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Modelling the risk of natural hazards for society, ecosystems, and the economy is subject to strong uncertainties, even more so in the context of a changing climate, evolving societies, growing economies, and declining ecosystems. Here, we present a new feature of the climate-risk modelling platform CLIMADA (CLIMate ADAptation), which allows us to carry out global uncertainty and sensitivity analysis. CLIMADA underpins the Economics of Climate Adaptation (ECA) methodology which provides decision-makers with a fact base to understand the impact of weather and climate on their economies, communities, and ecosystems, including the appraisal of bespoke adaptation options today and in future. We apply the new feature to an ECA analysis of risk from tropical cyclone storm surge to people in Vietnam to showcase the comprehensive treatment of uncertainty and sensitivity of the model outputs, such as the spatial distribution of risk exceedance probabilities or the benefits of different adaptation options. We argue that broader application of uncertainty and sensitivity analysis will enhance transparency and intercomparison of studies among climate-risk modellers and help focus future research. For decision-makers and other users of climate-risk modelling, uncertainty and sensitivity analysis has the potential to lead to better-informed decisions on climate adaptation. Beyond provision of uncertainty quantification, the presented approach does contextualize risk assessment and options appraisal, and might be used to inform the development of storylines and climate adaptation narratives.

ABSTRACT: Injuries and plumage damage (PD) are important indicators of welfare. First priority in turkey fattening is to reduce injurious pecking, which includes aggressive pecking (agonistic behavior) and additionally severe feather pecking (SFP) and cannibalism with their multifactorial reasons. Still, there are few studies available evaluating different genotypes for their welfare status under organic conditions. The aim of this study was to investigate the effects of genotype and husbandry with 100% organic feeding (2 variants with different riboflavin content: V1 and V2) on injuries and PD. During rearing nonbeaktrimmed male turkeys of a slow- (Auburn, n = 256) and fast-growing (B.U.T.6, n = 128) genotype were kept in 2 indoor housing systems (without environmental enrichment (EE) = H1−, n = 144 and with EE = H2+, n = 240). During fattening 13 animals per pen of H2+ were relocated to a free-range system (H3 MS, n = 104). EE included pecking stones, elevated seating platforms and silage feeding. The study included five 4-wk feeding phases. At the end of each phase, injuries and PD were scored to assess animal welfare. Injury scores ranged from 0 (=no damage) to 3 (=severe damage) and PD from 0 to 4. Injurious pecking was observed from the 8th week onward (injuries: 16.5% and PD: 31.4%). Binary logistic regression models showed that both indicators were affected by genotype (each P < 0.001), husbandry (each P < 0.001), feeding (injuries P = 0.004; PD P = 0.003), and age (each P < 0.001). Auburn showed less injuries and PD than B.U.T.6. H1− had the fewest injuries and PD for Auburn animals compared to H2+ or H3 MS. In summary, the use of alternative genotypes (Auburn) in organic fattening improved welfare, but keeping them in free-range systems or in husbandry with EE, does not lead to a reduction of injurious pecking. Therefore, further studies are needed with more and changing enrichment materials, further management measures, changes in housing structure, and even more intensive animal care.

Abstract The numerical understanding of cichlids and stingrays was examined regarding addition and subtraction abilities within the number space of one to five. Experiments were conducted as two-alternative forced-choice experiments, using a delayed matching to sample technique. On each trial, fish had to perform either an addition or subtraction, based on the presentation of two-dimensional objects in two distinct colors, with the color signaling a particular arithmetic process. Six cichlids and four stingrays successfully completed training and recognized specific colors as symbols for addition and subtraction. Cichlids needed more sessions than stingrays to reach the learning criterion. Transfer tests showed that learning was independent of straightforward symbol memorization. Individuals did not just learn to pick the highest or lowest number presented based on the respective color; instead, learning was specific to adding or subtracting ‘one’. Although group results were significant for both species in all tests, individual results varied. Addition was learned more easily than subtraction by both species. While cichlids learned faster than stingrays, and more cichlids than stingrays learned the task, individual performance of stingrays exceeded that of cichlids. Previous studies have provided ample evidence that fish have numerical abilities on par with those of other vertebrate and invertebrate species tested, a result that is further supported by the findings of the current study.

Abstract Background Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease of the skin affecting the elderly. BP is immunopathologically characterized by autoantibodies against BP180 and BP230. With the growing evidence of cell‐mediated autoimmunity in the pathogenesis of BP, it still remains unclear whether mast cells (MCs) are involved, due to conflicting data obtained from Kit‐dependent MC‐deficient mouse models. Objectives To clarify the role of MCs in experimental BP; the dynamics in cutaneous MC numbers, associated immune cells and the development of disease in Kit‐independent MC‐deficient mouse model. Methods Employing a recently established murine adult passive transfer model of BP induced by the transfer of pathogenic immunoglobulin G (IgG), lesional skin biopsies were investigated histologically and immunohistochemically for the time‐dependent MC accumulation and dermal infiltration. Results The numbers of cutaneous MCs increased following the induction of BP, in part, maintained by MC proliferation. Numbers of T cells, neutrophils and eosinophils in the skin also increased after BP induction, with eosinophils showing a preferential co‐localization with MCs. Furthermore, clinical disease manifestation in MC‐deficient Mcpt5Cre/Dicer fl/fl mice remained unchanged compared to MC‐sufficient Dicer fl/fl mice. The composition of the immune cell infiltration including as T cells, neutrophils and eosinophils was largely unaffected by the absence of MCs. Conclusion MCs do not play a pivotal role in the pathogenesis of passive IgG‐transfer mediated BP model. Their increase in number may be a bystander effect following tissue injury. We therefore suggest caution regarding the selection of MCs as sole targets for the development of novel drugs for BP.

IntroductionEnhanced Recovery After Surgery (ERAS) protocols represent a paradigm shift in perioperative care, aim to optimize patient outcomes and accelerate recovery. This manual presents findings from implementing the INCREASE study, a bicentric prospective randomized controlled trial focusing on ERAS in minimally invasive heart valve surgery.MethodsUtilizing the Consolidated Framework for Implementation Research (CFIR) and the Template for Intervention Description and Replication (TIDieR), the study examined contextual factors, intervention components, and implementation strategies.ResultsKey findings from the CFIR analysis revealed critical domains influencing implementation success. These included innovation characteristics, external and internal settings, and individual dynamics. The study showcased ERAS's adaptability to diverse healthcare systems, emphasizing its potential for successful integration across varying contexts. Furthermore, the importance of interprofessional collaboration emerged as a foundation of practical implementation, fostering teamwork, communication, and patient-centered care. Utilizing the TIDieR framework, this manual comprehensively describes ERAS intervention components, detailing preoperative counseling, intraoperative management, and postoperative care strategies. The manual underscored the importance of tailored, patient-centered approaches, highlighting the role of an academic ERAS nurse, early mobilization, and psychosomatic interventions in promoting optimal recovery outcomes.DiscussionIn conclusion, the INCREASE study provided valuable insights for creating an implementation manual for ERAS in cardiac surgery, emphasizing adaptability, collaboration, and ongoing evaluation as key drivers of successful implementation. These findings have broad implications for improving patient care outcomes and advancing perioperative practices in cardiac surgery settings.

Abstract FLASH-radiotherapy may provide significant sparing of healthy tissue through ultra-high dose rates in protons, electrons, and x-rays while maintaining the tumor control. Key factors for the FLASH effect might be oxygen depletion, the immune system, and the irradiated blood volume, but none could be fully confirmed yet. Therefore, further investigations are necessary. We investigated the protective (tissue sparing) effect of FLASH in proton treatment using an in-vivo mouse ear model. The right ears of Balb/c mice were irradiated with 20 MeV protons at the ion microprobe SNAKE in Garching near Munich by using three dose rates (Conv = 0.06 Gy/s, Flash9 = 9.3 Gy/s and Flash930 = 930 Gy/s) at a total dose of 23 Gy or 33 Gy. The ear thickness, desquamation, and erythema combined in an inflammation score were measured for 180 days. The cytokines TGF-β1, TNF-α, IL1α, and IL1β were analyzed in the blood sampled in the first 4 weeks and at termination day. No differences in inflammation reactions were visible in the 23 Gy group for the different dose rates. In the 33 Gy group, the ear swelling and the inflammation score for Flash9 was reduced by (57 ± 12) % and (67 ± 17) % and for Flash930 by (40 ± 13) % and (50 ± 17) % compared to the Conv dose rate. No changes in the cytokines in the blood could be measured. However, an estimation of the irradiated blood volume demonstrates, that 100-times more blood is irradiated when using Conv compared to using Flash9 or Flash930. This indicates that blood might play a role in the underlying mechanisms in the protective effect of FLASH.

Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.

Summary: Magnetic nanoparticles can be functionalized in many ways for biomedical applications. Here, we combine four advantageous features in a novel Fe-Pt-Yb2O3 core-shell nanoparticle. (a) The nanoparticles have a size of 10 nm allowing them to diffuse through neuronal tissue. (b) The particles are superparamagnetic after synthesis and ferromagnetic after annealing, enabling directional control by magnetic fields, enhance NMRI contrast, and hyperthermia treatment. (c) After neutron-activation of the shell, they carry low-energetic, short half-life β-radiation from 175Yb, 177Yb, and 177Lu. (d) Additionally, the particles can be optically visualized by plasmonic excitation and luminescence. To demonstrate the potential of the particles for cancer treatment, we exposed cultured human glioblastoma cells (LN-18) to non-activated and activated particles to confirm that the particles are internalized, and that the β-radiation of the radioisotopes incorporated in the neutron-activated shell of the nanoparticles kills more than 98% of the LN-18 cancer cells, promising for future anti-cancer applications.

Background and Purpose: Radiotherapy of thoracic tumours can lead to side effects in the lung, which may benefit from early diagnosis. We investigated the potential of X-ray dark-field computed tomography by a proof-of-principle murine study in a clinically relevant radiotherapeutic setting aiming at the detection of radiation-induced lung damage. Material and Methods: Six mice were irradiated with 20 Gy to the entire right lung. Together with five unirradiated control mice, they were imaged using computed tomography with absorption and dark-field contrast before and 16 weeks post irradiation. Mean pixel values for the right and left lung were calculated for both contrasts, and the right-to-left-ratio R of these means was compared. Radiologists also assessed the tomograms acquired 16 weeks post irradiation. Sensitivity, specificity, inter- and intra-reader accuracy were evaluated. Results: In absorption contrast the group-average of R showed no increase in the control group and increased by 7% (p = 0.005) in the irradiated group. In dark-field contrast, it increased by 2% in the control group and by 14% (p = 0.005) in the irradiated group. Specificity was 100% for both contrasts but sensitivity was almost four times higher using dark-field tomography. Two cases were missed by absorption tomography but were detected by dark-field tomography. Conclusions: The applicability of X-ray dark-field computed tomography for the detection of radiation-induced lung damage was demonstrated in a pre-clinical mouse model. The presented results illustrate the differences between dark-field and absorption contrast and show that dark-field tomography could be advantageous in future clinical settings.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. Innovative treatment concepts may enhance oncological outcome. Clinically relevant tumor models are essential in developing new therapeutic strategies. In the present study, we used two human PDAC cell lines for an orthotopic xenograft mouse model and compared treatment characteristics between this in vivo tumor model and PDAC patients. Tumor-bearing mice received stereotactic high-precision irradiation using arc technique after 3D-treatment planning. Induction of DNA damage in tumors and organs at risk (OARs) was histopathologically analyzed by the DNA damage marker γH2AX and compared with results after unprecise whole-abdomen irradiation. Our mouse model and preclinical setup reflect the characteristics of PDAC patients and clinical RT. It was feasible to perform stereotactic high-precision RT after defining tumor and OARs by CT imaging. After stereotactic RT, a high rate of DNA damage was mainly observed in the tumor but not in OARs. The calculated dose distributions and the extent of the irradiation field correlate with histopathological staining and the clinical example. We established and validated 3D-planned stereotactic RT in an orthotopic PDAC mouse model, which reflects the human RT. The efficacy of the whole workflow of imaging, treatment planning, and high-precision RT was proven by longitudinal analysis showing a significant improved survival. Importantly, this model can be used to analyze tumor regression and therapy-related toxicity in one model and will allow drawing clinically relevant conclusions.

Objective: To reliably compare the three-year clinical outcome and safety of XEN45 Gel Stent implantation (XEN) vs. trabeculectomy (TRAB) in patients with glaucoma., Subject/methods: We conducted a retrospective cohort study with patients with primary open angle or pseudoexfoliation glaucoma with uncontrolled intraocular pressure (IOP) undergoing XEN or TRAB at the Innsbruck University Clinic of Ophthalmology and Optometry, Austria and analysed changes in IOP, numbers of IOP-lowering medications, and complete surgical success (i.e., IOP ≤ 18 mmHg, ≥20% IOP reduction and not requiring IOP-lowering medication) up to 36 months postoperatively., Results: Between 2013 and 2019, we performed XEN Gel Stent implantation in 58 eyes and trabeculectomy in 84 eyes. From baseline to 36 months, mean IOP decreased from 23.4 to 13.8 mmHg (mean reduction 35%, 95% confidence interval 23-48%, p < 0.001) in the XEN group and from 25.1 to 11.2 mmHg (mean reduction 50%, 41-60%, p < 0.001) in the TRAB group. TRAB provided higher IOP reduction than XEN Gel Stent implantation at 12, 24, and 36 months (all p < 0.05). In XEN versus TRAB, IOP-lowering medication was required by 98.3% vs. 97.6% before surgery (p = 0.781), differed significantly at month 12 (43.2% vs. 2.0%, p < 0.001)but not at month 24 or 36. Complete surgical success was achieved in 40.0% vs. 62.8% at month 24 (adjusted odds ratio 2.70; 1.04-7.00, p = 0.040) and 27.3% vs. 56.8% at month 36 (4.36; 1.25-15.18, p = 0.021)., Conclusion: Compared to XEN, TRAB was associated with lower intraocular pressure, less IOP-lowering medication, and higher probability of achieving complete surgical success over a 36-month follow-up period., (© 2024. The Author(s).)

Objective: The study objective was to assess the role of CCL19 + lymph node stromal cells of the joint-draining popliteal lymph node (pLN) for the development of arthritis., Methods: CCL19 + lymph node stromal cells were spatiotemporally depleted for five days in the pLN before the onset of collagen-induced arthritis (CIA) using Ccl19-Cre × iDTR mice. In addition, therapeutic treatment with recombinant CCL19-immunoglobulin G (IgG), locally injected in the footpad, was used to confirm the results. RNA sequencing of lymph node stromal cells combined with T cell coculture assays using tropomyosin receptor kinase (Trk) family inhibitors together with in vivo local pLN small interfering RNA (siRNA) treatments were used to elucidate the pathway by which CCL19 + lymph node stromal cells initiate the onset of arthritis., Results: Spatiotemporal depletion of CCL19 + lymph node stromal cells prevented disease onset in CIA mice. These inhibitory effects could be mimicked by local CCL19-IgG treatment. The messenger RNA sequencing analyses showed that CCL19 + lymph node stromal cells down-regulated the expression of the tropomyosin receptor kinase A (TrkA) just before disease onset. Blocking TrkA in lymph node stromal cells led to increased T cell proliferation in in vitro coculture assays. Similar effects were observed with the pan-Trk inhibitor larotrectinib in cocultures of lymph node stromal cells of patients with rheumatoid arthritis and T cells. Finally, local pLN treatment with TrkA inhibitor and TrkA siRNA led to exacerbated arthritis scores., Conclusion: CCL19 + lymph node stromal cells are crucially involved in the development of inflammatory arthritis. Therefore, targeting of CCL19 + lymph node stromal cells via TRK could provide a tool to prevent arthritis., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Inline analytics in industrial processes reduce operating costs and production rejection. Dedicated sensors enable inline process monitoring and control tailored to the application of interest. Nuclear Magnetic Resonance is a well-known analytical technique but needs adapting for low-cost, reliable and robust process monitoring. A V-shaped low-field NMR sensor was developed for inline process monitoring and allows non-destructive and non-invasive measurements of materials, for example in a pipe. In this paper, the industrial application is specifically devoted to the quality control of anode slurries in battery production. The characterization of anode slurries was performed with the sensor to determine chemical composition and detect gas inclusions. Additionally, flow properties play an important role in continuous production processes. Therefore, the in- and outflow effects were investigated with the V-shaped NMR sensor as a basis for the future determination of slurry flow fields.

Background: In 2022, the United States experienced a national shortage of infant formula due to a global supply chain crisis and a large-scale domestic formula recall. The existing literature on healthcare providers' (HCPs) clinical decision-making during formula shortages is limited. This study aims to analyze the factors influencing pediatric HCP clinical decision-making when switching between amino acid formulas (AAF) for managing cow's milk protein allergy (CMPA) in infants under 24 months of age during an unprecedented national formula shortage., Methods: The study included pediatric HCPs with experience managing CMPA in infants and toddlers under 24 months during the formula shortage from January 2022 to November 2022. A de-identified survey comprising 26 questions examining driving factors used in clinical decision-making was administered to pediatric HCPs using a real-time mobile data collection tool., Results: Among the surveyed pediatric HCPs ( n  = 75), the factors most frequently considered as "extremely important" when switching to another AAF included safety (85%), tolerability (73%), and efficacy (83%). No statistically significant differences were found in HCP ratings among the listed examined factors of the four AAFs. The availability of specific formulas was the only factor that exhibited a statistically significant difference in perceived performance among pediatric HCPs when comparing the four AAFs ( p  < 0.05)., Discussion: This study elucidates the crucial aspects that influenced pediatric HCPs' selection of AAFs for CMPA management during the 2022 formula shortage. The findings highlight the significance of safety, tolerability, efficacy, and availability in the pediatric HCP decision-making processes., Competing Interests: MW has served as a consultant for Reckitt. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (© 2024 Baran, Brown, Farrar, Oliveros, Beacker, Lamos, Florio, Fabbrini and Wilsey.)

High-linear energy transfer (LET) radiation, such as heavy ions is associated with a higher relative biological effectiveness (RBE) than low-LET radiation, such as photons. Irradiation with low- and high-LET particles differ in the interaction with the cellular matter and therefore in the spatial dose distribution. When a single high-LET particle interacts with matter, it results in doses of up to thousands of gray (Gy) locally concentrated around the ion trajectory, whereas the mean dose averaged over the target, such as a cell nucleus is only in the range of a Gy. DNA damage therefore accumulates in this small volume. In contrast, up to hundreds of low-LET particle hits are required to achieve the same mean dose, resulting in a quasi-homogeneous damage distribution throughout the cell nucleus. In this study, we investigated the dependence of RBE from different spatial dose depositions using different focused beam spot sizes of proton radiation with respect to the induction of chromosome aberrations and clonogenic cell survival. Human-hamster hybrid (AL) as well as Chinese hamster ovary cells (CHO-K1) were irradiated with focused low LET protons of 20 MeV (LET = 2.6 keV/µm) beam energy with a mean dose of 1.7 Gy in a quadratic matrix pattern with point spacing of 5.4 × 5.4 µm2 and 117 protons per matrix point at the ion microbeam SNAKE using different beam spot sizes between 0.8 µm and 2.8 µm (full width at half maximum). The dose-response curves of X-ray reference radiation were used to determine the RBE after a 1.7 Gy dose of radiation. The RBE for the induction of dicentric chromosomes and cell inactivation was increased after irradiation with the smallest beam spot diameter (0.8 µm for chromosome aberration experiments and 1.0 µm for cell survival experiments) compared to homogeneous proton radiation but was still below the RBE of a corresponding high LET single ion hit. By increasing the spot size to 1.6-1.8 µm, the RBE decreased but was still higher than for homogeneously distributed protons. By further increasing the spot size to 2.7-2.8 µm, the RBE was no longer different from the homogeneous radiation. Our experiments demonstrate that varying spot size of low-LET radiation gradually modifies the RBE. This underlines that a substantial fraction of enhanced RBE originates from inhomogeneous energy concentrations on the µm scale (mean intertrack distances of low-LET particles below 0.1 µm) and quantifies the link between such energy concentration and RBE. The missing fraction of RBE enhancement when comparing with high-LET ions is attributed to the high inner track energy deposition on the nanometer scale. The results are compared with model results of PARTRAC and LEM for chromosomal aberration and cell survival, respectively, which suggest mechanistic interpretations of the observed radiation effects., (© 2024 by Radiation Research Society.)

It is well-known that trans and non-binary individuals experience worse health outcomes due to experiences of violence and discrimination. For this reason, accessible healthcare for trans and non-binary people is crucial. There is a lack of Canadian literature on the experiences of non-binary people within the healthcare system. This study sought to understand barriers to healthcare among non-binary people living in a mid-sized urban/rural region of Canada. Interviews were conducted between November 2019 to March 2020 with 12 non-binary individuals assigned female at birth, living in Waterloo Region, Ontario, Canada, as a part of a larger qualitative study exploring experiences within the community, healthcare and employment. Three broad themes were developed: erasure, barriers to access to healthcare, and assessing whether (or not) to come out. Sub-themes included institutional erasure, informational erasure, general healthcare barriers, medical transition healthcare barriers, anticipated discrimination, and assessing safety. Policy and institutional changes are needed to increase the safety and accessibility of healthcare services to non-binary individuals.

Objective: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI)., Methods: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing., Results: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment., Significance: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

In plants, light direction is perceived by the phototropin photoreceptors, which trigger directional growth responses known as phototropism. The formation of a phototropin activation gradient across a photosensitive organ initiates this response. However, the optical tissue properties that functionally contribute to phototropism remain unclear. In this work, we show that intercellular air channels limit light transmittance through various organs in several species. Air channels enhance light scattering in Arabidopsis hypocotyls, thereby steepening the light gradient. This is required for an efficient phototropic response in Arabidopsis and Brassica. We identified an embryonically expressed ABC transporter required for the presence of air channels in seedlings and a structure surrounding them. Our work provides insights into intercellular air space development or maintenance and identifies a mechanism of directional light sensing in plants.

Immune milieus play an important role in various types of cancer. The present study focuses on the effect of Th1 cytokines on pediatric acute lymphoblastic leukemia (ALL). The reaction of ALL cell lines and patient-derived xenografts (PDX) to the most important Th1 cytokines TNF-α (tumor necrosis factor alpha) and IFN-γ (interferon gamma) is analyzed and correlated with the respective cytokine receptors and the intracellular signaling molecules. ALL cell lines and ALL PDX display a great heterogeneity in cell death after incubation with TNF-α and IFN-γ. Several samples show a dose-dependent and additive induction of cell death by both cytokines; others do not react at all or even display an increased viability. Apoptosis is the main type of cell death induced by Th1 cytokines in ALL cells. Over all leukemia cells analyzed, IFN-γ receptor (IFNGR) shows a higher expression than both TNF-receptors, resulting in higher phosphorylation of STAT1 (signal transducer and activator of transcription) compared to phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B-cells) in the TNF pathway. The activation of STAT1 correlates with the amount of cell death after stimulation with Th1 cytokines. TNF-α and IFN-γ lead to heterogeneous reactions in ALL cell lines and ALL PDX but are able to induce cell death by apoptosis in the majority of ALL blasts. The correlation of a high expression of IFNGR and following activation of STAT1 with cell death indicates an important role for IFN-γ signaling in this setting., (© 2023. The Author(s).)

Mouse xenograft models play a vital role in tumor studies for research as well as for screening of drugs for the pharmaceutical industry. In particular, models with compromised immunity are favorable to increase the success of transplantation, such as, e.g. NOD/SCID and BALB/c Nude strains. The genomic sequence and alterations of many of these models still remain elusive and might hamper a model's further optimization or proper adapted usage. This can be in respect to treatments (e.g. NOD/SCID sensitivity to radiation), experiments or analysis of derived sequencing data of such models. Here we present the genome assemblies for the NOD/SCID and BALB/c Nude strains to overcome this short-coming for the future and improve our understanding of these models in the process. We highlight as well first insights into observed genomic differences for these models compared to the C57BL/6 reference genome. Genome assemblies for both are close to full-chromosome representations and provided with liftover annotations from the GRCm39 reference genome., Competing Interests: Conflicts of interest All authors were employees of JSR Life Sciences at the time the study was performed. The authors declare no other competing financial interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

CDC45-MCM2-7-GINS (CMG) helicase assembly is the central event in eukaryotic replication initiation. In yeast, a multi-subunit "pre-loading complex" (pre-LC) accompanies GINS to chromatin-bound MCM2-7, leading to CMG formation. Here, we report that DONSON, a metazoan protein mutated in microcephalic primordial dwarfism, is required for CMG assembly in vertebrates. Using AlphaFold to screen for protein-protein interactions followed by experimental validation, we show that DONSON scaffolds a vertebrate pre-LC containing GINS, TOPBP1, and DNA pol ε. Our evidence suggests that DONSON docks the pre-LC onto MCM2-7, delivering GINS to its binding site in CMG. A patient-derived DONSON mutation compromises CMG assembly and recapitulates microcephalic dwarfism in mice. These results unify our understanding of eukaryotic replication initiation, implicate defective CMG assembly in microcephalic dwarfism, and illustrate how in silico protein-protein interaction screening accelerates mechanistic discovery.

Context: Burosumab has been approved for the treatment of children and adults with X-linked hypophosphatemia (XLH). Real-world data and evidence for its efficacy in adolescents are lacking., Objective: To assess the effects of 12 months of burosumab treatment on mineral metabolism in children (aged <12 years) and adolescents (aged 12-18 years) with XLH., Design: Prospective national registry., Setting: Hospital clinics., Patients: A total of 93 patients with XLH (65 children, 28 adolescents)., Main Outcome Measures: Z scores for serum phosphate, alkaline phosphatase (ALP), and renal tubular reabsorption of phosphate per glomerular filtration rate (TmP/GFR) at 12 months., Results: At baseline, patients showed hypophosphatemia (-4.4 SD), reduced TmP/GFR (-6.5 SD), and elevated ALP (2.7 SD, each P < .001 vs healthy children) irrespective of age, suggesting active rickets despite prior therapy with oral phosphate and active vitamin D in 88% of patients. Burosumab treatment resulted in comparable increases in serum phosphate and TmP/GFR in children and adolescents with XLH and a steady decline in serum ALP (each P < .001 vs baseline). At 12 months, serum phosphate, TmP/GFR, and ALP levels were within the age-related normal range in approximately 42%, 27%, and 80% of patients in both groups, respectively, with a lower, weight-based final burosumab dose in adolescents compared with children (0.72 vs 1.06 mg/kg, P < .01)., Conclusions: In this real-world setting, 12 months of burosumab treatment was equally effective in normalizing serum ALP in adolescents and children, despite persistent mild hypophosphatemia in one-half of patients, suggesting that complete normalization of serum phosphate is not mandatory for substantial improvement of rickets in these patients. Adolescents appear to require lower weight-based burosumab dosage than children., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Butyrophilins are surface receptors belonging to the immunoglobulin superfamily. While several members of the butyrophilin family have been implicated in the development of unconventional T cells, butyrophilin 2a2 (Btn2a2) has been shown to inhibit conventional T cell activation. Here, we demonstrate that in steady state, the primary source of Btn2a2 are thymic epithelial cells (TEC). Absence of Btn2a2 alters thymic T cell maturation and bypasses central tolerance mechanisms. Furthermore, Btn2a2 -/- mice develop spontaneous autoimmunity resembling human primary Sjögren's Syndrome (pSS), including formation of tertiary lymphoid structures (TLS) in target organs. Ligation of Btn2a2 on developing thymocytes is associated with reduced TCR signaling and CD5 levels, while absence of Btn2a2 results in increased TCR signaling and CD5 levels. These results define a novel role for Btn2a2 in promoting central tolerance by modulating TCR signaling strength and indicate a potential mechanism of pSS development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Natural products are generally regarded as safe and have been shown to mediate anticancer activities against a variety of cell types. Zerumbone is a natural cyclic sesquiterpene derived from the rhizome of Zingiber zerumbet, which has attracted extensive attention in the recent decade for anticancer activities. The present study investigates the in vitro effect of zerumbone on rhabdomyosarcoma cells., Methods: Two rhabdomyosarcoma cell lines (RD and RH30) were used as the model system. The growth inhibition of zerumbone was measured by MTT-assay, apoptosis via flow cytometry, gene expression by real-time PCR, the migration by transwell assay, and intracellular signaling by Western blotting., Results: Zerumbone shows anticancer effects on RD and RH30 cells in a dose-dependent manner via cell growth inhibition and induction of apoptosis. Exposure of RD and RH30 cells on zerumbone also resulted in a decrease of migration and downregulation of the hedgehog pathway., Conclusions: Taken together, our study provided the first evidence that zerumbone imparted strong inhibitory and apoptotic effects on pediatric rhabdomyosarcoma cell lines and merit further investigation as a promising candidate for the anticancer therapy., (© 2022. The Author(s).)

Background: Overexpression of phosphodiesterase type 5 (PDE5) has been detected in many types of malignant tumors. Sildenafil, a potent and selective inhibitor of a cGMP-specific PDE5, has been found to enhance the cytotoxic activity of different chemotherapeutic agents including doxorubicin. The combined therapy of doxorubicin with Sildenafil might reduce the possible side effects of chemotherapy while maintaining synergistic anticancer activity. The present study explored for the first time the effects of Sildenafil, alone and in combination with doxorubicin, on pediatric RMS cells., Methods: Human RMS cells lines RH30 and RD were used. Western blotting and RT-PCR were performed to analyze PDE5 expression in RMS cells. Cell viability was determined using MTT assay. Cell migration was analyzed via transwell chambers, clonal growth and mitotic cell death were analyzed using the clonogenic assay. FACS analysis was performed to evaluate reactive oxygen species (ROS) and apoptosis., Results: Sildenafil significantly decreased cell viability and migration of RD and RH30 cells. The exposure of RMS cells to doxorubicin resulted in a dose-dependent decrease in their viability. Simultaneous administration of Sildenafil enhanced this effect. The incubation of the RMS cells with Sildenafil in the presence of doxorubicin significantly increased the proportion of apoptotic cells and ROS production compared to the treatment with Sildenafil alone., Conclusions: The results of our study indicate a link between PDE5 inhibition by Sildenafil and decreased calcium signalling leading to significantly impaired viability, migration, and colony forming of RMS cells. Increased ROS production and apoptosis are mechanisms relevantly contributing to this observation., (© 2022. The Author(s).)

Background/aim: Epigallocatechin gallate (EGCG), a major polyphenol of green tea, has been shown to inhibit cancer cell proliferation. In this study the effect of EGCG on cell metabolism and the human hedgehog signalling pathway (HH) in human rhabdomyosarcoma (RMS) cells was investigated., Materials and Methods: Two human RMS cell lines (RD and RH30) were incubated with EGCG. To evaluate the effects of EGCG on RMS cells, cell viability, colony formation, cell migration, and alteration of genes related to the HH signalling pathway were investigated., Results: EGCG showed cytostatic effects on RMS cells in a dose-dependent manner. Incubation with 25 μM EGCG resulted in a significant reduction of cell migration by 70% and downregulation of the HH pathway transcription factor GLI1., Conclusion: EGCG inhibits RMS cells in vitro by reducing cell proliferation and downregulating the HH signalling pathway. It may therefore be a promising agent in chemoresistant or advanced RMS in children., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: To create nomograms for better prediction of the oncological outcome in advanced laryngeal (LxCAs) or hypopharyngeal (HpxCAs) cancer after laryngopharyngectomy., Materials: 239 patients who underwent total laryngectomy or laryngopharyngectomy due to LxCA (52.7%) or HpxCA (47.3%) were included in this study. Based on clinical risk factors (tumor site, lymph node involvement, salvage setting), we created nomograms for prediction of disease-specific survival (DSS) and disease-free survival (DFS)., Results: HpxCAs showed a higher rate of lymph node involvement (p < 0.001), a 2.47-fold higher risk of a 2nd head and neck cancer (p = 0.009) and significantly worse loco-regional control rates (p = 0.003) compared to LxCAs. Positive neck nodes and salvage procedures were associated with significantly worse outcome. Nomograms demonstrated that hypopharyngeal tumors with positive neck nodes in salvage situations had the worst oncological outcome with a 5-year DSS of 15-20%., Conclusions: The oncological outcome is worse in hypopharyngeal carcinomas and could be easily quantified by our nomograms that are based on tumor site, lymph node involvement and salvage situation., (© 2022. The Author(s).)

Process monitoring and control require dedicated and reliable measures which reflect the status of the process under investigation. Although nuclear magnetic resonance is known to be a versatile analytical technique, it is only seldomly found in process monitoring. Single-sided nuclear magnetic resonance is one well known approach for being applied in process monitoring. The dedicated V-sensor is a recent approach that allows the inline investigation of materials in a pipe non-destructively and non-invasively. An open geometry of the radiofrequency unit is realized using a tailored coil, enabling the sensor to be applied for manifold mobile applications in in-line process monitoring. Stationary liquids were measured, and their properties were integrally quantified as the basis for successful process monitoring. The sensor, in its inline version, is presented along with its characteristics. An exemplary field of application is battery production in terms of anode slurries; thus, the first results on graphite slurries will demonstrate the added value of the sensor in process monitoring.

Targeted proteomics enables hypothesis-driven research by measuring the cellular expression of protein cohorts related by function, disease, or class after perturbation. Here, we present a pathway-centric approach and an assay builder resource for targeting entire pathways of up to 200 proteins selected from >10,000 expressed proteins to directly measure their abundances, exploiting sample multiplexing to increase throughput by 16-fold. The strategy, termed GoDig, requires only a single-shot LC-MS analysis, ~1 µg combined peptide material, a list of up to 200 proteins, and real-time analytics to trigger simultaneous quantification of up to 16 samples for hundreds of analytes. We apply GoDig to quantify the impact of genetic variation on protein expression in mice fed a high-fat diet. We create several GoDig assays to quantify the expression of multiple protein families (kinases, lipid metabolism- and lipid droplet-associated proteins) across 480 fully-genotyped Diversity Outbred mice, revealing protein quantitative trait loci and establishing potential linkages between specific proteins and lipid homeostasis., (© 2023. The Author(s).)

Ladder-type pentaphenyl chromophores have a rigid, planar π-system and show bright fluorescence featuring pronounced vibrational structure. Such moieties are ideal for studying interchromophoric interactions and delocalization of electronic excitations. We report the synthesis of helical polymers with a rigid square structure based on spiro-linked ladder-type pentaphenyl units. The variation of circular dichroism with increasing chain length provides direct evidence for delocalization of electronic excitations over at least 10 monomeric units. The change in the degree of circular polarization of the fluorescence across the vibronic side bands shows that vibrational motion can localize the excitation dynamically to almost one single unit through breakdown of the Born-Oppenheimer approximation. The dynamic conversion between delocalized and localized excited states provides a new paradigm for interpreting circular dichroism in helical polymers such as proteins and polynucleic acids., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background: Neuroblastoma (NB) is the most common paediatric extracranial solid malignancy. We analysed the role of the epitope detection in monocytes (EDIM) technique for liquid biopsy in NB patients., Methods: Tumour epitopes transketolase-like 1 (TKTL1), Apo10 (DNaseX) and GD2 were assessed: expression levels in seven NB tumour samples and five NB cell lines were analysed using RT-PCR and flow cytometry. LAN-1 cells were co-cultured with blood and assessed using EDIM. Peripheral blood macrophages of patients with neuroblastoma (n = 38) and healthy individuals (control group, n = 37) were labelled (CD14 + /CD16 + ) and assessed for TKTL1, Apo10 and GD2 using the EDIM technology., Results: mRNA expression of TKTL1 and DNaseX/Apo10 was elevated in 6/7 NB samples. Spike experiments showed upregulation of TKTL1, Apo10 and GD2 in LAN-1 cells following co-culturing with blood. TKTL1 and Apo10 were present in macrophages of 36/38 patients, and GD2 in 15/19 patients. The 37 control samples were all negative. EDIM expression scores of the three epitopes allowed differentiation between NB patients and healthy individuals., Conclusions: The EDIM test might serve as a non-invasive tool for liquid biopsy in children suffering from NB. Future studies are necessary for assessing risk stratification, tumour biology, treatment monitoring, and early detection of tumour relapses., (© 2022. The Author(s).)

Purpose: The aim of this retrospective analysis was to investigate whether trabeculectomy (TRAB) and XEN® Gel Stent implantation (XEN) - both filtrating surgery techniques - can slow down the deterioration of visual field (VF) parameters considering the floor effect, which could lead to a misestimation of pre- and postoperative VF rate of progression (ROP)., Methods: Included in this study were patients with open-angle glaucoma, who underwent either TRAB or XEN® gel stent implantation and who had at least three VF tests before and after surgery, over an observation period of 13 years. The annual ROP of the mean defect (MD) and the square root of loss variance (sLV) were calculated with two different censoring thresholds: by censored regression and by ordinary least squares regression (OLSR). In addition, the diagnostic range of sLV was calculated., Results: 48 eyes of 39 glaucoma patients were included in the study. The annual rate of MD progression was significantly reduced by filtering surgery when calculating the yearly ROP using OLSR (p = 0.006) and by censoring values exceeding a precalculated cut-off of 14.20 dB (p = 0.041) and a cut-off from the literature of 15.00 dB (p = 0.028). On average, the MD was impacted by a significant floor effect of 14.20 dB (95% CI: 12.83-15.56), corresponding to 17.7/59 absolute defects or 29.9% of the whole VF. When applying both OLSR and censored regression, the annual rate of sLV progression did not show a significant difference. The sLV showed a diagnostic boundary at a MD of 15.78 dB., Conclusion: This study shows that filtering surgery can reduce the progression of VF in patients with open-angle glaucoma, especially those whose disease develops aggressively. This is valid even if the floor effect in advanced cases is compensated by censored regression. On average, the ROP of MD is affected by a significant floor effect at about 29.9% absolute loss of the whole VF., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Biomarkers allowing characterization of pediatric rhabdomyosarcoma (RMS) are lacking. Epitope detection in monocytes (EDIM) is a novel method focused on detection of the biomarkers TKTL1 (transketolase-like protein 1) and Apo10 (epitope of DNaseX) in activated monocytes (CD14 + /CD16 + ) from patient's blood. We investigated the expression of these biomarkers in RMS cell lines, tumor material, and peripheral blood from RMS patients. Expression levels of TKTL1 and DNaseX/Apo10 in RMS cell lines (RH30, RD) and tumor samples were analyzed by RT-PCR and flow cytometry. Blood samples of 29 RMS patients were measured and compared to 27 healthy individuals. The percentages of activated CD14 + /CD16 + monocytes harboring TKTL1 and Apo10 were determined. EDIM-TKTL1 and EDIM-Apo10 expression scores were calculated. The relationship between TKTL1 expression and DNA-hypomethylation was evaluated. Both RMS cell lines and tumor samples showed significantly higher expression levels of TKTL1 and DNaseX/Apo10 compared to skeletal muscle cells (SkMC). EDIM-TKTL1 and EDIM-Apo10 scores were positive in 96.5% of patients with RMS. All healthy controls had negative corresponding scores. RMS cell lines show increased expression levels of the biomarkers TKTL1 and DNaseX/Apo10. The sensitivity of the EDIM blood test indicates that this assay might serve as an additional tool in pediatric RMS.

Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular events driven by abnormal platelet clotting effects. Platelets are produced by megakaryocytes, deriving from megakaryocyte erythrocyte progenitors (MEP) in the bone marrow. Increased megakaryocyte expansion across common autoimmune diseases was shown for RA, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). In this context, we evaluated the role of the microbial-derived short chain fatty acid (SCFA) propionate on hematopoietic progenitors in the collagen induced inflammatory arthritis model (CIA) as we recently showed attenuating effects of preventive propionate treatment on CIA severity.  In vivo , propionate treatment starting 21 days post immunization (dpi) reduced the frequency of MEPs in the bone marrow of CIA and naïve mice. Megakaryocytes numbers were reduced but increased the expression of the maturation marker CD61. Consistent with this, functional analysis of platelets showed an upregulated reactivity state following propionate-treatment. This was confirmed by elevated histone 3 acetylation and propionylation as well as by RNAseq analysis in Meg-01 cells. Taken together, we identified a novel nutritional axis that skews platelet formation and function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dürholz, Schmid, Frech, Azizov, Otterbein, Lucas, Rauh, Schett, Bruns and Zaiss.)

Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME)., Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing., Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME., Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME., Competing Interests: ET reports personal fees from EVER Pharma, Marinus, Argenix, Arvelle/Angelini, Medtronic, Bial – Portela, S.A., NewBridge, GL Pharma, GlaxoSmithKline, Hikma, Boehringer Ingelheim, LivaNova, Eisai, UCB, Biogen, Genzyme Sanofi, GW Pharmaceuticals, and Actavis outside the submitted work; his institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Osterreichischer Fond zur Wissenschaftsforderung, Bundesministerium fr Wissenschaft und Forschung, and Jubilaumsfond der sterreichischen Nationalbank outside the submitted work. GZ gratefully acknowledges the support of the WISS 2025 project; IDA-Lab Salzburg (20204-WISS/225/197-2019 and 20102-F1901166-KZP). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rainer, Kronbichler, Kuchukhidze, Trinka, Langthaler, Kronbichler, Said-Yuerekli, Kirschner, Zimmermann, Höfler, Schmid and Braun.)

Purpose: In advanced tumor stages, pediatric rhabdomyosarcoma (RMS) shows an intrinsic resistance to standard chemotherapy, which is associated with a dismal prognosis. Alternative therapeutic approaches and optimization of already existent treatment protocols are urgently needed in these conditions. The µ-opioid receptor (OPRM1) agonist, D,L-methadone is frequently used for analgesia in oncological patients. Recent evidence has shown that D,L-methadone in combination with chemotherapeutic agents may enhance their cytotoxic effect against cancer cells. There are no related data in pediatric rhabdomyosarcoma (RMS)., Methods: Antitumor effects of combined D,L-methadone and doxorubicin, carboplatin, and vincristine on RMS cell lines RD and RH30 were analyzed using following outcome data: expression of the OPRM1 receptor (Western blot), cell growth inhibition (MTT assay), cell migration (wound-healing assay), apoptosis induction (caspase-3/7 assay), and reactive oxygen species (ROS) production (flow cytometry)., Results: In both cell lines, OPRM1 expression was significantly increased after combined treatment of D,L-methadone with all three cytotoxic drugs tested, which resulted in suppression of tumor cell growth and increase of apoptosis rates. These effects were mediated by increased ROS production and up-regulation of caspase-3/7 activity. Doxorubicin combined with D,L-methadone significantly reduced cell migration in both cell lines. Carboplatin or vincristine in combination with D,L-methadone had only an impact on cell migration in RH30 cells., Conclusions: This new therapeutic approach in RMS provides strong antitumor effects in vitro. The combination of standard chemotherapy and D,L-methadone requires further investigation. Especially advanced tumors with a limited effectiveness of conventional treatment regimens seem a potential target of this approach., (© 2022. The Author(s).)

Shaded plants challenged with herbivores or pathogens prioritize growth over defense. However, most experiments have focused on the effect of shading light cues on defense responses. To investigate the potential interaction between shade-avoidance and wounding-induced Jasmonate (JA)-mediated signaling on leaf growth and movement, we used repetitive mechanical wounding of leaf blades to mimic herbivore attacks. Phenotyping experiments with combined treatments on Arabidopsis thaliana rosettes revealed that shade strongly inhibits the wound effect on leaf elevation. By contrast, petiole length is reduced by wounding both in the sun and in the shade. Thus, the relationship between the shade and wounding/JA pathways varies depending on the physiological response, implying that leaf growth and movement can be uncoupled. Using RNA-sequencing, we identified genes with expression patterns matching the hyponastic response (opposite regulation by both stimuli, interaction between treatments with shade dominating the wound signal). Among them were genes from the PKS (Phytochrome Kinase Substrate) family, which was previously studied for its role in phototropism and leaf positioning. Interestingly, we observed reduced shade suppression of the wounding effect in pks2pks4 double mutants while a PKS4 overexpressing line showed constitutively elevated leaves and was less sensitive to wounding. Our results indicate a trait-specific interrelationship between shade and wounding cues on Arabidopsis leaf growth and positioning. Moreover, we identify PKS genes as integrators of external cues in the control of leaf hyponasty further emphasizing the role of these genes in aerial organ positioning., Competing Interests: The authors have declared that no competing interests exist.

Glyphosate is controversially discussed because of its alleged harmful effects on human health and the environment. Although it is approved until December 2022 in the European Union, the Austrian government discusses a national ban. Research on farmers' intentions to deal with upcoming pesticide policy changes is limited and planned responses to a national glyphosate ban may inform accompanying measures and the development of weed management alternatives. Therefore, we have conducted 41 qualitative semi-structured interviews with farmers to explore their intended weed management if glyphosate-based herbicides were no longer available in Austria. The interviews were systematically analyzed, whereby the Theory of Planned Behavior (TPB) with its three social-psychological constructs served as guidance, i.e., attitude toward the planned behavior, subjective norm, and perceived behavioral control toward the planned behavior. We grouped farmers based on differences in their behavioral intentions toward glyphosate-free weed management, and identified four types of farmers by assigning group-specific attributes of the TPB constructs to the groups of farmers with similar behavioral intentions. Given a national glyphosate ban, the farmers intend to implement either mechanical or chemical alternatives, which would be solely applied or combined with changes in cultivation. Attitude toward the planned behavior, descriptive norms, and perceived behavioral control affect behavioral intentions, whereas injunctive norms do not differ much between the interviewed farmers. What unites the four types of farmers is that they would rather accept a glyphosate ban, if weed management alternatives with similar effectiveness and costs were available., (© 2022. The Author(s).)

Background: Amygdalae play a central role in emotional processing by interconnecting frontal cortex and other brain structures. Unilateral amygdala enlargement (AE) is associated with mesial temporal lobe epilepsy (mTLE). In a relatively large sample of patients with mTLE and AE, we aimed to evaluate functional integration of AE in emotion processing and to determine possible associations between fMRI activation patterns in amygdala and deficits in emotion recognition as assessed by neuropsychological testing., Methods: Twenty-two patients with drug resistant unilateral mTLE due to ipsilateral AE were prospectively recruited in a large epilepsy unit and compared with 17 healthy control subjects in terms of amygdala volume, fMRI activation patterns and performance in emotion recognition as assessed by comprehensive affect testing system (CATS) and Ekman faces. All patients underwent structural and functional 1.5 Tesla MRI, electro-clinical assessment and neuropsychological testing., Results: We observed BOLD signal ipsilateral to AE ( n = 7; group PAT1); contralateral to AE ( n = 6; group PAT2) and no activation ( n = 9; group PAT3). In the region of interest (ROI) analysis, beta estimates for fearful face > landscape contrast in the left amygdala region did not differ significantly in patients with left TLE vs. patients with right TLE [ T (16) = -1.481; p = 0.158]. However, beta estimates for fearful face > landscape contrast in the right amygdala region were significantly reduced in patients with right TLE vs. patients with left TLE [ T (16) = -2,922; p = 0.010]. Patients showed significantly lower total scores in CATS and Ekman faces compared to healthy controls., Conclusion: In our cohort, patients with unilateral mesial TLE and ipsilateral AE, an amygdala could display either functional integration in emotion recognition or dysfunction as demonstrated by fMRI. Perception and recognition of emotions were impaired more in right-sided mTLE as compared to left-sided mTLE. Neuropsychological tests showed deficits in emotion recognition in patients as compared to healthy controls., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kuchukhidze, Unterberger, Schmid, Zamarian, Siedentopf, Koppelstaetter, Gizewski, Kronbichler, Luef, Jokeit and Trinka.)