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Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

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Molecular Plant 2024年第6期17卷 884-899页

作者： Liping Zeng Maria Fernanda Gomez Mendez Jingzhe Guo Jishan Jiang Bailong Zhang Hao Chen Brandon Le Haiyan Ke Katayoon Dehesh Department of Botany and Plant Sciences Institute of Integrative Genome BiologyUniversity of CaliforniaRiversideRiversideCA 92521USA school of medicine University of CaliforniaRiversideRiversideCA 92521USA

Stress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant *** address this,we performed a suppressor screen of the ceh1 mutant,which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate(MEcPP)levels,and identified the gain-of-function mutant impα-9,which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened *** genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1(ASK1)abundance,a pivotal component in the proteasome degradation *** increase in ASK1 prompts the degradation of IMPα-***,we uncovered a protein-protein interaction between IMPα-9 and TPR2,a transcriptional co-suppressor and found that a reduction in IMPα-9 levels coincides with a decrease in TPR2 ***,the interaction between IMPα-9 and TPR2 was disrupted in impα-9 mutants,highlighting the critical role of a single amino acid alteration in maintaining their *** of their interaction results in the reversal of MEcPP-associated *** immunoprecipitation coupled with sequencing analyses revealed that TPR2 binds globally to stress-response genes and suggested that IMPα-9 associates with the *** function together to suppress the expression of stress-response genes under normal conditions,but this suppression is alleviated in response to stress through the degradation of the suppressing *** biological relevance of our discoveries was validated under high light stress,marked by MEcPP accumulation,elevated ASK1 levels,IMPα-9 degredation,reduced TPR2 abundance,and subsequent activation of a network of stress-response *** summary,our study collectively unveils fresh insights into plant adaptive mechanisms,highlighting intricate interactions among retrograde signaling,the proteasome,and nuclear transport machinery.

关键词： plastidial retrograde signal MEcPP ASK1 impα-9 TPR2

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COMPLETE KAHLER METRICS WITH POSITIVE HOLOMORPHIC SECTIONAL CURVATURES ON CERTAIN LINE BUNDLES(RELATED TO A COHOMOGENEITY ONE POINT OF VIEW ON A YAU CONJECTURE)

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Acta Mathematica Scientia 2024年第1期44卷 78-102页

作者：段晓曼关庄丹 school of Mathematics and Statistics Henan UniversityKaifeng475004China Department of Mathematics The University of California at RiversideRiversideCA92521USA

In this article,we study Kahler metrics on a certain line bundle over some compact Kahler manifolds to find complete Kahler metrics with positive holomorphic sectional(or bisectional)***,we apply a strategy to a famou... 详细信息

关键词： Kahler Metrics complete Riemannian metrics open complex manifolds holomorphic bisectional curvature C*bundle almost homogeneous manifolds

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Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus

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World Journal of Diabetes 2024年第2期15卷 142-153页

作者： Omar Ramos-Lopez medicine and Psychology school Autonomous University of Baja CaliforniaTijuana 22390Baja CaliforniaMexico

Globally,type 2 diabetes mellitus(T2DM)is one of the most common metabolic disorders.T2DM physiopathology is influenced by complex interrelationships between genetic,metabolic and lifestyle factors(including diet),which differ between populations and geographic *** fact,excessive consumptions of high fat/high sugar foods generally increase the risk of developing T2DM,whereas habitual intakes of plant-based healthy diets usually exert a protective ***,genomic studies have allowed the characterization of sequence DNA variants across the human genome,some of which may affect gene expression and protein functions relevant for glucose *** comprehensive literature review covers the impact of gene-diet interactions on T2DM susceptibility and disease progression,some of which have demonstrated a value as biomarkers of personal responses to certain nutritional ***,novel genotype-based dietary strategies have been developed for improving T2DM control in comparison to general lifestyle ***,progresses in other omics areas(epigenomics,metagenomics,proteomics,and metabolomics)are improving current understanding of genetic insights in T2DM clinical *** more investigation is still needed,the analysis of the genetic make-up may help to decipher new paradigms in the pathophysiology of T2DM as well as offer further opportunities to personalize the screening,prevention,diagnosis,management,and prognosis of T2DM through precision nutrition.

关键词： Type 2 diabetes mellitus Nutrigenetics Single nucleotide polymorphism Genotype Diet Precision nutrition

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A compartment and metapopulation model of Rocky Mountain spotted fever in southwestern United States and northern Mexico

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Infectious Disease Modelling 2024年第3期9卷 713-727页

作者： Laura Backus Patrick Foley Janet Foley school of Veterinary medicine Department of Medicine and EpidemiologyUniversity of CaliforniaDavisCAUSA Department of Biological Sciences California State UniversitySacramentoCAUSA

Rocky Mountain spotted fever(RMSF)is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st *** the US south-western border and across northern Mexico,the brown dog tick,Rhipicephalus sanguineus,is responsible for spreading the disease between dogs and *** widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the *** dogs are amplifying hosts for the Rickettsia rickettsii bacteria,transmission dynamics between dogs and ticks are critical for understanding the *** this paper,we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North *** discovered that there is an extended lag—as much as two years—between introduction of the pathogen to a naïve population and epidemic-level transmission,suggesting that infected ticks could disseminate extensively before disease is detected.A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller *** model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.

关键词： Compartment model Rocky mountain spotted fever SIR model Metapopulation Zoonosis

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The Effect of Retinoic Acid on Neutrophil Innate Immune Interactions With Cutaneous Bacterial Pathogens

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Infectious Microbes & Diseases 2024年第2期6卷 65-73页

作者： Alexandra Stream Ross Corriden Simon Döhrmann Richard L.Gallo Victor Nizet Ericka L.Anderson Division of Host-Microbe Systems and Therapeutics Department of PediatricsUniversity of California San Diego School of MedicineLa JollaCaliforniaUSA Department of Dermatology University of California San Diego School of MedicineLa JollaCaliforniaUSA Skaggs school of Pharmacy and Pharmaceutical Sciences University of California San DiegoLa JollaCaliforniaUSA

Vitamin A and its biologically active derivative,retinoic acid(RA),are important for many immune ***,in particular,is essential for the development of immune cells,including neutrophils,which serve as a front-line defense against *** vitamin A deficiency has been linked to higher susceptibility to infections,the precise role of vitamin A/RA in host-pathogen interactions remains poorly ***,we provided evidence that RA boosts neutrophil killing of methicillin-resistant Staphylococcus aureus(MRSA).RA treatment stimulated primary human neutrophils to produce reactive oxygen species,neutrophil extracellular traps and the antimicrobial peptide cathelicidin(LL-37).Because RA treatment was insufficient to reduce MRSA burden in an in vivo murine model of skin infection,we expanded our analysis to other infectious *** did not affect the growth of a number of common bacterial pathogens,including MRSA,Escherichia coli K1 and Pseudomonas aeruginosa;however,RA directly inhibited the growth of group A Streptococcus(GAS).This antimicrobial effect,likely in combination with RA-mediated neutrophil boosting,resulted in substantial GAS killing in neutrophil killing assays conducted in the presence of ***,in a murine model of GAS skin infection,topical RA treatment showed therapeutic potential by reducing both skin lesion size and bacterial *** findings suggest that RA may hold promise as a therapeutic agent against GAS and perhaps other clinically significant human pathogens.

关键词： retinoic acid neutrophil bacterial infection Staphylococcus aureus group A Streptococcus neutrophil extracellular traps antimicrobial peptide cathelicidin

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Bioceramic scaffolds with two-step internal/external modification of copper-containing polydopamine enhance antibacterial and alveolar bone regeneration capability

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 65-82页

作者： Xiaojian JIANG Lihong LEI Weilian SUN Yingming WEI Jiayin HAN Shuaiqi ZHONG Xianyan YANG Zhongru GOU Lili CHEN Department of Oral medicine the Second Affiliated HospitalZhejiang University School of MedicineHangzhou310009China Bio-nanomaterials and Regenerative medicine Research Division Zhejiang–California International Nanosystem InstituteZhejiang UniversityHangzhou310058China

Magnesium-doped calcium silicate(CS)bioceramic scaffolds have unique advantages in mandibular defect repair;however,they lack antibacterial properties to cope with the complex oral ***,for the first time,the CS scaffold was functionally modified with a novel copper-containing polydopamine(PDA(Cu^(2+)))rapid deposition method,to construct internally modified(*P),externally modified(@PDA),and dually modified(*P@PDA)*** morphology,degradation behavior,and mechanical properties of the obtained scaffolds were evaluated in *** results showed that the CS*P@PDA had a unique micro-/nano-structural surface and appreciable mechanical *** the prolonged immersion stage,the release of copper ions from the CS*P@PDA scaffolds was rapid in the early stage and exhibited long-term sustained *** in vitro evaluation revealed that the release behavior of copper ions ascribed an excellent antibacterial effect to the CS*P@PDA,while the scaffolds retained good cytocompatibility with improved osteogenesis and angiogenesis ***,the PDA(Cu^(2+))-modified scaffolds showed effective early bone regeneration in a critical-size rabbit mandibular defect ***,it was indicated that considerable antibacterial property along with the enhancement of alveolar bone regeneration can be imparted to the scaffold by the two-step PDA(Cu^(2+))modification,and the convenience and wide applicability of this technique make it a promising strategy to avoid bacterial infections on implants.

关键词： Copper-containing polydopamine Modification Antibacterial property Bone regeneration Angiogenesis Bioceramic scaffold

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Childhood opportunity and appropriate use of child safety restraints in motor vehicle collisions

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World Journal of Pediatric Surgery 2024年第2期7卷 142-149页

作者： Stephanie Y Chen Iris Garcia Shadassa Ourshalimian Chantel Lowery Pradip P Chaudhari Ryan G Spurrier Pediatric Surgery Children's Hospital Los AngelesLos AngelesCaliforniaUSA Injury Prevention Program Children's Hospital Los AngelesLos AngelesCaliforniaUSA Emergency and Transport medicine Children's Hospital Los AngelesLos AngelesCaliforniaUSA Pediatrics University of Southern California Keck School of MedicineLos AngelesCaliforniaUSA Surgery University of Southern California Keck School of MedicineLos AngelesCaliforniaUSA

Objectives Safety restraints reduce injuries from motor vehicle collisions(MVCs)but are often improperly applied or not *** Childhood Opportunity Index(COI)reflects social determinants of health and its study in pediatric trauma is *** hypothesized that MVC patients from low-opportunity neighborhoods are less likely to be appropriately *** A retrospective cross-sectional study was performed on children/adolescents≤18 years old in MVCs between January 1,2011 and December 31,*** were identified from the Children's Hospital Los Angeles trauma *** outcome was safety restraint use(appropriately restrained,not appropriately restrained).COI levels by home zip codes were stratified as very low,low,moderate,high,and very *** regression controlling for age identified factors associated with safety restraint *** Of 337 patients,73.9%were appropriately restrained and 26.1%were not appropriately *** with appropriately restrained patients,more not appropriately restrained patients were from low-COI(26.1%vs 20.9%),high-COI(14.8%vs 10.8%)and very high-COI(10.2%vs 3.6%)*** analysis demonstrated no significant associations in appropriate restraint use and *** was a non-significant trend that children/adolescents from moderate-COI neighborhoods were more likely than those from very low-COI neighborhoods to be appropriately restrained(OR=1.82,95%CI 0.78,4.28).Conclusion Injury prevention initiatives focused on safety restraints should target families of children from all neighborhood types.

关键词： MVC restrained neighborhood

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Implementation and evaluation of Exercise is medicine in primary care clinics within a large academic health system

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Family medicine and Community Health 2024年第1期12卷 16-27页

作者： John Kevin Ong Dayao Caroline E L Duffy Amalia M Cristiano Gene'Rusty'Kallenberg Sarah E Linke university of california San Diego school of medicine La JollaCaliforniaUSA Milken Institute of Public Health The George Washington UniversityWashingtonDistrict of ColumbiaUSA The university of Texas Medical Branch at Galveston school of medicine GalvestonTexasUSA Scripps Family medicine Residency Scripps Mercy Hospital Chula VistaChula VistaCaliforniaUSA Herbert Wertheim school of Public Health&Human Longevity Science University of California San DiegoLa JollaCaliforniaUSA Department of Family medicine University of California San DiegoLa JollaCaliforniaUSA Omada Health San FranciscoCaliforniaUSA

Objective Exercise is medicine(EIM)is a global initiative encouraging healthcare providers to routinely assess and promote physical activity(PA)among *** objective of this study was to evaluate the feasibility,adoption,implementation and effectiveness of EIM from patient,clinician and healthcare staff perspectives using a combination of electronic health record(EHR),survey and interview *** This study used a combination of the Practical Robust Implementation and Sustainability Model(PRISM)and the Learning Evaluation model to implement *** captured from the EHR,including Physical Activity Vital Sign(PAVS)scores,and data collected from qualitative surveys and interviews were used to evaluate the programme’s Reach,Effectiveness,Adoption,Implementation,Maintenance(RE-AIM,which is embedded within PRISM)from provider,staff and patient *** Five primary care clinics within a large academic health *** A total of 24443 patients from all participating clinics had at least one PAVS score during the study period.A total of 17 clinicians completed surveys,and 4 clinicians,8 medical assistants and 9 patients completed *** Implementation fidelity metrics varied widely between components and across clinics but were generally consistent over time,indicating a high degree of programme *** was highest during the first 6 months of the COVID-19 pandemic when most visits were *** PAVS scores increased from 57.7(95%CI:56 to 59.4)to 95.2(95%CI:91.6 to 98.8)min per week at 6 months for patients not meeting PA guidelines at baseline and decreased from 253.84(95%CI:252 to 255.7)to 208.3(95%CI:204.2 to 212.4)min per week at 6 months for patients meeting PA guidelines at *** EIM implementation,clinician-estimated time spent discussing PA with patients increased for 35%of providers and stayed the same for 53%.Conclusion Overall,this study established EIM’s feasibility,adoption,implementation

关键词： routine qualitative completed

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Recent advances and future therapy development for Alzheimer’s disease and related disorders

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Neural Regeneration Research 2024年第9期19卷 1877-1878页

作者： Megan Hong Gal Bitan Department of Neurology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA Department of Chemistry and Biochemistry University of California Los AngelesLos AngelesCAUSA Molecular Biology Institute University of California Los AngelesLos AngelesCAUSA Brain Research Institute University of CaliforniaLos AngelesCAUSA

Over 55 million people globally live with Alzheimer’s disease(AD)or related dementias(ADRD)and the number is expected to double every twenty *** i l recent l y,onl y symptomatic treatments were available to patients with AD,including acetylcholine esterase inhibitors,of which the last one,galantamine,was approved by the US Food and Drug Administration(FDA)in 2001.

关键词： Alzheimer globally patients

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Storylines of family medicine Ⅹ:standing up for diversity,equity and inclusion

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Family medicine and Community Health 2024年第S3期12卷 89-98页

作者： William B Ventres Leslie A Stone Wayne W Bryant Jr Mario F Pacheco Edgar Figueroa Francis N Chu Shailendra Prasad David N Blane Na'amah Razon Ranit Mishori Robert L Ferrer Garrett S Kneese Family and Preventive medicine University of Arkansas for Medical Sciences College of MedicineLittle RockArkansasUSA Family and Community medicine University of New Mexico School of MedicineAlbuquerqueNew MexicoUSA medicine Weill Cornell Medical CollegeNew YorkNew YorkUSA San Jose Family medicine Residency Kaiser PermanenteSan JoseCaliforniaUSA Family medicine and Community Health University of Minnesota Medical School—Twin Cities CampusMinneapolisMinnesotaUSA school of Health and Wellbeing University of GlasgowGlasgowUK Family and Community medicine University of CaliforniaDavisSacramentoCaliforniaUSA Family medicine Georgetown University School of MedicineWashingtonDistrict of ColumbiaUSA Family and Community medicine UT Health San Antonio Long School of MedicineSan AntonioTexasUSA UC San Diego Family medicine Residency Program San DiegoCaliforniaUSA

Storylines of Family medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine as interpreted by individual family physicians and medical educators in the USA and elsewhere around the ***‘Ⅹ:standing up for diversity,equity and inclusion’,authors address the following themes:‘The power of diversity—why inclusivity is essential to equity in healthcare’,‘Medical education for whom?’,‘Growing a diverse and inclusive workforce’,‘Therapeutic judo—an inclusive approach to patient care’,‘Global family medicine—seeing the world“upside down”’,‘The inverse care law‘,‘Social determinants of health as a lens for care’,‘Why family physicians should care about human rights’and‘Toward health equity—the opportunome’.May the essays that follow inspire readers to promote change.

关键词： illustration education family

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