JFH1-based Core-NS2 genotype variants of HCV with genetic stability in vivo and in vitro: Important tools in the evaluation of virus neutralization.

Background And Aims: HCV infection continues to be a major global health burden despite effective antiviral treatments. The urgent need for a protective vaccine is hindered by the scarcity of suitable HCV-permissive animal models tractable in vaccination and challenge studies. Currently, only antibody neutralization studies in infectious cell culture systems or studies of protection by passive immunization of human liver chimeric mice offer the possibility to evaluate the effect of vaccine-induced antibodies.

Spaceborne Evidence That Ice-Nucleating Particles Influence High-Latitude Cloud Phase.

Mixed-phase clouds (MPCs), which consist of both supercooled cloud droplets and ice crystals, play an important role in the Earth's radiative energy budget and hydrological cycle. In particular, the fraction of ice crystals in MPCs determines their radiative effects, precipitation formation and lifetime. In order for ice crystals to form in MPCs, ice-nucleating particles (INPs) are required.

The association of change in peak oxygen uptake with use of psychotropics in community-dwelling older adults - The Generation 100 study.

Background: The use of psychotropics is high among the older population and may have detrimental effects on their physical and mental health. Cardiorespiratory fitness (CRF) is a strong and modifiable measure of health and declines with age. We aimed to study the association of change in CRF with use of psychotropics in community-dwelling older adults.

[Detection, investigation, and management of delirium in hospitalized elderly].

Delirium is common in hospitalized older adults. The condition is frequently not recognized, or managed appropriately, and has a poor prognosis. This review finds that a proactive multicomponent interdisciplinary non-farmacological approach can reduce incidence.

Effect of 5 years of exercise training on the cardiovascular risk profile of older adults: the Generation 100 randomized trial.

Aims: The aim of this study was to compare the effects of 5 years of supervised exercise training (ExComb), and the differential effects of subgroups of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), with control on the cardiovascular risk profile in older adults.

Methods And Results: Older adults aged 70-77 years from Trondheim, Norway (n = 1567, 50% women), able to safely perform exercise training were randomized to 5 years of two weekly sessions of HIIT [∼90% of peak heart rate (HR), n = 400] or MICT (∼70% of peak HR, n = 387), together forming ExComb (n = 787), or control (instructed to follow physical activity recommendations, n = 780). The main outcome was a continuous cardiovascular risk score (CCR), individual cardiovascular risk factors, and peak oxygen uptake (VO2peak).

Biochemical and biophysical characterization of the OXA-48-like carbapenemase OXA-436.

The crystal structure of the class D β-lactamase OXA-436 was solved to a resolution of 1.80 Å. Higher catalytic rates were found at higher temperatures for the clinically important antibiotic imipenem, indicating better adaptation of OXA-436 to its mesophilic host than OXA-48, which is believed to originate from an environmental source.

[Assessment of older patients upon admission at the emergency department].

Older patients admitted to the emergency departments represent a heterogeneous group, some are frail with reduced reserve capacity and without ability to compensate to acute illness. They often present with nonspecific complaints and atypical presentation and are at-risk of complications and adverse events. These patients need a fast comprehensive interdisciplinary and multicomponent assessment and intervention to reduce the risk of further functional decline and to optimize their overall health status, independency and quality of life.

Contrasting genetic structuring in the closely related basidiomycetes Trichaptum abietinum and Trichaptum fuscoviolaceum (Hymenochaetales).

Trichaptum abietinum and Trichaptum fuscoviolaceum (Hymenochaetales, Basidiomycota) are closely related saprotrophic fungi, widely distributed on coniferous wood in temperate regions worldwide. Three intersterility groups have previously been detected in T. abietinum, while no prezygotic barriers have been proven within T.

Effect of exercise training for five years on all cause mortality in older adults-the Generation 100 study: randomised controlled trial.

Objective: To evaluate the effect of five years of supervised exercise training compared with recommendations for physical activity on mortality in older adults (70-77 years).

Design: Randomised controlled trial.

Setting: General population of older adults in Trondheim, Norway.

ZN148 Is a Modular Synthetic Metallo-β-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens .

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options.

A single ectomycorrhizal plant root system includes a diverse and spatially structured fungal community.

Although only a relatively small proportion of plant species form ectomycorrhizae with fungi, it is crucial for growth and survival for a number of widespread woody plant species. Few studies have attempted to investigate the fine scale spatial structure of entire root systems of adult ectomycorrhizal (EcM) plants. Here, we use the herbaceous perennial Bistorta vivipara to map the entire root system of an adult EcM plant and investigate the spatial structure of its root-associated fungi.

The biological assembly of OXA-48 reveals a dimer interface with high charge complementarity and very high affinity.

Many class D β-lactamases form dimers in solution. The functional basis of the dimerization of OXA-48-like class D β-lactamases is not known, but in order to understand the structural requirements for dimerization of OXA-48, we have characterized the dimer interface. Size exclusion chromatography, small angle X-ray scattering (SAXS), and nuclear magnetic resonance (NMR) were used to confirm the oligomeric state of OXA-48 in solution.

Long-term Changes in Depressive Symptoms and Estimated Cardiorespiratory Fitness and Risk of All-Cause Mortality: The Nord-Trøndelag Health Study.

Objective: To assess the independent and combined associations of long-term changes in depressive symptoms (DSs) and estimated cardiorespiratory fitness (eCRF) with all-cause mortality.

Participants And Methods: This is a longitudinal cohort study of 15,217 middle-aged and older individuals attending both the second (from August 15, 1995, through June 18, 1997) and third (from October 3, 2006, through June 25, 2008) health surveys of the Nord-Trøndelag Health Study, Norway, and followed until December 31, 2014. Depressive symptoms were estimated using the validated Hospital Anxiety and Depression Scale, and a validated nonexercise model estimated eCRF.

A synopsis of the saddle fungi (: ) in Europe - species delimitation, taxonomy and typification.

is a widespread, speciose genus of large apothecial ascomycetes (: ) that are found in terrestrial biomes of the Northern and Southern Hemispheres. This study represents a beginning on assessing species limits and applying correct names for species based on type material and specimens in the university herbaria (fungaria) of Copenhagen (C), Harvard (FH) and Oslo (O). We use morphology and phylogenetic evidence from four loci - heat shock protein 90 (), translation elongation factor alpha (), RNA polymerase II () and the nuclear large subunit ribosomal DNA (LSU) - to assess species boundaries in an expanded sample of specimens from Europe.

Efficacy of NS5A Inhibitors Against Hepatitis C Virus Genotypes 1-7 and Escape Variants.

Background & Aims: Inhibitors of the hepatitis C virus (HCV) NS5A protein are a key component of effective treatment regimens, but the genetic heterogeneity of HCV has limited the efficacy of these agents and mutations lead to resistance. We directly compared the efficacy of all clinically relevant NS5A inhibitors against HCV genotype 1-7 prototype isolates and resistant escape variants, and investigated the effects of pre-existing resistance-associated substitutions (RAS) on HCV escape from treatment.

Methods: We measured the efficacy of different concentrations of daclatasvir, ledipasvir, ombitasvir, elbasvir, ruzasvir, velpatasvir, and pibrentasvir in cultured cells infected with HCV recombinants expressing genotype 1-7 NS5A proteins with or without RAS.

Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis.

The first crystal structures of the class D β-lactamases OXA-181 and OXA-245 were determined to 2.05 and 2.20 Å resolution, respectively; in addition, the structure of a new crystal form of OXA-163 was resolved to 2.

Absolute and relative accelerometer thresholds for determining the association between physical activity and metabolic syndrome in the older adults: The Generation-100 study.

Background: When assessing population adherence to physical activity (PA) recommendation using accelerometers, absolute intensity threshold definition is applied despite having limited validity in those with low cardiorespiratory fitness (CRF), who are unable to reach them (e.g older adults). Thus, PA thresholds relative to CRF may be an alternative approach.

Efficient Hepatitis C Virus Genotype 1b Core-NS5A Recombinants Permit Efficacy Testing of Protease and NS5A Inhibitors.

Hepatitis C virus (HCV) strains belong to seven genotypes with numerous subtypes that respond differently to antiviral therapies. Genotype 1, and primarily subtype 1b, is the most prevalent genotype worldwide. The development of recombinant HCV infectious cell culture systems for different variants, permitted by the high replication capacity of strain JFH1 (genotype 2a), has advanced efficacy and resistance testing of antivirals.

Fungal diversity and seasonal succession in ash leaves infected by the invasive ascomycete Hymenoscyphus fraxineus.

High biodiversity is regarded as a barrier against biological invasions. We hypothesized that the invasion success of the pathogenic ascomycete Hymenoscyphus fraxineus threatening common ash in Europe relates to differences in dispersal and colonization success between the invader and the diverse native competitors. Ash leaf mycobiome was monitored by high-throughput sequencing of the fungal internal transcribed spacer region (ITS) and quantitative PCR profiling of H.

Proteome Analysis of Rheumatoid Arthritis Gut Mucosa.

Rheumatoid arthritis (RA) is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. To gain new insight into the systemic immune manifestations of RA, we characterized the colon mucosa proteome from 11 RA-patients and 10 healthy controls. The biopsies were extracted by colonoscopy and analyzed by label-free quantitative proteomics, enabling the quantitation of 5366 proteins.

Role of Residues W228 and Y233 in the Structure and Activity of Metallo-β-Lactamase GIM-1.

Metallo-β-lactamases (MBLs) hydrolyze virtually all β-lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs.

Discovery of Novel Inhibitor Scaffolds against the Metallo-β-lactamase VIM-2 by Surface Plasmon Resonance (SPR) Based Fragment Screening.

Metallo-β-lactamase (MBL) inhibitors can restore the function of carbapenem antibiotics and therefore help to treat infections of antibiotic resistant bacteria. In this study, we report novel fragments inhibiting the clinically relevant MBL Verona integron-encoded metallo-β-lactamase (VIM-2). The fragments were identified from a library of 490 fragments using an orthogonal screening approach based on a surface plasmon resonance (SPR) based assay combined with an enzyme inhibition assay.

New relative intensity ambulatory accelerometer thresholds for elderly men and women: the Generation 100 study.

Background: Public health initiatives world-wide recommend increasing physical activity (PA) to improve health. However, the dose and the intensity of PA producing the most benefit are still debated. Accurate assessment of PA is necessary in order to 1) investigate the dose-response relationship between PA and health, 2) shape the most beneficial public health initiatives and 3) test the effectiveness of such initiatives.