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Blobby is a synaptic active zone assembly protein required for memory in Drosophila
AbstractAt presynaptic active zones (AZs), scaffold proteins are critical for coordinating synaptic vesicle release and forming essential nanoarchitectures. However, regulatory principles steering AZ scaffold assembly, function, and plasticity remain insufficiently understood. We here identify an additional Drosophila AZ protein, “Blobby”, essential for proper AZ nano-organization. Blobby biochemically associates with the ELKS family AZ scaffold protein Bruchpilot (BRP) and integrates into newly forming AZs. Loss of Blobby results in fewer AZs forming, ectopic AZ scaffold protein accumulations (“blobs”) and disrupts nanoscale architecture of the BRP-AZ scaffold. Functionally, blobby mutants show diminished evoked synaptic currents due to reduced synaptic vesicle release probability and fewer functional release sites. Blobby is also present in adult brain synapses, and post-developmental knockdown of Blobby in the mushroom body impairs olfactory aversive memory consolidation. Thus, our analysis identifies an additional layer of AZ regulation critical for developmental AZ assembly but also for AZ-mediated plasticity controlling behavior.
Distorting crack-front geometry for enhanced toughness by manipulating bioinspired heterogeneity
Association between the triglyceride-glucose index and its combined obesity indicators and the risk of hypertension in middle-aged and older Chinese adults: A nationwide cross-sectional study
Objective This study aimed to explore the association between the triglyceride-Glucose Index (TyG) and its combination with obesity indicators in relation to the risk of hypertension among middle-aged and elderly individuals in China. Methods A total of 9,248 participants aged 45 and above were selected from the 2015 China Health and Retirement Longitudinal Study. Data on basic demographics, behavioral habits, medical history, physical examination results, and blood indicators were collected. The TyG and its obesity-related indicators, including TyG-BMI, TyG-WC, and TyG-WHtR were analyzed. These indicators were categorized into four groups based on quartiles, and the prevalence of hypertension within each group was assessed. Logistic regression analysis was conducted to evaluate the association between different TyG indices and obesity-related indicators with the risk of hypertension. Additionally, a restricted cubic spline model was employed to investigate the dose-response relationship between the TyG index, its combined obesity indicators, and the risk of hypertension. The receiver operating characteristic curve was utilized to determine the optimal predictive index for diagnosis. Results This study included a total of 9,248 middle-aged and elderly individuals aged 45 and above, comprising 4,274 males (46.21%), with an average age of 61.38 ± 9.28 years. The prevalence of hypertension exhibited an increasing trend as the quartiles of TyG, TyG-BMI, TyG-WC, and TyG-WHtR rose. After fully adjusting for covariates, comparisons between the first quartile (Q1) and the fourth quartile (Q4) of TyG, TyG-BMI, TyG-WC, and TyG-WHtR revealed that all these metrics at Q4 level were associated with an increased prevalence of hypertension. The odds ratios were as follows: TyG: OR = 1.80 (95% CI: 1.48–2.19); TyG-BMI: OR = 5.09 (95% CI: 4.33–5.98); TyG-WC: OR = 3.96 (95% CI: 3.38–4.65); TyG-WHtR: OR = 3.91 (95% CI: 3.33–4.60). A linear correlation was observed between TyG and the risk of hypertension (P for non-linearity = 0.2267), while non-linear correlations were noted between TyG-BMI, TyG-WC, and TyG-WHtR with the risk of hypertension (P for non-linearity < 0.001). The receiver operating characteristic curve indicated that TyG-WC demonstrated the highest diagnostic performance for hypertension, with an area under the curve of 0.642 (95% CI: 0.631–0.654). Conclusion As the levels of TyG, TyG-BMI, TyG-WC, and TyG-WHtR increased, the risk of hypertension among middle-aged and elderly individuals aged 45 and above in my country rises significantly. Among them, TyG-WC can be a predictor of hypertension in middle-aged and elderly people.
Natural and anthropogenic factors controlling organic carbon storage in riverine wetlands along South Korea’s four rivers
Spatiotemporal evolution and attribution analysis of ecological quality in the alpine meadow region of Shangri-La based on natural-social dimensions
Modeling saturation exponent of underground hydrocarbon reservoirs using robust machine learning methods
Atomic-scale understanding of oxide growth and dissolution kinetics of Ni-Cr alloys
Ultra-low power-consumption OLEDs via phosphor-assisted thermally-activated-delayed-fluorescence-sensitized narrowband emission
Techno-structural and 3-D geometric morphometric analysis applied for investigating the variability of Holocene unifacial tools in tropical Central Brazil
During the transition from the Pleistocene to the Holocene and in the early Holocene period, hunter-gatherer communities across tropical South America deployed a range of technological strategies to adapt to diverse environmental conditions. This period witnessed a rich tapestry of technological practices, from enduring, widely disseminated tools to local and sporadically utilized technologies, shaping a multifaceted landscape of technological traditions. Lithic technology during this period was mainly marked by localized sourcing of raw materials, the use of multifunctional tools, a variety of projectile point designs, and the frequently utilization of unifacial shaping technology. In tropical Central Brazil, the Itaparica technocomplex, with unique unifacial lithic tools like limaces, is a pivotal innovation from the Late Pleistocene through the Holocene. However, the factors influencing their morphological and structural variability remain largely unexplored, obscuring our understanding of their ergonomics and their role as mediators between humans and tropical environments. This study hypothesizes that the variability observed within and among unifacial tools from the GO-Ni sites in Central Brazil is a result of a combination of factors, including raw material availability and functional and ergonomic requirements. To test this hypothesis, a study of 67 unifacial tools from this region was conducted, employing techno-structural analysis and 3D geometric morphometrics. This approach was designed to precisely quantify tool geometry and uncover their functional potentials. The analysis revealed significant variability within the techno-structural groups, often intersecting with typological classifications. These results indicate that despite their production attributes, unifacially shaped artifacts demonstrate considerable morpho-structural diversity. The study delineated nine distinct techno-structural groups, each suggesting potentially different functional organizations and deviating from conventional typologies. These results indicate that unifacially shaped artifacts, while embodying a novel technological paradigm of production, exhibit a broader spectrum of variation mainly due to different tool functions. The combined approach adopted in this research highlights on the cultural significance of unifacial tools within Paleoamerican technological systems. It suggests probable unique tool concepts specific to the study area, challenges existing classifications, and enriches our comprehension of early lithic technology in South America.
Simulation study on catalytic oxidation of low concentration mine gas in an oxidation device
Deep learning-based discovery of compounds for blood pressure lowering effects
Health risks from heavy metals in cosmetic products available in the online consumer market
Titanium nitride sensor for selective NO2 detection
Time-series single-cell transcriptomic profiling of luteal-phase endometrium uncovers dynamic characteristics and its dysregulation in recurrent implantation failures
Rifampicin and isoniazid resistance not promote fluoroquinolone resistance in Mycobacterium smegmatis
Background The emergence of drug-resistant Tuberculosis (TB) has made treatment challenging. Although fluoroquinolones (FQs) are used as key drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB), the problem of FQs resistance is becoming increasingly serious. Rifampicin (RIF) resistance is considered a risk factor for FQs resistance. The objective of this study was to investigate the impact of RIF and isoniazid (INH) resistance on the FQs resistance in vitro experiment. Methods FQs resistant strains were selected in vitro from RIF and/or INH resistant Mycobacterium smegmatis (M.sm). The sequencing of the gyrA gene, and the minimum inhibitory concentration (MIC) of FQs (ciprofloxacin, levofloxacin, moxifloxacin and gatifloxacin) were performed for FQs-resistant strains. Results A total of 222 FQs-resistant M.sm strains were selected, all of which had the gyrA mutation. Seven gyrA mutations were detected, with mutations at loci 90 and 94 being the most common. There were no differences in FQs resistance developed from RIF and/or INH resistant M.sm. There was a significant difference in the MIC of the gyrA mutant types to FQs. The highest resistance to FQs was observed in the Gly88Cys mutant strains. M.sm with the identical gyrA mutation showed the highest resistance to ciprofloxacin and relatively low resistance to gatifloxacin and moxifloxacin. Conclusions In this study, we found no evidence that RIF and/or INH resistance directly affects FQs resistance in M.sm in vitro experiments. Resistance profiles of different gryA mutations to the four FQs drugs were also presented. These findings provide a more comprehensive understanding of FQs resistance.