Identifying the Gene Regulatory Network of the Starvation-Induced Transcriptional Activator Nla28.

Myxococcus xanthus copes with starvation by producing fruiting bodies filled with dormant and stress-resistant spores. Here, we aimed to better define the gene regulatory network associated with Nla28, a transcriptional activator/enhancer binding protein (EBP) and a key regulator of the early starvation response. Previous work showed that Nla28 directly regulates EBP genes that are important for fruiting body development.

Vision, future, cycle and effect: A community life course approach to prevent prenatal alcohol exposure in central Australia.

Issue Addressed: Prevention approaches specific to prenatal alcohol exposure (PAE) and foetal alcohol spectrum disorder (FASD) have been identified as urgently needed in Australia, including in Aboriginal and Torres Strait Islander communities. However, very little work has aimed to describe and evaluate health promotion initiatives, especially those developed in rural and remote areas.

Methods: A series of television commercial scripts (scripts) were developed with health promotion staff at an aboriginal and Torres Strait Islander Community Controlled Health Service and piloted with 35 community members across six yarning sessions.

Bacterial glycocalyx integrity drives multicellular swarm biofilm dynamism.

Exopolysaccharide (EPS) layers on the bacterial cell surface are key determinants of biofilm establishment and maintenance, leading to the formation of higher-order 3D structures that confer numerous survival benefits to a cell community. In addition to a specific cell-associated EPS glycocalyx, we recently revealed that the social δ-proteobacterium Myxococcus xanthus secretes a novel biosurfactant polysaccharide (BPS) to the extracellular milieu. Together, secretion of the two polymers (EPS and BPS) is required for type IV pilus (T4P)-dependent swarm expansion via spatio-specific biofilm expression profiles.

ICP-MS characterization of seven North American snake venoms.

Snake venoms are inherently complex. They are mixtures of multiple enzymes, peptides, lipids, carbohydrates, nucleosides, and metal ions. Metal ions make up a small portion of a snake's venom but play outsized roles in enzyme function and stability.

The Effect of Simulated Field Storage Conditions on Dental Restorative Materials for Military Field Use.

Introduction: Dental readiness, one critical component of medical readiness, is adversely impacted by dental emergencies. Many dental emergencies require restorative materials such as glass ionomers, resins, and zinc oxide eugenols to remedy them. The Authorized Dental Allowance List (ADAL) and Authorized Medical Allowance List (AMAL) contain the equipment and materials used by Navy dentists to treat Sailors and Marines.

Construction of a genetically modified T7Select phage system to express the antimicrobial peptide 1018.

Bacteriophage therapy was an ascendant technology for combating bacterial infections before the golden age of antibiotics, but the therapeutic potential of phages was largely ignored after the discovery of penicillin. Recently, with antibiotic-resistant infections on the rise, these phages are receiving renewed attention to combat problematic bacterial infections. Our approach is to enhance bacteriophages with antimicrobial peptides, short peptides with broad-spectrum antibiotic or antibiofilm effects.

Bacterial Surface Spreading Is More Efficient on Nematically Aligned Polysaccharide Substrates.

Biofilm-forming bacteria typically deposit layers of polysaccharides on the surfaces they inhabit; hence, polysaccharides are their immediate environment on such surfaces. Previously, we showed that many biofilm-forming bacteria preferentially spread in the direction of aligned and densely packed polysaccharide fibers in compressed substrates, a behavior we referred to as polymertropism. This arrangement of polysaccharide fibers is likely to be similar to that found in the "slime" trails deposited by many biofilm-forming bacteria and would explain previous observations that bacteria tend to follow these trails of polysaccharides.

Is weather related to the number of assaults seen at emergency departments?

Background: It is often suggested that the weather can effect behaviour, increasing the likelihood of assaults and resulting in increased admissions to emergency departments (ED). Therefor a better understanding of the effect of climatic conditions could be useful to help EDs in capacity planning. Whilst other studies have looked at this, none have used data collected specifically to look at ED attendance for assaults or have taken account of potential behaviour modifiers.

Polymertropism of rod-shaped bacteria: movement along aligned polysaccharide fibers.

In nature, bacteria often live in surface-associated communities known as biofilms. Biofilm-forming bacteria typically deposit a layer of polysaccharide on the surfaces they inhabit; hence, polysaccharide is their immediate environment on many surfaces. In this study, we examined how the physical characteristics of polysaccharide substrates influence the behavior of the biofilm-forming bacterium Myxococcus xanthus.

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression.

Intestinal barrier dysfunction in human necrotizing enterocolitis.

Background: Intestinal barrier dysfunction has been implicated in necrotizing enterocolitis (NEC), but has not been directly measured in human NEC.

Methods: Small intestines removed during surgery were immediately mounted in an Ussing chamber. mRNA expression of tight junction (TJ) proteins was measured with RT-PCR.

Promiscuous actions of small molecule inhibitors of the protein kinase D-class IIa HDAC axis in striated muscle.

PKD-mediated phosphorylation of class IIa HDACs frees the MEF2 transcription factor to activate genes that govern muscle differentiation and growth. Studies of the regulation and function of this signaling axis have involved MC1568 and Gö-6976, which are small molecule inhibitors of class IIa HDAC and PKD catalytic activity, respectively. We describe unanticipated effects of these compounds.

Selective class I histone deacetylase inhibition suppresses hypoxia-induced cardiopulmonary remodeling through an antiproliferative mechanism.

Rationale: Histone deacetylase (HDAC) inhibitors are efficacious in models of hypertension-induced left ventricular heart failure. The consequences of HDAC inhibition in the context of pulmonary hypertension with associated right ventricular cardiac remodeling are poorly understood.

Objective: This study was performed to assess the utility of selective small-molecule inhibitors of class I HDACs in a preclinical model of pulmonary hypertension.

Monodisperse 130 kDa and 260 kDa Recombinant Human Hemoglobin Polymers as Scaffolds for Protein Engineering of Hemoglobin-Based Oxygen Carriers.

A recombinant 130 kDa dihemoglobin which is made up of a single-chain tetra-α globin and four β globins has been expressed as a soluble protein in E. coli. The sequence of the single chain tetra-α is: αI-Gly-αII-(SerGlyGly)5Ser-αIII-Gly-αIV.

Emergence of fibroblasts with a proinflammatory epigenetically altered phenotype in severe hypoxic pulmonary hypertension.

Persistent accumulation of monocytes/macrophages in the pulmonary artery adventitial/perivascular areas of animals and humans with pulmonary hypertension has been documented. The cellular mechanisms contributing to chronic inflammatory responses remain unclear. We hypothesized that perivascular inflammation is perpetuated by activated adventitial fibroblasts, which, through sustained production of proinflammatory cytokines/chemokines and adhesion molecules, induce accumulation, retention, and activation of monocytes/macrophages.

Cardiac HDAC6 catalytic activity is induced in response to chronic hypertension.

Small molecule histone deacetylase (HDAC) inhibitors block adverse cardiac remodeling in animal models of heart failure. The efficacious compounds target class I, class IIb and, to a lesser extent, class IIa HDACs. It is hypothesized that a selective inhibitor of a specific HDAC class (or an isoform within that class) will provide a favorable therapeutic window for the treatment of heart failure, although the optimal selectivity profile for such a compound remains unknown.

Modeling Legionnaires' disease outbreaks: estimating the timing of an aerosolized release using symptom-onset dates.

Background: Over the last 30 years, there have been a number of reported Legionnaires' disease outbreaks resulting from the release of causative organisms from aerosol-producing devices.

Methods: We model a Legionnaires' disease epidemic curve as the convolution of an infection-time distribution (representing the aerosolized release) and an incubation-period distribution. The model is fitted to symptom-onset data from specific outbreaks to estimate the start and end dates of the release.

A high-performance liquid chromatography assay for quantification of cardiac myosin heavy chain isoform protein expression.

Stress signaling in the myocardium results in enhanced expression of fetal β-myosin heavy chain (β-MyHC) and reduced expression of adult α-myosin heavy chain (α-MyHC), with the net outcome of diminished myofibrillar ATPase activity and impaired contractility. Pharmacological approaches aimed at preventing this myosin isoform "switch" could provide therapeutic benefit to patients with heart failure. Myosin isoform protein expression is typically quantified using gel electrophoresis methods, which are time-consuming and prone to variability.

Identification of potent and selective amidobipyridyl inhibitors of protein kinase D.

The synthesis and biological evaluation of potent and selective PKD inhibitors are described herein. The compounds described in the present study selectively inhibit PKD among other putative HDAC kinases. The PKD inhibitors of the present study blunt phosphorylation and subsequent nuclear export of HDAC4/5 in response to diverse agonists.

A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase.

Class IIa histone deacetylases (HDACs) repress genes involved in pathological cardiac hypertrophy. The anti-hypertrophic action of class IIa HDACs is overcome by signals that promote their phosphorylation-dependent nuclear export. Several kinases have been shown to phosphorylate class IIa HDACs, including calcium/calmodulin-dependent protein kinase (CaMK), protein kinase D (PKD) and G protein-coupled receptor kinase (GRK).

Protein kinase D1 stimulates MEF2 activity in skeletal muscle and enhances muscle performance.

Skeletal muscle consists of type I and type II myofibers, which exhibit different metabolic and contractile properties. Type I fibers display an oxidative metabolism and are resistant to fatigue, whereas type II fibers are primarily glycolytic and suited for rapid bursts of activity. These properties can be modified by changes in workload, activity, and hormonal stimuli, facilitating muscle adaptation to physiological demand.

Risk determinants for catheter-associated blood stream infections in children and young adults with cancer.

Background: Catheter-associated blood stream infections (CABSI) are frequent complications encountered with cancer treatment. In order to understand which factors might predispose to CABSIs in children and young adults, we evaluated risk for infection in association with tumor type, catheter type, and setting of occurrence.

Methods: All pediatric oncology patients having a central venous catheter (CVC) with a tunneled external (TE) or totally implantable design (TID) were prospectively followed for the occurrence of a CABSI for 12 months.