An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

A multidimensional approach to assessing intervention fidelity in a process evaluation of audit and feedback interventions to reduce unnecessary blood transfusions: a study protocol

BACKGROUND: In England, NHS Blood and Transplant conducts national audits of transfusion and provides feedback to hospitals to promote evidence-based practice. Audits demonstrate 20% of transfusions fall outside guidelines. The AFFINITIE programme (Development & Evaluation of Audit and Feedback INterventions to Increase evidence-based Transfusion practIcE) involves two linked, 2×2 factorial, cluster-randomised trials, each evaluating two theoretically-enhanced audit and feedback interventions to reduce unnecessary blood transfusions in UK hospitals. The first intervention concerns the content/format of feedback reports. The second aims to support hospital transfusion staff to plan their response to feedback and includes a web-based toolkit and telephone support. Interpretation of trials is enhanced by comprehensively assessing intervention fidelity. However, reviews demonstrate fidelity evaluations are often limited, typically only assessing whether interventions were delivered as intended. This protocol presents methods for assessing fidelity across five dimensions proposed by the Behaviour Change Consortium fidelity framework, including intervention designer-, provider- and recipient-levels. METHODS: (1) Design: Intervention content will be specified in intervention manuals in terms of component behaviour change techniques (BCTs). Treatment differentiation will be examined by comparing BCTs across intervention/standard practice, noting the proportion of unique/convergent BCTs. (2) Training: draft feedback reports and audio-recorded role-play telephone support scenarios will be content analysed to assess intervention providers' competence to deliver manual-specified BCTs. (3) Delivery: intervention materials (feedback reports, toolkit) and audio-recorded telephone support session transcripts will be content analysed to assess actual delivery of manual-specified BCTs during the intervention period. (4) Receipt and (5) enactment: questionnaires, semi-structured interviews based on the Theoretical Domains Framework, and objective web-analytics data (report downloads, toolkit usage patterns) will be analysed to assess hospital transfusion staff exposure to, understanding and enactment of the interventions, and to identify contextual barriers/enablers to implementation. Associations between observed fidelity and trial outcomes (% unnecessary transfusions) will be examined using mediation analyses. DISCUSSION: If the interventions have acceptable fidelity, then results of the AFFINITIE trials can be attributed to effectiveness, or lack of effectiveness, of the interventions. Hence, this comprehensive assessment of fidelity will be used to interpret trial findings. These methods may inform fidelity assessments in future trials. TRIAL REGISTRATION: ISRCTN 15490813 . Registered 11/03/2015

Midday measurements of leaf water potential and stomatal conductance are highly correlated with daily water use of Thompson Seedless grapevines

A study was conducted to determine the relationship between midday measurements of vine water status and daily water use of grapevines measured with a weighing lysimeter. Water applications to the vines were terminated on August 24th for 9 days and again on September 14th for 22 days. Daily water use of the vines in the lysimeter (ETLYS) was approximately 40 L vine−1 (5.3 mm) prior to turning the pump off, and it decreased to 22.3 L vine−1 by September 2nd. Pre-dawn leaf water potential (ΨPD) and midday Ψl on August 24th were −0.075 and −0.76 MPa, respectively, with midday Ψl decreasing to −1.28 MPa on September 2nd. Leaf g s decreased from ~500 to ~200 mmol m−2 s−1 during the two dry-down periods. Midday measurements of g s and Ψl were significantly correlated with one another (r = 0.96) and both with ETLYS/ETo (r = ~0.9). The decreases in Ψl, g s, and ETLYS/ETo in this study were also a linear function of the decrease in volumetric soil water content. The results indicate that even modest water stress can greatly reduce grapevine water use and that short-term measures of vine water status taken at midday are a reflection of daily grapevine water us

COMPATIBILITY OF FLUOROCHROME LABELING PROTOCOL WITH RAMAN SPECTROSCOPY TO STUDY BONE FORMATION

Oral Communication presented at the ";Forum des Jeunes Chercheurs";, Brest (France) 2011

An evaluation of outlet calibration methods: a contribution to the study on collective action for water management below the outlet, Hakra 6-R Distributary

Irrigation management / Water management / Measurement / Calibrations / Watercourses / Distributary canals / Irrigation canals / Discharges / Irrigation design / Flow / Pakistan / Hakra

Transcriptional Evidence for the Role of Chronic Venlafaxine Treatment in Neurotrophic Signaling and Neuroplasticity Including also Glutatmatergic- and Insulin-Mediated Neuronal Processes.

OBJECTIVES: Venlafaxine (VLX), a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD). Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration. METHODS: Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day) VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment. RESULTS: Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2). Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3), glutamatergic transmission (Gria3, Grin2b and Grin2a), neuroplasticity (Camk2g/b, Cd47), synaptogenesis (Epha5a, Gad2) and cognitive processes (Clstn2). Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1). Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1), a mechanism that has recently been linked to neuroprotection, learning and memory. CONCLUSIONS: Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in regulatory networks of motor cortical areas. These results are consonant with the synaptic (network) hypothesis of depression and antidepressant-induced motor recovery after stroke

Risk factors for treatment non-completion among patients with syphilis

Background: With recent increases in syphilis, there is growing interest in expanding screening; however, treatment rates have historically been low. Objectives: This study examines demographic and clinical factors that may contribute to non-completion of syphilis treatment. Design: This is a retrospective comparative cohort study of all patients with syphilis from January through November 2018 at an urban, tertiary care hospital. Methods: Demographics and clinical information were extracted from the electronic medical record. Descriptive statistics and odds ratios (ORs) were calculated. Results: Of 171 patients with syphilis, 89 (52.0%) completed treatment. Patients ages 40-49 were least likely to complete treatment (OR 0.14; 95% CI 0.03-0.72, p = 0.02) compared to those ages 18-24. Non-heterosexual patients were significantly more likely to complete treatment (OR 3.60; 95% CI 1.13-11.49, p = 0.03) compared to heterosexual patients. Patients diagnosed in the emergency department completed treatment at the lowest rate. Conclusion: A major gap in syphilis treatment still exists, which must be addressed to achieve optimal impact from syphilis screening programs.</p