Identification of Synaptic Targets of Drosophila Pumilio

Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

Moderate to vigorous physical activity and sedentary behavior changes in self-isolating adults during the COVID-19 pandemic in Brazil: a cross-sectional survey exploring correlates

BackgroundThe COVID-19 pandemic imposed major changes on daily-life routine worldwide. To the best of our knowledge, no study quantified the changes on moderate to vigorous physical activity (MVPA) and sedentary behaviors (SB) and its correlates in Brazilians. This study aimed to (i) evaluate the changes (pre versus during pandemic) in time spent in MVPA and SB in self-isolating Brazilians during the COVID-19 pandemic, and (ii) to explore correlates.MethodsA cross-sectional, retrospective, self-report online web survey, evaluating the time spent in MVPA and SB pre and during the COVID-19 pandemic in self-isolating people in Brazil. Sociodemographic, behavioral, and clinical measures, and time in self-isolation were also obtained. Changes in MVPA and SB and their correlates were explored using generalized estimating equations (GEE). Models were adjusted for covariates.ResultsA total of 877 participants (72.7% women, 53.7% young adults [18-34 years]) were included. Overall, participants reported a 59.7% reduction (95% CI 35.6-82.2) in time spent on MVPA during the pandemic, equivalent to 64.28 (95% CI 36.06-83.33) minutes per day. Time spent in SB increased 42.0% (95% CI 31.7-52.5), corresponding to an increase of 152.3 (95% CI 111.9-192.7) minutes per day. Greater reductions in MVPA and increases in SB were seen in younger adults, those not married, those employed, and those with a self-reported previous diagnosis of a mental disorder.ConclusionsPeople in self-isolation significantly reduced MVPA levels and increased SB. Public health strategies are needed to mitigate the impact of self-isolation on MVPA and SB.Supplementary informationThe online version contains supplementary material available at 10.1007/s11332-021-00788-x

Predicting Functional Recovery after Acute Ankle Sprain

Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain.A secondary analysis of data from adult participants (N = 85) with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test) recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks) and medium term (4 months) follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery.Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34). Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20). Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49).The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further prospective research is required to highlight the factors that best inform the expected convalescent period, and risk of recurrence