Ascidians are simple chordates that are related to, and may resemble, vertebrate ancestors. Comparison of ascidian and vertebrate genomes is expected to provide insight into the molecular genetic basis of chordate/vertebrate evolution. We annotated muscle structural (contractile protein) genes in the completely determined genome sequence of the ascidian Ciona intestinalis, and examined gene expression patterns through extensive EST analysis. Ascidian muscle protein isoform families are generally of similar, or lesser, complexity in comparison with the corresponding vertebrate isoform families, and are based on gene duplication histories and alternative splicing mechanisms that are largely or entirely distinct from those responsible for generating the vertebrate isoforms. Although each of the three ascidian muscle types - larval tail muscle, adult body-wall muscle and heart - expresses a distinct profile of contractile protein isoforms, none of these isoforms are strictly orthologous to the smooth-muscle-specific, fast or slow skeletal muscle-specific, or heart-specific isoforms of vertebrates. Many isoform families showed larval-versus-adult differential expression and in several cases numerous very similar genes were expressed specifically in larval muscle. This may reflect different functional requirements of the locomotor larval muscle as opposed to the non-locomotor muscles of the sessile adult, and/or the biosynthetic demands of extremely rapid larval development.
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Biomolecules
January 2025
Department of Pharmacology and Immunology, Medical University of South Carolina, 173 Ashley Ave., MSC509, Charleston, SC 29425, USA.
Cutaneous T-cell lymphoma (CTCL) is a rare T-cell malignancy characterized by inflamed and painful rash-like skin lesions that may affect large portions of the body's surface. Patients experience recurrent infections due to a compromised skin barrier and generalized immunodeficiency resulting from a dominant Th2 immune phenotype of CTCL cells. Given the role of the unfolded protein response (UPR) in normal and malignant T-cell development, we investigated the impact of UPR-inducing drugs on the viability, transcriptional networks, and Th2 phenotype of CTCL.
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January 2025
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address:
Multiple myeloma is a clonal plasma cell (PC) dyscrasia that arises from precursors and has been studied utilizing approaches focused on CD138 cells. By combining single-cell RNA sequencing (scRNA-seq) with scB-cell receptor sequencing (scBCR-seq), we differentiate monoclonal/neoplastic from polyclonal/normal PCs and find more dysregulated genes, especially in precursor patients, than we would have by analyzing bulk PCs. To determine whether this approach can identify oncogenes that contribute to disease pathobiology, mitotic arrest deficient-2 like-1 (MAD2L1) and S-adenosylmethionine synthase isoform type-2 (MAT2A) are validated as targets with drug-like molecules that suppress myeloma growth in preclinical models.
View Article and Find Full Text PDFImmunohorizons
January 2025
Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, United States.
Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses.
View Article and Find Full Text PDFProtein Sci
February 2025
Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, Zaragoza, Spain.
PADI4 is one of the human isoforms of a family of enzymes involved in the conversion of arginine to citrulline. MDM2 is an E3 ubiquitin ligase that is critical for degradation of the tumor suppressor gene p53. We have previously shown that there is an interaction between MDM2 and PADI4 in cellulo, and that such interaction occurs through the N-terminal region of MDM2, N-MDM2, and in particular through residues Thr26, Val28, Phe91, and Lys98.
View Article and Find Full Text PDFAnn Hematol
January 2025
Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
Acute promyelocytic leukemia (APL) is driven by the specific fusion gene PML-RARA produced by chromosomal translocation. Three classic isoforms, L, V, and S, are found in more than 95% of APL patients. However, atypical PML-RARA isoforms are usually associated with uncertain disease progression and treatment prognosis.
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