Connectivity map Broad

BACKGROUND: The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. The brain-wide pattern of temporal co-activation between distinct brain regions, referred to as the functional connectome, underpins individual differences in behavior...

Participant-specific, functionally defined brain areas are usually mapped with functional localizers and estimated by making contrasts between responses to single categories of input. Naturalistic stimuli engage multiple brain systems in parallel, provide more ecologically plausible estimates of real-world statistics, and are friendly to special populations. The current study shows that cortical functional topographies in individual participants can be estimated with high fidelity from naturalistic stimuli...

BACKGROUND: The increasing use of smartphones, wearables, and connected devices has enabled the increasing application of digital technologies for research. Remote digital study platforms comprise a patient-interfacing digital application that enables multimodal data collection from a mobile app and connected sources. They offer an opportunity to recruit at scale, acquire data longitudinally at a high frequency, and engage study participants at any time of the day in any place. Few published descriptions of centralized digital research platforms provide a framework for their development...

BACKGROUND: Chinese gay, bisexual and other men who have sex with men (GBMSM) face discrimination in many facility-based health services, thus increasing the importance of online engagement. The purpose of this study was to examine online GBMSM community spaces and implications for HIV/STD prevention services. METHODS: We conducted a total of six online focus group discussions with Chinese GBMSM from Guangdong province on the chat-based platform WeChat in 2021. Focus group discussions were asynchronous, and participants were able to provide and map out online spaces that they had participated in and share their perspectives on online engagement...

Novel approaches are required to find new treatments for schizophrenia and other neuropsychiatric disorders. This study utilised a combination of in vitro transcriptomics and in silico analysis with the BROAD Institute's Connectivity Map to identify drugs that can be repurposed to treat psychiatric disorders. Human neuronal (NT2-N) cells were treated with a combination of atypical antipsychotic drugs commonly used to treat psychiatric disorders (such as schizophrenia, bipolar disorder, and major depressive disorder), and differential gene expression was analysed...

Global biodiversity hotspots are often remote, tectonically active areas undergoing climatic fluctuations, such as the Himalaya Mountains and neighboring Qinghai-Tibetan Plateau (QTP). They provide biogeographic templates upon which endemic biodiversity can be mapped to infer diversification scenarios. Yet, this process can be somewhat opaque for the Himalaya, given substantial data gaps separating eastern and western regions. To help clarify, we evaluated phylogeographic and phylogenetic hypotheses for a widespread fish (Snowtrout: Cyprininae; Schizothorax) by sequencing 1,140 base pair of mtDNA cytochrome-b (cytb) from Central Himalaya samples (Nepal: N = 53; Bhutan: N = 19), augmented with 68 GenBank sequences (N = 60 Schizothorax/N = 8 outgroups)...

Microtubule-targeting agents represent one of the most successful classes of anticancer agents. However, the development of drug resistance and the appearance of adverse effects hamper their clinical implementation. Novel microtubule-targeting agents without such limitations are urgently needed. By employing a gene expression-based drug repositioning strategy, this study identifies VU-0365114, originally synthesized as a positive allosteric modulator of human muscarinic acetylcholine receptor M5 (M5 mAChR), as a novel type of tubulin inhibitor by destabilizing microtubules...

Aquaporins provide a unique approach for imaging genetic activity in deep tissues by increasing the rate of cellular water diffusion, which generates a magnetic resonance contrast. However, distinguishing aquaporin signals from the tissue background is challenging because water diffusion is influenced by structural factors, such as cell size and packing density. Here, we developed a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on subtracting signals at two diffusion times can improve specificity by unambiguously isolating aquaporin signals from the tissue background...

The Intercalated Cells of the Amygdala (ITCs) are a fundamental processing structure in the amygdala that remain relatively understudied. They are phylogenetically conserved from insectivores through primates, inhibitory, and project to several of the main processing and output stations of the amygdala and basal forebrain. Through these connections, the ITCs are best known for their role in conditioned fear, where they are required for fear extinction learning and recall. Prior work on ITC connectivity is limited, and thus holistic characterization of their afferent and efferent connectivity in a genetically defined manner is incomplete...

Background: Research has recently begun to examine the potential intergenerational impacts of trauma on obesity. Objective: This scoping review examines the literature on the interactions between intergenerational trauma, epigenetics, and obesity in Indigenous populations. The review was conducted to identify what is known from the literature about how intergenerational trauma may epigenetically influence obesity in Indigenous populations. Methods: Following the PRISMA-ScR guidelines for scoping reviews, online databases were used to identify studies that included discussion of the four focus topics: trauma, epigenetics, obesity, and Indigeneity...

Youth depression has been associated with heterogenous patterns of aberrant brain connectivity. To make sense of these divergent findings, we conducted a systematic review encompassing 19 resting-state fMRI seed-to-whole-brain studies (1400 participants, comprising 795 youths with major depression and 605 matched healthy controls). We incorporated separate meta-analyses of connectivity abnormalities across the levels of the most commonly seeded brain networks (default-mode and limbic networks) and, based on recent additions to the literature, an updated meta-analysis of amygdala dysconnectivity in youth depression...

Understanding the geographic linkages among populations across the annual cycle is an essential component for understanding the ecology and evolution of migratory species and for facilitating their effective conservation. While genetic markers have been widely applied to describe migratory connections, the rapid development of new sequencing methods, such as low-coverage whole genome sequencing (lcWGS), provides new opportunities for improved estimates of migratory connectivity. Here, we use lcWGS to identify fine-scale population structure in a widespread songbird, the American Redstart (Setophaga ruticilla), and accurately assign individuals to genetically distinct breeding populations...

In primary gustatory cortex (GC), a subregion of the insular cortex, neurons show anticipatory activity, encode taste identity and palatability, and their activity is related to decision making. Inactivation of the gustatory thalamus, the parvicellular region of the ventral posteromedial thalamic nucleus (VPMpc), dramatically reduces GC taste responses, consistent with the hypothesis that VPMpc-GC projections carry taste information. Recordings in awake rodents reported that taste responsive neurons can be found across GC, without segregated spatial mapping, raising the possibility that projections from the taste thalamus may activate GC broadly...

BACKGROUND: Functional inactivation of ATRX characterizes large subgroups of malignant gliomas in adults and children. ATRX deficiency in glioma induces widespread chromatin remodeling, driving transcriptional shifts and oncogenic phenotypes. Effective strategies to therapeutically target these broad epigenomic sequelae remain undeveloped. METHODS: We utilized integrated mulit-omics and the Broad Institute Connectivity Map (CMAP) to identify drug candidates that could potentially revert ATRX-deficient transcriptional changes...

Shifts in gender roles, identities and relations since the 1980s are continuing to influence masculinities within intimate partner relationships. Forefront in men's contemporary heterosexual relationships have been calls for gender equality and gender equity as a means to promoting the mental health and well-being of partners and their families. Most previous research has focused on a pathologized role of men in relationships (e.g., intimate partner violence). Little is known about how men perceive intimate partner relationships using a strength-based perspective...

Gene expression profiles that connect drug perturbations, disease gene expression signatures, and clinical data are important for discovering potential drug repurposing indications. However, the current approach to gene expression reversal has several limitations. First, most methods focus on validating the reversal expression of individual genes. Second, there is a lack of causal approaches for identifying drug repurposing candidates. Third, few methods for passing and summarizing information on a graph have been used for drug repurposing analysis, with classical network propagation and gene set enrichment analysis being the most common...

Evidence indicating abnormal functional connectivity (FC) among the cortex, thalamus, and cerebellum in schizophrenia patients has increased. However, the role of the thalamus and cerebellum when integrated into intrinsic networks and how those integrated networks interact in schizophrenia patients are largely unknown. We generated an integrative network map by merging thalamic and cerebellar network maps, which were parcellated using a winner-take-all approach, onto a cortical network map. Using cognitive networks, the default mode network (DMN), the dorsal attention network (DAN), the salience network (SAL), and the central executive network (CEN) as regions of interest, the FC of 48 schizophrenia patients was compared with that of 57 healthy controls (HCs)...

Our ability to sense and move our bodies relies on proprioceptors, sensory neurons that detect mechanical forces within the body. Different subtypes of proprioceptors detect different kinematic features, such as joint position, movement, and vibration, but the mechanisms that underlie proprioceptor feature selectivity remain poorly understood. Using single-nucleus RNA sequencing (RNA-seq), we found that proprioceptor subtypes in the Drosophila leg lack differential expression of mechanosensitive ion channels...

The retinal pigment epithelium (RPE) and choroid are located behind the human retina and have multiple functions in the human visual system. Knowledge of the RPE and choroid cells and their gene expression profiles are fundamental for understanding retinal disease mechanisms and therapeutic strategies. Here, we sequenced the RNA of about 0.3 million single cells from human RPE and choroids across two regions and seven ages, revealing regional and age differences within the human RPE and choroid. Cell-cell interactions highlight the broad connectivity networks between the RPE and different choroid cell types...

The human brain is a complex network comprised of functionally and anatomically interconnected brain regions. A growing number of studies have suggested that empirical estimates of brain networks may be useful for discovery of biomarkers of disease and cognitive state. A prerequisite for realizing this aim, however, is that brain networks also serve as reliable markers of an individual. Here, using Human Connectome Project data, we build upon recent studies examining brain-based fingerprints of individual subjects and cognitive states based on cognitively demanding tasks that assess, for example, working memory, theory of mind, and motor function...