Loss-of-function variants in ZDHHC9 have been identified in patients with X-linked intellectual disability (XLID), with ~2% of XLID patients exhibiting mutations in ZDHHC9. Patients with XLID plus ZDHHC9 mutations also have an elevated incidence of epilepsy compared to XLID patients with intact ZDHHC9. The authors demonstrated that loss of Zdhhc9 could increase the ratio of excitatory-to-inhibitory synapses and disrupt proper dendritic arborization, presenting a plausible mechanism for how loss of ZDHHC9 function may contribute to XLID and epilepsy.
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The researchers conducted extensive analyses of the genomes, epigenomes and transcriptomes of Rhabdoid tumours (RTs) from multiple anatomical locations. Their work revealed that not only were tumours from the same anatomical location diverse, but in some cases, brain RTs were actually more similar to non-brain RTs than to other RTs within the brain. They identified five distinct subgroups, some that interacted extensively with the immune system.
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Biodiversity of Protists and Nematodes in the Wild Nonhuman Primate Gut

Documenting the natural diversity of eukaryotic organisms in the nonhuman primate (NHP) gut is important for understanding the evolution of the mammalian gut microbiome, its role in digestion, health and disease, and the consequences of anthropogenic change on primate biology and conservation. Despite the ecological significance of gut-associated eukaryotes, little is known about the factors that influence their assembly and…
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In Huntington disease (HD), the mutated HTT gene expresses with pathogenic gain-of-function activities. The authors present a comprehensive analysis of the HTT gene in nearly 2000 HD patients from 13 distinct populations across five continents, revealing which alleles of HTT offer targets for therapeutic suppression of mutant HTT in the most patients. The study provides a critically important road map to the development of selective HTT silencing therapies for HD patients from a range of ethnically distinct populations around the world.
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The cellular multipass transmembrane protein serine incorporator 5 (SERINC5) was recently identified to be a novel antiviral protein that restricts HIV infectivity. SERINC5 activity can be counteracted by the viral Nef protein, which internalizes SERINC5 from the plasma membrane of infected cells and prevents it from being loaded onto the surface of newly formed virions. The authors compared the ability of HIV Nef clones isolated from 45 elite and 46 untreated progressors to antagonize SERINC5.
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Acquired resistance to a drug treatment is a common problem across many cancers including prostate cancer (PCa) – one of the major factors for male mortality. The androgen receptor (AR) continues to be the main therapeutic PCa target and despite the success of modern targeted therapies such as enzalutamide, resistance to these drugs eventually develops. The AR has found many…
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In order to respond to foreign invaders and emerging cancers, specific cells of the immune system rely on a calcium current conveyed across their cell surface membranes to drive signals inside the immune cell when they engage and are challenged by pathogens. L-type calcium channels expressed in all mammals have traditionally been described in electrically excitable cells such as neuronal and muscle cells.
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Biological embedding occurs when life experience alters biological processes to affect later life health and well-being. Although extensive correlative data exist supporting the notion that epigenetic mechanisms such as DNA methylation underlie biological embedding, causal data are lacking. We describe specific epigenetic mechanisms and their potential roles in the biological embedding of experience. We also consider the nuanced relationships between…
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Outcomes for metastatic Ewing sarcoma and osteosarcoma are dismal and have not changed for decades. Oxidative stress attenuates melanoma metastasis, and melanoma cells must reduce oxidative stress to metastasize. We explored this in sarcomas by screening for oxidative stress sensitizers, which identified the class I HDAC inhibitor MS‐275 as enhancing vulnerability to reactive oxygen species (ROS) in sarcoma cells. Mechanistically,…
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Characterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), an organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH…
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