Regulation of mutant huntingtin mitochondrial toxicity by phosphomimetic mutations within its N-terminal region.

Huntington's disease (HD), a neurodegenerative disease, affects approximately 30,000 people in the United States, with 200,000 more at risk. Mitochondrial dysfunction caused by mutant huntingtin (mHTT) drives early HD pathophysiology. mHTT binds the translocase of mitochondrial inner membrane (TIM23) complex, inhibiting mitochondrial protein import and altering the mitochondrial proteome.

Designing, implementing and evaluating multidisciplinary healthcare training programmes in the wartime humanitarian context of Ukraine.

Introduction: Civilian healthcare workers (HCW) and medical facilities are directly and indirectly impacted by armed conflict. In the Russia-Ukraine war, acute trauma care needs grew, the workforce was destabilised by HCW migrating or shifting roles to meet conflict needs, and facilities faced surge events. Chemical, biological, radiological, nuclear and explosive (CBRNE) exposure risks created unique preparedness needs.

Two hit mitochondrial-driven model of synapse loss in neurodegeneration.

In healthy neurons, a mitochondrial membrane potential gradient exists whereby membrane potential is highest in the soma and decreases with distance from the nucleus. Correspondingly, distal mitochondria have more oxidative damage and slower protein import than somal mitochondria. Due to these differences, distal mitochondria have an intrinsic first stressor that somal mitochondria do not have, resulting in synaptic mitochondrial vulnerability.

Mutant huntingtin disrupts mitochondrial proteostasis by interacting with TIM23.

Mutant huntingtin (mHTT), the causative protein in Huntington's disease (HD), associates with the translocase of mitochondrial inner membrane 23 (TIM23) complex, resulting in inhibition of synaptic mitochondrial protein import first detected in presymptomatic HD mice. The early timing of this event suggests that it is a relevant and direct pathophysiologic consequence of mHTT expression. We show that, of the 4 TIM23 complex proteins, mHTT specifically binds to the TIM23 subunit and that full-length wild-type huntingtin (wtHTT) and mHTT reside in the mitochondrial intermembrane space.

[Chronic right ventricular failure in a patient with diffuse toxic goiter and alcoholic cirrhosis of the liver: case description].

We present a case of a patient with pronounced edematous‑ascitic syndrome. Initially, its causes were considered to be alcoholic cardiomyopathy (right ventricular failure) with heart rhythm disturbances and liver cirrhosis. Targeted treatment had a low clinical effect, which served as a basis for revising the diagnostic concept.

Mitochondria modulate programmed neuritic retraction.

Neuritic retraction in the absence of overt neuronal death is a shared feature of normal aging and neurodegenerative disorders, but the intracellular mechanisms modulating this process are not understood. We propose that cumulative distal mitochondrial protein damage results in impaired protein import, leading to mitochondrial dysfunction and focal activation of the canonical apoptosis pathway in neurites. This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon "neuritosis.

Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release.

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT), its associated G protein, and β-arrestins are on and within neuronal mitochondria. We discovered that the ligand melatonin is exclusively synthesized in the mitochondrial matrix and released by the organelle activating the mitochondrial MT signal-transduction pathway inhibiting stress-mediated cytochrome release and caspase activation.

Systemic antimiR-337-3p delivery inhibits cerebral ischemia-mediated injury.

Modulation of miRNA expression has been shown to be beneficial in the context of multiple diseases. The purpose of this study was to determine if an inhibitor of miR-337-3p is neuroprotective for hypoxic injury after tail vein injection. We evaluated miR-337-3p expression levels and in brain tissue in vivo before and after permanent middle cerebral artery occlusion (pMCAO) in mice.

An enzyme kinetics study of the pH dependence of chloride activation of oxygen evolution in photosystem II.

Oxygen evolution by photosystem II (PSII) involves activation by Cl ion, which is regulated by extrinsic subunits PsbQ and PsbP. In this study, the kinetics of chloride activation of oxygen evolution was studied in preparations of PSII depleted of the PsbQ and PsbP subunits (NaCl-washed and NaSO/pH 7.5-treated) over a pH range from 5.

Isolation of functionally active and highly purified neuronal mitochondria from human cortex.

Background: Functional and structural properties of mitochondria are highly tissue and cell dependent, but isolation of highly purified human neuronal mitochondria is not currently available.

New Method: We developed and validated a procedure to isolate purified neuronal mitochondria from brain tissue. The method combines Percoll gradient centrifugation to obtain synaptosomal fraction with nitrogen cavitation mediated synaptosome disruption and extraction of mitochondria using anti mitochondrial outer membrane protein antibodies conjugated to magnetic beads.

Jet energy measurement and its systematic uncertainty in proton-proton collisions at [Formula: see text] TeV with the ATLAS detector.

The jet energy scale (JES) and its systematic uncertainty are determined for jets measured with the ATLAS detector using proton-proton collision data with a centre-of-mass energy of [Formula: see text] TeV corresponding to an integrated luminosity of [Formula: see text][Formula: see text]. Jets are reconstructed from energy deposits forming topological clusters of calorimeter cells using the anti-[Formula: see text] algorithm with distance parameters [Formula: see text] or [Formula: see text], and are calibrated using MC simulations. A residual JES correction is applied to account for differences between data and MC simulations.

Two-particle Bose-Einstein correlations in collisions at [Formula: see text] 0.9 and 7 TeV measured with the ATLAS detector.

The paper presents studies of Bose-Einstein Correlations (BEC) for pairs of like-sign charged particles measured in the kinematic range [Formula: see text] 100 MeV and [Formula: see text] 2.5 in proton collisions at centre-of-mass energies of 0.9 and 7 TeV with the ATLAS detector at the CERN Large Hadron Collider.

Measurements of the Total and Differential Higgs Boson Production Cross Sections Combining the H→γγ and H→ZZ^{*}→4ℓ Decay Channels at sqrt[s]=8 TeV with the ATLAS Detector.

Measurements of the total and differential cross sections of Higgs boson production are performed using 20.3  fb^{-1} of pp collisions produced by the Large Hadron Collider at a center-of-mass energy of sqrt[s]=8  TeV and recorded by the ATLAS detector. Cross sections are obtained from measured H→γγ and H→ZZ^{*}→4ℓ event yields, which are combined accounting for detector efficiencies, fiducial acceptances, and branching fractions.

Search for the Standard Model Higgs boson produced in association with top quarks and decaying into [Formula: see text] in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.

A search for the Standard Model Higgs boson produced in association with a top-quark pair, [Formula: see text], is presented. The analysis uses 20.3 fb of collision data at [Formula: see text], collected with the ATLAS detector at the Large Hadron Collider during 2012.

Evidence of Wγγ Production in pp Collisions at sqrt[s]=8 TeV and Limits on Anomalous Quartic Gauge Couplings with the ATLAS Detector.

This Letter reports evidence of triple gauge boson production pp→W(ℓν)γγ+X, which is accessible for the first time with the 8 TeV LHC data set. The fiducial cross section for this process is measured in a data sample corresponding to an integrated luminosity of 20.3  fb^{-1}, collected by the ATLAS detector in 2012.

Search for a Heavy Neutral Particle Decaying to eμ, eτ, or μτ in pp Collisions at sqrt[s]=8 TeV with the ATLAS Detector.

This Letter presents a search for a heavy neutral particle decaying into an opposite-sign different-flavor dilepton pair, e^{±}μ^{∓}, e^{±}τ^{∓}, or μ^{±}τ^{∓} using 20.3  fb^{-1} of pp collision data at sqrt[s]=8  TeV collected by the ATLAS detector at the LHC. The numbers of observed candidate events are compatible with the standard model expectations.

Search for invisible decays of the Higgs boson produced in association with a hadronically decaying vector boson in collisions at [Formula: see text] TeV with the ATLAS detector.

A search for Higgs boson decays to invisible particles is performed using 20.3 [Formula: see text] of collision data at a centre-of-mass energy of 8 TeV recorded by the ATLAS detector at the Large Hadron Collider. The process considered is Higgs boson production in association with a vector boson ([Formula: see text] or ) that decays hadronically, resulting in events with two or more jets and large missing transverse momentum.

Constraints on the off-shell Higgs boson signal strength in the high-mass and final states with the ATLAS detector.

Measurements of the and final states in the mass range above the [Formula: see text] and [Formula: see text] thresholds provide a unique opportunity to measure the off-shell coupling strength of the Higgs boson. This paper presents constraints on the off-shell Higgs boson event yields normalised to the Standard Model prediction (signal strength) in the [Formula: see text], [Formula: see text] and [Formula: see text] final states. The result is based on collision data collected by the ATLAS experiment at the LHC, corresponding to an integrated luminosity of 20.

Search for a Charged Higgs Boson Produced in the Vector-Boson Fusion Mode with Decay H(±)→W(±)Z using pp Collisions at √s=8 TeV with the ATLAS Experiment.

A search for a charged Higgs boson, H(±), decaying to a W(±) boson and a Z boson is presented. The search is based on 20.3  fb(-1) of proton-proton collision data at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the LHC.

Search for New Phenomena in Dijet Angular Distributions in Proton-Proton Collisions at sqrt[s]=8 TeV Measured with the ATLAS Detector.

A search for new phenomena in LHC proton-proton collisions at a center-of-mass energy of sqrt[s]=8 TeV was performed with the ATLAS detector using an integrated luminosity of 17.3 fb^{-1}. The angular distributions are studied in events with at least two jets; the highest dijet mass observed is 5.