RESUMEN
Difficulty with attention is an important symptom in many conditions in psychiatry, including neurodiverse conditions such as autism. There is a need to better understand the neurobiological correlates of attention and leverage these findings in healthcare settings. Nevertheless, it remains unclear if it is possible to build dimensional predictive models of attentional state in a sample that includes participants with neurodiverse conditions. Here, we use 5 datasets to identify and validate functional connectome-based markers of attention. In dataset 1, we use connectome-based predictive modeling and observe successful prediction of performance on an in-scan sustained attention task in a sample of youth, including participants with a neurodiverse condition. The predictions are not driven by confounds, such as head motion. In dataset 2, we find that the attention network model defined in dataset 1 generalizes to predict in-scan attention in a separate sample of neurotypical participants performing the same attention task. In datasets 3-5, we use connectome-based identification and longitudinal scans to probe the stability of the attention network across months to years in individual participants. Our results help elucidate the brain correlates of attentional state in youth and support the further development of predictive dimensional models of other clinically relevant phenotypes.
Asunto(s)
Atención , Trastorno del Espectro Autista , Encéfalo , Conectoma , Humanos , Adolescente , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Conjuntos de Datos como Asunto , Masculino , Femenino , Encéfalo/fisiopatología , Encéfalo/ultraestructuraRESUMEN
Mitoribosome biogenesis is an expensive metabolic process that is essential to maintain cellular respiratory capacity and requires the stoichiometric accumulation of rRNAs and proteins encoded in two distinct genomes. In yeast, the ribosomal protein Var1, alias uS3m, is mitochondrion-encoded. uS3m is a protein universally present in all ribosomes, where it forms part of the small subunit (SSU) mRNA entry channel and plays a pivotal role in ribosome loading onto the mRNA. However, despite its critical functional role, very little is known concerning VAR1 gene expression. Here, we demonstrate that the protein Sov1 is an in bona fide VAR1 mRNA translational activator and additionally interacts with newly synthesized Var1 polypeptide. Moreover, we show that Sov1 assists the late steps of mtSSU biogenesis involving the incorporation of Var1, an event necessary for uS14 and mS46 assembly. Notably, we have uncovered a translational regulatory mechanism by which Sov1 fine-tunes Var1 synthesis with its assembly into the mitoribosome.
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Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética , Ribosomas Mitocondriales/metabolismo , Proteínas Ribosómicas/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , ADN Mitocondrial/genética , Regulación Fúngica de la Expresión Génica/genética , ARN Mensajero/genéticaRESUMEN
Introduction: Fall Risk Appraisal (FRA), a process that integrates perceived and objective fall risk measures, serves as a crucial component for understanding the incongruence between fear of falling (FOF) and physiological fall risk in older adults. Despite its importance, scant research has been undertaken to investigate how habitual physical activity (PA) levels, quantified in Monitor-Independent Movement Summary (MIMS), vary across FRA categories. MIMS is a device-independent acceleration summary metric that helps standardize data analysis across studies by accounting for discrepancies in raw data among research-grade and consumer devices. Objective: This cross-sectional study explores the associations between MIMS (volume and intensity) and FRA in a sample of older adults in the United States. Methods: We assessed FOF (Short Falls Efficacy Scale-International), physiological fall risk (balance: BTrackS Balance, leg strength: 30-s sit-to-stand test) and 7-day free-living PA (ActiGraph GT9X) in 178 community-dwelling older adults. PA volume was summarized as average daily MIMS (MIMS/day). PA intensity was calculated as peak 30-min MIMS (average of highest 30 non-consecutive MIMS minutes/day), representing a PA index of higher-intensity epochs. FRA categorized participants into following four groups: Rational (low FOF-low physiological fall risk), Irrational (high FOF-low physiological fall risk), Incongruent (low FOF-high physiological fall risk) and Congruent (high FOF-high physiological fall risk). Results: Compared to rational group, average MIMS/day and peak 30-min MIMS were, respectively, 15.8% (p = .025) and 14.0% (p = .004) lower in irrational group, and 16.6% (p = .013) and 17.5% (p < .001) lower in congruent group. No significant differences were detected between incongruent and rational groups. Multiple regression analyses showed that, after adjusting for age, gender, and BMI (reference: rational), only irrational FRA was significantly associated with lower PA volume (ß = -1,452.8 MIMS/day, p = .034); whereas irrational and congruent FRAs were significantly associated with lower "peak PA intensity" (irrational: ß = -5.40 MIMS/day, p = .007; congruent: ß = -5.43 MIMS/day, p = .004). Conclusion: These findings highlight that FOF is a significant barrier for older adults to participate in high-intensity PA, regardless of their balance and strength. Therefore, PA programs for older adults should develop tailored intervention strategies (cognitive reframing, balance and strength exercises, or both) based on an individual's FOF and physiological fall risk.
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While resistance training promotes muscle hypertrophy and strength, accessibility of equipment is a barrier. This study evaluated a wearable VAriable Resistance Suit (VARS) as a novel and alternative method to achieve muscle strength improvement. It was hypothesized that by providing adjustable, bi-directional and speed dependent resistance, VARS can target specific muscles to improve muscle strength via an accessible and portable device. Twelve untrained healthy male adults (22.08 ± 4.1 years old) participated in an 8-week long resistance training using VARS to strengthen four muscles (biceps brachii, triceps brachii, biceps femoris, rectus femoris) of their non-dominant arm and leg using VARS. The results showed significant improvements in the muscle strength measured by isokinetic dynamometer - 49.9±9.6% increase in isokinetic force and 30.6±7.6% increase in isometric force. Muscle size and body composition were also assessed using ultrasound imaging and bioelectrical impedance analysis, which did not show significant changes. The study demonstrates the efficacy and feasibility of VARS as a resistance training tool to achieve muscle strength improvement and its potential extension to clinical populations.
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Voluntarios Sanos , Contracción Isométrica , Fuerza Muscular , Músculo Esquelético , Entrenamiento de Fuerza , Humanos , Masculino , Entrenamiento de Fuerza/métodos , Fuerza Muscular/fisiología , Adulto Joven , Contracción Isométrica/fisiología , Adulto , Músculo Esquelético/fisiología , Dinamómetro de Fuerza Muscular , Dispositivos Electrónicos Vestibles , Composición Corporal , Impedancia Eléctrica , Brazo/fisiología , Pierna/fisiologíaRESUMEN
The individual effects of physical activity (PA) and sedentary behavior (SB) on health are well-recognized. However, little is known about the extent to which different combinations of these behaviors are associated with body composition and fall risk in older adults. This cross-sectional study examined the associations of mutually exclusive categories of PA and SB with body composition and fall risk in older women. Accelerometer-measured PA, body composition and fall risk (static and dynamic balance) parameters were assessed among 94 community-dwelling older women. The participants were categorized into four groups: active-low sedentary, active-high sedentary, inactive-low sedentary and inactive-high sedentary (active: ≥150 min/week moderate-to-vigorous PA (MVPA); low sedentary: lowest tertile of SB and light PA ratio). Compared to the inactive-high sedentary group, more favorable body composition and dynamic balance results were found in the active-low sedentary (body fat mass index (BFMI): ß = -4.37, p = 0.002; skeletal muscle mass index (SMI): ß = 1.23, p = 0.017; appendicular lean mass index (ALMI): ß = 1.89, p = 0.003; appendicular fat mass index (AFMI): ß = -2.19, p = 0.003; sit-to-stand: ß = 4.52, p = 0.014) and inactive-low sedentary (BFMI: ß = -3.14, p = 0.007; SMI: ß = 1.05, p = 0.014; AFMI: ß = -1.74, p = 0.005, sit-to-stand: ß = 3.28, p = 0.034) groups. Our results suggest that PA programs focusing on concurrently achieving sufficient MVPA and reduced SB might promote a healthy body composition and reduced fall risk among older adults.
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Ejercicio Físico , Conducta Sedentaria , Humanos , Femenino , Anciano , Estudios Transversales , Ejercicio Físico/fisiología , Composición Corporal , Índice de Masa Corporal , AcelerometríaRESUMEN
Studies utilizing eye-tracking methods have potential to promptly capture real-world dynamics of one of the core areas of vulnerability in autism spectrum disorders (ASD), selective social attention. So far, no studies have successfully reported utilizing the method to examine social attention in toddlers with neurodevelopmental vulnerabilities in real world and challenging settings such as an interactive face-to-face. This study examined the feasibility and validity of live eye-tracking method in response to live interaction occurring in several contexts in toddlers with and without ASD. Forty-seven toddlers with ASD, with atypical development (ATYP), or typically developing (TD), underwent a 30-s live eye-tracking procedure during a face-to-face interaction with a masked stranger using child-directed-speech (16 ASD, 14 ATYP, 17 TD; Mage = 23.44 months, SD = 6.02). Out of this group of toddlers, 29 (10 ASD, 8 ATYP, 11 TD, Mage = 21.97 months, SD = 5.76) underwent the same procedure with one of their maskless parent. Task completion rate, calibration accuracy, and affective response (feasibility measures) as well as attention to the task and the social partner (validity measures) were examined. Task completion rate and calibration accuracy were excellent. Despite the challenging context of face-to-face interaction, the toddlers exhibited a neutral affect, and high attention to the task and the speaker. As anticipated, toddlers with ASD looked less at the social partner compared with control groups. However, attention was comparable between the Stranger and Parent conditions, indicating that the effect was consistent regardless of presence of face covering or the familiarity of the interactive partner. The study demonstrates the high feasibility and validity of a live eye-tracking task involving face-to-face interaction in neurodiverse toddlers with social vulnerabilities. The effect of diminished attention to social partners in toddlers with autism is robust and present when interacting with an unfamiliar person and parent. The results suggest that a brief live eye-tracking method constitutes a promising ecologically valid candidate biomarker and potential intervention outcome in autism.
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Homophily, the tendency for individuals to preferentially interact with others similar to themselves is typically documented via self-report and, for children, adult report. Few studies have investigated homophily directly using objective measures of social movement. We quantified homophily in children with developmental disabilities (DD) and typical development (TD) using objective measures of position/orientation in preschool inclusion classrooms, designed to promote interaction between these groups of children. Objective measurements were collected using ultra-wideband radio-frequency tracking to determine social approach and social contact, measures of social movement and interaction. Observations of 77 preschoolers (47 with DD, and 30 TD) were conducted in eight inclusion classrooms on a total of 26 days. We compared DD and TD groups with respect to how children approached and shared time in social contact with peers using mixed-effects models. Children in concordant dyads (DD-DD and TD-TD) both moved toward each other at higher velocities and spent greater time in social contact than discordant dyads (DD-TD), evidencing homophily. DD-DD dyads spent less time in social contact than TD-TD dyads but were comparable to TD-TD dyads in their social approach velocities. Children's preference for similar peers appears to be a pervasive feature of their naturalistic interactions.