The Anti-inflammatory Effect of Alpha-1 Antitrypsin in Rhinovirus-infected Human Airway Epithelial Cells.

Objective: Excessive airway inflammation is seen in chronic obstructive pulmonary disease (COPD) patients experiencing acute exacerbations, which are often associated with human rhinovirus (HRV) infection. Alpha-1 antitrypsin (A1AT) has anti-inflammatory function in endothelial cells and monocytes, but its anti-inflammatory effect has not been investigated in COPD airway epithelial cells. We determined A1AT's anti-inflammatory function in COPD airway epithelial cells and the underlying mechanisms such as the role of caspase-1.

A novel mouse model of conditional IRAK-M deficiency in myeloid cells: application in lung Pseudomonas aeruginosa infection.

Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection.

Does intentional weight loss improve daytime sleepiness? A systematic review and meta-analysis.

Obesity is associated with excessive daytime sleepiness, but its causality remains unclear. We aimed to assess the extent to which intentional weight loss affects daytime sleepiness. Electronic databases were searched through 24 October 2016.

Capsaicin synergizes with camptothecin to induce increased apoptosis in human small cell lung cancers via the calpain pathway.

Small cell lung cancer (SCLC) is characterized by excellent initial response to chemotherapy and radiation therapy with a majority of the patients showing tumor shrinkage and even remission. However, the challenge with SCLC therapy is that patients inevitably relapse and subsequently do not respond to the first line treatment. Recent clinical studies have investigated the possibility of camptothecin-based combination therapy as first line treatment for SCLC patients.

Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction.

Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression. The long-lasting impact might be mediated by an enhancement of memory extinction or an impairment of memory reconsolidation. Here, we directly compared the effects of i.

Estimating the risk of a scuba diving fatality in Australia.

Introduction: There are few data available on which to estimate the risk of death for Australian divers. This report estimates the risk of a scuba diving fatality for Australian residents, international tourists diving in Queensland, and clients of a large Victorian dive operator.

Methodology: Numerators for the estimates were obtained from the Divers Alert Network Asia-Pacific dive fatality database.

The demographics and diving behaviour of DAN Asia-Pacific members with and without pre-existing medical conditions.

Introduction: This report examines Diver Alert Network Asia-Pacific (DAN AP) members with and without cardiac or respiratory conditions, diabetes or hypertension and compares their demographics, health and diving activities.

Methodology: Two online cross-sectional surveys of DAN AP members were conducted. The first sought information from 833 divers who applied for membership between July 2009 and August 2013 and who had declared the targeted medical conditions.

Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders.

Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects.

The Production and Utilization of GDP-glucose in the Biosynthesis of Trehalose 6-Phosphate by Streptomyces venezuelae.

Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme.

Veterans' Voice Through the Lens of Their Medical Records: What It Reveals About Congestive Heart Failure Readmissions.

Purpose Of Study: The medical record is a sea of information that can reveal what patients are trying to tell us about their health condition. It can reveal hints and trends as to why veterans with congestive heart failure (CHF) are being readmitted within 30 days after hospital discharge. These hints and trends lead caregivers to key contributing variables to veterans' readmission.

Biosynthesis of selenate reductase in Salmonella enterica: critical roles for the signal peptide and DmsD.

Salmonella enterica serovar Typhimurium is a Gram-negative bacterium with a flexible respiratory capability. Under anaerobic conditions, S. enterica can utilize a range of terminal electron acceptors, including selenate, to sustain respiratory electron transport.

Training in the adolescent brain: An fMRI training study on divergent thinking.

Prior research suggests that adolescence is a time of enhanced sensitivity for practice and learning. In this study we tested the neural correlates of divergent thinking training in 15- to 16-year-old adolescents relative to an age-matched active control group. All participants performed an alternative uses task, a valid measure to test divergent thinking, while functional magnetic resonance imaging (fMRI) images were acquired before and after a training program.

Structural characterization of EasH (Aspergillus japonicus) - an oxidase involved in cycloclavine biosynthesis.

Aj_EasH is a non-heme iron- and α-keto-glutarate-dependent oxidase that is responsible for an unusual cyclopropyl ring formation in the biosynthesis of the fungal ergot alkaloid cycloclavine. The three dimensional structure of Aj_EasH (2.2 Å resolution) reported here provides insight into the mechanism of this unusual and complex reaction.

Listen to the band! How sound can realize group identity and enact intergroup domination.

Recent research suggests that sound appraisal can be moderated by social identity. We validate this finding, and also extend it, by examining the extent to which sound can also be understood as instrumental in intergroup relations. We interviewed nine members of a Catholic enclave in predominantly Protestant East Belfast about their experiences of an outgroup (Orange Order) parade, where intrusive sound was a feature.

Nondestructive cryomicro-CT imaging enables structural and molecular analysis of human lung tissue.

Unlabelled: Micro-computed tomography (CT) enables three-dimensional (3D) imaging of complex soft tissue structures, but current protocols used to achieve this goal preclude cellular and molecular phenotyping of the tissue. Here we describe a radiolucent cryostage that permits micro-CT imaging of unfixed frozen human lung samples at an isotropic voxel size of (11 µm) under conditions where the sample is maintained frozen at -30°C during imaging. The cryostage was tested for thermal stability to maintain samples frozen up to 8 h.

Traumatic central cord syndrome: neurological and functional outcome at 3 years.

Study Design: Retrospective cohort analysis with prospective follow-up.

Objectives: To evaluate neurological and functional recovery following central cord syndrome.

Setting: Northern Ireland, population 1.

Oral health-related knowledge, attitudes and self-efficacy of Australian rural older adults.

Objective: A cross-sectional study was conducted involving older adults from social clubs within a regional local government area in the state of Victoria, Australia, to identify factors associated with knowledge, and attitudes about oral health, as well as perceived self-efficacy.

Methods: Participants underwent an oral health interview, followed by a comprehensive oral clinical examination.

Results: A total of 225 older adults participated in this study.

MUC18 Regulates Lung Rhinovirus Infection and Inflammation.

Background: MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood.

Substrate-Assisted Catalysis in Polyketide Reduction Proceeds via a Phenolate Intermediate.

SimC7 is a polyketide ketoreductase involved in biosynthesis of the angucyclinone moiety of the gyrase inhibitor simocyclinone D8 (SD8). SimC7, which belongs to the short-chain dehydrogenase/reductase (SDR) superfamily, catalyzes reduction of the C-7 carbonyl of the angucyclinone, and the resulting hydroxyl is essential for antibiotic activity. SimC7 shares little sequence similarity with characterized ketoreductases, suggesting it might have a distinct mechanism.

Trends in adult overweight and obesity prevalence in Mongolia, 2005-2013.

Objective: To analyze trends in the prevalence of overweight and obesity among Mongolian adults during the past decade as measured by body mass index (BMI) and waist circumference (WC).

Methods: Data from the repeated cross-sectional surveys on the prevalence of noncommunicable disease risk factors conducted in 2005, 2009, and 2013 in Mongolia were used. Linear regression was used to quantify trends in mean BMI and WC, adjusted for age group, sex, and survey year.

Ligand-bound Structures and Site-directed Mutagenesis Identify the Acceptor and Secondary Binding Sites of Streptomyces coelicolor Maltosyltransferase GlgE.

GlgE is a maltosyltransferase involved in α-glucan biosynthesis in bacteria that has been genetically validated as a target for tuberculosis therapies. Crystals of the Mycobacterium tuberculosis enzyme diffract at low resolution so most structural studies have been with the very similar Streptomyces coelicolor GlgE isoform 1. Although the donor binding site for α-maltose 1-phosphate had been previously structurally defined, the acceptor site had not.

Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection.

Background: Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g. neutrophils), but the underlying mechanisms remain unclear.