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1.
Earths Future ; 12(6): 1-17, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38993973

RESUMO

Climate impacts increasingly unfold in interlinked systems of people, nature, and infrastructure. The cascading consequences are revealing sometimes surprising connections across sectors and regions, and prospects for climate responses also depend on complex, difficult-to-understand interactions. In this commentary, we build on the innovations of the United States Fifth National Climate Assessment to suggest a framework for understanding and responding to complex climate challenges. This approach involves: (a) integration of disciplines and expertise to understand how intersectionality shapes complex climate impacts and the wide-ranging effects of climate responses, (b) collaborations among diverse knowledge holders to improve responses and better encompass intersectionality, and (c) sustained experimentation with and learning about governance approaches capable of handling the complexity of climate change. Together, these three pillars underscore that usability of climate-relevant knowledge requires transdisciplinary coordination of research and practice. We outline actionable steps for climate research to incorporate intersectionality, integration, and innovative governance, as is increasingly necessary for confronting climate complexity and sustaining equitable, ideally vibrant climate futures.

2.
Front Immunol ; 15: 1394114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873610

RESUMO

Introduction: Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system. Methods: This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations. Results: Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells. Discussion: The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Ativação Linfocitária , Vírus da Doença de Newcastle , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Vírus da Doença de Newcastle/imunologia , Vacinas contra COVID-19/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Ativação Linfocitária/imunologia , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia , Vacina BNT162/imunologia , Vacinação , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo
3.
Arch Microbiol ; 206(7): 328, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935150

RESUMO

Marine hydrocarbonoclastic bacteria can use polycyclic aromatic hydrocarbons as carbon and energy sources, that makes these bacteria highly attractive for bioremediation in oil-polluted waters. However, genomic and metabolic differences between species are still the subject of study to understand the evolution and strategies to degrade PAHs. This study presents Rhodococcus ruber MSA14, an isolated bacterium from marine sediments in Baja California, Mexico, which exhibits adaptability to saline environments, a high level of intrinsic pyrene tolerance (> 5 g L- 1), and efficient degradation of pyrene (0.2 g L- 1) by 30% in 27 days. Additionally, this strain demonstrates versatility by using naphthalene and phenanthrene as individual carbon sources. The genome sequencing of R. ruber MSA14 revealed a genome spanning 5.45 Mbp, a plasmid of 72 kbp, and three putative megaplasmids, lengths between 110 and 470 Kbp. The bioinformatics analysis of the R. ruber MSA14 genome revealed 56 genes that encode enzymes involved in the peripheral and central pathways of aromatic hydrocarbon catabolism, alkane, alkene, and polymer degradation. Within its genome, R. ruber MSA14 possesses genes responsible for salt tolerance and siderophore production. In addition, the genomic analysis of R. ruber MSA14 against 13 reference genomes revealed that all compared strains have at least one gene involved in the alkanes and catechol degradation pathway. Overall, physiological assays and genomic analysis suggest that R. ruber MSA14 is a new haloalkalitolerant and hydrocarbonoclastic strain toward a wide range of hydrocarbons, making it a promising candidate for in-depth characterization studies and bioremediation processes as part of a synthetic microbial consortium, as well as having a better understanding of the catabolic potential and functional diversity among the Rhodococci group.


Assuntos
Biodegradação Ambiental , Genoma Bacteriano , Genômica , Sedimentos Geológicos , Hidrocarbonetos Policíclicos Aromáticos , Rhodococcus , Rhodococcus/genética , Rhodococcus/metabolismo , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Sedimentos Geológicos/microbiologia , Naftalenos/metabolismo , Filogenia , Fenantrenos/metabolismo , Tolerância ao Sal , Pirenos
4.
Microbiol Resour Announc ; 13(7): e0033524, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38916305

RESUMO

We report the draft genome sequence of three marine bacteria belonging to Pseudomonas and Stutzerimonas genera, with hydrocarbonoclastic metabolism for oil and monoaromatic hydrocarbon degradation. The genomic information of these organisms contributes to the knowledge of natural and polluted marine environments with ubiquitous presence of hydrocarbons as a selective pressure.

5.
Free Radic Biol Med ; 221: 125-135, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38734269

RESUMO

Higher levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a TLR4 agonist, are associated with poor clinical outcomes in sepsis-induced acute lung injury (ALI). Little is known regarding the mechanisms by which eNAMPT is involved in ALI. Our recent work has identified a crucial role for mitochondrial dysfunction in ALI. Thus, this study aimed to determine if eNAMPT-mediated inflammatory injury is associated with the loss of mitochondrial function. Our data show that eNAMPT disrupted mitochondrial bioenergetics. This was associated with cytoskeleton remodeling and the loss of endothelial barrier integrity. These changes were associated with enhanced mitochondrial fission and blocked when Rho-kinase (ROCK) was inhibited. The increases in mitochondrial fission were also associated with the nitration-mediated activation of the small GTPase activator of ROCK, RhoA. Blocking RhoA nitration decreased eNAMPT-mediated mitochondrial fission and endothelial barrier dysfunction. The increase in fission was linked to a RhoA-ROCK mediated increase in Drp1 (dynamin-related protein 1) at serine(S)616. Another TLR4 agonist, lipopolysaccharide (LPS), also increased mitochondrial fission in a Drp1 and RhoA-ROCK-dependent manner. To validate our findings in vivo, we challenged C57BL/6 mice with eNAMPT in the presence and absence of the Drp1 inhibitor, Mdivi-1. Mdivi-1 treatment protected against eNAMPT-induced lung inflammation, edema, and lung injury. These studies demonstrate that mitochondrial fission-dependent disruption of mitochondrial function is essential in TLR4-mediated inflammatory lung injury and identify a key role for RhoA-ROCK signaling. Reducing mitochondrial fission could be a potential therapeutic strategy to improve ARDS outcomes.


Assuntos
Lesão Pulmonar Aguda , Citoesqueleto , Células Endoteliais , Dinâmica Mitocondrial , Receptor 4 Toll-Like , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP , Animais , Proteína rhoA de Ligação ao GTP/metabolismo , Camundongos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Quinases Associadas a rho/metabolismo , Humanos , Citoesqueleto/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Camundongos Endogâmicos C57BL , Lipopolissacarídeos , Masculino , Transdução de Sinais
6.
Vaccines (Basel) ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38543943

RESUMO

Bovine babesiosis, caused by the protozoan Babesia bigemina, is one of the most important hemoparasite diseases of cattle in Mexico and the world. An attenuated B. bigemina strain maintained under in vitro culture conditions has been used as a live attenuated vaccine; however, the biological mechanisms involved in attenuation are unknown. The objective of this study was to identify, through a comparative transcriptomics approach, the components of the B. bigemina virulent parasites that are differentially expressed in vivo, as opposed to those expressed by B. bigemina attenuated vaccine parasites when inoculated into naïve cattle. The biological material under study was obtained by inoculating spleen-intact cattle with infected erythrocytes containing either the attenuated strain or a virulent field strain. After RNA extraction, transcriptomic analysis (RNA-seq) was performed, followed by bioinformatic Differential Expression (DE) analysis and Gene Ontology (GO) term enrichment. The high-throughput sequencing results obtained by analyzing three biological replicates for each parasite strain ranged from 9,504,000 to 9,656,000, and 13,400,000 to 15,750,000 reads for the B. bigemina attenuated and virulent strains, respectively. At least 519 differentially expressed genes were identified in the analyzed strains. In addition, GO analysis revealed both similarities and differences across the three categories: cellular components, biological processes, and molecular functions. The attenuated strain of B. bigemina derived from in vitro culture presents global transcriptomic changes when compared to the virulent strain. Moreover, the obtained data provide insights into the potential molecular mechanisms associated with the attenuation or pathogenicity of each analyzed strain, offering molecular markers that might be associated with virulence or potential vaccine candidates.

7.
Microb Genom ; 10(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512312

RESUMO

A total of 14 973 alleles in 29 661 sequenced samples collected between March 2021 and January 2023 by the Mexican Consortium for Genomic Surveillance (CoViGen-Mex) and collaborators were used to construct a thorough map of mutations of the Mexican SARS-CoV-2 genomic landscape containing Intra-Patient Minor Allelic Variants (IPMAVs), which are low-frequency alleles not ordinarily present in a genomic consensus sequence. This additional information proved critical in identifying putative coinfecting variants included alongside the most common variants, B.1.1.222, B.1.1.519, and variants of concern (VOCs) Alpha, Gamma, Delta, and Omicron. A total of 379 coinfection events were recorded in the dataset (a rate of 1.28 %), resulting in the first such catalogue in Mexico. The most common putative coinfections occurred during the spread of Delta or after the introduction of Omicron BA.2 and its descendants. Coinfections occurred constantly during periods of variant turnover when more than one variant shared the same niche and high infection rate was observed, which was dependent on the local variants and time. Coinfections might occur at a higher frequency than customarily reported, but they are often ignored as only the consensus sequence is reported for lineage identification.


Assuntos
COVID-19 , Coinfecção , Humanos , México/epidemiologia , Coinfecção/epidemiologia , Alelos , SARS-CoV-2/genética , COVID-19/epidemiologia
8.
Antibiotics (Basel) ; 13(2)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38391562

RESUMO

BACKGROUND: First-line treatments for methicillin-susceptible S. aureus (MSSA) bacteraemia are nafcillin, oxacillin, or cefazolin. Regional shortages of these antibiotics force clinicians to use other options like dicloxacillin and cephalotin. This study aims to describe and compare the safety and efficacy of cephalotin and dicloxacillin for the treatment of MSSA bacteraemia. METHODS: This retrospective study was conducted in a referral centre in Mexico City. We identified MSSA isolates in blood cultures from 1 January 2012 to 31 December 2022. Patients ≥ 18 years of age, with a first episode of MSSA bacteraemia, who received cephalotin or dicloxacillin as the definitive antibiotic treatment, were included. The primary outcome was in-hospital all-cause mortality. RESULTS: We included 202 patients, of which 48% (97/202) received cephalotin as the definitive therapy and 52% (105/202) received dicloxacillin. In-hospital all-cause mortality was 20.7% (42/202). There were no differences in all-cause in-hospital mortality between patients receiving cephalotin or dicloxacillin (20% vs. 21%, p = 0.43), nor in 30-day all-cause mortality (14% vs. 18%, p = 0.57) or 90-day all-cause mortality (24% vs. 22%, p = 0.82). No severe adverse reactions were associated with either antibiotic. CONCLUSIONS: Cephalotin and dicloxacillin were equally effective for treating MSSA bacteraemia, and both showed an adequate safety profile.

9.
Redox Biol ; 70: 103049, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38295575

RESUMO

Once thought of in terms of bioenergetics, mitochondria are now widely accepted as both the orchestrator of cellular health and the gatekeeper of cell death. The pulmonary disease field has performed extensive efforts to explore the role of mitochondria in regulating inflammation, cellular metabolism, apoptosis, and oxidative stress. However, a critical component of these processes needs to be more studied: mitochondrial network dynamics. Mitochondria morphologically change in response to their environment to regulate these processes through fusion, fission, and mitophagy. This allows mitochondria to adapt their function to respond to cellular requirements, a critical component in maintaining cellular homeostasis. For that reason, mitochondrial network dynamics can be considered a bridge that brings multiple cellular processes together, revealing a potential pathway for therapeutic intervention. In this review, we discuss the critical modulators of mitochondrial dynamics and how they are affected in pulmonary diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), acute lung injury (ALI), and pulmonary arterial hypertension (PAH). A dysregulated mitochondrial network plays a crucial role in lung disease pathobiology, and aberrant fission/fusion/mitophagy pathways are druggable processes that warrant further exploration. Thus, we also discuss the candidates for lung disease therapeutics that regulate mitochondrial network dynamics.


Assuntos
Dinâmica Mitocondrial , Doença Pulmonar Obstrutiva Crônica , Humanos , Estresse Oxidativo , Inflamação , Metabolismo Energético
10.
bioRxiv ; 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38293033

RESUMO

Babesiosis, caused by protozoan parasites of the genus Babesia , is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of various Babesia species underscores the ongoing risk of new zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental shifts impacting the distribution and transmission dynamics of parasites, their vectors, and reservoir hosts. One such species, Babesia MO1, previously implicated in severe cases of human babesiosis in the midwestern United States, was initially considered closely related to B. divergens , the predominant agent of human babesiosis in Europe. Yet, uncertainties persist regarding whether these pathogens represent distinct variants of the same species or are entirely separate species. We show that although both B. MO1 and B. divergens share similar genome sizes, comprising three nuclear chromosomes, one linear mitochondrial chromosome, and one circular apicoplast chromosome, major differences exist in terms of genomic sequence divergence, gene functions, transcription profiles, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens , and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.

11.
Rev. Costarric. psicol ; 42(2): 241-262, jul.-dic. 2023. graf
Artigo em Espanhol | LILACS, SaludCR | ID: biblio-1559041

RESUMO

Resumen Estudio exploratorio-descriptivo sobre un grupo de profesionales costarricenses en psicología acerca de sus actitudes hacia la aplicación de los principios psicológicos en la práctica odontológica. La muestra fue de 377 psicólogos (activos en el Colegio de Profesionales en Psicología de Costa Rica). A partir del cuestionario original diseñado por Gómez y Gómez (2007), el cual fue construido para estimar la necesidad de conformar programas universitarios que integren la psicología y la odontología, se aplicó una adaptación consistente en una encuesta de 10 preguntas autoadministradas de selección simple, la cual se efectuó en línea a través del sistema QuestionPro®. Se pudo evidenciar que existe una actitud positiva ante el enfoque interdisciplinario entre la Odontología y la Psicología; se demostró que un 74% de la muestra sostiene que los aspectos psicosociales son "Bastante importantes" en el marco de la atención odontológica. A pesar de ello, la mayoría (57%) de las personas consultadas indicó que no ha tenido ocasión de aplicar sus conocimientos y experiencia en psicología al contexto odontológico. Asimismo, un 72% de los participantes considera "Bastante importante" que los profesionales en Odontología reciban capacitación básica en el área psicológica para la prevención o contención de ciertos síntomas que puedan incidir en la salud mental. Por otra parte, el 80% de quienes respondieron la encuesta indicaron que las iniciativas interdisciplinarias de colaboración científica (investigación) y aplicada (ejercicio profesional) son "Bastante importantes" para producir beneficios tangibles en la prestación de servicios integrales a los pacientes y el bienestar del personal sanitario.


Abstract Exploratory-descriptive study on a group of Costa Rican professionals in psychology about their attitudes towards the application of psychological principles in dental practice. The sample consisted of 377 psychologists (active in the Association of Psychology Professionals of Costa Rica). From the original questionnaire designed by Gómez and Gómez (2007), which was built to estimate the need to create university programs that integrate psychology and dentistry, an adaptation consisting of a survey of 10 self-administered questions of simple selection was applied, which was carried out online through the QuestionPro® system. It was possible to show that there is a positive attitude towards the interdisciplinary approach between Dentistry and Psychology; it was shown that 74% of the sample maintains that psychosocial aspects are "Quite important" in the context of dental care. Despite this, the majority (57%) of the people consulted indicated that they had not had the opportunity to apply their knowledge and experience as psychologists to the dental context. Likewise, 72% of the participants consider it "Quite important" that dental professionals receive basic training in the psychological area for the prevention or containment of certain symptoms that may affect mental health. On the other hand, 80% of the survey respondents indicated that interdisciplinary initiatives of professional scientific (research) and applied (practice) collaboration are "Quite important" to produce tangible benefits in the provision of comprehensive services to patients and wellbeing of health personnel.


Assuntos
Humanos , Masculino , Feminino , Psicologia , Atitude , Assistência Odontológica/psicologia , Costa Rica , Práticas Interdisciplinares
12.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139362

RESUMO

The disruption of mitochondrial dynamics has been identified in cardiovascular diseases, including pulmonary hypertension (PH), ischemia-reperfusion injury, heart failure, and cardiomyopathy. Mitofusin 2 (Mfn2) is abundantly expressed in heart and pulmonary vasculature cells at the outer mitochondrial membrane to modulate fusion. Previously, we have reported reduced levels of Mfn2 and fragmented mitochondria in pulmonary arterial endothelial cells (PAECs) isolated from a sheep model of PH induced by pulmonary over-circulation and restoring Mfn2 normalized mitochondrial function. In this study, we assessed the effect of increased expression of Mfn2 on mitochondrial metabolism, bioenergetics, reactive oxygen species production, and mitochondrial membrane potential in control PAECs. Using an adenoviral expression system to overexpress Mfn2 in PAECs and utilizing 13C labeled substrates, we assessed the levels of TCA cycle metabolites. We identified increased pyruvate and lactate production in cells, revealing a glycolytic phenotype (Warburg phenotype). Mfn2 overexpression decreased the mitochondrial ATP production rate, increased the rate of glycolytic ATP production, and disrupted mitochondrial bioenergetics. The increase in glycolysis was linked to increased hypoxia-inducible factor 1α (HIF-1α) protein levels, elevated mitochondrial reactive oxygen species (mt-ROS), and decreased mitochondrial membrane potential. Our data suggest that disrupting the mitochondrial fusion/fission balance to favor hyperfusion leads to a metabolic shift that promotes aerobic glycolysis. Thus, therapies designed to increase mitochondrial fusion should be approached with caution.


Assuntos
Hipertensão Pulmonar , Mitocôndrias , Animais , Trifosfato de Adenosina/metabolismo , Células Endoteliais/metabolismo , Glicólise , Hidrolases/metabolismo , Hipertensão Pulmonar/metabolismo , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ovinos , GTP Fosfo-Hidrolases/metabolismo
13.
Microb Genom ; 9(12)2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38112714

RESUMO

In Mexico, the BA.4 and BA.5 Omicron variants dominated the fifth epidemic wave (summer 2022), superseding BA.2, which had circulated during the inter-wave period. The present study uses genome sequencing and statistical and phylogenetic analyses to examine these variants' abundance, distribution, and genetic diversity in Mexico from April to August 2022. Over 35 % of the sequenced genomes in this period corresponded to the BA.2 variant, 8 % to the BA.4 and 56 % to the BA.5 variant. Multiple subvariants were identified, but the most abundant, BA.2.9, BA.2.12.1, BA.5.1, BA.5.2, BA.5.2.1 and BA.4.1, circulated across the entire country, not forming geographical clusters. Contrastingly, other subvariants exhibited a geographically restricted distribution, most notably in the Southeast region, which showed a distinct subvariant dynamic. This study supports previous results showing that this region may be a significant entry point and contributed to introducing and evolving novel variants in Mexico. Furthermore, a differential distribution was observed for certain subvariants among specific States through time, which may have contributed to the overall increased diversity observed during this wave compared to the previous ones. This study highlights the importance of sustaining genomic surveillance to identify novel variants that may impact public health.


Assuntos
COVID-19 , Humanos , México/epidemiologia , COVID-19/epidemiologia , Filogenia , SARS-CoV-2/genética
14.
Microbiol Resour Announc ; 12(11): e0079423, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37855632

RESUMO

Here, we report the draft genome sequences of six marine strains isolated from plastic samples incubated in the Mediterranean Sea. Genomic analyses place these strains within the Alkalihalobacillus, Bacillus, Halomonas, and Marinobacter genera. Examining the genomes of these non-typical environmental bacteria increases our comprehension of microorganism biology and their potential uses.

15.
Nitric Oxide ; 140-141: 50-57, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37659679

RESUMO

Endothelin (ET)-1 is an endothelial-derived peptide that exerts biphasic effects on nitric oxide (NO) levels in endothelial cells such that acute exposure stimulates-while sustained exposure attenuates-NO production. Although the mechanism involved in the decrease in NO generation has been identified but the signaling involved in the acute increase in NO is still unresolved. This was the focus of this study. Our data indicate that exposing pulmonary arterial endothelial cells (PAEC) to ET-1 led to an increase in NO for up to 30min after which levels declined. These effects were attenuated by ET receptor antagonists. The increase in NO correlated with significant increases in pp60Src activity and increases in eNOS phosphorylation at Tyr83 and Ser1177. The ET-1 mediated increase in phosphorylation and NO generation were attenuated by the over-expression of a pp60Src dominant negative mutant. The increase in pp60Src activity correlated with a reduction in the interaction of Caveolin-1 with pp60Src and the calcineurin-mediated dephosphorylation of caveolin-1 at three previously unidentified sites: Thr91, Thr93, and Thr95. The calcineurin inhibitor, Tacrolimus, attenuated the acute increase in pp60Src activity induced by ET-1 and a calcineurin siRNA attenuated the ET-1 mediated increase in eNOS phosphorylation at Tyr83 and Ser1177 as well as the increase in NO. By using a Caveolin-1 celluSpot peptide array, we identified a peptide targeting a sequence located between aa 41-56 as the pp60Src binding region. This peptide fused to the TAT sequence was found to decrease caveolin-pp60Src interaction, increased pp60Src activity, increased eNOS pSer1177 and NO levels in PAEC and induce vasodilation in isolated aortic rings in wildtype but not eNOS knockout mice. Together, our data identify a novel mechanism by which ET-1 acutely increases NO via a calcineurin-mediated dephosphorylation of caveolin-1 and the subsequent stimulation of pp60Src activity, leading to increases in phosphorylation of eNOS at Tyr83 and Ser1177.


Assuntos
Caveolina 1 , Óxido Nítrico , Animais , Camundongos , Calcineurina/metabolismo , Calcineurina/farmacologia , Caveolina 1/genética , Células Cultivadas , Células Endoteliais/metabolismo , Endotelina-1/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação
16.
PLoS One ; 18(9): e0291546, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37708134

RESUMO

The white potato worm Premnotrypes vorax (Hustache) (Coleoptera: Curculionidae) is one of the most destructive insect pests of potato crops in South America. Like many coleopteran insects, P. vorax shows low susceptibility to Cry insecticidal proteins produced by the bacterium Bacillus thuringiensis (Bt). However, the presence of Cry toxin receptors in the midgut of this this insect has never been studied. The main Cry-binding proteins described in other insect species are cadherin (CAD), aminopeptidase N (APN), alkaline phosphatase (ALP) and ATP-binding cassette (ABC) transporters. In this study, we analyzed and validated a de novo assembled transcriptome of Illumina sequencing data to identify and to characterize homologs of Cry toxin receptors. We identified the protein sequences in P. vorax that show high identity with their orthologous sequences of the Cry toxin binding proteins in other coleopteran larvae such as APN, ALP, CAD and ABC transporter. This study provides preliminary identification of putative receptor genes of Cry proteins that would be useful for future studies involving biocontrol of this important potato crop pest.


Assuntos
Besouros , Gorgulhos , Animais , Gorgulhos/genética , Transcriptoma , Proteínas de Insetos/genética , Transportadores de Cassetes de Ligação de ATP , Fosfatase Alcalina , Antígenos CD13/genética , Caderinas , Corantes
17.
Sci Adv ; 9(32): eadh0066, 2023 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-37556552

RESUMO

We breathe at the molecular level when mitochondria in our cells consume oxygen to extract energy from nutrients. Mitochondria are characteristic cellular organelles that derive from aerobic bacteria and carry out oxidative phosphorylation and other key metabolic pathways in eukaryotic cells. The precise bacterial origin of mitochondria and, consequently, the ancestry of the aerobic metabolism of our cells remain controversial despite the vast genomic information that is now available. Here, we use multiple approaches to define the most likely living relatives of the ancestral bacteria from which mitochondria originated. These bacteria live in marine environments and exhibit the highest frequency of aerobic traits and genes for the metabolism of fundamental lipids that are present in the membranes of eukaryotes, sphingolipids, and cardiolipin.


Assuntos
Mitocôndrias , Organelas , Mitocôndrias/genética , Mitocôndrias/metabolismo , Organelas/metabolismo , Bactérias/genética , Células Eucarióticas/metabolismo , Eucariotos , Metabolismo Energético
18.
Elife ; 122023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37498057

RESUMO

Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.


Assuntos
COVID-19 , Humanos , México/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2/genética , Evolução Biológica , Filogenia
19.
J Pediatr Gastroenterol Nutr ; 77(3): 327-331, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37229777

RESUMO

BACKGROUND: Little is known about ileal motility patterns and their utility in children. Here, we present our experience with children undergoing ileal manometry (IM). METHODS: A retrospective review of children with ileostomy comparing IM between 2 groups: A [chronic intestinal pseudo-obstruction (CIPO)] and B (feasibility of ileostomy closure in children with defecation disorders). We also compared the IM findings with those from antroduodenal manometry (ADM), and evaluated the joint effect of age, sex, and study indication group on IM results. RESULTS: A total of 27 children (median age 5.8 years old, range 0.5-16.74 years, 16 were female) were included (12 in group A and 15 in group B). There was no association between IM interpretation and sex; however younger age was associated with abnormal IM ( P = 0.021). We found a significantly higher proportion of patients with presence of phase III of the migrating motor complex (MMC) during fasting and normal postprandial response in group B than in group A ( P < 0.001). Logistic regression analysis revealed that only Group B was associated with normal IM ( P < 0.001). We found a moderate agreement for the presence of phase III MMC and postprandial response between IM and ADM (kappa = 0.698, P = 0.008 and kappa = 0.683, P = 0.009, respectively). CONCLUSION: IM is abnormal in patients with CIPO and normal in patients with defecation disorders, suggesting that IM may be not needed for ostomy closure in those with defecation disorders. IM has a moderate agreement with ADM and could be used as a surrogate for small bowel motility.


Assuntos
Defecação , Pseudo-Obstrução Intestinal , Criança , Humanos , Feminino , Lactente , Pré-Escolar , Adolescente , Masculino , Pseudo-Obstrução Intestinal/diagnóstico , Pseudo-Obstrução Intestinal/cirurgia , Motilidade Gastrointestinal/fisiologia , Complexo Mioelétrico Migratório/fisiologia , Intestino Delgado , Doença Crônica , Manometria/métodos
20.
Artigo em Inglês | MEDLINE | ID: mdl-37047934

RESUMO

Inadequate knowledge is one of the principal obstacles for preventing HIV/AIDS spread. Worldwide, it is reported that adolescents and young people have a higher vulnerability of being infected. Thus, the need to understand youths' knowledge towards HIV/AIDS becomes crucial. This study aimed to identify the determinants and develop a predictive model to estimate HIV/AIDS knowledge among this target population in Peru. Data from the 2019 DHS Survey were used. The software RStudio and RapidMiner were used for quasi-binomial logistic regression and computational model building, respectively. Five classification algorithms were considered for model development and their performance was assessed using accuracy, sensitivity, specificity, FPR, FNR, Cohen's kappa, F1 score and AUC. The results revealed an association between 14 socio-demographic, economic and health factors and HIV/AIDS knowledge. The accuracy levels were estimated between 59.47 and 64.30%, with the random forest model showing the best performance (64.30%). Additionally, the best classifier showed that the gender of the respondent, area of residence, wealth index, region of residence, interviewee's age, highest educational level, ethnic self-perception, having heard about HIV/AIDS in the past, the performance of an HIV/AIDS screening test and mass media access have a major influence on HIV/AIDS knowledge prediction. The results suggest the usefulness of the associations found and the random forest model as a predictor of knowledge of HIV/AIDS and may aid policy makers to guide and reinforce the planning and implementation of healthcare strategies.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Adolescente , Adulto Jovem , Modelos Logísticos , Peru/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Algoritmos , Aprendizado de Máquina , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde
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