The Neuroprotective Effect of the X Protein of Orthobornavirus Bornaense Type 1 in Amyotrophic Lateral Sclerosis.

In amyotrophic lateral sclerosis (ALS), early mitochondrial dysfunction may contribute to progressive motor neuron loss. Remarkably, the ectopic expression of the Orthobornavirus bornaense type 1 (BoDV-1) X protein in mitochondria blocks apoptosis and protects neurons from degeneration. Therefore, this study examines the neuroprotective effects of X protein in an ALS mouse model.

Relational conflicts during COVID-19: Impact of loss and reduction of employment due to prevention measures and the influence of sex and stress (in the iCARE study).

This study explored the association between pandemic-related loss/reduction of employment, sex, COVID-19-related stress and relational conflicts. A sample of 5103 Canadians from the iCARE study were recruited through an online polling firm between October 29, 2020, and March 23, 2021. Logistic regressions revealed that participants with loss/reduction of employment were 3.

Corrigendum to "Transport limited adsorption experiments give a new lower estimate of the turnover frequency of hydrogenase 1" BBA Advances 3 (2023) 100090.

[This corrects the article DOI: 10.1016/j.bbadva.

Building a Resilient Patient Safety Culture: A Large Healthcare Organization's Approach to Systematically Reviewing Serious Harm Events.

Across Canada, pressures related to staffing, burnout and funding continue to affect healthcare organizations and systems. These pressures impact the quality of care Canadians receive, most notably access to care. Evidence indicates that patients are more likely to suffer from preventable harm during periods of hospital overcrowding and, indeed, very recent data from the Canadian Institute for Health Information suggest that rates of preventable harm have increased modestly in Canadian hospitals.

Outer-sphere effects on the O sensitivity, catalytic bias and catalytic reversibility of hydrogenases.

The comparison of homologous metalloenzymes, in which the same inorganic active site is surrounded by a variable protein matrix, has demonstrated that residues that are remote from the active site may have a great influence on catalytic properties. In this review, we summarise recent findings on the diverse molecular mechanisms by which the protein matrix may define the oxygen tolerance, catalytic directionality and catalytic reversibility of hydrogenases, enzymes that catalyse the oxidation and evolution of H. These mechanisms involve residues in the second coordination sphere of the active site metal ion, more distant residues affecting protein flexibility through their side chains, residues lining the gas channel and even accessory subunits.

STK11/LKB1 alterations worsen the poor prognosis of KRAS mutated early-stage non-squamous non-small cell lung carcinoma, results based on the phase 2 IFCT TASTE trial.

Background: STK11/LKB1 mutations have been associated with primary resistance to PD-1 axis inhibitors and poor prognosis in advanced KRAS-mutant lung adenocarcinoma. This study aimed to assess the prognostic significance of STK11/LKB1 alterations in localized non-squamous non-small cell lung carcinoma (non-sq NSCLC).

Patients And Methods: Surgical samples from patients undergoing complete resection for stage IIa, IIb, or IIIa (N2 excluded) non-sq NSCLC in the randomized adjuvant phase II trial (NCT00775385 IFCT-1801 TASTE trial) were examined.

Cerebral Benefits Induced by Electrical Muscle Stimulation: Evidence from a Human and Rat Study.

Physical exercise (EX) is well established for its positive impact on brain health. However, conventional EX may not be feasible for certain individuals. In this regard, this study explores electromyostimulation (EMS) as a potential alternative for enhancing cognitive function.

Impact of Exercise Intensity on Cerebral BDNF Levels: Role of FNDC5/Irisin.

The positive effects of physical exercise (EX) are well known to be mediated by cerebral BDNF (brain-derived neurotrophic factor), a neurotrophin involved in learning and memory, the expression of which could be induced by circulating irisin, a peptide derived from Fibronectin type III domain-containing protein 5 (FNDC5) produced by skeletal muscle contraction. While the influence of EX modalities on cerebral BDNF expression was characterized, their effect on muscle FNDC5/Irisin expression and circulating irisin levels remains to be explored. The present study involved Wistar rats divided into four experimental groups: sedentary (SED), low- (40% of maximal aerobic speed, MAS), intermediate- (50% of MAS) and high- (70% of MAS) intensities of treadmill EX (30 min/day, 7 days).

Kinetic Modeling of the Reversible or Irreversible Electrochemical Responses of FeFe-Hydrogenases.

The enzyme FeFe-hydrogenase catalyzes H evolution and oxidation at an active site that consists of a [4Fe-4S] cluster bridged to a [Fe(CO)(CN)(azadithiolate)] subsite. Previous investigations of its mechanism were mostly conducted on a few "prototypical" FeFe-hydrogenases, such as that from (Cr HydA1), but atypical hydrogenases have recently been characterized in an effort to explore the diversity of this class of enzymes. We aim at understanding why prototypical hydrogenases are active in either direction of the reaction in response to a small deviation from equilibrium, whereas the homologous enzyme from (Tam HydS) shows activity only under conditions of very high driving force, a behavior that was referred to as "irreversible catalysis".

An allosteric redox switch involved in oxygen protection in a CO reductase.

Metal-dependent formate dehydrogenases reduce CO with high efficiency and selectivity, but are usually very oxygen sensitive. An exception is Desulfovibrio vulgaris W/Sec-FdhAB, which can be handled aerobically, but the basis for this oxygen tolerance was unknown. Here we show that FdhAB activity is controlled by a redox switch based on an allosteric disulfide bond.

B2LiVe, a label-free 1D-NMR method to quantify the binding of amphitropic peptides or proteins to membrane vesicles.

Amphitropic proteins and peptides reversibly partition from solution to membrane, a key process that regulates their functions. Experimental approaches classically used to measure protein partitioning into lipid bilayers, such as fluorescence and circular dichroism, are hardly usable when the peptides or proteins do not exhibit significant polarity and/or conformational changes upon membrane binding. Here, we describe binding to lipid vesicles (B2LiVe), a simple, robust, and widely applicable nuclear magnetic resonance (NMR) method to determine the solution-to-membrane partitioning of unlabeled proteins or peptides.

The impact of COVID-19 on the lives of Canadians with and without non-communicable chronic diseases: results from the iCARE Study.

Background: The COVID-19 pandemic and its prevention policies have taken a toll on Canadians, and certain subgroups may have been disproportionately affected, including those with non-communicable diseases (NCDs; e.g., heart and lung disease) due to their risk of COVID-19 complications and women due to excess domestic workload associated with traditional caregiver roles during the pandemic.

Molecular mechanisms underlying physical exercise-induced brain BDNF overproduction.

Accumulating evidence supports that physical exercise (EX) is the most effective non-pharmacological strategy to improve brain health. EX prevents cognitive decline associated with age and decreases the risk of developing neurodegenerative diseases and psychiatric disorders. These positive effects of EX can be attributed to an increase in neurogenesis and neuroplastic processes, leading to learning and memory improvement.

Kinetic modeling of 2e/1H and 2e/2H bidirectional catalytic cycles.

When a redox enzyme or synthetic catalyst is interfaced with an electrode, the electrochemical response depends on the details of the catalytic cycle. Here we focus on the steady-state catalytic waveshape of enzymes such as formate dehydrogenase (2e/1H), hydrogenases (2e/2H) and other bidirectional molecular catalysts that can be adsorbed on, and undergo direct electron transfer with an electrode. We seek to examine the relations between the dependence on pH of the waveshape, the sequence of events in the catalytic cycle, and the properties of the catalytic intermediates (their reduction potentials and pK's).

A Chimeric NiFe Hydrogenase Heterodimer to Assess the Role of the Electron Transfer Chain in Tuning the Enzyme's Catalytic Bias and Oxygen Tolerance.

The observation that some homologous enzymes have the same active site but very different catalytic properties demonstrates the importance of long-range effects in enzyme catalysis, but these effects are often difficult to rationalize. The NiFe hydrogenases 1 and 2 (Hyd 1 and Hyd 2) from both consist of a large catalytic subunit that embeds the same dinuclear active site and a small electron-transfer subunit with a chain of three FeS clusters. Hyd 1 is mostly active in H oxidation and resistant to inhibitors, whereas Hyd 2 also catalyzes H production and is strongly inhibited by O and CO.

Canadian healthcare workers' mental health and health behaviours during the COVID-19 pandemic: results from nine representative samples between April 2020 and February 2022.

Objective: In the context of COVID-19, Canadian healthcare workers (HCWs) worked long hours, both to respond to the pandemic and to compensate for colleagues who were not able to work due to infection and burnout. This may have had detrimental effects on HCWs' mental health, as well as engagement in health-promoting behaviours. This study aimed to identify changes in mental health outcomes and health behaviours experienced by Canadian HCWs throughout the COVID-19 pandemic.

Light-Driven Hydrogen Evolution Reaction Catalyzed by a Molybdenum-Copper Artificial Hydrogenase.

Orange protein (Orp) is a small bacterial metalloprotein of unknown function that harbors a unique molybdenum/copper (Mo/Cu) heterometallic cluster, [SMoSCuSMoS]. In this paper, the performance of Orp as a catalyst for the photocatalytic reduction of protons into H has been investigated under visible light irradiation. We report the complete biochemical and spectroscopic characterization of -Orp containing the [SMoSCuSMoS] cluster, with docking and molecular dynamics simulations suggesting a positively charged Arg, Lys-containing pocket as the binding site.

Transport limited adsorption experiments give a new lower estimate of the turnover frequency of hydrogenase 1.

Protein Film Electrochemistry is a technique in which a redox enzyme is directly wired to an electrode, which substitutes for the natural redox partner. In this technique, the electrical current flowing through the electrode is proportional to the catalytic activity of the enzyme. However, in most cases, the amount of enzyme molecules contributing to the current is unknown and the absolute turnover frequency cannot be determined.

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.

Background: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.

Methods: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group).

Gallocin A, an Atypical Two-Peptide Bacteriocin with Intramolecular Disulfide Bonds Required for Activity.

Streptococcus gallolyticus subsp. () is an opportunistic gut pathogen associated with colorectal cancer. We previously showed that colonization of the murine colon by in tumoral conditions was strongly enhanced by the production of gallocin A, a two-peptide bacteriocin.

Prevalence and Motivators of Getting a COVID-19 Booster Vaccine in Canada: Results from the iCARE Study.

Studies have shown that the protection afforded by COVID-19 vaccines against hospitalization and death decreases slowly over time due to the emergence of new variants and waning immunity. Accordingly, booster doses remain critical to minimizing the health impacts of the pandemic. This study examined the prevalence rate, sociodemographic determinants, and motivators of getting a COVID-19 booster vaccine within the Canadian population.

Assessing the Extent of Potential Inversion by Cyclic Voltammetry: Theory, Pitfalls, and Application to a Nickel Complex with Redox-Active Iminosemiquinone Ligands.

Potential inversion refers to the situation where a protein cofactor or a synthetic molecule can be oxidized or reduced twice in a cooperative manner; that is, the second electron transfer is easier than the first. This property is very important regarding the catalytic mechanism of enzymes that bifurcate electrons and the properties of bidirectional redox molecular catalysts that function in either direction of the reaction with no overpotential. Cyclic voltammetry is the most common technique for characterizing the thermodynamics and kinetics of electron transfer to or from these molecules.

Increasing the O Resistance of the [FeFe]-Hydrogenase CbA5H through Enhanced Protein Flexibility.

The high turnover rates of [FeFe]-hydrogenases under mild conditions and at low overpotentials provide a natural blueprint for the design of hydrogen catalysts. However, the unique active site (H-cluster) degrades upon contact with oxygen. The [FeFe]-hydrogenase from (CbA5H) is characterized by the flexibility of its protein structure, which allows a conserved cysteine to coordinate to the active site under oxidative conditions.