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INTRODUCTION: The role of IMP3, CDK4, MDM2 and ß-catenin proteins in Enchondroma and Central Chondrosarcoma is not totally understood. The aim of this study is to evaluate the immunoexpression of these proteins, associating histological grade, clinical data and prognosis to these tumors. METHODS: This is a retrospective-analytical study of 32 Enchondroma and 70 Central Chondrosarcoma. RESULTS: IMP3, CDK4, MDM2 and ß-catenin expression was observed in 22.82 %, 13.82 %, 17.17 % and in 8.8 % of cases, respectively. All Enchondromas positive for these immunomarkers were located in short tubular bones. The positivity for these antibodies is directly proportional to Chondrosarcoma's histological grade increase. No difference was found between Enchondroma and Chondrosarcoma, Grade 1 for IMP3, CDK4 and ß-catenin positivity. Significant metastasis outcome was observed for IMP3, CDK4, MDM2 and death for MDM2 expression. CONCLUSION: IMP3, CDK4, MDM2 and ß-catenin expression in Enchondromas of short bones phenotypically characterizes these tumors. Their expression has not proven to be useful either as diagnostic markers of these neoplasms or in distinguishing between Enchondroma and Chondrosarcoma, Grade 1. The significant immunoexpression of IMP3, CDK4 and MDM2 in metastatic Chondrosarcoma and the lower survival in those with positivity for MDM2 suggest a possible association of these proteins with tumor aggressiveness.
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Biomarcadores Tumorais , Neoplasias Ósseas , Condroma , Condrossarcoma , Quinase 4 Dependente de Ciclina , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-mdm2 , beta Catenina , Humanos , Condrossarcoma/patologia , Condrossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/análise , Masculino , Feminino , Neoplasias Ósseas/patologia , Neoplasias Ósseas/metabolismo , Pessoa de Meia-Idade , beta Catenina/análise , beta Catenina/metabolismo , Adulto , Estudos Retrospectivos , Biomarcadores Tumorais/análise , Prognóstico , Condroma/patologia , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 4 Dependente de Ciclina/análise , Idoso , Adulto Jovem , Adolescente , Gradação de Tumores , Criança , Proteínas de Ligação a RNARESUMO
Introducción. Los pacientes con patología abdominal quirúrgica que requieren manejo con abdomen abierto son susceptibles a la pérdida de proteínas desde la cavidad expuesta. El objetivo de este estudio fue caracterizar la pérdida proteica a través de dos tipos de cierre temporal abdominal. Métodos. Se realizó un estudio decohorte prospectivo, con pacientes críticos manejados durante el año 2021 con abdomen abierto mediante dos tipos de cierre temporal: bolsa de Bogotá y ABThera™. Se recolectaron muestras intraoperatorias seriadas de líquido peritoneal (días 1, 3 y 5). Se calcularon frecuencias y promedios, y se compararon con las pruebas de Chi cuadrado y t de Student. Resultados. Se incluyeron 25 pacientes. El promedio de pérdida de proteínas en líquido peritoneal fue mayor con el sistema ABThera™ (44,38 g/L) comparado con la bolsa de Bogotá (25,18 g/L; p=0,0185). Durante el seguimiento se observó la tendencia a la disminución del promedio de proteínas perdidas por ambos sistemas, pero con ABThera™ se perdieron en promedio 15,47 gr/L más de proteínas, independientemente del estado nutricional y del aporte proteico recibido (p=0,042). No hubo diferencias según la etiología que llevó al manejo con abdomen abierto, los procedimientos quirúrgicos realizados o el estado de infección por COVID-19. Conclusiones. El abdomen abierto representa una fuente importante de pérdida de proteínas, que es diferente según el tipo de cierre temporal usado. Estas pérdidas deberían considerarse en los cálculos de soporte nutricional en la unidad de cuidado intensivo.
Introduction. Patients with surgical abdominal pathology requiring management with an open abdomen are susceptible to protein loss from the exposed cavity. The objective of this study was to characterize protein loss through two types of temporary abdominal closure. Methods. A prospective cohort study was carried out with critically ill patients managed during 2021 with an open abdomen using two types of temporary closure: Bogota bag and ABThera™. Serial intraoperative peritoneal fluid samples were collected (days 1, 3, and 5). Frequencies and averages were calculated and compared with the Chi square and Student's t tests. Results. Twenty-five patients were included. The average protein loss in peritoneal fluid was higher with the ABThera™ system (44.38 g/L) compared to the Bogota bag (25.18 g/L; p-value=0.0185). During follow-up, a tendency to decrease the average protein lost by both systems was observed, but with ABThera™ an average of 15.47 gr/L more protein was lost, regardless of the nutritional status and protein intake received (p=0.042). There were no differences based on etiology leading to open abdomen management, surgical procedures performed, or Covid-19 infection status. Conclusions. The open abdomen represents an important source of protein loss, which is different depending on the type of temporary closure used. These losses should be considered in calculations of nutritional support in the intensive care unit.
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Humanos , Líquido Ascítico , Técnicas de Abdome Aberto , Cavidade Peritoneal , Programas de Nutrição , Proteínas , COVID-19RESUMO
Over three decades ago, two independent groups of investigators identified free D-aspartic and later D-serine in specific brain nuclei and endocrine glands. This finding revealed a novel, non-proteinogenic role of these molecules. Moreover, the finding that aged proteins from the human eye crystallin, teeth, bone, blood vessels or the brain incorporate D-aspartic acids to specific primary protein sequences fostered the hypothesis that aging might be related to D-amino acid isomerization of body proteins. The experimental confirmation that schizophrenia and neurodegenerative diseases modify plasma free D-amino acids or tissue levelsnurtured the opportunity of using D-amino acids as therapeutic agents for several disease treatments, a strategy that prompted the successful current application of D-amino acids to human medicine.
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Aminoácidos , Humanos , Aminoácidos/química , Aminoácidos/metabolismo , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Serina/química , Serina/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Envelhecimento/metabolismo , Estereoisomerismo , Animais , Ácido D-Aspártico/metabolismo , Ácido D-Aspártico/química , Encéfalo/metabolismo , Relevância ClínicaRESUMO
Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl-/-) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, postsynaptic density protein 95 (PSD-95), synaptophysin and synapsin, and the activity of Na+, K+-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl-/- male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl+/+) males and Kl-/- females. Also, Kl-/- male and female mice show reduced É2/É3-NaK and Mg2+-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg2+-ATPase activities in both the regions. Our findings suggest that α-Klotho could influence the expression of AMPAR and the activity of NaK isoforms in the cerebellum in a sex-dependent manner, and these changes may contribute, in part, to cognitive decline.
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Cerebelo , Hipocampo , Proteínas Klotho , Receptores de AMPA , Caracteres Sexuais , ATPase Trocadora de Sódio-Potássio , Animais , Feminino , Masculino , Camundongos , Cerebelo/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Proteína 4 Homóloga a Disks-Large/genética , Hipocampo/metabolismo , Proteínas Klotho/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de AMPA/metabolismo , Receptores de AMPA/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/genética , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , Sinapsinas/metabolismo , Sinapsinas/genética , Sinaptofisina/metabolismoRESUMO
Alternative protein sources have been required to meet the significant plant protein demand. Agro-industrial by-products such as leaves have considerable potential as a source of macromolecules once they are mostly discarded as waste. The current study evaluated dried cassava leaves as a protein source. First, alkaline extraction parameters (solid-liquid ratio, pH, and temperature) were optimized and the run that result in the highest protein yield were acidified at pH 2.5 or 4. The influence of carbohydrate solubilized on protein precipitation was also evaluated by removing it via alcoholic extraction prior to precipitation. The experimental design showed that high pH and temperature conditions associated with a low solid-liquid ratio led to increased protein yields. The presence of carbohydrates in the supernatant significantly influenced protein precipitation. The protein concentrate had around 17.51% protein when it was obtained from a supernatant with carbohydrates, while protein content increased to 26.88% when it was obtained from carbohydrate-free supernatant. The precipitation pH also influenced protein content, whereas protein content significantly decreased when pH increased from 2.5 to 4. The natural interaction between carbohydrates and proteins from cassava leaves positively influenced the emulsion stability index and the foaming capacity and stability. Thus, the presented results bring insights into challenges in extracting and precipitation proteins from agro-industrial by-products.
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Precipitação Química , Manihot , Folhas de Planta , Proteínas de Plantas , Temperatura , Manihot/química , Folhas de Planta/química , Concentração de Íons de Hidrogênio , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/química , Emulsões/químicaRESUMO
Following consumer trends and market needs, the food industry has expanded the use of unconventional sources to obtain proteins. In parallel, 3D and 4D food printing have emerged with the potential to enhance food processing. While 3D and 4D printing technologies show promising prospects for improving the performance and applicability of unconventional sourced proteins (USP) in food, this combination remains relatively unexplored. This review aims to provide an overview of the application of USP in 3D and 4D printing, focusing on their primary sources, composition, rheological, and technical-functional properties. The drawbacks, challenges, potentialities, and prospects of these technologies in food processing are also examined. This review underscores the current necessity for greater regulation of food products processed by 3D and 4D printing. The data presented here indicate that 3D and 4D printing represent viable, sustainable, and innovative alternatives for the food industry, emphasizing the potential for further exploration of 4D printing in food processing. Additional studies are warranted to explore their application with unconventional proteins.
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Manipulação de Alimentos , Impressão Tridimensional , Manipulação de Alimentos/métodos , Reologia , Proteínas , Indústria AlimentíciaRESUMO
This project studied the use of lentil protein (LP) and quinoa protein (QP) in their native and modified states as carrier material in the encapsulation process by the ionic gelation technique of annatto seed extract. Soy protein (SP) was used as a model of carrier material and encapsulated bioactive compounds, respectively. The plant proteins were modified by enzymatic hydrolysis, N acylation, and N-cationization to improve their encapsulating properties. Additionally, the secondary structure, differential scanning calorimetry (DSC), solubility as a function of pH, isoelectric point (pI), molecular weight (MW), the content of free thiol groups (SH), the absorption capacity of water (WHC) and fat (FAC), emulsifier activity (EAI), emulsifier stability (ESI), and gelation temperature (Tg) were assessed on proteins in native and modified states. The results obtained demonstrated that in a native state, LP (80.52% and 63.82%) showed higher encapsulation efficiency than QP (73.63% and 45.77%), both for the hydrophilic dye and for the annatto extract. Structural modifications on proteins improve some functional properties, such as solubility, WHC, FAC, EAI, and ESI. However, enzymatic hydrolysis on the proteins decreased the gels' formation, the annatto extract's encapsulated efficiency, and the hydrophilic dye by the ionic gelation method. On the other hand, the modifications of N-acylation and N-cationization increased but did not generate statistically significant differences (p-value > 0.05) in the encapsulation efficiency of both the annatto extract and the hydrophilic dye compared to those obtained with native proteins. This research contributes to understanding how plant proteins (LP and QP) can be modified to enhance their encapsulating and solubility properties. The better encapsulation of bioactive compounds (like annatto extract) can improve product self-life, potentially benefiting the development of functional ingredients for the food industry.
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The objective of this study was to evaluate the chemical composition of two chickpea varieties, 'Costa 2004' and 'El Patrón', and to characterize their proteins to determine their technological potential for the food industry. For this purpose, chickpea samples of both varieties from the 2019 harvest region of Guanajuato, Mexico, were obtained and chemically characterized to determine the protein fractions using electrophoretic and amino acid profiling. The chickpea variety 'Costa 2004' contained 3% less protein and 7% less dietary fiber content than the variety 'El Patrón'; whereas, the carbohydrate content of 'Costa 2004' was 4% greater. Additionally, the chickpeas demonstrated an antioxidant capacity ranging from 319 to 387 µMET/g and total phenol levels exceeding 500 mg/g. Among the protein fractions, globulins represented the highest proportion in both varieties of chickpea, at approximately 8.73 g/100 g ('Costa 2004') and 10.42 g/100 g ('El Patrón'), followed by albumin, at approximately 1.24 g/100 g and 1.47 g/100 g, respectively. The chickpea proteins ranged in molecular weight between 100 and 25 kDa, with particularly strong signals in the albumin and globulin bands. Regarding the amino acid profile, histidine was predominant in both varieties. In conclusion, both varieties of chickpea have high nutritional value and broad potential for technological use in the food industry.
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Background: Recent advancements reveal saliva as a crucial source of diagnostic biomarkers for various diseases, notably gastric cancer. This systematic review evaluates these biomarkers, emphasizing their clinical applicability and potential in early detection. Methods: An extensive electronic search was conducted across PubMed/MEDLINE, Scopus, and Web of Science to identify relevant studies. Salivary biomarkers were analyzed as independent variables, with gastric cancer as the dependent variable. The study adhered to a protocol registered with PROSPERO (CRD42021259519). Results: Our analysis identified a range of biomarkers, highlighting three proteins - cystatin-B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1) - as particularly accurate for gastric cancer diagnosis. Conclusions: Salivary biomarkers hold substantial promise for the early detection of gastric cancer. Future research should aim to refine study design and validation for enhancing the quality and applicability of these biomarkers.
Introducción: Avances recientes revelan la saliva como una fuente crucial de biomarcadores diagnósticos para diversas enfermedades, especialmente el cáncer gástrico. Esta revisión sistemática evalúa estos biomarcadores, con énfasis en su aplicabilidad clínica y potencial para la detección temprana. Métodos: Se realizó una extensa búsqueda electrónica en PubMed/MEDLINE, Scopus y Web of Science para identificar estudios relevantes. Los biomarcadores salivales fueron analizados como variables independientes, con el cáncer gástrico como variable dependiente. El estudio siguió un protocolo registrado en PROSPERO (CRD42021259519). Resultados: Nuestro análisis identificó una gama de biomarcadores entre los que destacan tres proteínas: cistatina-B (CSTB), triosa fosfato isomerasa (TPI1) y proteína 1 eliminada en tumores cerebrales malignos (DMBT1), como particularmente precisas para el diagnóstico del cáncer gástrico. Conclusiones: : Los biomarcadores salivales tienen un gran potencial para la detección temprana del cáncer gástrico. La investigación futura debería apuntar a refinar el diseño del estudio y la validación para mejorar la calidad y aplicabilidad de estos biomarcadores.
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The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.
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COVID-19 , Pré-Eclâmpsia , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , COVID-19/fisiopatologia , COVID-19/imunologia , Gravidez , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/imunologia , SARS-CoV-2/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Sistema Renina-AngiotensinaRESUMO
Nitrogen is an essential macronutrient critical for plant growth and productivity. Plants have the capacity to uptake inorganic nitrate and ammonium, with nitrate playing a crucial role as a signaling molecule in various cellular processes. The availability of nitrate and the signaling pathways involved finely tune the processes of nitrate uptake and assimilation. NIN-like proteins (NLPs), a group of transcription factors belonging to the RWP-RK gene family, act as major nitrate sensors and are implicated in the primary nitrate response (PNR) within the nucleus of both non-leguminous and leguminous plants through their RWP-RK domains. In leguminous plants, NLPs are indispensable for the initiation and development of nitrogen-fixing nodules in symbiosis with rhizobia. Moreover, NLPs play pivotal roles in plant responses to abiotic stresses, including drought and cold. Recent studies have identified NLP homologs in oomycete pathogens, suggesting their potential involvement in pathogenesis and virulence. This review article delves into the conservation of RWP-RK genes, examining their significance and implications across different plant species. The focus lies on the role of NLPs as nitrate sensors, investigating their involvement in various processes, including rhizobial symbiosis in both leguminous and non-leguminous plants. Additionally, the multifaceted functions of NLPs in abiotic stress responses, developmental processes, and interactions with plant pathogens are explored. By comprehensively analyzing the role of NLPs in nitrate signaling and their broader implications for plant growth and development, this review sheds light on the intricate mechanisms underlying nitrogen sensing and signaling in various plant lineages.
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Cardiac amyloidosis (CA) is an infiltrative disease characterized by the deposition of misfolded proteins in cardiac interstitial tissue. Interest towards studying this pathology has been growing in the last decade, as new epidemiological insights have revealed that it is not as uncommon as previously believed. Likewise, advances in non-invasive diagnostic approaches and the identification of molecules that modify its long-term progression, even in terms of mortality, have also bolstered interest in CA. Despite this global panorama, in Venezuela, limitations remain regarding the diagnosis of CA, partly associated with a lack of knowledge of the disease. Therefore, additional efforts are necessary for clinical cardiologists to hone their diagnostic skills regarding this disease, as opportune identification is an essential step for its effective management.
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Amiloidose , Cardiomiopatias , Humanos , Venezuela , Amiloidose/diagnóstico , Cardiomiopatias/diagnósticoRESUMO
The toxicity of methylmercury (MeHg) during embryonic development is a relevant issue that remains unclear and deserves investigation. In this sense, there is evidence that links the intake of contaminated food with cardiovascular pathologies in human adults and children. Thus, this study aimed to verify the impact of MeHg on the structure and integrity of extraembryonic and cardiac blood vessels and the contractile function of cardiomyocytes, also evaluating embryonic weight and the cardiosomatic index (CSI). Thus, chicken embryos, used as an experimental model, were exposed to a single dose of 0.1 µg MeHg/50 µl saline at E1.5 and analyzed at E10. After exposure, an increase in the number of extraembryonic blood vessels and the veins of the cardiac tissue was observed. These increases were accompanied by a reduction in the content of VEGF and VCAM proteins related to vessel growth and adhesiveness. Together, these results were related to reduced nitrite (NOx) levels. Furthermore, MeHg reduces the number of sarcomeres and increases the content of cardiac troponin I (cTnI), a protein that regulates contraction. In general, exposure to MeHg affected the integrity of extraembryonic and cardiac vessels and the contractile function of cardiomyocytes, which had a systemic impact evidenced by the reduction in embryonic weight gain and CSI.
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Compostos de Metilmercúrio , Contração Miocárdica , Miócitos Cardíacos , Miócitos Cardíacos/efeitos dos fármacos , Animais , Embrião de Galinha , Compostos de Metilmercúrio/toxicidade , Contração Miocárdica/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Troponina I/metabolismoRESUMO
This study was designed to investigate the expression of HPV16 L1-protein in biopsies of oral mucosa samples. The expression of HPV16 L1 protein was investigated in biopsies taken from oral mucosa from patients who required pathological diagnosis of oral lesions. Seventy-two samples were incubated with anti-L1 protein monoclonal antibodies and protein detection was revealed with diaminobenzidine. Expression of L1 protein was performed by a pathologist blinded for tissue diagnosis under light microscopy. Most of the lesions of oral mucosa were present in lining mucosa (75 %) and the most frequent lesion were mucocele (n = 17, 23.6 %), epithelial hyperplasia (n = 6, 8.33 %), fibroma (n = 5, 6.9 %) and inflammatory hyperplasia (n = 5, 6.9 %). L1 protein expression was observed only in five (6.9 %) samples (two squamous cell carcinomas, two epithelial hyperplasia, and one gingival hyperplasia). We concluded that L1 expression in oral biopsies presented a low frequency in oral mucosal biopsies samples.
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Proteínas do Capsídeo , Mucosa Bucal , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Humanos , Biópsia , Feminino , Mucosa Bucal/virologia , Mucosa Bucal/patologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/virologia , Adulto , Masculino , Proteínas Oncogênicas Virais/genética , Pessoa de Meia-Idade , Equador/epidemiologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Adulto Jovem , Adolescente , Idoso , Prevalência , Doenças da Boca/virologia , Doenças da Boca/patologia , Doenças da Boca/epidemiologia , Papillomavirus Humano 16/genética , Imuno-Histoquímica , Neoplasias Bucais/virologia , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnósticoRESUMO
Staphylococcus pseudintermedius, which is part of the skin microbiome of dogs, causes a variety of opportunistic infections. These infections may become more difficult to treat due to the formation of biofilm. The capacity of S. pseudintermedius to form biofilm, as well as the associated genes, has not been elucidated. This study evaluated the production and composition of S. pseudintermedius biofilm. Samples were collected from both infected dogs and asymptomatic dogs. Isolates were identified using mass spectrometry and Multiplex-PCR. Biofilm production and composition were assessed using a quantitative microtiter plate assay. The presence of ica operon genes and sps genes was investigated using conventional PCR. The investigation of Agr type and virulence genes was conducted in silico on 24 sequenced samples. All strains could produce strong biofilms, with most of the isolates presenting a polysaccharide biofilm. 63.6% of the isolates carried the complete ica operon (ADBC). All samples showed the presence of the genes spsK, spsA, and spsL, while the distribution of other genes varied. Agr type III was the most prevalent (52.2%). All sequenced samples carried the cytotoxins hlb, luk-S, luk-F, as well as the exfoliative toxins siet and se_int. No isolate displayed other exfoliative toxins. Only LB1733 presented a set of different enterotoxins (sea, seb, sec_canine, seh, sek, sel, and seq). Our findings suggest that S. pseudintermedius is a strong producer of biofilm and carries virulence genes.
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Biofilmes , Doenças do Cão , Staphylococcus , Animais , Biofilmes/crescimento & desenvolvimento , Cães , Doenças do Cão/microbiologia , Virulência/genética , Staphylococcus/genética , Staphylococcus/isolamento & purificação , Staphylococcus/patogenicidade , Staphylococcus/classificação , Staphylococcus/fisiologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/veterinária , Fatores de Virulência/genética , Proteínas de Bactérias/genética , ÓperonRESUMO
Platyhelminthes, also known as flatworms, is a phylum of bilaterian invertebrates infamous for their parasitic representatives. The classes Cestoda, Monogenea, and Trematoda comprise parasitic helminths inhabiting multiple hosts, including fishes, humans, and livestock, and are responsible for considerable economic damage and burden on human health. As in other animals, the genomes of flatworms have a wide variety of paralogs, genes related via duplication, whose origins could be mapped throughout the evolution of the phylum. Through in-silico analysis, we studied inparalogs, i.e., species-specific duplications, focusing on their biological functions, expression changes, and evolutionary rate. These genes are thought to be key players in the adaptation process of species to each particular niche. Our results showed that genes related with specific functional terms, such as response to stress, transferase activity, oxidoreductase activity, and peptidases, are overrepresented among inparalogs. This trend is conserved among species from different classes, including free-living species. Available expression data from Schistosoma mansoni, a parasite from the trematode class, demonstrated high conservation of expression patterns between inparalogs, but with notable exceptions, which also display evidence of rapid evolution. We discuss how natural selection may operate to maintain these genes and the particular duplication models that fit better to the observations. Our work supports the critical role of gene duplication in the evolution of flatworms, representing the first study of inparalogs evolution at the genome-wide level in this group.
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Evolução Molecular , Duplicação Gênica , Platelmintos , Animais , Platelmintos/genética , Platelmintos/classificação , Genoma Helmíntico , Especificidade da Espécie , FilogeniaRESUMO
The relationship between protein stability and functional evolution is little explored in proteins purified from natural sources. Here, we investigated a novel family of egg proteins (Perivitellin-1, PV1) from Pomacea snails. Their remarkable stability and clade-related functions in most derived clades (Canaliculata and Bridgesii) make them excellent candidates for exploring this issue. To that aim, we studied PV1 (PpaPV1) from the most basal lineage, Flagellata. PpaPV1 displays unparalleled structural and kinetic stability, surpassing PV1s from derived clades, ranking among the most hyperstable proteins documented in nature. Its spectral features contribute to a pale egg coloration, exhibiting a milder glycan binding lectin activity with a narrower specificity than PV1s from the closely related Bridgesii clade. These findings provide evidence for substantial structural and functional changes throughout the genus' PV1 evolution. We observed that structural and kinetic stability decreased in a clade-related fashion and was associated with large variations in defensive traits. For instance, pale PpaPV1 lectin turns potent in the Bridgesii clade, adversely affecting gut morphology, while giving rise to brightly colored PV1s providing eggs with a conspicuous, probably warning signal in the Canaliculata clade. This work provides a comprehensive comparative analysis of PV1s from various apple snail species within a phylogenetic framework, offering insights into the interplay among their structural features, stability profiles and functional roles. More broadly, our work provides one of the first examples from natural evolution showing the crucial link among protein structure, stability and evolution of new functions.
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Proteínas do Ovo , Filogenia , Caramujos , Animais , Caramujos/genética , Caramujos/fisiologia , Caramujos/química , Proteínas do Ovo/genética , Proteínas do Ovo/química , Proteínas do Ovo/metabolismo , Estabilidade Proteica , Óvulo/química , Óvulo/metabolismoRESUMO
Genetically modified (GM) crops, expressing Bacillus thuringiensis (Bt) insecticidal toxins, have substantially transformed agriculture. Despite rapid adoption, their environmental and economic benefits face scrutiny due to unsustainable agricultural practices and the emergence of resistant pests like Spodoptera frugiperda, known as the fall armyworm (FAW). FAW's adaptation to Bt technology in corn and cotton compromises the long-term efficacy of Bt crops. To advance the understanding of the genetic foundations of resistance mechanisms, we conducted an exploratory comparative transcriptomic analysis of two divergent FAW populations. One population exhibited practical resistance to the Bt insecticidal proteins Cry1A.105 and Cry2Ab2, expressed in the genetically engineered MON-89Ø34 - 3 maize, while the other population remained susceptible to these proteins. Differential expression analysis supported that Cry1A.105 and Cry2Ab2 significantly affect the FAW physiology. A total of 247 and 254 differentially expressed genes were identified in the Cry-resistant and susceptible populations, respectively. By integrating our findings with established literature and databases, we underscored 53 gene targets potentially involved in FAW's resistance to Cry1A.105 and Cry2Ab2. In particular, we considered and discussed the potential roles of the differentially expressed genes encoding ABC transporters, G protein-coupled receptors, the P450 enzymatic system, and other Bt-related detoxification genes. Based on these findings, we emphasize the importance of exploratory transcriptomic analyses to uncover potential gene targets involved with Bt insecticidal proteins resistance, and to support the advantages of GM crops in the face of emerging challenges.
Assuntos
Toxinas de Bacillus thuringiensis , Proteínas de Bactérias , Endotoxinas , Proteínas Hemolisinas , Resistência a Inseticidas , Spodoptera , Transcriptoma , Spodoptera/efeitos dos fármacos , Spodoptera/genética , Animais , Endotoxinas/genética , Endotoxinas/farmacologia , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Resistência a Inseticidas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/parasitologia , Zea mays/genética , Zea mays/parasitologia , Perfilação da Expressão GênicaRESUMO
CONTEXT: Geometrical knots are rare structural arrangements in proteins in which the polypeptide chain ties itself into a knot, which is very intriguing due to the uncertainty of their impact on the protein properties. Presently, classical molecular dynamics is the most employed technique in the few studies found on this topic, so any information on how the presence of knots affects the reactivity and electronic properties of proteins is even scarcer. Using the electronic structure methods and quantum chemical descriptors analysis, we found that the same amino-acid residues in the knot core have statistically larger values for the unknotted protein, for both hard-hard and soft-soft interaction descriptors. In addition, we present a computationally feasible protocol, where we show it is possible to separate the contribution of the geometrical knot to the reactivity and other electronic structure properties. METHODS: In order to investigate these systems, we used PRIMoRDiA, a new software developed by our research group, to explore the electronic structure of biological macromolecules. We evaluated several local quantum chemical descriptors to unveil relevant patterns potentially originating from the presence of the geometrical knot in two proteins, belonging to the ornithine transcarbamylase family. We compared several sampled structures from these two enzymes that are highly similar in both tertiary structure and function, but one of them has a knot whereas the other does not. The sampling was carried out through molecular dynamics simulations using ff14SB force field along 50 ns, and the semiempirical convergence was performed with PM7 Hamiltonian.
Assuntos
Simulação de Dinâmica Molecular , Ornitina Carbamoiltransferase , Ornitina Carbamoiltransferase/química , Ornitina Carbamoiltransferase/metabolismo , Conformação Proteica , Modelos MolecularesRESUMO
Muscular dystrophies (MDs) are a heterogeneous group of diseases of genetic origin characterized by progressive skeletal muscle degeneration and weakness. There are several types of MDs, varying in terms of age of onset, severity, and pattern of the affected muscles. However, all of them worsen over time, and many patients will eventually lose their ability to walk. In addition to skeletal muscle effects, patients with MDs may present cardiac and respiratory disorders, generating complications that could lead to death. Interdisciplinary management is required to improve the surveillance and quality of life of patients with an MD. At present, pharmacological therapy is only available for Duchene muscular dystrophy (DMD)-the most common type of MD-and is mainly based on the use of corticosteroids. Other MDs caused by alterations in dystrophin-associated proteins (DAPs) are less frequent but represent an important group within these diseases. Pharmacological alternatives with clinical potential in patients with MDs and other proteins associated with dystrophin have been scarcely explored. This review focuses on drugs and molecules that have shown beneficial effects, mainly in experimental models involving alterations in DAPs. The mechanisms associated with the effects leading to promising results regarding the recovery or maintenance of muscle strength and reduction in fibrosis in the less-common MDs (i.e., with respect to DMD) are explored, and other therapeutic targets that could contribute to maintaining the homeostasis of muscle fibers, involving different pathways, such as calcium regulation, hypertrophy, and maintenance of satellite cell function, are also examined. It is possible that some of the drugs explored here could be used to affordably improve the muscular function of patients until a definitive treatment for MDs is developed.