A genome-scale metabolic reconstruction provides insight into the metabolism of the thermophilic bacterium Rhodothermus marinus.

The thermophilic bacterium Rhodothermus marinus has mainly been studied for its thermostable enzymes. More recently, the potential of using the species as a cell factory and in biorefinery platforms has been explored, due to the elevated growth temperature, native production of compounds such as carotenoids and EPSs, the ability to grow on a wide range of carbon sources including polysaccharides, and available genetic tools. A comprehensive understanding of the metabolism of cell factories is important.

A genome-wide association meta-analysis links hidradenitis suppurativa to common and rare sequence variants causing disruption of the Notch and Wnt/β-catenin signaling pathways.

Background: The contributions of genetic and environmental risk factors to hidradenitis suppurativa (HS) are both poorly understood.

Objective: To identify sequence variants that associate with HS and determine the contribution of environmental risk factors and inflammatory diseases to HS pathogenesis.

Methods: A genome-wide association meta-analysis of 4,814 HS cases (Denmark: 1,977; Iceland: 1,266; Finland: 800; UK: 569 and US: 202) and 1.

Novel loci and biomedical consequences of iron homoeostasis variation.

Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.

Transformers significantly improve splice site prediction.

Mutations that affect RNA splicing significantly impact human diversity and disease. Here we present a method using transformers, a type of machine learning model, to detect splicing from raw 45,000-nucleotide sequences. We generate embeddings with residual neural networks and apply hard attention to select splice site candidates, enabling efficient training on long sequences.

Corroborating written history with ancient DNA: The case of the Well-man described in an Old Norse .

The potential of ancient DNA analyses to provide independent sources of information about events in the historical record remains to be demonstrated. Here we apply palaeogenomic analysis to human remains excavated from a medieval well at the ruins of Sverresborg Castle in central Norway. In , the Old Norse of King Sverre Sigurdsson, one passage details a 1197-CE raid on the castle and mentions a dead man thrown into the well.

Sequence variants associated with BMI affect disease risk through BMI itself.

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement.

A partial loss-of-function variant in STAT6 protects against type 2 asthma.

Background: Signal transducer and activator of transcription 6 (STAT6) is central to type 2 (T2) inflammation, and common noncoding variants at the STAT6 locus associate with various T2 inflammatory traits, including diseases, and its pathway is widely targeted in asthma treatment.

Objective: We sought to test the association of a rare missense variant in STAT6, p.L406P, with T2 inflammatory traits, including the risk of asthma and allergic diseases, and to characterize its functional consequences in cell culture.

Monoallelic de novo variants in DDX17 cause a neurodevelopmental disorder.

DDX17 is an RNA helicase shown to be involved in critical processes during the early phases of neuronal differentiation. Globally, we compiled a case-series of 11 patients with neurodevelopmental phenotypes harbouring de novo monoallelic variants in DDX17. All 11 patients in our case series had a neurodevelopmental phenotype, whereby intellectual disability, delayed speech and language, and motor delay predominated.

Developmental language disorder - heritability and genetic correlations with other disorders affecting language.

Developmental language disorder (DLD) is a neurodevelopmental disorder primarily affecting language in the absence of a known biomedical condition, which may have a large impact on a person's life and mental health. Family-based studies indicate a strong genetic component in DLD, but genetic studies of DLD are scarce. In this study we estimated the heritability of DLD and its genetic correlations with related disorders and traits in sample of >25,000 individuals from the Danish Blood Donor Study for whom we had both genotype data and questionnaire data on language disorder and language support.

Mass spectrometry identifies tau C-terminal phosphorylation cluster during neuronal hyperexcitation.

Tau is a microtubule-associated protein implicated in Alzheimer's disease (AD) and other neurodegenerative disorders termed tauopathies. Pathological, aggregated forms of tau form neurofibrillary tangles (NFTs), impairing its ability to stabilize microtubules and promoting neurotoxicity. Indeed, NFTs correlate with neuronal loss and cognitive impairment.

Polygenic Interactions With Environmental Exposures in Blood Pressure Regulation: The HUNT Study.

Background: The essential hypertension phenotype results from an interplay between genetic and environmental factors. The influence of lifestyle exposures such as excess adiposity, alcohol consumption, tobacco use, diet, and activity patterns on blood pressure (BP) is well established. Additionally, polygenic risk scores for BP traits are associated with clinically significant phenotypic variation.

Elevated expression of Aurora-A/AURKA in breast cancer associates with younger age and aggressive features.

Background And Objective: Aurora kinase A (AURKA) is reported to be overexpressed in breast cancer. In addition to its role in regulating cell cycle and mitosis, studies have reported AURKA involvements in oncogenic signaling in suppressing BRCA1 and BRCA2. We aimed to characterize AURKA protein and mRNA expression in a breast cancer cohort of the young, investigating its relation to clinico-pathologic features and survival, and exploring age-related AURKA-associated biological processes.

Homozygosity for a stop-gain variant in CCDC201 causes primary ovarian insufficiency.

Age at menopause (AOM) has a substantial impact on fertility and disease risk. While many loci with variants that associate with AOM have been identified through genome-wide association studies (GWAS) under an additive model, other genetic models are rarely considered. Here through GWAS meta-analysis under the recessive model of 174,329 postmenopausal women from Iceland, Denmark, the United Kingdom (UK; UK Biobank) and Norway, we study low-frequency variants with a large effect on AOM.