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1.
Proc Natl Acad Sci U S A ; 120(50): e2314335120, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38055743

RESUMO

Successful chromosome segregation into gametes depends on tightly regulated interactions between the parental chromosomes. During meiosis, chromosomes are aligned end-to-end by an interface called the synaptonemal complex, which also regulates exchanges between them. However, despite the functional and ultrastructural conservation of this essential interface, how protein-protein interactions within the synaptonemal complex regulate chromosomal interactions remains poorly understood. Here, we describe a genetic interaction in the C. elegans synaptonemal complex, comprised of short segments of three proteins, SYP-1, SYP-3, and SYP-4. We identified the interaction through a saturated suppressor screen of a mutant that destabilizes the synaptonemal complex. The specificity and tight distribution of suppressors suggest a charge-based interface that promotes interactions between synaptonemal complex subunits and, in turn, allows intimate interactions between chromosomes. Our work highlights the power of genetic studies to illuminate the mechanisms that underlie meiotic chromosome interactions.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/metabolismo , Complexo Sinaptonêmico/genética , Complexo Sinaptonêmico/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Meiose/genética , Pareamento Cromossômico , Proteínas Nucleares/metabolismo
2.
Nucleic Acids Res ; 50(4): 2287-2301, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35137150

RESUMO

Subdomain 5BSL3.2 of hepatitis C virus RNA lies at the core of a network of distal RNA-RNA contacts that connect the 5' and 3' regions of the viral genome and regulate the translation and replication stages of the viral cycle. Using small-angle X-ray scattering and NMR spectroscopy experiments, we have determined at low resolution the structural models of this subdomain and its distal complex with domain 3'X, located at the 3'-terminus of the viral RNA chain. 5BSL3.2 adopts a characteristic 'L' shape in solution, whereas the 5BSL3.2-3'X distal complex forms a highly unusual 'Y'-shaped kissing junction that blocks the dimer linkage sequence of domain 3'X and promotes translation. The structure of this complex may impede an effective association of the viral polymerase with 5BSL3.2 and 3'X to start negative-strand RNA synthesis, contributing to explain the likely mechanism used by these sequences to regulate viral replication and translation. In addition, sequence and shape features of 5BSL3.2 are present in functional RNA motifs of flaviviruses, suggesting conserved regulatory processes within the Flaviviridae family.


Assuntos
Flaviviridae , Hepacivirus , Regiões 3' não Traduzidas , Genoma Viral , Hepacivirus/genética , Modelos Estruturais , Conformação de Ácido Nucleico , RNA Viral/química , RNA Viral/genética , Replicação Viral/genética
3.
J Clin Child Adolesc Psychol ; 53(1): 66-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36998122

RESUMO

OBJECTIVE: Latinx youth exhibit disproportionately higher internalizing symptoms than their peers from other racial/ethnic groups. This study compares depression and anxiety symptoms between referred students of Latinx and non-Latinx backgrounds before and during the COVID-19 pandemic and examines key determinants within the Latinx sample. METHOD: Data are analyzed from four academic years - two before and two during the pandemic - from 1220 5th through 8th grade students (Mage = 12.1; 59.6% female; 59.9% Latinx or mixed-Latinx) referred for services across 59 Chicago Public School District (CPS) elementary schools. Using the Children's Depression Inventory (CDI) and the Revised Child Anxiety and Depression Scale (RCADS), mean scores and risk levels for depression, social anxiety, and generalized anxiety are examined. RESULTS: Higher internalizing risk and comorbidity rates were found in the second year of the pandemic, compared to pre-pandemic levels. Latinx students reported higher depression, social anxiety, and generalized anxiety symptoms than non-Latinx students. During the pandemic, more Latinx students were classified as having comorbid depression and anxiety, and scored in the clinical range for depression, generalized anxiety, and social anxiety than non-Latinx students. Within the Latinx sample, girls and gender non-conforming students reported the highest maladjustment. CONCLUSIONS: Results highlight the pressing need to examine the long-term impact of COVID-19 on the mental health of Latinx children and adolescents, and to address their internalizing problems.


Assuntos
COVID-19 , Hispânico ou Latino , Adolescente , Criança , Feminino , Humanos , Masculino , Ansiedade/psicologia , Depressão/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Pandemias , COVID-19/epidemiologia , COVID-19/etnologia , COVID-19/psicologia , Chicago/epidemiologia , Pessoas em não Conformidade de Gênero/psicologia , Pessoas em não Conformidade de Gênero/estatística & dados numéricos
4.
Nano Lett ; 23(7): 2883-2889, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37001024

RESUMO

Strong hot-spots can facilitate photocatalytic reactions potentially providing effective solar-to-chemical energy conversion pathways. Although it is well-known that the local electromagnetic field in plasmonic nanocavities increases as the cavity size reduces, the influence of hot-spots on photocatalytic reactions remains elusive. Herein, we explored hot-spot dependent catalytic behaviors on a highly controlled platform with varying interparticle distances. Plasmon-meditated dehalogenation of 4-iodothiophenol was employed to observe time-resolved catalytic behaviors via in situ surface-enhanced Raman spectroscopy on dimers with 5, 10, 20, and 30 nm interparticle distances. As a result, we show that by reducing the gap from 20 to 10 nm, the reaction rate can be sped up more than 2 times. Further reduction in the interparticle distance did not improve reaction rate significantly although the maximum local-field was ∼2.3-fold stronger. Our combined experimental and theoretical study provides valuable insights in designing novel plasmonic photocatalytic platforms.

5.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731832

RESUMO

Cancer is a disease that encompasses multiple and different malignant conditions and is among the leading causes of death in the world. Therefore, the search for new pharmacotherapeutic options and potential candidates that can be used as treatments or adjuvants to control this disease is urgent. Natural products, especially those obtained from plants, have played an important role as a source of specialized metabolites with recognized pharmacological properties against cancer, therefore, they are an excellent alternative to be used. The objective of this research was to evaluate the action of the monoterpene isoespintanol (ISO) against the human tumor cell lines MDA-MB-231, A549, DU145, A2780, A2780-cis and the non-tumor line MRC-5. Experiments with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and fluorescence with propidium iodide (PI), 4',6-diamidino-2-phenylindole dilactate (DAPI) and green plasma revealed the cytotoxicity of ISO against these cells; furthermore, morphological and chromogenic studies revealed the action of ISO on cell morphology and the inhibitory capacity on reproductive viability to form colonies in MDA-MB-231 cells. Likewise, 3D experiments validated the damage in these cells caused by this monoterpene. These results serve as a basis for progress in studies of the mechanisms of action of these compounds and the development of derivatives or synthetic analogues with a better antitumor profile.


Assuntos
Monoterpenos , Humanos , Linhagem Celular Tumoral , Monoterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos
6.
Molecules ; 29(18)2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39339412

RESUMO

Candida sp. infections are a threat to global health, with high morbidity and mortality rates due to drug resistance, especially in immunocompromised people. For this reason, the search for new alternatives is urgent, and in recent years, a combined therapy with natural compounds has been proposed. Considering the biological potential of isoespintanol (ISO) and continuing its study, the objective of this research was to assess the effect of ISO in combination with the antifungals fluconazole (FLZ), amphotericin B (AFB) and caspofungin (CASP) against clinical isolates of C. tropicalis and to evaluate the cytotoxic effect of this compound in the acute phase (days 0 and 14) and chronic phase (days 0, 14, 28, 42, 56, 70 and 84) in female mice (Mus musculus) of the Balb/c lineage. The results show that ISO can potentiate the effect of FLZ, AFB and CASP, showing synergism with these antifungals. An evaluation of the mice via direct observation showed no behavioral changes or variations in weight during treatment; furthermore, an analysis of the cytokines IFN-γ and TNF in plasma, peritoneal cavity lavage (PCL) and bronchoalveolar lavage (BAL) indicated that there was no inflammation process. In addition, histopathological studies of the lungs, liver and kidneys showed no signs of toxicity caused by ISO. This was consistent with an analysis of oxaloacetic transaminases (GOT) and pyruvic transaminases (GPT), which remained in the standard range. These findings indicate that ISO does not have a cytotoxic effect at the doses evaluated, placing it as a monoterpene of interest in the search for compounds with pharmacological potential.


Assuntos
Antifúngicos , Sinergismo Farmacológico , Camundongos Endogâmicos BALB C , Animais , Antifúngicos/farmacologia , Camundongos , Feminino , Monoterpenos/farmacologia , Testes de Sensibilidade Microbiana , Anfotericina B/farmacologia , Anfotericina B/toxicidade , Candidíase/tratamento farmacológico , Candida tropicalis/efeitos dos fármacos , Fluconazol/farmacologia , Citocinas/metabolismo , Citocinas/sangue , Caspofungina/farmacologia
7.
Folia Primatol (Basel) ; : 1-26, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39317367

RESUMO

Adequate knowledge and learning about local biodiversity are a prerequisite for effective attitudinal changes in favour of species protection. Outreach activities are considered a useful tool for sharing information with local stakeholders who play a crucial role in conserving wildlife. We conducted two outreach campaigns focused on schoolchildren in two villages to share information on the natural history of the Bolivian endemic titi monkeys, Plecturocebus olallae and Plecturocebus modestus, to promote their conservation. We assessed the students' ability to retain new information and their understanding of biodiversity through pre- and post-questionnaires, finding an improvement in the knowledge about these two endemic primates from pre- to post-talk assessments, as well as an increase in their awareness about local efforts to preserve biodiversity between outreach campaigns. We also found signals of appropriate experiential learning on wildlife value and its relationship with human activities. Additional outreach work across two decades resulted in important achievements that reflect positive attitudinal changes in favour of the endemic primates and biodiversity, with a remarkable involvement of local people. In this way, we show how outreach work can promote important local support for biodiversity conservation, how primates can act as flagship species, and the need to reinforce knowledge acquisition and learning processes to consolidate conservation actions in the long-term.

8.
Int Ophthalmol ; 44(1): 125, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431898

RESUMO

PURPOSE: To evaluate the association between LASIK and early cataract phacoemulsification surgery (PE). METHODS: A matched case-control study was conducted. Cases were otherwise healthy adults with a history of LASIK. Groups were paired according to corrected-distance visual acuity (CDVA), axial length, and cataract grade. RESULTS: A total of 213 patients were included. 85 patients were classified as post-LASIK group and 128 as controls. The mean age at the time of LASIK was 42.32 ± 9.24 years. The mean CDVA before PE was 0.29 ± 0.19 Log MAR in post-LASIK group and 0.34 ± 0.22 Log MAR in controls (p = 0.07). The mean axial length was 23.99 ± 1.78 mm in post-LASIK group and 23.62 ± 0.98 mm in controls (p = 0.085). The mean nuclear cataract grading was 1.36 in post-LASIK group and 1.47 in controls (p = 0.34). The mean age at the time of PE was 60.18 ± 7.46 years in post-LASIK group and 67.35 ± 9.28 in controls (p < 0.0005). The difference between the mean age of LASIK and the mean age of PE was 17.85 ± 5.72 years. There was a positive association between the post-LASIK group and the age of PE ≤ 55 years (OR: 4.917, 95% CI: 2.21-10.90, p < 0.001). CONCLUSION: LASIK may be associated with early PE. Patients with LASIK had a 7-year earlier PE compared to a matched control group.


Assuntos
Extração de Catarata , Catarata , Ceratomileuse Assistida por Excimer Laser In Situ , Facoemulsificação , Adulto , Humanos , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos de Casos e Controles , Catarata/complicações
9.
J Clin Microbiol ; 61(4): e0003623, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36975783

RESUMO

Nontuberculous mycobacteria (NTM) are gaining interest with the increased number of infected patients. NTM Elite agar is designed specifically for the isolation of NTM without the decontamination step. We assessed the clinical performance of this medium combined with Vitek mass spectrometry (MS) matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) technology for the isolation and identification of NTM in a prospective multicenter study, including 15 laboratories (24 hospitals). A total of 2,567 samples from patients with suspected NTM infection were analyzed (1,782 sputa, 434 bronchial aspirates, 200 bronchoalveolar lavage samples, 34 bronchial lavage samples, and 117 other samples). A total of 220 samples (8.6%) were positive with existing laboratory methods against 330 with NTM Elite agar (12.8%). Using the combination of both methods, 437 isolates of NTM were detected in 400 positive samples (15.6% of samples). In total, 140 samples of the standard procedures (SP) and 98 of the NTM Elite agar were contaminated. NTM Elite agar showed a higher performance for rapidly growing mycobacteria (RGM) species than SP (7% versus 3%, P < 0.001). A trend has been noted for the Mycobacterium avium complex (4% with SP versus 3% with NTM Elite agar, P = 0.06). The time to positivity was similar (P = 0.13) between groups. However, the time to positivity was significantly shorter for the RGM in subgroup analysis (7 days with NTM and 6 days with SP, P = 0.01). NTM Elite agar has been shown to be useful for the recovery of NTM species, especially for the RGM. Using NTM Elite agar + Vitek MS system in combination with SP increases the number of NTM isolated from clinical samples.


Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Humanos , Micobactérias não Tuberculosas , Ágar , Estudos Prospectivos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Complexo Mycobacterium avium , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
10.
Retina ; 43(8): 1377-1385, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37071923

RESUMO

PURPOSE: To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions." METHODS: Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS: Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography. CONCLUSION: Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.


Assuntos
Corioidite , Humanos , Coroidite Multifocal , Estudos Retrospectivos , Fundo de Olho , Corioidite/diagnóstico , Corioide/patologia , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos
11.
J Math Biol ; 87(1): 9, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37329353

RESUMO

The Kuramoto model was developed to describe the coupling of oscillators, motivated by the natural synchronization phenomena. We are interested in modeling an epileptic seizure considering it as the synchronization of action potentials using and modifying this model. In this article, we propose to modify this model, changing the constant coupling force for a function with logistic growth to simulate the onset and epileptic seizure level in an adult male rat caused by the administration of lithium-pilocarpine. Later, we select some frequencies and their respective amplitude values using an algorithm based on the fast Fourier transform (FFT) from an electroencephalography signal when the rat is in basal conditions. Then, we take these values as the natural frequencies of the oscillators in the modified Kuramoto model, considering every oscillator as a single neuron to simulate the emergence of an epileptic seizure numerically by increasing the synchronization value in the coupling function. Finally, using Dynamic Time Warping algorithm, we compare the simulated signal by the Kuramoto model with an FFT approximation of the epileptic seizure.


Assuntos
Epilepsia , Convulsões , Masculino , Ratos , Animais , Convulsões/diagnóstico , Epilepsia/diagnóstico , Eletroencefalografia , Algoritmos , Neurônios
12.
Euro Surveill ; 28(24)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37318762

RESUMO

BackgroundAppropriate vaccination strategies have been key to controlling the outbreak of mpox outside endemic areas in 2022, yet few studies have provided information on mpox vaccine effectiveness (VE).AimTo assess VE after one dose of a third-generation smallpox vaccine against mpox when given as post-exposure prophylaxis (PEP) within 14 days.MethodsA survival analysis in a prospective cohort of close contacts of laboratory-confirmed mpox cases was conducted from the beginning of the outbreak in the region of Madrid in May 2022. The study included contacts of cases in this region diagnosed between 17 May and 15 August 2022. Follow up was up to 49 days. A multivariate proportional hazard model was used to evaluate VE in the presence of confounding and interaction.ResultsInformation was obtained from 484 close contacts, of which 230 were vaccinated within 14 days of exposure. Of the close contacts, 57 became ill during follow-up, eight vaccinated and 49 unvaccinated. The adjusted effectiveness of the vaccine was 88.8% (95% CI: 76.0-94.7). Among sexual contacts, VE was 93.6% (95% CI: 72.1-98.5) for non-cohabitants and 88.6% (95% CI: 66.1-96.2) for cohabitants.ConclusionPost-exposure prophylaxis of close contacts of mpox cases is an effective measure that can contribute to reducing the number of cases and eventually the symptoms of breakthrough infections. The continued use of PEP together with pre-exposure prophylaxis by vaccination and other population-targeted prevention measures are key factors in controlling an mpox outbreak.


Assuntos
Mpox , Humanos , Estudos Prospectivos , Espanha/epidemiologia , Eficácia de Vacinas , Surtos de Doenças/prevenção & controle
13.
Euro Surveill ; 28(27)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37410383

RESUMO

BackgroundSince May 2022, an mpox outbreak affecting primarily men who have sex with men (MSM) has occurred in numerous non-endemic countries worldwide. As MSM frequently reported multiple sexual encounters in this outbreak, reliably determining the time of infection is difficult; consequently, estimation of the incubation period is challenging.AimWe aimed to provide valid and precise estimates of the incubation period distribution of mpox by using cases associated with early outbreak settings where infection likely occurred.MethodsColleagues in European countries were invited to provide information on exposure intervals and date of symptom onset for mpox cases who attended a fetish festival in Antwerp, Belgium, a gay pride festival in Gran Canaria, Spain or a particular club in Berlin, Germany, where early mpox outbreaks occurred. Cases of these outbreaks were pooled; doubly censored models using the log-normal, Weibull and Gamma distributions were fitted to estimate the incubation period distribution.ResultsWe included data on 122 laboratory-confirmed cases from 10 European countries. Depending on the distribution used, the median incubation period ranged between 8 and 9 days, with 5th and 95th percentiles ranging from 2 to 3 and from 20 to 23 days, respectively. The shortest interval that included 50% of incubation periods spanned 8 days (4-11 days).ConclusionCurrent public health management of close contacts should consider that in approximately 5% of cases, the incubation period exceeds the commonly used monitoring period of 21 days.


Assuntos
Homossexualidade Masculina , Mpox , Humanos , Masculino , Berlim/epidemiologia , Surtos de Doenças , Férias e Feriados , Período de Incubação de Doenças Infecciosas , Mpox/epidemiologia , Minorias Sexuais e de Gênero
14.
J Environ Manage ; 329: 117038, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36528941

RESUMO

The long-term success of forest restoration programs can be improved using climate-based species distribution models (SDMs) to predict which tree species will tolerate climate change. However, as SDMs cannot estimate if species will recruit at these habitats, determining whether their predictions apply to early life-cycle stages of trees is critical to support such a usage. For this, we propose sowing seeds of the focal tree species under the current climate and simulated climate change conditions in target restoration sites. Thus, using of SDMs to design climate-adaptive forest restoration programs would be supported if the differences in habitat occupancy probabilities of species they predict between the current and future climate concurs with the observed differences in recruitment rates of species when sowed under the current climate and simulated climate change conditions. To test this hypothesis, we calibrated SDMs for Vachellia pennatula and Prosopis laevigata, two pioneer tree species widely recommended to restore human-degraded drylands in Mexico, and transferred them to climate change scenarios. After that, we applied the experimental approach proposed above to validate the predictions of SDMs. These models predicted that V. pennatula will decrease its habitat occupancy probabilities across Mexico, while P. laevigata was predicted to keep out their current habitat occupancy probabilities, or even increase them, in climate change scenarios. The results of the field experiment supported these predictions, as recruitment rates of V. pennatula were lower under simulated climate change than under the current climate, while no differences were found for the recruitment rates of P. laevigata between these environmental conditions. These findings demonstrate that SDMs provide meaningful insights for designing climate-adaptive forest restoration programs but, before applying this methodology, predictions of these models must be validated with field experiments to determine whether the focal tree species will recruit under climate change conditions. Moreover, as the pioneer trees used to test our proposal seem to be differentially sensitive to climate change, this approach also allows establishing what species must be prescribed to restore forests with a view to the future and what species must be avoided in these practices.


Assuntos
Mudança Climática , Florestas , Árvores , Humanos , Ecossistema , Previsões , México
15.
Int Ophthalmol ; 43(9): 3257-3262, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37140835

RESUMO

PURPOSE: To evaluate the prevalence and clinical characteristics of neurotrophic keratopathy (NK) in northeastern Mexico. METHODS: Retrospective cross-sectional study in which NK patients admitted to our ophthalmology clinic between 2015 and 2021 were consecutively enrolled. Data regarding demographics, clinical characteristics, and comorbidities were collected at the time diagnosis of NK was made. RESULTS: In the period from 2015 to 2021, a total of 74,056 patients were treated and of these 42 had a diagnosis of neurotrophic keratitis. The prevalence found was 5.67 [CI95 3.95-7.38] in 10,000 cases. The mean age observed was 59 ± 17.21 years occurring more frequently in males in 59% and with corneal epithelial defects in 66.7%. The most frequent antecedents were the use of topical medications in 90%, the presence of diabetes mellitus 2 in 40.5% and systemic arterial hypertension in 26.2%. A higher proportion of male patients with corneal alterations and a higher proportion of female patients with corneal ulcerations and/or perforation were observed. CONCLUSION: Neurotrophic keratitis is an underdiagnosed disease with a broad clinical spectrum. The antecedents that were contracted corroborate what was reported in the literature as risk factors. The prevalence of the disease in this geographical area was not reported, so it is expected to increase over time when searching for it intentionally.


Assuntos
Distrofias Hereditárias da Córnea , Ceratite , Doenças do Nervo Trigêmeo , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Prevalência , Estudos Transversais , México/epidemiologia , Ceratite/diagnóstico , Ceratite/epidemiologia , Córnea , Hispânico ou Latino
16.
Pharmacogenet Genomics ; 32(3): 101-110, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34693928

RESUMO

OBJECTIVE: To investigate the impact of single nucleotide polymorphisms (SNPs) from APOA5, APOC3, CETP, ATP binding cassette transporter A1 and SIK3 genes in the development of hypertriglyceridemia in HIV patients under antiretroviral therapy. MATERIAL AND METHODS: A case-control study was developed. Leukocytic genomic DNA was extracted and genotyping for SNPs rs662799, rs964184, rs5128, rs2854116, rs2854117, rs3764261, rs4149310, rs4149267 and rs139961185 was performed by real time-PCR using TaqMan allelic discrimination assays, in Mexican mestizo patients with HIV infection, with hypertriglyceridemia (>1.7 mmol/L) under antiretroviral therapy. Genetic variants were also investigated in a control group of normolipidemic HIV patients (≤ 1.7 mmol/L). Haplotypes and gene interactions were analyzed. RESULTS: A total of 602 HIV patients were genotyped (316 cases and 286 controls). Age and antiretroviral regimen based on protease inhibitors were associated with hypertriglyceridemia (P = 0.0001 and P = 0.0002. respectively). SNP rs964184 GG genotype in APOA5 gene exhibited the highest association with hypertriglyceridemia risk (OR, 3.2, 95% CI, 1.7-5.8, P = 0.0001); followed by SNP rs139961185 in SIK3 gene (OR = 2.3; (95% CI, 1.1-4.8; P = 0.03 for AA vs. AG genotype; and APOC3 rs5128 GG genotype, (OR, 2.2; 95% CI, 1.1-4.9; P = 0.04) under codominant models. These associations were maintained in the adjusted analysis by age and protease inhibitors based antiretroviral regimens. CONCLUSIONS: This study reveals an association between rs964184 in APOA5; rs5128 in APOC3 and rs139961185 in SIK3 and high triglyceride concentrations in Mexican HIV-patients receiving protease inhibitors. These genetic factors may influence the adverse effects related to antiretroviral therapy.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Hipertrigliceridemia , Transportador 1 de Cassete de Ligação de ATP/genética , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/uso terapêutico , Apolipoproteína A-V/genética , Apolipoproteína C-III/genética , Estudos de Casos e Controles , Proteínas de Transferência de Ésteres de Colesterol/genética , Genótipo , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/genética , México , Polimorfismo de Nucleotídeo Único , Proteínas Quinases , Triglicerídeos
17.
RNA ; 26(2): 186-198, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31694875

RESUMO

The 3'X domain of hepatitis C virus has been reported to control viral replication and translation by modulating the exposure of a nucleotide segment involved in a distal base-pairing interaction with an upstream 5BSL3.2 domain. To study the mechanism of this molecular switch, we have analyzed the structure of 3'X mutants that favor one of the two previously proposed conformations comprising either two or three stem-loops. Only the two-stem conformation was found to be stable and to allow the establishment of the distal contact with 5BSL3.2, and also the formation of 3'X domain homodimers by means of a universally conserved palindromic sequence. Nucleotide changes disturbing the two-stem conformation resulted in poorer replication and translation levels, explaining the high degree of conservation detected for this sequence. The switch function attributed to the 3'X domain does not occur as a result of a transition between two- and three-stem conformations, but likely through the sequestration of the 5BSL3.2-binding sequence by formation of 3'X homodimers.


Assuntos
Regiões 3' não Traduzidas/genética , Hepacivirus/genética , Hepatite C/virologia , Conformação de Ácido Nucleico , RNA Viral/genética , Proteínas não Estruturais Virais/genética , Pareamento de Bases , Dimerização , Hepacivirus/fisiologia , Humanos , Sequências Repetidas Invertidas , Modelos Moleculares , Mutação , Nucleotídeos , Dobramento de RNA , RNA Viral/química , Replicação Viral/genética
18.
Appl Environ Microbiol ; 88(1): e0148321, 2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-34705552

RESUMO

Lactococcus lactis strains residing in the microbial community of a complex dairy starter culture named "Ur" are hosts to prophages belonging to the family Siphoviridae. L. lactis strains (TIFN1 to TIFN7) showed detectable spontaneous phage production and release (109 to 1010 phage particles/ml) and up to 10-fold increases upon prophage induction, while in both cases we observed no obvious cell lysis typically described for the lytic life cycle of Siphoviridae phages. Intrigued by this phenomenon, we investigated the host-phage interaction using strain TIFN1 (harboring prophage proPhi1) as a representative. We confirmed that during the massive phage release, all bacterial cells remain viable. Further, by monitoring phage replication in vivo, using a green fluorescence protein reporter combined with flow cytometry, we demonstrated that the majority of the bacterial population (over 80%) is actively producing phage particles when induced with mitomycin C. The released tailless phage particles were found to be engulfed in lipid membranes, as evidenced by electron microscopy and lipid staining combined with chemical lipid analysis. Based on the collective observations, we propose a model of phage-host interaction in L. lactis TIFN1 where the phage particles are engulfed in membranes upon release, thereby leaving the producing host intact. Moreover, we discuss possible mechanisms of chronic, or nonlytic, release of LAB Siphoviridae phages and its impact on the bacterial host. IMPORTANCE In complex microbial consortia such as fermentation starters, bacteriophages can alter the dynamics and diversity of microbial communities. Bacteriophages infecting Lactococcus lactis are mostly studied for their detrimental impact on industrial dairy fermentation processes. In this study, we describe a novel form of phage-bacterium interaction in an L. lactis strain isolated from a complex dairy starter culture: when the prophages harbored in the L. lactis genome are activated, the phage particles are engulfed in lipid membranes upon release, leaving the producing host intact. Findings from this study provide additional insights into the diverse manners of phage-bacterium interactions and coevolution, which are essential for understanding the population dynamics in complex microbial communities like fermentation starters.


Assuntos
Bacteriófagos , Lactococcus lactis , Siphoviridae , Bacteriófagos/genética , Fermentação , Prófagos/genética , Siphoviridae/genética
19.
Phys Rev Lett ; 129(17): 173603, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36332262

RESUMO

Tin-vacancy centers in diamond are promising spin-photon interfaces owing to their high quantum efficiency, large Debye-Waller factor, and compatibility with photonic nanostructuring. Benchmarking their single-photon indistinguishability is a key challenge for future applications. Here, we report the generation of single photons with 99.7_{-2.5}^{+0.3}% purity and 63(9)% indistinguishability from a resonantly excited tin-vacancy center in a single-mode waveguide. We obtain quantum control of the optical transition with 1.71(1)-ns-long π pulses of 77.1(8)% fidelity and show it is spectrally stable over 100 ms. A modest Purcell enhancement factor of 12 would enhance the indistinguishability to 95%.

20.
J Plant Res ; 135(3): 453-463, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35226225

RESUMO

Most tree species native to arid and semiarid ecosystems produce seeds with physical dormancy, which have impermeable coats that protect them from desiccation and prevent germination when the environmental conditions are unfavorable for seedling establishment. This dormancy mechanism may confer some degree of tolerance to seeds facing warmer and drier conditions, as those expected in several regions of the world because of climate change. Scarification of these seeds (removal of protective coats) is required for stimulating germination and seedling development. However, as scarification exposes seeds to the external environmental conditions, it can promote desiccation and viability loss in the future. To test these hypotheses, we performed field experiments and sowed scarified and unscarified seeds of a pioneer tree native to semiarid ecosystems of Mesoamerica (Vachellia pennatula) under the current climate and simulated climate change conditions. The experiments were conducted at abandoned fields using open-top chambers to increase temperature and rainout shelters to reduce rainfall. We measured microenvironmental conditions within the experimental plots and monitored seedling emergence and survival during a year. Air temperature and rainfall in climate change simulations approached the values expected for the period 2041-2080. Seedling emergence rates under these climatic conditions were lower than under the current climate. Nevertheless, emergence rates in climate change simulations were even lower for scarified than for unscarified seeds, while the converse occurred under the current climate. On the other hand, although survival rates in climate change simulations were lower than under the current climate, no effects of the scarification treatment were found. In this way, our study suggests that climate change will impair the recruitment of pioneer trees in semiarid environments, even if they produce seeds with physical dormancy, but also indicates that these negative effects will be stronger if seeds are scarified.


Assuntos
Mudança Climática , Fabaceae , Ecossistema , Germinação , México , Plântula , Sementes , Árvores
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