Plants have evolved a family of unique membrane receptor kinases to orchestrate the growth and development of their cells, tissues, and organs. Receptor kinases also form the first line of defense of ...the plant immune system and allow plants to engage in symbiotic interactions. Here, we discuss recent advances in understanding, at the molecular level, how receptor kinases with lysin-motif or leucine-rich-repeat ectodomains have evolved to sense a broad spectrum of ligands. We summarize and compare the established receptor activation mechanisms for plant receptor kinases and dissect how ligand binding at the cell surface leads to activation of cytoplasmic signaling cascades. Our review highlights that one family of plant membrane receptors has diversified structurally to fulfill very different signaling tasks.
In stream ecosystems, bacterial communities play an important role in nutrient and energy cycling processes as they are among the most numerous and active organisms at the basal trophic level of the ...stream food web. Bacterial communities in stream biofilms have been shown to correlate well with different catchment land use and therefore provide an opportunity for the development of a novel ecological indicator of stream ecosystem health. In this study, a bacterial community index (BCI) model was developed and validated using a national data set of biofilm bacterial community profiles collected from 223 streams across seven geographical regions in New Zealand. The six‐component BCI model was generated using the partial least squares regression method to associate the multivariate bacterial community profile with the macroinvertebrate community index, which is a well‐established indicator of stream health. Despite strong regional clustering of the bacterial community profiles, the BCI was indicative of the level of disturbance in the catchment, as shown by significant correlations with a wide range of independent indicators of water quality, macroinvertebrate community data, ecosystem functioning and catchment land‐use data. The BCI was able to explain 35% of the variation in a multi‐metric index incorporating ten common ecological parameters, suggesting that the stream bacterial communities could provide useful information about the ecosystem integrity. The BCI provides a novel ecosystem assessment tool, which can be used to complement existing stream health measures in the management of anthropogenic impacts on freshwater streams and rivers.
Muscle synergy has been widely acknowledged as a possible strategy of neuromotor control, but current research has ignored the potential inhibitory components in muscle synergies. Our study aims to ...identify and characterize the inhibitory components within motor modules derived from electromyography (EMG), investigate the impact of aging and motor expertise on these components, and better understand the nervous system's adaptions to varying task demands. We utilized a rectified latent variable model (RLVM) to factorize motor modules with inhibitory components from EMG signals recorded from ten expert pianists when they played scales and pieces at different tempo-force combinations. We found that older participants showed a higher proportion of inhibitory components compared with the younger group. Senior experts had a higher proportion of inhibitory components on the left hand, and most inhibitory components became less negative with increased tempo or decreased force. Our results demonstrated that the inhibitory components in muscle synergies could be shaped by aging and expertise, and also took part in motor control for adapting to different conditions in complex tasks.
Ryanodine receptors (RyRs) form channels responsible for the release of Ca(2+) from the endoplasmic and sarcoplasmic reticulum. The SPRY2 domain in the skeletal muscle isoform (RyR1) has been ...proposed as a direct link with L-type calcium channels (CaV1.1), allowing for direct mechanical coupling between plasma membrane depolarization and Ca(2+) release. Here we present the crystal structures of the SPRY2 domain from RyR1 and RyR2 at 1.34-1.84 Å resolution. They form two antiparallel β sheets establishing a core, and four additional modules of which several are required for proper folding. A buried disease mutation, linked to hypertrophic cardiomyopathy and loss-of-function, induces local misfolding and strong destabilization. Isothermal titration calorimetry experiments negate the RyR1 SPRY2 domain as the major link with CaV1.1. Instead, docking into full-length RyR1 cryo-electron microscopy maps suggests that the SPRY2 domain forms a link between the N-terminal gating ring and the clamp region.
Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported ...to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor.
Abstract
Infections remain a common cause of lung nodules, masses, and cavities. Safe tissue sampling is required to establish a diagnosis, differentiate between malignant and infectious causes, and ...provide microbiological material for characterization and sensitivity analysis. Tissue samples could be obtained bronchoscopically, percutaneously, or through surgical biopsy. Among these, bronchoscopy is the safest by avoiding the complications of pleural and chest wall puncture including pneumothorax, pain, pleural contamination and empyema, and hemothorax. However, the diagnostic yield with conventional bronchoscopy for small, peripheral lesions is poor. Electromagnetic navigation bronchoscopy (ENB) is a technique where the bronchoscope and working channel are guided through the bronchial tree to accurately reach a peripheral lesion. It dramatically improves on the diagnostic yield of peripheral lesions especially of small lesions, and its role has developed beyond diagnosis to treatment enablement and to direct therapy. Its role in infection is less defined, but it has value especially in the diagnosis of fungal and mycobacterial infections and in cavitating lesions. This review will explore what electromagnetic navigation bronchoscopy is, its use in diagnosis and therapy, and its role in the management of pulmonary infections. The potential for local therapy delivery for infection is also discussed.
The setting of numeric instream objectives (effects-based criteria) and catchment limits for major agricultural Stressors, such as nutrients and fine sediment, is a promising policy instrument to ...prevent or reduce degradation of stream ecosystem health. We explored the suitability of assemblage thresholds, defined as a point at which a small increase in a Stressor will result in a disproportionally large change in assemblage structure relative to other points across the Stressor gradient, to inform instream nutrient and sediment objectives. Identification and comparison of thresholds for macroinvertebrate, periphyton, and bacterial assemblages aimed at making the setting of objectives more robust and may further provide a better understanding of the underlying mechanisms of nutrient and fine sediment effects. Gradient forest, a novel approach to assemblage threshold identification based on regression-tree-based random forest models for individual taxa, allowed inclusion of multiple predictors to strengthen the evidence of cause and effect between Stressors and multispecies responses. The most prominent macroinvertebrate and periphyton assemblage threshold across the nitrogen (N) gradient was located at very low levels and mainly attributed to declines of multiple taxa. This provided strong evidence for stream assemblages being significantly affected when N concentrations exceed reference conditions and for effects cascading through the ecosystem. The most prominent macroinvertebrate assemblage threshold across a gradient of suspended fine sediment was also located at very low levels and attributed to declines of multiple taxa. However, this threshold did not correspond with periphyton assemblage thresholds, suggesting that the sensitivity of macroinvertebrate assemblages is unrelated to sediment effects on periphyton assemblages. Overall, the spectrum of N concentrations and fine sediment levels within which these stream assemblages changed most dramatically were relatively narrow given the wide gradients tested. We conclude that assemblage thresholds can inform the setting of generic instream nutrient and sediment objectives for stream ecosystem health. For example, the most stringent objective for instream N concentration should be set at values similar to reference concentrations for full protection of sensitive taxa or overall stream biodiversity. To avoid severe degradation of stream biodiversity, the least stringent N objective should stay well below the point where significant turnover subsided.
Ryanodine Receptors (RyRs) are huge Ca2+ release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain ...in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain salt bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.
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► Crystal structures of a central RyR domain contain phosphorylation sites ► Eleven RyR1 disease mutations cluster on two opposite faces of the domain ► The RyR1 L2867G mutation causes a drastic destabilization ► In vitro phosphorylation identifies 5 PKA and 4 CaMKII targets
A surge in demand for single port VATS wedge resection may be on the horizon, especially if more evidence emerges supporting sublobar resection for small non-small cell lung cancer tumours. 1 Since ...2010, single-port (uniport) VATS has extended its application to major lung resections, and is gaining in popularity across the world.
Healthy ageing modifies neuromuscular control of human overground walking. Previous studies found that ageing changes gait biomechanics, but whether there is concurrent ageing-related modulation of ...neuromuscular control remains unclear. We analyzed gait kinematics and electromyographic signals (EMGs; 14 lower-limb and trunk muscles) collected at three speeds during overground walking in 11 healthy young adults (mean age of 23.4 years) and 11 healthy elderlies (67.2 years). Neuromuscular control was characterized by extracting muscle synergies from EMGs and the synergies of both groups were <inline-formula> <tex-math notation="LaTeX">{k} </tex-math></inline-formula>-means-clustered. The synergies of the two groups were grossly similar, but we observed numerous cluster- and muscle-specific differences between the age groups. At the population level, some hip-motion-related synergy clusters were more frequently identified in elderlies while others, more frequent in young adults. Such differences in synergy prevalence between the age groups are consistent with the finding that elderlies had a larger hip flexion range. For the synergies shared between both groups, the elderlies had higher inter-subject variability of the temporal activations than young adults. To further explore what synergy characteristics may be related to this inter-subject variability, we found that the inter-subject variance of temporal activations correlated negatively with the sparseness of the synergies in elderlies but not young adults during slow walking. Overall, our results suggest that as humans age, not only are the muscle synergies for walking fine-tuned in structure, but their temporal activation patterns are also more heterogeneous across individuals, possibly reflecting individual differences in prior sensorimotor experience or ageing-related changes in limb neuro-musculoskeletal properties.
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