Effects of Nitrate Supplementation on In Vivo Muscle Torque Recovery From BaCl2-Induced Injury

During repair from muscle injury, muscle satellite cells depend on nitric oxide production by immune cells to proliferate and differentiate. Nitrate supplementation has been shown to improve muscle endurance and oxygen consumption, but little is known about the ability of nitrate supplementation to interfere with muscle regeneration following injury. PURPOSE: To investigate whether nitrate supplementation affects muscle recovery of force after muscle injury produced by intramuscular injection of barium chloride. METHODS: Transgenic male mice (12 weeks old) that express Td-Tomato fluorescent protein in Pax7+ cells (i.e., satellite cells; Pax7CreER-Ai9 mice) were treated with tamoxifen (2 mg in corn oil, i.p.) once a day for 5 days. Four days after the last tamoxifen injection, both legs were subjected to stimulation of the peroneal nerve to evoke contractions of the anterior crural muscles at different frequencies of stimulation (1-200 Hz; i.e., Torque-frequency curve), followed by intramuscular injections of 1.2% BaCl2 (w/v) to produce injury of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of the right leg. The contralateral leg served as a non-injured control. Torque-frequency curves were tested for both legs on days 2, 7, 14 and 21 post injury. At day 21, mice were euthanized, and muscles were dissected for histology (TA) and ex-vivo muscle contractility (EDL). A group of mice was treated with 1 g/L of NaNO3 in drinking water (nitrate group) 1 week before muscle injury, and a second group of mice was not treated (water group). RESULTS: Mice treated with NaNO3 (nitrate group) showed smaller torque in the non-injured leg compared to water group (103 ± 3 vs 84 ± 2 Nmm/kg, for water vs nitrate groups, respectively). However, the torque produced by the injured leg normalized by the torque developed by the non-injured leg was not different between groups on days 2 (28 ± 13% vs 25 ± 1%), 7 (41 ± 4% vs 35 ± 2%), 14 (81 ± 7% vs 87 ± 1%) and 21 (104 ± 3% vs 105 ± 3%) for water and nitrate groups respectively. CONCLUSION: The data suggest that nitrate supplementation decreases nerve-stimulated torque development in uninjured leg but does not change the recovery of torque after BaCl2 injury. Support: TRDRP grant # T29KT0397CA (to L.N.

Enabling violence: the ethics of writing and reading rape in South Africa

This thesis is concerned with describing the stakes of reading, writing and criticising fictional depictions of rape in a country plagued by high levels of sexual violence. I consider the capacity of rape representations to cause harm to women and rape survivors, and worsen the various injuries suffered by survivors as a direct or indirect consequence of rape. The possibility of such harm prompts me to examine the role and responsibilities of readers and critics in facilitating or preventing such harm. I further discuss the potential strategies of harm prevention that readers of novelistic portrayals of rape might adopt as well as the positive outcomes that such reading strategies make possible, and which might balance out the risks that accompany them. My description of the potential harm of rape representations combines postmodern critical feminist analysis with Miranda Fricker’s work on epistemic justice and Judith Herman’s work on trauma in order to illustrate the way that these representations shape our conception of rape in a manner that affects everything from how it is enacted to our treatment of survivors to the possibility of their recovery from posttraumatic stress disorder. In order to situate my analysis in the context of South African literature and to explore the notion of responsibility in relation to the writing of scenes of rape, I utilise a close reading of J.M. Coetzee’s Disgrace. Furthermore, I discuss the utility and limits of the critical feminist strategy of using a normative critical approach to rape representations in order to prevent harm. Ultimately, I argue that the use of such a strategy, along with the development of a purpose-honed adaptive critical style, is essential to the fulfilment of our responsibilities as readers and to the prevention of further suffering

Enabling violence: the ethics of writing and reading rape in South Africa

This thesis is concerned with describing the stakes of reading, writing and criticising fictional depictions of rape in a country plagued by high levels of sexual violence. I consider the capacity of rape representations to cause harm to women and rape survivors, and worsen the various injuries suffered by survivors as a direct or indirect consequence of rape. The possibility of such harm prompts me to examine the role and responsibilities of readers and critics in facilitating or preventing such harm. I further discuss the potential strategies of harm prevention that readers of novelistic portrayals of rape might adopt as well as the positive outcomes that such reading strategies make possible, and which might balance out the risks that accompany them. My description of the potential harm of rape representations combines postmodern critical feminist analysis with Miranda Fricker’s work on epistemic justice and Judith Herman’s work on trauma in order to illustrate the way that these representations shape our conception of rape in a manner that affects everything from how it is enacted to our treatment of survivors to the possibility of their recovery from posttraumatic stress disorder. In order to situate my analysis in the context of South African literature and to explore the notion of responsibility in relation to the writing of scenes of rape, I utilise a close reading of J.M. Coetzee’s Disgrace. Furthermore, I discuss the utility and limits of the critical feminist strategy of using a normative critical approach to rape representations in order to prevent harm. Ultimately, I argue that the use of such a strategy, along with the development of a purpose-honed adaptive critical style, is essential to the fulfilment of our responsibilities as readers and to the prevention of further suffering

Single-Leg Resistance Exercise Training in Mice Leads to a Fast Increase in In Vivo Torque of Anterior Crural Muscles

Resistance exercise is known to produce muscle hypertrophy. However, little is known about the role of muscle satellite cells in generating new myofibers or in incorporating satellite cells to live myofibers during exercise training. PURPOSE: To investigate whether single-leg resistance exercise training can activate the incorporation of muscle satellite cells in mice. METHODS: Transgenic male mice (12 weeks old) that express Td-Tomato fluorescent protein in Pax7+ (i.e., satellite cells) cells (Pax7CreER-Ai9) were treated with tamoxifen (2 mg in corn oil, i.p.) once a day for 5 days. Three days later, mice were single-leg exercise trained (i.e stimulation of the peroneal nerve of the right leg of each mouse to evoke fused tetanic contractions [100 Hz] of the anterior crural muscles), 3x per week for either 1 or 2 weeks. Each training session was composed of 3-s contractions with 7 s recovery between contractions, 10 contractions each set, 5 sets with 5 min rest between sets. Before the first training session and 3 days after the last training session (1 week or 2 weeks training), torque produced by the ankle was measured at different frequencies of pulse-stimulation (1-200 Hz), mice were euthanized, and muscles were frozen for histological measurements. RESULTS: During each session of training, peak torque developed at the last contraction was ~30% of the torque developed in the initial contraction of the session suggesting fatigue development. Between sessions of training, initial torque was not significantly different suggesting that muscle recovered function between sessions. Torque measurements at different frequencies of stimulation 3 days after 1 week or 2 weeks of training showed a ~50% increase in maximal tetanic torque relative to the mice body weight, after 1 week of training but there were no additional changes at 2 weeks of training. Tibialis anterior muscle cross sectional area and number of Td-tomato positive myofibers were also measured in these mice. CONCLUSION: Resistance exercise training in mice by using single-leg electrical stimulations leads to a fast (i.e., 1 week) increase in muscle force development

Meiosis in allopolyploid Arabidopsis suecica

Polyploidy is a major force shaping eukaryote evolution but poses challenges for meiotic chromosome segregation. As a result, first-generation polyploids often suffer from more meiotic errors and lower fertility than established wild polyploid populations. How established polyploids adapt their meiotic behaviour to ensure genome stability and accurate chromosome segregation remains an active research question. We present here a cytological description of meiosis in the model allopolyploid species Arabidopsis suecica (2n = 4x = 26). In large part meiosis in A. suecica is diploid-like, with normal synaptic progression and no evidence of synaptic partner exchanges. Some abnormalities were seen at low frequency, including univalents at metaphase I, anaphase bridges and aneuploidy at metaphase II; however, we saw no evidence of crossover formation occurring between non-homologous chromosomes. The crossover number in A. suecica is similar to the combined number reported from its diploid parents Arabidopsis thaliana (2n = 2x = 10) and Arabidopsis arenosa (2n = 2x = 16), with an average of approximately 1.75 crossovers per chromosome pair. This contrasts with naturally evolved autotetraploid A. arenosa, where accurate chromosome segregation is achieved by restricting crossovers to approximately 1 per chromosome pair. Although an autotetraploid donor is hypothesized to have contributed the A. arenosa subgenome to A. suecica, A. suecica harbours diploid A. arenosa variants of key meiotic genes. These multiple lines of evidence suggest that meiosis in the recently evolved allopolyploid A. suecica is essentially diploid like, with meiotic adaptation following a very different trajectory to that described for autotetraploid A. arenosa.ISSN:0960-7412ISSN:1365-313

CDKG1 Is Required for Meiotic and Somatic Recombination Intermediate Processing in Arabidopsis

The Arabidopsis (Arabidopsis thaliana) cyclin-dependent kinase G1 (CDKG1) is necessary for recombination and synapsis during male meiosis at high ambient temperature. In the cdkg1-1 mutant, synapsis is impaired and there is a dramatic reduction in the number of class I crossovers, resulting in univalents at metaphase I and pollen sterility. Here, we demonstrate that CDKG1 is necessary for the processing of recombination intermediates in the canonical ZMM recombination pathway and that loss of CDKG1 results in increased class II crossovers. While synapsis and events associated with class I crossovers are severely compromised in a cdkg1-1 mutant, they can be restored by increasing the number of recombination intermediates in the double cdkg1-1 fancm-1 mutant. Despite this, recombination intermediates are not correctly resolved, leading to the formation of chromosome aggregates at metaphase I. Our results show that CDKG1 acts early in the recombination process and is necessary to stabilize recombination intermediates. Finally, we show that the effect on recombination is not restricted to meiosis and that CDKG1 is also required for normal levels of DNA damage-induced homologous recombination in somatic tissues

Preliminary Findings from the Gulf War Women\u27s Cohort: Reproductive and Children\u27s Health Outcomes among Women Veterans

Reproductive outcomes, such as preterm birth, miscarriage/stillbirth, and pre-eclampsia, are understudied in veterans, particularly among Gulf War veterans (GWVs). During deployment, women GWVs were exposed to toxicant and nontoxicant exposures that may be associated with adverse reproductive and developmental outcomes. The data come from a survey of 239 participants from northeastern and southern U.S. cohorts of women veterans. The questionnaire collected information about the service history, current and past general health, reproductive and family health, demographic information, and deployment exposures. Odds ratios were computed with 95% confidence intervals between exposures in theater and reproductive/children\u27s health outcomes. GWVs experienced adverse reproductive outcomes: 25% had difficulty conceiving, and 31% had a pregnancy that ended in a miscarriage or stillbirth. Pregnancy complications were common among GWVs: 23% had a high-risk pregnancy, and 16% were diagnosed with pre-eclampsia. About a third of GWVs reported their children (38%) had a developmental disorder. Use of pesticide cream during deployment was associated with higher odds of all reproductive and developmental outcomes. The results demonstrate that GWVs experienced reproductive and children\u27s health outcomes at potentially high rates, and exploratory analyses suggest pesticide exposure as associated with higher odds of adverse reproductive outcomes. Future longitudinal studies of women veterans should prioritize examining reproductive and children\u27s health outcomes

Perceptions and experiences of medical student first responders: a mixed methods study

Context Medical Student First Responders (MSFRs) are volunteers who respond to emergency calls, managing patients before ambulance staff attend. The MSFR role provides opportunities to manage acutely unwell patients in the prehospital environment, not usually offered as part of formal undergraduate medical education. There are few previous studies describing activities or experiences of MSFRs or exploring the potential educational benefits. We aimed to investigate the activity of MSFRs and explore their experiences, particularly from an educational perspective. Methods We used a mixed methods design, combining quantitative analysis of ambulance dispatch data with qualitative semi-structured interviews of MSFRs. Dispatch data were from South Central and East Midlands Ambulance Service NHS Trusts from 1st January to 31st December 2019. Using propensity score matching, we compared incidents attended by MSFRs with those attended by other Community First Responders (CFRs) and ambulance staff. We interviewed MSFRs from five English (UK) medical schools in those regions about their experiences and perceptions and undertook thematic analysis supported by NVivo 12. Results We included 1,939 patients (median age 58.0 years, 51% female) attended by MSFRs. Incidents attended were more urgent category calls (category 1 n = 299, 14.9% and category 2 n = 1,504, 77.6%), most commonly for chest pain (n = 275, 14.2%) and shortness of breath (n = 273, 14.1%). MSFRs were less likely to attend patients of white ethnicity compared to CFRs and ambulance staff, and more likely to attend incidents in areas of higher socioeconomic deprivation (IMD – index of multiple deprivation) (p < 0.05). Interviewees (n = 16) consistently described positive experiences which improved their clinical and communication skills. Conclusion MSFRs’ attendance at serious medical emergencies provide a range of reported educational experiences and benefits. Further studies are needed to explore whether MSFR work confers demonstrable improvements in educational or clinical performance