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1.
Clin Obes ; : e12688, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38943556

ABSTRACT

Obesity increases serum triglycerides and decreases high-density lipoprotein cholesterol (HDL-C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1-OB) and III (G3-OB) obesity and effects of bariatric surgery on G3-OB. Fifteen G3-OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1-OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3-OB had higher triglycerides and lower HDL-C; G1-OB had higher triglycerides than NW but HDL-C was equal. Compared to NW, HDL size was smaller in G3-OB but equal in G1-OB. One year after bariatric surgery, BMI and triglycerides of G3-OB decreased (p < .0001 and p = .0012, respectively) and HDL-C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3-OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL-C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.

2.
Environ Res ; 241: 117548, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37939803

ABSTRACT

The retreat of glaciers in Antarctica has increased in the last decades due to global climate change, influencing vegetation expansion, and soil physico-chemical and biological attributes. However, little is known about soil microbiology diversity in these periglacial landscapes. This study characterized and compared bacterial and fungal diversity using metabarcoding of soil samples from the Byers Peninsula, Maritime Antarctica. We identified bacterial and fungal communities by amplification of bacterial 16 S rRNA region V3-V4 and fungal internal transcribed spacer 1 (ITS1). We also applied 14C dating on soil organic matter (SOM) from six profiles. Physico-chemical analyses and attributes associated with SOM were evaluated. A total of 14,048 bacterial ASVs were obtained, and almost all samples had 50% of their sequences assigned to Actinobacteriota and Proteobacteria. Regarding the fungal community, Mortierellomycota, Ascomycota and Basidiomycota were the main phyla from 1619 ASVs. We found that soil age was more relevant than the distance from the glacier, with the oldest soil profile (late Holocene soil profile) hosting the highest bacterial and fungal diversity. The microbial indices of the fungal community were correlated with nutrient availability, soil reactivity and SOM composition, whereas the bacterial community was not correlated with any soil attribute. The bacterial diversity, richness, and evenness varied according to presence of permafrost and moisture regime. The fungal community richness in the surface horizon was not related to altitude, permafrost, or moisture regime. The soil moisture regime was crucial for the structure, high diversity and richness of the microbial community, specially to the bacterial community. Further studies should examine the relationship between microbial communities and environmental factors to better predict changes in this terrestrial ecosystem.


Subject(s)
Ice Cover , Microbiota , Antarctic Regions , Fungi/genetics , Bacteria/genetics , Soil/chemistry , Soil Microbiology
3.
J Chem Theory Comput ; 2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36622950

ABSTRACT

Molecular dynamics with excited normal modes (MDeNM) is an enhanced sampling method for exploring conformational changes in proteins with minimal biases. The excitation corresponds to injecting kinetic energy along normal modes describing intrinsic collective motions. Herein, we developed a new automated open-source implementation, MDexciteR (https://github.com/mcosta27/MDexciteR), enabling the integration of MDeNM with two commonly used simulation programs with GPU support. Second, we generalized the method to include the excitation of principal components calculated from experimental ensembles. Finally, we evaluated whether the use of coarse-grained normal modes calculated with elastic network representations preserved the performance and accuracy of the method. The advantages and limitations of these new approaches are discussed based on results obtained for three different protein test cases: two globular and a protein/membrane system.

4.
J. Health NPEPS ; 7(2)jul - dez, 2022.
Article in Portuguese | LILACS, BDENF - Nursing, Coleciona SUS | ID: biblio-1416503

ABSTRACT

Objetivo:avaliar os fatores associados ao baixo Apgar em recém-nascidos de Angola. Método:estudo analíticoe transversal, quali-quantitativo, em umHospital Geral de Luanda, Angola, entre março e maio de 2021. Realizou-se entrevistas em sala de observação e consulta aos prontuários das parturientes. Os dados foram analisados pelo teste qui-quadrado (X2) e regressão logística. Resultados:prevaleceu parturientes entre 19-35 anos (70,0%), 7º-9º ano (57,5%), multíparas (75%), multigestas (75,0%), sem histórico de aborto (72,5%), idade gestacional de 40 semanas (60,0%), usuárias de bebidas alcoólicas (77,5%), baixa frequência de consultas pré-natais (52,5%), com parto natural (82,5%) e recém-nascidos com peso normal (52,5%). Mulheres de região periurbana [OR:6,85 (95% CI:0.65-71,2), p=0,108] e rural [OR:4,47 (95% CI:0.47-48,4), p=0,184] apresentaram maior chance de terem recém-nascidos com baixo Apgar, assim como as usuárias de álcool [OR:3,28 (95% CI:0,58-18,3), p=0,176] e recém-nascidos que nasceram com peso normal [OR:1,75 (95% CI:0,49­6,22), p=0,387]. Não houve associação estatística entre os dados sociodemográficos e maternos. Conclusão:a faixa etária, local de residência, consumo de álcool materno e peso do recém-nascido podem implicar em baixo Apgar.


Objective: to evaluate the factors associated with low Apgar in newborns in Angola. Method:analytical and cross-sectional, quali-quantitative study, in a General Hospital in Luanda, Angola, between March and May 2021. Interviews were carried out in an observation room and consultation of the parturients' medical records. Data were analyzed using the chi-square test (X2) and logistic regression.Results: pregnant women aged 19-35 years (70.0%), 7th-9th year(57.5%), multiparous (75%), multiparous (75.0%), without a history of abortion (72.5%), prevailed. gestational age of 40 weeks (60.0%), users of alcoholic beverages (77.5%), low frequency of prenatal consultations (52.5%), with natural childbirth (82.5%) and newborns with normal weight (52.5%). Women from peri-urban regions [OR:6.85 (95% CI:0.65-71.2), p=0.108] and rural [OR:4.47 (95% CI:0.47-48.4), p=0.184] were more likely to have low Apgar newborns, as well as alcohol users [OR:3.28 (95% CI:0.58-18.3), p=0.176] and newborns who were born with normal [OR:1.75 (95% CI:0.49­6.22), p=0.387]. There was no statistical association between sociodemographic and maternal data.Conclusion: age group, place of residence, maternal alcohol consumption and newborn weight may imply low Apgar.


Objetivo: evaluar los factores asociados al Apgar bajo en recién nacidos en Angola.Método: estudio analítico y transversal, cuali-cuantitativo, en un Hospital General de Luanda, Angola, entre marzo y mayo de 2021. Se realizaron entrevistas en sala de observación y consulta de las historias clínicas de las parturientas. Los datos se analizaron mediante la prueba de chi-cuadrado (X2) y regresión logística. Resultados: gestantes de 19 a 35 años (70,0%), de 7° a 9° año (57,5%), multíparas (75%), multíparas (75,0%), sin antecedente de aborto (72,5%), predominó la edad gestacional de 40 semanas (60,0%), usuarias de bebidas alcohólicas (77,5%), baja frecuencia de consultas prenatales (52,5%), con parto natural (82,5%) y recién nacidos con normopeso (52,5%). Las mujeres de regiones periurbanas [OR:6,85 (IC 95%:0,65-71,2), p=0,108] y rurales [OR:4,47 (IC 95%:0,47-48,4), p=0,184] tenían más probabilidades de tener bajo Recién nacidos Apgar, así como consumidores de alcohol [OR:3,28 (IC 95%:0,58-18,3), p=0,176] y recién nacidos que nacieron con normalidad [OR:1,75 (IC 95%:0,49-6,22), p=0,387]. No hubo asociación estadística entre datos sociodemográficos y maternos. Conclusión: el grupo de edad, el lugar de residencia, el consumo materno de alcohol y el peso del recién nacido pueden implicar un Apgar bajo.


Subject(s)
Apgar Score , Infant, Newborn , Postpartum Period , Hospitals, Maternity , Angola
5.
Sci Total Environ ; 853: 158432, 2022 Dec 20.
Article in English | MEDLINE | ID: mdl-36057308

ABSTRACT

The Amazon Continental Shelf (ACS) has a coastline of ∼1000 km and is situated in a humid equatorial region with two distinct seasons, wet and dry, and two transitional climatic periods. A total of eight oceanographic cruises were conducted to investigate the dynamics of the inorganic nutrients dissolved in the surface layer of the water column of the ACS and their associations with Sargassum blooms. An excess of nitrogen-N* (NH4+ = 0.01-9.30 µmol l-1) was verified through the salinity gradient from the continent to the ACS, mainly during the period of maximum discharge of the Amazon and Tocantins-Pará rivers. The highest NH4+ concentrations coincided with the occurrence of macrophyte (Sargassum sp.) blooms in the mesohaline and oceanic regions. During this period the high values of NH4+ accompany the low values of Sea Surface Salinity (SSS), indicating the advection of the Amazonian plume towards the Caribbean Sea. In the Sargassum belts we observed a N:P ratio = 60:1 during wet period, while outside this region, the N:P ratio was 34:1. According to DIN vs. AOU ratio, we observed that heterotrophic processes prevail over productive processes, mainly in the mesohaline and low salinity regions. Nitrogen concentrations from runoff, mainly from hydrographic basins, showed significant increases in the last decade, mainly due to anthropogenic factors such as agriculture, deforestation, livestock, urban sewage (domestic and industrial), and demographic growth of the population in the Tocantins-Pará Basin. Additionally, associations of diatoms and cyanobacteria provide more nitrogen in the mesohaline and oceanic regions that nourishes Sargassum blooms. Seasonal comparisons (October and April) of Sargassum belts with other studies, indicated that currents play a fundamental role in the transport of these macrophytes from the east edge (Africa) to the west edge (Brazil and French Guiana) towards the Caribbean Sea in the tropical Atlantic.


Subject(s)
Sargassum , Sewage , Rivers , Nitrogen , Water
6.
Odontol. Clín.-Cient. (Online) ; 20(2): 32-36, abr.-maio 2021. ilus
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1369191

ABSTRACT

A pesquisa teve como objetivo determinar os níveis de ansiedade e depressão dos estudantes de graduação de odontologia em uma instituição de ensino superior. O estudo é de caráter transversal, realizado em 2018 com 263 estudantes de graduação em odontologia utilizando a Escala Hospitalar de Ansiedade e Depressão (EHAD) em forma de questionário com variáveis sociodemográficas para avaliação dos níveis de ansiedade e depressão apresentados por esses discentes. Um total de 74,52% da amostra apresentou sintomas sugestivos de ansiedade e depressão, sendo 53,62% representada por mulheres e apenas 20,09% representado por homens. Apenas 25,48% dos participantes não apresentaram sintomas de ansiedade e depressão. As implicações que os transtornos emocionais causam no desempenho acadêmico precisam de medidas de diagnóstico precoce para evitar a evolução da doença, trabalhando também na difusão de informações visando a busca de meios que garantam uma melhora na saúde mental dos participantes da pesquisa... (AU)


The research aimed to determine the anxiety and depression levels of undergraduate dentistry students at a higher education institution. The cross-sectional study was carried out in 2018 with 263 undergraduate dentistry students using a Hospital Anxiety and Depression Scale (EHAD) in the form of a questionnaire with sociodemographic variables to assess the levels of anxiety and depression due to these students. A total of 74.52% of the sample presented symptoms suggestive of anxiety and depression, with 53.62% represented by women and only 20.09% represented by men. Only 25.48% of participants were not dependent on anxiety and depression. As a result that emotional disorders cause academic performance, early diagnosis measures are needed to prevent the disease from developing, also working on the dissemination of integrated information and the search for ways to guarantee an improvement in the mental health of the research participants... (AU)


Subject(s)
Humans , Male , Female , Anxiety , Students, Dental , Depression , Mental Health , Cross-Sectional Studies , Dentistry , Early Diagnosis , Academic Performance
7.
Environ Monit Assess ; 193(5): 308, 2021 Apr 28.
Article in English | MEDLINE | ID: mdl-33909164

ABSTRACT

The water quality and trends in 12 tropical rivers in northeastern Brazil over a 27-year period (1990-2016; N = 39,008 samples) were evaluated. The analyzed parameters included temperature, conductivity, pH, dissolved oxygen (DO), biochemical oxygen demand (BOD), nitrogen (NH4+), total phosphorus (P), and fecal coliforms. Densely populated basins (> 1000 inhab km-2) presented lower DO values (average 3.4 mg l-1; 43% DO saturation), while those with low demographic density (< 100 inhab km-2) presented values that aligned well with the recommendations of environmental legislation (average 5.8 mg l-1; 75% DO saturation). The NH4+ and P compound concentrations were typical of water bodies affected by urban inputs. The average p values were above the allowable limit (< 0.1 mg l-1) at all stations. The NH4+ values were high at the stations showing low DO concentrations, which suggested that due to reducing conditions after NH4+ accumulation was favored in those aquatic systems. In densely populated basins, the average fecal coliform concentrations were > 40,000 MPN 100 ml-1, indicating the input of improperly treated domestic/industrial liquid wastes. For the period from 1990 to 2016, 45% of the stations (N = 19) showed a rate of DO reduction that ranged from 0.01 to 0.17 mg l-1.O2 year-1. An increase in NH4+ concentrations was observed in 33% of the stations (N = 14), with an estimated average increase rate from 0.013 to 1.8 mg l-1 NH4+ year-1. These results demonstrated that the rates of increase in anthropogenic factors were significant (p < 0.05), while the natural factors remained constant.


Subject(s)
Rivers , Water Pollutants, Chemical , Brazil , Environmental Monitoring , Nitrogen/analysis , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Water Quality
8.
Ecancermedicalscience ; 14: 1115, 2020.
Article in English | MEDLINE | ID: mdl-33209106

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has changed health systems across the world, both in general hospitals and in oncology institutes or centres.For cancer specialists, particularly breast cancer (BC), the COVID-19 pandemic represents a combination of challenges since the hospital resources and staff have become more limited; this has obliged oncology specialists to seek a consensus and establish which patients with BC require more urgent attention and which patients can wait until there is a better control of this pandemic. The health system in Latin America has some special characteristics; in some of the countries, there are shortages which limit access to several specialities (surgery, clinical oncology and radiotherapy) in some regions. OBJECTIVE: After a systematic review of the most recent literature regarding the management of BC during the COVID-19 pandemic, the main objective is to understand the position of the different Latin American Societies of Mastology in terms of available alternatives for the treatment of BC. METHODS: After carrying out a comprehensive and exhaustive search of the most recent guides on the management of BC during the COVID-19 pandemic, the board members of the Latin American Federation of Mastology invited, via email, different specialists, all experts in BC care, to complete an anonymous survey online.The survey was distributed between 30 and 10 May 2020. The survey included 27 questions on four topics: demographic information, consultations, imaging and treatment of BC.The questionnaire was sent and then distributed to various health specialists including breast surgeons, clinical oncologists, radiation oncologists and radiologists via the Presidents of the different Latin American Societies of Mastology in 18 countries. The results are summarised as tallies based on the number of responses to each question. RESULTS: A total of 499 responses were received. The majority of the respondents were males (275 (55.11%)); 290 participants were over 45 years (58.11%).The questionnaire presented those surveyed with three possible answers (agree, disagree and neither agree nor disagree). The results reflect that there was consensus in the majority of situations presented. Only seven questions revealed disagreement among those responding. The results are presented as recommendations. CONCLUSION: The management of patients with BC presents unique challenges during the current world health situation produced by COVID-19 pandemic. Breast care specialists (surgical oncologists, breast care clinicians, clinical oncologists, radiation oncologists and radiologists) from 18 countries in Central and South America submitted through their responses and recommendations for the treatment of BC during the COVID-19 pandemic.

9.
Proteins ; 88(12): 1675-1687, 2020 12.
Article in English | MEDLINE | ID: mdl-32683717

ABSTRACT

Network theory methods and molecular dynamics (MD) simulations are accepted tools to study allosteric regulation. Indeed, dynamic networks built upon correlation analysis of MD trajectories provide detailed information about communication paths between distant sites. In this context, we aimed to understand whether the efficiency of intramolecular communication could be used to predict the allosteric potential of a given site. To this end, we performed MD simulations and network theory analyses in cathepsin K (catK), whose allosteric sites are well defined. To obtain a quantitative measure of the efficiency of communication, we designed a new protocol that enables the comparison between properties related to ensembles of communication paths obtained from different sites. Further, we applied our strategy to evaluate the allosteric potential of different catK cavities not yet considered for drug design. Our predictions of the allosteric potential based on intramolecular communication correlate well with previous catK experimental and theoretical data. We also discuss the possibility of applying our approach to other proteins from the same family.


Subject(s)
Cathepsin K/chemistry , Cathepsin K/metabolism , Protein Interaction Domains and Motifs , Allosteric Regulation , Allosteric Site , Binding Sites , Communication , Humans , Models, Molecular , Molecular Dynamics Simulation , Protein Binding , Protein Conformation
10.
Immunogenetics ; 72(5): 333-337, 2020 07.
Article in English | MEDLINE | ID: mdl-32556498

ABSTRACT

The aim of this study was to evaluate the expression of human leukocyte antigen G (HLA-G) in leprosy. Biopsy and serum samples were collected from 18 patients presenting with leprosy and from healthy controls. Samples were analyzed using immunohistochemistry and ELISA techniques. HLA-G expression was observed in biopsy samples of all patients. The healthy control samples were consistently negative for HLA-G expression. Control plasma samples displayed significantly higher HLA-G expression than those from the patients (p < 0.01). These results are the first demonstration of the expression of HLA-G in leprosy.


Subject(s)
HLA-G Antigens/metabolism , Leprosy/metabolism , Adult , Aged , Biomarkers/metabolism , Female , Humans , Leprosy/classification , Male , Middle Aged , Skin/metabolism , Young Adult
11.
Oncol Lett ; 19(4): 3003-3010, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32218857

ABSTRACT

The objective of the present study was to evaluate the epigenetic changes occurring in early stages of breast cancer. The present study investigated the methylation profile of the ATM, p14ARF and p16INK4a promoters in total blood and plasma cell-free DNA (cfDNA) from women with impalpable breast lesions compared with in total blood of a control cohort of women without breast lesions. The samples were evaluated using the methylation-specific PCR method. The Fisher's exact test was used to evaluate statistical significance between the methylation and clinical variables. A total of 111 women were evaluated, including 56 women with impalpable breast cancer (39/56 also had paired plasma cfDNA) and 55 women in the control cohort (55 blood DNA). For blood DNA from women with malignant impalpable breast lesions, p16INK4a exhibited the greatest percentage of methylation (48%), followed by ATM (37.5%) and p14ARF (27%) promoters, regardless of age variation. For plasma cfDNA, the methylation rates for ATM, p14ARF and p16INK4a were 26, 26 and 10%, respectively. The methylation rates for the blood DNA of controls were the lowest for ATM (9%), p14ARF (7%) and p16INK4a (7%). The women with impalpable breast lesions (benign and malignant lesions) exhibited the highest methylation rate, regardless of age, compared with the paired plasma cfDNA and controls. This epigenetic change was statistically significant for the promoters of ATM (P=0.009) and p16INK4a (P=0.001) (impalpable breast lesions vs. control). The present study demonstrated that epigenetic changes occurring in the ATM and CDKN2A genes detectable in liquid biopsy were associated with the development of impalpable breast lesions.

12.
J Chem Inf Model ; 60(5): 2419-2423, 2020 05 26.
Article in English | MEDLINE | ID: mdl-31944765

ABSTRACT

Previous studies demonstrated the efficiency of the Molecular Dynamics with excited Normal Modes (MDeNM) method on the characterization of large structural changes at a low computational cost. We present here MDeNM-EMfit, an extension of the original method designed to the flexible fit of structures into cryo-EM maps. Here, instead of a uniform exploration of the collective motions described by normal modes, sampling is directed toward conformations with increased correlations with the experimental map. Future perspectives to improve the accuracy of fitting and speed of calculations are discussed in light of the results.


Subject(s)
Molecular Dynamics Simulation , Cryoelectron Microscopy , Protein Conformation
13.
Biochim Biophys Acta Proteins Proteom ; 1868(1): 140248, 2020 01.
Article in English | MEDLINE | ID: mdl-31279935

ABSTRACT

Fungi cellulases are used to degrade cellulose-containing biomass for bioethanol production. Industrial cellulases such as Cel7A from Trichoderma reesei (TrCel7A) are critical in this process. Thus, the understanding of structure and dynamics is crucial for engineering variants with improved cellulolytic activity. This cellulase consists of two domains connected by a flexible and highly glycosylated linker. However, the linker flexibility has hindered the determination of Cel7A complete structure. Herein, based on atomic and sparse data, we applied integrative modelling to build a model of the complete enzyme structure. Next, through simulations, we studied the glycosylation effects on the structure and dynamics of a solubilized TrCel7A. Essential dynamics analysis showed that O-glycosylation in the linker led to the stabilization of protein overall dynamics. O-linked glycans seem to restrict protein dihedral angles distribution in this region, selecting more elongated conformations. Besides the reduced flexibility, functional interdomain motions occurred in a more concerted way in the glycosylated system. In contrast, in the absence of glycosylation, we observed vast conformational plasticity with the functional domains frequently collapsing. We report here evidence that targeting Cel7A linker flexibility by point mutations including modification of glycosylation sites could be a promising design strategy to improve cellulase activity.


Subject(s)
Cellulase/chemistry , Models, Molecular , Trichoderma/enzymology , Fungal Proteins/chemistry , Glycosylation , Protein Conformation
14.
J. Bras. Patol. Med. Lab. (Online) ; 56: e1632020, 2020. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1134636

ABSTRACT

ABSTRACT The human leukocyte antigen-G (HLA-G) is a non-classical molecule of the major histocompatibility complex. HLA-G has been associated with the process of tumorigenesis and tumor escape. In this study, we aim to evaluate the HLA-G expression in melanocytic lesions and in melanoma for determining when melanocytic lesions start its expression. Twenty-two skin biopsies samples were submitted to immunohistochemistry; HLA-G expression was detected in 63.6% of the samples. This expression in melanocytic cells was significantly higher in melanoma than in benign melanocytic lesions (p < 0.002). Our results suggest that HLA-G expression starts late in the process of tumorigenesis.


RESUMEN El antígeno leucocitario humano G (HLA-G) es una molécula no clásica del complejo principal de histocompatibilidad que ha sido asociada al proceso de tumorigénesis y escape tumoral. En este estudio, nuestro objetivo es evaluar la expresión de HLA-G en lesiones melanocíticas y en el melanoma para determinar cuando las lesiones melanocíticas comienzan su expresión. Veintidós muestras de biopsias de piel se estudiaron mediante inmunohistoquímica; se detectó la expresión de HLA-G en el 63,6% de las muestras. Esa expresión en las células melanocíticas fue significativamente mayor en el melanoma que en lesiones melanocíticas benignas (p < 0,002). Nuestros resultados sugieren que la expresión de HLA-G empieza tardíamente en el proceso de tumorigénesis.


RESUMO O antígeno leucocitário humano G (HLA-G) é uma molécula não clássica do complexo principal de histocompatibilidade que tem sido associada ao processo de tumorigênese e escape tumoral. Neste estudo, objetivamos avaliar a expressão de HLA-G em lesões melanocíticas e no melanoma para determinar quando as lesões melanocíticas iniciam sua expressão. Vinte e duas amostras de biópsias de pele foram submetidas à imuno-histoquímica; a expressão de HLA-G foi observada em 63,6% das amostras. Essa expressão nas células melanocíticas foi significativamente maior no melanoma do que em lesões melanocíticas benignas (p < 0,002). Nossos resultados sugerem que a expressão de HLA-G se inicia tardiamente no processo da tumorigênese.

15.
Int J Mol Sci ; 20(19)2019 Oct 02.
Article in English | MEDLINE | ID: mdl-31581693

ABSTRACT

The aim of this study was to identify genes with higher expression in solid tumor cells by comparing human tumor biopsies with healthy blood samples using both in silico statistical analysis and experimental validations. This approach resulted in a novel panel of 80 RNA biomarkers with high discrimination power to detect circulating tumor cells in blood samples. To identify the 80 RNA biomarkers, Affymetrix HG-U133 plus 2.0 microarrays datasets were used to compare breast tumor tissue biopsies and breast cancer cell lines with blood samples from patients with conditions other than cancer. A total of 859 samples were analyzed at the discovery stage, consisting of 417 mammary tumors, 41 breast lines, and 401 control samples. To confirm this discovery, external datasets of eight types of tumors were used, and experimental validation studies (NanoString n-counter gene expression assay) were performed, totaling 5028 samples analyzed. In these analyses, the 80 biomarkers showed higher expression in all solid tumors analyzed relative to healthy blood samples. Experimental validation studies using NanoString assay confirmed the results were not dependent of the gene expression platform. A panel of 80 RNA biomarkers was described here, with the potential to detect solid tumor cells present in the blood of multiple tumor types.


Subject(s)
Biomarkers, Tumor , Neoplasms/genetics , Transcriptome , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Neoplastic Cells, Circulating/metabolism , Reproducibility of Results
17.
Sci Rep ; 9(1): 4197, 2019 03 12.
Article in English | MEDLINE | ID: mdl-30862893

ABSTRACT

Riboswitches are RNA sensors that affect post-transcriptional processes through their ability to bind to small molecules. Thiamine pyrophosphate (TPP) riboswitch class is the most widespread riboswitch occurring in all three domains of life. Even though it controls different genes involved in the synthesis or transport of thiamine and its phosphorylated derivatives in bacteria, archaea, fungi, and plants, the TPP aptamer has a conserved structure. In this study, we aimed at understanding differences in the structural dynamics of TPP riboswitches from Escherichia coli and Arabidopsis thaliana, based on their crystallographic structures (TPPswec and TPPswat, respectively) and dynamics in aqueous solution, both in apo and holo states. A combination of Molecular Dynamics Simulations and Network Analysis empowered to find out slight differences in the dynamical behavior of TPP riboswitches, although relevant for their dynamics in bacteria and plants species. Our results suggest that distinct interactions in the microenvironment surrounding nucleotide U36 of TPPswec (and U35 in TPPswat) are related to different responses to TPP. The network analysis showed that minor structural differences in the aptamer enable enhanced intramolecular communication in the presence of TPP in TPPswec, but not in TPPswat. TPP riboswitches of plants present subtler and slower regulation mechanisms than bacteria do.


Subject(s)
Arabidopsis/chemistry , Escherichia coli/chemistry , Molecular Dynamics Simulation , RNA, Bacterial/chemistry , RNA, Plant/chemistry , Riboswitch , Thiamine Pyrophosphatase , Arabidopsis/genetics , Escherichia coli/genetics , RNA, Bacterial/genetics , RNA, Plant/genetics
18.
PLoS One ; 14(1): e0209491, 2019.
Article in English | MEDLINE | ID: mdl-30629624

ABSTRACT

There is evidence that in southern US, leprosy is a zoonosis infecting wild Dasypus novemcinctus armadillos but the extent of this finding is unknown. This ecological study investigated leprosy in rural communities and in wild armadillos from the Brazilian Amazon. The study area was the Mamiá Lake of Coari municipality, Amazonas State, Northern region, a hyper endemic leprosy area where residents live on subsistence farming, fishing and armadillo hunting and its meat intake are frequent. The leprosy survey was conducted in sixteen communities by a visiting team of specialists. Local partakers provided wild armadillos to investigate M. leprae infection. Volunteers had complete dermato-neurological examination by a dermatologist with expertise in leprosy diagnosis, suspect skin lesions were biopsied for histopathology (Hematoxylin-eosin/HE, Fite-Faraco/FF staining); slit skin smears were collected. Armadillos' tissue fragments (skins, spleens, livers, lymph nodes, adrenal glands, others) were prepared for histopathology (HE/FF) and for M. leprae repetitive element-RLEP-qPCR. Among 176 volunteers, six new indeterminate leprosy cases were identified (incidence = 3.4%). Suspect skin sections and slit skin smears were negative for bacilli. Twelve wild D. novemcinctus were investigated (48 specimens/96 slides) and histopathological features of M. leprae infection were not found, except for one skin presenting unspecific inflammatory infiltrate suggestive of indeterminate leprosy. Possible traumatic neuroma, granuloma with epithelioid and Langhans cells, foreign-body granuloma were also identified. Granulomatous/non-granulomatous dermatitides were periodic-acid-Schiff/PAS negative for fungus. M. leprae-RLEP-qPCR was negative in all armadillos' tissues; no bacillus was found in histopathology. Our survey in rural communities confirmed the high endemicity for leprosy while one armadillo was compatible with paucibacillary M. leprae infection. At least in the highly endemic rural area of Coari, in the Brazilian Amazon region where infectious sources from untreated multibacillary leprosy are abundant, M. leprae infected armadillos may not represent a major source of infection nor a significant public health concern.


Subject(s)
Armadillos/microbiology , Leprosy/epidemiology , Leprosy/veterinary , Zoonoses/epidemiology , Adolescent , Adult , Animals , Brazil/epidemiology , Disease Reservoirs/microbiology , Ecosystem , Female , Humans , Incidence , Leprosy/microbiology , Leprosy, Paucibacillary/epidemiology , Leprosy, Paucibacillary/veterinary , Leprosy, Paucibacillary/virology , Male , Mycobacterium leprae/genetics , Mycobacterium leprae/isolation & purification , Rural Population , Skin/microbiology , Skin/pathology , Surveys and Questionnaires , Young Adult , Zoonoses/microbiology
19.
s.l; s.n; 2019. 13 p. ilus, mapas.
Non-conventional in English | Sec. Est. Saúde SP, HANSEN, Hanseníase Leprosy, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1097760

ABSTRACT

There is evidence that in southern US, leprosy is a zoonosis infecting wild Dasypus novemcinctus armadillos but the extent of this finding is unknown. This ecological study investigated leprosy in rural communities and in wild armadillos from the Brazilian Amazon. The study area was the Mamia´ Lake of Coari municipality, Amazonas State, Northern region, a hyper endemic leprosy area where residents live on subsistence farming, fishing and armadillo hunting and its meat intake are frequent. The leprosy survey was conducted in sixteen communities by a visiting team of specialists. Local partakers provided wild armadillos to investigate M. leprae infection. Volunteers had complete dermato-neurological examination by a dermatologist with expertise in leprosy diagnosis, suspect skin lesions were biopsied for histopathology (Hematoxylin-eosin/HE, Fite-Faraco/FF staining); slit skin smears were collected. Armadillos' tissue fragments (skins, spleens, livers, lymph nodes, adrenal glands, others) were prepared for histopathology (HE/FF) and for M. leprae repetitive elementRLEP-qPCR. Among 176 volunteers, six new indeterminate leprosy cases were identified (incidence = 3.4%). Suspect skin sections and slit skin smears were negative for bacilli. Twelve wild D. novemcinctus were investigated (48 specimens/96 slides) and histopathological features of M. leprae infection were not found, except for one skin presenting unspecific inflammatory infiltrate suggestive of indeterminate leprosy. Possible traumatic neuroma, granuloma with epithelioid and Langhans cells, foreign-body granuloma were also identified. Granulomatous/non-granulomatous dermatitides were periodic-acid-Schiff/ PAS negative for fungus. M. leprae-RLEP-qPCR was negative in all armadillos' tissues; no bacillus was found in histopathology. Our survey in rural communities confirmed the high endemicity for leprosy while one armadillo was compatible with paucibacillary M. leprae infection. At least in the highly endemic rural area of Coari, in the Brazilian Amazon region where infectious sources from untreated multibacillary leprosy are abundant, M. leprae infected armadillos may not represent a major source of infection nor a significant public health concern.


Subject(s)
Humans , Animals , Male , Female , Adolescent , Adult , Young Adult , Armadillos/microbiology , Rural Population , Disease Reservoirs/microbiology , Zoonoses , Ecosystem , Leprosy, Paucibacillary/veterinary , Leprosy, Paucibacillary/epidemiology , Leprosy, Paucibacillary/virology , Leprosy/microbiology , Leprosy/veterinary , Leprosy/epidemiology , Mycobacterium leprae/isolation & purification , Mycobacterium leprae/genetics , Skin
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