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1.
Phys Chem Chem Phys ; 26(6): 5621-5632, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38288508

RESUMO

In this work we performed a detailed numerical analysis to investigate the static and dynamic magnetic properties of hexagonal cells of square and circular cobalt nanodots as a function of the distance between them and the external magnetic field to which they are subjected. By simulating hysteresis curves with the external magnetic field applied parallel and perpendicular to the plane of these nanostructures, we can conclude that the cobalt nanodots presented a significant perpendicular magnetic anisotropy. We also obtained that the coercivity increases with decreasing volume, which implies that the circular dots have a higher coercivity than the square dots. Furthermore, we studied the dynamic susceptibility of these systems and found that it is possible to control both the position and the number of resonance peaks by controlling the geometry and the distance between the magnetic nanodots. This work provides useful information on the behaviour of cobalt nanodot arrays, opening paths for the design and improvement of two-dimensional technological devices.

2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731851

RESUMO

COVID-19 is characterized by a wide range of clinical manifestations, where aging, underlying diseases, and genetic background are related to worse outcomes. In the present study, the differential expression of seven genes related to immunity, IRF9, CCL5, IFI6, TGFB1, IL1B, OAS1, and TFRC, was analyzed in individuals with COVID-19 diagnoses of different disease severities. Two-step RT-qPCR was performed to determine the relative gene expression in whole-blood samples from 160 individuals. The expression of OAS1 (p < 0.05) and IFI6 (p < 0.05) was higher in moderate hospitalized cases than in severe ones. Increased gene expression of OAS1 (OR = 0.64, CI = 0.52-0.79; p = 0.001), IRF9 (OR = 0.581, CI = 0.43-0.79; p = 0.001), and IFI6 (OR = 0.544, CI = 0.39-0.69; p < 0.001) was associated with a lower risk of requiring IMV. Moreover, TGFB1 (OR = 0.646, CI = 0.50-0.83; p = 0.001), CCL5 (OR = 0.57, CI = 0.39-0.83; p = 0.003), IRF9 (OR = 0.80, CI = 0.653-0.979; p = 0.03), and IFI6 (OR = 0.827, CI = 0.69-0.991; p = 0.039) expression was associated with patient survival. In conclusion, the relevance of OAS1, IRF9, and IFI6 in controlling the viral infection was confirmed.


Assuntos
2',5'-Oligoadenilato Sintetase , COVID-19 , Fator Gênico 3 Estimulado por Interferon, Subunidade gama , SARS-CoV-2 , Humanos , 2',5'-Oligoadenilato Sintetase/genética , COVID-19/genética , COVID-19/imunologia , COVID-19/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/genética , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Proteínas Nucleares/genética , Adulto , Idoso , Proteínas Mitocondriais
3.
Neurobiol Learn Mem ; 204: 107794, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37473985

RESUMO

The influence of the Rescorla-Wagner model cannot be overestimated, despite that (1) the model does not differ much computationally from its predecessors and competitors, and (2) its shortcomings are well-known in the learning community. Here we discuss the reasons behind its widespread influence in the cognitive and neural sciences, and argue that it is the constant search for general-process theories by learning scholars which eventually produced a model whose application spans many different areas of research to this day. We focus on the theoretical and empirical background of the model, the theoretical connections that it has with later developments across Marr's levels of analysis, as well as the broad variety of research that it has guided and inspired.


Assuntos
Aprendizagem por Associação , Condicionamento Clássico , Aprendizagem
4.
PLoS Comput Biol ; 18(9): e1010410, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36084131

RESUMO

In the natural world, stimulus-outcome associations are often ambiguous, and most associations are highly complex and situation-dependent. Learning to disambiguate these complex associations to identify which specific outcomes will occur in which situations is critical for survival. Pavlovian occasion setters are stimuli that determine whether other stimuli will result in a specific outcome. Occasion setting is a well-established phenomenon, but very little investigation has been conducted on how occasion setters are disambiguated when they themselves are ambiguous (i.e., when they do not consistently signal whether another stimulus will be reinforced). In two preregistered studies, we investigated the role of higher-order Pavlovian occasion setting in humans. We developed and tested the first computational model predicting direct associative learning, traditional occasion setting (i.e., 1st-order occasion setting), and 2nd-order occasion setting. This model operationalizes stimulus ambiguity as a mechanism to engage in higher-order Pavlovian learning. Both behavioral and computational modeling results suggest that 2nd-order occasion setting was learned, as evidenced by lack and presence of transfer of occasion setting properties when expected and the superior fit of our 2nd-order occasion setting model compared to the 1st-order occasion setting or direct associations models. These results provide a controlled investigation into highly complex associative learning and may ultimately lead to improvements in the treatment of Pavlovian-based mental health disorders (e.g., anxiety disorders, substance use).


Assuntos
Aprendizagem por Associação , Aprendizagem por Discriminação , Condicionamento Clássico , Sinais (Psicologia) , Humanos , Aprendizagem
5.
Int J Mol Sci ; 25(1)2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38203550

RESUMO

Cutaneous squamous cell carcinoma (CSCC) is one of the most common cancers in the skin. CSCC belongs to the non-melanoma skin cancers, and its incidence is increasing every year around the world. The principal routes of tumor progression are related to angiogenesis and lymphangiogenesis. In this study, we assess the gene expression of the relevant biomarkers of both routes in 49 formalin-fixed paraffin-embedded (FFPE) CSCC samples in an attempt to determine a molecular profile that correlates with the tumor progression and disease-free survival (DFS). The results were enhanced by a posttranscriptional analysis using an immunofluorescence assay. Overexpression of the vascular endothelial growth factor C (VEGFC) gene was found in patients with tumor progression (p = 0.022) and in patients with perineural invasion (p = 0.030). An increased expression of protein VEGFC in samples with tumor progression supported these results (p = 0.050). In addition, DFS curves showed differences (p = 0.027) for tumors with absent-low VEGFC expression versus those with high levels of VEGFC expression. No significant influence on DFS was detected for the remaining analyzed genes. VEGFC expression was found to be a risk factor in the disease progression (HR = 2.675; 95% CI: 1.089-6.570; p = 0.032). Our main results suggest that VEGFC gene expression is closely related to tumor progression, DFS, and the presence of perineural invasion.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Carcinoma de Células Escamosas/genética , Intervalo Livre de Doença , Expressão Gênica , Neoplasias Cutâneas/genética , Fator C de Crescimento do Endotélio Vascular/genética
6.
Learn Mem ; 29(7): 160-170, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35710303

RESUMO

Theories of learning distinguish between elemental and configural stimulus processing depending on whether stimuli are processed independently or as whole configurations. Evidence for elemental processing comes from findings of summation in animals where a compound of two dissimilar stimuli is deemed to be more predictive than each stimulus alone, whereas configural processing is supported by experiments using similar stimuli in which summation is not found. However, in humans the summation effect is robust and impervious to similarity manipulations. In three experiments in human predictive learning, we show that summation can be obliterated when partially reinforced cues are added to the summands in training and tests. This lack of summation only holds when the partially reinforced cues are similar to the reinforced cues (experiment 1) and seems to depend on participants sampling only the most salient cue in each trial (experiments 2a and 2b) in a sequential visual search process. Instead of attributing our and others' instances of lack of summation to the customary idea of configural processing, we offer a formal subsampling rule that might be applied to situations in which the stimuli are hard to parse from each other.


Assuntos
Aprendizagem por Associação , Sinais (Psicologia) , Animais , Condicionamento Clássico , Humanos
7.
Learn Mem ; 29(1): 16-28, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34911800

RESUMO

It has been suggested that there are two distinct and parallel mechanisms for controlling instrumental behavior in mammals: goal-directed actions and habits. To gain an understanding of how these two systems interact to control behavior, it is essential to characterize the mechanisms by which the balance between these systems is influenced by experience. Studies in rodents have shown that the amount of training governs the relative expression of these two systems: Behavior is goal-directed following moderate training, but the more extensively an instrumental action is trained, the more it becomes habitual. It is less clear whether humans exhibit similar training effects on the expression of goal-directed and habitual behavior, as human studies have reported contradictory findings. To tackle these contradictory findings, we formed a consortium, where four laboratories undertook a preregistered experimental induction of habits by manipulating the amount of training. There was no statistical evidence for a main effect of the amount of training on the formation and expression of habits. However, exploratory analyses suggest a moderating effect of the affective component of stress on the impact of training over habit expression. Participants who were lower in affective stress appeared to be initially goal-directed, but became habitual with increased training, whereas participants who were high in affective stress were already habitual even after moderate training, thereby manifesting insensitivity to overtraining effects. Our findings highlight the importance of the role of moderating variables such as individual differences in stress and anxiety when studying the experimental induction of habits in humans.


Assuntos
Condicionamento Operante , Objetivos , Animais , Hábitos , Humanos , Motivação
8.
Behav Brain Sci ; 45: e265, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36353862

RESUMO

Understanding how culture evolves in society is an extremely difficult task. The bifocal stance theory (BST) deploys two copying strategies which can be linked to dual-system theories of behavior. BST would benefit from incorporating results from these theories, such as the evolution of attention to goals or steps of a behavioral sequence, and the role of the environment in prompting different copying strategies.


Assuntos
Hábitos , Humanos
9.
Curr Issues Mol Biol ; 43(3): 2167-2176, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34940125

RESUMO

Formalin-fixed paraffin-embedded (FFPE) tumour samples may provide crucial data regarding biomarkers for neoplasm progression. Analysis of gene expression is frequently used for this purpose. Therefore, mRNA expression needs to be normalized through comparison to reference genes. In this study, we establish which of the usually reported reference genes is the most reliable one in cutaneous malignant melanoma (MM) and cutaneous squamous cell carcinoma (CSCC). ACTB, TFRC, HPRT1 and TBP expression was quantified in 123 FFPE samples (74 MM and 49 CSCC biopsies) using qPCR. Expression stability was analysed by NormFinder and Bestkeeper softwares, and the direct comparison method between means and SD. The in-silico analysis with BestKeeper indicated that HPRT1 was more stable than ACTB and TFRC in MM (1.85 vs. 2.15) and CSCC tissues (2.09 vs. 2.33). The best option to NormFinder was ACTB gene (0.56) in MM and TFRC (0.26) in CSCC. The direct comparison method showed lower SD means of ACTB expression in MM (1.17) and TFRC expression in CSCC samples (1.00). When analysing the combination of two reference genes for improving stability, NormFinder indicated HPRT1 and ACTB to be the best for MM samples, and HPRT1 and TFRC genes for CSCC. In conclusion, HPRT1 and ACTB genes in combination are the most appropriate choice for normalization in gene expression studies in MM FFPE tissue, while the combination of HPRT1 and TFRC genes are the best option in analysing CSCC FFPE samples. These may be used consistently in forthcoming studies on gene expression in both tumours.


Assuntos
Biomarcadores Tumorais , Expressão Gênica , Histocitoquímica , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Feminino , Perfilação da Expressão Gênica/métodos , Histocitoquímica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inclusão em Parafina , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Cutâneas/patologia , Fixação de Tecidos
10.
BMC Infect Dis ; 21(1): 1169, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798820

RESUMO

BACKGROUND: SARS-CoV-2 stability and infection persistence has been studied on different surfaces, but scarce data exist related to personal protective equipment (PPE), moreover using realist viral loads for infection. Due to the importance for adequate PPE management to avoid risk of virus infection, RNA stability was evaluated on PPE. METHODS: Persistence of SARS-CoV-2 infection and detection of genomic RNA in PPE (gowns and face masks) were determined by in-vitro assays and RT-qPCR, respectively. Samples were infected with a clinical sample positive for SARS-CoV-2 (Clin-Inf), and with a heat-inactivated SARS-CoV-2 strain sample (Str-Inf) as a control. RESULTS: PPE samples infected with Clin-Inf were positive for the 3 viral genes on gowns up to 5 days post-infection, whereas these overall genes were detected up to 30 days in the case of face masks. However, gowns and FFP2 masks samples contaminated with Clin-Inf showed a cytopathic effect over VERO cells up to 5-7 days post-infection. CONCLUSIONS: SARS-CoV-2 RNA was detected on different PPE materials for 5 to 30 days, but PPE contaminated with the virus was infectious up to 5-7 days. These findings demonstrate the need to improve PPE management and to formulate strategies to introduce viricidal compounds in PPE fabrics.


Assuntos
COVID-19 , Equipamento de Proteção Individual , Animais , Chlorocebus aethiops , Pessoal de Saúde , Humanos , Controle de Infecções , RNA Viral/genética , SARS-CoV-2 , Células Vero
11.
MMWR Morb Mortal Wkly Rep ; 69(43): 1591-1594, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34463672

RESUMO

Data on transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among college athletes are limited. In August 2020, the Chicago Department of Public Health (CDPH) was notified of a cluster of COVID-19 cases among a university's men's and women's soccer teams. CDPH initiated an investigation, interviewed members of both teams, and collated laboratory data to understand transmission of SARS-CoV-2 within the teams. Numerous social gatherings with limited mask use or social distancing preceded the outbreak. Transmission resulted in 17 laboratory-confirmed COVID-19 cases across both teams (n = 45), likely from a single source introduction of SARS-CoV-2 (based on whole genome sequencing) and subsequent transmission during multiple gatherings. Colleges and universities are at risk for COVID-19 outbreaks because of shared housing and social gatherings where recommended prevention guidance is not followed. Improved strategies to promote mask use and social distancing among college-aged adults need to be implemented, as well as periodic repeat testing to identify asymptomatic infections and prevent outbreaks among groups at increased risk for infection because of frequent exposure to close contacts in congregate settings on and off campus.


Assuntos
Atletas/estatística & dados numéricos , COVID-19/epidemiologia , Surtos de Doenças , Futebol , Estudantes/estatística & dados numéricos , Universidades , Adolescente , COVID-19/prevenção & controle , COVID-19/transmissão , Teste para COVID-19 , Chicago/epidemiologia , Busca de Comunicante , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Masculino , Máscaras/estatística & dados numéricos , Distanciamento Físico , Quarentena , SARS-CoV-2/isolamento & purificação , Adulto Jovem
12.
J Toxicol Environ Health A ; 83(8): 313-329, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32378477

RESUMO

Exposure to contaminants might directly affect organisms and alter their associated microbiota. The objective of the present study was to determine the impact of the petroleum-water-accommodated fraction (WAF) from a light crude oil (API gravity 35) on a benthic fish species native from the Gulf of Mexico (GoM). Ten adults of Achirus lineatus (Linnaeus, 1758) were exposed to a sublethal WAF/water solution of 50% v/v for 48 hr. Multiple endpoints were measured including tissue damage, presence of polycyclic aromatic hydrocarbons (PAHs) metabolites in bile and gut microbiota analyses. Atrophy and fatty degeneration were observed in livers. Nodules and inflammation were detected in spleen, and structural disintegration and atrophy in the kidney. In gills hyperplasia, aneurysm, and gills lamellar fusion were observed. PAHs metabolites concentrations in bile were significantly higher in exposed organisms. Gut microbiome taxonomic analysis showed significant shifts in bacterial structure and composition following WAF exposure. Data indicate that exposure to WAF produced toxic effects in adults of A. lineatus, as evidenced by histological alterations and dysbiosis, which might represent an impairment to long-term subsistence of exposed aquatic organisms.


Assuntos
Linguados/microbiologia , Microbiota/efeitos dos fármacos , Petróleo/análise , Petróleo/toxicidade , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bile/química , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
13.
Physiol Genomics ; 50(8): 658-667, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29883262

RESUMO

Microribonucleic acids (miRNAs) mediate adaptive responses to exercise and may serve as biomarkers of exercise intensity/capacity. Expression of miRNAs is altered in skeletal muscle, plasma, and saliva following exertion. Women display unique physiologic responses to endurance exercise, and miRNAs respond to pathologic states in sex-specific patterns. However sex-specific miRNA responses to exercise remain unexplored. This study utilized high-throughput RNA sequencing to measure changes in salivary RNA expression among 25 collegiate runners following a single long-distance run. RNA concentrations in pre- and post-run saliva was assessed through alignment and quantification of 4,694 miRNAs and 27,687 mRNAs. Pair-wise Wilcoxon rank-sum test identified miRNAs with significant [false discovery rate (FDR) < 0.05] post-run changes. Associations between miRNA levels and predicted mRNA targets were explored with Pearson correlations. Differences in miRNA patterns between men ( n = 13) and women ( n = 12) were investigated with two-way analysis of variance. Results revealed 122 salivary miRNAs with post-run changes. The eight miRNAs with the largest changes were miR-3671, miR-5095 (downregulated); and miR-7154-3p, miR-200b-5p, miR-5582-3p, miR-6859-3p, miR-6751-5p, miR-4419a (upregulated). Predicted mRNA targets for these miRNAs represented 15 physiologic processes, including glycerophospholipid metabolism (FDR = 0.042), aldosterone-regulated sodium reabsorption (FDR = 0.049), and arrhythmogenic ventricular cardiomyopathy (FDR = 0.018). Twenty-six miRNA/mRNA pairs had associated changes in post-run levels. Three miRNAs (miR-4675, miR-6745, miR-6746-3p) demonstrated sex-specific responses to exercise. Numerous salivary miRNAs change in response to endurance running and target the expression of genes involved in metabolism, fluid balance, and musculoskeletal adaptations. A subset of miRNAs may differentiate the metabolic response to exercise in men and women.


Assuntos
Metabolismo dos Lipídeos/genética , MicroRNAs/genética , Músculo Esquelético/metabolismo , Miosinas/genética , Corrida , Equilíbrio Hidroeletrolítico , Adolescente , Exercício Físico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , MicroRNAs/sangue , Miosinas/metabolismo , RNA Mensageiro/genética , Saliva/metabolismo , Fatores Sexuais , Adulto Jovem
14.
Ecotoxicol Environ Saf ; 147: 1056-1064, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29976008

RESUMO

Salvinia minima was assessed for its ability to accumulate lead (Pb) by exposing it to concentrations of 40µM Pb(NO3)2 during 24h. At the same time, the expression levels were quantified, of four genes coding for transporters: SmABCC (ABCC-MRP), SmATPase (ATPase-P3A), SmNhaD (Type-Na+/H+) and SmABCG (ABCG-WBC). In the absence of lead, S. minima had very low expression of those genes, when plants were exposed to the metal however, those genes showed a rapid (in just three hours or less) and sharp increase (up to 60 times) in their expression, particularly the SmNhaD (Type-Na+/H+) gene. This sharp increase in expression levels of the genes studied, occurred at the same time that the plant accumulated the highest content of lead in its tissues. The first two genes, are apparently implicated in detoxification and lead accumulation mechanisms, while the other two genes are apparently involved in maintaining cell balance (homeostatic control) and membrane integrity. Our results confirmed that S. minima is efficient for phytoremediation of water bodies contaminated by lead, as it is efficient in accumulating this metal in its tissues (bioconcentration factor; BCF) values greater than 1000, in short times of exposure. More importantly, our data on the expression profiles of four genes coding for transporters, represent a first sight scenario of the molecular basis for understanding the different mechanism of detoxification, apparently present in this aquatic fern.


Assuntos
Gleiquênias/genética , Chumbo/toxicidade , Proteínas de Membrana Transportadoras/genética , Proteínas de Plantas/genética , Poluentes Químicos da Água/toxicidade , Biodegradação Ambiental , Gleiquênias/efeitos dos fármacos , Gleiquênias/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Chumbo/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Plantas/metabolismo , Poluentes Químicos da Água/metabolismo
15.
Fish Physiol Biochem ; 44(1): 73-85, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28900798

RESUMO

Red drum (Sciaenops ocellatus) is a euryhaline fish commonly found in the Gulf of Mexico and along the Atlantic coast of North America. Because of high commercial demand and its euryhaline characteristics, aquaculture of this species has diversified from marine to low-salinity aquaculture systems. In recent years, interest in the feasibility of producing red drum in inland freshwater systems has grown and this prompted us to investigate its osmoregulatory capacity after rearing for 8 months in a freshwater aquaculture system. We compared the activities of several genes and enzymes involved in the osmoregulatory process in freshwater-acclimatized (FW) and seawater (SW) red drum. The gene expression profiles were variable: the expression of genes encoding Na+/K+-ATPase (NKA) and the cystic fibrosis transmembrane regulator (CFTR) was slightly higher in SW than FW fish, while phosphoenolpyruvate carboxykinase (PEPCK) and the glucocorticoid receptor messenger RNA (mRNA) levels were higher in FW red drum. The total plasma K concentration was 60.3% lower, and gill NKA activity was 63.5% lower in FW than in SW fish. PEPCK activity was twofold higher in FW than in SW red drum. Similarly, liver glycogen was 60% higher in FW fish. In summary, both gene expression and the enzyme activity data support the phenotypic plasticity of red drum and suggest that the limited capacity for ion homeostasis observed, in particular the low plasma K concentration, was due to the composition of freshwater and does not necessarily reflect a physiological inability to osmoregulate.


Assuntos
Peixes/fisiologia , Água Doce , Regulação da Expressão Gênica/fisiologia , Aclimatação/fisiologia , Animais , Organismos Aquáticos , Brânquias/metabolismo , Osmorregulação , RNA Mensageiro/metabolismo , Salinidade , Água do Mar , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia
16.
Bull Environ Contam Toxicol ; 100(6): 798-802, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29569062

RESUMO

The present study reports partial sequences of a group of genes used as exposure and effect biomarkers of organic contaminants and/or heavy metals in Syacium gunteri. In order to isolate these sequences, cDNA was used to amplify fragments between 200 and 800 bp, which were then cloned and sequenced. The sequences presented high percentages of identity with genes involved in the metabolism of xenobiotic biotransformation (cytochrome P4501A and glutathione S-transferase), oxidative stress (catalase, glutathione reductase, glutathione peroxidase and superoxide dismutase), reproductive system (vitellogenin) and with the tumor suppressor protein p53 reported in the GenBank database. Subsequently, from the deduced sequence of amino acids of each fragment, their tridimensional structure was predicted, using homologous proteins from the Protein Data Base. This study generates an important base of molecular biomarkers for the monitoring of environmental health in the Gulf of Mexico.


Assuntos
Linguados/genética , Metais Pesados/análise , Estresse Oxidativo/genética , Animais , Biomarcadores/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Golfo do México , RNA Mensageiro/metabolismo , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53/genética
17.
J Gen Virol ; 98(7): 1702-1712, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28691657

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been responsible for a serious outbreak of disease in South and Central America. Infection with ZIKV has been associated with severe neurological symptoms and the development of microcephaly in unborn fetuses. Many of the regions involved in the current outbreak are known to be endemic for another flavivirus, dengue virus (DENV), which indicates that a large percentage of the population may have pre-existing DENV immunity. Thus, it is vital to investigate what impact pre-existing DENV immunity has on ZIKV infection. Here, we use primary human myeloid cells as a model for ZIKV enhancement in the presence of DENV antibodies. We show that sera containing DENV antibodies from individuals living in a DENV-endemic area are able to enhance ZIKV infection in a human macrophage-derived cell line and primary human macrophages. We also demonstrate altered pro-inflammatory cytokine production in macrophages with enhanced ZIKV infection. Our study indicates an important role for pre-existing DENV immunity on ZIKV infection in primary human immune cells and establishes a relevant in vitro model to study ZIKV antibody-dependent enhancement.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Facilitadores/imunologia , Vírus da Dengue/imunologia , Macrófagos/imunologia , Infecção por Zika virus/patologia , Zika virus/imunologia , Adulto , Linhagem Celular Tumoral , Criança , Pré-Escolar , Reações Cruzadas/imunologia , Citocinas/biossíntese , Dengue/imunologia , Dengue/virologia , Surtos de Doenças , Feminino , Humanos , Lactente , Masculino , Células U937 , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia
18.
Clin Infect Dis ; 59(11): 1511-8, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25100864

RESUMO

BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests. RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Idoso , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Masculino , Arábia Saudita , Viagem , Estados Unidos
19.
Proc Natl Acad Sci U S A ; 108(24): 9975-80, 2011 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-21628558

RESUMO

During the early stages of HIV-1 replication the conical capsid composed of p24(CA) protein dissociates from the rest of the cytoplasmic viral complex by a process called uncoating. Although proper uncoating is known to be required for HIV-1 infection, many questions remain about the timing and factors involved in the process. Here we have used two complementary assays to study the process of uncoating in HIV-1-infected cells, specifically looking at the timing of uncoating and its relationship to reverse transcription. We developed a fluorescent microscopy-based uncoating assay that detects the association of p24(CA) with HIV-1 viral complexes in cells. We also used an owl monkey kidney (OMK) cell assay that is based on timed TRIM-CypA-mediated restriction of HIV-1 replication. Results from both assays indicate that uncoating is initiated within 1 h of viral fusion. In addition, treatment with the reverse transcriptase inhibitor nevirapine delayed uncoating in both assays. Analysis of reverse transcription products in OMK cells revealed that the generation of early reverse transcription products coincides with the timing of uncoating in these assays. Collectively, these results suggest that some aspect of reverse transcription has the ability to influence the kinetics of uncoating.


Assuntos
HIV-1/genética , Proteínas do Vírus da Imunodeficiência Humana/genética , Transcrição Reversa , Replicação Viral/genética , Animais , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Ciclosporina/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Proteína do Núcleo p24 do HIV/genética , Proteína do Núcleo p24 do HIV/metabolismo , HIV-1/metabolismo , Células HeLa , Proteínas do Vírus da Imunodeficiência Humana/metabolismo , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Macrolídeos/farmacologia , Microscopia de Fluorescência , Nevirapina/farmacologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Fatores de Tempo , Vírion/genética , Vírion/metabolismo , Replicação Viral/efeitos dos fármacos , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vpr do Vírus da Imunodeficiência Humana/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-38661631

RESUMO

Our theory of positively reinforced free-operant behavior (Perez & Dickinson, 2020) assumes that responding is controlled by two systems. One system is sensitive to the correlation between response and reinforcement rates and controls goal-directed behavior, whereas a habitual system learns by reward prediction error. We present an extension of this theory to the aversive domain that explains why free-operant avoidance responding increases with both the experienced rate of negative reinforcement and the difference between this rate and that programmed by the avoidance schedule. The theory also assumes that the habitual component is reinforced by the acquisition of aversive inhibitory properties by the feedback stimuli generated by responding, which then act as safety signals that reinforce habit performance. Our analysis suggests that the distinction between habitual and goal-directed control of rewarded behavior can also be applied to the aversive domain. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

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