Publications by authors named "David Vilchez"

Programmed cell death occurring during plant development (dPCD) is a fundamental process integral for plant growth and reproduction. Here, we investigate the connection between developmentally controlled PCD and fungal accommodation in roots, focusing on the root cap-specific transcription factor ANAC033/SOMBRERO (SMB) and the senescence-associated nuclease BFN1. Mutations of both dPCD regulators increase colonization by the beneficial fungus , primarily in the differentiation zone.

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  • Scientists found that a bad version of a gene called FUS causes some really serious types of ALS, a disease that affects muscles and movement.
  • The FUS gene gets too tangled with another protein called H1.2, which can make the disease worse, but if scientists lower the levels of H1.2 or stop a process called PARylation, it can help reduce the problems caused by FUS.
  • In tiny worms called C. elegans, cutting down on H1.2 and a similar protein helped stop the FUS problems, showing us that learning about these relations can help us find treatments for ALS.
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  • PolyQ diseases are serious brain disorders caused by a repeated section of DNA, and they currently have no good treatments.
  • Researchers tested many drugs and found that clofazimine, a medication used for leprosy, can help reduce the toxicity caused by a harmful protein related to Huntington's disease.
  • The study shows that clofazimine works by improving cell energy production and may help treat polyQ diseases in the future.
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Deubiquitinating enzymes (DUBs) are emerging as key factors for the infection of human cells by pathogens such as bacteria and parasites. In this review, we discuss the most recent studies on the role of deubiquitinase activity in exploiting and manipulating ubiquitin (Ub)-dependent host processes during infection. The studies discussed here highlight the importance of DUB host-pathogen research and underscore the therapeutic potential of inhibiting pathogen-specific DUB activity to prevent infectious diseases.

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In humans, aggregation of polyglutamine repeat (polyQ) proteins causes disorders such as Huntington's disease. Although plants express hundreds of polyQ-containing proteins, no pathologies arising from polyQ aggregation have been reported. To investigate this phenomenon, we expressed an aggregation-prone fragment of human huntingtin (HTT) with an expanded polyQ stretch (Q69) in Arabidopsis thaliana plants.

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Huntington's disease (HD) is a movement disorder caused by a mutation in the Huntingtin gene that leads to severe neurodegeneration. Molecular mechanisms of HD are not sufficiently understood, and no cure is currently available. Here, we demonstrate neuroprotective effects of hepatoma-derived growth factor (HDGF) in cellular and mouse HD models.

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Stress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals.

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Background: Autoimmune neuropathies can result in long-term disability and incomplete recovery, despite adequate first-line therapy. Kinesin-5 inhibition was shown to accelerate neurite outgrowth in different preclinical studies. Here, we evaluated the potential neuro-regenerative effects of the small molecule kinesin-5 inhibitor monastrol in a rodent model of acute autoimmune neuropathies, experimental autoimmune neuritis.

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In recent decades, economic crises and political reforms focused on employment flexibilization have increased the use of non-standard employment (NSE). National political and economic contexts determine how employers interact with labour and how the state interacts with labour markets and manages social welfare policies. These factors influence the prevalence of NSE and the level of employment insecurity it creates, but the extent to which a country's policy context mitigates the health influences of NSE is unclear.

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Aging is a primary risk factor for neurodegenerative disorders that involve protein aggregation. Because lowering body temperature is one of the most effective mechanisms to extend longevity in both poikilotherms and homeotherms, a better understanding of cold-induced changes can lead to converging modifiers of pathological protein aggregation. Here, we find that cold temperature (15 °C) selectively induces the trypsin-like activity of the proteasome in Caenorhabditis elegans through PSME-3, the worm orthologue of human PA28γ/PSME3.

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Mitochondrial fitness is critical to organismal health and its impairment is associated with aging and age-related diseases. As such, numerous quality control mechanisms exist to preserve mitochondrial stability, including the unfolded protein response of the mitochondria (UPR). The UPR is a conserved mechanism that drives the transcriptional activation of mitochondrial chaperones, proteases, autophagy (mitophagy), and metabolism to promote restoration of mitochondrial function under stress conditions.

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Stress granules are membrane-less ribonucleoprotein organelles that assemble upon exposure to stress conditions, but rapidly disassemble upon removal of stress. However, chronic stress can lead to persistent stress granules, a feature of distinct age-related neurodegenerative disorders. Among them, Huntington's disease (HD), which is caused by mutant expansion of the polyglutamine (polyQ) repeats of huntingtin protein (HTT), leading to its aggregation.

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The high substrate selectivity of the ubiquitin/proteasome system is mediated by a large group of E3 ubiquitin ligases. The ubiquitin ligase CHIP regulates the degradation of chaperone-controlled and chaperone-independent proteins. To understand how CHIP mediates substrate selection and processing, we performed a structure-function analysis of CHIP and addressed its physiological role in Caenorhabditis elegans and human cells.

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Protein homeostasis (proteostasis) is maintained by a tightly regulated and interconnected network of biological pathways, preventing the accumulation and aggregation of damaged or misfolded proteins. Thus, the proteostasis network is essential to ensure organism longevity and health, while proteostasis failure contributes to the development of aging and age-related diseases that involve protein aggregation. The model organism has proved invaluable for the study of proteostasis in the context of aging, longevity and disease, with a number of pivotal discoveries attributable to the use of this organism.

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Protein homeostasis, or proteostasis, is essential for cell function and viability. Unwanted, damaged, misfolded and aggregated proteins are degraded by the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway. Growing evidence indicates that alterations in these major proteolytic mechanisms lead to a demise in proteostasis, contributing to the onset and development of distinct diseases.

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The biological purpose of plant stem cells is to maintain themselves while providing new pools of differentiated cells that form organs and rejuvenate or replace damaged tissues. Protein homeostasis or proteostasis is required for cell function and viability. However, the link between proteostasis and plant stem cell identity remains unknown.

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Ageing is driven by a loss of cellular integrity. Given the major role of ubiquitin modifications in cell function, here we assess the link between ubiquitination and ageing by quantifying whole-proteome ubiquitin signatures in Caenorhabditis elegans. We find a remodelling of the ubiquitinated proteome during ageing, which is ameliorated by longevity paradigms such as dietary restriction and reduced insulin signalling.

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Protein aggregation causes intracellular changes in neurons, which elicit signals to modulate proteostasis in the periphery. Beyond the nervous system, a fundamental question is whether other organs also communicate their proteostasis status to distal tissues. Here, we examine whether proteostasis of the germ line influences somatic tissues.

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Cumulative evidence indicates that excessive consumption of calories from saturated fat contributes to the development of Alzheimer's disease (AD). Here, we assess the triggering and progression of AD pathology induced by a high-fat diet (HFD), and the effects of resveratrol, a polyphenol found in common dietary sources with pleiotropic neuroprotective activities. Over 16 weeks, male wild type (WT) and AD transgenic 5XFAD mice were fed a control diet, HFD (60% kcal from fat), or HFD supplemented with 0.

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The proteostasis network adjusts protein composition and maintains protein integrity, which are essential processes for cell function and viability. Current efforts, given their intrinsic characteristics, regenerative potential and fundamental biological functions, have been directed to define proteostasis of stem cells. These insights demonstrate that embryonic stem cells and induced pluripotent stem cells exhibit an endogenous proteostasis network that not only modulates their pluripotency and differentiation but also provides a striking ability to suppress aggregation of disease-related proteins.

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Article Synopsis
  • Histones are important for gene expression regulation and chromatin structure, but how they are degraded is not well understood, especially in human embryonic stem cells (hESCs).
  • In hESCs, the enzyme UBE2K is highly expressed and is essential for controlling histone H3 modification; loss of UBE2K leads to increased repression of genes involved in differentiation due to higher levels of a trimethyltransferase called SETDB1.
  • UBE2K not only promotes the breakdown of histone H3 but also influences the levels of repressive H3K9 trimethylation, showing that this mechanism is conserved across species, as seen in worms too.
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CAG-repeat expansions in at least eight different genes cause neurodegeneration. The length of the extended polyglutamine stretches in the corresponding proteins is proportionally related to their aggregation propensity. Although these proteins are ubiquitously expressed, they predominantly cause toxicity to neurons.

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