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Membrane protein Bcsdr2 mediates biofilm integrity, hyphal growth and virulence of Botrytis cinerea.Applied Microbiology and Biotechnology Jun 2024Grey mould caused by Botrytis cinerea is a devastating disease responsible for large losses to agricultural production, and B. cinerea is a necrotrophic model fungal...
Grey mould caused by Botrytis cinerea is a devastating disease responsible for large losses to agricultural production, and B. cinerea is a necrotrophic model fungal plant pathogen. Membrane proteins are important targets of fungicides and hotspots in the research and development of fungicide products. Wuyiencin affects the permeability and pathogenicity of B. cinerea, parallel reaction monitoring revealed the association of membrane protein Bcsdr2, and the bacteriostatic mechanism of wuyiencin was elucidated. In the present work, we generated and characterised ΔBcsdr2 deletion and complemented mutant B. cinerea strains. The ΔBcsdr2 deletion mutants exhibited biofilm loss and dissolution, and their functional activity was illustrated by reduced necrotic colonisation on strawberry and grape fruits. Targeted deletion of Bcsdr2 also blocked several phenotypic defects in aspects of mycelial growth, conidiation and virulence. All phenotypic defects were restored by targeted gene complementation. The roles of Bcsdr2 in biofilms and pathogenicity were also supported by quantitative real-time RT-PCR results showing that phosphatidylserine decarboxylase synthesis gene Bcpsd and chitin synthase gene BcCHSV II were downregulated in the early stages of infection for the ΔBcsdr2 strain. The results suggest that Bcsdr2 plays important roles in regulating various cellular processes in B. cinerea. KEY POINTS: • The mechanism of wuyiencin inhibits B. cinerea is closely associated with membrane proteins. • Wuyiencin can downregulate the expression of the membrane protein Bcsdr2 in B. cinerea. • Bcsdr2 is involved in regulating B. cinerea virulence, growth and development.
Topics: Botrytis; Biofilms; Virulence; Hyphae; Plant Diseases; Fragaria; Fungal Proteins; Membrane Proteins; Vitis; Spores, Fungal; Gene Deletion
PubMed: 38940906
DOI: 10.1007/s00253-024-13238-8 -
Diabetes Care Jun 2024Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information...
OBJECTIVE
Women with a history of gestational diabetes mellitus (GDM) are at increased risk of developing type 2 diabetes (T2D). It remains unclear whether genetic information improves prediction of incident T2D in these women.
RESEARCH DESIGN AND METHODS
Using five independent cohorts representing four different ancestries (n = 1,895), we investigated whether a genome-wide T2D polygenic risk score (PRS) is associated with increased risk of incident T2D. We also calculated the area under the receiver operating characteristics curve (AUROC) and continuous net reclassification improvement (NRI) following the incorporation of T2D PRS into clinical risk models to assess the diagnostic utility.
RESULTS
Among 1,895 women with previous history of GDM, 363 (19.2%) developed T2D in a range of 2 to 30 years. T2D PRS was higher in those who developed T2D (-0.08 vs. 0.31, P = 2.3 × 10-11) and was associated with an increased risk of incident T2D (odds ratio 1.52 per 1-SD increase, 95% CI 1.05-2.21, P = 0.03). In a model that includes age, family history of diabetes, systolic blood pressure, and BMI, the incorporation of PRS led to an increase in AUROC for T2D from 0.71 to 0.74 and an intermediate improvement of NRI (0.32, 95% CI 0.15-0.49, P = 3.0 × 10-4). Although there was variation, a similar trend was observed across study cohorts.
CONCLUSIONS
In cohorts of GDM women with diverse ancestry, T2D PRS was significantly associated with future development of T2D. A significant but small improvement was observed in AUROC when T2D PRS was integrated into clinical risk models to predict incident T2D.
PubMed: 38940851
DOI: 10.2337/dc24-0022 -
Parasitology Research Jun 2024As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and... (Review)
Review
As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.
Topics: Animals; Molluscacides; Snails; Glucose; Fresh Water
PubMed: 38940835
DOI: 10.1007/s00436-024-08274-2 -
The Journal of Experimental Biology Jun 2024Predictive models of ectotherm responses to environmental change often rely on thermal performance data from the literature. For insects, the majority of these data...
Predictive models of ectotherm responses to environmental change often rely on thermal performance data from the literature. For insects, the majority of these data focus on two traits, development rate and thermal tolerance limits. Data are also often limited to the adult stage. Consequently, predictions based on these data generally ignore other measures of thermal performance and do not account for the role of ontogenetic variation in thermal physiology across the complex insect life cycle. Theoretical syntheses for predicting metabolic rate also make similar assumptions despite the strong influence of body size as well as temperature on metabolic rate. The aim of this study was to understand the influence of ontogenetic variation on ectotherm physiology and its potential impact on predictive modeling. To do this we examined metabolic rate-temperature (MR-T) relationships across the larval stage in a laboratory strain of the Spongy moth (Lymantria dispar dispar). Routine metabolic rates (RMR) of larvae were assayed at eight temperatures across the first five instars of the larval stage. After accounting for differences in body mass, larval instars showed significant variation in MR-T. Both the temperature sensitivity and allometry of RMR increased and peaked during the third instar, then declined in the fourth and fifth instar. Generally, these results show that insect thermal physiology does not remain static during larval ontogeny and suggest that ontogenetic variation should be an important consideration when modeling thermal performance.
PubMed: 38940758
DOI: 10.1242/jeb.247912 -
Cancer Biology & Medicine Jun 2024Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. This cancer is determined by multiple (epi)genetic and environmental factors; can occur at... (Review)
Review
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. This cancer is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.
PubMed: 38940675
DOI: 10.20892/j.issn.2095-3941.2024.0124 -
Alzheimer's & Dementia : the Journal of... Jun 2024Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is... (Review)
Review
Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed.
PubMed: 38940631
DOI: 10.1002/alz.14057 -
Small (Weinheim An Der Bergstrasse,... Jun 2024For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more...
For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more comprehensive analytical techniques always rely on expensive and bulky instruments and large laboratories. Here, a fully integrated and high-throughput microfluidic system is proposed for ultra-multiple point-of-care immunoassay, termed Dac system. Specifically, the Dac system only requires a handheld portable device to automatically recycle repetitive multi-step reactions including on-demand liquid releasing, dispensing, metering, collecting, oscillatory mixing, and discharging. The Dac system performs high-precision enzyme-linked immunosorbent assays for up to 17 samples or targets simultaneously on a single chip. Furthermore, reagent consumption is only 2% compared to conventional ELISA, and microbubble-accelerated reactions shorten the assay time by more than half. As a proof of concept, the multiplexed detections are achieved by detecting at least four infection targets for two samples simultaneously on a singular chip. Furthermore, the barcode-based multi-target results can rapidly distinguish between five similar cases, allowing for accurate therapeutic interventions. Compared to bulky clinical instruments, the accuracy of clinical inflammation classification is 92.38% (n = 105), with a quantitative correlation coefficient of R = 0.9838, while the clinical specificity is 100% and the sensitivity is 98.93%.
PubMed: 38940626
DOI: 10.1002/smll.202401848 -
Journal of Integrative Plant Biology Jun 2024Tiller angle is a key agricultural trait that establishes plant architecture, which in turn strongly affects grain yield by influencing planting density in rice. The...
Tiller angle is a key agricultural trait that establishes plant architecture, which in turn strongly affects grain yield by influencing planting density in rice. The shoot gravity response plays a crucial role in the regulation of tiller angle in rice, but the underlying molecular mechanism is largely unknown. Here, we report the identification of the BIG TILLER ANGLE2 (BTA2), which regulates tiller angle by controlling the shoot gravity response in rice. Loss-of-function mutation of BTA2 dramatically reduced auxin content and affected auxin distribution in rice shoot base, leading to impaired gravitropism and therefore a big tiller angle. BTA2 interacted with AUXIN RESPONSE FACTOR7 (ARF7) to modulate rice tiller angle through the gravity signaling pathway. The BTA2 protein was highly conserved during evolution. Sequence variation in the BTA2 promoter of indica cultivars harboring a less expressed BTA2 allele caused lower BTA2 expression in shoot base and thus wide tiller angle during rice domestication. Overexpression of BTA2 significantly increased grain yield in the elite rice cultivar Huanghuazhan under appropriate dense planting conditions. Our findings thus uncovered the BTA2-ARF7 module that regulates tiller angle by mediating the shoot gravity response. Our work offers a target for genetic manipulation of plant architecture and valuable information for crop improvement by producing the ideal plant type.
PubMed: 38940609
DOI: 10.1111/jipb.13726 -
The Journal of Craniofacial Surgery Jun 2024The pathogenesis of craniosynostosis, characterized by the premature fusion of calvarial sutures, is multifaceted and often the result of an amalgamation of contributing...
The pathogenesis of craniosynostosis, characterized by the premature fusion of calvarial sutures, is multifaceted and often the result of an amalgamation of contributing factors. The current study seeks examine the possible contributors to craniosynostosis development and its surgical trends over time. A multicenter/national retrospective cohort study was conducted of patients who underwent surgical repair of craniosynostosis (n=11,279) between 2012 and 2021 identified in the American College of Surgeons National Surgical Quality Improvement Program Pediatric Data File. Main outcome measures included risk factors and trends relating to surgical repair of craniosynostosis. Nationwide reports of craniosynostosis in the NSQIP-P database have increased between 2012 and 2021 by 195%. The prevalence of craniosynostosis per overall cases has remained between 1.0% and 1.3%. There were predominantly more White male patients in the craniosynostosis cohort (P<0.001). Craniosynostosis patients had significantly greater birth weights, gestational ages, and were less likely to be premature (P<0.05). Linear regression demonstrated that operative time, anesthesia time, and length of stay significantly decreased over the study period (P<0.001). This national data analysis highlights trends in craniosynostosis repair indicating potential improvements in safety and patient outcomes over time. While these findings offer insights for health care professionals, caution is warranted in extrapolating beyond the data's scope. Future research should focus on diverse patient populations, compare outcomes across institutions, and employ prospective study designs to enhance the evidence base for craniosynostosis management. These efforts will help refine diagnostic and treatment strategies, potentially leading to better outcomes for patients.
PubMed: 38940557
DOI: 10.1097/SCS.0000000000010434 -
The Journal of Craniofacial Surgery Jun 2024Deformational plagiocephaly (DP) can be classified into 5 severity types using the Argenta scale (AS). Patients with type III or higher require referral to craniofacial...
INTRODUCTION
Deformational plagiocephaly (DP) can be classified into 5 severity types using the Argenta scale (AS). Patients with type III or higher require referral to craniofacial surgery for management. Primary care pediatricians (PCPs) are often the first to encounter patients with DP, but current screening methods are subjective, increasing the risk of bias, especially for clinicians with little exposure to this population. The authors propose the use of artificial intelligence (AI) to classify patients with DP using the AS and to make recommendations for referral to craniofacial surgery.
METHODS
Vertex photographs were obtained for patients diagnosed with unilateral DP from 2019 to 2020. Using the photographs, an AI program was created to characterize the head contour of these infants into 3 groups based on the AS. The program was trained using photographs from patients whose DP severity was confirmed clinically by craniofacial surgeons. To assess the accuracy of the software, the AS predicted by the program was compared with the clinical diagnosis.
RESULTS
Nineteen patients were assessed by the AI software. All 3 patients with type I DP were correctly classified by the program (100%). In addition, 4 patients with type II were correctly identified (67%), and 7 were correctly classified as type III or greater (70%).
CONCLUSIONS
Using vertex photographs and AI, the authors were able to objectively classify patients with DP based on the AS. If converted into a smartphone application, the program could be helpful to PCPs in remote or low-resource settings, allowing them to objectively determine which patients require referral to craniofacial surgery.
PubMed: 38940555
DOI: 10.1097/SCS.0000000000010449