Publications by authors named "W B Ruzicka"

Article Synopsis
  • - Substance use disorders (SUD) and drug addiction significantly impact public health, particularly among individuals and their communities, with a notable overlap between SUD and human immunodeficiency virus (HIV) infections.
  • - The connection between SUD and HIV is complex, as HIV can increase the risk of SUD through chronic pain treatment, while those with SUD are more likely to contract HIV, highlighting the need for integrated research.
  • - The SCORCH consortium aims to utilize single-cell genomics to examine the interactions between SUD and HIV at a cellular level, leveraging human brain tissue collections and animal models for in-depth study.
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Article Synopsis
  • Schizophrenia's complexity has made it difficult to understand its mechanisms and develop effective treatments; a new study addresses this by examining transcriptomic changes at the single-cell level in the human prefrontal cortex of 140 individuals.
  • The researchers found that excitatory neurons were the most affected, with changes related to neurodevelopment and synapse function, and identified both common and rare genetic risk factors influencing these neuronal alterations.
  • Their findings reveal two distinct groups of individuals with schizophrenia based on specific excitatory and inhibitory neuron states, linking genetic risk to cellular changes and enhancing our understanding of schizophrenia's underlying biology.
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Genome-wide association studies (GWASs) have successfully identified 145 genomic regions that contribute to schizophrenia risk, but linkage disequilibrium makes it challenging to discern causal variants. We performed a massively parallel reporter assay (MPRA) on 5,173 fine-mapped schizophrenia GWAS variants in primary human neural progenitors and identified 439 variants with allelic regulatory effects (MPRA-positive variants). Transcription factor binding had modest predictive power, while fine-map posterior probability, enhancer overlap, and evolutionary conservation failed to predict MPRA-positive variants.

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Recent studies describe distinct DNA methylomes among phenotypic subclasses of neurons in the human brain, but variation in DNA methylation between common neuronal phenotypes distinguished by their function within distinct neural circuits remains an unexplored concept. Studies able to resolve epigenetic profiles at the level of microcircuits are needed to illuminate chromatin dynamics in the regulation of specific neuronal populations and circuits mediating normal and abnormal behaviors. The Illumina HumanMethylation450 BeadChip was used to assess genome-wide DNA methylation in stratum oriens GABAergic interneurons sampled by laser-microdissection from two discrete microcircuits along the trisynaptic pathway in postmortem human hippocampus from eight control, eight schizophrenia, and eight bipolar disorder subjects.

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