187 research outputs found

    History Department 2020 Summer Reading Suggestions

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    This list of readings was collected by USM History Department faculty at the University of Southern Maine. From the guide: An important part of the anti-racist work of dismantling racial inequities is self-education, doing the work of learning about the hundreds of years of oppression and injustice that provide the context to our contemporary struggles. For historians, context is key to all that we do. Faculty members in the Department of History at USM have come together to suggest a series of texts that we find both personally significant and think will be helpful in coming to a greater understanding of the events, actions, and inactions that have led us to this current moment in the United States and globally. This list reflects our diverse geographical areas of expertise and research, and is by no means exhaustive. We continue to learn from one another, and from our students. We welcome student suggestions on books and pieces you think we should read; this is a conversation. We encourage you to cast a wide net in your anti-racist reading and learning. Here is a place to start

    Sporadic ALS has compartment-specific aberrant exon splicing and altered cell–matrix adhesion biology

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (P ≤ 10−3) and 411 aberrantly spliced genes (P ≤ 10−5). The aberrantly spliced genes were highly enriched in cell adhesion (P ≤ 10−57), especially cell–matrix as opposed to cell–cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell–matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration. Data deposition: GeneChip raw data (CEL-files) have been deposited for public access in the Gene Expression Omnibus (GEO), www.ncbi.nlm.nih.gov/geo, accession number GSE18920

    Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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    Human matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn(2+) atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes
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