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Whole-genome sequencing provides lists of genes of putative relevance to organismal biology. However, in all metazoans, a large fraction of inferred genes has no known functions, in some cases with no orthologs in related species, and even orthology at the DNA-sequence level often not providing indisputable evidence of gene function. A first step towards resolving the functional features of gene encyclopedias in multicellular species is to evaluate the tissues in which individual genes are expressed. Here, we report on assays of expression for the full sets of protein-coding and long-noncoding RNA (lncRNA) genes across eight tissues of the microcrustacean Daphnia pulex. We also take advantage of a large database on levels of polymorphism and divergence for each gene to infer various features of selection operating on genes expressed in different tissues, including novel genes restricted to particular Daphnia lineages. In addition to generating a resource for future work on the molecular, cellular, and developmental biology of the model species D. pulex, this study highlights a number of novel findings. These include the identification of sets of genes experiencing unusual forms of positive selection, the discovery of unusual patterns of evolution in the pool of testes-specific genes, rapid turnover and sequence evolution of lncRNA genes, and the pervasive operation of selection on genes thought to be D. pulex-specific.
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http://dx.doi.org/10.1101/2025.05.01.651673 | DOI Listing |
J Am Soc Nephrol
September 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Background: Genetic modifiers are believed to play an important role in the onset and severity of polycystic kidney disease (PKD), but identifying these modifiers has been challenging due to the lack of effective methodologies.
Methods: We generated zebrafish mutants of IFT140, a skeletal ciliopathy gene and newly identified autosomal dominant PKD (ADPKD) gene, to examine skeletal development and kidney cyst formation in larval and juvenile mutants. Additionally, we utilized ift140 crispants, generated through efficient microhomology-mediated end joining (MMEJ)-based genome editing, to compare phenotypes with mutants and conduct a pilot genetic modifier screen.
JCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
View Article and Find Full Text PDFJCI Insight
September 2025
Division of Nephrology, Boston University Chobanian & Avedisian School of Medicine, Boston, United States of America.
Background: Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects that attenuate acute kidney injury (AKI) in animal models.
Methods: We conducted a phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among 150 critically ill adult patients at high-risk of moderate-to-severe AKI. The primary endpoint was a hierarchical composite of death, kidney replacement therapy (KRT), and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure.
J Clin Invest
September 2025
Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, United Kingdom.
Understanding the genetic causes of diseases affecting pancreatic β cells and neurons can give insights into pathways essential for both cell types. Microcephaly, epilepsy and diabetes syndrome (MEDS) is a congenital disorder with two known aetiological genes, IER3IP1 and YIPF5. Both genes encode proteins involved in endoplasmic reticulum (ER) to Golgi trafficking.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
Florida Museum of Natural History, University of Florida, Gainesville, FL 32611.
The origin and phylogenetic distribution of symbiotic associations between nodulating angiosperms and nitrogen-fixing bacteria have long intrigued biologists. Recent comparative evolutionary analyses have yielded alternative hypotheses: a multistep pathway of independent gains and losses of root nodule symbiosis vs. a single gain followed by numerous losses.
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