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The aggregation of high-affinity immunoglobulin E (IgE) receptors (FcεRI) on mast cells is a critical event in the initiation of an allergic reaction. Coengagement of FcεRI with immunoglobulin G (IgG) low-affinity receptor FcγRIIB/CD32 inhibits degranulation and the release of inflammatory mediators from mast cells and has therefore been proposed as a new therapeutic approach for the treatment of allergies. In this study, we investigated whether FcγRIIB, besides inhibiting degranulation, negatively regulates other signalling pathways downstream of FcεRI. For this, we determined the phosphorylation and/or expression of proteins involved in the regulation of mast-cell apoptosis. Coaggregation led to an attenuation of Akt phosphorylation but did not inhibit phosphorylation of transcription factor Foxo3a or its proapoptotic target, Bim. Similarly, FcεRI-dependent expression of the prosurvival gene A1 was not affected by coaggregation. Our data demonstrate that coengagement of FcεRI and FcγRIIB inhibits degranulation but not the signalling pathways regulating Bcl-2 family members Bim and A1.

Driven nanomechanical resonators based on low-dimensional materials are routinely and efficiently detected with electrical mixing measurements. However, the measured signal is a non-trivial combination of the mechanical eigenmode displacement and an electrical contribution, which makes the extraction of the driven mechanical response challenging. Here, we report a simple yet reliable method to extract solely the driven mechanical vibrations by eliminating the contribution of pure electrical origin. This enables us to measure the spectral mechanical response as well as the driven quadratures of motion. This method is crucial for nanomechanical vibrations in the nonlinear regime, since the shape of the mechanical response depends on the physics at work. We further show how to calibrate the measured signal into units of displacement. Our method marks a key step forward in the study of nanoelectromechanical resonators based on low-dimensional materials in the nonlinear regime. [ABSTRACT FROM AUTHOR]

A patient developed clinical and histological interstitial cystitis as an adverse effect of treatment with tiaprofenic acid for rheumatism. After cessation of the drug, full symptomatic recovery was obtained. Bladder biopsies 6 months later demonstrated normalization of detrusor muscle histology. [ABSTRACT FROM AUTHOR]

Abstract Background Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI.

We report the first study on the thermal behavior of the stiffness of individual carbon nanotubes, which is achieved by measuring the resonance frequency of their fundamental mechanical bending modes. We observe a reduction of the Young's modulus over a large temperature range with a slope -(173±65) ppm/K in its relative shift. These findings are reproduced by two different theoretical models based on the thermal dynamics of the lattice. These results reveal how the measured fundamental bending modes depend on the phonons in the nanotube via the Young's modulus. An alternative description based on the coupling between the measured mechanical modes and the phonon thermal bath in the Akhiezer limit is discussed. [ABSTRACT FROM AUTHOR]

The digital transformation of the production sector is setting the scene for a major industrial change. The need for supporting companies in this transformation is currently covered by several maturity models, generally operationalized through standardized questionnaires, which provide, as an outcome, an assessment of the current maturity stage and a set of general improvement recommendations according to it. However, to provide companies with a more tangible support, there is a need for more individual approach. In order to deal with this need, this paper proposes, following a design science research framework, a novel approach based on Problem-Based Learning for structuring the assessment procedure as a dialectic process. This approach aims at facilitating the contextualization of the assessed company and, consequently, the identification of context-specific improvement recommendations. The proposed approach, supported by a maturity model used for framing information collected during the assessment process, is tested in three industrial cases. Although these have been assessed at the same maturity stage, different improvement recommendations have been proposed according to contextual factors such as strategic goals, core processes and key performance indicators. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to examine the impact of 8 days of immobilization during a Special Support and Reconnaissance mission (SSR) on muscle mass, contraction dynamics, maximum jump height/power, and body composition.Methods: Unilateral maximal voluntary contraction, rate of force development, and maximal jump height were tested to assess muscle strength/power along with whole-body impedance analysis before and after SSR.Results: Body weight, fat-free mass, and total body water decreased (4-5%) after SSR, along with impairments in maximal jump height (-8%) and knee extensor maximal voluntary contraction (-10%). Furthermore, rate of force development was severely affected (-15-30%).Conclusions: Eight days of immobilization during a covert SSR mission by Special Forces soldiers led to substantial decrements in maximal muscle force and especially in rapid muscle force capacity. This may negatively influence the ability for rapid exfiltration and redeployment, respectively. [ABSTRACT FROM AUTHOR]

Ongoing climate change poses an increasing threat to biodiversity. To avoid decline or extinction, species need to either adjust or adapt to new environmental conditions or track their climatic niches across space. In sessile organisms such as plants, phenotypic plasticity can help maintain fitness in variable and even novel environmental conditions and is therefore likely to play an important role in allowing them to survive climate change, particularly in the short term. Understanding a species' response to rising temperature is crucial for planning well-targeted and cost-effective conservation measures. We sampled seeds of three Hypericum species ( H. maculatum , H. montanum , and H. perforatum ), from a total of 23 populations originating from different parts of their native distribution areas in Europe. We grew them under four different temperature regimes in a greenhouse to simulate current and predicted future climatic conditions in the distribution areas. We measured flowering start, flower count, and subsequent seed weight, allowing us to study variations in the thermal plasticity of flowering phenology and its relation to fitness. Our results show that individuals flowered earlier with increasing temperature, while the degree of phenological plasticity varied among species. More specifically, the plasticity of H. maculatum varied depending on population origin, with individuals from the leading range edge being less plastic. Importantly, we show a positive relationship between higher plasticity and increased flower production, indicating adaptive phenological plasticity. The observed connection between plasticity and fitness supports the idea that plasticity may be adaptive. This study underlines the need for information on plasticity for predicting species' potential to thrive under global change and the need for studies on whether higher phenotypic plasticity is currently being selected as natural populations experience a rapidly changing climate., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)

Spontaneous rhythmic movements are part of everyday life, e.g., in walking, clapping or music making. Humans perform such spontaneous motor actions at different rates that reflect specific biomechanical constraints of the effector system in use. However, there is some evidence for intra-individual consistency of specific spontaneous rates arguably resulting from common underlying processes. Additionally, individual and contextual factors such as musicianship and circadian rhythms have been suggested to influence spontaneous rates. This study investigated the relative contributions of these factors and provides a comprehensive picture of rates among different spontaneous motor behaviors, i.e., melody production, walking, clapping, tapping with and without sound production, the latter measured online before and in the lab. Participants (n = 60) exhibited high intra-individual stability across tasks. Task-related influences included faster tempi for spontaneous production rates of music and wider ranges of spontaneous motor tempi (SMT) and clapping rates compared to walking and music making rates. Moreover, musicians exhibited slower spontaneous rates across tasks, yet we found no influence of time of day on SMT as measured online in pre-lab sessions. Tapping behavior was similar in pre-lab and in-lab sessions, validating the use of online SMT assessments. Together, the prominent role of individual factors and high stability across domains support the idea that different spontaneous motor behaviors are influenced by common underlying processes., (© 2024. The Author(s).)

In a previous experiment, we found evidence for a bodily hierarchy governing interlimb coordination of rhythm and beat, using five effectors: 1) Left foot, 2) Right foot, 3) Left hand, 4) Right hand and 5) Voice. The hierarchy implies that, during simultaneous rhythm and beat performance and using combinations of two of these effectors, executing the task by performing the rhythm with an effector that has a higher number than the beat effector is significantly easier than vice versa. To investigate the neural underpinnings of this proposed bodily hierarchy, we here scanned 46 professional musicians using fMRI as they performed a rhythmic pattern with one effector while keeping the beat with another. The conditions combined the voice and the right hand (V + RH), the right hand and the left hand (RH + LH), and the left hand and the right foot (LH + RF). Each effector combination was performed with and against the bodily hierarchy. Going against the bodily hierarchy increased tapping errors significantly and also increased activity in key brain areas functionally associated with top-down sensorimotor control and bottom-up feedback processing, such as the cerebellum and SMA. Conversely, going with the bodily hierarchy engaged areas functionally associated with the default mode network and regions involved in emotion processing. Theories of general brain function that hold prediction as a key principle, propose that action and perception are governed by the brain's attempt to minimise prediction error at different levels in the brain. Following this viewpoint, our results indicate that going against the hierarchy induces stronger prediction errors, while going with the hierarchy allows for a higher degree of automatization. Our results also support the notion of a bodily hierarchy in motor control that prioritizes certain conductive and supportive tapping roles in specific effector combinations., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and cotranscriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to abscisic acid (ABA). When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to overaccumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Background and Aims: Climate-change induced warmer spring temperatures advance tree leaf-out and result in earlier shading of the forest floor. Climate change also leads to more frequent droughts. Forest understorey herbs may respond to these environmental changes by varying traits at different hierarchical levels of organization. While trait mean variation at the inter-individual level in response to environmental changes is well-studied, little is known about how variation at the intra-individual level responds., Methods: We sampled genets of the forest understorey herb Galium odoratum from 21 populations in three regions in Germany, varying in microclimatic conditions. The genets were transplanted into a common garden, where we applied shading and drought treatments. We measured plant height and leaf length and width, and calculated the coefficient of variation (CV) at different hierarchical levels: intra-population, intra-genet, intra-ramet and intra-shoot., Key Results: Variance partitioning showed that intra-shoot CV represented most of the total variation, followed by intra-ramet CV. We found significant variation in CV of plant height and leaf width among populations of origin, indicating that CV is at least partly genetically based. The soil temperature at populations' origins correlated negatively with CV in plant height, suggesting adaptation to local conditions. Furthermore, we observed that early shade led to increased intra-ramet CV in leaf length, while drought reduced intra-shoot CV in leaf width. Finally, intra-shoot leaf width mean and CV were independent under control conditions but correlated under drought., Conclusions: Our experimental results reveal correlations of intra-individual variation with soil temperature, indicating that intra-individual variation can evolve and may be adaptive. Intra-individual variation responded plastically to drought and shading, suggesting functional changes to improve light capture and reduce evapotranspiration. In conclusion, intra-individual variation makes up the majority of total trait variation in this species and can play a key role in plant adaptation to climatic change., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Addressable quantum states well isolated from the environment are of considerable interest for quantum information science and technology. Carbon nanotubes are an appealing system, since a perfect crystal can be grown without any missing atoms and its cylindrical structure prevents ill-defined atomic arrangement at the surface. Here, we develop a reliable process to fabricate compact multielectrode circuits that can sustain the harsh conditions of the nanotube growth. Nanotubes are suspended over multiple gate electrodes, which are themselves structured over narrow dielectric ridges to reduce the effect of the charge fluctuators of the substrate. We measure high-quality double- and triple-quantum dot charge stability diagrams. Transport measurements through the triple-quantum dot indicate long-range tunneling of single electrons between the left and right quantum dots. This work paves the way to the realization of a new generation of condensed-matter devices in an ultraclean environment, including spin qubits, mechanical qubits, and quantum simulators.

Little is known about expertise-related plasticity of neural mechanisms for auditory feature integration. Here, we contrast two diverging hypotheses that musical expertise is associated with more independent or more integrated predictive processing of acoustic features relevant to melody perception. Mismatch negativity (MMNm) was recorded with magnetoencephalography (MEG) from 25 musicians and 25 non-musicians, exposed to interleaved blocks of a complex, melody-like multi-feature paradigm and a simple, oddball control paradigm. In addition to single deviants differing in frequency (F), intensity (I), or perceived location (L), double and triple deviants were included reflecting all possible feature combinations (FI, IL, LF, FIL). Following previous work, early neural processing overlap was approximated in terms of MMNm additivity by comparing empirical MMNms obtained with double and triple deviants to modeled MMNms corresponding to summed constituent single-deviant MMNms. Significantly greater subadditivity was found in musicians compared to non-musicians, specifically for frequency-related deviants in complex, melody-like stimuli. Despite using identical sounds, expertise effects were absent from the simple oddball paradigm. This novel finding supports the integrated processing hypothesis whereby musicians recruit overlapping neural resources facilitating more integrative representations of contextually relevant stimuli such as frequency (perceived as pitch) during melody perception. More generally, these specialized refinements in predictive processing may enable experts to optimally capitalize upon complex, domain-relevant, acoustic cues., 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 Hansen, Højlund, Møller, Pearce and Vuust.)

Interlimb coordination is critical to the successful performance of simple activities in everyday life and it depends on precisely timed perception-action coupling. This is particularly true in music-making, where performers often use body-movements to keep the beat while playing more complex rhythmic patterns. In the current study, we used a musical rhythmic paradigm of simultaneous rhythm/beat performance to examine how interlimb coordination between voice, hands and feet is influenced by the inherent figure-ground relationship between rhythm and beat. Sixty right-handed participants-professional musicians, amateur musicians and non-musicians-performed three short rhythmic patterns while keeping the underlying beat, using 12 different combinations of voice, hands and feet. Results revealed a bodily hierarchy with five levels (1) left foot, (2) right foot, (3) left hand, (4) right hand, (5) voice, i.e., more precise task execution was observed when the rhythm was performed with an effector occupying a higher level in the hierarchy than the effector keeping the beat. The notion of a bodily hierarchy implies that the role assigned to the different effectors is key to successful interlimb coordination: the performance level of a specific effector combination differs considerably, depending on which effector holds the supporting role of the beat and which effector holds the conducting role of the rhythm. Although performance generally increased with expertise, the evidence of the hierarchy was consistent in all three expertise groups. The effects of expertise further highlight how perception influences action. We discuss the possibility that musicians' more robust metrical prediction models make it easier for musicians to attenuate prediction errors than non-musicians. Overall, the study suggests a comprehensive bodily hierarchy, showing how interlimb coordination is influenced by hierarchical principles in both perception and action., (© 2022. The Author(s).)

The core plant microprocessor consists of DICER-LIKE 1 (DCL1), SERRATE (SE), and HYPONASTIC LEAVES 1 (HYL1) and plays a pivotal role in microRNA (miRNA) biogenesis. However, the proteolytic regulation of each component remains elusive. Here, we show that HYL1-CLEAVAGE SUBTILASE 1 (HCS1) is a cytoplasmic protease for HYL1-destabilization. HCS1-excessiveness reduces HYL1 that disrupts miRNA biogenesis, while HCS1-deficiency accumulates HYL1. Consistently, we identified the HYL1 K154A mutant that is insensitive to the proteolytic activity of HCS1, confirming the importance of HCS1 in HYL1 proteostasis. Moreover, HCS1-activity is regulated by light/dark transition. Under light, cytoplasmic CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) E3 ligase suppresses HCS1-activity. COP1 sterically inhibits HCS1 by obstructing HYL1 access into the catalytic sites of HCS1. In contrast, darkness unshackles HCS1-activity for HYL1-destabilization due to nuclear COP1 relocation. Overall, the COP1-HYL1-HCS1 network may integrate two essential cellular pathways: the miRNA-biogenetic pathway and light signaling pathway., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

Background: Lungs from donation after circulatory death (DCD) may be an underused resource for transplantation. The aim was to investigate, with a DCD pig model, if it was possible to recondition lungs exposed for up to 2 h of warm ischaemia with ex vivo lung perfusion (EVLP)., Methods: Danish domestic pigs (N = 17) were randomized into three groups. In the two study groups, lungs were exposed to either 1 or 2 h of warm ischaemia. All lungs were reconditioned and evaluated after 83 ± 38 minutes of perfusion at FiO2 1.0 and 0.21 with EVLP. Outcome measures were gas exchange, pulmonary physiology, inflammatory markers, and histopathologic assessment score., Results: Lungs exposed for 2 h of warm ischaemia did not meet the criteria: PaO2 > 13 kPa required for donation compared with lungs subjected to 0 and 1 h of warm ischaemia (11.0 kPa vs. 14.2 kPa, P < 0.001). These lungs also developed an increased amount of foam and fluid in the airways. No differences in PaCO2, compliance, or pulmonary vascular resistance were observed., Conclusion: Results show that while lungs subjected to 0 or 1 h of warm ischaemia meet the criteria for transplantation based on EVLP evaluation, lungs subjected to 2 h of warm ischaemia did not.