Ligand binding kinetics to evaluate the function and stability of AR in nanodiscs.

G-protein-coupled receptors (GPCRs) represent one of the largest classes of therapeutic targets. However, developing successful therapeutics to target GPCRs is a challenging endeavor, with many molecules failing during in vivo clinical trials due to a lack of efficacy. The in vitro identification of drug-target residence time (1/k) has been suggested to improve predictions of in vivo success.

Gender Selectively Mediates the Association Between Sex and Memory in Cognitively Normal Older Adults.

Background And Objectives: Sex and gender are important topics of increasing interest in aging and dementia research. Few studies have jointly examined sex (as a biological attribute) and gender (as a sociocultural and behavioral characteristic) within a single study. We explored a novel data mining approach to include both sex and gender as potentially related influences in memory aging research.

Effect factors for marine invasion impacts on biodiversity.

Purpose: Marine vertebrate populations have halved in the past decades, and invasive species are a major driver for this loss. While many model the spread of invasive species, a model to assess impacts of marine invasions, after introduction, has hitherto been missing. We present the first regionalized effect factors for marine invasions.

Drug-related emergency department visits: external validation of an assessment tool in a general emergency department population.

Background: The process of identifying drug-related hospitalisations is subjective and time-consuming. Assessment tool for identifying hospital admissions related to medications (AT-HARM10) was developed to simplify and objectify this process. AT-HARM10 has not previously been externally validated, thus the predictive precision of the tool is uncertain.

Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders.

Background And Hypothesis: The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood.

A comprehensive analysis of pneumococcal two-component system regulatory networks.

Two-component systems are key signal-transduction systems that enable bacteria to respond to a wide variety of environmental stimuli. The human pathogen, (pneumococcus) encodes 13 two-component systems and a single orphan response regulator, most of which are significant for pneumococcal pathogenicity. Mapping the regulatory networks governed by these systems is key to understand pneumococcal host adaptation.

LCA of recycling aluminium incineration bottom ash, dross and shavings in a rotary furnace and environmental benefits of salt-slag valorisation.

Recycling aluminium in a rotary furnace with salt-fluxes allows recovering valuable alloys from hard-to-recycle waste/side-streams such as packaging, dross and incinerator bottom ash. However, this recycling route generates large amounts of salt-slag/salt-cake hazardous wastes which can pose critical environmental risks if landfilled. To tackle this issue, the metallurgical industry has developed processes to valorise the salt-slag residues into recyclable salts and aluminium concentrates, while producing by-products such as ammonium sulphate and non-metallic compounds (NMCs), with applications in the construction or chemical industries.

Clinical value of Alzheimer's disease biomarker testing.

Introduction: In the Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia (IMPACT-AD BC) study, we aimed to understand how Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarker testing-used in medical care-impacted medical decision-making (medical utility), personal decision-making (personal utility), and health system economics.

Methods: The study was designed as an observational, longitudinal cohort study. A total of 149 patients were enrolled between February 2019 and July 2021.

Genome-scale metabolic models reveal determinants of phenotypic differences in non-Saccharomyces yeasts.

Background: Use of alternative non-Saccharomyces yeasts in wine and beer brewing has gained more attention the recent years. This is both due to the desire to obtain a wider variety of flavours in the product and to reduce the final alcohol content. Given the metabolic differences between the yeast species, we wanted to account for some of the differences by using in silico models.

The economic impact of decreased mortality and increased growth associated with preventing, replacing or improving current methods for delousing farmed Atlantic salmon in Norway.

Impacts of salmon lice is a major concern for a sustainable production of farmed Atlantic salmon in Norway. Most treatment methods for removal of salmon lice have associated increased mortality and decreased growth in a period after delousing, which affects the profitability of the farmer, and causes poor welfare and sustainability. In addition, the variance in mortality and growth, especially after non-medicinal treatment methods, is high, which makes it hard for a farmer to decide which control measure to apply to keep lice levels below the legal limit.

Contact with primary care physicians among adults with pre-existing common mental health problems during the COVID-19 pandemic: a registry-based study from Norway.

Background: During the COVID-19 pandemic, individuals with pre-existing mental health problems may have experienced additional stress, which could worsen symptoms or trigger relapse. Thus, this study aimed to investigate if the number of consultations with general practitioners (GPs) among individuals with a pre-existing common mental health problem during the pandemic differed from pre-pandemic years.

Methods: Data on consultations with GPs among 18-65-year-olds registered with common mental health problems in 2017-2021 were retrieved from the Norwegian Control and Payment of Health Reimbursements Database.

The dementia-inclusive choices in exercise project: Using participatory action research to improve physical activity supports for persons with dementia.

Persons with dementia have the right to equal inclusion in rehabilitation, including physical activity. However, the perspectives of persons with dementia are rarely integrated into decision-making related to physical activity programming, services, and supports. Here, we describe the participatory action research (PAR) approach used to develop the Dementia-Inclusive Choices for Exercise (DICE) toolkit, which aims to increase the quality and number of physical activity opportunities available to persons with dementia.

Incidence rates of treated mental disorders before and during the COVID-19 pandemic-a nationwide study comparing trends in the period 2015 to 2021.

Background: There is a concern that exposure to psychosocial stressors during the COVID-19 pandemic may have led to a higher incidence of mental disorders. Thus, this study aimed to compare trends in incidence rates of depressive disorder, anxiety disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and eating disorders in primary- and specialist health care before (2015-2019) and during the COVID-19 pandemic (2020-2021).

Methods: We used aggregated population registry data to calculate incidence rates of mental disorders from primary- (The Norwegian Control and Payment of Health Reimbursements Registry (KUHR)) and specialist (The Norwegian Patient Registry (NPR)) health care.

Quantitative Lipidomic Analysis of Serum Phospholipids Reveals Dissociable Markers of Alzheimer's Disease and Subcortical Cerebrovascular Disease.

Background: Circulating phospholipid species have been shown to predict Alzheimer's disease (AD) prognosis but the link between phospholipid disturbances and subcortical small vessel cerebrovascular disease (CeVD) common in AD patients is not known.

Objective: Mass-spectrometry lipidomics was applied to quantify serum diacyl, alkenyl (ether), alkyl, and lyso phospholipid species in individuals with extensive CeVD (n = 29), AD with minimal CeVD (n = 16), and AD with extensive CeVD (n = 14), and compared them to age-matched controls (n = 27). Memory was assessed using the California Verbal Learning Test.

Parameter inference for enzyme and temperature constrained genome-scale models.

The metabolism of all living organisms is dependent on temperature, and therefore, having a good method to predict temperature effects at a system level is of importance. A recently developed Bayesian computational framework for enzyme and temperature constrained genome-scale models (etcGEM) predicts the temperature dependence of an organism's metabolic network from thermodynamic properties of the metabolic enzymes, markedly expanding the scope and applicability of constraint-based metabolic modelling. Here, we show that the Bayesian calculation method for inferring parameters for an etcGEM is unstable and unable to estimate the posterior distribution.

Vitamin D is associated with visual memory in young northern adolescents.

Background: Vitamin D status has been linked to visual memory in adults. We hypothesized a similar association in young adolescents.

Methods: Participants were 9-13 years.

Advances in nanodisc platforms for membrane protein purification.

Membrane scaffold protein nanodiscs (MSPNDs) are an invaluable tool for improving purified membrane protein (MP) stability and activity compared to traditional micellar methods, thus enabling an increase in high-resolution MP structures, particularly in concert with cryogenic electron microscopy (cryo-EM) approaches. In this review we highlight recent advances and breakthroughs in MSPND methodology and applications. We also introduce and discuss saposin-lipoprotein nanoparticles (salipros) and copolymer nanodiscs which have recently emerged as authentic MSPND alternatives.

Global transcriptional responses of pneumococcus to human blood components and cerebrospinal fluid.

(pneumococcus) is a leading cause of severe invasive infectious diseases such as sepsis and meningitis. Understanding how pneumococcus adapts and survive in the human bloodstream environment and cerebrospinal fluid (CSF) is important for development of future treatment strategies. This study investigates the global transcriptional response of pneumococcus to human blood components and CSF acquired from discarded and anonymized patient samples.

Discovery of Ervogastat (PF-06865571): A Potent and Selective Inhibitor of Diacylglycerol Acyltransferase 2 for the Treatment of Non-alcoholic Steatohepatitis.

Discovery efforts leading to the identification of ervogastat (PF-06865571), a systemically acting diacylglycerol acyltransferase (DGAT2) inhibitor that has advanced into clinical trials for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis, are described herein. Ervogastat is a first-in-class DGAT2 inhibitor that addressed potential development risks of the prototype liver-targeted DGAT2 inhibitor PF-06427878. Key design elements that culminated in the discovery of ervogastat are (1) replacement of the metabolically labile motif with a 3,5-disubstituted pyridine system, which addressed potential safety risks arising from a cytochrome P450-mediated -dearylation of PF-06427878 to a reactive quinone metabolite precursor, and (2) modifications of the amide group to a 3-THF group, guided by metabolite identification studies coupled with property-based drug design.

Brain Imaging Abnormalities in Mixed Alzheimer's and Subcortical Vascular Dementia.

Background: A large proportion of Alzheimer's disease (AD) patients have coexisting subcortical vascular dementia (SVaD), a condition referred to as mixed dementia (MixD). Brain imaging features of MixD presumably include those of cerebrovascular disease and AD pathology, but are difficult to characterize due to their heterogeneity.

Objective: To perform an exploratory analysis of conventional and non-conventional structural magnetic resonance imaging (MRI) abnormalities in MixD and to compare them to those observed in AD and SVaD.

csdR, an R package for differential co-expression analysis.

Background: Differential co-expression network analysis has become an important tool to gain understanding of biological phenotypes and diseases. The CSD algorithm is a method to generate differential co-expression networks by comparing gene co-expressions from two different conditions. Each of the gene pairs is assigned conserved (C), specific (S) and differentiated (D) scores based on the co-expression of the gene pair between the two conditions.

Robust bacterial co-occurence community structures are independent of r- and K-selection history.

Selection for bacteria which are K-strategists instead of r-strategists has been shown to improve fish health and survival in aquaculture. We considered an experiment where microcosms were inoculated with natural seawater and the selection regime was switched from K-selection (by continuous feeding) to r-selection (by pulse feeding) and vice versa. We found the networks of significant co-occurrences to contain clusters of taxonomically related bacteria having positive associations.