Integrated safety analysis of filgotinib for ulcerative colitis: Results from SELECTION and SELECTIONLTE.

Background: Filgotinib 200 mg (FIL200) is an approved treatment for adults with moderately to severely active ulcerative colitis (UC).

Aim: To report integrated safety data from the phase 2b/3 SELECTION study (NCT02914522) and its ongoing long-term extension study SELECTIONLTE (NCT02914535).

Methods: Safety outcomes were analysed in adults with moderately to severely active UC who received FIL200, filgotinib 100 mg (FIL100) or placebo once daily throughout the 11-week SELECTION induction study, the 47-week SELECTION maintenance study (if applicable) and SELECTIONLTE (if applicable).

Corticosteroid-Sparing Effects of Filgotinib in Moderately to Severely Active Ulcerative Colitis: Data from the Phase 2b/3 SELECTION Study.

Background And Aims: Corticosteroid-free remission is an important treatment goal for patients with ulcerative colitis [UC]. The corticosteroid-sparing effects of filgotinib, an oral, Janus kinase 1 preferential inhibitor, were assessed in SELECTION, a placebo-controlled, phase 2b/3 trial in moderately to severely active UC.

Methods: These post hoc analyses assessed 1-, 3-, 6-, and 8-month rates of corticosteroid-free clinical remission at Week 58 and change in median daily prednisone-equivalent dose over time.

An Experimental Model of Neuromyelitis Optica Spectrum Disorder-Optic Neuritis: Insights Into Disease Mechanisms.

Optic neuritis (ON) is a common inflammatory optic neuropathy, which often occurs in neuromyelitis optica spectrum disease (NMOSD). An experimental model of NMOSD-ON may provide insight into disease mechanisms. To examine the pathogenicity of autoantibodies targeting the astrocyte water channel aquaporin-4 [aquaporin-4 (AQP4)-immunoglobulin G (AQP4-IgG)] in the optic nerve.

Meltome atlas-thermal proteome stability across the tree of life.

We have used a mass spectrometry-based proteomic approach to compile an atlas of the thermal stability of 48,000 proteins across 13 species ranging from archaea to humans and covering melting temperatures of 30-90 °C. Protein sequence, composition and size affect thermal stability in prokaryotes and eukaryotic proteins show a nonlinear relationship between the degree of disordered protein structure and thermal stability. The data indicate that evolutionary conservation of protein complexes is reflected by similar thermal stability of their proteins, and we show examples in which genomic alterations can affect thermal stability.

A metagenome-derived thermostable β-glucanase with an unusual module architecture which defines the new glycoside hydrolase family GH148.

The discovery of novel and robust enzymes for the breakdown of plant biomass bears tremendous potential for the development of sustainable production processes in the rapidly evolving new bioeconomy. By functional screening of a metagenomic library from a volcano soil sample a novel thermostable endo-β-glucanase (EngU) which is unusual with regard to its module architecture and cleavage specificity was identified. Various recombinant EngU variants were characterized.

Comparative characterization of all cellulosomal cellulases from reveals high diversity in endoglucanase product formation essential for complex activity.

Background: is a paradigm for efficient cellulose degradation and a promising organism for the production of second generation biofuels. It owes its high degradation rate on cellulosic substrates to the presence of supra-molecular cellulase complexes, cellulosomes, which comprise over 70 different single enzymes assembled on protein-backbone molecules of the scaffold protein CipA.

Results: Although all 24 single-cellulosomal cellulases were described previously, we present the first comparative catalogue of all these enzymes together with a comprehensive analysis under identical experimental conditions, including enzyme activity, binding characteristics, substrate specificity, and product analysis.

Integration of known DNA, RNA and protein biomarkers provides prediction of anti-TNF response in rheumatoid arthritis: results from the COMBINE study.

Objective: In rheumatoid arthritis (RA) several recent efforts have sought to discover means of predicting which patients would benefit from treatment. However, results have been discrepant with few successful replications. Our objective was to build a biobank with DNA, RNA and protein measurements to test the claim that the current state-of-the-art precision medicine will benefit RA patients.

The effect of acute exercise on collagen turnover in human tendons: influence of prior immobilization period.

Mechanical loading of human tendon stimulates collagen synthesis, but the relationship between acute loading responses and training status of the tendon is not clear. We tested the effect of prolonged load deprivation on the acute loading-induced collagen turnover in human tendons, by applying the same absolute load to a relative untrained Achilles tendon (2-week immobilization period prior to acute loading) and a habitually loaded contra-lateral Achilles tendon, respectively, within the same individuals. Eight untrained, healthy males had one lower limb totally immobilized for 2 weeks, whereas the contra-lateral leg was used habitually.

Glucagon-like Peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation.

Liraglutide is a glucagon-like peptide-1 (GLP-1) analog developed for type 2 diabetes. Long-term liraglutide exposure in rodents was associated with thyroid C-cell hyperplasia and tumors. Here, we report data supporting a GLP-1 receptor-mediated mechanism for these changes in rodents.

The influence of training status on the drop in muscle strength after acute exercise.

Skeletal muscles fatigue after exercise, and reductions in maximal force appear. A difference in training status between the legs was introduced by unilateral immobilization of the calf muscles for 2 weeks in young men, who were randomly assigned to two groups, either a RUN group (n = 8) that was exposed to prolonged exercise (1-h running: individual pace) or a REST group (n = 12) that did no exercise after immobilization. Cross-sectional area (CSA) of the triceps-surae muscles was calculated by magnetic resonance imaging (MRI), and maximal voluntary contraction (MVC) force of the plantar flexors was measured before and after immobilization and after the running protocol.

Flow sorting from organ material by intracellular markers.

Background: Fluorescence-activated cell sorting (FACS) is an attractive technique for gene or protein expression studies in rare cell populations. For cell types where specific surface markers are not known, intracellular markers can be used. However, this approach is currently held to be difficult, as the required fixation and permeabilization may cause protein modification and RNA degradation.

Allergen-specific polyclonal antibodies reduce allergic disease in a mouse model of allergic asthma.

Background: Recombinant allergen-specific immunoglobulin G (IgG) antibody therapy can reduce allergic asthma symptoms by inhibiting the immunoglobulin E (IgE)-mediated allergic response. This study investigated the effect of intranasally administered allergen-specific monoclonal (mAb) and polyclonal (pAb) antibody on airway inflammation and hyperresponsiveness (AHR) in a mouse model of human asthma.

Methods: Ovalbumin (OVA)-specific IgG2b antibodies were generated by phage display using spleens from OVA-immunized mice, and screening against OVA and finally expressed in CHO cells.

Motor responses to stimulation during isoflurane anaesthesia in pigs.

Objective: To investigate motor responses to stimulation during the transition from 'deep' (burst suppression) to 'light' isoflurane anaesthesia in pigs.

Study Design: Prospective, randomized observational study.

Animals: Five castrated male and five female Norwegian landrace pigs, weighing 19-29 kg.

Electroencephalographic and cardiovascular indicators of nociception during isoflurane anaesthesia in pigs.

Objective To evaluate electroencephalographic indices, invasive arterial blood pressure and pulse rate as indicators of nociception during isoflurane anaesthesia in pigs. Animals Ten Norwegian Landrace pigs, five castrated males and five females, weighing between 19 and 29 kg. Materials and methods The pigs were anaesthetized with isoflurane and prepared for the measurement of heart rate (HR), mean arterial pressure (MAP) and the electroencephalogram (EEG).

In situ cytokine therapy: redistribution of clonally expanded T cells.

Immunity to tumors relies on recirculating antigen-specific T cells. Whilst induction of antigen-specific T cells by immunotherapy has been convincingly proven, direct evidence for recirculation of such cells is still lacking. Here, employing a recently established in situ immunotherapy model for murine melanoma we directly demonstrate the redistribution of clonally expanded T cells.

Effects of intravenous infusion of guaifenesin on electroencephalographic variables in pigs.

Objective: To investigate the sedative effects of guaifenesin in pigs by use of electroencephalography.

Animals: 10 Norwegian Landrace pigs (5 castrated males and 5 sexually intact females).

Procedure: Guaifenesin (150 mg/kg of body weight, IV) was administered during a 5-minute period.

Comparative delineation of T cell clonotypes in coexisting syngeneic B16 melanoma.

B16 is a murine melanoma of C57B1/6 origin, which rapidly develops as a tumor when inoculated into syngeneic immunocompetent hosts. Nevertheless, B16 tumors are considered to be immunogenic since tumor regression can be induced by means of immunotherapeutic intervention. Furthermore, B16 melanoma cells express several melanoma-associated antigens that may serve as targets for autologous T cells.

Recombinant aprotinin in coronary artery bypass graft operations.

Objective: To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery.

Design: An open-label, randomized, controlled study evaluating two dosage levels of recombinant aprotinin.

Setting: Two acute care hospitals (Northwestern Memorial Hospital, Chicago, Ill.