Evaluation of candidate vaccine approaches for MERS-CoV.

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates.

Home Help Service Staffs' Descriptions of Their Role in Promoting Everyday Activities Among Older People in Sweden Who Are Dependent on Formal Care.

The study aimed to explore how home help service staff described their role in improving the abilities of older people, in particular, older women with chronic pain who are dependent on formal care, to perform everyday activities. Three focus group interviews were conducted, and a qualitative inductive thematic content analysis was used. The analysis resulted in one theme: struggling to improve the care recipients' opportunities for independence but being inhibited by complex environmental factors.

Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial.

Background: Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes.

Development of a recombinant human ovarian (BG1) cell line containing estrogen receptor α and β for improved detection of estrogenic/antiestrogenic chemicals.

Estrogenic endocrine-disrupting chemicals are found in environmental and biological samples, commercial and consumer products, food, and numerous other sources. Given their ubiquitous nature and potential for adverse effects, a critical need exists for rapidly detecting these chemicals. The authors developed an estrogen-responsive recombinant human ovarian (BG1Luc4E2) cell line recently accepted by the US Environmental Protection Agency (USEPA) and Organisation for Economic Co-operation and Development (OECD) as a bioanalytical method to detect estrogen receptor (ER) agonists/antagonists.

Serotonin Receptor Agonist 5-Nonyloxytryptamine Alters the Kinetics of Reovirus Cell Entry.

Unlabelled: Mammalian orthoreoviruses (reoviruses) are nonenveloped double-stranded RNA viruses that infect most mammalian species, including humans. Reovirus binds to cell surface glycans, junctional adhesion molecule A (JAM-A), and the Nogo-1 receptor (depending on the cell type) and enters cells by receptor-mediated endocytosis. Within the endocytic compartment, reovirus undergoes stepwise disassembly, which is followed by release of the transcriptionally active viral core into the cytoplasm.

Micronucleus formation by single and mixed heavy metals/loids and PAH compounds in HepG2 cells.

Humans and other organisms are exposed to multi-chemical mixtures including commonly found carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and heavy metal/loids. The joint effects of these chemicals as beyond the binary mixtures have not been well characterised. In this study, we evaluated the combined genotoxicity of mixtures of PAHs and heavy metal/loids containing benzo(a)pyrene (B[a]P), naphthalene (Nap), phenanthrene (Phe), pyrene (Pyr), arsenic (As), cadmium (Cd) and chromium (Cr) using in vitro micronucleus (MN) test in HepG2 cells.

Associations of mood symptoms with ante- and postnatal weight change in obese pregnancy are not mediated by cortisol.

Background: Both maternal obesity and disordered mood have adverse effects on pregnancy outcome. We hypothesized that maternal very severe obesity (SO) is associated with increased anxiety and depression (A&D) symptoms during pregnancy, with adverse effects on gestational weight gain (GWG), postpartum mood and postpartum weight retention (PPWR) and explored any mediation by circulating glucocorticoids.

Method: We measured A&D symptoms with validated questionnaires at weeks 17 and 28 of pregnancy and 3 months postpartum in 135 lean [body mass index (BMI) ⩽25 kg/m2] and 222 SO (BMI ⩾40 kg/m2) pregnant women.

Ligand-induced Dimerization of Middle East Respiratory Syndrome (MERS) Coronavirus nsp5 Protease (3CLpro): IMPLICATIONS FOR nsp5 REGULATION AND THE DEVELOPMENT OF ANTIVIRALS.

All coronaviruses, including the recently emerged Middle East respiratory syndrome coronavirus (MERS-CoV) from the β-CoV subgroup, require the proteolytic activity of the nsp5 protease (also known as 3C-like protease, 3CL(pro)) during virus replication, making it a high value target for the development of anti-coronavirus therapeutics. Kinetic studies indicate that in contrast to 3CL(pro) from other β-CoV 2c members, including HKU4 and HKU5, MERS-CoV 3CL(pro) is less efficient at processing a peptide substrate due to MERS-CoV 3CL(pro) being a weakly associated dimer. Conversely, HKU4, HKU5, and SARS-CoV 3CL(pro) enzymes are tightly associated dimers.

Naturally occurring marine brominated indoles are aryl hydrocarbon receptor ligands/agonists.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates the toxic and biological effects of structurally diverse chemicals, including the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of a larger effort to identify the full spectrum of chemicals that can bind to and activate the AhR, we have examined the ability of several naturally occurring marine-derived brominated indoles and brominated (methylthio)indoles (collectively referred to as brominated indoles) to bind to the AhR and stimulate AhR-dependent gene expression. Incubation of mouse, rat, and guinea pig recombinant cell lines containing a stably transfected AhR-responsive luciferase reporter gene with eight brominated indoles revealed that all compounds stimulated luciferase reporter gene activity, although some species-specific differences were observed.

An Aryl Hydrocarbon Receptor from the Salamander Ambystoma mexicanum Exhibits Low Sensitivity to 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

Structural features of the aryl hydrocarbon receptor (AHR) can underlie species- and population-specific differences in its affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These differences often explain variations in TCDD toxicity. Frogs are relatively insensitive to dioxin, and Xenopus AHRs bind TCDD with low affinity.

A comparison of commercial light-emitting diode baited suction traps for surveillance of Culicoides in northern Europe.

Background: The response of Culicoides biting midges (Diptera: Ceratopogonidae) to artificial light sources has led to the use of light-suction traps in surveillance programmes. Recent integration of light emitting diodes (LED) in traps improves flexibility in trapping through reduced power requirements and also allows the wavelength of light used for trapping to be customized. This study investigates the responses of Culicoides to LED light-suction traps emitting different wavelengths of light to make recommendations for use in surveillance.

Mutations in coronavirus nonstructural protein 10 decrease virus replication fidelity.

Unlabelled: Coronaviruses (CoVs) are unique in encoding a 3'→5' exoribonuclease within nonstructural protein 14 (nsp14-ExoN) that is required for high-fidelity replication, likely via proofreading. nsp14 associates with the CoV RNA-dependent RNA polymerase (nsp12-RdRp), and nsp14-ExoN activity is enhanced by binding nsp10, a small nonenzymatic protein. However, it is not known whether nsp10 functions in the regulation of CoV replication fidelity.

High prevalence of "Candidatus Rickettsia andeanae" and apparent exclusion of Rickettsia parkeri in adult Amblyomma maculatum (Acari: Ixodidae) from Kansas and Oklahoma.

Amblyomma maculatum (the Gulf Coast tick), an aggressive, human-biting, Nearctic and Neotropical tick, is the principal vector of Rickettsia parkeri in the United States. This pathogenic spotted fever group Rickettsia species has been identified in 8-52% of questing adult Gulf Coast ticks in the southeastern United States. To our knowledge, R.

Pityriazepin and other potent AhR ligands isolated from Malassezia furfur yeast.

Malassezia furfur yeast strains isolated from diseased human skin preferentially biosynthesize indole alkaloids which can be detected in the human skin and are highly potent activators of the aryl hydrocarbon receptor (AhR) and AhR-dependent gene expression. Chemical analysis of an EtOAc extract of a M. furfur strain obtained from diseased human skin and grown on l-tryptophan agar revealed several known AhR active tryptophan metabolites along with a previously unidentified compound, pityriazepin.

Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway.

Unlabelled: Recent studies have established that metformin (MET), an oral anti-diabetic drug, possesses antioxidant activity and is effective against different types of cancer in several carcinogen-induced animal models and cell lines. However, whether MET can protect against breast cancer has not been reported before. Therefore, the overall objectives of the present study are to elucidate the potential chemopreventive effect of MET in non-cancerous human breast MCF10A cells and explore the underlying mechanism involved, specifically the role of cytochrome P4501A1 (CYP1A1)/aryl hydrocarbon receptor (AhR) pathway.

Incomplete adherence among treatment-experienced adults on antiretroviral therapy in Tanzania, Uganda and Zambia.

Objectives: To characterize antiretroviral therapy (ART) adherence across different programmes and examine the relationship between individual and programme characteristics and incomplete adherence among ART clients in sub-Saharan Africa.

Design: A cross-sectional study.

Methods: Systematically selected ART clients (≥18 years; on ART ≥6 months) attending 18 facilities in three countries (250 clients/facility) were interviewed.

Characterisation and implementation of the ERE-CALUX bioassay on indoor dust samples of kindergartens to assess estrogenic potencies.

Estrogen-like endocrine disrupting chemicals (EEDCs) can be found abundantly in the environment. Due to their low-dose effects and the large amount of unknown EEDCs, it is difficult to assess and manage possible human health risks. For young children, who are particularly vulnerable to endocrine disruption due to their development rate, indoor dust is one of the main routes of exposure.

"The sky is the limit": adhering to antiretroviral therapy and HIV self-management from the perspectives of adolescents living with HIV and their adult caregivers.

Introduction: Worldwide, HIV-related mortality among adolescents living with HIV (ALHIV) increased by 50% from 2005 to 2012 and is attributed in part to a lack of support for adolescent retention to care and adherence to antiretroviral therapy (ART). This vulnerability reinforces the need to better understand incomplete ART adherence among ALHIV, particularly in sub-Saharan Africa, where the majority of the world's 2.1 million ALHIV reside.

Efficacy of metformin in pregnant obese women: a randomised controlled trial.

Introduction: Increasing evidence suggests obesity has its origins prior to birth. There is clear correlation between maternal obesity, high birthweight and offspring risk of obesity in later life. It is also clear that women who are obese during pregnancy are at greater risk of adverse outcomes, including gestational diabetes and stillbirth.

A mechanistic study of thioester hydrolysis with heavy atom kinetic isotope effects.

The carbonyl-C, carbonyl-O, and leaving-S kinetic isotope effects (KIEs) were determined for the hydrolysis of formylthiocholine. Under acidic conditions, (13)k(obs) = 1.0312, (18)k(obs) = 0.

Spaceflight induces specific alterations in the proteomes of Arabidopsis.

Life in spaceflight demonstrates remarkable acclimation processes within the specialized habitats of vehicles subjected to the myriad of unique environmental issues associated with orbital trajectories. To examine the response processes that occur in plants in space, leaves and roots from Arabidopsis (Arabidopsis thaliana) seedlings from three GFP reporter lines that were grown from seed for 12 days on the International Space Station and preserved on orbit in RNAlater were returned to Earth and analyzed by using iTRAQ broad-scale proteomics procedures. Using stringent criteria, we identified over 1500 proteins, which included 1167 leaf proteins and 1150 root proteins we were able to accurately quantify.

Chemicals having estrogenic activity can be released from some bisphenol A-free, hard and clear, thermoplastic resins.

Background: Chemicals that have estrogenic activity (EA) can potentially cause adverse health effects in mammals including humans, sometimes at low doses in fetal through juvenile stages with effects detected in adults. Polycarbonate (PC) thermoplastic resins made from bisphenol A (BPA), a chemical that has EA, are now often avoided in products used by babies. Other BPA-free thermoplastic resins, some hypothesized or advertised to be EA-free, are replacing PC resins used to make reusable hard and clear thermoplastic products such as baby bottles.

Screening and management of gestational diabetes mellitus in Scottish obstetric units: a national survey.

Background And Aims: The last study of screening practices for gestational diabetes (GDM) in the UK concluded that a lack of consensus about screening was due to a lack of clinical guidelines. We aimed to determine current practices in Scotland since new guidelines recommended that diagnosis should be made at a lower level of hyperglycaemia.

Method And Results: An online questionnaire designed to investigate the screening and management of GDM was distributed to all maternity units in Scotland managing women with GDM (n = 15) for completion by relevant clinical team members.

Mutations across murine hepatitis virus nsp4 alter virus fitness and membrane modifications.

Unlabelled: A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation.