Project description:This is a subset of the data set generated by the UK Brain Expression Consortium. This subset has been used specifically to study the effects of age on gene expression in multiple human tissues, and all samples originate from a single brain bank, the MRC Sudden Death Brain and Tissue Bank in Edinburgh. The UK Brain Expression Consortium has generated gene expression data on a large cohort of neurologically and neuropathologically normal individuals in order to better understand gene expression differences across the human brain. 932 samples are analysed in total originating from 100 Caucasian individuals. From each individual, up to ten brain regions were sampled and analysed.
Project description:Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive cognitive impairment and neurodegeneration as a result of abnormal neuronal loss. To elucidate the molecular systems associated with AD, we characterized the gene expression changes associated with multiple clinical and neuropathological traits in 1,053 postmortem brain samples across 19 brain regions from 125 persons dying with varying severities of dementia and variable AD-neuropathology severities. 125 human brains were accessed from the Mount Sinai/JJ Peters VA Medical Center Brain Bank (MSBB). This brain resource was assembled after applying stringent inclusion/exclusion criteria and represents the full spectrum of clinical and neuropathological disease severity in the absence of discernable non-AD neuropathology. RNA samples from 19 brain regions isolated from the 125 MSBB specimens were collected and profiled using Affymetrix Genechip microarrays. There were 50 to 60 subjects per brain region with varying degrees of AD pathological abnormalities.
Project description:Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus – brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively – from individuals spanning the neuropathological progression of AD. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. The brain tissue used in this study were sourced from the Biobank for Aging Studies (LIM-22) in the Department of Pathology at the University of Sao Paulo, as well as from the Neurodegenerative Diseases Brain Bank in the Memory and Aging Center at the University of California, San Francisco. Detailed neuropathological, clinical and genetic data are available under request. Please contact gerolab@gmail.com and lea.grinberg@ucsf.edu.
Project description:Survey of gene expression in 7 brain regions at 6-8wks of age in 20 inbred strains of laboratory mice. Autism is a highly heritable neurodevelopmental disorder with no consistent neuropathological hallmarks, diagnosed through behavioral inventory rather than a biomarker. The genetic etiology of autism is complex and likely has a significant interaction with the environment. To investigate the molecular and genetic nature of autism, we modeled the core symptom of social deficits in inbred strains of mice. Using gene expression profiles and behavioral phenotyping relevant to social deficits, we have identified basic cellular functions that may be dysregulated in the brain in autism. Correlations between these two complex datasets indicate cell morphology, proliferation, and migration may be perturbed in disorders of altered social behavior. Furthermore, these data in the mouse show significant overlap with published expression profiling in lymphoblastoid lines from autistic individuals. Keywords: Comparison between inbred strains and brain regions.
Project description:The temporal lobe is the cerebral cortex with critical function. The superior and middle gyrus of temporal lobe have been well studied, however, present perceptions on inferior temporal gyrus remains limited. The understanding of age-related protein profile change in human inferior temporal gyrus has not yet been well established. This 3-plex TMT labeled proteomic study is performed based on the human brain bank at the Chinese Academy of Medical Sciences & Peking Union Medical College. Age distribution of the donors ranges from 22 to 90 years old, and were assigned to three age groups: 20-50, 50-70, and 70-90 years of death age. In this ageing cohort, no neurodegenerative disorders or major stroke events were identified via standard neuropathological classification. Proteomics and bioinformatics strategies were applied to identify the perturbations of protein expression and associated pathways. Among all the ITG samples, 3113 proteins were isolated, with 37 proteins upregulated and 21 proteins downregulated.
Project description:The title compound, C(29)H(37)NO(2), crystallized with two independent mol-ecules in an asymmetric unit in which the conformation of the cyclo-hexyl ring of the pregnene moiety bonded to the 3?-(1,3-dioxoisoindolin-2-yl)- ring system differs: in one mol-ecule it is in a chair conformation, while in the other it exhibits a half-chair conformation. The other six-membered rings in the pregnene moiety are in chair conformations and the five-membered rings are in envelope forms in both mol-ecules. In both mol-ecules, the 3?-(1,3-dioxoisoindolin-2-yl)- ring systems are individually approximately planar, with r.m.s. devtaions 0.0148 and 0.0264?Å. The structure is consolidated by inter-molecular C-H?O hydrogen-bonding inter-actions involving the carbonyl O atoms and methyl, methyl-ene and methyl-idyne groups, resulting in a two-dimensional structure.
Project description:In the pregnene fragment of the title compound, C27H38ClN, the three six-membered rings exhibit chair conformations and the five-membered ring has a distorted envelope form with the fused C atom not bearing a methyl group as the flap atom. The amino group is involved in the formation of an intra-molecular N-H?Cl hydrogen bond. The crystal packing exhibits no short inter-molecular contacts.