Ex vivo rapamycin generates apoptosis-resistant donor Th2 cells that persist in vivo and prevent hemopoietic stem cell graft rejection

Because ex vivo rapamycin generates murine Th2 cells that prevent Graft-versus-host disease more potently than control Th2 cells, we hypothesized that rapamycin would generate Th2/Tc2 cells (Th2/Tc2.R cells) that abrogate fully MHC-disparate hemopoietic stem cell rejection more effectively than control Th2/Tc2 cells. In a B6-into-BALB/c graft rejection model, donor Th2/Tc2.R cells were indeed enriched in their capacity to prevent rejection; importantly, highly purified CD4+ Th2.R cells were also highly efficacious for preventing rejection. Rapamycin-generated Th2/Tc2 cells were less likely to die after adoptive transfer, accumulated in vivo at advanced proliferative cycles, and were present in 10-fold higher numbers than control Th2/Tc2 cells. Th2.R cells had a multifaceted, apoptosis-resistant phenotype, including: 1) reduced apoptosis after staurosporine addition, serum starvation, or CD3/CD28 costimulation; 2) reduced activation of caspases 3 and 9; and 3) increased anti-apoptotic Bcl-xL expression and reduced proapoptotic Bim and Bid expression. Using host-versus-graft reactivity as an immune correlate of graft rejection, we found that the in vivo efficacy of Th2/Tc2.R cells 1) did not require Th2/Tc2.R cell expression of IL-4, IL-10, perforin, or Fas ligand; 2) could not be reversed by IL-2, IL-7, or IL-15 posttransplant therapy; and 3) was intact after therapy with Th2.R cells relatively devoid of Foxp3 expression. We conclude that ex vivo rapamycin generates Th2 cells that are resistant to apoptosis, persist in vivo, and effectively prevent rejection by a mechanism that may be distinct from previously described graft-facilitating T cells.     

Cardiovascular evaluation,including resting and exercise electrocardiography,before participation in competitive sports: cross sectional study

Objective To evaluate the clinical usefulness of complete preparticipation cardiovascular screening in a large cohort of sports participants.Design Cross sectional study of data over a five year period.Setting Institute of Sports Medicine in Florence, Italy.Participants 30 065 (23 570 men) people seeking to obtain clinical eligibility for competitive sports.Main outcome measures Results of resting and exercise 12 lead electrocardiography.Results Resting 12 lead ECG patterns showed abnormalities in 1812 (6%) participants, with the most common abnormalities (>80%) concerning innocent ECG changes. Exercise ECG showed an abnormal pattern in 1459 (4.9%) participants. Exercise ECG showed cardiac anomalies in 1227 athletes with normal findings on resting ECG. At the end of screening, 196 (0.6%) participants were considered ineligible for competitive sports. Among the 159 participants who were disqualified at the end of the screening for cardiac reasons, a consistent proportion (n=126, 79.2%) had shown innocent or negative findings on resting 12 lead ECG but clear pathological alterations during the exercise test. After adjustment for possible confounders, logistic regression analysis showed that age >30 years was significantly associated with an increased risk of being disqualified for cardiac findings during exercise testing.Conclusions Among people seeking to take part in competitive sports, exercise ECG can identify those with cardiac abnormalities. Follow-up studies would show if disqualification of such people would reduce the incidence of CV events among athletes.     

Cross-species gene-family fluctuations reveal the dynamics of horizontal transfers

Prokaryotes vary their protein repertoire mainly through horizontal transfer and gene loss. To elucidate the links between these processes and the cross-species gene-family statistics, we perform a large-scale data analysis of the cross-species variability of gene-family abundance (the number of members of the family found on a given genome). We find that abundance fluctuations are related to the rate of horizontal transfers. This is rationalized by a minimal theoretical model, which predicts this link. The families that are not captured by the model show abundance profiles that are markedly peaked around a mean value, possibly because of specific abundance selection. Based on these results, we define an abundance variability index that captures a family''s evolutionary behavior (and thus some of its relevant functional properties) purely based on its cross-species abundance fluctuations. Analysis and model, combined, show a quantitative link between cross-species family abundance statistics and horizontal transfer dynamics, which can be used to analyze genome ‘flux’. Groups of families with different values of the abundance variability index correspond to genome sub-parts having different plasticity in terms of the level of horizontal exchange allowed by natural selection.     

Possible Brucellosis in an Early Hominin Skeleton from Sterkfontein,South Africa

We report on the paleopathological analysis of the partial skeleton of the late Pliocene hominin species Australopithecus africanus Stw 431 from Sterkfontein, South Africa. A previous study noted the presence of lesions on vertebral bodies diagnosed as spondylosis deformans due to trauma. Instead, we suggest that these lesions are pathological changes due to the initial phases of an infectious disease, brucellosis. The macroscopic, microscopic and radiological appearance of the lytic lesions of the lumbar vertebrae is consistent with brucellosis. The hypothesis of brucellosis (most often associated with the consumption of animal proteins) in a 2.4 to 2.8 million year old hominid has a host of important implications for human evolution. The consumption of meat has been regarded an important factor in supporting, directing or altering human evolution. Perhaps the earliest (up to 2.5 million years ago) paleontological evidence for meat eating consists of cut marks on animal remains and stone tools that could have made these marks. Now with the hypothesis of brucellosis in A. africanus, we may have evidence of occasional meat eating directly linked to a fossil hominin.     

Are elite track and field athletes on track? The impact of COVID-19 outbreak on sleep behavior and training characteristics

The Covid-19 outbreak forced many governments to enter a nationwide lockdown. The aim of this study was to evaluate, by means of a survey, changes in sleep parameters and physical activity characteristics of elite track and field athletes in three periods: before the lockdown (T0), during the lockdown (09th March – 03rd May 2020, T1) and the first month after the lockdown (T2). This study was conducted from May 2020 to June 2020 and data were collected using an offline survey with 89 elite track and field athletes (mean age: 24.7 ± 5.4; n = 43 males; n = 46 females). The survey consisted of demographic data and questions on physical activity and sleep behavior at T0, T1 and T2. Athletes reported lower sleep quality scores at T1 compared to T0 and T2 (p < 0.0001) and registered delayed bedtime, wake-up time and longer sleep latency during the lockdown compared to pre-lockdown and post-lockdown whereas no changes in total sleep time were reported. No inter-group differences were detected in sleep characteristics between short- and long-term disciplines and between genders. The weekly training volume decreased from 16.1 ± 5.7 hours at T0 to 10.7 ± 5.7 hours at T1 (p < 0.0001) whereas no significant differences were detected in training volume during the lockdown in relation to the square footage of the house (p = 0.309). Alcohol (p = 0.136) and caffeine intake (p = 0.990) and use of electronic devices (p = 0.317) were similar pre-, during, and post-lockdown. The unprecedented circumstances of the Covid-19 pandemic had negative impacts on the Italian track and field athletes’ sleep and training volumes.     

Predicting the actigraphy-based acrophase using the Morningness–Eveningness Questionnaire (MEQ) in college students of North Italy

Actigraphy is the reference objective method to measure circadian rhythmicity. One simpler subjective approach to assess the circadian typology is the Morningness–Eveningness Questionnaire (MEQ) by Horne and Ostberg. In this study, we compared the MEQ score against the actigraphy-based circadian parameters MESOR, amplitude and acrophase in a sample of 54 students of the University of Milan in Northern Italy. MEQ and the acrophase resulted strongly and inversely associated (r = ?0.84, p < 0.0001), and their relationship exhibited a clear-cut linear trend. We thus used linear regression to develop an equation enabling us to predict the value of the acrophase from the MEQ score. The parameters of the regression model were precisely estimated, with the slope of the regression line being significantly different from 0 (p < 0.0001). The best-fit linear equation was: acrophase (min) = 1238.7–5.49·MEQ, indicating that each additional point in the MEQ score corresponded to a shortening of the acrophase of approximately 5 min. The coefficient of determination, R², was 0.70. The residuals were evenly distributed and did not show any systematic pattern, thus indicating that the linear model yielded a good, balanced prediction of the acrophase throughout the range of the MEQ score. In particular, the model was able to accurately predict the mean values of the acrophase in the three chronotypes (Morning-, Neither-, and Evening-types) in which the study subjects were categorized. Both the confidence and prediction limits associated to the regression line were calculated, thus providing an assessment of the uncertainty associated with the prediction of the model. In particular, the size of the two-sided prediction limits for the acrophase was about ±100 min in the midrange of the MEQ score. Finally, k-fold cross-validation showed that both the model’s predictive ability on new data and the model’s stability to changes in the data set used for parameter estimation were good. In conclusion, the actigraphy-based acrophase can be predicted using the MEQ score in a population of college students of North Italy.