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1.
Cancers (Basel) ; 15(19)2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37835434

ABSTRACT

Glioblastoma (GB) is the most aggressive primary malignant brain tumor and is associated with short survival. O-GlcNAcylation is an intracellular glycosylation that regulates protein function, enzymatic activity, protein stability, and subcellular localization. Aberrant O-GlcNAcylation is related to the tumorigenesis of different tumors, and mounting evidence supports O-GlcNAc transferase (OGT) as a potential therapeutic target. Here, we used two human GB cell lines alongside primary human astrocytes as a non-tumoral control to investigate the role of O-GlcNAcylation in cell proliferation, cell cycle, autophagy, and cell death. We observed that hyper O-GlcNAcylation promoted increased cellular proliferation, independent of alterations in the cell cycle, through the activation of autophagy. On the other hand, hypo O-GlcNAcylation inhibited autophagy, promoted cell death by apoptosis, and reduced cell proliferation. In addition, the decrease in O-GlcNAcylation sensitized GB cells to the chemotherapeutic temozolomide (TMZ) without affecting human astrocytes. Combined, these results indicated a role for O-GlcNAcylation in governing cell proliferation, autophagy, cell death, and TMZ response, thereby indicating possible therapeutic implications for treating GB. These findings pave the way for further research and the development of novel treatment approaches which may contribute to improved outcomes and increased survival rates for patients facing this challenging disease.

2.
Viruses ; 15(2)2023 02 13.
Article in English | MEDLINE | ID: mdl-36851730

ABSTRACT

The Salmonella enterica bacteriophage P22 is one of the most promising models for the development of virus-like particle (VLP) nanocages. It possesses an icosahedral T = 7 capsid, assembled by the combination of two structural proteins: the coat protein (gp5) and the scaffold protein (gp8). The P22 capsid has the remarkable capability of undergoing structural transition into three morphologies with differing diameters and wall-pore sizes. These varied morphologies can be explored for the design of nanoplatforms, such as for the development of cargo internalization strategies. The capsid proteic nature allows for the extensive modification of its structure, enabling the addition of non-native structures to alter the VLP properties or confer them to diverse ends. Various molecules were added to the P22 VLP through genetic, chemical, and other means to both the capsid and the scaffold protein, permitting the encapsulation or the presentation of cargo. This allows the particle to be exploited for numerous purposes-for example, as a nanocarrier, nanoreactor, and vaccine model, among other applications. Therefore, the present review intends to give an overview of the literature on this amazing particle.


Subject(s)
Bacteriophage P22 , Viroids , Capsid , Capsid Proteins/genetics , Cell Nucleus , Nanotechnology
3.
J Chem Phys ; 157(9): 094706, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36075730

ABSTRACT

The present work attempts to systematically explore the surfactant sorption at liquid-liquid interfaces with coarse-grained models targeting thermodynamic properties of reference liquid solutions. We employ dissipative particle dynamics with soft-core forcefield tested against experimental data on micellization of surfactants in water, and the previous results are reproduced in this work. We consider three different nonionic surfactants: hexaethylene glycol monododecyl ether (C12E6), 2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethanol) known as Triton X-100 (TX-100), and two alkyl glucoside surfactants (CnG1) with n-alkane tail fragments and a saccharide hydrophilic head at decane-water and toluene-water interfaces. For TX-100, we composed a model based on the literature forcefield and found good agreement with the experimental critical micelle concentrations (CMCs). The head-head interactions are of different origins for different surfactant groups: entropic repulsion between ethylene oxide chains of C12E6 and TX-100, and more chemically specific and complex interactions between the maltose heads of alkyl glucosides. We interpret our results with the Redlich-Peterson equation of monolayer adsorption in order to relate the adsorption to the bulk concentration of the surfactant and the interfacial tension. The densities of the adsorbed monolayer at CMC mostly agree with the experimental data, and a reasonable agreement was obtained for the interfacial tension at CMC. At the same time, we found significant discrepancies between the simulated and experimental adsorption isotherms. We explain them by the oversimplified forcefield: when the parameters are fitted to the free energies of bulk solutions, they may not correctly reproduce the interfacial free energies.


Subject(s)
Micelles , Surface-Active Agents , Adsorption , Surface Tension , Surface-Active Agents/chemistry , Water/chemistry
4.
Virus Evol ; 8(2): veac064, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35996592

ABSTRACT

The emergence and global dissemination of Severe Acute Respiratory Syndrome virus 2 (SARS-CoV-2) variants of concern (VOCs) have been described as the main factor driving the Coronavirus Disease 2019 pandemic. In Brazil, the Gamma variant dominated the epidemiological scenario during the first period of 2021. Many Brazilian regions detected the Delta variant after its first description and documented its spread. To monitor the introduction and spread of VOC Delta, we performed Polymerase Chain Reaction (PCR) genotyping and genome sequencing in ten regional sentinel units from June to October 2021 in the State of Minas Gerais (MG). We documented the introduction and spread of Delta, comprising 70 per cent of the cases 8 weeks later. Comparing the viral loads of the Gamma and Delta dominance periods, we provide additional evidence that the latter is more transmissible. The spread and dominance of Delta did not culminate in the increase in cases and deaths, suggesting that the vaccination may have restrained the epidemic growth. Analysis of 224 novel Delta genomes revealed that Rio de Janeiro state was the primary source for disseminating this variant in the state of MG. We present the establishment of Delta, providing evidence of its enhanced transmissibility and showing that this variant shift did not aggravate the epidemiological scenario in a high immunity setting.

5.
J Neurochem ; 162(6): 501-513, 2022 09.
Article in English | MEDLINE | ID: mdl-35797221

ABSTRACT

Glioblastoma is the most common and malignant type of primary brain tumor. Previous studies have shown that alterations in centrosome amplification and its components are frequently found in treatment-resistant tumors and may be associated with tumor progression. A centrosome protein essential for centrosome biogenesis is the centromere protein J (CENPJ), known to control the proliferation of neural progenitors and hepatocarcinoma cells, and also neuronal migration. However, it remains unknown the role of CENPJ in glioblastoma. Here we show that CENPJ is overexpressed in human glioblastoma cell lines in comparison to human astrocytes. Using bioinformatics analysis, we find that high Cenpj expression is associated with poor prognosis in glioma patients. Examining Cenpj loss of function in glioblastoma by siRNA transfection, we find impairments in cell proliferation and migration. Using a Cenpj mutant version with the deleted PN2-3 or TCP domain, we found that a conserved PN2-3 region is required for glioblastoma migration. Moreover, Cenpj downregulation modulates glioblastoma morphology resulting in microtubules stabilization and actin filaments depolymerization. Altogether, our findings indicate that CENPJ controls relevant aspects of glioblastoma progression and might be a target for therapeutic intervention and a biomarker for glioma malignancy.


Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Brain Neoplasms/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Centromere/metabolism , Centromere/pathology , Gene Expression Regulation, Neoplastic , Glioblastoma/metabolism , Glioma/metabolism , Humans
6.
Surg Oncol ; 39: 101660, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34555692

ABSTRACT

OBJECTIVE: To evaluate the results of a cohort of patients submitted to a new technique of oncoplastic mammoplasty, referred to as Disguised Geometric Compensation Mammoplasty (GCM), which is suitable for tumours involving the glandular tissue in the pillars of the mammoplasty. MATERIALS AND METHODS: Twenty-five breast tumours involving the pillars of the mammoplasty were included, 20 (80.0%) invasive ductal carcinomas, 3 (12.0%) phyllodes tumours, 1 (4.0%) invasive lobular carcinoma, and 1 (4.0%) in situ ductal carcinoma. Preoperative markings followed the "Wise-pattern" technique. The resection of the tumour in the pillar, preserving the overlying skin, was geometrically compensated with a corresponding area coming from the lower poles, which folded over itself and maintained the skin vascularity in the pillar. One patient was converted to classic GCM due to a positive skin margin in the frozen section. Another patient combined a Classic GCM for the inner quadrants and a Disguised GCM for the outer quadrants on the same breast. One patient decided to undergo a bilateral mastectomy after some months because of a BRCA 1 mutation. Immediate fat grafting was done in one case. Approval from the ethics committee: n. 2.322.212. RESULTS: Mean age was 47.0 ± 9.5 years. Mean clinical tumour size was 47.2 ± 22.2mm before chemotherapy and 36.7 ± 22.5mm, after. There were 11 (44.0%) locally advanced and 1 (4.00%) multicentric tumours. Nine (36.0%) were submitted to neoadjuvant chemotherapy. Adjuvant treatment was indicated according to the necessity. Ptosis was corrected in all cases. The aesthetic results were rated as excellent or good in 21 (95.5%) cases, by the Harris scale and the BCCT.core. The BREAST-Q scores for the satisfaction with the breasts and satisfaction with outcomes were 81.5 (±15.0) and 90.4 (±11.7), respectively. Intraoperative frozen sections were done in 12 (48%) cases. There was 1 (4.0%) focus of DCIS in the skin margin treated with radiotherapy. Minor complications occurred in 6 (24.0%) patients. There was 1 (4.0%) local recurrence treated with radical mastectomy, and 1 (4.0%) metastasis after 3 months. No deaths were observed within a mean follow-up time of 16.3 ± 11.4 months. CONCLUSIONS: The disguised geometric compensation mammoplasty allowed breast conservation in situations requiring large resection in the pillars of the mammoplasty, with a high rate of free margins, correction of ptosis, satisfactory symmetry, and few complications.


Subject(s)
Breast Neoplasms/surgery , Mammaplasty/methods , Mastectomy, Segmental/methods , Adult , Brazil , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Cohort Studies , Female , Humans , Middle Aged , Treatment Outcome
7.
Nutrition ; 90: 111359, 2021 10.
Article in English | MEDLINE | ID: mdl-34243042

ABSTRACT

OBJECTIVE: Many studies have shown an inverse association between higher dietary total antioxidant capacity (DTAC) and chronic non-communicable diseases, including cancer. The aim of this study was to evaluate the association of the DTAC with anthropometric and biochemical indicators and clinical outcomes in hospitalized patients with cancer. METHODS: A cross-sectional study was carried out with 196 hospitalized patients diagnosed with cancer. The DTAC, determined by the ferric-reducing antioxidant power method, was calculated using a validated standard spreadsheet. Multivariate linear regression was used to assess the association, identifying anthropometric indicators that were associated with DTAC and the variables of interest. P < 0.05 was statistically significant. RESULTS: The individuals included in the last tertile of DTAC presented lower occurrences of death (P = 0.032), constipation (P = 0.010), dysphagia (P = 0.010), painful swallowing and chewing (P = 0.019), and dehydration (P = 0.032) than individuals in the first tertile. The C-reactive protein values were significantly lower (P = 0.010) and handgrip strength values were higher (P = 0.037) in individuals in the third tertile than in the other participants. CONCLUSIONS: DTAC was associated with a better prognosis of hospitalized cancer patients, considering signs and symptoms of nutritional impact, as well as the inflammatory state of the patients. These factors may influence the length of hospital stay and mortality. The findings of this research provide important information for a preventive and nutritional management perspective in this population.


Subject(s)
Antioxidants , C-Reactive Protein , Diet , Neoplasms/diagnosis , C-Reactive Protein/analysis , Cross-Sectional Studies , Hand Strength , Humans
8.
Clin Nutr ESPEN ; 44: 331-336, 2021 08.
Article in English | MEDLINE | ID: mdl-34330486

ABSTRACT

BACKGROUND & AIMS: This longitudinal, qualitative, descriptive, and exploratory study aimed to identify and understand the food preferences and aversions arising from hematopoietic stem cell transplantation (HSCT), chemotherapy, and/or radiotherapy treatment. METHODS: An open and individual interview was carried out with patients diagnosed with hematological diseases or cancer, submitted to HSCT, chemotherapy, and/or radiotherapy treatment. The participants answered the following questions: "Have you experienced any changes in taste since the beginning of radiotherapy/chemotherapy?"; "Have you experienced any strange taste in your mouth, aversion or preference for a certain food that did not exist before the beginning of radiotherapy/chemotherapy?" The software IRAMUTEQ (R Interface for Multidimensional Analysis of Texts and Questionnaires) version 0.7 alpha 2 was used for textual analysis, with similarity analysis and word cloud. RESULTS: One hundred and forty six patients were included in the study, 50% (n = 73) female and 73% (n = 50) elderly. The main words reported by the participants in regards to food aversions were "meat", "beef" and "chicken", which are related to dysphagia. Regarding food preferences, the most mentioned words were "fruits", "juices" and "soups", whose consumption was associated with an improvement in gastrointestinal symptoms, especially nausea. CONCLUSION: Adjustments in the diet plan based on this information can contribute to a better acceptance of the diet, and clinical and nutritional prognosis.


Subject(s)
Food Preferences , Hematopoietic Stem Cell Transplantation , Aged , Diet , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Meat , Taste
9.
Saúde Soc ; 30(4): e210085, 2021. tab
Article in Portuguese | LILACS | ID: biblio-1341694

ABSTRACT

Resumo A Atenção Básica (AB) refere-se ao nível de atenção que permite cidadãos(ãs) acessarem o Sistema Único de Saúde (SUS) longitudinal e continuadamente. A proposta e operacionalização da gestão em Saúde reafirmam valores sociais como o direito à saúde. Com o objetivo de analisar qualitativamente perspectivas relacionadas a este nível de atenção entrevistou-se gestores(as) de diferentes níveis hierárquicos da AB de um município de Mato Grosso. As informações produzidas foram submetidas à Análise de Conteúdo na modalidade temática, referenciada pelo pensamento e planejamento estratégicos em saúde, no âmbito da Saúde Coletiva. Os dados relativos à gestão em saúde na AB e ao atendimento à população produziram núcleos temáticos envolvendo gestão rotativa, atuação fragmentada e emergencial; oposição entre humanização e técnica; promoção vertical da saúde. Os(as) gestores(as) demonstraram compromisso e busca pela manutenção dos serviços por meio de ações assistenciais e pontuais. A organização top-down, na qual não está prevista a participação dos usuários(as) como condição para o planejamento, parece ter reforçado incoerências entre a proposta abrangente da AB e os diuturnos imprevistos estruturais, dificultando a problematização necessária à transformação dos processos de trabalho. Fortalecer institucionalmente a rede de AB exige investimento, qualificação profissional permanente e participação ativa dos sujeitos.


Abstract Primary Care refers to level of care that allows citizens to access the Brazilian National Health System (SUS) longitudinally and continuously. Proposal and operationalization of health management reaffirm social values, such as right to health. To qualitatively analyze perspectives related to this level of care, we interviewed managers from different hierarchical levels of Primary Care in a municipality of Mato Grosso. The data collected underwent a thematic Content Analysis, referenced by strategic thinking and planning in Public Health. Data concerning health management in Primary Care and the care provided to the population produced thematic nuclei involving rotational management, fragmented and emergency actions; opposition between humanization and technique; vertical health promotion. Managers showed commitment and search for the maintenance of services via assistance and specific actions. Top-down organization, which excludes user participation in planning, seems to have reinforced inconsistencies between the comprehensive proposal of Primary care and the daily structural unforeseen events, hindering the problematization necessary to transform the work processes. Institutionally strengthening the Primary Care network requires investment, permanent professional qualification, and active participation of subjects.


Subject(s)
Humans , Male , Female , Primary Health Care , Unified Health System , Strategic Planning , Health Services Administration , Qualitative Research
10.
Clin Nutr ESPEN ; 39: 210-214, 2020 10.
Article in English | MEDLINE | ID: mdl-32859318

ABSTRACT

BACKGROUND & AIMS: Hand Grip Strength (HGS) has been proposed as an indicator of nutritional status, being an easy and non-invasive method and presenting high reliability among evaluators. However, there are no cut-off points. To compare HGS with objective methods of nutritional assessment and to propose a cut-off point for its use as a predictor of malnutrition in cancer patients. METHODS: This is a retrospective study with 76 patients (52.6% females, 56.8 ± 16.6 years old) admitted with a diagnosis of cancer in hospitals of Belo Horizonte (MG, Brazil). We evaluated the HGS of the dominant hand, Body Mass Index (BMI), calf circumference (CC), and arm circumference (AC), using the Receiver Operator Characteristic (ROC) curve analysis, being the Patient-Generated Subjective Global Assessment (PG-SGA) the reference method. Statistical tests were performed according to the distribution of the variables, verified by the Shapiro-Wilk test. The level of significance adopted was 5%. RESULTS: The HGS was higher in men (p = 0.001) and adults (p = 0.002). The HGS presented a better performance in the prediction of malnutrition (AUC = 0.766, 95% CI = 0.656-0.936) compared to the anthropometric indicators, with a cut-off point of 32.5 kg (sensitivity of 90.5% and specificity of 61.5%). The prevalence of malnutrition was 82.9% and 81.6% for PG-SGA and proposed cut-off point for HGS, respectively. CONCLUSIONS: The HGS was more sensitive to identify individuals at risk of malnutrition compared to other recognized indicators of nutritional status, indicating its application in a hospital setting with cancer patients.


Subject(s)
Malnutrition , Neoplasms , Adolescent , Adult , Female , Hand Strength , Humans , Inpatients , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Neoplasms/complications , Reproducibility of Results , Retrospective Studies
11.
An Acad Bras Cienc ; 91(4): e20191031, 2019.
Article in English | MEDLINE | ID: mdl-31800712

ABSTRACT

Diosmin is a flavone glycoside clinically used as the main component of Daflon for the treatment of venous diseases. Several studies demonstrated that this natural compound can induce apoptosis in different tumors. However, isolated diosmin has not been studied regarding its effects on glioblastoma so far. Since glioblastoma is a highly lethal and fast-growing brain tumor, new therapeutic strategies are urgently needed. Herein, we evaluated the role of this flavonoid against glioblastoma cells using in vitro assays. Diosmin significantly reduced the viability of GBM95, GBM02, and U87MG glioblastoma cells, but not of healthy human astrocytes, as verified by MTT assay. Vimentin immunostaining showed that diosmin induced morphological changes in GBM95 and GBM02 cells, making them smaller and more polygonal. Diosmin did not inhibit GBM95 and GBM02 cell proliferation, but it caused DNA fragmentation, as verified by the TUNEL assay, and increased cleaved caspase-3 expression in these cells. In summary, diosmin is able to induce caspase-dependent apoptosis specifically in tumor cells and, therefore, could be considered a promising therapeutic compound against glioblastoma.


Subject(s)
Apoptosis/drug effects , Diosmin/pharmacology , Brain Neoplasms/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/pathology , Humans , Signal Transduction/drug effects
12.
Bioorg Chem ; 83: 87-97, 2019 03.
Article in English | MEDLINE | ID: mdl-30343205

ABSTRACT

A new series of 1,4-disubstituted-1,2,3-triazole derivatives were synthesized through the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (Click chemistry) and their inhibitory activities were evaluated against different human glioblastoma (GBM) cell lines, including highly drug-resistant human cell lines GBM02, GBM95. The most effective compounds were 9d, containing the methylenoxy moiety linked to triazole and the tosyl-hydrazone group, and the symmetrical bis-triazole 10a, also containing methylenoxy moiety linked to triazole. Single crystal X-ray diffraction analysis was employed for structural elucidation of compound 9d. In silico analyses of physicochemical, pharmacokinetic, and toxicological properties suggest that compounds 8a, 8b, 8c, 9d, and 10a are potential candidates for central nervous system-acting drugs.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Glioblastoma/drug therapy , Triazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glioblastoma/pathology , Humans , Molecular Structure , Rats , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry , Tumor Cells, Cultured
13.
Maturitas ; 115: 31-36, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30049344

ABSTRACT

Decreased gait velocity is associated with limited mobility, community participation, cognitive decline, and increased risk of falls in elderly women. Therefore, early detection of reduced gait velocity allows proper monitoring and treatment to prevent or delay the associated limitations. This study determined the age of major gait velocity decline in a large sample of women. The participants were 653 healthy women, aged 18-89 years, who were divided in five age groups: ≤26, 36-45, 46-60, 61-70 and ≥71 years. Their spatiotemporal gait parameters were collected using the GAITRite® computerized carpet. Two piecewise regression models - known and estimated breakpoint - with age as the independent variable and gait velocity as the dependent variable were used to determine the age of major gait velocity decline. ANOVAs were performed to identify differences in gait spatiotemporal variables between the five age groups with α = 0.05. The estimated age of major gait velocity decline was 71 years. Age significantly predicted gait velocity (p < 0.0001), explaining 23% of its variability. Gait velocity decline starts at 65 years and becomes more pronounced at 71 years. The estimated model showed that an increase of one year in age decreases gait velocity on average by 0.31 cm/s. If age is>71 years, velocity will decrease on average by 1.75 cm/s per year. The average velocity of women over the age of 71 years was 115.4 cm/s, which as 7.8% less than a decade earlier. The five age groups demonstrated differences in gait velocity, step length, stance, swing, step, and double support time. This is the first study conducted in a large sample of women to have determined 71 years as the age of major gait decline. Identifying the age of gait velocity decline of healthy women could allow timely interventions to slow the general decline associated with lower gait velocities, such as falls, lower mobility, frailty, and death. Therefore, women near and above 71 years of age should be closely monitored due to the adverse health effects associated with reduced gait velocity.


Subject(s)
Aging/physiology , Gait/physiology , Accidental Falls , Adolescent , Adult , Aged , Aged, 80 and over , Cognitive Dysfunction , Female , Frailty , Humans , Middle Aged , Young Adult
14.
Mol Immunol ; 93: 133-143, 2018 01.
Article in English | MEDLINE | ID: mdl-29175593

ABSTRACT

Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.


Subject(s)
Antigens, Helminth/immunology , Immunodominant Epitopes/immunology , Schistosoma mansoni/immunology , Amino Acid Sequence , Animals , Antibodies, Helminth/blood , Antibodies, Helminth/immunology , Antigens, Helminth/genetics , CD4-Positive T-Lymphocytes/immunology , Combinatorial Chemistry Techniques , Drug Design , Drug Evaluation, Preclinical , Female , HLA-DRB1 Chains/immunology , Helminth Proteins/chemistry , Helminth Proteins/immunology , Histocompatibility Antigens Class II/immunology , Histocompatibility Antigens Class II/metabolism , Humans , Immunodominant Epitopes/genetics , Immunodominant Epitopes/metabolism , Lymphocyte Activation , Membrane Proteins/chemistry , Membrane Proteins/immunology , Mice , Mice, Inbred C57BL , Models, Molecular , Molecular Docking Simulation , Protein Conformation , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/immunology , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Schistosoma haematobium/immunology , Schistosoma mansoni/genetics , Schistosomiasis mansoni/blood , Schistosomiasis mansoni/immunology , Sequence Alignment , Vaccines, Subunit/immunology , Vaccines, Synthetic/immunology
15.
Gene ; 639: 34-43, 2018 Jan 10.
Article in English | MEDLINE | ID: mdl-28974474

ABSTRACT

In prokaryotic cells, the UvrB protein plays a central role in nucleotide excision repair, which is involved in the recognition of bulky DNA lesions generated by chemical or physical agents. The present investigation aimed to characterize the uvrB gene of Corynebacterium pseudotuberculosis (CpuvrB) and evaluate its involvement in the DNA repair system of this pathogenic organism. In computational analysis, the alignment of the UvrB protein sequences of Escherichia coli, Mycobacterium tuberculosis, Bacillus caldotenax and Corynebacterium pseudotuberculosis showed high similarity and the catalytic amino acid residues and functional domains are preserved. A CpUvrB model was constructed by comparative modeling and presented structural similarity with the UvrB of E. coli. Moreover, in molecular docking analysis CpUvrB showed favorable interaction with EcUvrA and revealed a preserved ATP incorporation site. Heterologous functional complementation assays using E. coli uvrB-deficient cells exposed to UV irradiation showed that the CpUvrB protein contributed to an increased survival rate in relation to those in the absence of CpUvrB. Damaged oligonucleotides containing thymine dimer or 8-oxoguanine lesion were synthesized and incubated with CpUvrB protein, which was able to recognize and excise UV irradiation damage but not 8-oxoguanine. These results suggest that CpUvrB is involved in repairing lesions derived from UV light and encodes a protein orthologous to EcUvrB.


Subject(s)
Bacterial Proteins/genetics , Corynebacterium pseudotuberculosis/genetics , DNA Damage , Escherichia coli/genetics , Guanine/analogs & derivatives , Ultraviolet Rays , Amino Acid Sequence , Bacterial Proteins/metabolism , Cloning, Molecular , Corynebacterium pseudotuberculosis/metabolism , Corynebacterium pseudotuberculosis/radiation effects , Gene Knockdown Techniques , Guanine/metabolism , Sequence Homology, Amino Acid
16.
Arq. ciências saúde UNIPAR ; 21(3): 99-104, set-dez. 2017. tab, ilus
Article in Portuguese | LILACS | ID: biblio-879606

ABSTRACT

Os jogos reduzidos constituem a base de muitos programas de formação no futebol. A partir destes jogos, são realizadas modificações com o intuito de estimular um determinado fluxo de ações (técnico-táticas) em contexto real de jogo. Entre as principais estratégias está o aumento ou diminuição do número de jogadores para um determinado tamanho de campo. Contudo, ainda hoje, apesar da ampla utilização de modificações de jogos reduzidos como estratégia de ensino, aprendizagem e treinamento no futebol estas intervenções carecem de demonstração científica acerca da sua utilidade e eficácia. Esta falta de evidências empíricas perpetua o famigerado abismo entre teoria e prática e a construção de atividades de treino, unicamente, baseada na subjetividade do treinador. Assim, o objetivo do presente estudo foi analisar o efeito do número de jogadores na frequência e distribuição das ações técnico-táticas em uma escolinha de futebol e futsal. Participaram do estudo 18 jogadores de uma escolinha de futebol e futsal do Paraná. As situações analisadas foram 4vs4 + goleiros e 5vs5 + goleiros. A análise das ações técnico-táticas foi adaptada dos critérios originalmente propostos no Team Sport Assessment Procedure (TSAP). Os jogos foram gravados em câmera digital e posteriormente analisados em vídeo. De modo geral, os resultados demostraram maior frequência de ações técnico-táticas em situação de 4vs4 + goleiros comparada a situação de 5vs5 + goleiros. Contudo é necessário a intervenção do treinador, incluindo modificações destes jogos reduzidos, para permitir exercitação mais homogênea entre os jogadores


Small-sided games form the basis of many youth soccer programs. From these games, modifications are made in order to stimulate a certain flow of technical-tactical actions in real game context. Among the most common strategies are the increase or decrease of the number of player to a given field size. However, despite the wide use of small-sided games as a teaching strategy in soccer, these interventions lack of scientific evidence to demonstrate their utility and efficacy. This lack of evidence strengthens the gap between theory and practice and the design of small-sided games based, solely, on coaches' subjectivity. Thus, the present study analyzed the effect of the number of players on the frequency and distribution of technical-tactical actions in a soccer academy. Participated in the study 18 players from a soccer and futsal academy from Paraná. Situations analyzed were 4vs4 + goalkeepers and 5vs5 + goalkeepers. Analysis of technical-tactical actions were adapted from the criteria originally proposed in the Team Sport Assessment Procedure (TSAP). Games were recorded using a digital camera and saved for posterior computer analysis. Overall, results elicited more frequency of technical-tactical actions in 4vs4 + goalkeepers compared to 5vs5 + goalkeepers. However, it is needed coach's intervention, including other game modifications, to allow a more homogeneous participation among players


Subject(s)
Soccer
17.
Nat Struct Mol Biol ; 24(8): 652-657, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28671667

ABSTRACT

The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105-356 Myr ago, and compare them with titin fragments from some of their modern descendants. We demonstrate that the resurrected titin molecules are rich in disulfide bonds and display high mechanical stability. These mechanochemical elements have changed over time, creating a paleomechanical trend that seems to correlate with animal body size, allowing us to estimate the sizes of extinct species. We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods.


Subject(s)
Chemical Phenomena , Connectin/genetics , Connectin/metabolism , Evolution, Molecular , Mechanical Phenomena , Animals , Disulfides/analysis , Phylogeny , Spectrum Analysis , Vertebrates
18.
Genet. mol. biol ; 40(2): 480-490, Apr.-June 2017. tab, graf
Article in English | LILACS | ID: biblio-892413

ABSTRACT

Abstract The barley HvAACT1 gene codes for a citrate transporter associated with tolerance to acidic soil. In this report, we describe a single nucleotide polymorphism (SNP) in the HvAACT1 coding region that was detected as T-1,198 (in genotypes with lower root growth on acidic soil) or G-1,198 (greater root growth) and resulted in a single amino acid change (L/V-172). Molecular dynamic analysis predicted that HvAACT1 proteins with L or V-172 were stable, although the substitution led to structural changes within the protein. To evaluate the effect of the SNP on tolerance to acidic soil, barley accessions were separated into haplotypes based on the presence of a 1 kb insertion in the HvAACT1 promoter and a 21 bp insertion/deletion. These markers and the SNP-1,198 allowed the identification of five haplotypes. Short-term soil experiments showed no difference in root growth for most of the accessions containing the 21 bp insertion and T or G-1,198. In contrast, genotypes showing both the 21 bp deletion and G-1,198, with one of them having the 1 kb insertion, showed greater root growth. These results indicate that the SNP was not advantageous or deleterious when genotypes from the same haplotype were compared. The occurrence of the SNP was highly correlated with the 21 bp insertion/deletion that, together with the 1 kb insertion, explained most of the barley tolerance to acidic soil.

19.
Genet Mol Biol ; 40(2): 480-490, 2017.
Article in English | MEDLINE | ID: mdl-28486573

ABSTRACT

The barley HvAACT1 gene codes for a citrate transporter associated with tolerance to acidic soil. In this report, we describe a single nucleotide polymorphism (SNP) in the HvAACT1 coding region that was detected as T-1,198 (in genotypes with lower root growth on acidic soil) or G-1,198 (greater root growth) and resulted in a single amino acid change (L/V-172). Molecular dynamic analysis predicted that HvAACT1 proteins with L or V-172 were stable, although the substitution led to structural changes within the protein. To evaluate the effect of the SNP on tolerance to acidic soil, barley accessions were separated into haplotypes based on the presence of a 1 kb insertion in the HvAACT1 promoter and a 21 bp insertion/deletion. These markers and the SNP-1,198 allowed the identification of five haplotypes. Short-term soil experiments showed no difference in root growth for most of the accessions containing the 21 bp insertion and T or G-1,198. In contrast, genotypes showing both the 21 bp deletion and G-1,198, with one of them having the 1 kb insertion, showed greater root growth. These results indicate that the SNP was not advantageous or deleterious when genotypes from the same haplotype were compared. The occurrence of the SNP was highly correlated with the 21 bp insertion/deletion that, together with the 1 kb insertion, explained most of the barley tolerance to acidic soil.

20.
Sci Justice ; 53(4): 402-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24188341

ABSTRACT

In many crimes, the elapsed time between production and collecting fingermark traces is crucial. and a method able to detect the aging of latent prints would represent an improvement in forensic procedures. Considering that as the latent print gets older, substantial changes in the relative proportion of individual components secreted by skin glands could affect the morphology of ridges, morphometry could be a potential tool to assess the aging of latent fingermarks. Then, considering the very limited research in the field, the present work aims to evaluate the morphometry of latent palmprint ridges, as a function of time, in order to identify an aging pattern. The latent marks were deposited by 20 donors on glass microscope slides considering pressure and contact angle, and then were maintained under controlled environmental conditions. The morphometric study was conducted on marks developed with magnetic powder in 7 different time intervals after deposition (0, 5, 10, 15, 20, 25 or 30 days); 60 ridges were evaluated for each developed mark. The results showed that: 1) the method for the replacement and mixing of skin secretions on the palm was appropriate to ensure reproducibility of latent prints, and 2) considering the studied group, there was a time-dependent reduction in the width of ridges and on the percentage of visible ridges over 30 days. Results suggest the possibility of using the morphometric method to determine an aging profile of latent palmprints on glass surface, aiming for forensic purposes.


Subject(s)
Dermatoglyphics , Hand/anatomy & histology , Skin/ultrastructure , Adult , Female , Humans , Linear Models , Male , Time Factors , Young Adult
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