The CONSTANS gene of arabidopsis promotes flowering and encodes a protein showing similarities to zinc finger transcription factors

AbstractThe vegetative and reproductive (flowering) phases of Arabidopsis development are clearly separated. The onset of flowering is promoted by long photoperiods, but the constans (co) mutant flowers later than wild type under these conditions. The CO gene was isolated, and two zinc fingers that show a similar spacing of cysteines, but little direct homology, to members of the GATA1 family were identified in the amino acid sequence. co mutations were shown to affect amino acids that are conserved in both fingers. Some transgenic plants containing extra copies of CO flowered earlier than wild type, suggesting that CO activity is limiting on flowering time. Double mutants were constructed containing co and mutations affecting gibberellic acid responses, meristem identity, or phytochrome function, and their phenotypes suggested a model for the role of CO in promoting flowering

Patient reported outcomes in large vessel vasculitides

Purpose of Review: The goal of this paper is to review current and future uses of patient-reported outcomes in large vessel vasculitis. The large vessel vasculitides comprise Giant Cell Arteritis and Takayasu arteritis; both are types of systemic vasculitis which affect the larger blood vessels. Patient-reported outcomes (PROs) capture the impact of these diseases on health-related quality of life. Recent Findings: Generic PROs such as the SF-36 are currently used to compare HRQOL of people with GCA and TAK within clinical trials and observational studies and to make comparisons with the general population and HRQoL in other diseases. The development of a disease-specific PRO for GCA is currently underway. Beyond clinical trials, there is much interest in the use of PROs within routine clinical care, particularly E-PROs for remote use. Summary: Further work will be needed to complete the development of disease-specific PROs for people with large vessel vasculitis and to establish feasibility, acceptability, and utility of E-PROs

Vasilisa and the Witch\u27s fire

1 volume, 4 pages. Title from cardboard slipcase cover. Pattern cloth over cover boards. Lasercut silhouette illustrations, with pages that fold out concertina style. In paper box, 14 x 14 x 2 cm. Certificate of authenticity ([6] pages ; illustrations ; 10 x 10 cm) includes instructions on how to display the book. A papercut re-telling of Vasilisa the Beautiful\u27s flight from the hut of Baba Yaga the Witch --Certificate of authenticity. Book no. 16 of 30 was completed by Joanna Robson in Edinburgh, United Kingdom, on 11/1/2019 --Certificate of authenticity.https://digitalcommons.risd.edu/specialcollections_artistsbooks/1175/thumbnail.jp

Assessing glucocorticoid toxicity: Are the measures sensitive enough?

The Glucocorticoid Toxicity Index (GTI) is a composite instrument designed to capture change in glucocorticoid-related morbidity over time.1 It was developed through consensus methods and multi-criteria decisions among 19 medical specialists, with relative domain weights decided via clinician consensus.2 The GTI has now been used in more than 45 studies, including 12 phase 3 clinical trials.1The GTI comprises eight domains: body mass index, blood pressure, glucose tolerance, lipid metabolism, glucocorticoid myopathy, skin toxicity, neuropsychiatric effects and infections. Two overall scores are calculated: the cumulative worsening score (CWS), which includes transient and permanent GC toxicity from baseline to specific time points, and the Aggregate Improvement Score (AIS), which accounts for improvement as well as worsening GC-toxicity.1 In The Lancet Rheumatology, Naomi Patel and colleagues3 present an analysis of domain scores of the GTI using data from the phase 3 ADVOCATE trial.4 In a clinical trial context where the GTI is used to produce repeated measures to demonstrate differences between (and within) groups of patients taking different dosages of glucocorticoids, and to measure the impact of steroid sparing agents, it is expected to have a high level of measurement validity and reliability

Unlocking the bacterial SecY translocon

SummaryThe Sec translocon performs protein secretion and membrane protein insertion at the plasma membrane of bacteria and archaea (SecYEG/β), and the endoplasmic reticular membrane of eukaryotes (Sec61). Despite numerous structures of the complex, the mechanism underlying translocation of pre-proteins, driven by the ATPase SecA in bacteria, remains unresolved. Here we present a series of biochemical and computational analyses exploring the consequences of signal sequence binding to SecYEG. The data demonstrate that a signal sequence-induced movement of transmembrane helix 7 unlocks the translocon and that this conformational change is communicated to the cytoplasmic faces of SecY and SecE, involved in SecA binding. Our findings progress the current understanding of the dynamic action of the translocon during the translocation initiation process. The results suggest that the converging effects of the signal sequence and SecA at the cytoplasmic face of SecYEG are decisive for the intercalation and translocation of pre-protein through the SecY channel

Mixed methods study of clinicians' perspectives on barriers to implementation of treat to target in psoriatic arthritis

Objectives: In treat to target (T2T), the patient is treated to reach and maintain specified and sequentially measured goals, such as remission or low disease activity. T2T in psoriatic arthritis (PsA) has demonstrated improved clinical and patient-reported outcomes and is recommended in European guidelines. However, most clinicians do not use T2T in PsA. This study examined the barriers and enablers to implementation in practice. Methods: Sequential mixed methods comprising a qualitative design (interviews and focus group) to inform a quantitative design (survey). Qualitative data were analysed thematically, and quantitative statistics were analysed descriptively. Results: Nineteen rheumatology clinicians participated in telephone interviews or a face-to-face focus group. An overarching theme 'Complexity' (including 'PsA vs Rheumatoid Arthritis', 'Measurement' and 'Resources') and an underpinning theme 'Changes to current practice' (including 'Reluctance due to organisational factors' and 'Individual determination to make changes') were identified. 153 rheumatology clinicians responded to an online survey. Barriers included limited clinical appointment time to collect outcome data (54.5%) and lack of training in assessing skin disease (35%). Enablers included provision of a protocol (86.4%), a local implementation lead (80.9%), support in clinic to measure outcomes (83.3%) and training in T2T (69.8%). The importance of regular audit with feedback, specialist PsA clinics and a web-based electronic database linked to hospital/national information technology (IT) systems were also identified as enablers. Conclusions: Implementation of T2T in PsA requires an integrated approach to address the support, training and resource needs of individual clinicians, rheumatology teams, local IT systems and service providers to maximise success

Comment on: Benchmarking tocilizumab use for giant cell arteritis

It is with great interest we read the editorial on tocilizumab (TCZ) use in giant cell arteritis (GCA) published on 9th May, 2022 by Conway et al [1]. We write to share some of our data to add weight to the views expressed, particularly in relation to use of TCZ beyond one yearin refractory cases with visual involvement

Systemic vasculitis and patient-reported outcomes: how the assessment of patient preferences and perspectives could improve outcomes.

The systemic vasculitides are a group of multisystem diseases, which can be life and organ threatening. High-dose immunosuppressants are required to control inflammation in vital organs, such as the kidneys, lungs, skin, joints, and eyes. Patients report a range of impacts on their health-related quality of life due to symptoms, irreversible damage, and the adverse effects of medications. The measurement of patient perspectives within clinical studies in vasculitis is essential to capture outcomes of greatest importance to patients. Validated generic, disease-specific and symptom-specific patient-reported outcomes available for use in patients with systemic vasculitis are reviewed here

A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

PurposeTo describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.MethodsUsing direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.ResultsOnly one mutation in OTX2 was identified. A novel heterozygous p.S138X stop mutation was identified in a seven-year-old male who had an infantile onset retinal dystrophy. The mutation was not present in either parent or in 181 blood donor samples. There was a history of failure to thrive in infancy, poor feeding, and growth hormone deficiency. Poor vision and nyctalopia was present from the first year. Funduscopy revealed a hyperpigmented peripapillary ring with a fine granular pigmentation of the RPE throughout the fundus. The scotopic bright flash ERG a-wave was subnormal and the waveform electronegative, in keeping with dysfunction both at the level of the photoreceptor and post-phototransduction. Visual function has been stable to date.ConclusionsMutations in OTX2 have been reported in association with major developmental malformations of the eye, with retinal dystrophies such as LCA, and with pituitary dysfunction and seizure activity in some cases. This case adds further support for a role of OTX2 both in retinal development and pituitary function, and highlights a novel retinal dystrophy phenotype seen in association with mutations in OTX2