rehabilitation program. Main outcome measure(s): The primary outcome measure was arterial wave reflection (Augmentation index [AIx]), with central and peripheral blood pressures also reported. Data are presented as mean (SD) and effect sizes (partial eta squared; η2 p). Results: There was a significant reduction in AIx (30 ± 18–21 ± 15%; η2 p=0.75) and mean arterial pressure (89 ± 11–82 ± 10 mmHg; η2 p=0.47) following completion of the RGT program (both P &lt; 0.05). There were no changes in these measures for the control group. Although not significantly different, medium to large effects were observed in favor of RGT for all other central and peripheral measures (η2 p=0.06–0.21), except for heart rate and pulse pressure (η2 p&lt;0.04). Conclusions: RGT using an exoskeleton is a promising therapy for improving cardiovascular health in patients with SCI. Specifically, this study indicates decreased arterial wave reflection and supports the need for larger randomized controlled trials

The validity and reliability of continuous-wave near -infrared spectroscopy for the assessment of leg blood volume during an orthostatic challenge.

Near-infrared spectroscopy (NIRS) can potentially be used to assess the cardiovascular autonomic system by monitoring orthostatic challenge-induced shifts in lower limb blood volume. However, in order to be of clinical utility the test must be valid, reliable, and relatively simple to conduct. Purpose: To induce lower limb blood volume shifts using a 10min 70o head-up tilt, and: (1) in the soleus, determine the validity of an inexpensive continuous wave (cw)-NIRS device by comparing to a criterion frequency-domain (fd-) NIRS device, (2) determine the between-day reliability of soleus assessments obtained from cw-NIRS and fd-NIRS; and, (3) compare the between-day reliability for fd-NIRS assessments obtained at the soleus (standard) and gastrocnemius (simpler alternative). Methods: Fifteen non-smoking healthy adults were tested on 3 different mornings, under standardized conditions, separated by a maximum of 7 days. Total haemoglobin concentration (tHb) was continuously monitored bi-laterally in the medial soleus using cw-NIRS and fd-NIRS. For site comparison, tHb was measured in the medial gastrocnemius using fd-NIRS. Results: (1) The area under the curve (AUC) for cw-NIRS and fd-NIRS assessments at the soleus were not significantly different (p =.619). (2) The criterion (0.75) intra-class correlation coefficient (ICC) was exceeded for both cw-NIRS and fd-NIRS. (3) The criterion ICC was exceeded for both soleus and gastrocnemius assessments. Conclusion: Continuous-wave NIRS can be used to monitor orthostatic stress-induced shifts in lower leg blood volume with acceptable validity and reliability. This orthostatic test may present a relatively simple and inexpensive approach for assessing the cardiovascular autonomic nervous system

The Association between Y-Balance and the Delos Postural Proprioceptive System in Professional Basketball Players

Background/Purpose: Lower extremity injury is common in professional basketball. The Y-Balance Test (YBT) and the Delos Postural Proprioceptive System (DPPS) have been purported to assess dynamic postural control and balance, which has been associated with injury in elite athletics. It has been reported that performance on balance assessments is influenced by many factors that include mobility, strength, and proprioception. The purpose of this exploratory study was to investigate the relationship between DPPS and YBT performance in professional basketball players. Methods: 13 professional basketball players (age=25.5 yrs +/- 3.9, height = 2.00 m +/- .079 weight = 99.89 kg +/- 12.38, BMI = 24.66 +/- 1.89) participated. YBT and Delos Measurements were completed as part of preseason mobility screening prior to the 2018-19 NBA season. A Friedman’s ANOVA was used to investigate the differences between the DPPS and YBT, using individuals scoring below 1SD on both the static and dynamic Delos cutoff score (90) for both left and right lower extremities. The ICC was used to investigate the relationship between (right or left) dynamic and static Delos scores to scores on the respective y-balance test. Results: The Delos Static and Dynamic tests for the right side were statistically different than the YBT composite scores. The ICC for the Delos static (right) score was -.910 and the Delos dynamic (right) score was -.999 with a 95% confidence interval from -7.127 to .962 (F(2,10)=.671,p Conclusion: This exploratory study suggests that the direct correlation between the YBT and the DPPS should be further investigated. The YBT may be an assessment that is more sensitive to factors related to strength and mobility while the DPPS may be more representative of proprioceptive function. Clinical Relevance: Balance and mobility is influenced by many factors. Understanding the association between the Delos and Y-Balance can give clinicians a better understanding of the utility and value these assessments when working with elite athletes.https://ecommons.udayton.edu/dpt_symposium/1001/thumbnail.jp

Food Consumption Patterns and Body Composition in Children: Moderating Effects of Prop Taster Status

This cross-sectional study determined whether 6-n-propylthiouracil (PROP) taster status moderates the relationship between food consumption patterns and body composition in children. Children were recruited (n = 342, 50% female, 8–10 y) from across New Zealand. Using a food frequency questionnaire, these food consumption patterns were derived: Processed Foods, Fruit and Vegetables, and Breakfast Foods. Body composition variables included: body fat (%), fat mass (kg), fat mass index (FMI, kg/m2), body mass index (kg/m2) and waist to height ratio (W:Ht). Following adjustment for confounders, Processed Foods were positively associated with %fat (p = 0.015), fat mass (p = 0.004) and FMI (p = 0.016). Taste test strips determined PROP status. For Breakfast Foods, there were small negative associations with all body composition variables (p ≤ 0.001 to 0.037). The population sample was also stratified by PROP taster status. For the non-tasters, there were small to moderate negative associations between Breakfast Foods and each body composition variable (p = 0.003–0.045) except W:Ht (p = 0.112), and these relationships were stronger for girls compared to boys. For the tasters, there were small to moderate positive associations between Processed Foods with %fat (p = 0.030), fat mass (p ≤ 0.001) and FMI (p = 0.014). In conclusion, sensitivity to bitterness may moderate the relationship between food consumption patterns and body composition in children

Physical Activity, Mental Health and Wellbeing of Adults within and during the Easing of COVID-19 Restrictions, in the United Kingdom and New Zealand

Physical activity (PA) participation was substantially reduced at the start of the COVID-19 pandemic. The purpose of this study was to assess the association between PA, mental health, and wellbeing during and following the easing of COVID-19 restrictions in the United Kingdom (UK) and New Zealand (NZ). In this study, 3363 adults completed online surveys within 2–6 weeks of initial COVID-19 restrictions (April/May 2020) and once restrictions to human movement had been eased. Outcome measures included the International Physical Activity Questionnaire Short-Form, Depression Anxiety and Stress Scale-9 (mental health) and World Health Organisation-5 Wellbeing Index. There were no differences in PA, mental health or wellbeing between timepoints (p > 0.05). Individuals engaging in moderate or high volume of PA had significantly better mental health (−1.1 and −1.7 units, respectively) and wellbeing (11.4 and 18.6 units, respectively) than individuals who engaged in low PA (p < 0.001). Mental health was better once COVID-19 restrictions were eased (p < 0.001). NZ had better mental health and wellbeing than the UK (p < 0.001). Participation in moderate-to-high volumes of PA was associated with better mental health and wellbeing, both during and following periods of COVID-19 containment, compared to participation in low volumes of PA. Where applicable, during the current or future pandemic(s), moderate-to-high volumes of PA should be encouraged

Targeting Sedentary Behavior in Minority Populations as a Feasible Health Strategy during and beyond COVID-19: On Behalf of ACSM-EIM and HL-PIVOT

Increased sedentary behavior has been an unintended consequence of social and physical distancing restrictions needed to limit transmission of SARS-CoV-2, the novel coronavirus that causes COVID-19. Sedentary behavior is defined as any waking behavior characterized by an energy expenditure ≤1.5 METs while in a sitting, reclining, or lying posture. These restrictions negatively affect peoples’ cardiometabolic and mental health and disproportionately affect certain sectors of the population, including racial/ethnic minorities. In part, the higher risk for complications of COVID-19 could be the result of an increased prevalence of comorbid diseases. Further, regular participation and adherence to current physical activity guidelines, defined as at least 150 min·wk−1 of moderate-intensity physical activity or muscle strengthening activities on 2 or more days a week, is challenging for many and may be especially difficult to achieve during the COVID-19 pandemic. A practical strategy to promote health and well-being during COVID-19 is reducing sedentary behavior. Reducing sedentary behaviors (e.g., breaking up periods of prolonged sitting with light-intensity physical activity) may be more easily achieved than physical activity for all individuals, including individuals of racial/ethnic decent, as it does not require purchasing equipment nor require compromising the physical restrictions necessary to slow the spread of COVID-19. The purpose of this commentary is to argue that sedentary behavior is a feasible, independent target to modify during COVID-19, particularly in minority populations, and to address this behavior we need to consider individual, environmental, and policy-level factors.N/

Physical activity, mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis

ObjectivesTo assess physical activity (PA), mental health and well-being of adults in the United Kingdom (UK), Ireland, New Zealand and Australia during the initial stages of National governments’ Coronavirus disease (COVID-19) containment responses.DesignObservational, cross-sectional.MethodsAn online survey was disseminated to adults (n = 8,425; 44.5 ± 14.8y) residing in the UK, Ireland, New Zealand and Australia within the first 2-6 weeks of government-mandated COVID-19 restrictions. Main outcome measures included: Stages of Change scale for exercise behaviour change; International Physical Activity Questionnaire (short-form); World Health Organisation-5 Well-being Index; and the Depression Anxiety and Stress Scale-9.ResultsParticipants who reported a negative change in exercise behaviour from before initial COVID-19 restrictions to during the initial COVID-19 restrictions demonstrated poorer mental health and well-being compared to those demonstrating either a positive-or no change in their exercise behaviour (p < 0.001). Whilst women reported more positive changes in exercise behaviour, young people (18-29y) reported more negative changes (both p < 0.001). Individuals who had more positive exercise behaviours reported better mental health and well-being (p < 0.001). Although there were no differences in PA between countries, individuals in New Zealand reported better mental health and well-being (p < 0.001).ConclusionThe initial COVID-19 restrictions have differentially impacted upon PA habits of individuals based upon their age and sex, and therefore have important implications for international policy and guideline recommendations. Public health interventions that encourage PA should target specific groups (e.g., men, young adults) who are most vulnerable to the negative effects of physical distancing and/or self-isolation