Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
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http://dx.doi.org/10.1038/nature08160 | DOI Listing |
Mol Neurobiol
January 2025
Department of Neurology, School of Medicine, Affiliated ZhongDa Hospital, Southeast University, Dingjiaqiao 87, Nanjing, 210009, Jiangsu, China.
The dysregulation of lipid metabolism has been associated with the etiology and progression of the neurological pathology. However, the roles of lipid metabolism and the molecular mechanism in epilepsy and the use of antiepileptic drugs (AEDs) are relatively understudied. Gene expression profiles of GSE143272 from blood samples were included for differential analysis, and the lipid metabolism-related differentially expressed genes (DEGs) were identified.
View Article and Find Full Text PDFJ Clin Immunol
January 2025
Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Reduced function or hypomorphic variants in recombination-activating genes (RAG) 1 or 2 result in a broad clinical phenotype including common variable immunodeficiency (CVID) and even adult-onset disease. Milder RAG variants are less characterized. Here we describe the longitudinal course of a milder combined RAG deficiency in 3 of 7 siblings sharing the same RAG2 mutations over a 50-year study.
View Article and Find Full Text PDFJ Neurol
January 2025
Morehouse School of Medicine, Neuroscience Institute, 720 Westview Drive SW, Atlanta, GA, 30310, USA.
Objectives: The ability to differentiate epileptic- and non-epileptic events is challenging due to a lack of reliable molecular seizure biomarker that provide a retrospective diagnosis. Here, we use next generation sequencing methods on whole blood samples to identify changes in RNA expression following seizures.
Methods: Blood samples were obtained from 32 patients undergoing video electroencephalogram (vEEG) monitoring.
Funct Integr Genomics
January 2025
Department of Exercise Science and Health Promotion, Florida Atlantic University, Boca Raton, FL, USA.
Large-scale, pan-cancer analysis is enabled by data driven knowledge bases that link tumor molecular profiles with phenotypes. A debilitating cancer-related phenotype is skeletal muscle loss, or cachexia, which occurs partly from tumor products secreted into circulation. Using the LinkedOmicsKB knowledge base assembled from the Clinical Proteomics Tumor Analysis Consortium proteogenomic analysis, along with catalogs of human secretome proteins, ligand-receptor pairs and molecular signatures, we sought to identify candidate pan-cancer proteins secreted to blood that could regulate skeletal muscle phenotypes in multiple solid cancers.
View Article and Find Full Text PDFJ Exp Med
February 2025
Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163, Imagine Institute, University Paris Cité, Paris, France.
IKKα, encoded by CHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. The absence of IKKα causes fetal encasement syndrome in humans, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and causes combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features.
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