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1.
Artigo em Inglês | MEDLINE | ID: mdl-39321008

RESUMO

Variable interactivity is crucial in biological multivariate time series analysis. This research suggests using graph structures to represent such interactions for more explainable decision-making processes. However, measuring the variable interaction in a graph is an open problem with no unique solution. Existing graph construction methods are either computationally costly, require extensive training, or disregard the inherent data nonlinearities and nonstationarity. We propose using the Fuzzy Synchronization Likelihood (FSL) criterion to address these challenges in constructing a graph and examining the qualitative similarity and dependency among variables. We propose applying this strategy to automated rehabilitation exercise evaluations based on human joint motion data. This multivariate time series application benefits from FSL-constructed graphs by offering further insight into the kinematics of joint interactions. Finally, we extend the convolutional layer in the Deep Mixture Density Neural Network (DMDN) to process the FSL-constructed graph, extracting practical information regarding task-based variable dependencies. An ablation study shows that the proposed FSL Graph-based Deep Neural Network (FSLGDN) outperforms its competitive approaches that use linear correlations and human anatomy for graph construction. Results also indicate that task-based consideration of joint motion data interactions is more beneficial than anatomy. Furthermore, the inherent nonstationarity of motion data leads to the extraction of more information than its linear correlation counterpart. Finally, while the proposed approach ranks competitively with a DMDN, the proposed approach's graph construction and representation of feature dependencies are more intuitive, leading to more explainable decision-making processes.

2.
Sci Diabetes Self Manag Care ; : 26350106241279813, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320149

RESUMO

PURPOSE: The purpose of the study was to assess self-efficacy among adolescents with type 1 diabetes mellitus and to identify its contributing factors using a new measure based on the International Society for Pediatric and Adolescent Diabetes Guidelines: the Type 1 Diabetes Mellitus Self-Efficacy Scale (T1DM-SES). METHOD: A descriptive, cross-sectional design was used to collect data from 161 adolescents ages between 12 and 18 via an online questionnaire survey, including demographic and management-related variables and the 21 items of T1DM-SES. RESULTS: Results demonstrated that adolescents had high self-efficacy levels regarding the basic needs to manage their diabetes and relatively moderate and low levels regarding more sophisticated needs, such as adjusting insulin dose to correct fluctuated glucose levels, covering carbohydrates, and managing ketoacidosis at home. Adolescent females and adolescents who have working mothers or caregivers demonstrated higher levels of self-efficacy, whereas adolescents who have another family member with T1DM reported lower levels. CONCLUSION: Assessing adolescents' self-efficacy using evidence-based measures is crucial for informing health education plans. There should be a greater focus on acquiring the advanced knowledge and skills necessary for adolescents to manage the constantly evolving challenges of diabetes management. Access to health care and sufficient health insurance coverage that encompasses modern technology are fundamental for the effective management of T1DM.

3.
bioRxiv ; 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39314407

RESUMO

Collagen fibers are the main load-bearing component of soft tissues but difficult to incorporate into models. Whilst simplified homogenization models suffice for some applications, a thorough mechanistic understanding requires accurate prediction of fiber behavior, including both detailed fiber-level strains and long-distance transmission. Our goal was to compare the performance of a continuum model of the optic nerve head (ONH) built using conventional techniques with a fiber model we recently introduced which explicitly incorporates the complex 3D organization and interaction of collagen fiber bundles [1]. To ensure a fair comparison, we constructed the continuum model with identical geometrical, structural, and boundary specifications as for the fiber model. We found that: 1) although both models accurately matched the intraocular pressure (IOP)-induced globally averaged displacement responses observed in experiments, they diverged significantly in their ability to replicate specific 3D tissue-level strain patterns. Notably, the fiber model faithfully replicated the experimentally observed depth-dependent variability of radial strain, the ring-like pattern of meridional strain, and the radial pattern of circumferential strain, whereas the continuum model failed to do so; 2) the continuum model disrupted the strain transmission along each fiber, a feature captured well by the fiber model. These results demonstrate limitations of the conventional continuum models that rely on homogenization and affine deformation assumptions, which render them incapable of capturing some complex tissue-level and fiber-level deformations. Our results show that the strengths of explicit fiber modeling help capture intricate ONH biomechanics. They potentially also help modeling other fibrous tissues.

4.
Pediatr Blood Cancer ; : e31326, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289855

RESUMO

BACKGROUND AND PURPOSE: The use of traditional and complementary medicine (T&CM) is common in children with cancer globally. We aimed to assess the prevalence, types, reasons, perceived effectiveness, and disclosure rate of T&CM use among children with cancer in Southern Egypt. We also investigated whether T&CM use contributed to delays in initial presentation and treatment. MATERIALS AND METHODS: A cross-sectional design was utilized. Data were collected via an interviewer-administered questionnaire. Eligible children and their caregivers at the South Egypt Cancer Institute were invited to participate. RESULTS: Eighty-six children completed the study (response rate = 86%). T&CM use was reported by 52 (60.5%) patients, with six (11.5%) experienced delayed presentation. The reasons for T&CM use were complementary for 37 (71%) and alternative for 15 (29%) of the participants. The types of T&CM used included herbal (63%), nutritional (33%), witchcraft (29%), and religious (19%) therapies. Approximately 48% of users employed multiple T&CM types. Family members recommended T&CM for 60% of the users. Most patients (65%) perceived T&CM as effective, with 71% initiating its use during the early phases of treatment. Almost all participants (98%) reported that healthcare providers did not inquire about T&CM use. T&CM usage was more prevalent among wealthier families (p = .023). There was no significant relationship between T&CM use and patient gender, diagnosis, residence, or paternal educational level. CONCLUSIONS: The significant utilization of T&CM among children with cancer highlights the need for healthcare providers to engage in open and early discussions with families regarding T&CM use.

5.
Angew Chem Int Ed Engl ; : e202414998, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39263721

RESUMO

Tryptophan and its non-canonical variants play critical roles in pharmaceutical molecules and enzymes. Facile access to this privileged class of amino acids from readily available building blocks remains a long-standing challenge. Here, we report a regioselective synthesis of non-canonical tryptophans bearing C4-C7 substituents via Rh-catalyzed annulation between structurally diverse tert-butyloxycarbonyl (Boc)-protected anilines and alkynyl chlorides readily prepared from amino acid building blocks. This transformation harnesses Boc-directed C-H metalation and demetalation to afford a wide range of C2-unsubstituted indole products in a redox-neutral fashion. This umpolung approach compared to the classic Larock indole synthesis offers a novel mechanism for heteroarene annulation and will be useful for the synthesis of natural products and drug molecules containing non-canonical tryptophan residues in a highly regioselective manner.

6.
Sci Rep ; 14(1): 21235, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261635

RESUMO

Predictive models for spatial correlation play an effective role in the assessment of seismic risk associated with distributed infrastructure and building portfolios. However, existing models often rely on simplified approaches, assuming isotropy and stationarity. This paper verifies these assumptions by presenting a comprehensive study using a database of 3D physics-based simulated broadband ground motions for Istanbul, generated by the SPEED software. The results reveal significant event-to-event variability and nonstationary and anisotropic characteristics of spatial correlation influenced by source, path, and site effects. The development of nonstationary correlation models requires exploring influential metrics beyond spatial proximity and gaining a deep understanding of their impact, which is the focus of this study. Analysis of the spatial correlations of peak ground displacement, peak ground velocity, peak ground acceleration, and response spectral accelerations at different periods, employing both stationary and nonstationary correlation modelling methods and considering the finite fault model, indicates that the slip distribution pattern, direction and distance of station pairs relative to earthquake rupture, soil softness, and homogeneity of soil properties significantly influence the spatial correlations of near-field earthquake ground motions. Implementation of the introduced parameters in predictive spatial correlation models enhances the precision of regional seismic hazard assessments.

7.
J Family Med Prim Care ; 13(8): 3393-3397, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39228531

RESUMO

Background: Hyperkalemia is a potentially life-threatening electrolyte disturbance that if not diagnosed on time may lead to devastating conditions and sudden cardiac death. Blood sampling for potassium level checks is time-consuming and can delay the treatment of severe hyperkalemia on time. So, we propose a non-invasive method for correct and rapid hyperkalemia detection. Methods: The cardiac signal of patients referred to the Pediatrics Emergency room of Shahid Rejaee Hospital was measured by a 12-lead Philips electrocardiogram (ECG) device. Immediately, the blood samples of the patients were sent to the laboratory for potassium serum level determination. We defined 16 features for each cardiac signal at lead 2 and extracted them automatically using the algorithm developed. With the help of the principal component analysis (PCA) algorithm, the dimension reduction operation was performed. The algorithms of decision tree (DT), random forest (RF), logistic regression, and support vector machine (SVM) were used to classify serum potassium levels. Finally, we used the receiver operation characteristic (ROC) curve to display the results. Results: In the period of 5 months, 126 patients with a serum level above 4.5 (hyperkalemia) and 152 patients with a serum potassium level below 4.5 (normal potassium) were included in the study. Classification with the help of a RF algorithm has the best result. Accuracy, Precision, Recall, F1, and area under the curve (AUC) of this algorithm are 0.71, 0.87, 0.53, 0.66, and 0.69, respectively. Conclusions: A lead2-based RF classification model may help clinicians to rapidly detect severe dyskalemias as a non-invasive method and prevent life-threatening cardiac conditions due to hyperkalemia.

8.
Nucleus ; 15(1): 2399247, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39282864

RESUMO

The nuclear pore complex (NPC) is a critical gateway regulating molecular transport between the nucleus and cytoplasm. It allows small molecules to pass freely, while larger molecules require nuclear transport receptors to traverse the barrier. This selective permeability is maintained by phenylalanine-glycine-rich nucleoporins (FG-Nups), intrinsically disordered proteins that fill the NPC's central channel. The disordered and flexible nature of FG-Nups complicates their spatial characterization with conventional structural biology techniques. To address this challenge, polymer physics offers a valuable framework for describing FG-Nup behavior, reducing their complex structures to a few key parameters. In this review, we explore how polymer physics models FG-Nups using these parameters and discuss experimental efforts to quantify them in various contexts, providing insights into the conformational properties of FG-Nups.


Assuntos
Proteínas Intrinsicamente Desordenadas , Complexo de Proteínas Formadoras de Poros Nucleares , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/química , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Humanos , Polímeros/química , Polímeros/metabolismo , Animais , Poro Nuclear/metabolismo , Poro Nuclear/química , Fenilalanina/química , Fenilalanina/metabolismo , Glicina/metabolismo , Glicina/química
9.
BJUI Compass ; 5(9): 865-873, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39323923

RESUMO

Objective: This study aimed to evaluate the association of dynamic contrast enhancement (DCE) with clinically significant prostate cancer (csPCa, Gleason Grade Group ≥2) and compare biparametric magnetic resonance imaging (bpMRI) and multiparametric MRI (mpMRI) nomograms. Subjects/patients and methods: We identified a retrospective cohort of biopsy naïve patients who underwent pre-biopsy MRI separated by individual MRI series from 2018 to 2022. csPCa detection rates were calculated for patients with peripheral zone (PZ) lesions scored 3-5 on diffusion weighted imaging (DWI) with available DCE (annotated as - or +). bpMRI Prostate Imaging Reporting and Data System (PIRADS) (3 = 3-, 3+; 4 = 4-, 4+; 5 = 5-, 5+) and mpMRI PIRADS (3 = 3-; 4 = 3+, 4-, 4+; 5 = 5-, 5+) approaches were compared in multivariable logistic regression models. Nomograms for detection of csPCa and ≥GG3 PCa incorporating all biopsy naïve patients who underwent prostate MRI were generated based on available serum biomarkers [PHI, % free prostate-specific antigen (PSA), or total PSA] and validated with an independent cohort. Results: Patients (n = 1010) with highest PIRADS lesion in PZ were included in initial analysis with 127 (12.6%) classified as PIRADS 3+ (PIRADS 3 on bpMRI but PIRADS 4 on mpMRI). On multivariable analysis, PIRADS 3+ lesions were associated with higher csPCa rates compared to PIRADS 3- (3+ vs. 3-: OR 1.86, p = 0.024), but lower csPCa rates compared to PIRADS DWI 4 lesions (4 vs. 3+: OR 2.39, p < 0.001). csPCa rates were 19% (3-), 31% (3+), 41.5% (4-), 65.9% (4+), 62.5% (5-), and 92.3% (5+). bpMRI nomograms were non-inferior to mpMRI nomograms in the development (n = 1410) and independent validation (n = 353) cohorts. Risk calculators available at: https://rossnm1.shinyapps.io/MynMRIskCalculator/. Conclusion: While DCE positivity by itself was associated with csPCa among patients with highest PIRADS lesions in the PZ, nomogram comparisons suggest that there is no significant difference in performance of bpMRI and mpMRI. bpMRI may be considered as an alternative to mpMRI for prostate cancer evaluation in many situations.

10.
Sci Rep ; 14(1): 19043, 2024 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152138

RESUMO

Greenhouses located at high latitudes and in cloudy areas often experience a low quality and quantity of light, especially during autumn and winter. This low daily light integral (DLI) reduces production rate, quality, and nutritional value of many crops. This study was conducted on Sakhiya RZ F1 tomato plants to evaluate the impact of LED lights on the growth and nutritional value of tomatoes in a greenhouse with low daily light due to cloudy weather. The treatments included LED growth lights in three modes: top lighting, intra-canopy lighting, and combined top and intra-canopy lighting. The results showed that although the combined top and intra-canopy lighting reached the maximum increase in tomato yield, exposure to intra-canopy LED lighting alone outperformed in tomato fruit yield increase (28.46%) than exposure to top LED lighting alone (12.12%) when compared to no supplemental lighting during the entire production year. Intra-canopy exposure demonstrated the highest increase in tomato lycopene (31.3%), while top and intra-canopy lighting exhibited the highest increase in vitamin C content (123.4%) compared to the control. The LED light treatment also had a very positive effect on the expression of genes responsible for metabolic cycles, including Psy1, LCY-ß, and VTC2 genes, which had collinearity with the increase in tomato fruit production.


Assuntos
Ácido Ascórbico , Regulação da Expressão Gênica de Plantas , Iluminação , Licopeno , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/efeitos da radiação , Solanum lycopersicum/metabolismo , Ácido Ascórbico/metabolismo , Ácido Ascórbico/biossíntese , Licopeno/metabolismo , Luz , Carotenoides/metabolismo , Frutas/genética , Frutas/metabolismo , Frutas/efeitos da radiação
11.
RSC Adv ; 14(35): 25685-25694, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39148760

RESUMO

The waste management sector is moving towards sustainable approaches for facilitating resource-recovery possibilities. Agriculture residue (rice straw), cow dung (cattle waste), and clam shells from the ocean are the primary waste materials possessing a huge value addition opportunity. In this study, the effective usage of rice straw and anaerobic sludge from cow dung for bio-energy production was studied. Cow dung was initially anaerobically processed for the generation of biomethane and sludge in a digester for a retention time of 40 days. The anaerobic sludge with rice straw was hydrothermally processed in varying proportions of 1 : 0, 0 : 1, 1 : 1,1 : 2, 2 : 1, 3 : 1, 1 : 3 and temperatures of 240-360 °C for 1 hour with varying biomass loads of 50, 75, 100, 125, and 150 g. Additionally, clam shells, one of the best bioresources, were used as a catalyst in the hydrothermal process at concentrations of 0.2-1 wt%. The maximum bio-oil produced was 36.23 wt% at a temperature of 320 °C, with a biomass load of 100 g, mixed proportion of 2 : 1 and catalyst loading of 0.6 wt%. The produced bio-oil comprised hydrocarbons, aldehydes, and carboxylic acids, as confirmed through GC-MS. In the anaerobic study, ≈0.018 m3 cumulative gas was produced at a retention time of 40 days. The biochar had a higher carbon content and its feasibility for further usage shows promise towards sustainability.

12.
J Gene Med ; 26(8): e3721, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39114903

RESUMO

To date, 3,900 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our March 2023 update, we have entries on 3,900 trials undertaken in 46 countries. We have analyzed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and which genes have been transferred. Details of the analyses presented, and our searchable database are on The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at https://a873679.fmphost.com/fmi/webd/GTCT. We also provide an overview of the progress being made around the world, and discuss key trends since the previous review, namely the unprecedented increase in gene therapy clinical trial activity, including the implementation of genome editing technology with the potential to transform the field moving forward.


Assuntos
Ensaios Clínicos como Assunto , Terapia Genética , Humanos , Terapia Genética/métodos , Terapia Genética/tendências , Edição de Genes/métodos , Vetores Genéticos
13.
J Diabetes ; 16(8): e13590, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39136500

RESUMO

BACKGROUND: While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well-established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up-to-date systematic review and meta-analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. METHODS: The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM-complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow-up of at least 12 months. RESULTS: Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43-1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta-analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48-0.97; p = 0.03; I2 = 31%). CONCLUSION: This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM-complicated pregnancy and highlights the need for further studies, including pharmacotherapy.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/prevenção & controle , Gravidez , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Fatores de Risco , Hipoglicemiantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Incidência
14.
Structure ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39216472

RESUMO

Non-heme iron-dependent sulfoxide/selenoxide synthases (NHISS) constitute a unique metalloenzyme class capable of installing a C-S/Se bond onto histidine to generate thio/selenoimidazole antioxidants, such as ergothioneine and ovothiol. These natural products are increasingly recognized for their health benefits. Among associated ergothioneine-biosynthetic enzymes, type IV EgtBs stand out, as they exhibit low sequence similarity with other EgtB subfamilies due to their recent divergence from the ovothiol-biosynthetic enzyme OvoA. Herein, we present crystal structures of two representative EgtB-IV enzymes, offering insights into the basis for this evolutionary convergence and enhancing our understanding of NHISS active site organization more broadly. The ability to interpret how key residues modulate substrate specificity and regioselectivity has implications for downstream identification of divergent reactivity within the NHISS family. To this end, we identify a previously unclassified clade of OvoA-like enzymes with a seemingly hybrid set of characteristics, suggesting they may represent an evolutionary intermediate between OvoA and EgtB-IV.

15.
Nat Chem ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143299

RESUMO

Selenium is an essential micronutrient, but its presence in biology has been limited to protein and nucleic acid biopolymers. The recent identification of a biosynthetic pathway for selenium-containing small molecules suggests that there is a larger family of selenometabolites that remains to be discovered. Here we identify a recently evolved branch of abundant and uncharacterized metalloenzymes that we predict are involved in selenometabolite biosynthesis using a bioinformatic search strategy that relies on the mapping of composite active site motifs. Biochemical studies confirm this prediction and show that these enzymes form an unusual C-Se bond onto histidine, thus giving rise to a distinct selenometabolite and potent antioxidant that we have termed ovoselenol. Aside from providing insights into the evolution of this enzyme class and the structural basis of C-Se bond formation, our work offers a blueprint for charting the microbial selenometabolome in the future.

16.
J Neurosurg Case Lessons ; 8(8)2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39159498

RESUMO

BACKGROUND: Odontoid process fractures make up 10%-20% of all cervical spine fractures, with type III fractures having a considerable amount of heterogeneity. Most simple type III fractures can be managed nonoperatively. However, 21% of complex type III fractures with significant displacement and angulation are inadequately treated with external immobilization and require surgery. Achieving a reduction via traction can pose a great challenge during intraoperative manipulation, especially when presentation is delayed. OBSERVATIONS: A 36-year-old male patient, who presented 2 weeks after a motor vehicle crash, had a Glasgow Coma Scale score of 14 and intact motor and sensory function. A craniocervical computed tomograpy scan revealed a normal brain with a type III odontoid fracture. The patient underwent anterior odontoid screw fixation (AOSF) aided by a transoral digital manipulation to achieve a reduction of the irreducible proximal fracture segment at 8 weeks postinjury. The treatment resulted in preserved neurological function and a satisfactory odontoid fracture reduction. LESSONS: Delayed presentation of a complex type III odontoid fracture can be challenging to treat; however, AOSF with the aid of transoral digital manipulation of the irreducible proximal segment can help to achieve good reduction and fusion with the preservation of neurological function in a young patient. https://thejns.org/doi/10.3171/CASE24294.

18.
Bioinformatics ; 40(8)2024 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-38985218

RESUMO

MOTIVATION: Proteins with unknown function are frequently compared to better characterized relatives, either using sequence similarity, or recently through similarity in a learned embedding space. Through comparison, protein sequence embeddings allow for interpretable and accurate annotation of proteins, as well as for downstream tasks such as clustering for unsupervised discovery of protein families. However, it is unclear whether embeddings can be deliberately designed to improve their use in these downstream tasks. RESULTS: We find that for functional annotation of proteins, as represented by Gene Ontology (GO) terms, direct fine-tuning of language models on a simple classification loss has an immediate positive impact on protein embedding quality. Fine-tuned embeddings show stronger performance as representations for K-nearest neighbor classifiers, reaching stronger performance for GO annotation than even directly comparable fine-tuned classifiers, while maintaining interpretability through protein similarity comparisons. They also maintain their quality in related tasks, such as rediscovering protein families with clustering. AVAILABILITY AND IMPLEMENTATION: github.com/mofradlab/go_metric.


Assuntos
Proteínas , Proteínas/química , Algoritmos , Análise por Conglomerados , Ontologia Genética , Biologia Computacional/métodos , Bases de Dados de Proteínas , Anotação de Sequência Molecular/métodos
19.
J Cell Sci ; 137(15)2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-39056156

RESUMO

Small GTPases switch between GDP- and GTP-bound states during cell signaling. The ADP-ribosylation factor (ARF) family of small GTPases is involved in vesicle trafficking. Although evolutionarily well conserved, little is known about ARF and ARF-like GTPases in plants. We characterized biochemical properties and cellular localization of the essential small ARF-like GTPase TITAN 5 (TTN5; also known as HALLIMASCH, ARL2 and ARLC1) from Arabidopsis thaliana, and two TTN5 proteins with point mutants in conserved residues, TTN5T30N and TTN5Q70L, that were expected to be unable to perform nucleotide exchange and GTP hydrolysis, respectively. TTN5 exhibited very rapid intrinsic nucleotide exchange and remarkably low GTP hydrolysis activity, functioning as a non-classical small GTPase being likely present in a GTP-loaded active form. We analyzed signals from YFP-TTN5 and HA3-TTN5 by in situ immunolocalization in Arabidopsis seedlings and through use of a transient expression system. Colocalization with endomembrane markers and pharmacological treatments suggests that TTN5 can be present at the plasma membrane and that it dynamically associates with membranes of vesicles, Golgi stacks and multivesicular bodies. Although TTN5Q70L mirrored wild-type TTN5 behavior, the TTN5T30N mutant differed in some aspects. Hence, the unusual rapid nucleotide exchange activity of TTN5 is linked with its membrane dynamics, and TTN5 likely has a role in vesicle transport within the endomembrane system.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Guanosina Trifosfato/metabolismo , Membrana Celular/metabolismo , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Hidrólise , Complexo de Golgi/metabolismo
20.
Front Vet Sci ; 11: 1385469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978633

RESUMO

Introduction: Anxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy. Methods: Nine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification. Results: Following FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged. Discussion: Behavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT's potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

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