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1.
Emerg Microbes Infect ; 13(1): 2332680, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38497329

RESUMO

After the use of facemasks, other isolation measures enacted during the SARS-CoV-2 pandemic were lifted, respiratory pathogens, such as RSV, reappeared, but until the November 2023 WHO alert for China, M. pneumoniae had virtually disappeared. After observing a similar reappearance in our hospital, a retrospective analysis of the number of positive M. pneumoniae tests. Between 2018 and December 2023, 1619 PCR tests were ordered and 43 (2.6%) of them were positive. Two outbreaks, one in 2018 and one in 2023, accounted for the majority of cases. Tests were usually ordered in an outpatient setting (53.54%, n = 23) and most of them were paediatric patients with a mean age (sd) of 10.2 (6.2) years. As for the severity of the cases, in the 2018 outbreak, of 15 children who tested positive, 53.3% (n = 8) were admitted to the ward and 6.7% (n = 1) at the intensive care unit. Whereas in 2023, 2 patients were tested in the ward (10.5%) and one in the intensive care unit (5.2%) from a total of 19 patients. The positive rate in 2023 was significantly higher in comparison with years 2020, 2021 and 2022 and significantly lower in comparison with 2018 (P-value=0.003). The outbreak in late 2023 can be explained by the seasonality of Mycoplasma pneumonia alone, which has shown outbreaks every 3-5 years, and it does not appear to be more severe than the previous one.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , Criança , Mycoplasma pneumoniae/genética , Espanha/epidemiologia , Estudos Retrospectivos , Pneumonia por Mycoplasma/epidemiologia , China/epidemiologia
4.
Plant Direct ; 8(1): e566, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38250458

RESUMO

The eukaryote-specific ribosomal protein of the small subunit eS6 is phosphorylated through the target of rapamycin (TOR) kinase pathway. Although this phosphorylation event responds dynamically to environmental conditions and has been studied for over 50 years, its biochemical and physiological significance remains controversial and poorly understood. Here, we report data from Arabidopsis thaliana, which indicate that plants expressing only a phospho-deficient isoform of eS6 grow essentially normally under laboratory conditions. The eS6z (RPS6A) paralog of eS6 functionally rescued a double mutant in both rps6a and rps6b genes when expressed at approximately twice the wild-type dosage. A mutant isoform of eS6z lacking the major six phosphorylatable serine and threonine residues in its carboxyl-terminal tail also rescued the lethality, rosette growth, and polyribosome loading of the double mutant. This isoform also complemented many mutant phenotypes of rps6 that were newly characterized here, including photosynthetic efficiency, and most of the gene expression defects that were measured by transcriptomics and proteomics. However, compared with plants rescued with a phospho-enabled version of eS6z, the phospho-deficient seedlings retained a mild pointed-leaf phenotype, root growth was reduced, and certain cell cycle-related mRNAs and ribosome biogenesis proteins were misexpressed. The residual defects of the phospho-deficient seedlings could be understood as an incomplete rescue of the rps6 mutant defects. There was little or no evidence for gain-of-function defects. As previously published, the phospho-deficient eS6z also rescued the rps6a and rps6b single mutants; however, phosphorylation of the eS6y (RPS6B) paralog remained lower than predicted, further underscoring that plants can tolerate phospho-deficiency of eS6 well. Our data also yield new insights into how plants cope with mutations in essential, duplicated ribosomal protein isoforms.

5.
Viruses ; 15(7)2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37515153

RESUMO

Flaviviruses, including Dengue (DENV), Zika (ZIKV), and Yellow Fever (YFV) viruses, represent a significant global health burden. The development of effective antiviral therapies against these viruses is crucial to mitigate their impact. This study investigated the antiviral potential of the cholesterol-lowering drugs atorvastatin and ezetimibe in monotherapy and combination against DENV, ZIKV, and YFV. In vitro results demonstrated a dose-dependent reduction in the percentage of infected cells for both drugs. The combination of atorvastatin and ezetimibe showed a synergistic effect against DENV 2, an additive effect against DENV 4 and ZIKV, and an antagonistic effect against YFV. In AG129 mice infected with DENV 2, monotherapy with atorvastatin or ezetimibe significantly reduced clinical signs and increased survival. However, the combination of both drugs did not significantly affect survival. This study provides valuable insights into the potential of atorvastatin and ezetimibe as antiviral agents against flaviviruses and highlights the need for further investigations into their combined therapeutic effects.


Assuntos
Vírus da Dengue , Dengue , Infecções por Flavivirus , Flavivirus , Infecção por Zika virus , Zika virus , Animais , Camundongos , Antivirais/farmacologia , Antivirais/uso terapêutico , Atorvastatina , Reposicionamento de Medicamentos , Ezetimiba , Colesterol
6.
Plant Physiol ; 190(1): 794-812, 2022 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-35703946

RESUMO

Leaves and flowers are produced by the shoot apical meristem (SAM) at a certain distance from its center, a process that requires the hormone auxin. The amount of auxin and the pattern of its distribution in the initiation zone determine the size and spatial arrangement of organ primordia. Auxin gradients in the SAM are formed by PIN-FORMED (PIN) auxin efflux carriers whose polar localization in the plasma membrane depends on the protein kinase PINOID (PID). Previous work determined that ERECTA (ER) family genes (ERfs) control initiation of leaves. ERfs are plasma membrane receptors that enable cell-to-cell communication by sensing extracellular small proteins from the EPIDERMAL PATTERNING FACTOR/EPF-LIKE (EPF/EPFL) family. Here, we investigated whether ERfs regulate initiation of organs by altering auxin distribution or signaling in Arabidopsis (Arabidopsis thaliana). Genetic and pharmacological data suggested that ERfs do not regulate organogenesis through PINs while transcriptomics data showed that ERfs do not alter primary transcriptional responses to auxin. Our results indicated that in the absence of ERf signaling the peripheral zone cells inefficiently initiate leaves in response to auxin signals and that increased accumulation of auxin in the er erecta-like1 (erl1) erl2 SAM can partially rescue organ initiation defects. We propose that both auxin and ERfs are essential for leaf initiation and that they have common downstream targets. Genetic data also indicated that the role of PID in initiation of cotyledons and leaves cannot be attributed solely to regulation of PIN polarity and PID is likely to have other functions in addition to regulation of auxin distribution.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Mutação , Proteínas Serina-Treonina Quinases
7.
AIDS ; 36(7): 997-1005, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35220350

RESUMO

OBJECTIVE: To investigate the dynamics of phylogenetic transmission clusters involving immigrants of Portuguese Speaking Countries living in Portugal. DESIGN/METHODS: We included genomic sequences, sociodemographic and clinical data from 772 HIV migrants followed in Portugal between 2001 and 2017. To reconstruct HIV-1 transmission clusters, we applied phylogenetic inference from 16 454 patients: 772 migrants, 2973 Portuguese and 12 709 global controls linked to demographic and clinical data. Transmission clusters were defined using: clusters with SH greater than 90% (phylogenetic support), genetic distance less than 3.5% and clusters that included greater than 66% of patients from one specific geographic origin compared with the total of sequences within the cluster. Logistic regression was performed to assess factors associated with clustering. RESULTS: Three hundred and six (39.6%) of migrants were included in transmission clusters. This proportion differed substantially by region of origin [Brazil 54% vs. Portuguese Speaking African Countries (PALOPs) 36%, P < 0.0001] and HIV-1 infecting subtype (B 52%, 43% subtype G and 32% CRF02_AG, P < 0.001). Belonging to a transmission cluster was independently associated with treatment-naive patients, CD4+ greater than 500, with recent calendar years of sampling, origin from PALOPs and with seroconversion. Among Brazilian migrants - mainly infected with subtype B - 40.6% were infected by Portuguese. Among migrants from PALOPs - mainly infected with subtypes G and CFR02_AG - the transmission occurred predominantly within the migrants' community (53 and 80%, respectively). CONCLUSION: The acquisition of infection among immigrants living in Portugal differs according to the country of origin. These results can contribute to monitor the HIV epidemic and prevent new HIV infections among migrants.


Assuntos
Emigrantes e Imigrantes , Infecções por HIV , HIV-1 , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Filogenia , Portugal/epidemiologia
8.
Heliyon ; 7(11): e08301, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34816028

RESUMO

Agricultural soils need monitoring systems to address pesticide risks for humans and the environment. The purpose of this paper was to obtain leaching risk maps of the pesticides imidacloprid, lambda-cyhalothrin, and chlorpyrifos in agricultural soil under an onion (Allium cepa L.) crop in Tibasosa, Boyacá, Colombia. This was obtained by studying the soil types in the area, analyzing the behavior of pollutants in the soil profile, using a delay factor and an attenuation factor to finally include GIS allowing visualization of the areas of greater potential risk in the study area.

9.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809231

RESUMO

The synthesis of cyclometalated osmium complexes is usually more complicated than of other transition metals such as Ni, Pd, Pt, Rh, where cyclometalation reactions readily occur via direct activation of C-H bonds. It differs also from their ruthenium analogs. Cyclometalation for osmium usually occurs under more severe conditions, in polar solvents, using specific precursors, stronger acids, or bases. Such requirements expand reaction mechanisms to electrophilic activation, transmetalation, and oxidative addition, often involving C-H bond activations. Osmacycles exhibit specific applications in homogeneous catalysis, photophysics, bioelectrocatalysis and are studied as anticancer agents. This review describes major synthetic pathways to osmacycles and related compounds and discusses their practical applications.

10.
Clin Infect Dis ; 72(3): 503-509, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32227124

RESUMO

Human immunodeficiency virus-2 (HIV-2) is endemic in some countries in West Africa. Due to the lower prevalence in industrialized countries, there is limited experience and knowledge on the management of individuals living with HIV-2 in Europe. Compared to HIV-1, there are differential characteristics of HIV-2 regarding diagnostic procedures, the clinical course, and, most importantly, antiretroviral therapy. We integrated the published literature on HIV-2 (studies and reports on epidemiology, diagnostics, the clinical course, and treatment), as well as expert experience in diagnosing and clinical care, to provide recommendations for a present standard of medical care of those living with HIV-2 in Western European countries, including an overview of strategies for diagnosis, monitoring, and treatment, with suggestions for effective drug combinations for first- and second-line treatments, post-exposure prophylaxis, and the prevention of mother-to-child transmission, as well as listings of mutations related to HIV-2 drug resistance and C-C motif chemokine receptor type 5 and C-X-C motif chemokine receptor type 4 coreceptor tropism.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , África Ocidental , Fármacos Anti-HIV/uso terapêutico , Criança , Europa (Continente) , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-2/genética , Humanos , Transmissão Vertical de Doenças Infecciosas , Padrão de Cuidado
11.
Viruses ; 12(11)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143301

RESUMO

INTRODUCTION: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). OBJECTIVE: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. METHODS: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. RESULTS AND DISCUSSION: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). CONCLUSIONS: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Fármacos Anti-HIV/farmacologia , Feminino , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Portugal/epidemiologia , Prevalência , Saúde Pública/métodos , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto Jovem
12.
Wiley Interdiscip Rev RNA ; 11(6): e1597, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32367681

RESUMO

The molecular machinery for protein synthesis is profoundly similar between plants and other eukaryotes. Mechanisms of translational gene regulation are embedded into the broader network of RNA-level processes including RNA quality control and RNA turnover. However, over eons of their separate history, plants acquired new components, dropped others, and generally evolved an alternate way of making the parts list of protein synthesis work. Research over the past 5 years has unveiled how plants utilize translational control to defend themselves against viruses, regulate translation in response to metabolites, and reversibly adjust translation to a wide variety of environmental parameters. Moreover, during seed and pollen development plants make use of RNA granules and other translational controls to underpin developmental transitions between quiescent and metabolically active stages. The economics of resource allocation over the daily light-dark cycle also include controls over cellular protein synthesis. Important new insights into translational control on cytosolic ribosomes continue to emerge from studies of translational control mechanisms in viruses. Finally, sketches of coherent signaling pathways that connect external stimuli with a translational response are emerging, anchored in part around TOR and GCN2 kinase signaling networks. These again reveal some mechanisms that are familiar and others that are different from other eukaryotes, motivating deeper studies on translational control in plants. This article is categorized under: Translation > Translation Regulation RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.


Assuntos
Regulação da Expressão Gênica de Plantas/genética , Plantas/genética , Processamento de Proteína Pós-Traducional , RNA/genética
13.
Viruses ; 12(3)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121161

RESUMO

Migration is associated with HIV-1 vulnerability. OBJECTIVES: To identify long-term trends in HIV-1 molecular epidemiology and antiretroviral drug resistance (ARV) among migrants followed up in Portugal Methods: 5177 patients were included between 2001 and 2017. Rega, Scuel, Comet, and jPHMM algorithms were used for subtyping. Transmitted drug resistance (TDR) and Acquired drug resistance (ADR) were defined as the presence of surveillance drug resistance mutations (SDRMs) and as mutations of the IAS-USA 2015 algorithm, respectively. Statistical analyses were performed. RESULTS: HIV-1 subtypes infecting migrants were consistent with the ones prevailing in their countries of origin. Over time, overall TDR significantly increased and specifically for Non-nucleoside reverse transcriptase inhibitor (NNRTIs) and Nucleoside reverse transcriptase inhibitor (NRTIs). TDR was higher in patients from Mozambique. Country of origin Mozambique and subtype B were independently associated with TDR. Overall, ADR significantly decreased over time and specifically for NRTIs and Protease Inhibitors (PIs). Age, subtype B, and viral load were independently associated with ADR. CONCLUSIONS: HIV-1 molecular epidemiology in migrants suggests high levels of connectivity with their country of origin. The increasing levels of TDR in migrants could indicate an increase also in their countries of origin, where more efficient surveillance should occur.


Assuntos
Genótipo , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/genética , Migrantes , Adulto , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/história , HIV-1/efeitos dos fármacos , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Portugal/epidemiologia , Portugal/etnologia , Vigilância em Saúde Pública , RNA Viral , Carga Viral , Produtos do Gene pol do Vírus da Imunodeficiência Humana
14.
Plant Cell ; 32(4): 1161-1178, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32079667

RESUMO

Cytosolic mRNA translation is subject to global and mRNA-specific controls. Phosphorylation of the translation initiation factor eIF2α anchors a reversible regulatory switch that represses cytosolic translation globally. The stress-responsive GCN2 kinase is the only known kinase for eIF2α serine 56 in Arabidopsis (Arabidopsis thaliana). Here, we show that conditions that generate reactive oxygen species (ROS) in the chloroplast, including dark-light transitions, high light, and the herbicide methyl viologen, rapidly activated GCN2 kinase, whereas mitochondrial and endoplasmic reticulum stress did not. GCN2 activation was light dependent and mitigated by photosynthesis inhibitors and ROS quenchers. Accordingly, the seedling growth of multiple Arabidopsis gcn2 mutants was retarded under excess light conditions, implicating the GCN2-eIF2α pathway in responses to light and associated ROS. Once activated, GCN2 kinase preferentially suppressed the ribosome loading of mRNAs for functions such as mitochondrial ATP synthesis, the chloroplast thylakoids, vesicle trafficking, and translation. The gcn2 mutant overaccumulated transcripts functionally related to abiotic stress, including oxidative stress, as well as innate immune responses. Accordingly, gcn2 displayed defects in immune priming by the fungal elicitor, chitin. Therefore, we provide evidence that reactive oxygen species produced by the photosynthetic apparatus help activate the highly conserved GCN2 kinase, leading to eIF2α phosphorylation and thus affecting the status of the cytosolic protein synthesis apparatus.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Arabidopsis/efeitos da radiação , Cloroplastos/metabolismo , Cloroplastos/efeitos da radiação , Luz , Biossíntese de Proteínas/efeitos da radiação , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Quitina/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Ontologia Genética , Herbicidas/toxicidade , Peróxido de Hidrogênio/farmacologia , Mutação/genética , Fosforilação/efeitos da radiação , Fotossíntese/efeitos dos fármacos , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Ribossomos/efeitos da radiação , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/efeitos da radiação , Transcriptoma/genética
15.
PLoS One ; 14(9): e0218226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31568476

RESUMO

BACKGROUND: Portugal has one of the most severe HIV-1 epidemics in Western Europe. Two subtypes circulate in parallel since the beginning of the epidemic. Comparing their transmission patterns and its association with transmitted drug resistance (TDR) is important to pinpoint transmission hotspots and to develop evidence-based treatment guidelines. METHODS: Demographic, clinical and genomic data were collected from 3599 HIV-1 naive patients between 2001 and 2014. Sequences obtained from drug resistance testing were used for subtyping, TDR determination and transmission clusters (TC) analyses. RESULTS: In Portugal, transmission of subtype B was significantly associated with young males, while transmission of subtype G was associated with older heterosexuals. In Portuguese originated people, there was a decreasing trend both for prevalence of subtype G and for number of TCs in this subtype. The active TCs that were identified (i.e. clusters originated after 2008) were associated with subtype B-infected males residing in Lisbon. TDR was significantly different when comparing subtypes B (10.8% [9.5-12.2]) and G (7.6% [6.4-9.0]) (p = 0.001). DISCUSSION: TC analyses shows that, in Portugal, the subtype B epidemic is active and fueled by young male patients residing in Lisbon, while transmission of subtype G is decreasing. Despite similar treatment rates for both subtypes in Portugal, TDR is significantly different between subtypes.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1 , Fatores Etários , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Feminino , Seguimentos , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Razão de Chances , Portugal/epidemiologia , Prevalência , Vigilância em Saúde Pública , Fatores Sexuais , Fatores Socioeconômicos , Adulto Jovem
16.
J Mol Graph Model ; 93: 107444, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31494534

RESUMO

A zwitterionic-based chemical, the 3,3'-(octadecylamino)dipropionic acid, was quantum-theoretically designed to be applied as a corrosion inhibitor for protecting oxidized iron surfaces against the attack of very corrosive gasolines. Its performance, as well as those of worldwide-employed nitrogen-free carboxylic-diacid-based corrosion inhibitors, were experimentally evaluated and compared. Through Density-Functional-Theory calculations of the molecular interactions of the corrosion inhibitors with an iron-oxide cluster model, along with the experimental corrosion-inhibiting evaluations, it is revealed that the zwitterionic-based chemical substantially overcomes the performance of nitrogen-free chemicals. It is shown by the theoretical results that the two carboxylic heads of either, the zwitterionic-based or the nitrogen-free corrosion inhibitors, reinforce the octahedral coordination around the exposed Fe3+ atom of the iron oxide. Furthermore, when the zwitterionic-based chemical is bonded to the Fe3+ atom, a two-rings chelate is formed, in contrast to the one-ring chelate formed by the nitrogen-free corrosion inhibitors. Finally, it is theoretically predicted that oleic solvents improve the performance of the zwitterionic-based corrosion inhibitor because preclude the steric hindrance of nitrogen.


Assuntos
Corrosão , Compostos Férricos/química , Ferro/química , Modelos Moleculares , Nitrogênio/química , Teoria Quântica , Propriedades de Superfície
17.
J Mol Graph Model ; 91: 204-213, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31265937

RESUMO

The formation in solution of supramolecular complexes type zwitterion-cation have been shown. The industrial grade zwitterion surfactants cocamidopropyl hydroxysultaine and cocamidopropyl betaine with sodium ion were studied. A combined experimental and theoretical point of view was performed, through the use of Ultra-Performance Liquid Chromatography/Mass Spectrometry/ElectroSpray Ionization with positive mode (UPLC/MS/ESI+) analytic technique and Density Functional Theory (DFT) theoretical approach. Then, the supramolecular complex zwitterion-cation-anion triplets are shown to be viable. Mass/Charge (m/z) relationships have been determined through MS/ESI using positive mode as an ionization source, obtaining five and four molecular species for industrial grade sultaine and betaine chemical products, respectively. Also, molecular zwitterion-NaCl complexes were theoretically studied in three different dielectric constants corresponding to water, methanol, and acetone solvents. It was found that acetone, the lower dielectric constant solvent studied, shows the higher interaction energy. In both vacuum neutral, zwitterion-NaCl, and vacuum positive, zwitterion-Na+, molecular complexes the interaction of the cocamidopropyl hydroxysultaine pairs is less strong than cocamidopropyl betaine ones.


Assuntos
Teoria da Densidade Funcional , Sódio/química , Espectrometria de Massas por Ionização por Electrospray , Tensoativos/química , Cátions , Cromatografia Líquida de Alta Pressão , Conformação Molecular , Peso Molecular , Cloreto de Sódio/química
18.
J Infect Dis ; 220(2): 233-243, 2019 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-30805610

RESUMO

BACKGROUND: Estimation of temporal changes in human immunodeficiency virus (HIV) transmission patterns can help to elucidate the impact of preventive strategies and public health policies. METHODS: Portuguese HIV-1 subtype B and G pol genetic sequences were appended to global reference data sets to identify country-specific transmission clades. Bayesian birth-death models were used to estimate subtype-specific effective reproductive numbers (Re). Discrete trait analysis (DTA) was used to quantify mixing among transmission groups. RESULTS: We identified 5 subtype B Portuguese clades (26-79 sequences) and a large monophyletic subtype G Portuguese clade (236 sequences). We estimated that major shifts in HIV-1 transmission occurred around 1999 (95% Bayesian credible interval [BCI], 1998-2000) and 2000 (95% BCI, 1998-2001) for subtypes B and G, respectively. For subtype B, Re dropped from 1.91 (95% BCI, 1.73-2.09) to 0.62 (95% BCI,.52-.72). For subtype G, Re decreased from 1.49 (95% BCI, 1.39-1.59) to 0.72 (95% BCI, .63-.8). The DTA suggests that people who inject drugs (PWID) and heterosexuals were the source of most (>80%) virus lineage transitions for subtypes G and B, respectively. CONCLUSIONS: The estimated declines in Re coincide with the introduction of highly active antiretroviral therapy and the scale-up of harm reduction for PWID. Inferred transmission events across transmission groups emphasize the importance of prevention efforts for bridging populations.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/genética , Teorema de Bayes , Infecções por HIV/virologia , Humanos , Epidemiologia Molecular , Filogenia , Portugal/epidemiologia , Saúde Pública , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
19.
Cancer Lett ; 440-441: 145-155, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30339780

RESUMO

Targeting specific tumor metabolic needs represents an actively investigated therapeutic strategy to bypass tumor resistance mechanisms. In this study, we describe an original approach to impact the cancer metabolism by exploiting the redox properties of a ruthenium organometallic compound. This organometallic complex induced p53-independent cytotoxicity and reduced size and vascularization of patients-derived tumor explants that are resistant to platinum drugs. At the molecular level, the ruthenium complex altered redox enzyme activities and the intracellular redox state by increasing the NAD+/NADH ratio and ROS levels. Pathway analysis pointed to HIF-1 as a top deregulated metabolite pathway. Unlike cisplatin, treatment with the ruthenium complex decreased HIF1A protein levels and expression of HIF1A target genes. The rapid downregulation of HIF1A protein levels involved a direct interaction of the ruthenium compound with the redox enzyme PHD2, a HIF1A master regulator. HIF1A inhibition led to decreased angiogenesis in patient-derived xenografted using fragments of primary human colon tumors. Altogether, our results show that a ruthenium compound impacts metabolic pathways acting as anticancer agents in colon cancer via an original mechanism of action that affects redox enzymes differently than platinum-based drugs.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos/farmacologia , Cisplatino/farmacologia , Neoplasias Colorretais/irrigação sanguínea , Feminino , Células HCT116 , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Compostos Organometálicos/química , Oxirredução , Rutênio/química , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Rev. latinoam. bioét ; 18(2): 62-79, jul.-dic. 2018. tab
Artigo em Espanhol | LILACS | ID: biblio-985646

RESUMO

Resumen El presente artículo es el resultado de un ejercicio de reflexión desde la bioética social de los conflictos de género y la necesidad de vincular las masculinidades tanto en el campo de estudios de género como en los movimientos sociales y las políticas públicas. Se presenta una genealogía de algunas fuerzas sociales que han dinamizado los estudios de género a partir de comprender la violencia basada en el género, la salud pública, la alimentación y la degradación ambiental, en clave diferencial y de bioproblemas. Desde esta perspectiva se plantean algunos retos que enfrenta la sociedad al vincular estas comprensiones y estrategias de cambio, si de construir un horizonte de accionar político se trata. Desde las políticas públicas, la sociedad y la academia, es necesario continuar un trabajo frente a los factores estructurales que hacen que permanezcan las violencias contra las mujeres, la legitimación de violencia entre hombres y la vinculación a grupos armados, así como la promoción del ejercicio de las paternidades y las éticas del cuidado y la incidencia de estas en la política y la economía, como puntos del debate necesario para la construcción de sociedades más igualitarias.


Abstract The present article is the result of reflecting, from social bioethics, on gender conflicts and the need to link masculinities both to gender studies and to social movements and public policies. A genealogy of certain social forces that have invigorated gender studies from the understanding of gender-based violence, public health, food and environmental degradation is presented in terms of differences and bio-problems. From this perspective, there are some challenges that society faces in connecting these understandings and change strategies, when it comes to building a horizon of political action. From public policies, society and academia, it is necessary to continue working on the structural factors that perpetuate violence against women, the legitimization of violence among men and their enrollment in armed groups, as well as the promotion of the exercise of paternity and the ethics of care and their impact on politics and the economy. These topics need to be debated in order to build more egalitarian societies.


Resumo Este artigo é o resultado de um exercício de reflexão a partir da bioética social dos conflitos de gênero e da necessidade de vincular as masculinidades tanto no campo de estudos de gênero quanto nos movimentos sociais e nas políticas públicas. Apresenta-se a genealogia de algumas forças sociais que vêm dinamizando os estudos de gênero a partir de compreender a violência baseada no gênero, na saúde pública, na alimentação e na degradação ambiental, em termos diferenciais e bioproblemáticos. Sob essa perspectiva, expõem-se alguns desafios que a socie dade enfrenta ao vincular essas compreensões e estratégias de mudança, quando de construir um horizonte de atuação política se trata. Das políticas públicas, da sociedade e da academia, é necessário continuar o trabalho diante dos fatores estruturais que fazem com que permaneçam as violências contra as mulheres, a legitimação de violência entre homens e a vinculação a grupos armados, bem como a promoção do exercício das paternidades e das éticas do cuidado e a incidência destas na política e na economia, como pontos do debate urgente para a construção de sociedades mais igualitárias.


Assuntos
Humanos , Bioética , Sexualidade , Estudos de Gênero , Ciências Humanas
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