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1.
Cereb Cortex ; 34(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39191664

RESUMEN

Calcium ions (Ca2+) play crucial roles in almost every cellular process, making the detection of changes in intracellular Ca2+ essential to understanding cell function. The fluorescence indicator method has garnered widespread application due to its exceptional sensitivity, rapid analysis, cost-effectiveness, and user-friendly nature. It has successfully delineated the spatial and temporal dynamics of Ca2+ signaling across diverse cell types. However, it is vital to understand that different indicators have varying levels of accuracy, sensitivity, and stability, making choosing the right inspection method crucial. As optical detection technologies advance, they continually broaden the horizons of scientific inquiry. This primer offers a systematic synthesis of the current fluorescence indicators and optical imaging modalities utilized for the detection of intracellular Ca2+. It elucidates their practical applications and inherent limitations, serving as an essential reference for researchers seeking to identify the most suitable detection methodologies for their calcium-centric investigations.


Asunto(s)
Calcio , Colorantes Fluorescentes , Imagen Óptica , Calcio/metabolismo , Calcio/análisis , Humanos , Imagen Óptica/métodos , Animales , Señalización del Calcio/fisiología
2.
Proc Natl Acad Sci U S A ; 121(36): e2405168121, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39196620

RESUMEN

Multidimensional solitons are prevalent in numerous research fields. In orientationally ordered soft matter system, three-dimensional director solitons exemplify the localized distortion of molecular orientation. However, their precise manipulation remains challenging due to unpredictable and uncontrolled generation. Here, we utilize preimposed programmable photopatterning in nematics to control the kinetics of director solitons. This enables both unidirectional and bidirectional generation at specific locations and times, confinement within micron-scaled patterns of diverse shapes, and directed propagation along predefined trajectories. A focused dynamical model provides insight into the origins of these solitons and aligns closely with experimental observations, underscoring the pivotal role of anchoring conditions in soliton manipulation. Our findings pave the way for diverse fundamental research avenues and promising applications, including microcargo transportation and optical information processing.

3.
Clin Epigenetics ; 16(1): 94, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026267

RESUMEN

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.


Asunto(s)
Envejecimiento , Epigénesis Genética , Análisis de la Aleatorización Mendeliana , Caminata , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Caminata/fisiología , Epigénesis Genética/genética , Envejecimiento/genética , Envejecimiento/fisiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Reino Unido , Conducta Sedentaria , Metilación de ADN/genética
4.
Proc Natl Acad Sci U S A ; 121(25): e2406788121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38865267

RESUMEN

Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.


Asunto(s)
Fertilidad , Hemípteros , Rickettsia , Razón de Masculinidad , Simbiosis , Animales , Rickettsia/fisiología , Hemípteros/microbiología , Hemípteros/fisiología , Femenino , Masculino , Hormonas Juveniles/metabolismo , China
5.
Curr Biol ; 34(11): 2359-2372.e9, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38692276

RESUMEN

Host reproduction can be manipulated by bacterial symbionts in various ways. Parthenogenesis induction is the most effective type of reproduction manipulation by symbionts for their transmission. Insect sex is determined by regulation of doublesex (dsx) splicing through transformer2 (tra2) and transformer (tra) interaction. Although parthenogenesis induction by symbionts has been studied since the 1970s, its underlying molecular mechanism is unknown. Here we identify a Wolbachia parthenogenesis-induction feminization factor gene (piff) that targets sex-determining genes and causes female-producing parthenogenesis in the haplodiploid parasitoid Encarsia formosa. We found that Wolbachia elimination repressed expression of female-specific dsx and enhanced expression of male-specific dsx, which led to the production of wasp haploid male offspring. Furthermore, we found that E. formosa tra is truncated and non-functional, and Wolbachia has a functional tra homolog, termed piff, with an insect origin. Wolbachia PIFF can colocalize and interact with wasp TRA2. Moreover, Wolbachia piff has coordinated expression with tra2 and dsx of E. formosa. Our results demonstrate the bacterial symbiont Wolbachia has acquired an insect gene to manipulate the host sex determination cascade and induce parthenogenesis in wasps. This study reveals insect-to-bacteria horizontal gene transfer drives the evolution of animal sex determination systems, elucidating a striking mechanism of insect-microbe symbiosis.


Asunto(s)
Transferencia de Gen Horizontal , Simbiosis , Avispas , Wolbachia , Animales , Wolbachia/fisiología , Wolbachia/genética , Avispas/fisiología , Avispas/microbiología , Avispas/genética , Simbiosis/genética , Femenino , Masculino , Partenogénesis/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Procesos de Determinación del Sexo/genética
6.
Artículo en Inglés | MEDLINE | ID: mdl-38570918

RESUMEN

CONTEXT: Medullary thyroid cancer (MTC) often exhibits aggressive growth with distant organ metastasis, leading to poor survival. OBJECTIVE: The question of whether primary tumor resection (PTR) is beneficial for patients with metastatic MTC remains a subject of debate. In this study, we evaluated the prognostic significance of organ-specific metastases and the number of metastatic organs in these patients, and we also conducted an analysis to determine the therapeutic value of PTR in managing this rare malignancy. MATERIALS AND METHODS: Patients initially diagnosed with metastatic MTC were identified within the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox proportional hazards regression models were performed to identify survival predictors. Survival outcomes were calculated using the Kaplan-Meier method and compared using the log-rank tests. RESULTS: A total of 186 patients with metastatic MTC at initial diagnosis from 2010 to 2020 were included. Bone, lung and liver were the most common metastatic organs. Patients with brain metastasis had significantly worse overall survival (OS) (p = 0.007) and cancer-specific survival (CSS) (p = 0.0013). Among all patients, 105 (56.45%) underwent PTR, and this group showed reduced overall mortality (OM) and cancer-specific mortality (CSM) (all p < 0.05). When analyzing different metastatic patterns, PTR significantly lowered the risk of OM and CSM for patients with bone, lung, liver, or distant lymph node (DLN) involvement (all p < 0.05). Additionally, among patients with one or two metastases, those undergoing surgical resection were significantly associated with favorable OS (p = 0.008) and CSS (p = 0.0247). CONCLUSIONS: PTR may confer therapeutic benefits for carefully selected individuals with metastatic MTCs. To integrate these insights into clinical decision-making settings, it is imperative to undertake multicenter prospective studies in the future.

7.
Mol Metab ; 84: 101944, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38642891

RESUMEN

High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1. DCA failed to promote colitis and ferroptosis in intestine-specific HIF-2α-null mice. Notably, byak-angelicin inhibited DCA-induced pro-inflammatory and pro-ferroptotic effects through blocking the up-regulation of HIF-2α by DCA. Moreover, fat intake was positively correlated with disease activity in UC patients consuming HFD, with ferroptosis being more pronounced. Collectively, our findings demonstrated that HFD exacerbated colonic inflammation by promoting DCA-mediated ferroptosis, providing new insights into diet-related bile acid dysregulation in UC.


Asunto(s)
Ácido Desoxicólico , Dieta Alta en Grasa , Ferroptosis , Ratones Endogámicos C57BL , Animales , Ácido Desoxicólico/metabolismo , Ácido Desoxicólico/farmacología , Ácido Desoxicólico/efectos adversos , Dieta Alta en Grasa/efectos adversos , Ferroptosis/efectos de los fármacos , Ratones , Masculino , Humanos , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Inflamación/metabolismo , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/patología , Colon/metabolismo , Colon/patología , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/patología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Noqueados
8.
Nat Prod Res ; : 1-9, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38684021

RESUMEN

Three isocoumarins, ascoisocoumarin A (1), embeurekol (2), and sclerotinin A (3), and five biosynthetically related derivatives, ascospinols A-C (4, 6, and 7), and talaflavuols C and B (5 and 8), together with twelve polyketides or terpenes (9-20) were isolated from the fungus Aspergillus sp. LY-1-2 inhabited in a sample of Cordyceps sp. Most of them belong to the family of oxygen-containing aromatic compounds and compounds 1, 4, 6, and 7 are previously undescribed compounds. Their planar structures were established by a combined spectroscopic analysis of HRESIMS and NMR, and their stereochemistry was determined by 13C NMR calculations with sorted training set (STS) protocol analysis, and ECD calculations. New compounds 1 and 6 displayed potential anti-inflammatory effects in lipopolysaccharide (LPS)-induced BV2 microglia cells.

9.
Microbiol Res ; 282: 127660, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38442454

RESUMEN

Nonresponse to biologic agents in patients with inflammatory bowel disease (IBD) poses a significant public health burden, and the prediction of response to biologics offers valuable insights for IBD management. Given the pivotal role of gut microbiota and their endogenous metabolites in IBD, we conducted a systematic review to investigate the potential of fecal microbiota and mucosal microbiota and endogenous metabolomic markers as predictors for biotherapy response in IBD patients. A total of 38 studies were included in the review. Following anti-TNF-α treatment, the bacterial community characteristics of IBD patients exhibited a tendency to resemble those observed in healthy controls, indicating an improved clinical response. The levels of endogenous metabolites butyrate and deoxycholic acid were significantly associated with clinical remission following anti-TNF-α therapy. IBD patients who responded well to vedolizumab treatment had higher levels of specific bacteria that produce butyrate, along with increased levels of metabolites such as butyrate, branched-chain amino acids and acetamide following vedolizumab treatment. Crohn's disease patients who responded positively to ustekinumab treatment showed higher levels of Faecalibacterium and lower levels of Escherichia/Shigella. In conclusion, fecal microbiota and mucosal microbiota as well as their endogenous metabolites could provide a predictive tool for assessing the response of IBD patients to various biological agents and serve as a valuable reference for precise drug selection in clinical IBD patients.


Asunto(s)
Productos Biológicos , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Bacterias , Productos Biológicos/uso terapéutico , Butiratos , Heces/microbiología , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/microbiología , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico
10.
EBioMedicine ; 100: 104967, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38241975

RESUMEN

The incidence of cancer has shown a great increase during the past decades and poses tough challenges to cancer treatment. Anti-tumour immunotherapy, represented by immune checkpoint inhibitors (ICIs), possesses favorable remission in unrestricted spectrum of cancer types. However, its efficacy seems to be heterogeneous among accumulating studies. Emerging evidences suggest that gut microbiota can modulate anti-tumour immuno-response and predict clinical prognosis. Therefore, remodeling microbiota characteristics with fecal microbiota transplantation (FMT) may be capable of reinforcing host ICIs performance by regulating immune-tumour cell interactions and altering microbial metabolites, thereby imperceptibly shifting the tumour microenvironment. However, the long-term safety of FMT is under concern, which calls for more rigorous screening. In this review, we examine current experimental and clinical evidences supporting the FMT efficacy in boosting anti-tumour immuno-response and lessening tumour-related complications. Moreover, we discuss the challenges in FMT and propose feasible resolutions, which may offer crucial guidance for future clinical operations.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Neoplasias , Humanos , Trasplante de Microbiota Fecal , Neoplasias/terapia , Inmunoterapia , Microambiente Tumoral
11.
J Oral Rehabil ; 51(4): 639-647, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38100233

RESUMEN

BACKGROUND: Sleep disorders are associated with temporomandibular disorders (TMDs). Limited studies have focused on excessive daytime sleepiness (EDS) and its impact on jaw functions in TMD patients. OBJECTIVE: The aim of the present investigation was to identify the impact of EDS on pain and jaw function in TMD patients. METHODS: A total of 338 TMD patients (50 males and 288 females) was included. The Epworth Sleepiness Scale (ESS) was used to classify patients into EDS group (score ≥ 10) and non-EDS group (score < 10). The Jaw Functional Limitation Scale 8-item (JFLS-8) was used to assess the severity of jaw dysfunction. Pain intensity was evaluated using the Visual Analogue Scale (VAS). Anxiety and depression were evaluated using the Generalised Anxiety Disorder 7-item (GAD-7) and the Patient Health Questionnaire 9-item (PHQ-9). All included patients were diagnosed with pain-related TMD (PT), intra-articular TMD (IT) or combined TMD (CT). RESULTS: Compared with non-EDS patients, EDS patients exhibited more severe jaw dysfunction, greater pain intensity and higher PHQ-9 scores (p < .05). Multivariate analyses showed that EDS (B = 3.69), female gender (B = 3.69), and elevated GAD-7 score (B = 0.73) were significantly associated with an increased score on the JFLS-8 (p < .05). Moreover, bivariate logistic regression analysis indicated a significant relationship between EDS and PT (OR = 2.70, p = .007). CONCLUSION: The presence of EDS was more closely related to PT, but the causal relationship between them needs to be further confirmed. More concern and intervention to alleviate poor sleep quality might be highlighted during the treatment of TMD, especially PT subtype.


Asunto(s)
Trastornos del Sueño-Vigilia , Trastornos de la Articulación Temporomandibular , Masculino , Humanos , Femenino , Dimensión del Dolor , Ansiedad , Dolor , Trastornos de la Articulación Temporomandibular/complicaciones
12.
Pediatr Emerg Care ; 39(12): 957-962, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38019715

RESUMEN

OBJECTIVE: This study aimed to describe the demographic and clinical characteristics of severe acute toxic ingestions in children in Jilin Province and provide a reference for seeking effective measures to prevent poisoning accidents. METHODS: The clinical data of patients diagnosed with acute toxic ingestions and who presented with severe life-threatening symptoms or organ dysfunction at the Pediatric Intensive Care Unit of the First Hospital of Jilin University were retrospectively analyzed. Patients with incomplete clinical medical records, unclear toxic substance, and loss to follow-up within 6 months of discharge are excluded. We sorted out these children's demographic characteristics, types of poisoning, clinical manifestations, treatment process, and follow-up, etc. RESULTS: This study enrolled 141 cases with no significant differences in sex and region; adolescents accounted for 44.68%. The most common poisons were pesticides and insecticides for rural areas and internal medication for urban areas. With poisoning details as a grouping variable, there was no statistical difference between sex groupings (χ2 = 6.018, P = 0.198) and no difference between region groups (χ2 = 3.775, P = 0.289). However, there were statistical differences between age groups (χ2 = 28.22, P = 0.001). In this research, patients younger than 6 years are mainly unintentionally poisoned, whereas the suicide rate of the urban group (P < 0.05), adolescents (P < 0.01), and girls (P < 0.01) has increased significantly; moreover, the suicide group is more likely to take more overdose medication or pesticides and insecticides (P < 0.01). In addition, there was a statistical difference between suicide and length of intensive care unit stay (r = 0.268, P < 0.01). A total of 90.78% of the patients were successfully discharged after comprehensive treatment. Children aged younger than 12 years had good psychological and intellectual development during the follow-up period, whereas adolescents diagnosed with depression often required long-term psychological and medication intervention. CONCLUSIONS: This study identified poisoning details in different ages, regions, and sex of acute severe oral poisoning in children from Jilin Province. The results presentation of different prevention priorities should vary among children of different ages and emphasize adolescent suicide being a reality in Jilin Province. There is an urgent need for further culture-specific research in this area.


Asunto(s)
Insecticidas , Plaguicidas , Intoxicación , Femenino , Adolescente , Humanos , Niño , Estudios Retrospectivos , China/epidemiología , Demografía , Ingestión de Alimentos , Intoxicación/epidemiología , Intoxicación/terapia
13.
J Vis Exp ; (200)2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37902337

RESUMEN

Epilepsy is a neurological disorder characterized by recurrent seizures, partially correlated with genetic origin, affecting over 70 million individuals worldwide. Despite the clinical importance of epilepsy, the functional analysis of neural activity in the central nervous system is still to be developed. Recent advancements in imaging technology, in combination with stable expression of genetically encoded calcium indicators, such as GCaMP6, have revolutionized the study of epilepsy at both brain-wide and single-cell resolution levels. Drosophila melanogaster has emerged as a tool for investigating the molecular and cellular mechanisms underlying epilepsy due to its sophisticated molecular genetics and behavioral assays. In this study, we present a novel and efficient protocol for ex vivo calcium imaging in GCaMP6-expressing adult Drosophila to monitor epileptiform activities. The whole brain is prepared from cac, a well-known epilepsy gene, knockdown flies for calcium imaging with a confocal microscope to identify the neural activity as a follow-up to the bang-sensitive seizure-like behavior assay. The cac knockdown flies showed a higher rate of seizure-like behavior and abnormal calcium activities, including more large spikes and fewer small spikes than wild-type flies. The calcium activities were correlated to seizure-like behavior. This methodology serves as an efficient methodology in screening the pathogenic genes for epilepsy and exploring the potential mechanism of epilepsy at the cellular level.


Asunto(s)
Drosophila , Epilepsia , Animales , Humanos , Drosophila melanogaster/genética , Calcio , Epilepsia/diagnóstico por imagen , Epilepsia/genética , Convulsiones/patología
14.
Front Endocrinol (Lausanne) ; 14: 1007192, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37818092

RESUMEN

Objective: To explore the relationship between folic acid supplementation and the recovery rate of gestational diabetes mellitus (GDM) in women with methylenetetrahydrofolate (MTHFR) 677 TT genotypes in mid-late pregnancy. Methods: 9, 096 pregnant women were recruited with their MTHFR gene genotyped. 5,111 women underwent a 75-g oral glucose tolerance test (OGTT) and 2,097 were confirmed with GDM. The association between MTHFR genotypes and GDM risk was estimated using logistic and log-binomial regression, with age and parity set as the covariates to control their confounding effects. Further assessment of GDM risk on glucose levels was done using the ANCOVA model. As an open-label intervention study, 53 GDM patients with TT genotype were prescribed 800µg/day of folic acid as the high-dose group, while 201 GDM patients were given 400µg/day as the standard-dose group at their 24-28 weeks of pregnancy. A rate ratio (RR) of GDM recovery was estimated at each available time point for both groups. The time-to-GDM persistence events were analyzed with the Kaplan-Meier method and Cox-regression model. The trend of glucose levels over time was estimated using the linear model. Results: MTHFR 677 TT genotype has no significant association with the glucose levels and GDM risk, with an adjusted OR of 1.105 (95% CI 0.853, 1.431; p=0.452) and an adjusted PR of 1.050 (95% CI 0.906, 1.216; p=0.518) compared to the wildtype CC group. Patients in the high-dose group (n=38; 15 drop-outs; 40.69 days (95% CI 33.22, 48.15)) recovered from GDM approximately 27 days faster than those in the standard-dose group (n=133; 68 drop-outs; 68.09 days (95% CI 63.08, 73.11)). Concomitantly, the RR of GDM recovery rose and reached 1.247 (95% CI 1.026, 1.515) at 100 days of treatment with the standard-dose group as reference. Conclusion: High-dose folic acid supplement intake in mid-late pregnancy is associated with faster GDM relief in patients with MTHFR 677 TT genotype compared to the standard dose, which would be served as a novel and low-cost alternative therapy for the treatment of GDM.


Asunto(s)
Diabetes Gestacional , Ácido Fólico , Embarazo , Humanos , Femenino , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/genética , Suplementos Dietéticos , Genotipo , Glucosa , Metilenotetrahidrofolato Reductasa (NADPH2)/genética
15.
Front Plant Sci ; 14: 1209834, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37711312

RESUMEN

Cymbidium sinense is one of the most important traditional Chinese Orchids due to its unique and highly ornamental floral organs. Although the ABCDE model for flower development is well-established in model plant species, the precise roles of these genes in C. sinense are not yet fully understood. In this study, four SEPALLATA-like genes were isolated and identified from C. sinense. CsSEP1 and CsSEP3 were grouped into the AGL9 clade, while CsSEP2 and CsSEP4 were included in the AGL2/3/4 clade. The expression pattern of CsSEP genes showed that they were significantly accumulated in reproductive tissues and expressed during flower bud development but only mildly detected or even undetected in vegetative organs. Subcellular localization revealed that CsSEP1 and CsSEP4 were localized to the nucleus, while CsSEP2 and CsSEP3 were located at the nuclear membrane. Promoter sequence analysis predicted that CsSEP genes contained a number of hormone response elements (HREs) and MADS-box binding sites. The early flowering phenotype observed in transgenic Arabidopsis plants expressing four CsSEP genes, along with the expression profiles of endogenous genes, such as SOC1, LFY, AG, FT, SEP3 and TCPs, in both transgenic Arabidopsis and C. sinense protoplasts, suggested that the CsSEP genes played a regulatory role in the flowering transition by influencing downstream genes related to flowering. However, only transgenic plants overexpressing CsSEP3 and CsSEP4 caused abnormal phenotypes of floral organs, while CsSEP1 and CsSEP2 had no effect on floral organs. Protein-protein interaction assays indicated that CsSEPs formed a protein complex with B-class CsAP3-2 and CsSOC1 proteins, affecting downstream genes to regulate floral organs and flowering time. Our findings highlighted both the functional conservation and divergence of SEPALLATA-like genes in C. sinense floral development. These results provided a valuable foundation for future studies of the molecular network underlying floral development in C. sinense.

16.
Front Endocrinol (Lausanne) ; 14: 1165825, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37529615

RESUMEN

Introduction: It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model. Methods: Different Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila. Results: We found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility. Discussion: Overall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression.


Asunto(s)
Proteínas de Drosophila , Infertilidad Masculina , Humanos , Animales , Masculino , Drosophila , Testículo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Semen/metabolismo , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Proteínas de Unión a Calmodulina/metabolismo , Ubiquitina-Proteína Ligasas/genética
17.
Front Mol Neurosci ; 16: 1121877, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37152436

RESUMEN

Introduction: With the advent of trio-based whole-exome sequencing, the identification of epilepsy candidate genes has become easier, resulting in a large number of potential genes that need to be validated in a whole-organism context. However, conducting animal experiments systematically and efficiently remains a challenge due to their laborious and time-consuming nature. This study aims to develop optimized strategies for validating epilepsy candidate genes using the Drosophila model. Methods: This study incorporate behavior, morphology, and electrophysiology for genetic manipulation and phenotypic examination. We utilized the Gal4/UAS system in combination with RNAi techniques to generate loss-of-function models. We performed a range of behavioral tests, including two previously unreported seizure phenotypes, to evaluate the seizure behavior of mutant and wild-type flies. We used Gal4/UAS-mGFP flies to observe the morphological alterations in the brain under a confocal microscope. We also implemented patch-clamp recordings, including a novel electrophysiological method for studying synapse function and improved methods for recording action potential currents and spontaneous EPSCs on targeted neurons. Results: We applied different techniques or methods mentioned above to investigate four epilepsy-associated genes, namely Tango14, Klp3A, Cac, and Sbf, based on their genotype-phenotype correlation. Our findings showcase the feasibility and efficiency of our screening system for confirming epilepsy candidate genes in the Drosophila model. Discussion: This efficient screening system holds the potential to significantly accelerate and optimize the process of identifying epilepsy candidate genes, particularly in conjunction with trio-based whole-exome sequencing.

18.
Chemistry ; 29(36): e202300776, 2023 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-37073779

RESUMEN

The incorporation of the privileged amino functionality is of paramount importance in organic synthesis. In contrast to the well-developed amination methods for alkenes, the dearomative amination of arenes is largely underexplored due to the inherently inert reactivity of arene π-bonds and selectivity challenges. Herein, we report an intermolecular dearomative aminofunctionalization via direct nucleophilic addition of simple amines to chromium-bound arenes. This multicomponent 1,2-amination/carbonylation reaction enables rapid access to complicated alicyclic compounds containing amino and amide functionalities from benzene derivatives under CO-gas-free conditions, which also represents the first application of nitrogen-based nucleophiles in η6 -coordination-induced arene dearomatizations.

19.
ACS Chem Neurosci ; 14(7): 1220-1225, 2023 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-36939323

RESUMEN

Tau plays a major role in Alzheimer's disease (AD) and several other neurodegenerative diseases. Tau undergoing liquid-liquid phase separation (LLPS) performs specific physiological functions, induces pathological processes, and contributes to neurodegeneration. Regulating Tau phase separation helps maintain physiological functions of Tau and inhibits pathological aggregation. Here, we show that the 14-3-3 zeta isoform (14-3-3ζ) participates in Tau LLPS. 14-3-3ζ can undergo co-phase separation with WT Tau, participate in and stabilize Tau droplets, and inhibit Tau droplet-driven tubulin assembly. On the other hand, 14-3-3ζ disrupts the LLPS of phosphorylated and glycated Tau, thereby inhibiting the amyloid aggregation initiated by LLPS.


Asunto(s)
Enfermedad de Alzheimer , Proteínas tau , Humanos , Proteínas tau/metabolismo , Proteínas 14-3-3/metabolismo , Enfermedad de Alzheimer/patología , Isoformas de Proteínas
20.
Support Care Cancer ; 31(3): 180, 2023 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-36820904

RESUMEN

PURPOSE: Although the antidepressant effects of physical activity have been well established, the underlying psychological mechanisms are understudied among cancer survivors. The present study aims to examine the parallel mediating effects of posttraumatic growth and body image on the association between walking activity and emotional distress (anxiety and depression) among Chinese breast cancer survivors. METHODS: Chinese breast cancer survivors (n = 235) completed a cross-sectional questionnaire that assessed walking activity, anxiety, depression, posttraumatic growth, and body image over the past week. Path analysis was conducted to test the hypothesized mediation model. RESULTS: The hypothesized model was supported: walking activity was positively associated with posttraumatic growth and body image satisfaction, which were then negatively associated with anxiety and depression. After controlling for the mediators, the direct effect of physical activity on depression was still significant, whereas the direct effect of physical activity on anxiety was no longer significant. CONCLUSION: Our findings suggest that posttraumatic growth and body image may be essential psychological pathways underlying the association between walking activity and emotional distress among Chinese breast cancer survivors. Researchers and health practitioners should consider supplementing physical activity interventions with mental health services that facilitate psychological growth and a positive body image to enhance the potential psychological benefits of physical activity.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Crecimiento Psicológico Postraumático , Distrés Psicológico , Humanos , Femenino , Imagen Corporal/psicología , Neoplasias de la Mama/psicología , Supervivientes de Cáncer/psicología , Estudios Transversales , Depresión/psicología , Ansiedad/psicología , Caminata , Estrés Psicológico/psicología , Adaptación Psicológica
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