MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes1,2. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site3. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules. Hyperphosphorylated, aggregation-prone tau forms the hallmark inclusions of tauopathies4. Mutations in MAPT cause familial frontotemporal dementia, and common variations forming the MAPT H1 haplotype are a significant risk factor in many tauopathies5 and Parkinson's disease. Notably, expression of MAPT-AS1 or minimal essential sequences from MAPT-AS1 (including MIR) reduces-whereas silencing MAPT-AS1 expression increases-neuronal tau levels, and correlate with tau pathology in human brain. Moreover, we identified many additional NATs with embedded MIRs (MIR-NATs), which are overrepresented at coding genes linked to neurodegeneration and/or encoding IDPs, and confirmed MIR-NAT-mediated translational control of one such gene, PLCG1. These results demonstrate a key role for MAPT-AS1 in tauopathies and reveal a potentially broad contribution of MIR-NATs to the tightly controlled translation of IDPs6, with particular relevance for proteostasis in neurodegeneration.

Effect of a resistance exercise at acute moderate altitude on muscle health biomarkers.

The intensification of the stress response during resistance training (RT) under hypoxia conditions could trigger unwanted effects that compromise muscle health and, therefore, the ability of the muscle to adapt to longer training periods. We examined the effect of acute moderate terrestrial hypoxia on metabolic, inflammation, antioxidant capacity and muscle atrophy biomarkers after a single RT session in a young male population. Twenty healthy volunteers allocated to the normoxia (N < 700 m asl) or moderate altitude (HH = 2320 m asl) group participated in this study. Before and throughout the 30 min following the RT session (3 × 10 reps, 90 s rest, 70% 1RM), venous blood samples were taken and analysed for circulating calcium, inorganic phosphate, cytokines (IL-6, IL-10 and TNF-α), total antioxidant capacity (TAC) and myostatin. Main results displayed a marked metabolic stress response after the RT in both conditions. A large to very large proportional increase in the adjusted to pre-exercise change of inflammatory and anti-inflammatory markers favoured HH (serum TNF-α [ES = 1.10; p = 0.024] and IL-10 [ES = 1.31; p = 0.009]). The exercise produced a similar moderate increment of myostatin in both groups, followed by a moderate non-significant reduction in HH throughout the recovery (ES = - 0.72; p = 0.21). The RT slightly increased the antioxidant response regardless of the environmental condition. These results revealed no clear impact of RT under acute hypoxia on the metabolic, TAC and muscle atrophy biomarkers. However, a coordinated pro/anti-inflammatory response balances the potentiated effect of RT on systemic inflammation.

A preliminary study on the association between social media at night and sleep quality: The relevance of FOMO, cognitive pre-sleep arousal, and maladaptive cognitive emotion regulation.

Research shows that nighttime social media is negatively associated with sleep quality and that it might be utilized to cope with aversive psychological states related to cognitive pre-sleep arousal (i.e., transdiagnostic psychopathology variables, referring to maladaptive repetitive thought), namely Fear of Missing Out (FoMO). The use of nighttime social media to cope with other aversive cognitive states (i.e., worry/rumination), their relationship with FoMO, and these variables' association with sleep are not fully understood. This study explored the relationships between nighttime social media, sleep quality, FoMO, cognitive pre-sleep arousal, and maladaptive cognitive emotion regulation (i.e., worry/rumination). The present correlational study followed a cross-sectional design. Participants were 525 university students, ranging in age from 18 to 64 (M = 22.39, SD = 5.62). Measures of sleep quality, morningness/eveningness, cognitive pre-sleep arousal, worry, rumination, FoMO, nighttime screen, and social media use were collected online or in pencil-paper format. Multiple linear regression analyses were performed. Nighttime social media and FoMO were associated with rumination, worry (H1) and cognitive pre-sleep arousal. Both FoMO and worry predicted higher levels of cognitive pre-sleep arousal (H2) and nighttime social media use (H3). Nighttime social media use independently predicted poor sleep quality (H4). These results suggest that worry and FoMO may potentially affect sleep quality by increasing cognitive pre-sleep arousal and nighttime social media. A possible explanation for these findings is that nighttime social media might be used as a strategy to cope with aversive cognitive states. These conclusions may contribute to improving sleep intervention in this population.

Subcutaneous granuloma annulare induced by acetazolamide.

A 9-year-old boy presented with recurring subcutaneous nodules on both legs and knees temporally related each time to acetazolamide treatment for idiopathic intracranial hypertension. A biopsy of one of the lesions revealed palisaded granulomas in the hypodermis around necrobiotic collagen and interstitial accumulation of mucin, compatible with subcutaneous granuloma annulare (SGA). To the best of our knowledge, this is the first case that establishes an association between SGA and acetazolamide.

Chronotype, Time of Day, and Children's Cognitive Performance in Remote Neuropsychological Assessment.

Research on the influence of chronotype and time of day (TOD) on cognitive performance, especially in children, is limited. We explored potential interactive effects, hypothesizing that performance differs when comparing preferred vs. non-preferred TOD. In total, 76 morning-type (MT = 37) or evening-type (ET = 39) children from the third and fourth grades (48.7% girls; M age = 8.05; SD age = 0.51), identified through the Children Chronotype Questionnaire, completed two 30-min neuropsychological assessment sessions via videoconference on the first (9:00) or last hour (16:00) of the school day. The protocol included neuropsychological tests targeting memory, language, and attention/executive domains. The results revealed an interactive effect of medium size between chronotype and TOD on a Rapid Alternating Stimulus (Naming) Task. MT and ET performed faster in asynchrony conditions (morning for ET; afternoon for MT). Additionally, ET outperformed MT in a Backward Digit Span Task, irrespective of TOD. TOD also influenced performance on an Alternating Verbal Fluency Task, with both MT and ET children performing better in the morning. These results underscore the importance of chronotype and TOD in children's cognitive performance, particularly in working memory and verbal fluency. Children assessed during non-preferred TOD exhibited better performance on some cognitive tasks, challenging the assumption that optimal times always yield superior results.

Altitude differentially alters the force-velocity relationship after 3 weeks of power-oriented resistance training in elite judokas.

This study investigated the effects of a 3-week power-oriented resistance training programme performed at moderate altitude on the lower-limb maximal theoretical power and force-velocity (F-V) imbalance of elite judokas. Twenty-two elite male judokas were randomly assigned to either a hypobaric hypoxia or normoxia group. Mechanical outputs from an incremental loaded countermovement jump test were assessed at sea level, before and after training, and 1 week later. Results indicated an increase in the maximal theoretical force and a reduction in the F-V imbalance both at moderate altitude and sea level. Altitude training induced additional benefits when compared to sea level for F-V imbalance (8.4%; CI: 0.3, 17.3%), maximal theoretical power (2.09 W·kg-1; CI: 0.13, 4.52 W·kg-1) and force (1.32 N·kg-1; CI: -0.12, 2.96 N·kg-1), jump height (3.24 cm; CI: 2.02, 4.80 cm) and optimal maximal theoretical force (1.61 N·kg-1; CI: 0.06, 3.60 N·kg-1) and velocity (0.08 m·s-1; CI: 0.00, 0.17 m·s-1) after the training period. The hypoxia group achieved their best results immediately after the training period, while the normoxia group achieved them one week later. These results suggest that a power-oriented resistance training programme carried out at moderate altitude accelerates and improves the gains in lower-limb muscle power, while minimizing lower-limb imbalances. Therefore, it seems appropriate to compete immediately after the return to sea level and/or use altitude training as a tool to improve muscle power levels of athletes without tapering goals, especially in highly trained power athletes, since their window of adaptation for further power enhancement is smaller.HighlightsA 3-week power-oriented resistance training programme improved lower-limb mechanical outputs of elite judokas both at moderate altitude and sea level; training at moderate altitude increases and accelerates these improvements, reducing athletes' imbalances.It may be optimal for judokas to compete immediately after the return to sea level and/or use altitude training as a tool to improve muscle power levels of athletes without tapering goals, especially in highly trained power athletes, since their window of adaptation for further power enhancement is attenuated.Athletes should ensure they possess adequate strength levels before employing a power-oriented training programme to potentiate further improvements in muscle power.

Mitochondrial Dysfunction and Decreased Cytochrome c in Cell and Animal Models of Machado-Joseph Disease.

Mitochondrial dysfunction has been described in many neurodegenerative disorders; however, there is less information regarding mitochondrial deficits in Machado-Joseph disease (MJD), a polyglutamine (polyQ) disorder caused by CAG repeat expansion in the ATXN3 gene. In the present study, we characterized the changes in mitochondrial function and biogenesis markers in two MJD models, CMVMJD135 (MJD135) transgenic mice at a fully established phenotype stage and tetracycline-regulated PC6-3 Q108 cell line expressing mutant ataxin-3 (mATXN3). We detected mATXN3 in the mitochondrial fractions of PC6-3 Q108 cells, suggesting the interaction of expanded ATXN3 with the organelle. Interestingly, in both the cerebella of the MJD135 mouse model and in PC6-3 Q108 cells, we found decreased mitochondrial respiration, ATP production and mitochondrial membrane potential, strongly suggesting mitochondrial dysfunction in MJD. Also, in PC6-3 Q108 cells, an additional enhanced glycolytic flux was observed. Supporting the functional deficits observed in MJD mitochondria, MJD135 mouse cerebellum and PC6-3 Q108 cells showed reduced cytochrome c mRNA and protein levels. Overall, our findings show compromised mitochondrial function associated with decreased cytochrome c levels in both cell and animal models of MJD.

Inter-set rest configuration effect on acute physiological and performance-related responses to a resistance training session in terrestrial vs simulated hypoxia.

Background: Metabolic stress is considered a key factor in the activation of hypertrophy mechanisms which seems to be potentiated under hypoxic conditions.This study aimed to analyze the combined effect of the type of acute hypoxia (terrestrial vs simulated) and of the inter-set rest configuration (60 vs 120 s) during a hypertrophic resistance training (RT) session on physiological, perceptual and muscle performance markers. Methods: Sixteen active men were randomized into two groups based on the type of hypoxia (hypobaric hypoxia, HH: 2,320 m asl; vs normobaric hypoxia, NH: FiO2 of 15.9%). Each participant completed in a randomly counterbalanced order the same RT session in four separated occasions: two under normoxia and two under the corresponding hypoxia condition at each prescribed inter-set rest period. Volume-load (load × set × repetition) was calculated for each training session. Muscle oxygenation (SmO2) of the vastus lateralis was quantified during the back squat exercise. Heart rate (HR) was monitored during training and over the ensuing 30-min post-exercise period. Maximal blood lactate concentration (maxLac) and rating of perceived exertion (RPE) were determined after the exercise and at the end of the recovery period. Results: Volume-load achieved was similar in all environmental conditions and inter-set rest period length did not appreciably affect it. Shorter inter-set rest periods displayed moderate increases in maxLac, HR and RPE responses in all conditions. Compared to HH, NH showed a moderate reduction in the inter-set rest-HR (ES > 0.80), maxLac (ES > 1.01) and SmO2 (ES > 0.79) at both rest intervals. Conclusions: Results suggest that the reduction in inter-set rest intervals from 120 s to 60 s provide a more potent perceptual, cardiovascular and metabolic stimulus in all environmental conditions, which could maximize hypertrophic adaptations in longer periods of training. The abrupt exposure to a reduced FiO2 at NH seems to reduce the inter-set recovery capacity during a traditional hypertrophy RT session, at least during a single acute exposition. These results cannot be extrapolated to longer training periods.

Perceived Causes and Attitudes Regarding Overindebtedness and Their Effects on Public Agreement With Government Financial Aid.

In order to better understand how the problem of overindebtedness is perceived from a laypeople standpoint, Study 1 inquired both overindebted and non-overindebted consumers on the perceived causes of and attitudes toward the overindebted. Situational and dispositional factors were perceived to have similar impact as causes of overindebtedness, but non-overindebted consumers showed stronger agreement with those causes than overindebted consumers. Regarding attitudes, non-overindebted consumers tended to blame overindebted people for their situation rather than perceiving them as victims, whereas overindebted consumers showed the opposite pattern. Study 2 used a sample of (non-overindebted) consumers to assess the impact of perceived causes of overindebtedness, attitudes toward the overindebted, and political orientation on public support of government policies for aiding overindebted people. We discuss the contributions of the present findings to design public policies aimed at aiding overindebted households that are more aligned with the beliefs and attitudes of the general public.

Attitudes Toward Money and Control Strategies of Financial Behavior: A Comparison Between Overindebted and Non-overindebted Consumers.

This paper addresses whether overindebted and non-overindebted consumers differ in their attitude toward money (specifically, the degree to which consumers care about money and feel difficulties keeping track of their money) and how this attitude impacts three different financial behavior categories: record keeping (e.g., recording spending in writing), adjusting balance (e.g., trying to find ways to decrease one's expenses to match income), and monitoring balance (e.g., monitoring one's spending to see if it is in line with what is expected). Overindebted consumers were recruited via an NGO for consumer defense and were categorized (whenever possible) into two subgroups: consumers who became overindebted due to internal causes (e.g., bad financial management) and consumers who became overindebted due to external causes (e.g., unemployment). Non-overindebted consumers were a convenience sample. Non-overindebted consumers showed more positive attitudes toward money than both groups of overindebted consumers and overindebted due to external causes showed more positive attitudes than overindebted consumers due to internal causes. All groups share similar financial management behaviors except for monitoring balance, which was more frequent among non-overindebted consumers. Furthermore, a regression analysis indicates that money attitudes helped explain financial behavior differences between consumers above and beyond their indebtedness status. Consumers' attitude predicted financial behaviors, even when controlling for relevant socioeconomic variables (education, income, age, and gender). Further analyses comparing money attitudes and financial behavior for the three subgroups (non-overindebted, overindebted due to internal causes, and overindebted due to external causes) showed no differences.

On the Relation Between Over-Indebtedness and Well-Being: An Analysis of the Mechanisms Influencing Health, Sleep, Life Satisfaction, and Emotional Well-Being.

This paper aims to explore the association between over-indebtedness and two facets of well-being - life satisfaction and emotional well-being. Although prior research has associated over-indebtedness with lower life satisfaction, this study contributes to the extant literature by revealing its effects on emotional well-being, which is a crucial component of well-being that has received less attention. Besides subjective well-being (SWB), reported health, and sleep quality were also assessed. The findings suggest that over-indebted (compared to non-over-indebted) consumers have lower life satisfaction and emotional well-being, as well as poorer (reported) health and sleep quality. Furthermore, over-indebtedness impacts life satisfaction and emotional well-being through different mechanisms. Consumers decreased perceived control accounts for the impact of over-indebtedness on both facets of well-being (as well as on reported health and sleep). Financial well-being (a specific component of life satisfaction), partly mediates the impact of indebtedness status on overall life satisfaction. The current study contributes to research focusing on the relationship between indebtedness, well-being, health, and sleep quality, and provides relevant theoretical and practical implications.

Neuromuscular Adaptations after an Altitude Training Camp in Elite Judo Athletes.

The aim of this study was to investigate neuromuscular adaptations in elite judo athletes after three weeks of power-oriented strength training at terrestrial altitude (2320 m). Nineteen men were assigned to altitude training (AL) (22.1 ± 2.3 years) and sea level training (SL) (22.6 ± 4.1 years). Neuromuscular assessment consisted of: (1) maximal isometric knee extensor (KE) torque, (2) KE rate of torque development (RTD), (3) quadriceps activity and voluntary activation, (4) soleus H-reflex, (5) quadriceps single (TTW) and double twitch torque (TDB100) and contraction time (CTTW). There were no significant differences between groups at baseline for any of the observed parameters. Significant differences were found between groups in terms of change in RTD (p = 0.04). Cohen's d showed a positive significant effect (0.43) in the SL group and a negative significant effect (-0.58) in the AL group. The difference between groups in changes in CTTW as a function of altitude was on the edge of significance (p = 0.077). CTTW increased by 8.1 ± 9.0% in the AL group (p = 0.036) and remained statistically unchanged in the SL group. Only the AL group showed a relationship between changes in TTW and TDB100 and changes in RTD at posttest (p = 0.022 and p = 0.016, respectively). Altitude induced differences in muscular adaptations likely due to greater peripheral fatigue.