Single-cell-based system to monitor carrier driven cellular auxin homeostasis

Background: Abundance and distribution of the plant hormone auxin play important roles in plant development. Besides other metabolic processes, various auxin carriers control the cellular level of active auxin and, hence, are major regulators of cellular auxin homeostasis. Despite the developmental importance of auxin transporters, a simple medium-to-high throughput approach to assess carrier activities is still missing. Here we show that carrier driven depletion of cellular auxin correlates with reduced nuclear auxin signaling in tobacco Bright Yellow-2 (BY-2) cell cultures. Results: We developed an easy to use transient single-cell-based system to detect carrier activity. We use the relative changes in signaling output of the auxin responsive promoter element DR5 to indirectly visualize auxin carrier activity. The feasibility of the transient approach was demonstrated by pharmacological and genetic interference with auxin signaling and transport. As a proof of concept, we provide visual evidence that the prominent auxin transport proteins PIN-FORMED (PIN) 2 and PIN5 regulate cellular auxin homeostasis at the plasma membrane and endoplasmic reticulum (ER), respectively. Our data suggest that PIN2 and PIN5 have different sensitivities to the auxin transport inhibitor 1-naphthylphthalamic acid (NPA). Also the putative PIN-LIKES (PILS) auxin carrier activity at the ER is insensitive to NPA in our system, indicating that NPA blocks intercellular, but not intracellular auxin transport. Conclusions: This single-cell-based system is a useful tool by which the activity of putative auxin carriers, such as PINs, PILS and WALLS ARE THIN1 (WAT1), can be indirectly visualized in a medium-to-high throughput manner. Moreover, our single cell system might be useful to investigate also other hormonal signaling pathways, such as cytokinin

Attitudes Toward the Adoption of 2 Artificial Intelligence-Enabled Mental Health Tools Among Prospective Psychotherapists: Cross-sectional Study

BACKGROUND: Despite growing efforts to develop user-friendly artificial intelligence (AI) applications for clinical care, their adoption remains limited because of the barriers at individual, organizational, and system levels. There is limited research on the intention to use AI systems in mental health care. OBJECTIVE: This study aimed to address this gap by examining the predictors of psychology students' and early practitioners' intention to use 2 specific AI-enabled mental health tools based on the Unified Theory of Acceptance and Use of Technology. METHODS: This cross-sectional study included 206 psychology students and psychotherapists in training to examine the predictors of their intention to use 2 AI-enabled mental health care tools. The first tool provides feedback to the psychotherapist on their adherence to motivational interviewing techniques. The second tool uses patient voice samples to derive mood scores that the therapists may use for treatment decisions. Participants were presented with graphic depictions of the tools' functioning mechanisms before measuring the variables of the extended Unified Theory of Acceptance and Use of Technology. In total, 2 structural equation models (1 for each tool) were specified, which included direct and mediated paths for predicting tool use intentions. RESULTS: Perceived usefulness and social influence had a positive effect on the intention to use the feedback tool (P<.001) and the treatment recommendation tool (perceived usefulness, P=.01 and social influence, P<.001). However, trust was unrelated to use intentions for both the tools. Moreover, perceived ease of use was unrelated (feedback tool) and even negatively related (treatment recommendation tool) to use intentions when considering all predictors (P=.004). In addition, a positive relationship between cognitive technology readiness (P=.02) and the intention to use the feedback tool and a negative relationship between AI anxiety and the intention to use the feedback tool (P=.001) and the treatment recommendation tool (P<.001) were observed. CONCLUSIONS: The results shed light on the general and tool-dependent drivers of AI technology adoption in mental health care. Future research may explore the technological and user group characteristics that influence the adoption of AI-enabled tools in mental health care

Dabigatran etexilate for thromboprophylaxis in over 5000 hip or knee replacement patients in a real-world clinical setting

BACKGROUND: Thromboprophylaxis is recommended for patients undergoing total hip or total knee replacement (THR, TKR). An international, open-label, prospective, observational, single-arm study in a routine clinical setting was performed to assess the safety and efficacy of dabigatran etexilate 220 mg once daily in patients undergoing THR or TKR, and in subgroups of patients with potentially increased risk of bleeding or venous thromboembolism (VTE). MATERIALS AND METHODS: Patients were ≥18 years and required to be eligible to receive dabigatran 220 mg once daily (first dose 110 mg 1–4 h after THR/TKR surgery) according to the European Summary of Product Characteristics. The primary safety and efficacy outcomes were incidence of major bleeding events (MBEs), and the composite incidence of symptomatic VTE events and all-cause mortality, respectively. RESULTS: In total, 5292 patients (median age 64 years) were enrolled and received dabigatran (2734 THR and 2558 TKR). Median drug exposure was 31 days (THR 34 days; TKR 27 days). Overall incidence of MBEs was 0.72 % (95 % confidence interval [CI] 0.51, 0.98), and this rate was comparable between types of surgery and was not significantly affected by protocol-defined risk factors. The overall incidence of symptomatic VTE and all-cause mortality was 1.04 % (95 % CI 0.78, 1.35); the only significant risk factor was history of VTE events (odds ratio 5.59; 95 % CI 2.53, 11.08). A post-hoc analysis showed that the incidence of MBEs in this observational study was similar to or lower than those reported in previous phase 3 trials. CONCLUSIONS: Results from this observational study of dabigatran etexilate administered to patients undergoing THR or TKR surgery are reassuring and supportive of those obtained in dabigatran phase 3 trials. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00846807. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12959-016-0082-4) contains supplementary material, which is available to authorized users

Predictors of Recurrent Stroke After Embolic Stroke of Undetermined Source in the RE‐SPECT ESUS Trial

Risk factors; Secondary prevention; Stroke predictorsFactores de riesgo; Prevención secundaria; Predictores de accidentes cerebrovascularesFactors de risc; Prevenció secundària; Predictors d'accidents cerebrovascularsBackground We sought to determine recurrent stroke predictors among patients with embolic strokes of undetermined source (ESUS). Methods and Results We applied Cox proportional hazards models to identify clinical features associated with recurrent stroke among participants enrolled in RE‐SPECT ESUS (Randomized, Double‐Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) trial, an international clinical trial evaluating dabigatran versus aspirin for patients with ESUS. During a median follow‐up of 19 months, 384 of 5390 participants had recurrent stroke (annual rate, 4.5%). Multivariable models revealed that stroke or transient ischemic attack before the index event (hazard ratio [HR], 2.27 [95% CI, 1.83–2.82]), creatinine clearance <50 mL/min (HR, 1.69 [95% CI, 1.23–2.32]), male sex (HR, 1.60 [95% CI, 1.27–2.02]), and CHA2DS2‐VASc ≥4 (HR, 1.55 [95% CI, 1.15–2.08] and HR, 1.66 [95% CI, 1.21–2.26] for scores of 4 and ≥5, respectively) versus CHA2DS2‐VASc of 2 to 3, were independent predictors for recurrent stroke. Conclusions In RE‐SPECT ESUS trial, expected risk factors previously linked to other common stroke causes were associated with stroke recurrence. These data help define high‐risk groups for subsequent stroke that may be useful for clinicians and for researchers designing trials among patients with ESUS.This study was supported by Boehringer Ingelheim

Canvas White Paper 3 Attitudes and Opinions Regarding Cybersecurity

As we rely more and more on information and communication technology, cybersecurity becomes both essential and problematic to our societies. On the one hand, cybersecurity is essential to pre-vent cyber threats from undermining citizens’ trust and confidence not only in the digital infrastruc-ture but in policy makers and state authorities as well. On the other hand, cybersecurity is problem-atic because enforcing it may endanger fundamental values like equality, fairness, autonomy, or pri-vacy. The CANVAS project aims to foster value-driven cybersecurity, with respect to European values and fundamental rights. Its first milestone is to consolidate existing knowledge and data related to cyber-security in four areas, namely the ethical, legal, empirical, and technological domains. This White Paper summarises currently available empirical data about attitudes and opinions of citizens and state actors regarding cybersecurity. It describes what these stakeholders generally think, what they feel, and what they do about cyber threats and security (counter)measures. For citizens’ perspectives, three social spheres of particular interest are exam-ined: 1) health, 2) business, 3) police and national security. This unique synthesis builds on a variety of sources with both quantitative and qualitative data. For citizens’ perspectives, our sources include reports from EU projects and Eurobarometer surveys, as well as additional scientific papers. As for state actors’ perspectives, they rely essentially on policy documents, as they are the most relevant data available

Xyloglucan Remodeling Defines Auxin-Dependent Differential Tissue Expansion in Plants

Size control is a fundamental question in biology, showing incremental complexity in plants, whose cells possess a rigid cell wall. The phytohormone auxin is a vital growth regulator with central importance for differential growth control. Our results indicate that auxin-reliant growth programs affect the molecular complexity of xyloglucans, the major type of cell wall hemicellulose in eudicots. Auxin-dependent induction and repression of growth coincide with reduced and enhanced molecular complexity of xyloglucans, respectively. In agreement with a proposed function in growth control, genetic interference with xyloglucan side decorations distinctly modulates auxin-dependent differential growth rates. Our work proposes that auxin-dependent growth programs have a spatially defined effect on xyloglucan's molecular structure, which in turn affects cell wall mechanics and specifies differential, gravitropic hypocotyl growth

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence

Peer reviewe

Auxin influx inhibitors 1-NOA, 2-NOA, and CHPAA interfere with membrane dynamics in tobacco cells

The phytohormone auxin is transported through the plant body either via vascular pathways or from cell to cell by specialized polar transport machinery. This machinery consists of a balanced system of passive diffusion combined with the activities of auxin influx and efflux carriers. Synthetic auxins that differ in the mechanisms of their transport across the plasma membrane together with polar auxin transport inhibitors have been used in many studies on particular auxin carriers and their role in plant development. However, the exact mechanism of action of auxin efflux and influx inhibitors has not been fully elucidated. In this report, the mechanism of action of the auxin influx inhibitors (1-naphthoxyacetic acid (1-NOA), 2-naphthoxyacetic acid (2-NOA), and 3-chloro-4-hydroxyphenylacetic acid (CHPAA)) is examined by direct measurements of auxin accumulation, cellular phenotypic analysis, as well as by localization studies of Arabidopsis thaliana L. auxin carriers heterologously expressed in Nicotiana tabacum L., cv. Bright Yellow cell suspensions. The mode of action of 1-NOA, 2-NOA, and CHPAA has been shown to be linked with the dynamics of the plasma membrane. The most potent inhibitor, 1-NOA, blocked the activities of both auxin influx and efflux carriers, whereas 2-NOA and CHPAA at the same concentration preferentially inhibited auxin influx. The results suggest that these, previously unknown, activities of putative auxin influx inhibitors regulate overall auxin transport across the plasma membrane depending on the dynamics of particular membrane vesicles

A citizen science approach: A detailed ecological assessment of subtropical reefs at point lookout, Australia

Subtropical reefs provide an important habitat for flora and fauna, and proper monitoring is required for conservation. Monitoring these exposed and submerged reefs is challenging and available resources are limited. Citizen science is increasing in momentum, as an applied research tool and in the variety of monitoring approaches adopted. This paper aims to demonstrate an ecological assessment and mapping approach that incorporates both top-down (volunteer marine scientists) and bottom-up (divers/community) engagement aspects of citizen science, applied at a subtropical reef at Point Lookout, Southeast Queensland, Australia. Marine scientists trained fifty citizen scientists in survey techniques that included mapping of habitat features, recording of substrate, fish and invertebrate composition, and quantifying impacts (e.g., occurrence of substrate damage, presence of litter). In 2014 these volunteers conducted four seasonal surveys along semi-permanent transects, at five sites, across three reefs. The project presented is a model on how citizen science can be conducted in a marine environment through collaboration of volunteer researchers, non-researchers and local marine authorities. Significant differences in coral and algal cover were observed among the three sites, while fluctuations in algal cover were also observed seasonally. Differences in fish assemblages were apparent among sites and seasons, with subtropical fish groups observed more commonly in colder seasons. The least physical damage occurred in the most exposed sites (Flat Rock) within the highly protected marine park zones. The broad range of data collected through this top-down/bottomup approach to citizen science exemplifies the projects' value and application for identifying ecosystem trends or patterns. The results of the project support natural resource and marine park management, providing a valuable contribution to existing scientific knowledge and the conservation of local reefs