Targeting the hSSB1-INTS3 Interface: A Computational Screening Driven Approach to Identify Potential Modulators.

Human single-stranded DNA binding protein 1 (hSSB1) forms a heterotrimeric complex, known as a sensor of single-stranded DNA binding protein 1 (SOSS1), in conjunction with integrator complex subunit 3 (INTS3) and C9ORF80. This sensory protein plays an important role in homologous recombination repair of double-strand breaks in DNA to efficiently recruit other repair proteins at the damaged sites. Previous studies have identified elevated hSSB1-mediated DNA repair activities in various cancers, highlighting its potential as an anticancer target.

Head and thorax elevation during cardiopulmonary resuscitation using circulatory adjuncts is associated with improved survival.

Background: Survival after out-of-hospital cardiac arrest (OHCA) remains poor. A physiologically distinct cardiopulmonary resuscitation (CPR) strategy consisting of (1) active compression-decompression CPR and/or automated CPR, (2) an impedance threshold device, and (3) automated controlled elevation of the head and thorax (ACE) has been shown to improve neurological survival significantly versus conventional (C) CPR in animal models. This resuscitation device combination, termed ACE-CPR, is now used clinically.

Faster time to automated elevation of the head and thorax during cardiopulmonary resuscitation increases the probability of return of spontaneous circulation.

Objectives: Resuscitation in the Head Up position improves outcomes in animals treated with active compression decompression cardiopulmonary resuscitation and an impedance threshold device (ACD + ITD CPR).We assessed impact of time to deployment of an automated Head Up position (AHUP) based bundle of care after out-of-hospital cardiac arrest on return of spontaneous circulation (ROSC).

Methods: Observational data were analyzed from a patient registry.

Absence of Coronary Artery Calcium During Positron Emission Tomography Stress Testing in Patients Without Known Coronary Artery Disease Identifies Individuals With Very Low Risk of Cardiac Events.

Background: Myocardial perfusion imaging, including positron emission tomography/computed tomography (PET/CT), is often used to assess for high-grade coronary artery disease (CAD) requiring revascularization. The use of coronary artery calcium (CAC) to predict risk of major adverse cardiovascular events in asymptomatic patients is accepted. However, little is known regarding the use of CAC in PET/CT patients without known CAD in identifying patients unlikely to need revascularization.

Implementation of a cardiac PET stress program: comparison of outcomes to the preceding SPECT era.

Background: Cardiac positron emission testing (PET) is more accurate than single photon emission computed tomography (SPECT) at identifying coronary artery disease (CAD); however, the 2 modalities have not been thoroughly compared in a real-world setting. We conducted a retrospective analysis of 60-day catheterization outcomes and 1-year major adverse cardiovascular events (MACE) after the transition from a SPECT- to a PET-based myocardial perfusion imaging (MPI) program.

Methods: MPI patients at Intermountain Medical Center from January 2011-December 2012 (the SPECT era, n = 6,777) and January 2014-December 2015 (the PET era, n = 7,817) were studied.

Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S.

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumour microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analysed tumour-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models.

Proteomic comparison of Hypnale hypnale (hump-nosed pit-viper) and Calloselasma rhodostoma (Malayan pit-viper) venoms.

Unlabelled: Treatment of Hypnale hypnale bites with commercial antivenoms, even those raised against its sister taxon Calloselasma rhodostoma, has never been clinically successful. As these two genera have been separated for 20million years, we tested to see whether significant variations in venom had accumulated during this long period of evolutionary divergence, and thus could be responsible for the failure of antivenom. Proteomic analyses of C.

Comparative genomics of early-diverging Brucella strains reveals a novel lipopolysaccharide biosynthesis pathway.

Unlabelled: Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1T and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted.

Comparative genomics of early-diverging Brucella strains reveals a novel lipopolysaccharide biosynthesis pathway.

Unlabelled: Brucella species are Gram-negative bacteria that infect mammals. Recently, two unusual strains (Brucella inopinata BO1(T) and B. inopinata-like BO2) have been isolated from human patients, and their similarity to some atypical brucellae isolated from Australian native rodent species was noted.

Distribution of nitrogen fixation and nitrogenase-like sequences amongst microbial genomes.

Background: The metabolic capacity for nitrogen fixation is known to be present in several prokaryotic species scattered across taxonomic groups. Experimental detection of nitrogen fixation in microbes requires species-specific conditions, making it difficult to obtain a comprehensive census of this trait. The recent and rapid increase in the availability of microbial genome sequences affords novel opportunities to re-examine the occurrence and distribution of nitrogen fixation genes.

Effects of exercise and antioxidant supplementation on endothelial gene expression.

Background: The molecular mechanisms of exercise training induced cardiovascular protection are poorly understood. There is growing evidence that reactive oxygen species may be involved in a number of these adaptations and that antioxidants may be used to investigate this effect.

Objective: To determine the effects of exercise training and/or antioxidant supplementation on myocardial endothelium and vascular endothelium gene expression.

Proteolytic networks in cancer.

Proteases are important for multiple processes during malignant progression, including tumor angiogenesis, invasion and metastasis. Recent evidence reveals that tumor-promoting proteases function as part of an extensive multidirectional network of proteolytic interactions, in contrast to the unidirectional caspase cascade. These networks involve different constituents of the tumor microenvironment and key proteases, such as cathepsin B, urokinase-type plasminogen activator and several matrix metalloproteinases, occupy central nodes for amplifying proteolytic signals passing through the network.

The role of HIF-1 in hypoxic response in the skeletal muscle.

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress, and the muscle's ability to cope with and improve its function through that stress is central to its role in the body. The primary transcriptional response factor for hypoxic adaptation is hypoxia inducible factor-1alpha (HIF-1alpha), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1alpha in endurance training, we have created mice specifically lacking skeletal muscle HIF-1alpha and subjected them to an endurance training protocol.

HIF-1alpha in endurance training: suppression of oxidative metabolism.

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1alpha (HIF-1alpha), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1alpha in endurance training, we have created mice specifically lacking skeletal muscle HIF-1alpha and subjected them to an endurance training protocol.

Assay optimization: a statistical design of experiments approach.

With the transition from manual to robotic HTS in the last several years, assay optimization has become a significant bottleneck. Recent advances in robotic liquid handling have made it feasible to reduce assay optimization timelines with the application of statistically designed experiments. When implemented, they can efficiently optimize assays by rapidly identifying significant factors, complex interactions, and nonlinear responses.

Dietary Supplementation of Vitamin E and α-Lipoic Acid Upregulates Cell Growth and Signaling Genes in Rat Myocardium.

The efficacy of antioxidant supplementation in the prevention of cardiovascular disease appears equivocal, however the use of more potent antioxidant combinations than those traditionally used may exert a more positive effect. We have shown previously that supplementation of vitamin E and α-lipoic acid increases cardiac performance during post-ischemia reperfusion in older rats and increases Bcl-2 levels in endothelial cells. The purpose of this study was to examine the effects of vitamin E and α-lipoic acid supplementation on myocardial gene expression with a view to determine their mechanism of action.

Brain interface research for asynchronous control applications.

The Neil Squire Society has developed asynchronous, direct brain switches for self-paced control applications with mean activation rates of 73% and false positive error rates of 2%. This report summarizes our results to date, lessons learned, and current directions, including research into implanted brain interface designs.

Real-time control of a video game with a direct brain--computer interface.

Mason and Birch have developed a direct brain-computer interface for intermittent control of devices such as environmental control systems and neuroprotheses. This EEG-based brain switch, named the LF-ASD, has been used in several off-line studies, but little is known about its usability with real-world devices and computer applications. In this study, able-bodied individuals and people with high-level spinal injury used the LF-ASD brain switch to control a video game in real time.

Loss of skeletal muscle HIF-1alpha results in altered exercise endurance.

The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia is thus a critical parameter in muscle function, influencing production of ATP, utilization of energy-producing substrates, and manufacture of exhaustion-inducing metabolites. Glycolysis is the central source of anaerobic energy in animals, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha).

Current trends in brain-computer interface research at the Neil Squire Foundation.

The Neil Squire Foundation (NSF) is a Canadian nonprofit organization whose purpose is to create opportunities for independence for individuals who have significant physical disabilities. Over the last ten years, our team in partnership with researchers at the Electrical and Computer Engineering Department, the University of British Columbia, has been working to develop a direct brain-controlled switch for individuals with significant physical disabilities. The NSF Brain Interface Project primarily focuses on the development of brain-computer interface switch technologies for intermittent (or asynchronous) control in natural environments.

A general framework for brain-computer interface design.

The Brain-Computer Interface (BCI) research community has acknowledged that researchers are experiencing difficulties when they try to compare the BCI techniques described in the literature. In response to this situation, the community has stressed the need for objective methods to compare BCI technologies. Suggested improvements have included the development and use of benchmark applications and standard data sets.