Regional Changes Research Articles

Parotid Gland Suspension Combined with Rhytidectomy to Recontour the Lower Face and Neck Enlargement Caused by Benign Parotid Hypertrophy.

Lower face and neck aging and facial shape changes are usually caused by soft tissue descent. During lower face and neck enlargement, parotid hypertrophy is an important influence factor of morphologic changes in the periauricular regions. Most plastic surgery techniques greatly improve the shape of the lower face and neck, but ignore the manipulation of the parotid gland. We aimed to resolve the lower face and neck enlargement caused by parotid hypertrophy. Thus, we performed parotid gland suspension combined with rhytidectomy to improve the lower face and neck contour. This retrospective study recruited 22 patients who underwent parotid gland suspension combined with rhytidectomy from 2012 to 2020. The evaluation of patient outcomes was performed by selecting items from the FACE-Q scale. Surgical procedures involved parotid gland exposure and parotid fascia suspension. Patient-perceived age appraisal indicated a younger appearance with follow-ups for approximately 3-10year after the surgery (mean ± standard deviation - 5.53 ± 3.67). Patients had a high satisfaction level for facial appearance (67.15 ± 16.84), lower face (74.69 ± 21.22), and contour of the parotid gland areas of the neck (65.76 ± 23.62). The lower face and neck contours were narrowed and tightened. The parotid gland area showed a remarkable improvement after surgery. Parotid gland suspension combined with rhytidectomy obtained an outstanding improvement. This method can achieve a better lower face and neck contour, especially in patients with benign parotid hypertrophy or lower face and neck enlargement in periauricular regions. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Environmental changes and human impacts over the past 1200 years: Evidence from high-resolution pollen records from peat in the Yunnan-Guizhou Plateau, Southwest China

Over the past millennium, the understanding of vegetation and climate changes in mountainous regions, driven by both natural and anthropogenic forces, remains unclear. In this study, we provide a high-resolution vegetation record spanning the past 1200 years from a subalpine peatland in the Niangniang Mountains, southwestern China. By analyzing pollen, charcoal, and loss-on-ignition from the peat sediment, we elucidate the interactions between vegetation, fire, and human impact. Our findings reveal that before 1150 CE, the mountains were covered with dense broadleaf forests and experienced minimal human activity. Natural forcings, primarily climatic conditions, drove vegetation succession and forest fires. After 1150 CE, the Human Influence Index (HII) increased sharply, coinciding with a rise in cereal-type pollen. Significant agricultural activities in the southwestern mountainous regions of China began after 1150 CE, which is later than those in the low-altitude lake basins of southwestern China. During the Medieval Climate Anomaly (MCA, 836–1400 CE), the Niangniang Mountains were characterized by warm and humid climatic conditions, a stable forested landscape, and a high peat carbon accumulation rate. Although human activities increased markedly during this period, the arbors did not undergo notable changes, and climate forcings continued to have a greater impact on vegetation than anthropogenic forcings. During the Little Ice Age (LIA, 1400–1900 CE), the regional vegetation landscape transitioned from dense forests to open grasslands as climate conditions became cold and dry, reducing peat carbon accumulation rate. This period also saw increased forest fires and significant human-driven deforestation, with anthropogenic forcings becoming dominant. After 1900 CE, vegetation changes were increasingly influenced by government policies. Comparison with major climate forcings and spectrum analysis have shown that variations in monsoon intensity, regulated by solar and volcanic activity, have influenced the climate and peat depositional environment in the Niangniang Mountains. Our research offers meaningful insights into forest conservation in the mountainous regions of the Yunnan-Guizhou Plateau.

Subject-based assessment of large-scale integration dynamics in epileptic brain networks: insights from the intrinsic ignition framework.

This study examined the dynamic properties of brain regions involved in the genesis and spread of seizures in 10 individuals diagnosed with pharmacoresistant focal epilepsy. The patients and 30 healthy controls underwent resting-state functional magnetic resonance imaging scans and the brain's functional network dynamics were analyzed using the intrinsic ignition framework. Comparative statistical analyses examined the differences in the integration and metastability measures in both groups in the whole brain and specific local brain regions. Invasive electroencephalography evaluations validated the findings of significant global and regional changes in the patient's brain network dynamics. There was a marked increase in global integration and metastability across the brain, reflecting substantial alterations in the overall connectivity and flexibility of the functional networks. Specific brain regions exhibited paradoxical dynamics within the seizure onset zone, with decreased intrinsic ignition and increased metastability. Increased intrinsic ignition was observed in remote brain regions, suggesting a reorganization of the brain network hubs and potential pathways for seizure propagation. Using the intrinsic ignition framework provided insights into dynamic alterations in the brain networks of patients with epilepsy. These have increased our understanding of the mechanisms underlying epileptic seizures and may guide the development of diagnostic biomarkers and targeted therapeutic interventions.

Structural basis of α-latrotoxin transition to a cation-selective pore

The potent neurotoxic venom of the black widow spider contains a cocktail of seven phylum-specific latrotoxins (LTXs), but only one, α-LTX, targets vertebrates. This 130 kDa toxin binds to receptors at presynaptic nerve terminals and triggers a massive release of neurotransmitters. It is widely accepted that LTXs tetramerize and insert into the presynaptic membrane, thereby forming Ca2+-conductive pores, but the underlying mechanism remains poorly understood. LTXs are homologous and consist of an N-terminal region with three distinct domains, along with a C-terminal domain containing up to 22 consecutive ankyrin repeats. Here we report cryoEM structures of the vertebrate-specific α-LTX tetramer in its prepore and pore state. Our structures, in combination with AlphaFold2-based structural modeling and molecular dynamics simulations, reveal dramatic conformational changes in the N-terminal region of the complex. Four distinct helical bundles rearrange and together form a highly stable, 15 nm long, cation-impermeable coiled-coil stalk. This stalk, in turn, positions an N-terminal pair of helices within the membrane, thereby enabling the assembly of a cation-permeable channel. Taken together, these data give insight into a unique mechanism for membrane insertion and channel formation, characteristic of the LTX family, and provide the necessary framework for advancing novel therapeutics and biotechnological applications.

Cholinergic Basal Forebrain Integrity and Cognition in Parkinson's Disease: A Reappraisal of Magnetic Resonance Imaging Evidence.

Cognitive impairment is a well-recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost-effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1- and diffusion-weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross-sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Climate change impacts on hydrology and water resources in East Africa considering CMIP3, CMIP5, and CMIP6

Climate change impacts on the hydrology and water resources in East Africa require proper planning of regional adaptation measures. Past studies on the subject matter tended to focus on catchment instead of regional scale. To support actionable policy regarding regional planning of water resources management, this paper reviewed studies conducted in East Africa based on CMIP3, CMIP5, and CMIP6. Compared to the historical condition, temperature of East Africa over the mid- to late 21st century will increase by varying extents over the range 0.17–7°C with about 2.6°C on average. Future precipitation over East Africa will increase by 8.5% on average. Changes in discharge based on CMIP3, CMIP5, and CMIP6 will vary from −25.3 to +60.5%, −42.5 to 129%, and −23.4 to 69%, respectively. Ensemble means of the changes in discharge across the study area based on CMIP3, CMIP5, and CMIP6 will be by 25.2, 19.2, and 19.1%, respectively. Future peak river discharge across East Africa will increase by 8% on average. These results are important for planning regional climate change adaptation across East Africa. To support local or catchment adaptation, results of climate change impacts of temperature, precipitation and discharge of about 50 catchments across East Africa can be found summarized in this review paper. It is recommended that both regional and local policies or approaches should be considered for climate change adaptation to ensure a balanced, effective and sustainable framework for climate resilience in support of measures for tackling broad and specific needs cohesively.

Utilizing sentinel-1 SAR for delineation of narrow intertidal zones and habitat types in Svalbard

ABSTRACT Intertidal habitats have been significantly impacted by accelerated climate change in Arctic regions over the past few decades, particularly in Svalbard. New substrates are exposed as glacier retreat, making them accessible to benthic vegetation. Remote sensing techniques, including Sentinel-1 synthetic aperture radar (SAR) imagery and drones, provide the opportunity to acquire and study submerged habitats when they are exposed to the atmosphere during low tide. St. Jonsfjorden, Eidembukta, and Trygghamna were the three bays in Svalbard where this research was conducted. We used SAR imagery to determine relatively narrow intertidal zones, acknowledging that the spatial resolution of Sentinel-1 SAR imagery is limited to 10 m. Although this limitation posed a challenge when attempting to classify these narrow intertidal zones due to the coarse resolution of the data, we categorized the intertidal zones into three habitat types: vegetated rock, rock, and mixed sediment. The accuracy of this classification was consistently reliable, with a range of 64–78%. The classification results indicated that 25% of the total intertidal zone is composed of substrates that are suitable for macroalgae growth. It is remarkable that 80% of this substrate is vegetated. Additionally, this investigation demonstrated that vegetation is significantly absent in areas adjacent to glaciers. The magnitude of the glacier appears to influence the extent of this vegetation-free zone.

Assessment of the spatial-temporal impact of the Longhai Railway transportation corridor on land cover changes and landscape patterns

IntroductionTransportation corridors, as special economic corridors, have a greater impact on land cover and landscape pattern changes.MethodsTherefore, 10 buffer zones were established at 1 km intervals on both sides of the Longhai Railway as the centerline to trace the impact of the railroad corridor on the land use change and regional landscape pattern change of the cities along the line from 1985 to 2020.ResultThe results show that: (1) The land cover changes along the railroad corridor during the 35 years are mainly characterized by the conversion between cropland, grassland, and construction land. Compared with 1985, in 2020, the construction land increased by 161.96%, the grassland area decreased by 11.83%, and the cropland area decreased by 15.83%. (2) The fragmentation of land patches and vegetation coverage is negatively and positively correlated with the buffer zone distance, respectively. In the same year, the comprehensive land-use dynamic degree is smaller as it is further away from the railway. The nighttime light index in the buffer zone is significantly correlated with the land aggregation index and average patch area, and the closer to the railroad, the higher the land aggregation index of construction land. (3) In terms of zoning, the intensity of land cover and landscape pattern changes in the eastern section is higher than that in the western section, with a higher degree of land fragmentation and more agglomeration of construction land, and the transportation corridor has a greater impact on the change of integrated land use motives in this region. The results of the study can provide a scientific basis for optimising the spatial pattern of land and improving the ecological environment in the construction of cross-regional transport corridors.

Palygorskite Mineralization in the Induan Sediments of the Moscow Syneclise as an Effect of Regional and Global Paleogeographic Changes at the Permian–Triassic Boundary

Palygorskite Mineralization in the Induan Sediments of the Moscow Syneclise as an Effect of Regional and Global Paleogeographic Changes at the Permian–Triassic Boundary

Directly mining and identifying a cellobiose 2-epimerase with isomerization activity by phylogenetic analysis

The isomerization activity of cellobiose 2-epimerase (CE) offers the potential for conversion of lactose into lactulose. However, the isomerization activity of reported CEs is low and identifying CE with isomerization activity is still challenging and time consuming. Here, we developed a strategy for directly mining CE with isomerization activity through phylogeny analysis and a novel CE from Dictyoglomus sp (XVH1-CE) was identified which has isomerization activity as expected. The isomerization activity of XVH1-CE could reach 4.3 U mg−1 at 85 °C and pH 7.5, which is highest among all reported CEs. Moreover, Molecular Dynamics (MD) simulation further revealed that XVH1-CE presents a significant region change influenced by lactulose, and statistic special binding pose seen as important for lactulose catalysis performed a high frequency. Our research demonstrated enzyme-mining strategy based on phylogeny analysis can offers new opportunities for the development of lactulose production by CE.

To What Extent Does Discounting ‘Hot’ Climate Models Improve the Predictive Skill of Climate Model Ensembles?

AbstractIt depends. The Intergovernmental Panel on Climate Change's (IPCC) Assessment Report Six (AR6) took a step toward ending so‐called ‘model democracy’ by discounting climate models that are too warm over the historical period (i.e., models that ‘run hot’) when making projections of global temperature change. However, the IPCC did not address whether this procedure is reliable for other quantities. Here, we explore the implications of weighting climate models according to their skill in reproducing historical global‐mean surface temperature using three other climate variables of interest: global average precipitation change, regional average temperature change, and regional average precipitation change. We find that the temperature‐based weighting scheme leads to an improved prediction of global average precipitation, though we show that this prediction could be overconfident. On regional scales, we find a heterogeneous pattern of error reduction in future regional precipitation. This stands in sharp contrast with the broad regional pattern of error reduction in future temperature projections, though we do find regions where error is not significantly reduced. Our results demonstrate that practitioners using weighted climate model ensembles for climate projections must take care when weighting by temperature alone, lest they produce unreliable climate projections that result from an inappropriate weighting procedure.

Morphological characteristics of CT blend sign predict hematoma expansion and outcomes in intracerebral hemorrhage in elderly patients.

The underlying basis of the blend sign on brain computed tomography (CT) in patients with intracerebral hemorrhage (ICH) is unclear. Few studies have examined the morphological alterations in the CT blend sign in ICH. Therefore, we assessed changes in the CT blend sign and their association with hematoma expansion (HE) and adverse outcomes in ICH patients. We recorded the clinical and radiographic parameters of patients with ICH and blend sign on brain CT. The patients were categorized into two groups, with changes in the relatively hypoattenuating region of the blend sign (CHB group) and with no changes in the relatively hypoattenuating region of the blend sign (NHB groups). We performed univariate and multivariate logistic regression analyses to examine the correlations between CHB and HE and poor outcomes. Furthermore, receiver operating characteristic curve analysis was used to confirm the predictive power of CHB. In total, 183 patients were included in the study, of whom 74 (40.4%) demonstrated changes in the hypoattenuating region of the blend sign, whereas 109 (59.6%) did not. Compared with the NHB group, patients in the CHB group exhibited significantly higher levels of HE and adverse outcomes. After adjustment for confounding factors, CHB was independently associated with HE (odds ratio, 19.401 [95% CI, 7.217-52.163]; p < 0.001) and poor 3-month outcomes (odds ratio, 2.638 [95% CI, 1.391-5.003]; p = 0.003) in the multivariate analysis. The sensitivity, specificity, positive predictive value, and negative predictive value of CHB for predicting HE were 0.877, 0.768, 0.791, and 0.862, respectively, whereas these values for predicting poor outcomes were 0.789, 0.641, 0.688, and 0.752, respectively. Changes of a hypoattenuating region within the blend sign have good predictive accuracy for HE and short-term adverse outcomes in elderly patients with ICH. ClinicalTrials.gov, NCT05548530.

Analysing Thermal Land Surface Characteristics and Urban Expansion in Kenitra City, Morocco, using Remote Sensing and GIS

Abstract This research investigates how land use and cover the affect land surface temperature in Kenitra. It employs Geographic Information System techniques and remote sensing methods to monitor and control surface temperature changes. The present study integrates remote sensing and geographic information system to process satellite images. Furthermore, it focuses, also, on analyzing land surface temperature and its correlation with land cover changes over three time periods (1989, 2000, 2020) using landsat satellite data. Thus, supervised classification is employed to map these changes and derive urban heat islands from thermal band data. This study provides a comprehensive evaluation of the relationship between land use and land surface temperature. It utilizese a landscape dynamics assessment based on multi-source and multi-sensor remote sensing technologies. Specifically, the study uses landsat satellite data (TM for 1989 and OLI-8 for 2002 and 2020) to assess the effects of land use and land cover changes on land surface temperature distribution in the Kenitra city. Spatial and statistical analyses are performed by comparing maps from remotely sensed data generated using geographic information system. Therefore, these analyses reveal various changes in the kenitra region between 1989 and 2020. The primary changes observed include an increase in built-up areas and bare ground with a decrease alongside in natural areas (vegetation, etc.). The average temperatures in 1989, 2002, and 2020 were 29°C, 31.05°C, and 32°C, respectively. The obtained results are valuable for planning and managing climate scientists, land-use planners, and researchers focusing on sustainable urbanization areas. The study’s findings will assist urban planners and policymakers in adopting appropriate measures for sustainable planning in the city to mitigate the adverse effects of land surface temperature.

Evolution: A kit for fooling your rivals

Some male swordtail fish mimic female 'pregnancy spots' to reduce aggression from rival males and gain a fitness advantage. This sexual mimicry is linked to evolutionary changes in the regulatory region of the kit-liganda gene that controls melanocyte development.

Future Change in the Contribution of Riming and Depositional Growth to the Surface Solid Precipitation in Hokkaido, Japan

Abstract This study examined future changes in the microphysical properties of surface solid precipitation over Hokkaido, Japan. A process-tracking model that predicts the mass of the hydrometeors generated by each cloud microphysical process was implemented in a meteorological model. This implementation aimed to analyze the mass fraction of hydrometeors resulting from depositional growth and the riming process to the total mass of surface solid precipitation. Results from pseudo–global warming experiments suggest two potential future changes in the characteristics of surface solid precipitation over Hokkaido. First, the rimed particles are expected to increase and be dominant over the west and northwest coast of Hokkaido, where heavy snowfall occurs primarily due to the lake effect. Second, the mass fraction from depositional growth under relatively higher temperatures is expected to increase. This increase is anticipated to be dominant over the eastern part and mountainous area of Hokkaido. Additionally, the fraction of liquid precipitation to total precipitation is expected to increase in the future. These results suggest that the microphysical properties of solid precipitation in Hokkaido are expected to be similar to those observed in the current climate over Hokuriku, the central part of Japan even in warmer climate conditions. Significance Statement This study examines potential future changes in the growth processes contributing to surface precipitation particles in Hokkaido, Japan. The surface solid precipitation particles in the western and eastern regions of Hokkaido are mainly generated through depositional growth that occurs within the temperature ranges −36° to −20°C and −20° to −10°C, respectively. A future shift is anticipated, with riming becoming the primary process. This shift suggests that snowfall particles will be heavier than those in the current climate, which would increase the snow-removal workload. The change in precipitation characteristics could influence adaptation and mitigation strategies for climate change in cold regions.

Investigating climatic drivers of snow phenology by considering key-substage heterogeneity

Investigating the main climatic drivers responsible for changes in snow cover phenology (SCP) is crucial for making scientific countermeasures to ensure water resources security in global mountainous regions. However, most studies have explored drivers of SCP changes using a fixed substage division scheme and correlation analysis (referred to as the traditional method), potentially limiting reliability and accuracy in mountainous areas with complex terrain and climate. Here, a novel method is developed to efficiently identify main climatic drivers of SCP changes. This method employs a flexible scheme to account for the spatial heterogeneity of the dominant sub-period (the sub-period with the major climatic effect) in combination with regression analysis. Using the arid region of China as a case study, the new method was applied to three SCP parameters including snow cover days, snow start date, and snow end date, based on a seamless snow cover dataset from 2002 to 2019. The method’s effectiveness was evaluated by comparing it with the traditional method. The results indicate significant spatial heterogeneity in the dominant sub-period(s), closely associated with local temperature and elevation. The traditional method failed to accurately identify the main drivers of SCP changes, as evidenced by sub-region and elevation zone analyses showing adjusted coefficient of determination (R2) of < 0.5 in most cases. This inadequacy is attributed to its fixed and inappropriate scheme of substage division. In contrast, the new method, with its flexible scheme, achieved much higher adjusted R2 values (mostly > 0.5) and exhibited better performances in predicting SCP changes. Thanks to the new method, climatic causes of SCP changes were successfully identified in 12 hotspots (regions with significant SCP changes), all with adjusted R2 > 0.5. The climatic causes were found to vary significantly across different hotspot regions and SCP parameters. The proposed method holds significant potential to enhance the reliability of analyses concerning main climatic drivers of SCP changes in mountainous regions globally.

Future Global River Ice in CMIP6 Models under Climate Change

Abstract River ice changes due to climate change significantly impact river hydrology, economies, and societies. This study employed the CMIP6 data and a river ice model to predict global river ice changes in response to climate change. Results indicate significant declines in global river ice due to global warming. With each 1°C increase in surface air temperature (SAT) in the future, river ice extent of ice-affected rivers decrease by 2.11 percentage points, and ice duration shorten by 8.4 days. Under the shared socioeconomic pathways 2-4.5 (SSP2-4.5) scenario, the long-term mean SAT is 1.2°–2.5°C higher than in the near term. This leads to a 1.9–4.4-percentage-point decrease in global river ice extent, a 6.8–15.1-day decrease in river ice duration, and ice-free rivers increasing by up to 4.02%. The SSP5-8.5 scenario predicts a warmer long-term mean SAT, leading to greater reductions in river ice. Geographically, river ice loss is most notable in North America, Europe, Siberia, and the Tibetan Plateau (TIB), particularly in peninsular, coastal, and mountainous regions due to the combined effects of initial temperatures and temperature increases. Overall, the eastern Europe (EEU) shows the greatest loss of river ice on average. Monthly analyses show the most substantial decreases from October to June, indicating pronounced seasonal variability. This study provides valuable insights for addressing challenges related to river ice changes in high-latitude and high-elevation regions. Significance Statement River ice has a significant impact on various aspects, including hydrology, ecology, and the economy. The ongoing global warming phenomenon has resulted in a decline in river ice. This ice acts as a barrier, affecting river gas exchange and influencing the metabolism of the river, which is crucial for regulating greenhouse gas (GHG) emissions. The primary objective of this research is to examine the response of river ice to future climate change. The outcomes of this study will play a role in estimating future GHG emissions and understanding river metabolism, as well as providing a valuable reference for tackling emerging challenges in resource acquisition in high-latitude and high-altitude regions.

Isotopic seasonality of fluvial-derived greenhouse gases implies active layer deepening

Abstract Climate change in the northern circumpolar regions is rapidly thawing organic-rich permafrost soils, releasing substantial dissolved CO2 and CH4 into fluvial systems. This mobilization impacts local ecosystems and global climate feedback loops, playing a crucial role in the Arctic carbon cycle. Here, we analyze the stable carbon (δ13C) and radiocarbon (F14C) isotopic composition of dissolved CO2 and CH4 in the Sagavanirktok and Kuparuk River watersheds on the North Slope, Alaska. By examining spatial and seasonal variations in these isotopic signatures, we identify patterns of carbon release and transport along the river continuum. We find consistent CO2 isotopic signatures across the fluvial continuum, reflecting a mixture of geogenic and biogenic sources integrated throughout the watershed. Bayesian mixing models further demonstrate a systematic depletion in 13C and 14C signatures of dissolved CO2 sources from spring to fall, indicating increasing contributions of aged carbon as the active layer deepens seasonally. This seasonal deepening allows percolating groundwater to access deeper, older soil horizons, transporting CO2 produced by aerobic and anaerobic soil respiration to streams and rivers. In contrast, we observe no clear relationships between the 13C and 14C compositions of dissolved CH4 and landscape properties. Given the reduced solubility of CH4, which facilitates outgassing and limits its transport in aquatic systems, the isotopic signatures are likely indicative of localized contributions from streambeds, adjacent water saturated soils, and lake outflows. Our study demonstrates that dissolved greenhouse gases are sensitive indicators of the release of old carbon from thawing permafrost and serve as early warning signals for permafrost carbon feedback. It establishes a crucial baseline for understanding their role in regional carbon cycling and Arctic environmental change.&amp;#xD;

The mechanism of allosteric activation of SYK kinase derived from multiple phospho-ITAM-bound structures.

Spleen tyrosine kinase (SYK) is central to adaptive and innate immune signaling. It features a regulatory region containing tandem SH2 (tSH2) domains separated by a helical "hinge" segment keeping SYK inactive by associating with the kinase domain. SYK activation is triggered when the tSH2 domains bind to a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) found on receptor tails. Past mutational studies have indicated that ITAM binding disrupts the hinge-kinase interaction, leading to SYK phosphorylation and activation. However, the mechanism of this process is unclear, as the ITAM interaction occurs far from the hinge region. We have determined crystal structures of three phospho-ITAMs in complex with the tSH2 domains, revealing a highly conserved binding mechanism. These structures, together with mutational studies and biophysical analyses, reveal that phospho-ITAM binding restricts SH2 domain movement and causes allosteric changes in the hinge region. These changes are not compatible with the association of the kinase domain, leading to kinase activation.

Causal influences of testosterone on brain structure change rate: A sex-stratified Mendelian randomization study.

The impact of testosterone levels on changes in brain structure has been reported. However, it is still unclear which specific brain region could be affected. This study approached Mendelian randomization method to reveal the causal relationship between testosterone levels and the rate of longitudinal structural changes in the brain. The testosterone-related GWAS data were determined from 425,097 European participants. The GWAS data on the rate of longitudinal structural changes in the brain came from the ENIGMA consortium, which included 15,640 all-age participants from 40 longitudinal cohorts. The inverse variance weighted was considered as the main estimate, MR Egger and weighted median methods were used to supplement IVW. A positive correlation was found between total testosterone levels and bioavailable testosterone levels in women and age-independent longitudinal changes in cerebral WM and surface area. The sex hormone-binding globulin levels were found a negative correlation with age-dependent longitudinal structural changes of cortical GM in men. Additionally, we also found that the bioavailable testosterone level in males was negatively associated with the quadratic age-dependent longitudinal change rate in the globus pallidum. We also found estradiol levels and sex hormone-binding globulin levels were negatively associated with the quadratic age-dependent longitudinal change rate of total brain in men. Moreover, we found a positive correlation between total testosterone levels and linear age-dependent longitudinal changes in the hippocampus in both males and females. The testosterone levels in different genders may have varying degrees of causal effects on the structural changes of brain regions. These findings provide evidence for the influence of the brain glandular axis on brain structure, particularly during female brain development.