Patterns of Cerebellar-Cortical Structural Covariance Mirror Anatomical Connectivity of Sensorimotor and Cognitive Networks.

The cortex and cerebellum are densely connected through reciprocal input/output projections that form segregated circuits. These circuits are shown to differentially connect anterior lobules of the cerebellum to sensorimotor regions, and lobules Crus I and II to prefrontal regions. This differential connectivity pattern leads to the hypothesis that individual differences in structure should be related, especially for connected regions.

Disentangling the effect of sex from brain size on brain organization and cognitive functioning.

Neuroanatomical sex differences estimated in neuroimaging studies are confounded by total intracranial volume (TIV) as a major biological factor. Employing a matching approach widely used for causal modeling, we disentangled the effect of TIV from sex to study sex-differentiated brain aging trajectories, their relation to functional networks and cytoarchitectonic classes, brain allometry, and cognition. Using data from the UK Biobank, we created subsamples that removed, maintained, or exaggerated the TIV differences in the original sample.

Considering the interconnected nature of social identities in neuroimaging research.

Considerable heterogeneity exists in the expression of complex human behaviors across the cognitive, personality and mental health domains. It is increasingly evident that individual variability in behavioral expression is substantially affected by sociodemographic factors that often interact with life experiences. Here, we formally address the urgent need to incorporate intersectional identities in neuroimaging studies of behavior, with a focus on research in mental health.

Tetra-benzimidazoles flanking divinyl-phenothiazine: AIEgens as aza-Michael acceptors in concentration-tuned responses to biogenic amine vapors.

Tetra-benzimidazole rotors flanking a divinyl-phenothiazine stator are realized as red AIEgens and newly identified as efficient aza-Michael acceptors for the identification of biogenic amine vapors. Weakly red-emissive solids display a blue-shifted turn-on emission by rapid aza-Michael addition and simultaneous reverse Knoevenagel reactions. Concentration variation imposes better crystallinity and facilitates radiative decay, offering distinct emissions.

Hippocampal atrophy over two years in relation to tau, amyloid-β and memory in older adults.

In this longitudinal brain imaging study, we aimed to characterize hippocampal tau accumulation and subfield atrophy relative to cortical amyloid-β and memory performance. We measured tau-PET in regions associated with Braak stages I to VI, global amyloid-PET burden, hippocampal subfield volumes and memory assessments from 173 participants aged 55-85. Eighty-six of these participants were tested again two years later.

Unveiling the Long-Awaited Aldehyde Intermediate in Oxidative Dephosphorylation: A Unique Approach to Access Useful Carboxaldehydes.

Oxidative dephosphorylation reactions usually generate symmetrically substituted alkenes from organophosphonates. Even the ubiquitous presence of oxygen can produce such alkenes inadvertently as a side product in small amounts from Wittig/Horner-Wadsworth-Emmons (HWE) reactions. So far, aldehydes have been expected to be the on-pathway intermediate since their discovery, but there was no substantial experimental evidence to support this.

Increased structural covariance of cortical measures in individuals with an at-risk mental state.

An anomalous pattern of structural covariance has been reported in schizophrenia, which has been suggested to represent connectome changes during brain maturation and neuroprogressive processes. It remains unclear whether similar differences exist in a clinical high-risk state for psychosis, and if they are associated with a prodromal phenotype and/or later psychosis onset. This multicenter magnetic resonance imaging study cross-sectionally examined structural covariance in a large at-risk mental state (ARMS) sample with different outcomes.

Association of Changes in Cerebral and Hypothalamic Structure With Sleep Dysfunction in Patients With Genetic Frontotemporal Dementia.

Background And Objectives: Sleep dysfunction is common in patients with neurodegenerative disorders; however, its neural underpinnings remain poorly characterized in genetic frontotemporal dementia (FTD). Hypothalamic nuclei important for sleep regulation may be related to this dysfunction. Thus, we examined changes in hypothalamic structure across the lifespan in patients with genetic FTD and whether these changes related to sleep dysfunction.

Prenatal cannabis exposure in the clinic and laboratory: What do we know and where do we need to go?

Coincident with the legalisation of cannabis in many nations, rates of cannabis use during pregnancy have increased. Like prior investigations on smoking and alcohol, understanding how prenatal cannabis exposure (PCE) impacts offspring outcomes across the lifespan will be critical for informing choices for pregnant people, clinicians, and policy makers alike. A thorough characterization of the life-long impacts is especially urgent for supporting all of these stakeholders in the decision-making process.

Aging-dependent loss of functional connectivity in a mouse model of Alzheimer's disease and reversal by mGluR5 modulator.

Amyloid accumulation in Alzheimer's disease (AD) is associated with synaptic damage and altered connectivity in brain networks. While measures of amyloid accumulation and biochemical changes in mouse models have utility for translational studies of certain therapeutics, preclinical analysis of altered brain connectivity using clinically relevant fMRI measures has not been well developed for agents intended to improve neural networks. Here, we conduct a longitudinal study in a double knock-in mouse model for AD (App/hMapt), monitoring brain connectivity by means of resting-state fMRI.

A standardized image processing and data quality platform for rodent fMRI.

Functional magnetic resonance imaging in rodents holds great potential for advancing our understanding of brain networks. Unlike the human community, there remains no standardized resource in rodents for image processing, analysis and quality control, posing significant reproducibility limitations. Our software platform, Rodent Automated Bold Improvement of EPI Sequences, is a pipeline designed to address these limitations for preprocessing, quality control, and confound correction, along with best practices for reproducibility and transparency.

Access to Diverse Glutamic Acid Dendrons and a Janus Peptide Dendrimer Using an Atypical Solid Phase Synthesis.

The negligible cytotoxicity of anion surface-linked dendrons makes glutamic acid-based dendrons a potential candidate for materials and biological applications. Despite the inherent drawbacks of the conventional solution phase synthesis of glutamic acid-based dendrons, there have been no advancements in these protocols. Herein, we demonstrate the first-ever convergent solid phase synthesis of dendrons, up to fourth generation, having glutamic acid branching points produced by preactivation of dicarboxylic acid groups with -hydroxysuccinimide and simultaneous coupling with amine groups of two growing peptide chains, with excellent yields (30-70%).

Network enrichment significance testing in brain-phenotype association studies.

Functional networks often guide our interpretation of spatial maps of brain-phenotype associations. However, methods for assessing enrichment of associations within networks of interest have varied in terms of both scientific rigor and underlying assumptions. While some approaches have relied on subjective interpretations, others have made unrealistic assumptions about spatial properties of imaging data, leading to inflated false positive rates.

Multimodal identification of the mouse brain using simultaneous Ca imaging and fMRI.

Individual differences in neuroimaging are of interest to clinical and cognitive neuroscientists based on their potential for guiding the personalized treatment of various heterogeneous neurological conditions and diseases. Despite many advantages, the workhorse in this arena, BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI) suffers from low spatiotemporal resolution and specificity as well as a propensity for noise and spurious signal corruption. To better understand individual differences in BOLD-fMRI data, we can use animal models where fMRI, alongside complementary but more invasive contrasts, can be accessed.

Immune Alterations in the Intrauterine Environment Shape Offspring Brain Development in a Sex-Specific Manner.

Exposure to immune dysregulation in utero or in early life has been shown to increase risk for neuropsychiatric illness. The sources of inflammation can be varied, including acute exposures due to maternal infection or acute stress, or persistent exposures due to chronic stress, obesity, malnutrition, or autoimmune diseases. These exposures may cause subtle alteration in brain development, structure, and function that can become progressively magnified across the lifespan, potentially increasing the likelihood of developing a neuropsychiatric conditions.

Effects of diazepam on hippocampal blood flow in people at clinical high risk for psychosis.

Elevated hippocampal perfusion has been observed in people at clinical high risk for psychosis (CHR-P). Preclinical evidence suggests that hippocampal hyperactivity is central to the pathophysiology of psychosis, and that peripubertal treatment with diazepam can prevent the development of psychosis-relevant phenotypes. The present experimental medicine study examined whether diazepam can normalize hippocampal perfusion in CHR-P individuals.

Longitudinal inference of multiscale markers in psychosis: from hippocampal centrality to functional outcome.

Multiscale neuroscience conceptualizes mental illness as arising from aberrant interactions across and within multiple biopsychosocial scales. We leverage this framework to propose a multiscale disease progression model of psychosis, in which hippocampal-cortical dysconnectivity precedes impairments in episodic memory and social cognition, which lead to more severe negative symptoms and lower functional outcome. As psychosis represents a heterogeneous collection of biological and behavioral alterations that evolve over time, we further predict this disease progression for a subtype of the patient sample, with other patients showing normal-range performance on all variables.

Histomorphometric and Immunohistochemical Diagnosis of Renal Cell Carcinoma: Review Article.

Renal cell carcinoma (RCC) is derived from renal tubular epithelial cells and is among the 10 most common cancers worldwide. Incidence of renal cell carcinoma is 400,000 individuals worldwide per year. The age of diagnosis is approximately 60years, and twice as many men are diagnosed as women.

Targeting hexokinase 2 for oral cancer therapy: structure-based design and validation of lead compounds.

The pursuit of small molecule inhibitors targeting hexokinase 2 (HK2) has significantly captivated the field of cancer drug discovery. Nevertheless, the creation of selective inhibitors aimed at specific isoforms of hexokinase (HK) remains a formidable challenge. Here, we present a multiple-pharmacophore modeling approach for designing ligands against HK2 with a marked anti-proliferative effect on FaDu and Cal27 oral cancer cell lines.

The impact of quality control on cortical morphometry comparisons in autism.

Structural magnetic resonance imaging (MRI) quality is known to impact and bias neuroanatomical estimates and downstream analysis, including case-control comparisons, and a growing body of work has demonstrated the importance of careful quality control (QC) and evaluated the impact of image and image-processing quality. However, the growing size of typical neuroimaging datasets presents an additional challenge to QC, which is typically extremely time and labour intensive. One of the most important aspects of MRI quality is the accuracy of processed outputs, which have been shown to impact estimated neurodevelopmental trajectories.

Isomeric Benzenediol-Linked Organophosphonates as a Handy Reusable Emitting Platform: Diversity in Polyamine Vapor Detection.

This work introduces metal/column-free facile quantitative access to conformationally twisted catechol-linked organophosphonate () as a blue-emitting solid that could reversibly detect only 1,3-diaminopropane (DAP) and 1,2-ethylenediamine (EDA) vapors, belonging to industrially and pharmaceutically abundant crucial diamines. In , two adjacent hydroxy groups in a benzene ring facilitate selective diamine-dihydroxy (amine-phenol type) interactions in the solid phase, leading to a quenched emission with selectively smaller aliphatic PAs, that is, DAP and EDA. The disparity was noticed with an isomeric resorcinol-linked emitter (), detecting various polyamine vapors with superior sensitivity.

Parkinson's disease CA2-CA3 hippocampal atrophy is accompanied by increased cholinergic innervation in patients with normal cognition but not in patients with mild cognitive impairment.

Although brain cholinergic denervation has been largely associated with cognitive decline in patients with Parkinson's disease (PD), new evidence suggests that cholinergic upregulation occurs in the hippocampus of PD patients without cognitive deficits. The specific hippocampal sectors and potential mechanisms of this cholinergic compensatory process have been further studied here, using MRI volumetry and morphometry coupled with molecular imaging using the PET radiotracer [F]-Fluoroethoxybenzovesamicol ([F]-FEOBV). Following a thorough screening procedure, 18 participants were selected and evenly distributed in three groups, including cognitively normal PD patients (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and healthy volunteers (HV).