Identification of small molecule inhibitors of G3BP-driven stress granule formation.

Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the RNA-binding proteins G3BP1/2. Stress granules have been implicated in several disease states, including cancer and neurodegeneration. Consequently, compounds that limit stress granule formation or promote their dissolution have potential as both experimental tools and novel therapeutics.

Relationship between saxagliptin use and left ventricular diastolic function assessed by cardiac MRI.

Aims: Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM.

Identification of small molecule inhibitors of G3BP-driven stress granule formation.

Stress granule formation is triggered by the release of mRNAs from polysomes and is promoted by the action of the paralogs G3BP1 and G3BP2. G3BP1/2 proteins bind mRNAs and thereby promote the condensation of mRNPs into stress granules. Stress granules have been implicated in several disease states, including cancer and neurodegeneration.

Prognostic Value of Different Thresholds for Myocardial Scar Quantification on Cardiac MRI Late Gadolinium Enhancement Images in Patients Receiving Implantable Cardioverter Defibrillators.

Purpose: To compare the predictive value of different myocardial scar quantification thresholds using cardiac MRI for appropriate implantable cardioverter defibrillator (ICD) shock and mortality.

Materials And Methods: In this retrospective, two-center observational cohort study, patients with ischemic or nonischemic cardiomyopathy underwent cardiac MRI prior to ICD implantation. Late gadolinium enhancement (LGE) was first determined visually and then quantified by blinded cardiac MRI readers using different SDs above the mean signal of normal myocardium, full-width half-maximum, and manual thresholding.

Targeted Synthesis of 3,3'-, 3,4'- and 3,6'-Phenylpropanoid Sucrose Esters.

In this study, we report on an orthogonal strategy for the precise synthesis of 3,3'-, 3,4'-, and 3,6'-phenylpropanoid sucrose esters (PSEs). The strategy relies on carefully selected protecting groups and deprotecting agents, taking into consideration the reactivity of the four free hydroxyl groups of the key starting material: di-isopropylidene sucrose . The synthetic strategy is general, and potentially applies to the preparation of many natural and unnatural PSEs, especially those substituted at 3-, 3'-, 4'- and 6'-positions of PSEs.

Evaluation of left atrial remodeling using cardiovascular magnetic resonance imaging in breast cancer patients treated with adjuvant trastuzumab.

Objectives: We evaluated left atrial (LA) remodeling using cardiac MRI (CMR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer during and after trastuzumab therapy.

Methods: In this prospective 2-center longitudinal study, 41 women with HER2-positive breast cancer received adjuvant trastuzumab for 12 months, in addition to standard chemotherapy. Serial CMRs were performed at baseline, 6, 12, and 18 months after initiation of trastuzumab.

The Learning, Social and Emotion Adaptation Questionnaire-Short Form: A Measure of Adaptive Behavior for Primary School Students with Autism Spectrum Disorder.

Students with autism spectrum disorder (ASD) studying in mainstream classrooms have diverse adjustment difficulties in learning, social interaction, and emotion regulation. It is crucial to identify the areas these students find most challenging so that teachers can provide training and support accordingly. We therefore developed, examined, and provided norms for the Learning, Social and Emotion Adaptation Questionnaire-Short Form (LSEAQ-S), a teacher report instrument measuring 53 essential adaptive behaviors for mainstream primary school students in Hong Kong.

Ankyrin repeats as a dimerization module.

Legionella pneumophila is a pathogen, causing severe pneumonia in humans called Legionnaires' disease. AnkC (LegA12) is a poorly characterized 495-residue effector protein conserved in multiple Legionella species. Here, we report the crystal structure of a C-terminally truncated AnkC (2-384) at 3.

Crystal structure of the Legionella effector Lem22.

Legionella pneumophila is a pathogen causing severe pneumonia in humans called Legionnaires' disease. Lem22 is a previously uncharacterized effector protein conserved in multiple Legionella strains. Here, we report the crystal structure of Lem22 from the Philadelphia strain, also known as lpg2328, at 1.

Safety of Active Rehabilitation for Persistent Symptoms After Pediatric Sport-Related Concussion: A Randomized Controlled Trial.

Objectives: To examine the safety and tolerability of an active rehabilitation program for adolescents who are slow to recover from a sport-related concussion, and secondarily to estimate the treatment effect for this intervention.

Design: Single-site, parallel, open-label, randomized controlled trial comparing treatment as usual (TAU) to TAU plus active rehabilitation.

Setting: Outpatient concussion clinic.

Divergent evolution of Di-lysine ER retention vs. farnesylation motif-mediated anchoring of the AnkB virulence effector to the Legionella-containing vacuolar membrane.

Within macrophages and amoeba, the Legionella-containing vacuole (LCV) membrane is derived from the ER. The bona fide F-box AnkB effector protein of L. pneumophila strain AA100/130b is anchored to the cytosolic side of the LCV membrane through host-mediated farnesylation of its C-terminal eukaryotic "CaaX" motif.

Structural Mimicry by a Bacterial F Box Effector Hijacks the Host Ubiquitin-Proteasome System.

Ankyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains.

Crystal Structure of the Salmonella Typhimurium Effector GtgE.

Salmonella Typhimurium GtgE is an effector protein contributing to the virulence of this pathogen. It was shown to possess highly selective proteolytic activity against a subset of Rab proteins that helps in evasion of Salmonella-containing vacuole (SCV) fusion with lysosomes. Cys45, His151 and Asp169 are essential for proteolytic activity.

Structure of the Legionella Effector, lpg1496, Suggests a Role in Nucleotide Metabolism.

Pathogenic Gram-negative bacteria use specialized secretion systems that translocate bacterial proteins, termed effectors, directly into host cells where they interact with host proteins and biochemical processes for the benefit of the pathogen. lpg1496 is a previously uncharacterized effector of Legionella pneumophila, the causative agent of Legionnaires disease. Here, we crystallized three nucleotide binding domains from lpg1496.

Structure of parkin reveals mechanisms for ubiquitin ligase activation.

Mutations in the PARK2 (parkin) gene are responsible for an autosomal recessive form of Parkinson's disease. The parkin protein is a RING-in-between-RING E3 ubiquitin ligase that exhibits low basal activity. We describe the crystal structure of full-length rat parkin.

Comparative hemodynamic effects of levosimendan alone and in conjunction with 4-aminopyridine or calcium chloride in a rodent model of severe verapamil poisoning.

Levosimendan (Levo) increases sensitivity of troponin-C to calcium, thus increasing myocardial contractility. It is also a vascular K+-ATP channel agonist producing peripheral vasodilation. Previous research with levosimendan revealed an increase in cardiac output (CO) but not blood pressure (BP) in experimental verapamil poisoning.

Overexpression of heat shock proteins (HSPs) in CHO cells for extended culture viability and improved recombinant protein production.

It has been widely reported that CHO cells undergo apoptosis in culture, despite supplementation of nutrients through fed-batch strategies. Improvement of cell viability in culture can effectively improve recombinant protein yield through extension of the culture's production lifespan, especially at high cell densities. Heat shock proteins (HSPs) have been reported to demonstrate anti-apoptotic effects against a wide range of physical and chemical stimuli through their ability to bind and act as antagonists to critical apoptotic molecules.

Enhanced IFNgamma production in adenosine-treated CHO cells: a mechanistic study.

Adenosine causes growth arrest in recombinant mammalian cell cultures, which results in enhanced productivity of the recombinant protein. Adenosine is also known to increase intracellular ATP level when added to mammalian cells. As a cell's energy level affects its protein expression capacity, we investigated the factors that contribute to the increase in recombinant protein productivity.

Transcriptome and proteome profiling to understanding the biology of high productivity CHO cells.

A combined transcriptome and proteome analysis was carried out to identify key genes and proteins differentially expressed in Chinese hamster ovary (CHO) cells producing high and low levels of dhfr-GFP fusion protein. Comparison of transcript levels was performed using a proprietary 15K CHO cDNA microarray chip, whereas proteomic analysis was performed using iTRAQ quantitative protein profiling technique. Microarray analysis revealed 77 differentially expressed genes, with 53 genes upregulated and 24 genes downregulated.