Publications by authors named "Rizo J"

Objectives: This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs).

Patient And Methods: This study was conducted on 53 adult patients with PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study.

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The Ca sensor synaptotagmin-1 (Syt1) triggers neurotransmitter release together with the neuronal sensitive factor attachment protein receptor (SNARE) complex formed by syntaxin-1, SNAP25, and synaptobrevin. Moreover, Syt1 increases synaptic vesicle (SV) priming and impairs spontaneous vesicle release. The Syt1 CB domain binds to the SNARE complex through a primary interface via two regions (I and II), but how exactly this interface mediates distinct functions of Syt1 and the mechanism underlying Ca triggering of release are unknown.

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Lysine acetylation is an evolutionarily conserved protein modification that changes protein functions and plays an essential role in many cellular processes, such as central metabolism, transcriptional regulation, chemotaxis, and pathogen virulence. It can alter DNA binding, enzymatic activity, protein-protein interactions, protein stability, or protein localization. In prokaryotes, lysine acetylation occurs non-enzymatically and by the action of lysine acetyltransferases (KAT).

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The Ca sensor synaptotagmin-1 triggers neurotransmitter release together with the neuronal SNARE complex formed by syntaxin-1, SNAP25 and synaptobrevin. Moreover, synaptotagmin-1 increases synaptic vesicle priming and impairs spontaneous vesicle release. The synaptotagmin-1 CB domain binds to the SNARE complex through a primary interface via two regions (I and II), but how exactly this interface mediates distinct functions of synaptotagmin-1, and the mechanism underlying Ca-triggering of release is unknown.

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Article Synopsis
  • Neurotransmitter release happens quickly through the interaction of calcium (Ca) with Synaptotagmin-1 and the formation of SNARE complexes, but how these interactions lead to membrane fusion is still unclear.
  • Synaptotagmin-1's Ca-binding loops were thought to help merge membranes, but new simulations show they might actually hinder SNARE function, contradicting older models.
  • Recent experiments suggest that when Ca binds to Synaptotagmin-1, it reorients the protein in a way that aids in bringing SNARE complexes together for membrane fusion, acting like a lever to enhance the process.
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The metaproteomic approach allows a deep microbiome characterization in different complex systems. Based on metaproteome data, microbial communities' composition, succession, and functional role in different environmental conditions can be established.The main challenge in metaproteomic studies is protein extraction, and although many protocols have been developed, a few are focused on the protein extraction of fermented foods.

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Article Synopsis
  • SNARE proteins (syntaxin-1, SNAP-25, synaptobrevin) play a crucial role in rapidly releasing neurotransmitters by forming complexes that fuse synaptic vesicles with cell membranes within microseconds.* -
  • Current theories suggest that these proteins work mechanically like rods, zipping together to bring membranes closer, but the exact mechanism of fast fusion is still unclear.* -
  • Molecular dynamics simulations propose a new model where the zippering of SNARE helices initiates fusion at a local level, expanding hydrophobic regions to form fusion pores, and indicates that polyunsaturated lipids might enhance the efficiency of this process.*
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  • Regulation of neurotransmitter release is crucial for different types of information processing in the brain, with Munc13 proteins being key players in this process.
  • Munc13-1 has specific domains, including a calmodulin binding (CaMb) domain for short-term plasticity and a CA domain that dimerizes and interacts with other proteins influencing presynaptic activity.
  • Research indicates that the Munc13-1's activity is inhibited by interactions between its domains but can be enhanced by other proteins like RIM2α and calmodulin, highlighting a complex mechanism of regulating neurotransmitter release.
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Postnatal development of the uterus involves the specification of undifferentiated epithelium into uterine-type epithelium. That specification is regulated by stromal-epithelial interactions as well as intrinsic cell-specific transcription factors and gene regulatory networks. Here, we present a co-culture system to study the effects of stromal-derived factors on epithelial cell growth and differentiation into organoids.

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Regulation of neurotransmitter release during presynaptic plasticity underlies varied forms of information processing in the brain. Munc13s play essential roles in release via their conserved C-terminal region, which contains a MUN domain involved SNARE complex assembly, and control multiple presynaptic plasticity processes. Munc13s also have a variable N-terminal region, which in Munc13-1 includes a calmodulin binding (CaMb) domain involved in short-term plasticity and a CA domain that forms an inhibitory homodimer.

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Article Synopsis
  • - The study focuses on the tau protein, which is linked to neurodegenerative diseases due to its role in amyloid formation, particularly highlighting mutations that affect its aggregation and microtubule-binding abilities.
  • - Researchers used a multi-disciplinary approach to design tau sequences that stabilize its structure and discovered that specific substitutions can reduce tau aggregation while maintaining its function.
  • - The findings suggest a mechanism that could help prevent the formation of harmful tau aggregates without compromising its biological roles, providing potential therapeutic strategies for treating neurodegenerative diseases.
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A series of six azaborahelicenes with varying electron-donor substitution at the 4-position of the aryl residue (, naphthyl) or with variable π-extension of the aryl residue (thianthrenyl, anthryl, pyrenyl) was prepared with an efficient and flexible synthetic protocol. These different types of functionalization afforded notably pronounced intramolecular charge-transfer (ICT) character for the dyes with the strongest electron donor substitution (NMe) or easiest to oxidize aryl residues, as evidenced by photophysical investigations. These effects also impact the corresponding chiroptical properties of the separated - and -enantiomers, which notably display circularly polarized luminescence (CPL) with dissymmetry factors in the order of magnitude of 10 to 10.

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Article Synopsis
  • - The protein tau is linked to neurodegenerative diseases due to its role in amyloid formation, with mutations related to frontotemporal dementia increasing tau aggregation and disrupting its ability to bind microtubules.
  • - A combination of methods like computational modeling and mass spectrometry was used to design tau sequences that prevent aggregation while retaining their biological function, focusing on modifications near the 'PGGG' beta-turn motif.
  • - The study suggests that by stabilizing tau's structure, specifically through designed sequences, it's possible to reduce the harmful aggregation that leads to diseases without losing tau's important roles in the cell, providing potential strategies for therapies against protein misfolding disorders.
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Josep Rizo is a Professor of Biophysics, Biochemistry and Pharmacology at the University of Texas Southwestern Medical Center, where he is Virginia Lazenby O'Hara Chair in Biochemistry. He is particularly interested in the study of the mechanisms of neurotransmitter release and intracellular membrane fusion using structural biology, a variety of biophysical techniques and reconstitution approaches. Jose has been a part of the FEBS Open Bio Editorial Board since 2021.

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Article Synopsis
  • α-Synuclein (aSyn) aggregation is linked to neurodegenerative diseases and acts similarly to prions, but the details of how this seeding occurs are not fully understood.
  • Researchers created a new assay to study aSyn aggregation and conducted mutations to uncover factors that either promote or inhibit this process.
  • They discovered key regions responsible for aSyn aggregation and developed a modified aSyn fragment that dramatically improves seeding activity, which could aid in diagnosing synucleinopathies by analyzing protein structure.
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Stimulation of autophagy could provide powerful therapies for multiple diseases, including cancer and neurodegeneration. An attractive drug target for this purpose is Bcl-2, which inhibits autophagy by binding to the Beclin 1 BH3-domain. However, compounds that preclude Beclin 1/Bcl-2 binding might also induce apoptosis, which is inhibited by binding of Bcl-2 to BH3-domains of pro-apoptosis factors such as Bax.

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  • TDP-43's low-complexity domain can switch between two structures, α-helical and β-strand, which affects its ability to self-associate and form protein droplets.
  • When exposed to hydrogen peroxide, the β-strand structure disassembles due to oxidation, transforming into an α-helical formation that can interact with lipids.
  • The study highlights the significance of oxidative stress in regulating protein behavior, potentially impacting translation processes in vertebrate cells, and emphasizes the role of backbone interactions in protein self-association.
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Objective: Safety concerns or contraindications in the use of hormones have resulted in a rise in the use of nutritional medicinal products for the management of menopausal symptoms. The aim of the present study was to demonstrate the efficacy and safety of Exelvit Menopause®.

Patients And Methods: A prospective, open, observational, and multicentre study was performed, including 156 menopausal women.

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Article Synopsis
  • - The study explores how the TDP-43 protein can switch between two structural forms—α-helical and β-strand—within a specific part of its low complexity domain, impacting its ability to self-associate and form protein droplets.
  • - When TDP-43 is exposed to hydrogen peroxide, it oxidizes key methionine residues, disrupting the β-strand structure and leading to a loss of self-association and phase separation, while facilitating the formation of the α-helical structure.
  • - The researchers suggest that this oxidative switch is crucial for controlling localized translation in vertebrate cells and highlight the importance of chemical interactions that affect the self-association of proteins with low sequence complexity.
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SNARE and Sec/Munc18 proteins are essential in synaptic vesicle exocytosis. Open form t-SNARE syntaxin and UNC-18 P334A are well-studied exocytosis-enhancing mutants. Here we investigate the interrelationship between the two mutations by generating double mutants in various genetic backgrounds in .

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Article Synopsis
  • The study focuses on how the uterus develops after birth, specifically how undifferentiated cells turn into specialized uterine cells, which is influenced by interactions between different cell types and specific genetic factors.
  • Researchers used mouse models and lab-grown organoids to examine these processes, finding that normal (wild-type) organoids formed a typical single layer of epithelial cells, while organoids lacking a certain gene developed an abnormal multilayered structure.
  • Additionally, when the abnormal organoids were mixed with normal uterine cells, the development of unwanted basal cells was reduced, and treatment with estrogen further affected the types of cells formed, indicating that the gene in question plays a crucial role in maintaining proper epithelial development in the uterus.
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  • Previous studies confirmed that WNK kinases 1 and 3 function as osmosensors and play a role in regulating cell volume.
  • Hydrostatic pressure affects WNK kinases by inducing phosphorylation in cell cultures and specific tubules, enhancing their activity and altering their structure.
  • Investigations using various techniques (like SEC-MALS and NMR) show that hydrostatic pressure changes the configuration of WNK3 from a dimer to a monomer, suggesting a complex relationship between pressure and osmosensing.
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As a prelude to fusion, the R-SNARE on one membrane zippers with Qa-, Qb-, and Qc-SNAREs from its apposed fusion partner, forming a four-helical bundle that draws the two membranes together. Because Qa- and Qb-SNAREs are anchored to the same membrane and are adjacent in the 4-SNARE bundle, their two anchors might be redundant. Using the recombinant pure protein catalysts of yeast vacuole fusion, we now report that the specific distribution of transmembrane (TM) anchors on the Q-SNAREs is critical for efficient fusion.

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Characterizing interactions of Synaptotagmin-1 with the SNARE complex is crucial to understand the mechanism of neurotransmitter release. X-ray crystallography revealed how the Synaptotagmin-1 C B domain binds to the SNARE complex through a so-called primary interface and to a complexin-1-SNARE complex through a so-called tripartite interface. Mutagenesis and electrophysiology supported the functional relevance of both interfaces, and extensive additional data validated the primary interface.

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This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule "molecular wire" consisting of a ∼100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule.

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