A salt stress-activated GSO1-SOS2-SOS1 module protects the Arabidopsis root stem cell niche by enhancing sodium ion extrusion.

Soil salinity impairs plant growth reducing crop productivity. Toxic accumulation of sodium ions is counteracted by the Salt Overly Sensitive (SOS) pathway for Na+ extrusion, comprising the Na+ transporter SOS1, the kinase SOS2, and SOS3 as one of several Calcineurin-B-like (CBL) Ca2 + sensors. Here, we report that the receptor-like kinase GSO1/SGN3 activates SOS2, independently of SOS3 binding, by physical interaction and phosphorylation at Thr16. Loss of GSO1 function renders plants salt sensitive and GSO1 is both sufficient and required for activating the SOS2-SOS1 module in yeast and in planta. Salt stress causes the accumulation of GSO1 in two specific and spatially defined areas of the root tip: in the endodermis section undergoing Casparian strip (CS) formation, where it reinforces the CIF-GSO1-SGN1 axis for CS barrier formation; and in the meristem, where it creates the GSO1-SOS2-SOS1 axis for Na+ detoxification. Thus, GSO1 simultaneously prevents Na+ both from diffusing into the vasculature, and from poisoning unprotected stem cells in the meristem. By protecting the meristem, receptor-like kinase-conferred activation of the SOS2-SOS1 module allows root growth to be maintained in adverse environments.

[Clinical Judgement and Relational Competence in the Psychotherapy of Older Patients]. / Klinische Urteilsbildung und Beziehungskompetenz in der Psychotherapie älterer PatientInnen.

The negative attitude of psychotherapists towards the treatment of older patients in the past has weakened in the recent past. Nevertheless, the question remains as to how therapists perceive older patients in comparison to younger patients, what clinical judgements they arrive at and how they perceive the relationship with them. In the present study, which was conducted as part of the ÄPP study (Older Patients in Psychotherapy), therapists were asked to assess a self-selected younger (<40 years) or an older patient (>65) with regard to various variables. A total of 527 completed questionnaires were available. Two-factor analyses of variance were used to show, among other things, that younger therapists (compared to their older colleagues) rate older patients more negatively in terms of suitability for psychotherapy, the patient's ability to establish a therapeutic working relationship and other parameters. In comparison with their older colleagues, younger therapists perceive themselves as less competent in their relationships with older patients. There are only slight differences with younger patients.

Originalbeiträge (Originals). Unterscheidet sich der therapeutische Stil in altershomogenen und altersheterogenen therapeutischen Dyaden?

Does the therapeutic style differ in age-homogeneous and age-heterogeneous therapeutic dyads? BACKGROUND AND AIMS: Differences between age-homogeneous and age-heterogeneous therapeutic dyads have rarely been the subject of research.The present study aimed to investigate differences in therapeutic style (Healing and Stressful Involvement). METHOD: A sample of 527 questionnaires completed by therapists of different ages was available. Therapy style was compared between two patient groups (under 40 and over 65 years old) and three therapist groups (25-39, 40-59, ≥ 60). RESULTS: The results show in particular more stress experienced by younger therapists in the treatment of older patients, while older therapists report less stress.There were no or fewer differences in the treatment of younger patients.The regression-analytical results show that the experience of stress in the therapy of older people is associated with a greater fear of old age. CONCLUSION: Finally, some conclusions are discussed with regard to training and supervision of therapists in the treatment of older people.

Quantum Trajectories for Time-Local Non-Lindblad Master Equations.

For the efficient simulation of open quantum systems, we often use quantum jump trajectories given by pure states that evolve stochastically to unravel the dynamics of the underlying master equation. In the Markovian regime, when the dynamics is described by a Gorini-Kossakowski-Sudarshan-Lindblad (GKSL) master equation, this procedure is known as Monte Carlo wave function approach. However, beyond ultraweak system-bath coupling, the dynamics of the system is not described by an equation of GKSL type, but rather by the Redfield equation, which can be brought into pseudo-Lindblad form. Here, negative dissipation strengths prohibit the conventional approach. To overcome this problem, we propose a pseudo-Lindblad quantum trajectory (PLQT) unraveling. It does not require an effective extension of the state space, like other approaches, except for the addition of a single classical bit. We test the PLQT for the eternal non-Markovian master equation for a single qubit and an interacting Fermi-Hubbard chain coupled to a thermal bath and discuss its computational effort compared to solving the full master equation.

Canonically Consistent Quantum Master Equation.

We put forth a new class of quantum master equations that correctly reproduce the asymptotic state of an open quantum system beyond the infinitesimally weak system-bath coupling limit. Our method is based on incorporating the knowledge of the reduced steady state into its dynamics. The correction not only steers the reduced system toward a correct steady state but also improves the accuracy of the dynamics, thereby refining the archetypal Born-Markov weak-coupling second-order master equations. In case of equilibrium, we use the exact mean-force Gibbs state to correct the Redfield quantum master equation. By benchmarking it with the exact solution of the damped harmonic oscillator, we show that our method also helps correct the long-standing issue of positivity violation, albeit without complete positivity. Our method of a canonically consistent quantum master equation opens a new perspective in the theory of open quantum systems leading to a reduced density matrix accurate beyond the commonly used Redfield and Lindblad equations, while retaining the same conceptual and numerical complexity.

A Pronucleotide Probe for Live-Cell Imaging of Protein AMPylation.

Conjugation of proteins to AMP (AMPylation) is a prevalent post-translational modification (PTM) in human cells, involved in the regulation of unfolded protein response and neural development. Here we present a tailored pronucleotide probe suitable for in situ imaging and chemical proteomics profiling of AMPylated proteins. Using straightforward strain-promoted azide-alkyne click chemistry, the probe provides stable fluorescence labelling in living cells.

Protein-AMPylierungs-Identifikation in lebenden Zellen.

Protein AMPylation is a prevalent protein post-translational modification in human cells involved in endoplasmic reticulum stress regulation and neural development. In this article we describe the design, synthesis and application of a pronucleotide probe suitable for in situ fluorescence imaging and chemical protemics profiling of AMPylated proteins. Our probe utilizes straightforward strain-promoted azidealkyne click reaction for fluorescence labeling in living cells.

Thermodynamic control of anvil cloud amount.

General circulation models show that as the surface temperature increases, the convective anvil clouds shrink. By analyzing radiative-convective equilibrium simulations, we show that this behavior is rooted in basic energetic and thermodynamic properties of the atmosphere: As the climate warms, the clouds rise and remain at nearly the same temperature, but find themselves in a more stable atmosphere; this enhanced stability reduces the convective outflow in the upper troposphere and decreases the anvil cloud fraction. By warming the troposphere and increasing the upper-tropospheric stability, the clustering of deep convection also reduces the convective outflow and the anvil cloud fraction. When clouds are radiatively active, this robust coupling between temperature, high clouds, and circulation exerts a positive feedback on convective aggregation and favors the maintenance of strongly aggregated atmospheric states at high temperatures. This stability iris mechanism likely contributes to the narrowing of rainy areas as the climate warms. Whether or not it influences climate sensitivity requires further investigation.

A tale of four kingdoms - isoxazolin-5-one- and 3-nitropropanoic acid-derived natural products.

Covering up to September 2016This review reports on natural compounds that derive from the isoxazolinone ring as well as the 3-nitropropanoic acid (3-NPA) moiety. These structural elements occur in compounds that have been identified in plants, insects, bacteria and fungi. In particular, plants belonging to the family of legumes produce such compounds. In the case of insects, isoxazolin-5-one and 3-NPA derivatives were found in leaf beetles of the subtribe Chrysomelina. A number of these natural products have been synthesized so far. In the case of the single compound 3-NPA, several synthetic strategies have been reported and some of the most efficient routes are reviewed. The toxicity of 3-NPA results from its ability to bind covalently to the catalytic center of succinate dehydrogenase causing irreversible inhibition of mitochondrial respiration. As a motif that is produced by many species of plants, leaf beetles and fungi, different detoxification mechanisms for 3-NPA have evolved in different species. These mechanisms are based on amide formation of 3-NPA with amino acids, reduction to ß-alanine, ester formation or oxidation to malonic acid semialdehyde. The biosynthetic pathways of 3-NPA and isoxazolin-5-one moieties have been studied in fungi, plants and leaf beetles. In the case of fungi, 3-NPA derives from aspartate, while leaf beetles use essential amino acids such as valine as ultimate precursors. In the case of plants, it is supposed that malonate serves as a precursor of 3-NPA, as indicated by feeding of 14C-labeled precursors to Indigofera spicata. In other leguminous plants it is suggested that asparagine is incorporated into compounds that derive from isoxazolin-5-one, which was indicated by 14C-labeled compounds as well. In the case of leaf beetles it was demonstrated that detection of radioactivity after 14C-labeling from a few precursors is not sufficient to unravel biosynthetic pathways.

Biosynthesis of isoxazolin-5-one and 3-nitropropanoic acid containing glucosides in juvenile Chrysomelina.

Stable-isotope-labeled precursors were used to establish the biosynthetic pathway leading from ß-alanine towards isoxazolin-5-one glucoside 1 and its 3-nitropropanoate (3-NPA) ester 2 in Chrysomelina larvae. Both structural elements originate from sequestered plant-derived ß-alanine or from propanoyl-CoA that is derived from the degradation of some essential amino acids, e.g. valine. ß-Alanine is converted into 3-NPA and isoxazolinone 5 by consecutive oxidations of the amino group of ß-Ala. Substituting the diphospho group of α-UDP-glucose with 5 generates the isoxazolin-5-one glucoside 1, which serves in the circulating hemolymph of the larva as a platform for esterification with 3-nitropropanoyl-CoA. The pathway was validated with larvae of Phaedon cochleariae, Chrysomela populi as well as Gastrophysa viridula.

Two Defensive Lines in Juvenile Leaf Beetles; Esters of 3-nitropropionic Acid in the Hemolymph and Aposematic Warning.

Juveniles of the leaf beetles in subtribe Chrysomelina have efficient defense strategies against predators. When disturbed, they transiently expose volatile deterrents in large droplets from nine pairs of defensive glands on their back. Here, we report on an additional line of defense consisting of the non-volatile isoxazolin-5-one glucoside and its 3-nitropropanoyl ester in the larval hemolymph. Because isoxazolin-5-one derivatives were not detectable in related leaf beetle taxa, they serve as a diagnostic marker for the Chrysomelina subtribe. Conjugation of isotopically labelled 3-nitropropionic acid to isoxazolin-5-one glucoside in vivo demonstrates its function as a carrier for the 3-nitropropanoyl esters. The previous identification of characteristic glucosides as precursors of the volatile deterrents underlines the general importance of glucosides for sequestration from food plants, and the subsequent transport in the hemolymph to the defense system. The combination of repellent volatiles with non-volatile toxic compounds in the hemolymph has the potential to create synergistic effects since the odorant stimulus may help predators learn to avoid some foods. The combination of the two defense lines has the advantage, that the hemolymph toxins provide reliable and durable protection, while the repellents may vary after a host plant change.

Sensitization of NO-Releasing Ruthenium Complexes to Visible Light.

We report a combined spectroscopical-theoretical investigation on the photosensitization of transition metal nitrosyl complexes. For this purpose, ruthenium nitrosyl complexes based on tetradentate biscarboxamide ligands were synthesized. A crystal structure analysis of a lithium-based ligand intermediate is described. The Ru complexes have been characterized regarding their photophysical and nitric oxide (NO) releasing properties. Quantum chemical calculations have been performed to unravel the influence of the biscarboxamide ligand frame with respect to the molecular electronic properties of the NO-releasing pathway. A quantitative measure for the ligand design within photosensitized Ru complexes is introduced and evaluated spectroscopically and theoretically by using time-dependent density functional theory.

Synthesis and photosensitivity of isoxazolin-5-one glycosides.

A novel procedure for the synthesis of isoxazolin-5-one glycosides starting from unprotected carbohydrates is described. The substrate scope of the one-pot synthetic protocol was explored using D-configured glucose, xylose, maltose, fructose, ribose and 2-deoxyribose. Naturally occurring 2-(ß-D-glucopyranosyl)-3-isoxazolin-5-one and four novel isoxazolin-5-one glycosides derived from xylose, maltose and fructose were synthesized and purified by flash chromatography. The compounds were characterized in terms of chemical structure, photophysical properties as well as pH stability. The photohydrolysis rates of the synthesized glycosides were compared with uridine as a standard to determine the quantum yields for the photoreactions in water.

Randomized feasibility trial for evaluating the impact of primary nursing on delirium duration during intensive care unit stay.

OBJECTIVE: We tested the feasibility of a randomized controlled trial for comparing primary nursing with standard care. RESEARCH METHODOLOGY: Elective cardiac surgical patients were eligible for inclusion. Patients with an intensive care unit stay of ≥ 3 days were followed up until intensive care unit discharge. Recruitment period was one year. SETTING: Two intensive care units at a university hospital specialized in cardiovascular and diabetic diseases. MAIN OUTCOME MEASURES: Primary outcomes were recruitment and delivery rate. Primary clinical outcome was duration of delirium, as assessed by the Confusion Assessment Method for Intensive Care Units. Secondary outcomes included the incidence of delirium, anxiety (10-point Numeric Rating Scale), and the satisfaction of patient relatives (validated questionnaire). RESULTS: Of 369 patients screened, 269 could be allocated to primary nursing (n = 134) or standard care (n = 135), of whom 46 patients and 48 patients, respectively, underwent an intensive care unit stay ≥ 3 days. Thus, recruitment and delivery rates were 73 and 26 %, respectively. During primary nursing and standard care, 18 and 24 patients developed a delirium, with a median duration of 32 (IQR: 14-96) and 24 (IQR: 8-44) hours (P = 0.10). The risk difference of delirium for primary nursing versus standard care was 11 % and the relative risk was 0.65 (95 % CI: 0.28-1.46; P = 0.29). The extent of anxiety was similar between groups (P = 0.13). Satisfaction could be assessed in 73.5 % of relatives, without substantial differences between groups. CONCLUSION: Data demonstrate that a trial for comparing primary nursing with standard care is generally feasible. However, the incidence of delirium may be a better primary outcome parameter than delirium duration, both in terms of long-term patient outcome and robustness of data quality. IMPLICATIONS FOR CLINICAL PRACTICE: A randomized clinical trial regarding nursing organization during intensive care unit stay requires detailed planning of patient recruitment, data evaluation, and power calculation.

Clinical and Humanistic Burden of Non-inhibitor Haemophilia A in Five European Countries: Insights from the CHESS II Study.

INTRODUCTION: Haemophilia A (HA) is a congenital bleeding disorder caused by a deficiency/absence of factor VIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESS II) study. METHODS: CHESS II was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18 years) individuals with haemophilia A or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. RESULTS: Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. CONCLUSION: This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

Clampless off-pump versus conventional coronary artery revascularization: a propensity score analysis of 788 patients.

BACKGROUND: This study aimed to assess if clampless off-pump coronary artery bypass grafting (CABG) decreases risk-adjusted mortality, stroke rate, and morbidity in unselected patients in comparison to conventional CABG. METHODS AND RESULTS: Between July 2009 and November 2010, data of 1282 consecutive patients undergoing isolated CABG were prospectively recorded. In 30.8% (n=395), clampless off-pump revascularization was used, either with the PAS-Port automated central venous anastomosis system (n=310) or as total arterial revascularization without central anastomoses (n=85). Propensity score (PS) matching was performed based on 15 preoperative risk variables to correct for selection bias. In-hospital mortality and stroke rate as primary end point, as well as major complications and follow-up outcome of clampless off-pump (lessOPCAB) and conventional CABG (cCABG) were compared in 394 matched patient pairs (total: 788 patients). The clampless off-pump technique decreased the in-hospital rate of death (odds ratio, 0.25; 95% confidence interval, 0.05-1.18, P=0.080) and stroke (odds ratio, 0.36; 95% confidence interval, 0.13-0.99, P=0.048) significantly. Complications such as low cardiac output syndrome, prolonged ventilation and rethoracotomy were also reduced by lessOPCAB. Over a 2-year follow-up period overall survival, cerebrovascular and major adverse event rate were significantly lower in the lessOPCAB group, while the repeat revascularization rate was comparable. CONCLUSIONS: In a retrospective PS-matched analysis, clampless off-pump CABG lowers mortality, stroke rate and other morbidity in an unselected group of patients with coronary artery disease.

Synthesis of isoxazolin-5-one glucosides by a cascade reaction.

A novel synthetic route was developed for the construction of isoxazolin-5-one glucosides using a cascade reaction. An X-ray crystal structure analysis of a isoxazolin-5-one glucoside confirmed the structure and stereochemistry of the heterocycle. The properties of the α- and ß-anomers of the isoxazolin-5-one glucosides were compared. The first synthesis of 2-[6'-(3″-nitropropanoyl)-ß-D-glucopyranosyl]-3-isoxazolin-5-one was realized by direct enzymatic esterification without need of further protective groups.

Analysis of the elemental species-dependent uptake of lanthanide complexes in Arabidopsis thaliana plants by LA-ICP-MS.

Gadolinium-based contrast agents (GBCAs) are found increasingly in different water bodies, making the investigation of their uptake and distribution behavior in plants a matter of high interest to assess their potential effects on the environment. Depending on the used complexing agent, they are classified into linear or macrocyclic GBCAs, with macrocyclic complexes being more stable. In this study, by using TbCl3, Gd-DTPA-BMA, and Eu-DOTA as model compounds for ionic, linear, and macrocyclic lanthanide species, the elemental species-dependent uptake into leaves of Arabidopsis thaliana under identical biological conditions was studied. After growing for 14 days on medium containing the lanthanide species, the uptake of all studied compounds was confirmed by means of laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Furthermore, the uptake rate of TbCl3 and the linear Gd-DTPA-BMA was similar, with Tb and Gd hotspots colocated in the areas of hydathodes and the trichomes of the leaves. In contrast, in the case of the macrocyclic Eu-DOTA, Eu was mainly located in the leaf veins. Additionally, Eu was colocated with Tb and Gd in the hydathode at the tip of the leave. Removal of the lanthanide species from the medium led to a decrease in signal intensities, indicating their subsequent release to some extent. However, seven days after the removal, depositions of Eu, Gd, and Tb were still present in the same areas of the leaves as before, showing that complete elimination was not achieved after this period of time. Overall, more Eu was present in the leaves compared to Gd and Tb, which can be explained by the high stability of the Eu-DOTA complex, potentially leading to a higher transport rate into the leaves, whereas TbCl3 and Gd-DTPA-BMA could interact with the roots, reducing their mobility.

[Containing, right hemisphere: projective identification as an interpersonal mechanism, the ability for affect regulation]. / Rechtshemisphärisch aushalten statt linkshemisphärisch deuten--Projektive Identifizierung als interpersonaler Mechanismus zur Entwicklung der Fähigkeit zur Affektregulation.

The capacity of affect regulation develops with priority in reciprocal, non-verbal communication processes between the early caregiver and the baby. In this process, the projective identification plays the role of crucial means of communication. Processes of projective identification which emerge in therapeutic and educational interactions can be understood as such an early form of communication which contributes to the afterward-ripening of the capacity of affect regulation. Before the background of recent neuro-psychological findings it becomes clear, why the reciprocal and non-verbal communication between the early caregiver and infant as well as between the therapist and the patient is of such fundamental importance for the structural (re-) maturation of the right cerebral hemisphere, as well as for the connections between the left and right hemisphere. In case the projective identification persists as a defensive strategy in dealing with other people, pathological interaction circles can develop which can be overcome only when, for example, the other person assumes the role of the "regulating other".

Transforming Chemical Proteomics Enrichment into a High-Throughput Method Using an SP2E Workflow.

Protein post-translational modifications (PTMs) play a critical role in the regulation of protein catalytic activity, localization, and protein-protein interactions. Attachment of PTMs onto proteins significantly diversifies their structure and function, resulting in proteoforms. However, the sole identification of post-translationally modified proteins, which are often cell type and disease-specific, is still a highly challenging task. Substoichiometric amounts and modifications of low abundant proteins necessitate the purification or enrichment of the modified proteins. Although the introduction of mass spectrometry-based chemical proteomic strategies has enabled the screening of protein PTMs with increased throughput, sample preparation remains highly time-consuming and tedious. Here, we report an optimized workflow for the enrichment of PTM proteins in a 96-well plate format, which could be extended to robotic automation. This platform allows us to significantly lower the input of total protein, which opens up the opportunity to screen specialized and difficult-to-culture cell lines in a high-throughput manner. The presented SP2E protocol is robust and time- and cost-effective, as well as suitable for large-scale screening of proteoforms. The application of the SP2E protocol will thus enable the characterization of proteoforms in various processes such as neurodevelopment, neurodegeneration, and cancer. This may contribute to an overall acceleration of the recently launched Human Proteoform Project.