Effects of climate warming on energetics and habitat of the world's largest marine ectotherm.

Responses of organisms to climate warming are variable and complex. Effects on species distributions are already evident and mean global surface ocean temperatures are likely to warm by up to 4.1 °C by 2100, substantially impacting the physiology and distributions of ectotherms.

Clinical and Immunological Impact of Ocrelizumab Extended Interval Dosing in Multiple Sclerosis: A Single-Center, Real-World Experience.

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs.

Identifying priority sites for whale shark ship collision management globally.

The expansion of the world's merchant fleet poses a great threat to the ocean's biodiversity. Collisions between ships and marine megafauna can have population-level consequences for vulnerable species. The Endangered whale shark (Rhincodon typus) shares a circumglobal distribution with this expanding fleet and tracking of movement pathways has shown that large vessel collisions pose a major threat to the species.

Case report: A novel mutation of glial fibrillary acidic protein gene causing juvenile-onset Alexander disease.

Alexander disease (AxD) is a rare inherited autosomal dominant (AD) disease with different clinical phenotypes according to the age of onset. It is caused by mutations in the glial fibrillary acid protein (GFAP) gene, which causes GFAP accumulation in astrocytes. A wide spectrum of mutations has been described.

Peripheral Biomarkers in Manifest and Premanifest Huntington's Disease.

Huntington's disease (HD) is characterized by clinical motor impairment (e.g., involuntary movements, poor coordination, parkinsonism), cognitive deficits, and psychiatric symptoms.

Global collision-risk hotspots of marine traffic and the world's largest fish, the whale shark.

Marine traffic is increasing globally yet collisions with endangered megafauna such as whales, sea turtles, and planktivorous sharks go largely undetected or unreported. Collisions leading to mortality can have population-level consequences for endangered species. Hence, identifying simultaneous space use of megafauna and shipping throughout ranges may reveal as-yet-unknown spatial targets requiring conservation.

Effects of head-up tilt-table test on the QT interval.

Background: The QT interval shortens in response to sympathetic stimulation and its response to epinephrine infusion (in healthy individuals and patients with long QT syndrome) has been thoroughly studied. Head-up tilt-table (HUT) testing is an easy way to achieve brisk sympathetic stimulation. Yet, little is known about the response of the QT interval to HUT.

N-acetylcholinesterase-induced apoptosis in Alzheimer's disease.

Background: Alzheimer's disease (AD) involves loss of cholinergic neurons and Tau protein hyper-phosphorylation. Here, we report that overexpression of an N-terminally extended "synaptic" acetylcholinesterase variant, N-AChE-S is causally involved in both these phenomena.

Methodology And Principal Findings: In transfected primary brain cultures, N-AChE-S induced cell death, morphological impairments and caspase 3 activation.

Human recombinant butyrylcholinesterase purified from the milk of transgenic goats interacts with beta-amyloid fibrils and suppresses their formation in vitro.

Background: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co-localizes with beta-amyloid (Abeta) fibrils.

Aims: In vitro testing of the significance of this phenomenon to AD progress.

Methods: A thioflavine T (ThT) fluorogenic assay, photo-induced cross-linking and quantifiable electron microscopy served to compare the effect on Abeta fibril formation induced by highly purified recombinant human BChE (rBChE) produced in the milk of transgenic goats with that of serum-derived human BChE.

Changes in readthrough acetylcholinesterase expression modulate amyloid-beta pathology.

Alzheimer's disease has long been known to involve cholinergic deficits, but the linkage between cholinergic gene expression and the Alzheimer's disease amyloid pathology has remained incompletely understood. One known link involves synaptic acetylcholinesterase (AChE-S), shown to accelerate amyloid fibrils formation. Here, we report that the 'Readthrough' AChE-R splice variant, which differs from AChE-S in its 26 C-terminal residues, inversely exerts neuroprotective effects from amyloid beta (Abeta) induced toxicity.

Calcium channel blockers and beta-blockers versus beta-blockers alone for preventing exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia.

Background: The mainstay of therapy for catecholaminergic polymorphic ventricular tachycardia (CPVT) is maximal doses of beta-blockers. However, although beta-blockers prevent exercise-induced ventricular tachycardia (VT), most patients continue to have ventricular ectopy during exercise, and some studies report high mortality rates despite beta-blockade.

Objective: The purpose of this study was to investigate whether combining a calcium channel blocker with beta-blockers would prevent ventricular arrhythmias during exercise better than beta-blockers alone since the mutations causing CPVT lead to intracellular calcium overload.

Peripheral site acetylcholinesterase blockade induces RACK1-associated neuronal remodeling.

Background: Peripheral anionic site (PAS) blockade of acetylcholinesterase (AChE) notably affects neuronal activity and cyto-architecture, however, the mechanism(s) involved are incompletely understood.

Objective: We wished to specify the PAS extracellular effects on specific AChE mRNA splice variants, delineate the consequent cellular remodeling events, and explore the inhibitory effects on interchanging RACK1 interactions.

Methods: We exposed rat hippocampal cultured neurons to BW284C51, the peripheral anionic site inhibitor of AChE, and to the non-selective AChE active site inhibitor, physostigmine for studying the neuronal remodeling of AChE mRNA expression and trafficking.

Acetylcholinesterase/C terminal binding protein interactions modify Ikaros functions, causing T lymphopenia.

Hematological changes induced by various stress stimuli are accompanied by replacement of the primary acetylcholinesterase (AChE) 3' splice variant acetylcholinesterase-S (AChE-S) with the myelopoietic acetylcholinesterase-R (AChE-R) variant. To search for putative acetylcholinesterase-S interactions with hematopoietic pathways, we employed a yeast two-hybrid screen. The transcriptional co-repressor C-terminal binding protein (CtBP) was identified as a protein partner of the AChE-S C terminus.

Shwachman--Diamond syndrome associated with autoimmune phenomena.

A 2-year-old boy was evaluated for failure to thrive, hypotonia and developmental delay. The child exhibited all the criteria of Shwachman-Diamond syndrome, i.e.

Butyrylcholinesterase attenuates amyloid fibril formation in vitro.

In Alzheimer's disease, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) colocalize with brain fibrils of amyloid-beta (Abeta) peptides, and synaptic AChE-S facilitates fibril formation by association with insoluble Abeta fibrils. Here, we report that human BChE and BSP41, a synthetic peptide derived from the BChE C terminus, inversely associate with the soluble Abeta conformers and delay the onset and decrease the rate of Abeta fibril formation in vitro, at a 1:100 BChE/Abeta molar ratio and in a dose-dependent manner. The corresponding AChE synthetic peptide (ASP)40 peptide, derived from the homologous C terminus of synaptic human (h)AChE-S, failed to significantly affect Abeta fibril formation, attributing the role of enhancing this process to an AChE domain other than the C terminus.

Native folding of aggregation-prone recombinant proteins in Escherichia coli by osmolytes, plasmid- or benzyl alcohol-overexpressed molecular chaperones.

When massively expressed in bacteria, recombinant proteins often tend to misfold and accumulate as soluble and insoluble nonfunctional aggregates. A general strategy to improve the native folding of recombinant proteins is to increase the cellular concentration of viscous organic compounds, termed osmolytes, or of molecular chaperones that can prevent aggregation and can actively scavenge and convert aggregates into natively refoldable species. In this study, metal affinity purification (immobilized metal ion affinity chromatography [IMAC]), confirmed by resistance to trypsin digestion, was used to distinguish soluble aggregates from soluble nativelike proteins.

Indomethacin-induced early patent ductus arteriosus closure cannot be predicted by a decrease in pulse pressure.

Wide pulse pressure is considered to be a sign of patent ductus arteriosus (PDA). We tested the hypothesis that, following indomethacin therapy, PDA closure is associated with a significant decrease in pulse pressure. Thirty-two ventilated preterm infants were echocardiographically diagnosed within the first 24 hours of life with PDA.

Aortic dissection in children and young adults: diagnosis, patients at risk, and outcomes.

Objective: To heighten the awareness of pediatricians and pediatric cardiologists to aortic dissection, a potentially dangerous medical condition.

Methods: We reviewed the charts of 13 patients, seen in four medical centers, who suffered acute or chronic aortic dissection over the period 1970 through 2000 whilst under the age of 25 years.

Results: There were seven male and six female patients, with the mean age at diagnosis being 12.

Dicarboxylic amino acids and glycine-betaine regulate chaperone-mediated protein-disaggregation under stress.

Active protein-disaggregation by a chaperone network composed of ClpB and DnaK + DnaJ + GrpE is essential for the recovery of stress-induced protein aggregates in vitro and in Escherichia coli cells. K-glutamate and glycine-betaine (betaine) naturally accumulate in salt-stressed cells. In addition to providing thermo-protection to native proteins, we found that these osmolytes can strongly and specifically activate ClpB, resulting in an increased efficiency of chaperone-mediated protein disaggregation.

Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses.

Salt and heat stresses, which are often combined in nature, induce complementing defense mechanisms. Organisms adapt to high external salinity by accumulating small organic compounds known as osmolytes, which equilibrate cellular osmotic pressure. Osmolytes can also act as "chemical chaperones" by increasing the stability of native proteins and assisting refolding of unfolded polypeptides.

Intracardiac echogenic focus: no apparent association with structural cardiac abnormality.

Objective: The aim of our study was to evaluate whether intracardiac echogenic foci (ICEFs) may be associated with increased risk for structural cardiac anomalies in the low-risk population.

Methods: During a 24-month period, 3,744 low-risk patients were prospectively screened for ICEFs by prenatal sonography. The study group was composed of 138 fetuses (3.

Size-dependent disaggregation of stable protein aggregates by the DnaK chaperone machinery.

Classic in vitro studies show that the Hsp70 chaperone system from Escherichia coli (DnaK-DnaJ-GrpE, the DnaK system) can bind to proteins, prevent aggregation, and promote the correct refolding of chaperone-bound polypeptides into native proteins. However, little is known about how the DnaK system handles proteins that have already aggregated. In this study, glucose-6-phosphate dehydrogenase was used as a model system to generate stable populations of protein aggregates comprising controlled ranges of particle sizes.

Temperature-controlled activity of DnaK-DnaJ-GrpE chaperones: protein-folding arrest and recovery during and after heat shock depends on the substrate protein and the GrpE concentration.

Heat-shock proteins DnaK, DnaJ, and GrpE (KJE) from Escherichia coli constitute a three-component chaperone system that prevents aggregation of denatured proteins and assists the refolding of proteins in an ATP-dependent manner. We found that the rate of KJE-mediated refolding of heat- and chemically denatured proteins is decreased at high temperatures. The efficiency and reversibility of protein-folding arrest during and after heat shock depended on the stability of the complex between KJE and the denatured proteins.