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1.
Mol Cell ; 81(5): 1058-1073.e7, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33421363

RESUMO

Homologous recombination (HR) is an essential DNA double-strand break (DSB) repair mechanism, which is frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated, resected DNA and catalyzes strand invasion into homologous duplex DNA. How RAD51 displaces RPA and assembles into long HR-proficient filaments remains uncertain. Here, we employed single-molecule imaging to investigate the mechanism of nematode RAD-51 filament growth in the presence of BRC-2 (BRCA2) and RAD-51 paralogs, RFS-1/RIP-1. BRC-2 nucleates RAD-51 on RPA-coated DNA, whereas RFS-1/RIP-1 acts as a "chaperone" to promote 3' to 5' filament growth via highly dynamic engagement with 5' filament ends. Inhibiting ATPase or mutation in the RFS-1 Walker box leads to RFS-1/RIP-1 retention on RAD-51 filaments and hinders growth. The rfs-1 Walker box mutants display sensitivity to DNA damage and accumulate RAD-51 complexes non-functional for HR in vivo. Our work reveals the mechanism of RAD-51 nucleation and filament growth in the presence of recombination mediators.


Assuntos
Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas de Transporte/genética , DNA de Helmintos/genética , Proteínas de Ligação a DNA/genética , Rad51 Recombinase/genética , Reparo de DNA por Recombinação , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Transporte/metabolismo , Quebras de DNA de Cadeia Dupla , DNA de Helmintos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mutação , Ligação Proteica , Rad51 Recombinase/metabolismo , Proteína de Replicação A/genética , Proteína de Replicação A/metabolismo , Transdução de Sinais , Imagem Individual de Molécula
2.
PLoS Genet ; 19(2): e1010666, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36809245

RESUMO

Chromosome movements and licensing of synapsis must be tightly regulated during early meiosis to ensure accurate chromosome segregation and avoid aneuploidy, although how these steps are coordinated is not fully understood. Here we show that GRAS-1, the worm homolog of mammalian GRASP/Tamalin and CYTIP, coordinates early meiotic events with cytoskeletal forces outside the nucleus. GRAS-1 localizes close to the nuclear envelope (NE) in early prophase I and interacts with NE and cytoskeleton proteins. Delayed homologous chromosome pairing, synaptonemal complex (SC) assembly, and DNA double-strand break repair progression are partially rescued by the expression of human CYTIP in gras-1 mutants, supporting functional conservation. However, Tamalin, Cytip double knockout mice do not exhibit obvious fertility or meiotic defects, suggesting evolutionary differences between mammals. gras-1 mutants show accelerated chromosome movement during early prophase I, implicating GRAS-1 in regulating chromosome dynamics. GRAS-1-mediated regulation of chromosome movement is DHC-1-dependent, placing it acting within the LINC-controlled pathway, and depends on GRAS-1 phosphorylation at a C-terminal S/T cluster. We propose that GRAS-1 coordinates the early steps of homology search and licensing of SC assembly by regulating the pace of chromosome movement in early prophase I.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Humanos , Camundongos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Pareamento Cromossômico , Segregação de Cromossomos , Mamíferos/genética , Meiose , Prófase Meiótica I , Complexo Sinaptonêmico/metabolismo
3.
PLoS Genet ; 18(10): e1010136, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36279281

RESUMO

Accurate chromosome segregation requires a cohesin-mediated physical attachment between chromosomes that are to be segregated apart, and a bipolar spindle with microtubule plus ends emanating from exactly two poles toward the paired chromosomes. We asked whether the striking bipolar structure of C. elegans meiotic chromosomes is required for bipolarity of acentriolar female meiotic spindles by time-lapse imaging of mutants that lack cohesion between chromosomes. Both a spo-11 rec-8 coh-4 coh-3 quadruple mutant and a spo-11 rec-8 double mutant entered M phase with separated sister chromatids lacking any cohesion. However, the quadruple mutant formed an apolar spindle whereas the double mutant formed a bipolar spindle that segregated chromatids into two roughly equal masses. Residual non-cohesive COH-3/4-dependent cohesin on separated sister chromatids of the double mutant was sufficient to recruit haspin-dependent Aurora B kinase, which mediated bipolar spindle assembly in the apparent absence of chromosomal bipolarity. We hypothesized that cohesin-dependent Aurora B might activate or inhibit spindle assembly factors in a manner that would affect their localization on chromosomes and found that the chromosomal localization patterns of KLP-7 and CLS-2 correlated with Aurora B loading on chromosomes. These results demonstrate that cohesin is essential for spindle assembly and chromosome segregation independent of its role in sister chromatid cohesion.


Assuntos
Caenorhabditis elegans , Proteínas Cromossômicas não Histona , Animais , Feminino , Caenorhabditis elegans/genética , Proteínas Cromossômicas não Histona/genética , Proteínas de Ciclo Celular/genética , Meiose/genética , Cromátides/genética , Segregação de Cromossomos/genética , Fuso Acromático/genética , Coesinas
4.
PLoS Genet ; 18(1): e1010025, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35081133

RESUMO

Genotoxic stress during DNA replication constitutes a serious threat to genome integrity and causes human diseases. Defects at different steps of DNA metabolism are known to induce replication stress, but the contribution of other aspects of cellular metabolism is less understood. We show that aminopeptidase P (APP1), a metalloprotease involved in the catabolism of peptides containing proline residues near their N-terminus, prevents replication-associated genome instability. Functional analysis of C. elegans mutants lacking APP-1 demonstrates that germ cells display replication defects including reduced proliferation, cell cycle arrest, and accumulation of mitotic DSBs. Despite these defects, app-1 mutants are competent in repairing DSBs induced by gamma irradiation, as well as SPO-11-dependent DSBs that initiate meiotic recombination. Moreover, in the absence of SPO-11, spontaneous DSBs arising in app-1 mutants are repaired as inter-homologue crossover events during meiosis, confirming that APP-1 is not required for homologous recombination. Thus, APP-1 prevents replication stress without having an apparent role in DSB repair. Depletion of APP1 (XPNPEP1) also causes DSB accumulation in mitotically-proliferating human cells, suggesting that APP1's role in genome stability is evolutionarily conserved. Our findings uncover an unexpected role for APP1 in genome stability, suggesting functional connections between aminopeptidase-mediated protein catabolism and DNA replication.


Assuntos
Aminopeptidases/genética , Caenorhabditis elegans/genética , Instabilidade Genômica , Aminopeptidases/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Ciclo Celular , Proliferação de Células , Replicação do DNA , Prolina/metabolismo
5.
Planta ; 259(3): 53, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294549

RESUMO

MAIN CONCLUSION: The biostimulant Hanseniaspora opuntiae regulates Arabidopsis thaliana root development and resistance to Botrytis cinerea. Beneficial microbes can increase plant nutrient accessibility and uptake, promote abiotic stress tolerance, and enhance disease resistance, while pathogenic microorganisms cause plant disease, affecting cellular homeostasis and leading to cell death in the most critical cases. Commonly, plants use specialized pattern recognition receptors to perceive beneficial or pathogen microorganisms. Although bacteria have been the most studied plant-associated beneficial microbes, the analysis of yeasts is receiving less attention. This study assessed the role of Hanseniaspora opuntiae, a fermentative yeast isolated from cacao musts, during Arabidopsis thaliana growth, development, and defense response to fungal pathogens. We evaluated the A. thaliana-H. opuntiae interaction using direct and indirect in vitro systems. Arabidopsis growth was significantly increased seven days post-inoculation with H. opuntiae during indirect interaction. Moreover, we observed that H. opuntiae cells had a strong auxin-like effect in A. thaliana root development during in vitro interaction. We show that 3-methyl-1-butanol and ethanol are the main volatile compounds produced by H. opuntiae. Subsequently, it was determined that A. thaliana plants inoculated with H. opuntiae have a long-lasting and systemic effect against Botrytis cinerea infection, but independently of auxin, ethylene, salicylic acid, or jasmonic acid pathways. Our results demonstrate that H. opuntiae is an important biostimulant that acts by regulating plant development and pathogen resistance through different hormone-related responses.


Assuntos
Arabidopsis , Botrytis , Hanseniaspora , Ácidos Indolacéticos
6.
Nutr Cancer ; 76(10): 985-993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39066469

RESUMO

Sarcopenia in cancer patients often negatively impacts various outcomes. Carboplatin, a first-line chemotherapy for non-small cell lung cancer (NSCLC), is dosed based on body weight, which doesn't account for sarcopenia. This study evaluated the association between sarcopenia and carboplatin-related toxicity in NSCLC patients. Patients with locally advanced or metastatic NSCLC treated with carboplatin were included. Toxicity events during the first two cycles of treatment were recorded. Sarcopenia was assessed using pretreatment computed tomography scans analyzed with Slice-O-Matic V4.2 software, defining sarcopenia as a skeletal muscle index (SMI) of <52.4 cm2/m2 for men and <38.5 cm2/m2 for women. Among 146 patients, 52% had sarcopenia. Hematological toxicity occurred in 71.2% of all patients and 77.6% of those with sarcopenia. The fat-free mass index (FFMI) was independently associated with hematological toxicity and dose-limiting toxicity (DLT), which was observed in 55.5% of patients. Sarcopenia significantly correlates with hematological toxicity and DLT during carboplatin treatment in NSCLC patients. Given its prevalence and noninvasive detection, further research is needed to understand its impact on treatment outcomes.


Assuntos
Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Humanos , Carboplatina/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/complicações , Sarcopenia/induzido quimicamente , Feminino , Masculino , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Tomografia Computadorizada por Raios X , Estudos Retrospectivos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/diagnóstico por imagem
7.
BMC Public Health ; 24(1): 498, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365644

RESUMO

BACKGROUND: Differences in type 2 diabetes risk have been reported for several sociodemographic determinants including sex/gender or socioeconomic status. From an intersectional perspective, it is important to not only consider the role of social dimensions individually, but also their intersections. This allows for a deeper understanding of diabetes risk and preventive needs among diverse population groups. METHODS: As an intersectionality-informed approach, multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) was used in a population-based sample of adults without known diabetes in Germany from the cross-sectional survey "Disease knowledge and information needs- Diabetes mellitus (2017)". Diabetes risk was assessed by the German Diabetes Risk Score (GDRS, range 0-122 points), estimating the individual risk of developing type 2 diabetes within the next 5 years based on established self-reported risk factors. Nesting individuals in 12 intersectional strata defined by combining sex/gender, educational level, and history of migration, we calculated measures to quantify the extent to which individual differences in diabetes risk were explained at strata level, and how much this was due to additive or multiplicative intersectional effects of social determinants. RESULTS: Drawing on data of 2,253 participants, we found good discriminatory accuracy of intersectional strata (variance partition coefficient = 14.00% in the simple intersectional model). Model-predicted GDRS means varied between 29.97 (corresponding to a "low risk" of < 2%) in women with high educational level and a history of migration, and 52.73 ("still low risk" of 2-5%) in men with low educational level without a history of migration. Variance in GDRS between strata was mainly explained by additive effects of social determinants (proportional change in variance to intersectional interaction model = 77.95%) with being male and having low educational level being associated with higher GDRS. There was no evidence of multiplicative effects in individual strata. CONCLUSIONS: Type 2 diabetes risk differed between intersectional strata and can to some extent be explained at strata level. The role of intersectional effects was minor and needs to be further investigated. Findings suggest a need for specific preventive measures targeted at large groups with increased diabetes risk, such as men and persons with low educational level.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Transversais , Enquadramento Interseccional , Escolaridade , Alemanha/epidemiologia
8.
Sensors (Basel) ; 24(19)2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39409328

RESUMO

Urban Heat Islands are a major environmental and public health concern, causing temperature increase in urban areas. This study used satellite imagery and machine learning to analyze the spatial and temporal patterns of land surface temperature distribution in the Metropolitan Area of Merida (MAM), Mexico, from 2001 to 2021. The results show that land surface temperature has increased in the MAM over the study period, while the urban footprint has expanded. The study also found a high correlation (r> 0.8) between changes in land surface temperature and land cover classes (urbanization/deforestation). If the current urbanization trend continues, the difference between the land surface temperature of the MAM and its surroundings is expected to reach 3.12 °C ± 1.11 °C by the year 2030. Hence, the findings of this study suggest that the Urban Heat Island effect is a growing problem in the MAM and highlight the importance of satellite imagery and machine learning for monitoring and developing mitigation strategies.

9.
Genes Dev ; 30(21): 2404-2416, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881602

RESUMO

N-terminal acetylation of the first two amino acids on proteins is a prevalent cotranslational modification. Despite its abundance, the biological processes associated with this modification are not well understood. Here, we mapped the pattern of protein N-terminal acetylation in Caenorhabditis elegans, uncovering a conserved set of rules for this protein modification and identifying substrates for the N-terminal acetyltransferase B (NatB) complex. We observed an enrichment for global protein N-terminal acetylation and also specifically for NatB substrates in the nucleus, supporting the importance of this modification for regulating biological functions within this cellular compartment. Peptide profiling analysis provides evidence of cross-talk between N-terminal acetylation and internal modifications in a NAT substrate-specific manner. In vivo studies indicate that N-terminal acetylation is critical for meiosis, as it regulates the assembly of the synaptonemal complex (SC), a proteinaceous structure ubiquitously present during meiosis from yeast to humans. Specifically, N-terminal acetylation of NatB substrate SYP-1, an SC structural component, is critical for SC assembly. These findings provide novel insights into the biological functions of N-terminal acetylation and its essential role during meiosis.


Assuntos
Caenorhabditis elegans/metabolismo , Acetiltransferase N-Terminal B/metabolismo , Complexo Sinaptonêmico/metabolismo , Acetilação , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/metabolismo , Meiose/genética , Mutação , Acetiltransferase N-Terminal B/genética , Proteínas Nucleares/metabolismo , Proteoma , Complexo Sinaptonêmico/química , Complexo Sinaptonêmico/genética
10.
Environ Manage ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271532

RESUMO

The complex relationship between water, energy, food, and ecological systems, known as the WEFE nexus, has emerged as a major topic in the debate about sustainable economic development and resource management. This subject is of special interest in Mediterranean coastal areas as rapid economic expansion driven by population growth, higher influx of tourists, and intensification of agriculture is leading to structural water scarcity conditions. However, addressing the diverse range of issues associated with the nexus is a difficult task due to the existence of intricate interconnections, interdependencies, and nonlinearities within and across its various components. Accordingly, this case study applies a combination of participatory systems modeling and network analysis tools to yield insights into the complexity of this nexus in Axarquia, a region with features that make it an example of water-stressed jurisdictions in the Mediterranean. Overall, our results provide a strong foundation to understand the dynamics that govern this nexus in regions where the availability of freshwater resources is a significant concern. Furthermore, they lay the groundwork for the development of models and scenarios to simulate the impact of various policies and interventions on the overall system.

11.
Z Gerontol Geriatr ; 57(5): 365-370, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38985210

RESUMO

While the biological hallmarks of aging are widely recognized as fundamental mechanisms of biological aging, more recently, there have been calls within geroscience to understand the aging process more comprehensively by adding a perspective of the social hallmarks of aging. Social and behavioral factors, such as socioeconomic status, life events or behavior and beliefs can alter the aging process per se and act in complex interactions with biological pathways. In addition, underlying biological pathways have been proposed for various psychosocial concepts, such as views on age and relationship quality. The aim of the present article is to provide narrative insights into theoretical and empirical developments between social and behavioral gerontology and geroscience or biogerontology. This article focuses on the potential of an interdisciplinary aging research but it also sets out the critical perspective that social gerontology provides.


Assuntos
Envelhecimento , Geriatria , Ciências Sociais , Humanos , Envelhecimento/psicologia , Envelhecimento/fisiologia , Idoso , Idoso de 80 Anos ou mais , Ciências do Comportamento , Masculino
12.
Anal Biochem ; 674: 115195, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37268197

RESUMO

In this work, a quantitative sandwich ELISA was optimized, through a full factorial design of experiments (DOE) in successive steps of a preliminary protocol obtained by the method of one factor at a time (OFAT). The specificity of the optimized ELISA, the lower limit of quantification, the quantification range and the analytical sensitivity of the antigen quantification curve were evaluated, in comparison with the curve obtained from the preliminary protocol. The full factorial DOE was linked to a simple statistical processing, which facilitates the interpretation of the results in those laboratories where there is no trained statistician. The step-by-step optimization of the ELISA and the successive incorporation into the protocol of the best combination of factors and levels, allowed obtaining a specific immunoassay, with an analytical sensitivity 20 times greater and with a lower limit of antigen quantification that decreased from 156.25 at 9.766 ng/mL. As far as we know, there are no reports of optimization of an ELISA following the step-by-step scheme used in this work. The optimized ELISA will be used for the quantification of the TT-P0 protein, the active principle of a vaccine candidate against sea lice.


Assuntos
Antígenos , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio
13.
BMC Gastroenterol ; 23(1): 229, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400812

RESUMO

BACKGROUND: Probiotics are effective for treating acute infectious diarrhoea caused by bacteria, but there are inconsistent results for the effectiveness of probiotics for diarrhoea caused by viruses. In this article we want to determine whether Sb supplementation has an effect on acute inflammatory viral diarrhoea diagnosed with the multiplex panel PCR test. The aim of this study was to evaluate the efficacy of Saccharomyces boulardii (Sb) as a treatment in patients diagnosed with viral acute diarrhoea. METHODS: From February 2021 to December 2021, 46 patients with a confirmed diagnosis of viral acute diarrhoea diagnosed with the polymerase chain reaction multiplex assay were enrolled in a double-blind, randomized placebo-controlled trial. Patients received paracetamol 500 mg as a standard analgesic and 200 mg of Trimebutine as an antispasmodic treatment plus 600 mg of Sb (n = 23, 1 × 109/100 mL Colony forming unit) or a placebo (n = 23) orally once daily for eight days. The improvement in and severity of symptoms were measured using a symptom diary, the Patient Global Impression and the Patient Global Impression of Change scales (days 4 and 8), both answered and recorded by the patient. RESULTS: Of the 46 patients who completed treatment, 24 (52%) were men and 22 (48%) were women. The average age was 35.6 ± 12.28 years (range 18 to 61 years). The average duration of the evolution of illness at the time of diagnosis was 0.85 ± 0.73 days (maximum 2 days). On day 4 after the diagnosis, 20% reported pain and 2% reported fever, but on day 8, no patient reported pain or fever. On day 4, 70% of patients in the Sb group and 26% in the placebo group reported improvement (P = 0.03), based on the Patients' Global Impression of Change scale, which assesses patient's rating of overall improvement. These findings suggest that 3 to 4 days of treatment with Sb helped to improve symptoms of diarrhoea caused by a virus. CONCLUSION: Treatment with Sb on acute inflammatory diarrhoea of viral aetiology shows no changes regarding the severity of the symptoms; nevertheless, it seems to impact improvement positively. TRIAL REGISTRATION: 22CEI00320171130 dated on 16/12/2020, NCT05226052 dated on 07/02/2022.


Assuntos
Enterite , Probióticos , Saccharomyces boulardii , Saccharomyces , Masculino , Humanos , Adulto , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Resultado do Tratamento , Saccharomyces cerevisiae , Diarreia/terapia , Diarreia/microbiologia , Probióticos/uso terapêutico , Método Duplo-Cego
14.
Surg Endosc ; 37(12): 9062-9069, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37964092

RESUMO

OBJECTIVE: Sphincter of Oddi dysfunction (SOD) has been used to describe patients with RUQ abdominal pain without an etiology. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of ES (endoscopic sphincterotomy) for SOD. METHODS: The study methodology follows the PRISMA guidelines. A comprehensive search was conducted using MEDLINE and EMBASE databases for RCTs with ES in patients with SOD. The primary outcome assessed was the improvement of abdominal pain after ES/sham. A random effects model was used to calculate pooled estimates for each outcome of interest. RESULTS: Of the initial 55 studies, 23 were screened and thoroughly reviewed. The final analysis included 3 studies. 340 patients (89.7% women) with SOD were included. All patients had a cholecystectomy. Most included patients had SOD type II and III. The pooled rate of technical success of ERCP was 100%. The average clinical success rate was 50%. The pooled cumulative rate of overall AEs related to all ERCP procedures was 14.6%. In the sensitivity analysis, only one study significantly affected the outcome or the heterogeneity. CONCLUSION: ES appears no better than placebo in patients with SOD type III. Sphincterotomy could be considered in patients with SOD type II and elevated SO basal pressure.


Assuntos
Disfunção do Esfíncter da Ampola Hepatopancreática , Esfíncter da Ampola Hepatopancreática , Humanos , Feminino , Masculino , Esfinterotomia Endoscópica/efeitos adversos , Esfinterotomia Endoscópica/métodos , Disfunção do Esfíncter da Ampola Hepatopancreática/cirurgia , Disfunção do Esfíncter da Ampola Hepatopancreática/etiologia , Esfíncter da Ampola Hepatopancreática/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Manometria , Dor Abdominal/etiologia
15.
PLoS Genet ; 16(11): e1008968, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175901

RESUMO

In the two cell divisions of meiosis, diploid genomes are reduced into complementary haploid sets through the discrete, two-step removal of chromosome cohesion, a task carried out in most eukaryotes by protecting cohesion at the centromere until the second division. In eukaryotes without defined centromeres, however, alternative strategies have been innovated. The best-understood of these is found in the nematode Caenorhabditis elegans: after the single off-center crossover divides the chromosome into two segments, or arms, several chromosome-associated proteins or post-translational modifications become specifically partitioned to either the shorter or longer arm, where they promote the correct timing of cohesion loss through as-yet unknown mechanisms. Here, we investigate the meiotic axis HORMA-domain protein HIM-3 and show that it becomes phosphorylated at its C-terminus, within the conserved "closure motif" region bound by the related HORMA-domain proteins HTP-1 and HTP-2. Binding of HTP-2 is abrogated by phosphorylation of the closure motif in in vitro assays, strongly suggesting that in vivo phosphorylation of HIM-3 likely modulates the hierarchical structure of the chromosome axis. Phosphorylation of HIM-3 only occurs on synapsed chromosomes, and similarly to other previously-described phosphorylated proteins of the synaptonemal complex, becomes restricted to the short arm after designation of crossover sites. Regulation of HIM-3 phosphorylation status is required for timely disassembly of synaptonemal complex central elements from the long arm, and is also required for proper timing of HTP-1 and HTP-2 dissociation from the short arm. Phosphorylation of HIM-3 thus plays a role in establishing the identity of short and long arms, thereby contributing to the robustness of the two-step chromosome segregation.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Complexo Sinaptonêmico/metabolismo , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/ultraestrutura , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/genética , Pareamento Cromossômico , Segregação de Cromossomos , Cromossomos , Meiose/fisiologia , Fosforilação , Prófase/fisiologia , Domínios Proteicos
16.
Am J Otolaryngol ; 44(2): 103764, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36587603

RESUMO

OBJECTIVE: The pathophysiology of Meniere's Disease (MD) involves endolymphatic hydrops (ELH) of the inner ear. Magnetic Resonance Imaging (MRI) has been shown to detect ELH, but changes in ELH have been poorly described using this modality. Our objective was to review MRI-measured changes in ELH over time and after medical and/or surgical intervention in patients with MD. We secondarily aim to associate changes in ELH with changes in MD symptomatology. DATABASES REVIEWED: Medline, Web of Science, and Embase databases. METHODS: A systematic review of articles was performed to identify studies utilizing MRI to measure ELH changes over time, and after medical or surgical treatment. Articles on non-human subjects and without direct measurement of ELH were excluded. RESULTS: Of 532 studies identified, 12 were included, involving 170 patients (mean age 56.3 years). Ten studies were prospective; two were retrospective. Five studies strictly utilized medical means of intervention, four utilized surgical treatments, one utilized both, and two observed temporal changes without treatment. Across all interventions, 72.1 % of patients exhibited the same or worsening ELH on imaging. In studies reporting vertigo outcomes, 95.9 % of patients exhibited improvement after the treatment period. CONCLUSION: Medical and surgical interventions often yield symptomatic relief of vertigo in MD patients despite stable or increasing ELH volume. MRI may have greater clinical utility in diagnosing ELH as opposed to assessing treatment response.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Hidropisia Endolinfática/diagnóstico por imagem , Hidropisia Endolinfática/patologia , Doença de Meniere/complicações , Doença de Meniere/diagnóstico por imagem , Doença de Meniere/patologia , Vertigem , Imageamento por Ressonância Magnética/métodos
17.
Am J Otolaryngol ; 44(1): 103682, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36306708

RESUMO

PURPOSE: Musculoskeletal disorders are prevalent among otolaryngologists and otologists with symptoms starting during residency. Prior data suggested that high-risk joint angles were often adopted at procedure onset, suggesting a detrimental "natural" operating position. Despite its importance, dedicated ergonomic teaching is not systematically introduced into residency training. The objective of this study was to compare initial ergonomic positioning during microscopic temporal bone surgery between those who receive "Just in Time" ergonomic teaching prior to starting dissection with those who did not. MATERIALS AND METHODS: This was a pilot, prospective trial in which otolaryngology residents at an urban, multicenter tertiary care academic institution (n = 14) wore ergonomic sensors (inertial measurement units) during microscopic temporal bone lab drilling. Prior to recording, participants were randomized to receive an instructional presentation on ergonomic principles (n = 8, intervention group) or not (n = 6, control group). The inertial measurement units analyzed neck and back angles for the initial 5 min of drilling. RESULTS: Of 14 trainees, 78.6 % had prior experience with otologic microscopic cases and 14.3 % reported prior surgical ergonomic training or instruction. The groups were matched in trainee height (P = 0.54), handedness (P = 0.83), stage of otolaryngology training (P = 0.64), prior otologic microscopic surgery experience (P = 0.35), prior temporal bone drilling experience (P = 0.35), and prior teaching in ergonomic principles (P = 0.47). Junior trainees (PGY 1-3) who did not receive "Just in Time" teaching adopted a posture with significantly higher risk back flexion compared to junior trainees who received the training (25.3° vs. 5.7°, P = 0.04). There was no difference in back positioning among senior trainees (12.6° vs. -5.7°, P = 0.13). While there was a trend towards those in the intervention group adopting safer procedural posture, there was no significant difference in the overall cohort between the intervention and control groups in both neck positioning (-11.0° vs. -19.1°, P = 0.17) and back positioning (8.6° vs. 19.1°, P = 0.18). CONCLUSIONS: Musculoskeletal related pain is prevalent among otolaryngologists and otologists with data suggesting that symptoms begin during residency. Targeted "Just in Time" teaching of ergonomic principles is feasible and may be effective for development of healthy postural habits, especially among junior trainees.


Assuntos
Doenças Musculoesqueléticas , Doenças Profissionais , Otolaringologia , Humanos , Estudos Prospectivos , Ergonomia/métodos , Doenças Musculoesqueléticas/prevenção & controle , Postura , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle
18.
J Dairy Res ; 90(2): 138-141, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37139948

RESUMO

Live weight (LW) is an important piece of information within production systems, as it is related to several other economic characteristics. However, in the main buffalo-producing regions in the world, it is not common to periodically weigh the animals. We develop and evaluate linear, quadratic, and allometric mathematical models to predict LW using the body volume (BV) formula in lactating water buffalo (Bubalus bubalis) reared in southeastern Mexico. The LW (391.5 ± 138.9 kg) and BV (333.62 ± 58.51 dm3) were measured in 165 lactating Murrah buffalo aged between 3 and 10 years. The goodness-of-fit of the models was evaluated using the Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), coefficient of determination (R2), mean-squared error (MSE) and root MSE (RMSE). In addition, the developed models were evaluated through cross-validation (k-folds). The ability of the fitted models to predict the observed values was evaluated based on the RMSEP, R2, and mean absolute error (MAE). LW and BV were significantly positively and strongly correlated (r = 0.81; P < 0.001). The quadratic model had the lowest values of MSE (2788.12) and RMSE (52.80). On the other hand, the allometric model showed the lowest values of BIC (1319.24) and AIC (1313.07). The Quadratic and allometric models had lower values of MSEP and MAE. We recommend the quadratic and allometric models to predict the LW of lactating Murrah buffalo using BV as a predictor.


Assuntos
Búfalos , Lactação , Feminino , Animais , Teorema de Bayes , México , Peso Corporal
19.
Rev Esp Enferm Dig ; 115(3): 110-114, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35656921

RESUMO

INTRODUCTION: retention is the most common adverse event of the small bowel capsule endoscopy procedure. Patency capsule (Medtronic, Dublin, Ireland) and magnetic resonance enterography are two diagnostic methods that can prevent small bowel capsule endoscopy retention. The aim of this study was to evaluate the predictive value of these two diagnostic methods. MATERIAL AND METHODS: a prospective, comparative and observational study was performed in patients with established Crohn's disease. All patients had undergone magnetic resonance enterography and patency capsule procedures. If the patency capsule was not retained, the patient underwent a small bowel capsule endoscopy; otherwise, double balloon enteroscopy was performed to locate the stenosis. Magnetic resonance enterography predictive criteria for retention were analyzed in all cases. Sensitivity, specificity, positive predictive value and negative predictive value of the patency capsule and magnetic resonance enterography compared to small bowel capsule endoscopy or double balloon enteroscopy were calculated. RESULTS: forty patients were included (24 female, 55 ± 13 years old). Retention criteria with capsule endoscopy or double balloon enteroscopy were found in six patients, agreeing in five cases with patency capsule and in three cases with magnetic resonance enterography. Sensitivity, specificity, positive predictive value, negative predictive value and Kappa coefficient for predicting retention with the patency capsule were 83 %, 100 %, 100 % and 97 %, respectively, and 50 %, 91 %, 50 % and 91 %, respectively, with magnetic resonance enterography. CONCLUSIONS: patency capsule has a higher sensitivity and positive predictive value than magnetic resonance enterography for preventing small bowel capsule endoscopy retention in Crohn's disease patients.


Assuntos
Endoscopia por Cápsula , Doença de Crohn , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doença de Crohn/diagnóstico , Endoscopia por Cápsula/métodos , Estudos Prospectivos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Espectroscopia de Ressonância Magnética
20.
Trop Anim Health Prod ; 55(5): 300, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37723326

RESUMO

This study aimed to predict Blackbelly sheep carcass tissue composition using ultrasound measurements and machine learning models. The models evaluated were decision trees, random forests, support vector machines, and multi-layer perceptrons and were used to predict the total carcass bone (TCB), total carcass fat (TCF), and total carcass muscle (TCM). The best model for predicting the three parameters, TCB, TCF, and TCM was random forests, with mean squared error (MSE) of 0.31, 0.33, and 0.53; mean absolute error (MAE) of 0.26, 0.29, and 0.53; and the coefficient of determination (R2) of 0.67, 0.69, and 0.76, respectively. The results showed that machine learning methods from in vivo ultrasound measurements can be used as determinants of carcass tissue composition, resulting in reliable results.


Assuntos
Aprendizado de Máquina , Músculos , Animais , Ovinos , Ultrassonografia/veterinária , Redes Neurais de Computação , Algoritmo Florestas Aleatórias
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