Clathrin Heavy Chain subunits coordinate endo- and exocytic traffic and affect stomatal movement

The current model for vesicular traffic to and from the plasma membrane is accepted but the molecular requirements for this coordination are not well defined. We have identified the has1 mutant, which has a stomatal function defect, as a clathrin heavy chain 1 (CHC1) mutant allele and show that it has a decreased rate of endocytosis and growth defects that are shared with other chc1 mutant alleles. We used chc1 alleles and the related chc2 mutant as tools to investigate the effects clathrin defects have on secretion pathways and plant growth. We show that secretion and endocytosis at the plasma membrane is sensitive to CHC1 and CHC2 function in seedling roots, and that chc mutants have physiological defects in stomatal function and plant growth that have not been previously described. These findings suggest that clathrin supports specific functions of multiple cell types. Stomata movement and gas exchange is altered in chc mutants, indicating clathrin is important for stomatal regulation. The aberrant function of chc mutant stomata is consistent with the growth phenotypes observed under different water and light conditions, which are also similar to those of the secretory SNARE mutant, syp121. The syp121 and chc mutants have impaired endo- and exocytosis compared to wild type, indicating a link between SYP121-dependent secretion and clathrin-dependent endocytosis at the plasma membrane. Our findings provide evidence that clathrin and SYP121 functions are important for the coordination of endo- and exocytosis, and have an impact on stomatal function, gas exchange, and vegetative growth in Arabidopsis

Exposure-response relationship for noise annoyance and sleep disturbance. An analysis of national data

Blootstelling-responsrelaties voor verkeersgeluid en hinder lijken schaalspecifiek te zijn: relaties opgesteld op internationaal niveau wijken soms af van relaties op nationaal niveau die op hun buurt weer afwijken van relaties op regionaal niveau. Voor beleid betekent dit dat bij toepassing van (inter-)nationale blootstelling-responsrelaties op lokale situaties terdege rekening dient te worden gehouden met de beperkingen en 'vertaalbaarheid' van de relatie naar de lokale situatie. Daarnaast blijkt dat ondanks het gebruik van standaardvragen voor hinder en slaapverstoring, vastgelegd in een ISO-norm, de wijze van operationaliseren van hinder en slaapverstoring van invloed is op de blootstelling-responsrelatie. Dit zijn de belangrijkste bevindingen uit een onderzoek naar de relatie tussen geluid van wegverkeer en hinder en slaapverstoring op basis van gegevens uit het EMPARA-geluidsmodel en de Hinderinventarisatie 2003. In Nederland en binnen de Europese Unie is de verstoring van de leefomgeving door geluid een belangrijk aandachtspunt van beleid, omdat blootstelling aan hoge geluidsniveaus kan leiden tot negatieve effecten op welbevinden en gezondheid, waaronder hinder en slaapverstoring. In het rapport is onderzocht of het mogelijk is om met bestaande Nederlandse onderzoeksgegevens relaties vast te stellen tussen blootstelling aan verkeersgeluid en het optreden van hinder en slaapverstoring. De resultaten zijn vergeleken met de voorstellen voor relaties die in Europees verband zijn gedaan en de uitkomsten van de Gezondheidskundige Evaluatie Schiphol. Hierbij traden belangrijke verschillen aan het licht. Een belangrijke kanttekening bij de resultaten is dat slechts een beperkt aantal deelnemers aan het onderzoek is blootgesteld aan hogere geluidbelastingniveaus waardoor de betrouwbaarheidsintervallen voor hoge blootstellingen groot zijn. Dit is het gevolg van de scheve (min of meer log-normale) verdeling van geluidblootstelling in de Nederlandse bevolking.Exposure-response relations for traffic sound and annoyance appear to be scale-specific: relationships established at international levels sometimes deviate from national relationships; in turn these relations can deviate from regional ones. For policy, this means that due consideration should be given to the limitations and transferability of (inter-) national exposure-response relationships used in local situations. The definition and operationalisation of the terms 'annoyance' and 'sleep disturbance' can have a profound impact on the results. Although survey questions on annoyance conform to the ISO standard, the different interpretations of annoyance found in the literature can result in differences between exposure-response relationships. These are the main findings from a study investigating the relation between traffic sound and annoyance and sleep disturbance on the basis of the EMPARA noise model and a periodic national Annoyance survey (2003). Disturbance of the living environment through noise exposure is of concern, both in the Netherlands and the European Union. Exposure to high levels of noise can have adverse effects (annoyance and sleep disturbance) on health and well-being. The study described used existing Dutch data for determining the relationship between exposure to transport noise, and annoyance and sleep disturbance. The results from the Annoyance survey and EMPARA were compared with the proposals of the EU Noise Expert Network and the outcome of the monitoring programme, Health Impact Assessment - Schiphol Airport. The comparison revealed significant differences. In the Annoyance survey only few respondents experienced relatively high exposure levels. This resulted in large confidence intervals at high exposures.MN

Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Background Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance. Methods 28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation). Results 13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01). Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1. Conclusions Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load

Assessing the quality and communicative aspects of patient decision aids for early-stage breast cancer treatment: a systematic review

Purpose: Decision aids (DAs) support patients in shared decision-making by providing balanced evidence-based treatment information and eliciting patients’ preferences. The purpose of this systematic review was to assess the quality and communicative aspects of DAs for women diagnosed with early-stage breast cancer. Methods: Twenty-one currently available patient DAs were identified through both published literature (MEDLINE, Embase, CINAHL, CENTRAL, and PsycINFO) and online sources. The DAs were reviewed for their quality by using the International Patient Decision Aid Standards (IPDAS) checklist, and subsequently assessed to what extent they paid attention to various communicative aspects, including (i) information presentation, (ii) personalization, (iii) interaction, (iv) information control, (v) accessibility, (vi) suitability, and (vii) source of information. Results: The quality of the DAs varied substantially, with many failing to comply with all components of the IPDAS criteria (mean IPDAS score = 64%, range 31–92%). Five aids (24%) did not include any probability information, 10 (48%) presented multimodal descriptions of outcome probabilities (combining words, numbers, and visual aids), and only 2 (10%) provided personalized treatment outcomes based on patients and tumor characteristics. About half (12; 57%) used interaction methods for eliciting patients’ preferences, 16 (76%) were too lengthy, and 5 (24%) were not fully accessible. Conclusions: In addition to the limited adherence to the IPDAS checklist, our findings suggest that communicative aspects receive even less attention. Future patient DA developments for breast cancer treatment should include communicative aspects that could influence the uptake of DAs in daily clinical practice

Role of CD14 in a Mouse Model of Acute Lung Inflammation Induced by Different Lipopolysaccharide Chemotypes

Background: Recognition of lipopolysaccharide (LPS) is required for effective defense against invading gram-negative bacteria. Recently, in vitro studies revealed that CD14 is required for activation of the myeloid differentiation factor (MyD)88dependent Toll-like receptor (TLR)4 signaling pathway by smooth (S)-LPS, but not by rough (R)-LPS. The present study investigated the role of CD14 in induction of lung inflammation in mice by these different LPS chemotypes. Methodology/Results: Neutrophil accumulation and tumor necrosis factor (TNF) release in bronchoalveolar lavage fluid were determined 6 hours after intranasal treatment of wild type (WT) and CD14 knock-out (KO) mice with different doses S-LPS or R-LPS. The contribution of CD14 to lung inflammation induced by S-LPS or R-LPS depended on the LPS dose. At low doses, S-LPS and R-LPS induced neutrophil influx in a CD14-dependent manner. Low dose S-LPS-induced cytokine release also depended on CD14. Strikingly, neutrophil influx and TNF release induced by high dose S-LPS or R-LPS was diminished in the presence of CD14. Intranasal administration of sCD14 to CD14 KO mice treated with S-LPS partially reversed the inflammatory response to the response observed in WT mice. Conclusions: In conclusion, CD14 modulates effects of both S-LPS and R-LPS within the lung in a similar way. Except for R-LPS-induced TNF release, S-LPS and R-LPS at low dose induced acute lung inflammation in a CD14-dependent manner