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1.
Acta Vet Hung ; 72(1): 1-10, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38578711

RESUMO

The authors aimed to investigate eight strains of Escherichia coli (E. coli) strains from Hungarian layer flocks for antimicrobial resistance genes (ARG), using metagenomic methods. The strains were isolated from cloacal swabs of healthy adult layers. This study employed shotgun sequencing-based genetic and bioinformatic analysis along with determining phenotypic minimum inhibitory concentrations. A total of 59 ARGs were identified in the eight E. coli isolates, carrying ARGs against 15 groups of antibiotics. Among these, 28 ARGs were identified as transferable. Specifically, four ARGs were plasmid-derived, 18 ARGs were phage-derived and an additional six ARGs were predicted to be mobile, contributing to their mobility and potential spread between bacteria.


Assuntos
Escherichia coli , Genes Bacterianos , Animais , Escherichia coli/genética , Hungria/epidemiologia , Antibacterianos/farmacologia , Bactérias
2.
Heliyon ; 10(6): e27583, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38509917

RESUMO

Silver nanoparticles (AgNPs) are known to affect the physiology and morphology of plants in various ways, but the exact mechanism by which they interact with plant cells remains to be elucidated. An unresolved question of silver nanotoxicology is whether the interaction is triggered by the physical features of the particles, or by silver ions leached from their surface. In this study, we germinated and grew Arabidopsis thaliana seedlings in synthetic medium supplemented with sub-morbid concentrations (4 µg/mL) of AgNPs and silver nitrate (AgNO3). This treatment led to in planta accumulation of 106 µg/g and 97 µg/g of silver in the AgNO3- and AgNP-exposed seedlings, respectively. Despite the statistically indistinguishable silver accumulation, RNA sequencing data demonstrated distinct changes in the transcriptome of the AgNP-exposed, but not in the AgNO3-exposed plants. AgNP exposure induced changes in the expression of genes involved in immune response, cell wall organization, photosynthesis and cellular defense against reactive oxygen species. AgNO3 exposure, on the other hand, caused the differential expression of only two genes, neither of which belonged to any AgNP-enriched gene ontology categories. Moreover, AgNP exposure led to a 39% reduction (p < 0.001) in total chlorophyll concentration relative to untreated plants which was associated with a 56.9% and 56.2% drop (p < 0.05) in carbon assimilation rate at ambient and saturating light, respectively. Stomatal conductance was not significantly affected by AgNP exposure, and limitations to carbon assimilation, as determined through analysis of light and carbon dioxide (A/Ci) curves, were attributed to rates of electron transport, maximum carboxylation rates and triose phosphate use. AgNO3-exposure, on the other hand, did not lead to significant reduction either in chlorophyll concentration or in carbon assimilation rate. Given these data, we propose that the impact of AgNPs cannot be simply attributed to the presence of the metal in plants, but is innate to the particulate nature of nanosilver.

3.
Plant Physiol Biochem ; 208: 108466, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38428158

RESUMO

Mitochondria are important sources of energy in plants and are implicated in coordination of a number of metabolic and physiological processes including stabilization of redox balance, synthesis and turnover of a number of metabolites, and control of programmed cell death. Mitochondrial electron transport chain (mETC) is the backbone of the energy producing process which can influence other processes as well. Accumulating evidence suggests that mETC can affect responses to environmental stimuli and modulate tolerance to extreme conditions such as drought or salinity. Screening for stress responses of 13 Arabidopsis mitochondria-related T-DNA insertion mutants, we identified ndufs8.2-1 which has an increased ability to withstand osmotic and oxidative stresses compared to wild type plants. Insertion in ndufs8.2-1 disrupted the gene that encodes the NADH dehydrogenase [ubiquinone] fragment S subunit 8 (NDUFS8) a component of Complex I of mETC. ndufs8.2-1 tolerated reduced water availability, retained photosynthetic activity and recovered from severe water stress with higher efficiency compared to wild type plants. Several mitochondrial functions were altered in the mutant including oxygen consumption, ROS production, ATP and ADP content as well as activities of genes encoding alternative oxidase 1A (AOX1A) and various alternative NAD(P)H dehydrogenases (ND). Our results suggest that in the absence of NDUFS8.2 stress-induced ROS generation is restrained leading to reduced oxidative damage and improved tolerance to water deficiency. mETC components can be implicated in redox and energy homeostasis and modulate responses to stresses associated with reduced water availability.


Assuntos
Arabidopsis , Mitocôndrias , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Oxirredução , Arabidopsis/metabolismo , Fotossíntese , Regulação da Expressão Gênica de Plantas
4.
Biomolecules ; 14(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38397377

RESUMO

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and, as such, provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may result in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in epigenetic regulation primarily by modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extranuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases, and we will discuss the potential of their inhibitors for lung injury prevention.


Assuntos
Células Endoteliais , Histona Desacetilases , Histona Desacetilases/metabolismo , Células Endoteliais/metabolismo , Epigênese Genética , Zinco/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Pulmão/metabolismo , Histonas/metabolismo
5.
Ann Rheum Dis ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373843

RESUMO

OBJECTIVES: To unveil biological milieus underlying low disease activity (LDA) and remission versus active systemic lupus erythematosus (SLE). METHODS: We determined differentially expressed pathways (DEPs) in SLE patients from the PRECISESADS project (NTC02890121) stratified into patients fulfilling and not fulfilling the criteria of (1) Lupus LDA State (LLDAS), (2) Definitions of Remission in SLE remission, and (3) LLDAS exclusive of remission. RESULTS: We analysed data from 321 patients; 40.8% were in LLDAS, and 17.4% in DORIS remission. After exclusion of patients in remission, 28.3% were in LLDAS. Overall, 604 pathways differed significantly in LLDAS versus non-LLDAS patients with an false-discovery rate-corrected p (q)<0.05 and a robust effect size (dr)≥0.36. Accordingly, 288 pathways differed significantly between DORIS remitters and non-remitters (q<0.05 and dr≥0.36). DEPs yielded distinct molecular clusters characterised by differential serological, musculoskeletal, and renal activity. Analysis of partially overlapping samples showed no DEPs between LLDAS and DORIS remission. Drug repurposing potentiality for treating SLE was unveiled, as were important pathways underlying active SLE whose modulation could aid attainment of LLDAS/remission, including toll-like receptor (TLR) cascades, Bruton tyrosine kinase (BTK) activity, the cytotoxic T lymphocyte antigen 4 (CTLA-4)-related inhibitory signalling, and the nucleotide-binding oligomerization domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome pathway. CONCLUSIONS: We demonstrated for the first time molecular signalling pathways distinguishing LLDAS/remission from active SLE. LLDAS/remission was associated with reversal of biological processes related to SLE pathogenesis and specific clinical manifestations. DEP clustering by remission better grouped patients compared with LLDAS, substantiating remission as the ultimate treatment goal in SLE; however, the lack of substantial pathway differentiation between the two states justifies LLDAS as an acceptable goal from a biological perspective.

6.
Heliyon ; 10(3): e25170, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38322875

RESUMO

Manufacturers use a large number of components in the production of modern rubber products. The selection of the constituents of the rubber recipe is primarily determined by the purpose of use. The different fields of applications of rubbers require the presence of appropriate mechanical properties. In this respect, it can be useful to know which substances forming the rubber recipe have significant influence on the different mechanical properties. In this study, the statistical analysis of the influence of rubber components on the hardness of natural rubber (NR) is proposed based on literature review. Based on the literature data, various statistical analyses, like linear regression, constrained linear regression, Ridge regression, Ridge sparse regression and binary classification decision trees were performed to determine which rubber components have the most significant effect on the hardness. In the statistical analyses, the effect of a total of 42 constituents of rubber compound on hardness was investigated. Most of the applied statistical methods confirmed that the traditional frequently used rubber components, such as carbon black and sulfur, have a primary effect on the hardness. However, the substances forming the rubber compound that are not widely used in practice or newly developed components appear differently in the lists of significant additives obtained by the different statistical methods.

7.
Prev Vet Med ; 224: 106119, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335830

RESUMO

Biosecurity is an essential tool for rearing healthy animals. Biosecurity measures (BMs) are well known in poultry production, but it is difficult to assess actual implementation on farms. The aims of this qualitative study were (1) to provide an overview of biosecurity implementation according to poultry farmers in Europe; and (2) to better understand the reported reasons and potential obstacles for not implementing the measures. In seven European Union Member States, 192 farmers (118 under contract with a company and 68 independents) working in seven different categories of poultry production were interviewed on 62 BMs to determine the frequency of implementation and the reasons for non-implementation. Most of the replies (n = 7791) concerning BM implementation were reported by the farmers as "always" implemented (81%), statistically higher for breeders (87%) and layers (82%) and lower for independent farms versus farms under contract with a company (79.5% and 82.5%, respectively). Regardless the poultry production category, the most frequently implemented BMs declared by the farmers were daily surveillance of birds, rodent control and feed storage protection. Standard hygiene practices were also mentioned as high-implementation measures for most production categories, with some deficiencies, such as rendering tank disinfection after each collection and, for meat poultry, disinfection of the feed silo and bacterial control of house cleaning and disinfection between each cycle. The entry of vehicles and individuals onto poultry farms, especially during critical points of eggs collection for breeders and layers, as well as the presence of other animals, such as the "all in/all out" practice, particularly in layers and ducks, were also reported as the least commonly practiced measures. The main reasons for not implementing the measures (n = 1683 replies) were low awareness and poor knowledge of the expected benefits of biosecurity ("no known advantages" 14%, and "not useful" 12%), the lack of training ("not enough training" 5% and "advice" 7%), lack of time (19%), and financial aspects (17%). Despite the good overall biosecurity mentioned by the farmers, these findings highlight certain deficiencies, suggesting room for improvement and the need for targeted and tailored support of poultry farmers in Europe.


Assuntos
Fazendeiros , Aves Domésticas , Animais , Humanos , Fazendas , Biosseguridade , Criação de Animais Domésticos , Inquéritos e Questionários , Europa (Continente)
8.
Plant Physiol ; 194(3): 1646-1661, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-37962583

RESUMO

In eukaryotic cells, phosphorus is assimilated and utilized primarily as phosphate (Pi). Pi homeostasis is mediated by transporters that have not yet been adequately characterized in green algae. This study reports on PHOSPHATE TRANSPORTER 4-7 (CrPHT4-7) from Chlamydomonas reinhardtii, a member of the PHT4 transporter family, which exhibits remarkable similarity to AtPHT4;4 from Arabidopsis (Arabidopsis thaliana), a chloroplastic ascorbate transporter. Using fluorescent protein tagging, we show that CrPHT4-7 resides in the chloroplast envelope membrane. Crpht4-7 mutants, generated by the CRISPR/Cas12a-mediated single-strand templated repair, show retarded growth, especially in high light, reduced ATP level, strong ascorbate accumulation, and diminished non-photochemical quenching in high light. On the other hand, total cellular phosphorous content was unaffected, and the phenotype of the Crpht4-7 mutants could not be alleviated by ample Pi supply. CrPHT4-7-overexpressing lines exhibit enhanced biomass accumulation under high light conditions in comparison with the wild-type strain. Expressing CrPHT4-7 in a yeast (Saccharomyces cerevisiae) strain lacking Pi transporters substantially recovered its slow growth phenotype, demonstrating that CrPHT4-7 transports Pi. Even though CrPHT4-7 shows a high degree of similarity to AtPHT4;4, it does not display any substantial ascorbate transport activity in yeast or intact algal cells. Thus, the results demonstrate that CrPHT4-7 functions as a chloroplastic Pi transporter essential for maintaining Pi homeostasis and photosynthesis in C. reinhardtii.


Assuntos
Arabidopsis , Chlamydomonas , Chlamydomonas/genética , Saccharomyces cerevisiae , Fotossíntese/genética , Cloroplastos , Homeostase , Ácido Ascórbico , Proteínas de Membrana Transportadoras
9.
Ann Rheum Dis ; 83(1): 15-29, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37827694

RESUMO

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.


Assuntos
Azatioprina , Lúpus Eritematoso Sistêmico , Humanos , Azatioprina/uso terapêutico , Tacrolimo/uso terapêutico , Rituximab/uso terapêutico , Metotrexato/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Imunossupressores/uso terapêutico , Ciclofosfamida/uso terapêutico , Hidroxicloroquina/uso terapêutico , Glucocorticoides/uso terapêutico , Inibidores Enzimáticos/uso terapêutico
10.
Acta Vet Hung ; 71(3-4): 137-141, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38090949

RESUMO

The darkling beetle, Alphitobius diaperinus, and the poultry red mite, Dermanysuss gallinae are among the most common pests of poultry farms. Both pests can be carriers and reservoirs of various pathogens including zoonotic ones like Salmonella. Salmonellosis is one of the most common foodborne diseases reported in the EU. We developed a semi-nested PCR method for the direct detection of Salmonella enterica. When testing the specificity of the novel PCR, we successfully detected various S. enterica strains, whereas Escherichia coli and Citrobacter strains gave negative results. The authenticity of the PCR products was confirmed by DNA sequencing. The sensitivity of the semi-nested PCR was tested on serial dilution of bacterial cultures and extracted DNA. We found our new method more sensitive than the previous PCRs. We also screened ectoparasite samples, collected from a poultry farm in Hungary, and three out of the eight samples were positive for S. Enteritidis. This novel PCR seems suitable for the detection of S. enterica strains in poultry ectoparasites without the need of sample pre-enrichment.


Assuntos
Doenças das Aves Domésticas , Salmonella enterica , Animais , Salmonella enterica/genética , Aves Domésticas , Galinhas , Reação em Cadeia da Polimerase/veterinária , Hungria/epidemiologia , Doenças das Aves Domésticas/diagnóstico , Doenças das Aves Domésticas/microbiologia
11.
Sensors (Basel) ; 23(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38005629

RESUMO

As the field of routine pathology transitions into the digital realm, there is a surging demand for the full automation of microscope scanners, aiming to expedite the process of digitizing tissue samples, and consequently, enhancing the efficiency of case diagnoses. The key to achieving seamless automatic imaging lies in the precise detection and segmentation of tissue sample regions on the glass slides. State-of-the-art approaches for this task lean heavily on deep learning techniques, particularly U-Net convolutional neural networks. However, since samples can be highly diverse and prepared in various ways, it is almost impossible to be fully prepared for and cover every scenario with training data. We propose a data augmentation step that allows artificially modifying the training data by extending some artifact features of the available data to the rest of the dataset. This procedure can be used to generate images that can be considered synthetic. These artifacts could include felt pen markings, speckles of dirt, residual bubbles in covering glue, or stains. The proposed approach achieved a 1-6% improvement for these samples according to the F1 Score metric.


Assuntos
Artefatos , Processamento de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Automação
12.
Vet Microbiol ; 287: 109909, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37925876

RESUMO

Mycoplasma iowae is a worldwide spread and economically important avian pathogen that mostly infects turkeys. Currently, multi-locus sequence typing (MLST) serves as the gold standard method for strain identification in M. iowae. However, additional robust genotyping methods are required to effectively monitor M. iowae infections and conduct epidemiological investigations. The first aim of this study was to develop genotyping assays with high resolution, that specifically target M. iowae, namely a multiple-locus variable number of tandem-repeats analysis (MLVA) and a core genome multi-locus sequence typing (cgMLST) schema. The second aim was the determination of relationships among a diverse selection of M. iowae strains and clinical isolates with a previous and the newly developed assays. The MLVA was designed based on the analyses of tandem-repeat (TR) regions in the six serotype reference strains (I, J, K, N, Q and R). The cgMLST schema was developed based on the coding sequences (CDSs) common in 95% of the examined 99 isolates. The samples were submitted for a previously published MLST assay for comparison with the developed methods. Out of 94 TR regions identified, 17 alleles were selected for further evaluation by PCR. Finally, seven alleles were chosen to establish the MLVA assay. Additionally, whole genome sequence analyses identified a total of 676 CDSs shared by 95% of the isolates, all of which were included into the developed cgMLST schema. The MLVA discriminated 19 distinct genotypes (GT), while with the cgMLST assay 79 sequence types (ST) could be determined with Simpson's diversity indices of 0.810 (MLVA) and 0.989 (cgMLST). The applied assays consistently identified the same main clusters among the diverse selection of isolates, thereby demonstrating their suitability for various genetic analyses and their ability to yield congruent results.


Assuntos
Mycoplasma iowae , Animais , Tipagem de Sequências Multilocus/métodos , Tipagem de Sequências Multilocus/veterinária , Genótipo , Técnicas de Genotipagem/veterinária , Sequências de Repetição em Tandem , Repetições Minissatélites/genética , Filogenia
13.
Lang Speech ; : 238309231193631, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737045

RESUMO

Sound symbolism is a non-arbitrary mapping between phonetic properties and meanings. The existence and nature of sound symbolism have long been the subject of empirical research. It is rarely recognized, however, that participants' intrinsic characteristics (e.g., age, gender, language knowledge), in addition to the commonly studied phonetic features, may also influence size ratings. Our study aims to empirically investigate the impact of participant-specific characteristics on size ratings: It also aims to examine whether these characteristics have a direct impact when considering the impact of phonetic features or they rather modify the effects of phonetic features. The current research reports a novel analysis of a previously published dataset with new research questions and previously unused (participant-specific) data. We show that (a) the participants' characteristics did not affect overall size ratings; however, (b) in some cases, they modify (intensify or weaken but do not reverse) the effect of phonetic features on size ratings. Our results emphasize a more comprehensive treatment of sound symbolism, one that considers not only phonetic but also non-phonetic factors in sound symbolism research.

14.
Front Vet Sci ; 10: 1231377, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37649565

RESUMO

Compliance with required on-farm biosecurity practices reduces the risk of contamination and spread of zoonotic and economically important diseases. With repeating avian influenza epidemics in the poultry industry, the need to monitor and improve the overall level of biosecurity is increasing. In practice, biosecurity compliance is assessed by various actors (e.g., academic, private and public institutions), and the results of such assessments may be recorded and gathered in databases which are seldom shared or thoroughly analyzed. This study aimed to provide an inventory of databases related to the assessment of biosecurity in poultry farms in seven major poultry-producing European countries to highlight challenges and opportunities associated with biosecurity data collection, sharing, and use. The institutions in charge of these databases were contacted and interviewed using a structured questionnaire to gather information on the main characteristics of the databases and the context of their implementation. A total of 20 databases were identified, covering the gamut of poultry species and production types. Most databases were linked to veterinary health authorities or academia, and to a lesser extent interbranch organizations. Depending on the institutions in charge, the databases serve various purposes, from providing advice to enforcing regulations. The quality of the biosecurity data collected is believed to be quite reliable, as biosecurity is mostly assessed by trained farm advisors or official veterinarians and during a farm visit. Some of the databases are difficult to analyze and/or do not offer information concerning which biosecurity measures are most or least respected. Moreover, some key biosecurity practices are sometimes absent from certain databases. Although the databases serve a variety of purposes and cover different production types, each with specific biosecurity features, their analysis should help to improve the surveillance of biosecurity in the poultry sector and provide evidence on the benefits of biosecurity.

15.
Am J Respir Cell Mol Biol ; 69(6): 678-688, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37639326

RESUMO

Acute lung injury (ALI) is characterized by lung vascular endothelial cell (EC) barrier compromise resulting in increased endothelial permeability and pulmonary edema. The infection of gram-negative bacteria that produce toxins like LPS is one of the major causes of ALI. LPS activates Toll-like receptor 4, leading to cytoskeleton reorganization, resulting in lung endothelial barrier disruption and pulmonary edema in ALI. However, the signaling pathways that lead to the cytoskeleton reorganization and lung microvascular EC barrier disruption remain largely unexplored. Here we show that LPS induces calpain activation and talin cleavage into head and rod domains and that inhibition of calpain attenuates talin cleavage, RhoA activation, and pulmonary EC barrier disruption in LPS-treated human lung microvascular ECs in vitro and lung EC barrier disruption and pulmonary edema induced by LPS in ALI in vivo. Moreover, overexpression of calpain causes talin cleavage and RhoA activation, myosin light chain (MLC) phosphorylation, and increases in actin stress fiber formation. Furthermore, knockdown of talin attenuates LPS-induced RhoA activation and MLC phosphorylation and increased stress fiber formation and mitigates LPS-induced lung microvascular endothelial barrier disruption. Additionally, overexpression of talin head and rod domains increases RhoA activation, MLC phosphorylation, and stress fiber formation and enhances lung endothelial barrier disruption. Finally, overexpression of cleavage-resistant talin mutant reduces LPS-induced increases in MLC phosphorylation in human lung microvascular ECs and attenuates LPS-induced lung microvascular endothelial barrier disruption. These results provide the first evidence that calpain mediates LPS-induced lung microvascular endothelial barrier disruption in ALI via cleavage of talin.


Assuntos
Lesão Pulmonar Aguda , Edema Pulmonar , Humanos , Lipopolissacarídeos/farmacologia , Calpaína/metabolismo , Talina/metabolismo , Pulmão/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Cadeias Leves de Miosina/metabolismo , Permeabilidade Capilar
16.
Int J Mol Sci ; 24(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37511603

RESUMO

Numerous in vitro and in vivo models of Parkinson's disease (PD) demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP) conveys its strong neuroprotective actions mainly via its specific PAC1 receptor (PAC1R) in models of PD. We recently described the decrease in PAC1R protein content in the basal ganglia of macaques in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD that was partially reversed by levodopa therapy. In this work, we tested whether these observations occur also in the rotenone model of PD in the rat. The rotarod test revealed motor skill deterioration upon rotenone administration, which was reversed by benserazide/levodopa (B/L) treatment. The sucrose preference test suggested increased depression level while the open field test showed increased anxiety in rats rendered parkinsonian, regardless of the received B/L therapy. Reduced dopaminergic cell count in the substantia nigra pars compacta (SNpc) diminished the dopaminergic fiber density in the caudate-putamen (CPu) and decreased the peptidergic cell count in the centrally projecting Edinger-Westphal nucleus (EWcp), supporting the efficacy of rotenone treatment. RNAscope in situ hybridization revealed decreased PACAP mRNA (Adcyap1) and PAC1R mRNA (Adcyap1r1) expression in the CPu, globus pallidus, dopaminergic SNpc and peptidergic EWcp of rotenone-treated rats, but no remarkable downregulation occurred in the insular cortex. In the entopeduncular nucleus, only the Adcyap1r1 mRNA was downregulated in parkinsonian animals. B/L therapy attenuated the downregulation of Adcyap1 in the CPu only. Our current results further support the evolutionarily conserved role of the PACAP/PAC1R system in neuroprotection and its recruitment in the development/progression of neurodegenerative states such as PD.


Assuntos
Núcleo de Edinger-Westphal , Doença de Parkinson , Animais , Ratos , Gânglios da Base/metabolismo , Dopamina/metabolismo , Regulação para Baixo , Núcleo de Edinger-Westphal/metabolismo , Levodopa/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Rotenona/metabolismo , Substância Negra/metabolismo
17.
Animals (Basel) ; 13(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37106972

RESUMO

The use of natural feed supplements is an alternative tool to diminish the damage caused by certain bacteria, improving animal health and productivity. The present research aimed to investigate the proinflammatory effect of flagellin released from the bacterial flagellum of Salmonella enterica serovar Typhimurium and to attenuate the induced inflammation with luteolin as a plant-derived flavonoid on a chicken primary hepatocyte-non-parenchymal cell co-culture. Cells were cultured in a medium supplemented with 250 ng/mL flagellin and 4 or 16 µg/mL luteolin for 24 h. Cellular metabolic activity, lactate dehydrogenase (LDH) activity, interleukin-6, 8, 10 (IL-6, IL-8, IL-10), interferon-α, γ (IFN-α, IFN-γ), hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations were determined. Flagellin significantly increased the concentration of the proinflammatory cytokine IL-8 and the ratio of IFN-γ/IL-10, while it decreased the level of IL-10, indicating that the model served adequate to study inflammation in vitro. Luteolin treatment at 4 µg/mL did not prove to be cytotoxic, as reflected by metabolic activity and extracellular LDH activity, and significantly reduced the flagellin-triggered IL-8 release of the cultured cells. Further, it had a diminishing effect on the concentration of IFN-α, H2O2 and MDA and restored the level of IL-10 and the ratio of IFN-γ/IL-10 when applied in combination with flagellin. These results suggest that luteolin at lower concentrations may protect hepatic cells from an excessive inflammatory response and act as an antioxidant to attenuate oxidative damage.

18.
BMC Plant Biol ; 23(1): 211, 2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37085756

RESUMO

BACKGROUND: Grafting is a horticultural practice used widely across woody perennial crop species to fuse together the root and shoot system of two distinct genotypes, the rootstock and the scion, combining beneficial traits from both. In grapevine, grafting is used in nearly 80% of all commercial vines to optimize fruit quality, regulate vine vigor, and enhance biotic and abiotic stress-tolerance. Rootstocks have been shown to modulate elemental composition, metabolomic profiles, and the shape of leaves in the scion, among other traits. However, it is currently unclear how rootstock genotypes influence shoot system gene expression as previous work has reported complex and often contradictory findings. RESULTS: In the present study, we examine the influence of grafting on scion gene expression in leaves and reproductive tissues of grapevines growing under field conditions for three years. We show that the influence from the rootstock genotype is highly tissue and time dependent, manifesting only in leaves, primarily during a single year of our three-year study. Further, the degree of rootstock influence on scion gene expression is driven by interactions with the local environment. CONCLUSIONS: Our results demonstrate that the role of rootstock genotype in modulating scion gene expression is not a consistent, unchanging effect, but rather an effect that varies over time in relation to local environmental conditions.


Assuntos
Interação Gene-Ambiente , Raízes de Plantas , Raízes de Plantas/metabolismo , Folhas de Planta/genética , Genótipo , Expressão Gênica
19.
Bioresour Technol ; 380: 129068, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37084984

RESUMO

Engineering cyanobacteria for the production of isoprene and other terpenoids has gained increasing attention in the field of biotechnology. Several studies have addressed optimization of isoprene synthesis in cyanobacteria via enzyme and pathway engineering. However, only little attention has been paid to the optimization of cultivation conditions. In this study, an isoprene-producing strain of Synechocystis sp. PCC 6803 and two control strains were grown under a variety of cultivation conditions. Isoprene production, as quantified by modified membrane inlet mass spectrometer (MIMS) and interpreted using Flux Balance Analysis (FBA), increased under violet light and at elevated temperature. Increase of thermotolerance in the isoprene producer was attributed to the physical presence of isoprene, similar to plants. The results demonstrate a beneficial effect of isoprene on cell survival at higher temperatures. This increased thermotolerance opens new possibilities for sustainable bio-production of isoprene and other products.


Assuntos
Synechocystis , Synechocystis/metabolismo , Temperatura , Hemiterpenos/metabolismo , Butadienos/metabolismo
20.
Ideggyogy Sz ; 76(1-2): 58-62, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36892294

RESUMO

IgG4-related (IgG4-RD) disease is a relatively newly identified, chronic autoimmune disorder that can affect any organ system. The disease is relatively rare. It has mostly systemic presentation, however it can also appear in isolated form in one single organ. In our report, we demonstrate an elderly male patient's case with IgG4-RD presented in the form of diffuse meningeal inflammation and hypertrophic pachymeningitis with one-sided cranial nerve and intraventricular involvement.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Meningite , Humanos , Masculino , Idoso , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G , Hipertrofia , Inflamação , Nervos Cranianos , Imageamento por Ressonância Magnética
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