Publications by authors named "Gervais V"

Introduction: Medially routed biceps-to-triceps tendon transfer for elbow extension reconstruction in spinal cord injury (SCI) has proven to be a reliable procedure. This technique classically places the tendon transfer superficial to a paralyzed ulnar nerve, with a theoretical risk of compression neuropathy.

Case Presentation: A 21-year-old male with a C5 American Spinal Injury Association Impairment Scale (AIS) grade B SCI who underwent bilateral biceps-to-triceps tendon transfers presented with new-onset paresthesias in the ring and small fingers 10.

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Background: The University of Sherbrooke's Hospital Center operating room has been affected by the COVID-19 pandemic, prompting surgeons to seek alternative ways to treat acute injuries requiring surgery. In the spring of 2020, we began performing percutaneous pinning of hand fractures in our outpatient clinic. We aimed to estimate the savings in 2021 by transferring these procedures from the operating room to the outpatient clinic.

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Single-stranded, positive-sense RNA ((+)RNA) viruses replicate their genomes in virus-induced intracellular membrane compartments. (+)RNA viruses dedicate a significant part of their small genomes (a few thousands to a few tens of thousands of bases) to the generation of these compartments by encoding membrane-interacting proteins and/or protein domains. Noroviruses are a very diverse genus of (+)RNA viruses including human and animal pathogens.

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Article Synopsis
  • Positive-sense RNA viruses, like SARS-CoV-2, rely on significant changes to host cell membranes for RNA synthesis, forming double-membrane vesicles (DMVs) that are crucial for replication.
  • The protein nsp3 plays a vital role in creating these DMVs, representing a potential target for new antiviral strategies, although its structural study is complicated by its integral membrane nature.
  • Researchers successfully produced the C-terminal region of nsp3 and used electron microscopy along with structural modeling to analyze its assembly, providing new insights into the molecular structure necessary for viral RNA export.
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The Ames MPF™ is a miniaturized, microplate fluctuation format of the Ames test. It is a standardized, commercially available product which can be used to assess mutagenicity in Salmonella and E. coli strains in 384-well plates using a color change-based readout.

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Transitioning from medical school to surgical residency is a difficult endeavor. To facilitate this period, the University of Montreal's plastic surgery program developed and implemented an intensive 1-month bootcamp rotation. It is the only one of its kind and length amongst plastic surgery residency programs in North America.

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The growing applications of therapeutic nucleic acids requires the concomitant development of vectors that are optimized to complex one type of nucleic acid, forming nanoparticles suitable for further trafficking and delivery. While fine-tuning a vector by molecular engineering to obtain a particular nanoscale organization at the nanoparticle level can be a challenging endeavor, we turned the situation around and instead screened the complexation preferences of dynamic constitutional frameworks toward different types of DNAs. Dynamic constitutional frameworks (DCF) are recently-identified vectors by our group that can be prepared in a versatile manner through dynamic covalent chemistry.

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MicroRNAs (miRNAs) are transcribed as long primary transcripts (pri-miRNAs) by RNA polymerase II. Plant pri-miRNAs encode regulatory peptides called miPEPs, which specifically enhance the transcription of the pri-miRNA from which they originate. However, paradoxically, whereas miPEPs have been identified in different plant species, they are poorly conserved, raising the question of the mechanisms underlying their specificity.

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  • Medicinal chemists are interested in finding molecules that can change protein-protein interactions (PPIs), particularly for potential cancer treatments.
  • In this study, researchers tested 76 compounds against the p8 protein, a validated target for cancer therapy, with 10% showing positive interactions in STD-NMR experiments.
  • Additional analysis revealed that 8 compounds could destabilize the p8 protein, indicating their potential as negative modulators and future anticancer agents.
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The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework.

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Guanine-quadruplexes (G4s) are targets for anticancer therapeutics. In this context, human telomeric DNA (HT-DNA) that can fold into G4s sequences are of particular interest, and their stabilization with small molecules through a visualizable process has become a challenge. As a new type of ligand for HT-G4, we designed a tetraimidazolium tetraphenylethene () as a water-soluble light-up G4 probe.

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In silico toxicology (IST) approaches to rapidly assess chemical hazard, and usage of such methods is increasing in all applications but especially for regulatory submissions, such as for assessing chemicals under REACH as well as the ICH M7 guideline for drug impurities. There are a number of obstacles to performing an IST assessment, including uncertainty in how such an assessment and associated expert review should be performed or what is fit for purpose, as well as a lack of confidence that the results will be accepted by colleagues, collaborators and regulatory authorities. To address this, a project to develop a series of IST protocols for different hazard endpoints has been initiated and this paper describes the genetic toxicity in silico (GIST) protocol.

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The original version of this Article contained errors in Figures 1 and 4. In Fig. 1b, the Mtb-SecB sequence was displayed incorrectly.

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SecB chaperones assist protein export by binding both unfolded proteins and the SecA motor. Certain SecB homologs can also control toxin-antitoxin (TA) systems known to modulate bacterial growth in response to stress. In such TA-chaperone (TAC) systems, SecB assists the folding and prevents degradation of the antitoxin, thus facilitating toxin inhibition.

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The International Council for Harmonization (ICH) M7 guideline describes a hazard assessment process for impurities that have the potential to be present in a drug substance or drug product. In the absence of adequate experimental bacterial mutagenicity data, (Q)SAR analysis may be used as a test to predict impurities' DNA reactive (mutagenic) potential. However, in certain situations, (Q)SAR software is unable to generate a positive or negative prediction either because of conflicting information or because the impurity is outside the applicability domain of the model.

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Article Synopsis
  • - The human transcription factor TFIIH is a complex made up of 10 subunits, with the small subunit p8 playing a crucial role in its stability and function in transcription and DNA repair.
  • - p8 can form different structures (homodimeric and heterodimeric) that affect how well TFIIH operates, and its absence diminishes overall transcription activity, suggesting its dimerization could be a target for cancer therapy.
  • - Researchers discovered small-molecule compounds that disrupt p8 dimerization, leading to reduced levels of TFIIH and transcriptional activity, providing a basis for further drug development aimed at regulating transcription in cancer cells.
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We report the implementation of coordination chemistry onto the generation of new types of metallosupramolecular complexes with laterally appended cationic moieties for DNA binding in buffered aqueous media. Utilization of an N,N,O-type coordination pocket along with an octahedral zinc(II) metal ion allowed us to obtain mono- and tetranuclear complexes in both solution and solid state, as confirmed by NMR spectroscopy and single-crystal X-ray diffraction, respectively. By using isothermal titration calorimetry and gel electrophoresis, multiply charged cationic assemblies were observed to effectively bind to DNA through multivalent electrostatic interactions.

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The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions.

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We provide a proof-of-principle that coordination chemistry drives the in situ self-assembly of an inactive ligand into a multivalent cluster capable of effectively complexing DNA. We show that metal coordination and scavenging can be used to switch the multivalency of the system. Thus, controlled DNA complexation and decomplexation could be achieved.

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  • MOZART1 is a small protein (8.5 kDa) that plays a role in the regulation of γ-tubulin ring complexes (γTuRCs), which are essential for microtubule formation.
  • Researchers developed a protocol to produce MOZART1 in E. coli and used various techniques like SEC-MALS and NMR to study its properties, revealing it forms heterogeneous oligomers in solution.
  • The study identified optimal conditions for NMR experiments, leading to insights about its structure and its interaction with GCP3, a protein involved in the γ-tubulin complex, suggesting MOZART1 facilitates multiple protein interactions during microtubule nucleation.
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Mitochondria exist as a highly interconnected network that is exquisitely sensitive to variations in nutrient availability, as well as a large array of cellular stresses. Changes in length and connectivity of this network, as well as alterations in the mitochondrial inner membrane (cristae), regulate cell fate by controlling metabolism, proliferation, differentiation, and cell death. Given the key roles of mitochondrial dynamics, the process by which mitochondria constantly fuse and fragment, the measure of mitochondrial length and connectivity provides crucial information on the health and activity of various cell populations.

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  • THAP11 is a cell cycle and growth regulator implicated in cancer, recognized for its unique transcription factor role and DNA-binding capabilities.
  • The study presents the crystal structure of THAP11’s C-terminal region, revealing the first 3D view of a coiled-coil motif within the THAP family.
  • Research into this structure using molecular dynamics and biophysical experiments shows that THAP11 forms a uniquely structured left-handed parallel homo-dimeric coiled-coil.
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We report herein the implementation of a dynamic covalent chemistry approach to the generation of multivalent clusters for DNA recognition. We show that biomolecular clusters can be expressed in situ by a programmed self-assembly process using chemoselective ligations. The cationic clusters are shown, by fluorescence displacement assay, gel electrophoresis and isothermal titration calorimetry, to effectively complex DNA through multivalent interactions.

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Genotoxicity hazard identification is part of the impurity qualification process for drug substances and products, the first step of which being the prediction of their potential DNA reactivity using in silico (quantitative) structure-activity relationship (Q)SAR models/systems. This white paper provides information relevant to the development of the draft harmonized tripartite guideline ICH M7 on potentially DNA-reactive/mutagenic impurities in pharmaceuticals and their application in practice. It explains relevant (Q)SAR methodologies as well as the added value of expert knowledge.

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