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The precise regulation of gene expression is fundamental to neurodevelopment, plasticity and cognitive function. Although several studies have profiled transcription in the developing human brain, there is a gap in understanding of accompanying translational regulation. In this study, we performed ribosome profiling on 73 human prenatal and adult cortex samples. We characterized the translational regulation of annotated open reading frames (ORFs) and identified thousands of previously unknown translation events, including small ORFs that give rise to human-specific and/or brain-specific microproteins, many of which we independently verified using proteomics. Ribosome profiling in stem-cell-derived human neuronal cultures corroborated these findings and revealed that several neuronal activity-induced non-coding RNAs encode previously undescribed microproteins. Physicochemical analysis of brain microproteins identified a class of proteins that contain arginine-glycine-glycine (RGG) repeats and, thus, may be regulators of RNA metabolism. This resource expands the known translational landscape of the human brain and illuminates previously unknown brain-specific protein products.

Introduction Methods Results Conclusion Black people had the highest prevalence of Alzheimer's disease and related dementias (ADRD) of any racial/ethnic group in the United States (US) as of 2020. As racial disparities in the prevalence of ADRD are being investigated, more evidence is necessary to determine the pathways and mechanisms that either slow ADRD progression or improve quality of life for those affected. Religion/spirituality (R/S) has been shown to affect health outcomes but has rarely been studied as a possible pathway for reducing ADRD risk. Crucially, Black people also report higher levels of R/S than other racial/ethnic groups in the United States. This research asks if R/S affects ADRD risk among Black adults and if any effects persist after controlling for hypertension.We conducted a secondary data analysis drawing from the Health and Retirement Study (HRS), a nationally representative longitudinal dataset with an oversampling of Black adults.We used logistic regression analysis to demonstrate how R/S has an ameliorating impact on ADRD risk among Black people, even after controlling for hypertension. Those who never attended religious services had 2.37 higher odds of being diagnosed with ADRD than those who attended more than once a week. Further, as R/S attendance increased, ADRD risk decreased linearly.These findings demonstrate the importance that existing cultural networks (e.g., R/S) can have for reducing ADRD burden for Black people and has important implications for the role of R/S in shaping ADRD symptomatology. [ABSTRACT FROM AUTHOR]

As cases of Alzheimer's disease and related dementias (ADRD) increase worldwide, research design has placed additional emphasis on social and behavioral factors that affect ADRD symptomatology and quality of life. Despite this, few studies have incorporated people living with ADRD as research partners. We propose 5 community-engaged recommendations for incorporating people living with ADRD into future research as full collaborators. The proposed recommendations center the experiences of people living with ADRD as crucial contributions to scientific inquiry. The guidelines are based on experiences at a 2-day "Empowering Partnerships" workshop in 2019; post workshop activity continued through 2021 with ongoing collaborations, analysis, and reflective practice. The workshop and subsequent conversations engaged a network of people living with ADRD, informal carepartners, and researchers to collectively build their capacities to partner in all aspects of person-centered research. To empower people living with ADRD as research partners, we recommend that research teams (a) create a flexible schedule of communication and/or meetings to accommodate a wide range of ADRD symptoms, (b) generate team-specific communication strategies/guidelines, (c) incorporate lived experiences of people living with ADRD into research protocols, (d) involve people living with ADRD in all aspects of a project, beginning in the developmental stages, and (e) incorporate skilled facilitators to facilitate communication between stakeholder groups. This multi-vocal approach to research will diversify ADRD research and ensure that projects align with the priorities and capacities of principal stakeholders by incorporating individuals with a wide range of cognitive capabilities that more fully represent the diversity of ADRD experiences. [ABSTRACT FROM AUTHOR]

ObjectivesMethodsResultsConclusionCOVID-19 escalated stress within family/neighborhood (local) and national/cultural (global) levels. However, the impact of socioecological levels of stress on pandemic emotion regulation remains largely unexplored.Thirty older adults from the Northeast US (63–92 years) reported on pandemic stress and emotion regulation in semi-structured interviews. Responses were coded into socioecological sources of local and global stress, and associated use of cognitive emotion regulation strategies from the Cognitive Emotion Regulation Questionnaire was explored.Older adults experienced significant distress at global levels, and perception of lacking top-down safety governance may have exacerbated local distress of engaging in daily activities during the COVID-19 pandemic. Participants endorsed coping with local stressors via perspective-taking, acceptance, and other adaptive strategies, while global sources of stress were associated with greater use of maladaptive strategies, including other-blame and rumination.Quantitative assessments may underestimate significant older adult distress and maladaptive coping toward global stressors. Findings should be replicated with more diverse populations beyond the COVID-19 context. [ABSTRACT FROM AUTHOR]

Mutations in MECP2 give rise to Rett syndrome (RTT), an X-linked neurodevelopmental disorder that results in broad cognitive impairments in females. While the exact etiology of RTT symptoms remains unknown, one possible explanation for its clinical presentation is that loss of MECP2 causes miswiring of neural circuits due to defects in the brain's capacity to respond to changes in neuronal activity and sensory experience. Here, we show that MeCP2 is phosphorylated at four residues in the mouse brain (S86, S274, T308, and S421) in response to neuronal activity, and we generate a quadruple knock-in (QKI) mouse line in which all four activity-dependent sites are mutated to alanines to prevent phosphorylation. QKI mice do not display overt RTT phenotypes or detectable gene expression changes in two brain regions. However, electrophysiological recordings from the retinogeniculate synapse of QKI mice reveal that while synapse elimination is initially normal at P14, it is significantly compromised at P20. Notably, this phenotype is distinct from the synapse refinement defect previously reported for Mecp2 null mice, where synapses initially refine but then regress after the third postnatal week. We thus propose a model in which activity-induced phosphorylation of MeCP2 is critical for the proper timing of retinogeniculate synapse maturation specifically during the early postnatal period. [ABSTRACT FROM AUTHOR]

Sensory stimuli drive the maturation and function of the mammalian nervous system in part through the activation of gene expression networks that regulate synapse development and plasticity. These networks have primarily been studied in mice, and it is not known whether there are species- or clade-specific activity-regulated genes that control features of brain development and function. Here we use transcriptional profiling of human fetal brain cultures to identify an activity-dependent secreted factor, Osteocrin (OSTN), that is induced by membrane depolarization of human but not mouse neurons. We find that OSTN has been repurposed in primates through the evolutionary acquisition of DNA regulatory elements that bind the activity-regulated transcription factor MEF2. In addition, we demonstrate that OSTN is expressed in primate neocortex and restricts activity-dependent dendritic growth in human neurons. These findings suggest that, in response to sensory input, OSTN regulates features of neuronal structure and function that are unique to primates., Author(s): Bulent Ataman [1]; Gabriella L. Boulting [1]; David A. Harmin [1]; Marty G. Yang [1]; Mollie Baker-Salisbury [1]; Ee-Lynn Yap [1]; Athar N. Malik [1]; Kevin Mei [1]; Alex [...]

Households in natural resource-dependent areas of the United States are particularly vulnerable to fuel poverty. Wood banks provide no-cost, local firewood to fuel-poor households. Little is known about key details such as where they are operating, who is accessing them, and why. To assess the mechanisms by which wood banks may help alleviate fuel poverty, we located 82 wood banks and identified that 20.7% of them operated in counties with high rates of poverty and firewood heating use, despite only 11.6% of counties satisfying those criteria, nationwide. Qualitative analysis of interviews with representatives from 21 wood banks identified four explanations for household fuel poverty preceding accessing a wood bank: economic poverty, health-related challenges, old age, and emergency need. In many cases, at least two of four vulnerabilities overlapped, indicating that a convergence of factors explains the establishment and use of a wood bank. [ABSTRACT FROM AUTHOR]

Abstract In this paper we present an approach to coordinate the motions of droplets in digital microfluidic systems, a new class of lab-on-a-chip systems for biochemical analysis. A digital microfluidic [...]