WDR79/TCAB1 plays a conserved role in the control of locomotion and ameliorates phenotypic defects in SMA models

SMN (Survival Motor Neuron) deficiency is the predominant cause of spinal muscular atrophy (SMA), a severe neurodegenerative disorder that can lead to progressive paralysis and death. Although SMN is required in every cell for proper RNA metabolism, the reason why its loss is especially critical in the motor system is still unclear. SMA genetic models have been employed to identify several modifiers that can ameliorate the deficits induced by SMN depletion. Here we focus on WDR79/TCAB1, a protein important for the biogenesis of several RNA species that has been shown to physically interact with SMN in human cells. We show that WDR79 depletion results in locomotion defects in both Drosophila and Caenorhabditis elegans similar to those elicited by SMN depletion. Consistent with this observation, we find that SMN overexpression rescues the WDR79 loss-of-function phenotype in flies. Most importantly, we also found that WDR79 overexpression ameliorates the locomotion defects induced by SMN depletion in both flies and worms. Our results collectively suggest that WDR79 and SMN play evolutionarily conserved cooperative functions in the nervous system and suggest that WDR79/TCAB1 may have the potential to modify SMA pathogenesis

Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma

Objectives: To assess the efficacy of an awake venovenous extracorporeal membrane oxygenation (VV-ECMO) management strategy in preventing clinically relevant barotrauma in patients with coronavirus disease 2019 (COVID-19) with severe acute respiratory distress syndrome (ARDS) at high risk for pneumothorax (PNX)/pneumomediastinum (PMD), defined as the detection of the Macklin-like effect on chest computed tomography (CT) scan. Design: A case series. Setting: At the intensive care unit of a tertiary-care institution. Participants: Seven patients with COVID-19-associated severe ARDS and Macklin-like radiologic sign on baseline chest CT. Interventions: Primary VV-ECMO under spontaneous breathing instead of invasive mechanical ventilation (IMV). All patients received noninvasive ventilation or oxygen through a high-flow nasal cannula before and during ECMO support. The study authors collected data on cannulation strategy, clinical management, and outcome. Failure of awake VV-ECMO strategy was defined as the need for IMV due to worsening respiratory failure or delirium/agitation. The primary outcome was the development of PNX/PMD. Measurements and Main Results: No patient developed PNX/PMD. The awake VV-ECMO strategy failed in 1 patient (14.3%). Severe complications were observed in 4 (57.1%) patients and were noted as the following: intracranial bleeding in 1 patient (14.3%), septic shock in 2 patients (28.6%), and secondary pulmonary infections in 3 patients (42.8%). Two patients died (28.6%), whereas 5 were successfully weaned off VV-ECMO and were discharged home. Conclusions: VV-ECMO in awake and spontaneously breathing patients with severe COVID-19 ARDS may be a feasible and safe strategy to prevent the development of PNX/PMD in patients at high risk for this complication

Characterization of MLO gene family in Rosaceae and gene expression analysis in Malus domestica

Background: Powdery mildew (PM) is a major fungal disease of thousands of plant species, including many cultivated Rosaceae. PM pathogenesis is associated with up-regulation of MLO genes during early stages of infection, causing down-regulation of plant defense pathways. Specific members of the MLO gene family act as PM-susceptibility genes, as their loss-of-function mutations grant durable and broad-spectrum resistance. Results: We carried out a genome-wide characterization of the MLO gene family in apple, peach and strawberry, and we isolated apricot MLO homologs through a PCR-approach. Evolutionary relationships between MLO homologs were studied and syntenic blocks constructed. Homologs that are candidates for being PM susceptibility genes were inferred by phylogenetic relationships with functionally characterized MLO genes and, in apple, by monitoring their expression following inoculation with the PM causal pathogen Podosphaera leucotricha. Conclusions: Genomic tools available for Rosaceae were exploited in order to characterize the MLO gene family. Candidate MLO susceptibility genes were identified. In follow-up studies it can be investigated whether silencing or a loss-of-function mutations in one or more of these candidate genes leads to PM resistance

Large Pelvic Mass in a Female Adolescent: Atypical Presentation and Successful Treatment of Extraskeletal Ewing Sarcoma

Extraskeletal Ewing sarcoma is a rare soft tissue tumor primarily affecting pediatric patients. The treatment is currently based on a multidisciplinary approach which allows, in cases of localized disease, good survival rates. We report the case of a 15-year-old female patient with a rapidly growing suspected pelvic mass misdiagnosed following the preliminary radiological exams, which assessed the findings as a mass of ovarian origin. The girl underwent surgery and, thanks to histopathological, immunohistochemical and real-time polymerase chain reaction (RT-PCR) examinations, it was possible to make the right diagnosis and to administer the best treatment in terms of surgery, chemotherapy and radiotherapy, obtaining a long disease-free interval and no recurrence to date

High intensity intermittent games-based activity and adolescents’ cognition: moderating effect of physical fitness

Background: An acute bout of exercise elicits a beneficial effect on subsequent cognitive function in adolescents. The effect of games-based activity, an ecologically valid and attractive exercise model for young people, remains unknown; as does the moderating effect of fitness on the acute exercise-cognition relationship. Therefore, the aim of the present study was to examine the effect of games-based activity on subsequent cognition in adolescents, and the moderating effect of fitness on this relationship. Methods: Following ethical approval, 39 adolescents (12.3 ± 0.7 year) completed an exercise and resting trial in a counterbalanced, randomised crossover design. During familiarisation, participants completed a multi-stage fitness test to predict VO2 peak. The exercise trial consisted of 60-min games-based activity (basketball), during which heart rate was 158 ± 11 beats∙min−1. A battery of cognitive function tests (Stroop test, Sternberg paradigm, trail making and d2 tests) were completed 30-min before, immediately following and 45-min following the basketball. Results: Response times on the complex level of the Stroop test were enhanced both immediately (p = 0.021) and 45-min (p = 0.035) post-exercise, and response times on the five item level of the Sternberg paradigm were enhanced immediately post-exercise (p = 0.023). There were no effects on the time taken to complete the trail making test or any outcome of the d2 test. In particular, response times were enhanced in the fitter adolescents 45-min post-exercise on both levels of the Stroop test (simple, p = 0.005; complex, p = 0.040) and on the three item level of the Sternberg paradigm immediately (p = 0.017) and 45-min (p = 0.008) post-exercise. Conclusions: Games-based activity enhanced executive function and working memory scanning speed in adolescents, an effect particularly evident in fitter adolescents, whilst the high intensity intermittent nature of games-based activity may be too demanding for less fit children

Effects of an individualized home-based unsupervised aerobic training on body composition and physiological parameters in obese adults are independent of gender

Purpose Evaluation of the efects of an individualized home-based unsupervised aerobic training on body composition, physical and physiological parameters in female and male obese adults. Methods Two hundred and twenty obese adults (age 47.9 ± 12.4 years; BMI 38.0 ± 7.2 kg/m2 ) entered the 4-month training program. Body composition, physiological and functional capacities were assessed pre- and postintervention. All subjects were requested to perform unsupervised aerobic training with the intensity based on heart rate, walking speed and OMNI-RPE score corresponding to the individual ventilatory threshold for at least 5 days/week. Results After 4-month study period, 40% of patients completed the protocol, 24% had high compliance (HC) (exercise ≥ 3 days/week), while 16% had low compliance (LC) to exercise prescription (exercise signifcantly increased while heart rate during 6MWT was signifcantly lower after training. No signifcant diferences were found in LC group between pre- and post-intervention in all variables. Interestingly, gender does not infuence the efects of training. Conclusions Our results indicate that subjects, independent of gender, with high compliance to the aerobic training based on a new individualized method can achieve a signifcant reduction in weight loss and also an improvement in physical and physiological parameters. This innovative personalized prescription could be a valuable tool for exercise physiologist, endocrinologists, and nutritionists to approach and correct life style of obese subjects

TGS1 impacts snRNA 3′-end processing, ameliorates survival motor neuron-dependent neurological phenotypes in vivo and prevents neurodegeneration

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5′-monomethylguanosine cap of small nuclear RNAs (snRNAs) to a trimethylguanosine cap. Here, we show that loss of TGS1 in Caenorhabditis elegans, Drosophila melanogaster and Danio rerio results in neurological phenotypes similar to those caused by survival motor neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3′ tails that are often uridylated. snRNAs with defective 3′ terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.Lewis Katz School of MedicineCancer and Cellular Biolog

L'educazione fisica in Italia: scenari, sfide, prospettive

Il documento di consenso è il tentativo, di un ampio gruppo di ricercatori italiani che si occupano di Educazione Fisica, di condividere contenuti, riferimenti culturali e prospettive della disciplina per rispondere alle sfide che gli anni ’20 del 2000 propongono. Non risulta sia mai stato fatto prima in questa forma collettiva. Lo scopo principale consiste nel contribuire ad una più chiara ed aggiornata definizione della disciplina che oggi è posta di fronte a pressanti richieste della collettività. C’è un’esigenza di chiarezza cui si è cercato di contribuire, innanzitutto, elaborando un articolato glossario di termini e concetti. Tante sono le “scienze” e le “pratiche” che hanno influenzato l’Educazione Fisica lasciando in eredità un linguaggio ampio, ma spesso confuso e non sempre coerente. Si è ritenuto che rendere esplicita questa complessità e proporre delle scelte possa servire a capirci meglio nella comunità di chi opera nell’Educazione Fisica e a farci meglio comprendere ed apprezzare da studenti e società. I riferimenti culturali della disciplina sono stati individuati, con un amplissimo confronto, sia attingendoli dalla tradizione che interpretando le attuali sollecitazioni della ricerca e dell’elaborazione culturale internazionali. Le indicazioni metodologico-didattiche per la progettazione e la conduzione dell’educazione Fisica cercano di riepilogare l’eterogeneità dei contributi della ricerca scientifica internazionale con ricadute necessarie e fondamentali anche nella formazione iniziale e in itinere dei docenti. Il contributo, frutto di un anno di lavoro da parte di una trentina di ricercatori di sedici università italiane, è a disposizione di insegnanti, ricercatori, responsabili di corsi universitari di scienze motorie e di politici. Le riflessioni, le critiche i suggerimenti che ci faranno pervenire aiuteranno a crescere tutta la comunità dell’Educazione Fisica italiana