Nonequivalence of Second Sphere "Noncatalytic" Residues in Pentaerythritol Tetranitrate Reductase in Relation to Local Dynamics Linked to H-Transfer in Reactions with NADH and NADPH Coenzymes.

Many enzymes that catalyze hydride transfer reactions work via a mechanism dominated by quantum mechanical tunneling. The involvement of fast vibrational modes of the reactive complex is often inferred in these reactions, as in the case of the NAD(P)H-dependent pentaerythritol tetranitrate reductase (PETNR). Herein, we interrogated the H-transfer mechanism in PETNR by designing conservative (L25I and I107L) and side chain shortening (L25A and I107A) PETNR variants and using a combination of experimental approaches (stopped-flow rapid kinetics, X-ray crystallography, isotope/temperature dependence studies of H-transfer and NMR spectroscopy).

Equatorial Active Site Compaction and Electrostatic Reorganization in Catechol--methyltransferase.

Catechol--methyltransferase (COMT) is a model S-adenosyl-l-methionine (SAM) dependent methyl transferase, which catalyzes the methylation of catecholamine neurotransmitters such as dopamine in the primary pathway of neurotransmitter deactivation in animals. Despite extensive study, there is no consensus view of the physical basis of catalysis in COMT. Further progress requires experimental data that directly probes active site geometry, protein dynamics and electrostatics, ideally in a range of positions along the reaction coordinate.

Investigation of Reduced ELISA Recovery of Almond and Hazelnut Traces from Roasted Nut Samples by SDS-PAGE and Mass Spectrometry.

Western society is facing an increase in the number of food-allergic individuals, with rising incidence in the past years. Therefore, allergen-free food and accurate and reliable analysis of allergen contamination are essential for the protection of consumers. Yet, there is limited understanding on the effect of food processing on allergenicity and on the ability of available methods to detect trace contamination in processed food.

Endorsement of the 66/68 Joint Count for the Measurement of Musculoskeletal Disease Activity: OMERACT 2018 Psoriatic Arthritis Workshop Report.

Objective: The Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials and longitudinal observational studies has recently been updated. The joint counts are central to the measurement of the peripheral arthritis component of the musculoskeletal (MSK) disease activity domain. We report the Outcome Measures in Rheumatology (OMERACT) 2018 meeting's approaches to seek endorsement of the 66/68 swollen and tender joint count (SJC66/TJC68) for inclusion in the PsA Core Outcome Measurement Set (COS).

PsAID12 Provisionally Endorsed at OMERACT 2018 as Core Outcome Measure to Assess Psoriatic Arthritis-specific Health-related Quality of Life in Clinical Trials.

Objective: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) psoriatic arthritis (PsA) working group is developing a Core Outcome Measurement Set for PsA clinical trials [randomized controlled trials (RCT) and longitudinal observational studies (LOS)] using the OMERACT Filter 2.1 instrument selection algorithm. Our objective was to assess the Psoriatic Arthritis Impact of Disease questionnaire (PsAID12) for the measurement of the core domain PsA-specific health-related quality of life (HRQOL).

Secukinumab provides sustained PASDAS-defined remission in psoriatic arthritis and improves health-related quality of life in patients achieving remission: 2-year results from the phase III FUTURE 2 study.

Background: Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study.

Methods: PASDAS (cut-off scores: remission ≤ 1.

Using Acute-phase Reactants to Inform the Development of Instruments for the Updated Psoriatic Arthritis Core Outcome Measurement Set.

Objective: Systemic inflammationˆ is assessed through measurement of acute-phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). With few exceptions, most randomized controlled trials (RCT) have assessed acute-phase reactants (CRP and ESR) as part of the American College of Rheumatology (ACR) 20 response criteria. As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) working group, we performed a systematic review of the literature to assess the performance of inflammatory biomarkers in psoriatic arthritis (PsA).

Report-Model studies of transmembrane interaction of FcεRIα/FcRγ reveal novel strategies to inhibit allergic responses.

The high-affinity IgE receptor complex plays an essential part in allergic responses and involved in downstream signaling, released inflammatory mediators that cause allergic responses. The transmembrane region of the high-affinity IgE has a conserved motif (LFAVDTGL) where a polar aspartate (D194) is important for the ligand binding. This modeling study proposes novel potential binding sites between high affinity immunoglobulin E receptor α subunit (FcεRIα) and FcRγ and as a consequence, we propose a new model of FcεRIα and FcRγ interaction (T194) which can mediate downstream signaling in allergic response.

Structural and functional studies of histidine biosynthesis in Acanthamoeba spp. demonstrates a novel molecular arrangement and target for antimicrobials.

Acanthamoeba is normally free-living, but sometimes facultative and occasionally opportunistic parasites. Current therapies are, by necessity, arduous and yet poorly effective due to their inabilities to kill cyst stages or in some cases to actually induce encystation. Acanthamoeba can therefore survive as cysts and cause disease recurrence.

Proceedings of the 2017 GRAPPA Collaborative Research Network Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN) is an endeavor that aims to address gaps in the knowledge of the etiopathogenesis and management of psoriatic disease by best using the large community of experienced investigators who are already collecting rich clinical phenotype data and biologic samples using validated techniques. Exemplar rheumatology and dermatology projects will inform strategies to implement the CRN, while input and funding from government organizations, charities, and industry will shape the CRN. The key immediate priorities to establish the CRN are discussed herein and include (1) strategies for building infrastructure to collect and store biosamples and associated clinical data, (2) best practices for sample collection and storage, (3) approaches to engage the GRAPPA community of investigators and industry to collaborate most effectively on shared priorities, and (4) agreement on a funding strategy.

GRAPPA 2017 Project Report.

At the 2017 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing educational and research efforts. Among them were updates on GRAPPA's continued education efforts; GRAPPA's continued research efforts, including the Biomarker Project, a collaborative research effort to identify and study biomarkers of joint damage; treatment recommendations, including recommendations and core principles related to biosimilars; efforts to update GRAPPA's Website and to create a GRAPPA smart-phone application (app); and the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network.

Content and Face Validity and Feasibility of 5 Candidate Instruments for Psoriatic Arthritis Randomized Controlled Trials: The PsA OMERACT Core Set Workshop at the GRAPPA 2017 Annual Meeting.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is in the process of selecting core instruments for PsA clinical trials. During a 2-h workshop and breakout group discussions at the GRAPPA 2017 annual meeting in Amsterdam, the Netherlands, participants discussed the first set of candidate instruments to be taken through the OMERACT Filter 2.1 instrument selection process: 66/68 swollen/tender joint count (66/68JC), Spondyloarthritis Consortium of Canada (SPARCC) enthesitis index, patient's global assessment (GRAPPA and OMERACT formulations), Health Assessment Questionnaire-Disability Index (HAQ-DI), Psoriatic Arthritis Impact of Disease (PsAID) questionnaires 9 and 12, and Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue.

Regional conformational flexibility couples substrate specificity and scissile phosphate diester selectivity in human flap endonuclease 1.

Human flap endonuclease-1 (hFEN1) catalyzes the divalent metal ion-dependent removal of single-stranded DNA protrusions known as flaps during DNA replication and repair. Substrate selectivity involves passage of the 5'-terminus/flap through the arch and recognition of a single nucleotide 3'-flap by the α2-α3 loop. Using NMR spectroscopy, we show that the solution conformation of free and DNA-bound hFEN1 are consistent with crystal structures; however, parts of the arch region and α2-α3 loop are disordered without substrate.

Comparative Molluscicidal and Schistosomicidal Potentiality of Two Species and Its Isolated Glycoalkaloids.

Unlabelled: Schistosomiasis is the most noteworthy parasitic disease after malaria. Furthermore, the significant activity of the genus against worms and its intermediate host snails reinforced the study of Andr. (SS) and L.

4-year results from the RAPID-PsA phase 3 randomised placebo-controlled trial of certolizumab pegol in psoriatic arthritis.

Objective: To report the efficacy, patient-reported, radiographic and safety outcomes of 4 years' certolizumab pegol (CZP) treatment in patients with psoriatic arthritis (PsA).

Methods: RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Week 24, dose-blind to Week 48 and open-label (OL) to Week 216. Patients were randomised 1:1:1 to either placebo or CZP 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W) (following 400 mg at Weeks 0/2/4).

Higher Coronary Plaque Burden in Psoriatic Arthritis Is Independent of Metabolic Syndrome and Associated With Underlying Disease Severity.

Objective: To examine the effect of metabolic syndrome and psoriatic disease-related variables on coronary plaque burden in psoriatic arthritis (PsA) patients.

Methods: Fifty PsA patients without symptoms of coronary artery disease (CAD) (25 with metabolic syndrome and 25 without metabolic syndrome) and 50 age- and sex-matched controls underwent 64-slice coronary computed tomography angiography. Plaque localization, segment involvement score (SIS), segment stenosis score (SSS), and total plaque volume (TPV) were calculated.

H, N and C backbone resonance assignments of pentaerythritol tetranitrate reductase from Enterobacter cloacae PB2.

Pentaerythritol tetranitrate reductase (PETNR) is a flavoenzyme possessing a broad substrate specificity and is a member of the Old Yellow Enzyme family of oxidoreductases. As well as having high potential as an industrial biocatalyst, PETNR is an excellent model system for studying hydrogen transfer reactions. Mechanistic studies performed with PETNR using stopped-flow methods have shown that tunneling contributes towards hydride transfer from the NAD(P)H coenzyme to the flavin mononucleotide (FMN) cofactor and fast protein dynamics have been inferred to facilitate this catalytic step.

Remission in psoriatic arthritis-where are we now?

Advances in treatments and treatment strategies for PsA have led to many patients responding well to management of their disease, and targeting remission as a treatment goal is now a possibility. Treat to target is a strategy aimed at maximizing benefit, irrespective of the type of medication used, by monitoring disease activity and using it to guide therapy. The measurement of response to treatment has been the subject of wide discussions among experts for some time, and many instruments exist.

A systematic review of measurement properties of patient reported outcome measures in psoriatic arthritis: A GRAPPA-OMERACT initiative.

Background: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016.

Objectives: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0.

H, N, C backbone resonance assignments of human phosphoglycerate kinase in a transition state analogue complex with ADP, 3-phosphoglycerate and magnesium trifluoride.

Human phosphoglycerate kinase (PGK) is an energy generating glycolytic enzyme that catalyses the transfer of a phosphoryl group from 1,3-bisphosphoglycerate (BPG) to ADP producing 3-phosphoglycerate (3PG) and ATP. PGK is composed of two α/β Rossmann-fold domains linked by a central α-helix and the active site is located in the cleft formed between the N-domain which binds BPG or 3PG, and the C-domain which binds the nucleotides ADP or ATP. Domain closure is required to bring the two substrates into close proximity for phosphoryl transfer to occur, however previous structural studies involving a range of native substrates and substrate analogues only yielded open or partly closed PGK complexes.

Clinical Features of Psoriatic Arthritis: a Comprehensive Review of Unmet Clinical Needs.

Psoriatic arthritis (PsA) is a form of inflammatory arthritis (IA) affecting approximately 0.25% of the population. It is a heterogeneous disorder associated with joint damage, disability, disfiguring skin disease and in severe cases, premature mortality.

GRAPPA 2016 Project Report.

At the 2016 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing research and educational efforts. Among them were updates on the FLARE instrument, the Biomarker Project, GRAPPA's logo and Website, continuing progress on the video training project, and numerous educational project efforts in 2016.

Proceedings of the GRAPPA 2016 Retreat.

In advance of its 2016 annual meeting, members of the steering committee of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) convened for a strategic planning meeting. The purpose of this advance meeting was to review the work of GRAPPA since its inception in 2003, ascertain and review the current priorities of the group, and devise a strategy for proceeding. The key accomplishments of GRAPPA to date, priorities and objectives for the next 5 years, and goals and opportunities for the GRAPPA committees were discussed.