Medical Doctrines of Heredity.

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Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis

Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2. Moreover, following isolation of preleukemic hematopoietic stem and progenitor cells irradiated in their native microenvironment, we identified the presence of Sfpi1 point mutations within a subpopulation of these preleukemic cells expanding rapidly (increasing from 6% to 55% in 21 days in peripheral blood in one case), hence identifying for the first time the presence of such cells within a living animal. Importantly, we also report a previously undescribed gender difference in the phenotype of the preleukemic cells and leukemia, suggesting a gender imbalance in the radiation-induced leukemic target cell. In conclusion, we provide novel insights into the sequence of molecular events occurring during the (radiation-induced) leukemic clonal evolution

T-lymphocyte-rich thymoma and myasthenia gravis in a Siberian tiger (Panthera tigris altaica)

A 10-year-old captive male Siberian tiger (Panthera tigris altaica) presented with acute onset collapse, vomiting and dyspnoea, preceded by a 6-month period of progressive muscle wasting. Following humane destruction, post-mortem examination revealed a large multilobulated mass in the cranial mediastinum, which was diagnosed as a T-lymphocyte-rich thymoma with the aid of immunohistochemistry. Retrospective serology for acetylcholine receptor antibodies (titre 3.90 nmol/l) confirmed a diagnosis of thymoma-associated myasthenia gravis. Thymomas are reported rarely in wild carnivores, but when detected they appear to be similar in morphology to those seen in domestic carnivores and may also be accompanied by paraneoplastic syndromes. The clinical signs of myasthenia gravis in the tiger were consistent with those reported in cats and dogs and the condition is proposed as an important differential diagnosis for generalized weakness in captive Felidae

Three Week Hypergravity Training Intervention Decreases Ground Contact Time During Repeated Jumping and Improves Sprinting and Shuttle Running Performance

International Journal of Exercise Science 9(2): 149-158, 2016. This study examined the effects of a non-traditional training method, hypergravity training (HT), on anaerobic performance. Highly active men (n = 9) completed a 3 week HT protocol in which weighted vests were worn 8 h/day, 4+ days/week separate from training. Vest loads were 11.2 ± 0.6% of body mass during week one, and increased to 13.2 ± 0.7% (week 2), and 16.1 ± 0.4% (week 3). Performance testing included power clean 1-RM (PC), counter movement jumps, 4 continuous jumps, 36.6 m sprints (SP), a 137.2 m short shuttle run (SSR), and a 274.3 m long shuttle run (LSR). A 3 week non-hypergravity training period (NHT) proceeded HT. Baseline SP improved from 4.69 ± 0.29 s to 4.58 ± 0.22 s post-treatment, and regressed after NHT (4.69 ± 0.24 s) (p = 0.006, ES = 1.80). Improvements in SSR (p = 0.012, ES = 1.71) occurred from baseline (26.7 ± 1.5 s) to post-treatment (26.2 ± 1.4 s), followed by a return to near-baseline values (26.9 ± 1.8 s). Jumping tasks displayed similar trends, but no statistical differences and modest effect sizes (0.51 - 0.62) were found except for improved ground contact time during repeated jumps post-HT (ES = 2.26). PC and LSR performances did not improve. Three weeks of HT significantly enhanced short running task performances and decreased ground contact time between 4 continuous jumps. HT may be incorporated into training programs prior to key points in an athletic season without hindering the quality of regular training session activities

Shared Ageing Research Models (ShARM) : a new facility to support ageing research

In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing. However, the time and cost needed to rear aged cohorts can limit research opportunities. Sharing of resources can provide an ethically and economically superior framework to overcome some of these issues but requires dedicated infrastructure. Shared Ageing Research Models (ShARM) (www.ShARMUK.org) is a new, not-for-profit organisation funded by Wellcome Trust, open to all investigators. It collects, stores and distributes flash frozen tissues from aged murine models through its biorepository and provides a database of live ageing mouse colonies available in the UK and abroad. It also has an online environment (MICEspace) for collation and analysis of data from communal models and discussion boards on subjects such as the welfare of ageing animals and common endpoints for intervention studies. Since launching in July 2012, thanks to the generosity of researchers in UK and Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000 mice registered in live ageing colonies. By providing the appropriate support, ShARM has been able to bring together the knowledge and experience of investigators in the UK and Europe to maximise research outputs with little additional cost and minimising animal use in order to facilitate progress in ageing research

Performance and perceptual responses of collegiate female soccer players to a practical external and internal cooling protocol

International Journal of Exercise Science 8(4): 331-340, 2015. This study examined practical pre- and mid practice cooling interventions on running performance, perceived exertion (RPE), and thermal sensation (TS) during soccer. During two formal pre-season practices female, NCAA Division II soccer players participated in three, 15 min scrimmage bouts followed by a 4th 10 min bout. Following the 1st, 2nd, and 3rd bouts, 8 field position players completed competitive sets of two, 30 yard sprints against other team members with time recorded between 5 and 30 yards. After the 4th bout, players completed an indoor shuttle running beep test (BT). In the treatment group (COOL) ice towels (IT) were applied to the head and neck regions and draped across both legs for 10 min following a standardized warm-up and for 10 min during a 15 min break between the 2nd and 3rd scrimmage sessions. Sport beverage slurries (350 mL; -0.3 °C, ~6% carbohydrate) were also served during IT cooling for COOL; while the control (CON) received no IT and drank the same ,uncooled sport beverage. No main effect was found for sprint performance (COOL = 3.55 ± 0.16 s; CON = 3.51 ± 0.07 s; P = 0.51) or numbers of reps completed in the BT (COOL = 17.6 ± 5.6; CON = 17.3 ± 6.0; P = 0.88). RPE did not differ following any performance test, but TS was lower following the 3rd sprint bout (P = 0.04) and the BT (P = 0.005) for COOL. COOL promoted lower TS, but had no effect on performance

Impact of contusion injury on intramuscular emm1 group a streptococcus infection and lymphatic spread.

Invasive group A Streptococcus (iGAS) is frequently associated with emm1 isolates, with an attendant mortality of around 20%. Cases occasionally arise in previously healthy individuals with a history of upper respiratory tract infection, soft tissue contusion, and no obvious portal of entry. Using a new murine model of contusion, we determined the impact of contusion on iGAS bacterial burden and phenotype. Calibrated mild blunt contusion did not provide a focus for initiation or seeding of GAS that was detectable following systemic GAS bacteremia, but instead enhanced GAS migration to the local draining lymph node following GAS inoculation at the same time and site of contusion. Increased migration to lymph node was associated with emergence of mucoid bacteria, although was not specific to mucoid bacteria. In one study, mucoid colonies demonstrated a significant increase in capsular hyaluronan that was not linked to a covRS or rocA mutation, but to a deletion in the promoter of the capsule synthesis locus, hasABC, resulting in a strain with increased fitness for lymph node migration. In summary, in the mild contusion model used, we could not detect seeding of muscle by GAS. Contusion promoted bacterial transit to the local lymph node. The consequences of contusion-associated bacterial lymphatic migration may vary depending on the pathogen and virulence traits selected