72,965 results match your criteria: "Department of Molecular Physiology and Biophysics; Vanderbilt University School of Medicine; Nashville[Affiliation]"

Organisms from all kingdoms of life depend on Late Embryogenesis Abundant (LEA) proteins to survive desiccation. LEA proteins are divided into broad families distinguished by the presence of family-specific motif sequences. The LEA_4 family, characterized by 11-residue motifs, plays a crucial role in the desiccation tolerance of numerous species.

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The Drosophila intrinsically disordered protein Ultrabithorax (Ubx) undergoes a series of phase transitions, beginning with noncovalent interactions between apparently randomly organized monomers, and evolving over time to form increasingly ordered coacervates. This assembly process ends when specific dityrosine covalent bonds lock the monomers in place, forming macroscale materials. Inspired by this hierarchical, multistep assembly process, we analyzed the impact of protein concentration, assembly time, and subphase composition on the early, noncovalent stages of Ubx assembly, which are extremely sensitive to their environment.

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The importance of preclinical models for cholangiocarcinoma drug discovery.

Expert Opin Drug Discov

January 2025

Center of Physiology, Pathophysiology and Biophysics, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.

Introduction: Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- and extrahepatic biliary system (intrahepatic and extrahepatic cholangiocarcinoma) and gallbladder cancer with the common feature of a poor prognosis, despite increasing molecular knowledge of associated genetic aberrations and possible targeted therapies. Therefore, the search for even more precise and individualized therapies is ongoing and preclinical tumor models are central to the development of such new approaches.

Areas Covered: The models described in the current review include simple and advanced in vitro and in vivo models, including cell lines, 2D monolayer, spheroid and organoid cultures, 3D bioprinting, patient-derived xenografts, and more recently, machine-perfusion platform-based models of resected liver specimens.

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Estrogen hormones are primarily associated with their role as female sex hormones responsible for primary and secondary sexual development. Estrogen receptors are known to undergo age-dependent decreases due to age-related changes in hormone production. In the mitochondria, estrogen functions by reducing the production of reactive oxygen species in the electron transport chain, inhibiting apoptosis, and regulating mitochondrial DNA content.

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Skeletal muscle (SM) is essential for movement, stability, and overall body function, and it readily adapts to changes in energy demand. Myogenesis is energy-intensive and involves complex molecular and cellular events. We recently demonstrated that the absence of lysosomal acid lipase (LAL) significantly impacts the SM phenotype, primarily by disrupting energy homeostasis and reducing ATP production.

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Elucidating the molecular basis of salt tolerance in potatoes through miRNA expression and phenotypic analysis.

Sci Rep

January 2025

Shandong Provincial Key Laboratory of Biophysics, Institute of Biophysics, Dezhou University, Dezhou, 253023, Shandong, China.

Potatoes are a critical staple crop worldwide, yet their yield is significantly constrained by salt stress. Understanding and enhancing salt tolerance in potatoes is crucial for ensuring food security. This study evaluated the salt tolerance of 17 diverse potato varieties using principal component analysis, membership function analysis, cluster analysis, and stepwise regression analysis.

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Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization.

Nat Commun

January 2025

CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen.

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Background: Accurate diagnosis of tuberculosis (TB) in children continues to be challenging, primarily due to the low bacterial load characteristic of the disease and the obstacles in collecting sputum samples. Furthermore, detecting cases of latent Mycobacterium tuberculosis (M.tb) infection (LTBI) that have a high risk of progressing to active TB disease remains a significant diagnostic hurdle.

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Precision, or personalized, medicine aims to stratify patients based on variable pathogenic signatures to optimize the effectiveness of disease prevention and treatment. This approach is favorable in the context of brain disorders, which are often heterogeneous in their pathophysiological features, patterns of disease progression and treatment response, resulting in limited therapeutic standard-of-care. Here we highlight the transformative role that human induced pluripotent stem cell (hiPSC)-derived neural models are poised to play in advancing precision medicine for brain disorders, particularly emerging innovations that improve the relevance of hiPSC models to human physiology.

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Corrigendum to "Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases" [Redox Biol. 79 (2025) 103464].

Redox Biol

January 2025

Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, UK; Department of Pharmacology and Molecular Sciences and Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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We show that a small biotin-binding RNA aptamer that folds into a pseudoknot structure acts as a substrate for bacterial RNase P RNA (RPR) with and without the RNase P C5 protein. Cleavage in the single-stranded region in loop 1 was shown to depend on the presence of a RCCA-motif at the 3' end of the substrate. The nucleobase and the 2'hydroxyl at the position immediately 5' of the cleavage site contribute to both cleavage efficiency and site selection, where C at this position induces significant cleavage at an alternative site, one base upstream of the main cleavage site.

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The nonsense-mediated mRNA decay (NMD) pathway triggers the degradation of defective mRNAs and governs the expression of mRNAs with specific characteristics. Current understanding indicates that NMD is often significantly suppressed during viral infections to protect the viral genome. In numerous viruses, this inhibition is achieved through direct or indirect interference with the RNA helicase UPF1, thereby promoting viral replication and enhancing pathogenesis.

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Myosin-IC (myo1c) is a class-I myosin that supports transport and remodeling of the plasma membrane and membrane-bound vesicles. Like other members of the myosin family, its biochemical kinetics are altered in response to changes in mechanical loads that resist the power stroke. However, myo1c is unique in that the primary force-sensitive kinetic transition is the isomerization that follows ATP binding, not ADP release as in other slow myosins.

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Background: While widefield microscopy has long been constrained by out-of-focus scattering, advancements have generated a solution in the form of confocal laser scanning microscopy (cLSM) and optical sectioning microscopy using structured illumination (OSM). In this study, we aim to investigate, using microglia branching, if cLSM and OSM can produce images with comparable morphological characteristics.

Results: By imaging the somatosensory microglia from a tissue slice of a 3-week-old mouse and establishing morphological parameters that characterizes the microglial branching pattern, we were able to show that there is no difference in total length of the branch tree, number of branches, mean branch length and number of primary to terminal branches.

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This study aimed to comprehensively review the global biobanks to visualize their geographical distribution. The protocol for this review consisted of the following steps: i. Developing a search strategy to identify biobanks from each continent, ii.

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Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.

Neurotherapeutics

January 2025

Department of Physiology & Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Center for Mitochondrial Research and Therapeutics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Electronic address:

Alzheimer's disease (AD) is characterized by progressive neurodegeneration, marked by the accumulation of amyloid-β (Aβ) plaques and tau tangles. Emerging evidence suggests that mitochondrial dysfunction plays a pivotal role in AD pathogenesis, driven by impairments in mitochondrial quality control (MQC) mechanisms. MQC is crucial for maintaining mitochondrial integrity through processes such as proteostasis, mitochondrial dynamics, mitophagy, and precise communication with other subcellular organelles.

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Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue.

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Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca channel (Ca1.2) and reduce Ca-dependent inactivation.

Acta Physiol (Oxf)

February 2025

Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK.

Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship.

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Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

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Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.

Nat Commun

January 2025

Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Department of Medicine, University of California, San Francisco, CA, 94143, USA.

The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) in the thymus and are implicated in clonal deletion, but the mechanisms by which they operate are not clear. Moreover, their role in central tolerance is obscured by redundancy among the Nr4a family members and by their reported functions in Treg generation and maintenance. Here we take advantage of competitive bone marrow chimeras and the OT-II/RIPmOVA model to show that Nr4a1 and Nr4a3 are essential for the upregulation of Bcl2l11/BIM and thymic clonal deletion by self-antigen.

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Ubiquitin-A structural perspective.

Mol Cell

January 2025

Ubiquitin Signalling Division, WEHI, Melbourne, VIC, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC, Australia. Electronic address:

The modification of proteins and other biomolecules with the small protein ubiquitin has enthralled scientists from many disciplines for decades, creating a broad research field. Ubiquitin research is particularly rich in molecular and mechanistic understanding due to a plethora of (poly)ubiquitin structures alone and in complex with ubiquitin machineries. Furthermore, due to its favorable properties, ubiquitin serves as a model system for many biophysical and computational techniques.

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Molecular determinants of condensate composition.

Mol Cell

January 2025

Center for Molecular and Cellular Bioengineering, Biotechnology Center, Technische Universität Dresden, Dresden, Germany. Electronic address:

Cells use membraneless compartments to organize their interiors, and recent research has begun to uncover the molecular principles underlying their assembly. Here, we explore how site-specific and chemically specific interactions shape the properties and functions of condensates. Site-specific recruitment involves precise interactions at specific sites driven by partially or fully structured interfaces.

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Programming of synthetic regulatory DNA for cell-type targeting in humans.

Mol Cell

January 2025

Randall Centre for Cell & Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK; Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, SE-412 96 Gothenburg, Sweden; Institute of Biotechnology, Life Sciences Centre, Vilnius University, Sauletekio al. 7, LT10257 Vilnius, Lithuania. Electronic address:

In a recent study in Nature, Gosai et al. introduce a framework to engineer and validate synthetic DNA regulatory elements showing cell-type-specific activity in human cell lines, closing the distance to the machine-driven design of functional regulatory sequences with therapeutic applications in humans.

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Many bacteria live in polymeric fluids, such as mucus, environmental polysaccharides, and extracellular polymers in biofilms. However, laboratory studies typically focus on cells in polymer-free fluids. Here, we show that interactions with polymers shape a fundamental feature of bacterial life-how they proliferate in space in multicellular colonies.

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Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking.

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