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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]

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]

Research collaboration is key to faculty career success in science, technology, engineering, and mathematics (STEM). Yet little research has considered how faculty from multiply marginalized identity groups experience collaboration compared to colleagues from majority groups. The present study fills that gap by examining similarities and differences in collaboration experiences of faculty across multiple marginalized groups, and the role of department climate in those experiences. A survey of STEM faculty at a large public research university found that faculty from underrepresented groups – in terms of gender, race, and sexual orientation – had more negative experiences with department-level research collaborations. Moreover, faculty with multiply marginalized identities had worse collaboration experiences than others with a single marginalized identity or none. They also perceived their department climate to be less inclusive, equitable, and transparent; and felt their opinions were less valued in their department than colleagues from majority groups. Negative department climate, in turn, mediated and predicted less hospitable experiences with department-level research collaborations. These data suggest that multiply marginalized faculty, across different identity groups, share some common experiences of a "chilly" department climate relative to their peers from majority groups that impede opportunities for scientific collaboration, a key ingredient for faculty success. These findings have policy implications for retention of diverse faculty in university STEM departments. [ABSTRACT FROM AUTHOR]

The article focuses on the use of desktop personal computers (PC) in high-performance simulations of turbulent clouds. It states that graphics processing units (GPU), field-programmable gate arrays, and a larger number of cores in central processing units allow PCs to perform intensive matrix projection calculations. It talks about methods of utilizing GPUs for parallel computing of weather models for use in atmospheric large-eddy simulations.

This paper describes a computational approach to designing a digital microfluidic system (DMFS) that can be rapidly reconfigured for new biochemical analyses. Such a "lab-on-a-chip" system for biochemical analysis, based on electrowetting or dielectrophoresis, must coordinate the motions of discrete droplets or biological cells using a planar array of electrodes. The authors have earlier introduced a layout-based system and demonstrated its flexibility through simulation, including the system's ability to perform multiple assays simultaneously. Since array-layout design and droplet-routing strategies are closely related in such a DMFS, their goal. is to provide designers with algorithms that enable rapid simulation and control of these DMFS devices. In this paper, the effects of variations in the basic array-layout design, droplet-routing control algorithms, and droplet spacing on system performance are characterized. DMFS arrays with hardware limited row-column addressing are considered, and a polynomial-time algorithm for coordinating droplet movement under such hardware limitations is developed. To demonstrate the capabilities of our system, we describe example scenarios, including dilution control and minimalist layouts, in which our system can be successfully applied. [ABSTRACT FROM AUTHOR]

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 system typically consists of a planar array of cells with electrodes that control the droplets. The primary challenge in using droplet-based systems is that they require the simultaneous coordination of a potentially large number of droplets on the array as the droplets move, mix, and split. In this paper we describe a general-purpose system that uses simple algorithms and yet is versatile. First, we present a semi-automated approach to generate the array layout in terms of components. Next, we discuss simple algorithms to select destination components for the droplets and a decentralized scheme for components to route the droplets on the array. These are then combined into a reconfigurable system that has been simulated in soft ware to perform analyses such as the DNA polymerase chain reaction. The algorithms have been able to successfully coordinate hundreds of droplets simultaneously and perform one or more chemical analyses in parallel. Because it is challenging to analytically characterize the behavior of such systems, simulation methods to detect potential system instability are proposed. [ABSTRACT FROM AUTHOR]

Synaptic activity regulates the expression of a set of neuronal gene products that are important for neuronal survival and differentiation, synaptogenesis and, ultimately, complex behaviour. Activity-dependent signalling pathways induce neuronal gene transcription by modulating the function of both transcriptional activators and repressors, and recent studies have revealed significant diversity in the mechanisms that control the activity of these transcriptional regulators. Investigators have begun to elucidate the distinct functions of individual activity-regulated transcription factors, and to explore how these factors cooperate to provide stimulus specificity in the initiation of neuronal transcriptional programmes. [ABSTRACT FROM AUTHOR]

Presents a study which reported that the treatment of endothelial and other drug-sensitive cell types leads to the activation of a type of a pathway causing an accumulation of a type of kinase inhibitor. Materials and methods; Results; Discussion.

Presents information on a study which hypothesized that fumagillin and ovacilin inhibit type 2 methionine aminopeptidase (MetAP2) by irreversible blockage of the active site. Features of fumagillin and ovacilin; Materials and methods; Results from the synthesis of deoxyfumagillin analogs.

Investigates the overexpression and purification of human calcineurin alpha from `Escherichia coli'. Assessment of the catalytic functions of residues surrounding the binuclear metal center; Importance of the binuclear metal center and its surrounding residues in catalysis by calcineurin; Performance of a systematic alanine-scan mutagenesis.

This article presents the findings of a survey that was distributed to students with disabilities at the University of Georgia to gain insight into their experience with the university's libraries. Key findings include: students with disabilities cite as barriers many of the same things that the student body in general cites as annoyances, in-class instruction from a librarian increases use of library services and resources, and students with disabilities ask classmates and friends for research help more often than they ask librarians. Grounded in real-world practice and the literature on both library engagement and disability studies, recommendations for inclusive libraries are presented that incorporate Universal Design and accommodations, viewing inclusion as an ongoing action rather than a fixed state that can be achieved. [ABSTRACT FROM AUTHOR]

Although on average women are underrepresented in academic science, technology, engineering, and mathematics (STEM) departments at universities, an underappreciated fact is that women’s representation varies widely across STEM disciplines. Past research is fairly silent on how local variations in gender composition impact faculty experiences. This study fills that gap. A survey of STEM departments at a large research university finds that women faculty in STEM are less professionally satisfied than male colleagues only if they are housed in departments where women are a small numeric minority. Gender differences in satisfaction are largest in departments with less than 25% women, smaller in departments with 25–35% women, and nonexistent in departments approaching 50% women. Gender differences in professional satisfaction in gender-unbalanced departments are mediated by women’s perception that their department’s climate is uncollegial, faculty governance is non-transparent, and gender relations are inequitable. Unfavorable department climates also predict retention risk for women in departments with few women, but not in departments closer to gender parity. Finally, faculty who find within-department mentors to be useful are more likely to have a favorable view of their department’s climate, which consequently predicts more professional satisfaction. Faculty gender and gender composition does not moderate these findings, suggesting that mentoring is equally effective for all faculty. [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]

Remote biopsy sampling is a valuable technique to collect data on free-ranging cetaceans. Numerous researchers have evaluated effects of biopsy darting on the target animal, but biopsy sampling may also have unintentional effects on nearby nontarget animals. We evaluated reactions of target and nontarget animals during remote biopsy sampling conducted on bottlenose dolphins (Tursiops truncatus) in August 2004 off Folly Beach, South Carolina, and Jekyll Island, Georgia, USA, and in February-March and July-August 2005 off Hilton Head, South Carolina. We examined external factors that might influence response of the target animal as well as other individuals in the group. Target animals reacted to biopsy attempts 90.9% (n = 475) of the time. Of these, 97.5% (n = 432) of reactions were to biopsy hits, and 84.4% (n = 320) of all hits had reactions recorded as low. Nontarget animals reacted 21.9% (n = 1,158) of the time; interanimal distance from target animal, season, sea state, and depth affected reactions of nontarget animals. Overall, however, biopsy effects appear to be minimal. We present a statistical tool for identifying factors that elicit greater reactions. This model could be adapted for species or locations, as needed, to identify factors that could influence effects of biopsy sampling. [ABSTRACT FROM AUTHOR]

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms ofmethylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNAmethylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system. [ABSTRACT FROM AUTHOR]

Summary: We report the results of a genetic screen to identify molecules important for synapse formation and/or maintenance. siRNAs were used to decrease the expression of candidate genes in neurons, and synapse development was assessed. We surveyed 22 cadherin family members and demonstrated distinct roles for cadherin-11 and cadherin-13 in synapse development. Our screen also revealed roles for the class 4 Semaphorins Sema4B and Sema4D in the development of glutamatergic and/or GABAergic synapses. We found that Sema4D affects the formation of GABAergic, but not glutamatergic, synapses. Our screen also identified the activity-regulated small GTPase Rem2 as a regulator of synapse development. A known calcium channel modulator, Rem2 may function as part of a homeostatic mechanism that controls synapse number. These experiments establish the feasibility of RNAi screens to characterize the mechanisms that control mammalian neuronal development and to identify components of the genetic program that regulate synapse formation and/or maintenance. [Copyright &y& Elsevier]

Summary: Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT. [Copyright &y& Elsevier]

In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated AAEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development. [ABSTRACT FROM AUTHOR]

Summary: Ephrin signaling through Eph receptor tyrosine kinases can promote attraction or repulsion of axonal growth cones during development. However, the mechanisms that determine whether Eph signaling promotes attraction or repulsion are not known. We show here that the Rho family GEF Vav2 plays a key role in this process. We find that, during axon guidance, ephrin binding to Ephs triggers Vav-dependent endocytosis of the ligand-receptor complex, thus converting an initially adhesive interaction into a repulsive event. In the absence of Vav proteins, ephrin-Eph endocytosis is blocked, leading to defects in growth cone collapse in vitro and significant defects in the ipsilateral retinogeniculate projections in vivo. These findings suggest an important role for Vav family GEFs as regulators of ligand-receptor endocytosis and determinants of repulsive signaling during axon guidance. [Copyright &y& Elsevier]

Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RTT), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RTT. [ABSTRACT FROM AUTHOR]

The transcription factor CREB mediates diverse responses in the nervous system. It is not known how CREB induces specific patterns of gene expression in response to different extracellular stimuli. We find that Ca2+ influx into neurons induces CREB phosphorylation at Ser133 and two additional sites, Ser142 and Ser143. While CREB Ser133 phosphorylation is induced by many stimuli, phosphorylation at Ser142 and Ser143 is selectively activated by Ca2+ influx. The triple phosphorylation of CREB is required for effective Ca2+ stimulation of CREB-dependent transcription, but the phosphorylation of Ser142 and Ser143, in addition to Ser133, disrupts the interaction of CREB with its cofactor CBP. These results suggest that Ca2+ influx triggers a specific program of gene expression in neurons by selectively regulating CREB phosphorylation. [Copyright &y& Elsevier]

Mutations in the methyl-DNA-binding repressor protein MeCP2 cause the devastating neurodevelopmental disorder Rett syndrome. It has been challenging to understand how MeCP2 regulates transcription because MeCP2 binds broadly across the genome and MeCP2 mutations are associated with widespread small-magnitude changes in neuronal gene expression. We demonstrate here that MeCP2 represses nascent RNA transcription of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex. By measuring the rates of transcriptional initiation and elongation directly in the brain, we find that MeCP2 has no measurable effect on transcriptional elongation, but instead represses the rate at which Pol II initiates transcription of highly methylated long genes. These findings suggest a new model of MeCP2 function in which MeCP2 binds broadly across highly methylated regions of DNA, but acts at transcription start sites to attenuate transcriptional initiation. • MeCP2 represses transcription of highly methylated long genes through NCoR • Direct measurements of transcriptional initiation and elongation rates in the mouse brain • MeCP2 reduces transcriptional initiation, not elongation, of highly methylated long genes • Gene body-TSS contacts position distal MeCP2 molecules at the TSS Mutations in MeCP2 cause the neurodevelopmental disorder Rett syndrome. Although MeCP2 binding is enriched in methylated gene bodies, Boxer et al. find that MeCP2 decreases the rate of transcriptional initiation, but not elongation, of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex. [ABSTRACT FROM AUTHOR]