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Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression

Existing evidence indicates that gut fungal dysbiosis might play a key role in the pathogenesis of colorectal cancer (CRC). We sought to explore whether reversing the fungal dysbiosis by terbinafine, an approved antifungal drug, might inhibit the development of CRC. A population-based study from Sweden identified a total of 185 patients who received terbinafine after their CRC diagnosis and found

IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage

Conventional dendritic cells (cDCs) consist of two major functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in committed cDC1 remains unclear. Here, we used Xcr1-cre to delete Irf8 in committed cDC1 and demons

Combined genetic deficiencies of the classical complement pathway are strongly associated with both systemic lupus erythematosus and primary Sjögren's syndrome

ObjectiveComplete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjögren's syndrome (pSS) has not been studied systematically. Here we investigated heterozygous C2 deficiency and C4 copy number variation in relation to clinical manifestations in SLE

Light, activity and sleep in my daily life: : Design of an online intervention targeting changes to routines and the home

Background: Older adults spend more time at home after retirement, and the home becomes a central place for activity. While research indicates that indoor lighting, exposure to daylight, physical activity and sleep interact to influence functioning, mood and daily rhythm, strategies are needed to promote behavioural changes to optimise these factors in daily life. The objective is to design an int

Interaction of leisure-time physical activity with body mass index on the risk of obesity-related cancers : A pooled study

Physical activity (PA) has been associated with a lower risk of some obesity-related cancers, but the combined association and interaction of PA and body weight on obesity-related cancer risk is less clear. We examined the association of leisure-time PA (high/low) and its combination with body mass index (BMI, <25 [low]/≥25 [high] kg/m2) on obesity-related cancer risk in 570 021 individuals, aged

Alternative splicing modulation by G-quadruplexes

Alternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand. RNA-seq data from mouse and human neurons reveals an enrichment of G4s at exons that were skipped

Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men

Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three

Compositional analysis of oxide-embedded III-V nanostructures

Nanowire growth enables creation of embedded heterostructures, where one material is completely surrounded by another. Through materials-selective post-growth oxidation it is also possible to combine amorphous oxides and crystalline, e.g. III-V materials. Such oxide-embedded structures pose a challenge for compositional characterization through transmission electron microscopy since the materials

Early and Late Migrating Avian Individuals Differ in Constitutive Immune Function and Blood Parasite Infections – But Patterns Depend on the Migratory Strategy

Billions of birds migrate every year. To conduct a successful migration, birds undergo a multitude of physiological adaptions. One such adaptation includes adjustments of immune function, however, little is known about intraspecies (between-individual) and interspecies (between-species) variation in immune modulations during migration. Here, we explore if early and late migrating individuals diffe

Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men

Testosterone is a hormone that plays a key role in carbohydrate, fat, and protein metabolism. Testosterone deficiency is associated with multiple comorbidities, e.g., metabolic syndrome and type 2 diabetes. Despite its importance in many metabolic pathways, the mechanisms by which it controls metabolism are not fully understood. The present study investigated the short-term metabolic changes of ph

eHealth literacy and socioeconomic and demographic characteristics of parents of children needing paediatric surgery in Sweden

Aim: The aim of the study was to describe different eHealth literacy domains among parents of children needing paediatric surgery in Sweden, and the correlation between these eHealth literacy domains and parents' socioeconomic factors and demographic characteristics. Design: Descriptive correlational design. Method: Thirty-five Swedish-speaking parents participated as a historical control group wi

High Disease Activity over Time and Persistent Inflammation Are Associated with Increased Risk of Cardiovascular Disease in Patients with Early Rheumatoid Arthritis

Background/Purpose:Rheumatoid arthritis (RA) is associated with an increased rate of cardiovascular (CV) disease. Systemic inflammation has been implicated as a key factor behind CV comorbidity in RA. The objective of this study was to investigate the impact of disease activity and inflammation over the first two years on the risk of subsequent CV events in patients with early RA.Methods:An incept

Graphene as an Adsorption Template for Studying Double Bond Activation in Catalysis

Hydrogenated graphene (H-Gr) is an extensively studied system not only because of its capabilities as a simplified model system for hydrocarbon chemistry but also because hydrogenation is a compelling method for Gr functionalization. However, knowledge of how H-Gr interacts with molecules at higher pressures and ambient conditions is lacking. Here we present experimental and theoretical evidence t

Dynamically upregulated mast cell CPA3 patterns in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis

Background: The mast cell-specific metalloprotease CPA3 has been given important roles in lung tissue homeostasis and disease pathogenesis. However, the dynamics and spatial distribution of mast cell CPA3 expression in lung diseases remain unknown. Methods: Using a histology-based approach for quantitative spatial decoding of mRNA and protein single cell, this study investigates the dynamics of CP

Uncovering the universality of self-replication in protein aggregation and its link to disease

Fibrillar protein aggregates are a hallmark of a range of human disorders, from prion diseases to dementias, but are also encountered in several functional contexts. Yet, the fundamental links between protein assembly mechanisms and their functional or pathological roles have remained elusive. Here, we analyze the aggregation kinetics of a large set of proteins that self-assemble by a nucleated-gr

Best Practices to Promote Data Utility and Reuse by the Non-Traditional Model Organism Community

The dramatic increase in accessibility to sequencing technologies has opened new avenues into studying different processes, cells, and animal models. In the amphibian models used for regeneration research, these new datasets have uncovered a variety of information about what genes define the regenerating limb as well as how genes and cells change over the course of regeneration. The accumulation o

Occupational risk of COVID-19 related hospital admission in Denmark 2020–2021 : a follow-up study

Objective: Mounting evidence indicates increased risk of COVID-19 among healthcare personnel, but the evidence on risks in other occupations is limited. In this study, we quantify the occupational risk of COVID-19-related hospital admission in Denmark during 2020-2021.Methods: The source population included 2.4 million employees age 20-69 years. All information was retrieved from public registers.

Photoprotection in metal halide perovskites by ionic defect formation

Photostability is critical for long-term solar cell operation. While light-triggered defects are usually reported as evidence of material degradation, we reveal that the formation of certain defects in metal halide perovskites is crucial for protection against intense or prolonged light exposure. We identify an inherent self-regulating cycle of formation and recovery of ionic defects under light e

Orthotopic Bone Formation by Streamlined Engineering and Devitalization of Human Hypertrophic Cartilage

Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, l