Investigation of the effects of the CFTR potentiator ivacaftor on human P-glycoprotein (ABCB1).

Ivacaftor is a potentiator of the CFTR chloride channel and is in worldwide clinical use for the chronic treatment of cystic fibrosis in patients. There is evidence that the bioavailability of ivacaftor in the body may be influenced by the multi-drug exporter P-glycoprotein. Here we have employed purified and reconstituted P-glycoprotein to study its interaction with ivacaftor as well as the ability of the drug to compete with a known transported substrate of the protein.

An automated method to detect and quantify fungiform papillae in the human tongue: Validation and relationship to phenotypical differences in taste perception.

Determination of the number of fungiform papillae (FP) on the human tongue is an important measure that has frequently been associated with individual differences in oral perception, including taste sensitivity. At present, there is no standardised method consistently used to identify the number of FP, and primarily scientists manually count papillae over a small region(s) of the anterior tip of a stained tongue. In this study, a rapid automated method was developed to quantify the number of FP across the anterior 2cm of an unstained tongue from high resolution digital images.

Home energy management (HEM) database: A list with coded attributes of 308 devices commercially available in the US.

Policymakers worldwide are currently discussing whether to include home energy management (HEM) products in their portfolio of technologies to reduce carbon emissions and improve grid reliability. However, very little data is available about these products. Here we present the results of an extensive review including 308 HEM products available on the US market in 2015-2016.

Improving Salt Tolerance of Chickpea Using Modern Genomics Tools and Molecular Breeding.

Introduction: The high protein value, essential minerals, dietary fibre and notable ability to fix atmospheric nitrogen make chickpea a highly remunerative crop, particularly in low-input food production systems. Of the variety of constraints challenging chickpea productivity worldwide, salinity remains of prime concern owing to the intrinsic sensitivity of the crop. In view of the projected expansion of chickpea into arable and salt-stressed land by 2050, increasing attention is being placed on improving the salt tolerance of this crop.

Modeling Transport of Chemotactic Bacteria in Granular Media with Distributed Contaminant Sources.

Chemotaxis has the potential to improve bioremediation strategies by enhancing the transport of pollutant-degrading bacteria to the source of contamination, leading to increased pollutant accessibility and biodegradation. This computational study extends work reported previously in the literature to include predictions of chemotactic bacterial migration in response to multiple localized contaminant sources within porous media. An advection-dispersion model, in which chemotaxis was represented explicitly as an additional advection-like term, was employed to simulate the transport of bacteria within a sand-packed column containing a distribution of chemoattractant sources.

Proton-Pump Inhibitors and Risk of Dementia.

Chronic use of a proton-pump inhibitor (PPI) has been associated with a number of unexpected negative outcomes. The most recent revision of the American Geriatrics Society Beers criteria recommends avoiding using longer than eight weeks unless the patient is at high risk. However, this recommendation is often overlooked in the long-term care setting.

Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants.

Objective: Infants born to mothers with obesity have greater adiposity, ectopic fat storage, and are at increased risk for childhood obesity and metabolic disease compared with infants of normal weight mothers, though the cellular mechanisms mediating these effects are unclear.

Methods: We tested the hypothesis that human, umbilical cord-derived mesenchymal stem cells (MSCs) from infants born to obese (Ob-MSC) versus normal weight (NW-MSC) mothers demonstrate altered fatty acid metabolism consistent with adult obesity. In infant MSCs undergoing myogenesis in vitro, we measured cellular lipid metabolism and AMPK activity, AMPK activation in response to cellular nutrient stress, and MSC DNA methylation and mRNA content of genes related to oxidative metabolism.

Entropion and ectropion repair: a snapshot of surgical practice in the United Kingdom.

We aim to provide a snapshot of the current surgical practice for correction of entropion and ectropion, the two most common oculoplastic procedures carried out in the UK, by surveying 135 consultant oculoplastic surgeons via the tool Survey Monkey. Forty-seven (35%) consultants responded. For entropion, 44% of surgeons opted for lateral tarsal strip (LTS) + everting sutures (ES).

Periocular manifestations of trigeminal trophic syndrome: A case series and literature review.

Trigeminal trophic syndrome (TTS) is a condition whereby persistent facial ulceration presents consequent to central or peripheral insult to the trigeminal nerve. Lesions are created by repetitive self-inflicted manipulation and trauma of dysaesthetic skin within the trigeminal dermatome. We discuss four cases with aetiologies varied from presumed microvascular compromise to resection of cerebral meningioma, cerebrovascular accident, and herpes zoster ophthalmicus.

A polar SxxS motif drives assembly of the transmembrane domains of Toll-like receptor 4.

Like all members of the Toll-like receptor (TLR) family, TLR4 comprises of a large ectodomain (ECD) involved in ligand recognition at the cell-surface, and a cytosolic Toll/interleukin-1 receptor (TIR) signalling domain, linked by a lipid membrane-anchored transmembrane (TM) domain (TMD). Binding of immunostimulatory pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharide (LPS) to myeloid differentiation factor 2 (MD-2) coreceptor-complexed TLR4 leads to its dimerization, resulting in productive juxtaposition of TIR domains and the initiation of pro-inflammatory innate immune responses. Whilst the process of PAMP recognition is relatively well understood, thanks to numerous high-resolution crystallographic structures of ECDs, the mechanism by which such recognition is translated into TMD dimerization and activating conformational changes is less clear.

Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New Guinea in the era of conjugate vaccines: study methods and challenges.

Background: Pneumonia and meningitis are common causes of severe childhood illness in Papua New Guinea (PNG). The etiology of both clinical conditions in PNG has not been recently assessed. Changes in lifestyle, provision and access to healthcare, antimicrobial utilization and resistance, and the national childhood vaccination schedule necessitate reassessment.

Metformin-induced ablation of microRNA 21-5p releases Sestrin-1 and CAB39L antitumoral activities.

Metformin is a commonly prescribed type II diabetes medication that exhibits promising anticancer effects. Recently, these effects were found to be associated, at least in part, with a modulation of microRNA expression. However, the mechanisms by which single modulated microRNAs mediate the anticancer effects of metformin are not entirely clear and knowledge of such a process could be vital to maximize the potential therapeutic benefits of this safe and well-tolerated therapy.

Evidence and Consequence of a Highly Adapted Clonal Haplotype within the Australian Population.

The Australian (Pass.) Labr. (syn.

A Novel Resistance Source to the Recently Evolved Highly Aggressive Australian Isolates.

Substantial yield losses and poor seed quality are frequently associated with Ascochyta blight infection of lentil caused by . Recently reported changes in aggressiveness of have led to decreased resistance within cultivars, such as Northfield and Nipper in Australia. Furthermore, the narrow genetic base of the current breeding program remains a risk for further selective pathogen evolution to overcome other currently used resistances.

Molecular Dynamics Flexible Fitting Simulations Identify New Models of the Closed State of the Cystic Fibrosis Transmembrane Conductance Regulator Protein.

Cystic fibrosis (CF) is a lethal, genetic disease found in particular in humans of European origin which is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. The search for CF therapies acting by modulating the impaired function of mutant CFTR will be greatly advanced by high resolution structures of CFTR in different states. To date, two medium resolution electron microscopy (EM) structures of CFTR are available (one of a distant zebrafish (Danio rerio) CFTR ortholog and one of human CFTR).

AMPK as a Therapeutic Target for Treating Metabolic Diseases.

The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation.

Dark Matter Search in a Proton Beam Dump with MiniBooNE.

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil.

An engineering design approach to systems biology.

Measuring and modeling the integrated behavior of biomolecular-cellular networks is central to systems biology. Over several decades, systems biology has been shaped by quantitative biologists, physicists, mathematicians, and engineers in different ways. However, the basic and applied versions of systems biology are not typically distinguished, which blurs the separate aspirations of the field and its potential for real-world impact.

Advising women with diabetes in pregnancy to express breastmilk in late pregnancy (Diabetes and Antenatal Milk Expressing [DAME]): a multicentre, unblinded, randomised controlled trial.

Background: Infants of women with diabetes in pregnancy are at increased risk of hypoglycaemia, admission to a neonatal intensive care unit (NICU), and not being exclusively breastfed. Many clinicians encourage women with diabetes in pregnancy to express and store breastmilk in late pregnancy, yet no evidence exists for this practice. We aimed to determine the safety and efficacy of antenatal expressing in women with diabetes in pregnancy.

Is ethnic prejudice declining in Britain? Change in social distance attitudes among ethnic majority and minority Britons.

Most literature on racial prejudice deals with the racial attitudes of the ethnic majority and ethnic minorities separately. This paper breaks this tradition. We examine the social distance attitudes of white and non-white British residents to test if these attitudes follow the same trends over time, whether they are driven by the same social processes and whether they are inter-related.