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H/ACA small RNA dysfunctions in disease reveal key roles for noncoding RNA modifications in hematopoietic stem cell differentiation

Noncoding RNAs control critical cellular processes, although their contribution to disease remains largely unexplored. Dyskerin associates with hundreds of H/ACA small RNAs to generate a multitude of functionally distinct ribonucleoproteins (RNPs). The DKC1 gene, encoding dyskerin, is mutated in the multisystem disorder X-linked dyskeratosis congenita (X-DC). A central question is whether DKC1 mut

rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells

How pseudouridylation (Ψ), the most common and evolutionarily conserved modification of rRNA, regulates ribosome activity is poorly understood. Medically, Ψ is important because the rRNA Ψ synthase, DKC1, is mutated in X-linked dyskeratosis congenita (X-DC) and Hoyeraal-Hreidarsson (HH) syndrome. Here, we characterize ribosomes isolated from a yeast strain in which Cbf5p, the yeast homolog of DKC1

Loss of function of the tumor suppressor DKC1 perturbs p27 translation control and contributes to pituitary tumorigenesis

Mutations in DKC1, encoding for dyskerin, a pseudouridine synthase that modifies rRNA and regulates telomerase activity, are associated with ribosomal dysfunction and increased cancer susceptibility in the human syndrome, X-linked dyskeratosis congenita (X-DC). In a mouse model for X-DC, impairments in DKC1 function affected the translation of specific mRNAs harboring internal ribosomal entry site

Deregulation of oncogene-induced senescence and p53 translational control in X-linked dyskeratosis congenita

Defects in ribosome biogenesis and function are present in a growing list of human syndromes associated with cancer susceptibility. One example is X-linked dyskeratosis congenita (X-DC) in which the DKC1 gene, encoding for an enzyme that modifies ribosomal RNA, is found to be mutated. How ribosome dysfunction leads to cancer remains poorly understood. A critical cellular response that counteracts

Reslizumab for Inadequately Controlled Asthma with Elevated Blood Eosinophil Levels : a Randomized Phase 3 Study

BACKGROUND: This phase 3 study further characterizes the efficacy and safety of reslizumab (a humanized anti-interleukin-5 monoclonal antibody) in patients aged 12-75 years with asthma inadequately controlled by at least a medium-dose inhaled corticosteroid, and blood eosinophils ≥400cells/μL.METHODS: Patients were randomized to receive reslizumab 0.3 or 3.0mg/kg or placebo once/every 4 weeks/16 w

The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use : Results from an Observational Study (ASSESS)

This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource u

Comorbidity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory condition, which is associated with an increased risk of comorbidity from other diseases. RA disease severity is a major predictor of development of cardiovascular disease, serious infections and malignant lymphoma. This reflects the role of chronic inflammation in the underlying pathology. Recent surveys indicate that although clinical outcomes

Undersökning av kalciumkarbonatförekomsten i Vombfältet

I en studie av neutralisationskapaciteten och kalkstenshalten i Sydvattens infiltrationsområde vid Vomb har fem prover från olika platser i fältet samlats in, siktats och surgjorts med saltsyra. Neutralisationskapaciteten mätt som kalciumkarbonathalt befanns variera i de olika sandproverna men var generellt hög (ca 2–14 % som vikt). Den totala massan av kalciumkarbonat i infiltrationsområdet bestäIn a study of the neutralization capacity and limestone content the artificial recharge area of the Sydvatten waterworks Vombverket in Vomb, Skåne, five samples from different locations in the area was collected, sieved and acidified with hydrochloric acid. The neutralization capacity measured as calcium carbonate content was found to vary in the different sandy soil samples but was generally high

An oat bran-based beverage reduce postprandial glycaemia equivalent to yoghurt in healthy overweight subjects.

An acute meal study was performed to determine postprandial glucose and insulin responses after consumption of two fermented oat bran-based beverages (with and without exopolysaccharides) and yoghurt. This randomized, single-blind, within-subject study included 18 healthy, overweight participants. Four breakfast meals, including a reference meal, were tested; all meals contained 50 g of available