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1.
Sci Rep ; 10(1): 1000, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969664

RESUMO

Bacterial physiology and adaptation are influenced by the exopolysaccharides (EPS) they produce. These polymers are indispensable for the assembly of the biofilm extracellular matrix in multiple bacterial species. In a previous study, we described the profound gene expression changes leading to biofilm assembly in B. cereus ATCC14579 (CECT148). We found that a genomic region putatively dedicated to the synthesis of a capsular polysaccharide (eps2) was overexpressed in a biofilm cell population compared to in a planktonic population, while we detected no change in the transcript abundance from another genomic region (eps1) also likely to be involved in polysaccharide production. Preliminary biofilm assays suggested a mild role for the products of the eps2 region in biofilm formation and no function for the products of the eps1 region. The aim of this work was to better define the roles of these two regions in B. cereus multicellularity. We demonstrate that the eps2 region is indeed involved in bacterial adhesion to surfaces, cell-to-cell interaction, cellular aggregation and biofilm formation, while the eps1 region appears to be involved in a kind of social bacterial motility. Consistent with these results, we further demonstrate using bacterial-host cell interaction experiments that the eps2 region is more relevant to the adhesion to human epithelial cells and the zebrafish intestine, suggesting that this region encodes a bacterial factor that may potentiate gut colonization and enhance pathogenicity against humans.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31969984

RESUMO

Biofilm formation is a strategy of many bacterial species to adapt to a variety of stresses and has become a part of infections, contaminations, or beneficial interactions. In this study, we demonstrate that profound physiological changes permit Bacillus cereus to switch from a floating to a sessile lifestyle, to undergo further maturation of the biofilm and to differentiate into the offensive or defensive features. We report that floating and biofilm cells are populations that differentiate metabolically, with members of each subpopulation developing different branches of certain metabolic pathways. Secondly, biofilm populations rearrange nucleotides, sugars, amino acids, and energy metabolism. Thirdly, this metabolic rearrangement coexists with: the synthesis of the extracellular matrix, sporulation, reinforcement of the cell wall, activation of the ROS detoxification machinery and production of secondary metabolites. This strategy contributes to defend biofilm cells from competitors. However, floating cells maintain a fermentative metabolic status that ensures a higher aggressiveness against hosts, evidenced by the production of toxins. The maintenance of the two distinct subpopulations is an effective strategy to face different environmental conditions found in the life styles of B. cereus.

3.
Angew Chem Int Ed Engl ; 59(6): 2204-2210, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31724281

RESUMO

Fragment-based drug discovery (FBDD) is a popular method in academia and the pharmaceutical industry for the discovery of early lead candidates. Despite its wide-spread use, the approach still suffers from laborious screening workflows and a limited diversity in the fragments applied. Presented here is the design, synthesis, and biological evaluation of the first fragment library specifically tailored to tackle both these challenges. The 3F library of 115 fluorinated, Fsp3 -rich fragments is shape diverse and natural-product-like with desirable physicochemical properties. The library is perfectly suited for rapid and efficient screening by NMR spectroscopy in a two-stage workflow of 19 F NMR and subsequent 1 H NMR methods. Hits against four diverse protein targets are widely distributed among the fragment scaffolds in the 3F library and a 67 % validation rate was achieved using secondary assays. This collection is the first synthetic fragment library tailor-made for 19 F NMR screening and the results demonstrate that the approach should find broad application in the FBDD community.

4.
Immunol Res ; 67(6): 478-485, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31873844

RESUMO

Extra-criteria manifestations such as thrombocytopenia and livedo are described associated with antiphospholipid syndrome (APS) but are not included in the current classification criteria. Their clinical expression might be important, as they may be associated with a high-risk profile of antiphospholipid antibodies (aPL) and thrombosis. We evaluated the association between the presence of extra-criteria manifestations in primary obstetric-APS (POAPS) and aPL profiles. We also evaluated whether the presence of extra-criteria manifestations in POAPS patients increases the risk of developing thrombosis during the follow-up period (median follow-up 5 years; range 3-9 years). We selected 79 women who were included in our study only if they were first diagnosed with POAPS (with no history of previous thrombosis) and reevaluated for the presence of thrombosis after the follow-up period. We evaluated the association between the aPL profile and extra-criteria manifestations. We also evaluated the relationship of thrombosis during the follow-up period with extra-criteria manifestations and other risk factors. Patients with three or more extra-criteria manifestations presented high rates of triple positivity for the aPL profile (75%) (p < 0.001). We also found a relationship between the presence of extra-criteria manifestations and the presence of high titers of aPL: 91.7% of patients with three or more extra-criteria manifestations had high titers of aPL (p < 0.01). We further evaluated the group of POAPS patients according to thrombotic events during the follow-up. Among these patients, 6 (7.6%) presented thrombosis. Notably, 100% of patients with a thrombotic event during the follow-up had more than three extra-criteria manifestations. POAPS patients with extra-criteria manifestations might have a high-risk aPL profile and a major risk of developing thrombosis.

5.
Environ Sci Pollut Res Int ; 26(34): 35266-35269, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31728943

RESUMO

In combination, pollution and pathogens represent a serious threat to the health of European eels that has been increasingly recognized. Thus, the impact of contaminants, cadmium, lead, mercury, and selenium, on anguillid herpesvirus 1 infection in wild European eels has been evaluated. Despite the small sample size, results indicate that selenium and mercury concentrations may compromise the European eel immune system as herpesvirus infection was more prevalent in specimens with higher Hg and Se hepatic concentrations.


Assuntos
Anguilla/virologia , Doenças dos Peixes/virologia , Infecções por Herpesviridae/veterinária , Compostos Inorgânicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Cádmio , Enguias , Herpesviridae , Fígado , Mercúrio , Alimentos Marinhos , Selênio
6.
Artigo em Inglês | MEDLINE | ID: mdl-31755055

RESUMO

We analysed exposure to Pb and its relationship with lead-based ammunition in seven species of terrestrial game birds-common woodpigeon (Columba palumbus), rock dove (Columba livia), stock dove (Columba oenas), European turtle-dove (Streptopelia turtur), red-legged partridge (Alectoris rufa), Barbary partridge (Alectoris barbara) and common quail (Coturnix coturnix)-from rural and urban areas in different parts of Spain (Valencia, Castilla-La Mancha, Castilla y León, Madrid, Islas Canarias and Navarra). A total of 530 liver samples were analysed, and the presence of Pb pellets was studied in the crop, gizzard and intestine; the state and appearance of these organs were also analysed. The number of specimens suspected to have ingested Pb shot was 28 (5.6%), and the geometric mean concentration of hepatic Pb was 0.054 µg g-1 (wet weight, ww). A low percentage of samples (4.8%) were above the abnormal exposure threshold (0.65 µg g-1 ww), and, in these specimens, renal Pb concentrations were determined. Common woodpigeons and rock doves from Madrid were found to have high concentrations of Pb in their livers, and, so, both species can be considered to be good bioindicators of Pb contamination in rural (common woodpigeons) and urban (rock doves) environments. Partridges bred for hunting may be more prone to ingesting pellets from the environment, a fact that should be taken into account in management decisions.

8.
Cancers (Basel) ; 11(9)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480291

RESUMO

Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

9.
FASEB J ; 33(11): 12146-12163, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31370706

RESUMO

The formation of biofilms provides structural and adaptive bacterial response to the environment. In Bacillus species, the biofilm extracellular matrix is composed of exopolysaccharides, hydrophobins, and several functional amyloid proteins. We report, using multiscale approaches such as solid-state NMR (SSNMR), electron microscopy, X-ray diffraction, dynamic light scattering, attenuated total reflection Fourier transform infrared (FTIR), and immune-gold labeling, the molecular architecture of B. subtilis and pathogenic B. cereus functional amyloids. SSNMR data reveal that the major amyloid component TasA in its fibrillar amyloid form contain ß-sheet and α-helical secondary structure, suggesting a nontypical amyloid architecture in B. subtilis. Proteinase K digestion experiments indicate the amyloid moiety is ∼100 aa long, and subsequent SSNMR and FTIR signatures for B. subtilis and B. cereus TasA filaments highlight a conserved amyloid fold, albeit with substantial differences in structural polymorphism and secondary structure composition. Structural analysis and coassembly data on the accessory protein TapA in B. subtilis and its counterpart camelysin in B. cereus reveal a catalyzing effect between the functional amyloid proteins and a common structural architecture, suggesting a coassembly in the context of biofilm formation. Our findings highlight nontypical amyloid behavior of these bacterial functional amyloids, underlining structural variations between biofilms even in closely related bacterial species.-El Mammeri, N., Hierrezuelo, J., Tolchard, J., Cámara-Almirón, J., Caro-Astorga, J., Álvarez-Mena, A., Dutour, A., Berbon, M., Shenoy, J., Morvan, E., Grélard, A., Kauffmann, B., Lecomte, S., de Vicente, A., Habenstein, B., Romero, D., Loquet, A. Molecular architecture of bacterial amyloids in Bacillus biofilms.

10.
Front Immunol ; 10: 1394, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281317

RESUMO

In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) are the most abundant component from the tumor microenvironment (TM). CAFs facilitate tumor progression by inducing angiogenesis, immune suppression and invasion, thus altering the organization/composition of the extracellular matrix (i.e., desmoplasia) and/or activating epithelial-mesenchymal transition (EMT). Soluble factors from the TM can also contribute to cell invasion through secretion of cytokines and recently, IL-33/ST2 pathway has gained huge interest as a protumor alarmin, promoting progression to metastasis by inducing changes in TM. Hence, we analyzed IL-33 and ST2 content in tumor and healthy tissue lysates and plasma from CRC patients. Tissue localization and distribution of these molecules was evaluated by immunohistochemistry (using localization reference markers α-smooth muscle actin or α-SMA and E-cadherin), and clinical/histopathological information was obtained from CRC patients. In vitro experiments were conducted in primary cultures of CAFs and normal fibroblasts (NFs) isolated from tumor and healthy tissue taken from CRC patients. Additionally, migration and proliferation analysis were performed in HT29 and HCT116 cell lines. It was found that IL-33 content increases in left-sided CRC patients with lymphatic metastasis, with localization in tumor epithelia associated with abundant desmoplasia. Although ST2 content showed similarities between tumor and healthy tissue, a decreased immunoreactivity was observed in left-sided tumor stroma, associated to metastasis related factors (advanced stages, abundant desmoplasia, and presence of tumor budding). A principal component analysis (including stromal and epithelial IL-33/ST2 and α-SMA immunoreactivity with extent of desmoplasia) allowed us to distinguish clusters of low, intermediate and abundant desmoplasia, with potential to develop a diagnostic signature with benefits for further therapeutic targets. IL-33 transcript levels from CAFs directly correlated with CRC cell line migration induced by CAFs conditioned media, with rhIL-33 inducing a mesenchymal phenotype in HT29 cells. These results indicate a role of IL-33/ST2 in tumor microenvironment, specifically in the interaction between CAFs and epithelial tumor cells, thus contributing to invasion and metastasis in left-sided CRC, most likely by activating desmoplasia.

11.
Ecancermedicalscience ; 13: 923, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281420

RESUMO

Introduction: The optimal management of breast lesions with atypia (BLA), detected in percutaneous biopsies after screening mammograms, is a controversial issue. The aim of this paper is to compare histological diagnosis by percutaneous biopsy with the results of the surgical biopsy of these lesions and to analyse the changes to clinical approach this would imply. Method: A retrospective study was carried out on patients operated on between June 2007 and June 2017 with a diagnosis of BLA. One hundred and forty-seven patients were identified with a pre-operative diagnosis of flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, lobular carcinoma in situ and other atypia. Results: The average age at diagnosis of BLAs was 52 ± 9.4 years. Radiologically, the lesions presented as microcalcifications in 79%, nodules in 15.6% and other lesions 5.4%. 73.5% of these were biopsied by means of digital stereotaxis. All of the patients analysed underwent a partial mastectomy. Changes in a biologically high-risk lesion were observed in 26.5% of the surgical specimens, of which 75.5% corresponded with ADH and FEA. In the percutaneous biopsies consistent with ADH (40.1%), ductal carcinoma was discovered in 6.8% (5.1% in situ and 1.7% invasive), which implied specific, multi-disciplinary management. Of the FEAs, 84.8% required a second treatment (surgery and/or hormone therapy ± radiotherapy, depending on whether it concerned FEA 59.6%, ADH 21.2% or ductal carcinoma in situ 3.8%). Conclusion: These data show the clinical relevance in the diagnosis of ADH and FEA in percutaneous biopsies. For the diagnosis of FEA in particular, the associated risk of biologically high-risk lesions and ductal carcinoma is made evident.

12.
Nat Commun ; 10(1): 1919, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015472

RESUMO

Bacteria of the genera Pseudomonas and Bacillus can promote plant growth and protect plants from pathogens. However, the interactions between these plant-beneficial bacteria are understudied. Here, we explore the interaction between Bacillus subtilis 3610 and Pseudomonas chlororaphis PCL1606. We show that the extracellular matrix protects B. subtilis colonies from infiltration by P. chlororaphis. The absence of extracellular matrix results in increased fluidity and loss of structure of the B. subtilis colony. The P. chlororaphis type VI secretion system (T6SS) is activated upon contact with B. subtilis cells, and stimulates B. subtilis sporulation. Furthermore, we find that B. subtilis sporulation observed prior to direct contact with P. chlororaphis is mediated by histidine kinases KinA and KinB. Finally, we demonstrate the importance of the extracellular matrix and the T6SS in modulating the coexistence of the two species on melon plant leaves and seeds.


Assuntos
Bacillus subtilis/genética , Cucurbitaceae/microbiologia , Matriz Extracelular/metabolismo , Regulação Bacteriana da Expressão Gênica , Interações Microbianas/genética , Pseudomonas chlororaphis/genética , Bacillus subtilis/crescimento & desenvolvimento , Bacillus subtilis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Contagem de Colônia Microbiana , Fosfotransferases/genética , Fosfotransferases/metabolismo , Folhas de Planta/microbiologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Pseudomonas chlororaphis/crescimento & desenvolvimento , Pseudomonas chlororaphis/metabolismo , Sementes/microbiologia , Esporos Bacterianos/genética , Esporos Bacterianos/crescimento & desenvolvimento , Esporos Bacterianos/metabolismo , Simbiose/fisiologia , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo
13.
Circulation ; 139(20): 2342-2357, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30818997

RESUMO

BACKGROUND: The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including that of the heart. Whereas ciliated cells have been described in developing heart, a role for primary cilia in adult heart has not been reported. This, coupled with the fact that mutations in genes coding for multiple ciliary proteins underlie polycystic kidney disease, a disorder with numerous cardiovascular manifestations, prompted us to identify cells in adult heart harboring a primary cilium and to determine whether primary cilia play a role in disease-related remodeling. METHODS: Histological analysis of cardiac tissues from C57BL/6 mouse embryos, neonatal mice, and adult mice was performed to evaluate for primary cilia. Three injury models (apical resection, ischemia/reperfusion, and myocardial infarction) were used to identify the location and cell type of ciliated cells with the use of antibodies specific for cilia (acetylated tubulin, γ-tubulin, polycystin [PC] 1, PC2, and KIF3A), fibroblasts (vimentin, α-smooth muscle actin, and fibroblast-specific protein-1), and cardiomyocytes (α-actinin and troponin I). A similar approach was used to assess for primary cilia in infarcted human myocardial tissue. We studied mice silenced exclusively in myofibroblasts for PC1 and evaluated the role of PC1 in fibrogenesis in adult rat fibroblasts and myofibroblasts. RESULTS: We identified primary cilia in mouse, rat, and human heart, specifically and exclusively in cardiac fibroblasts. Ciliated fibroblasts are enriched in areas of myocardial injury. Transforming growth factor ß-1 signaling and SMAD3 activation were impaired in fibroblasts depleted of the primary cilium. Extracellular matrix protein levels and contractile function were also impaired. In vivo, depletion of PC1 in activated fibroblasts after myocardial infarction impaired the remodeling response. CONCLUSIONS: Fibroblasts in the neonatal and adult heart harbor a primary cilium. This organelle and its requisite signaling protein, PC1, are required for critical elements of fibrogenesis, including transforming growth factor ß-1-SMAD3 activation, production of extracellular matrix proteins, and cell contractility. Together, these findings point to a pivotal role of this organelle, and PC1, in disease-related pathological cardiac remodeling and suggest that some of the cardiovascular manifestations of autosomal dominant polycystic kidney disease derive directly from myocardium-autonomous abnormalities.

14.
Histopathology ; 74(4): 597-607, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30565710

RESUMO

AIMS: Gallbladder cancer (GBC) is an aggressive tumour that is usually diagnosed at advanced stages and is characterised by a poor prognosis. Using public data of normal human tissues, we found that mRNA and protein levels of mucin 5B (MUC5B) and carbonic anhydrase 9 (CA9) were highly increased in gallbladder tissues. In addition, previous evidence has shown that claudin 18 (CLDN18) protein expression is higher in GBC. The aim of this study was to perform an analysis of these cell surface proteins during the histological progression of GBC in order to identify their theranostic potential. METHODS AND RESULTS: MUC5B expression, CA9 expression and CLDN18 expression were examined by immunohistochemistry in a series of 179 chronic cholecystitis (including 16 metaplastic tissues), 15 dysplasia and 217 GBC samples by the use of tissue microarray analysis. A composite staining score was calculated from staining intensity and percentage of positive cells. Immunohistochemical analysis showed high expression of MUC5B and CA9 among normal epithelium, metaplastic tissues, and dysplastic tissues. However, expression of both proteins was observed in roughly 50% of GBC samples. In contrast, CLDN18 was absent in normal epithelium, but its expression was higher in metaplastic cells. Among GBC cases, approximately half showed high CLDN18 expression. No associations were found between MUC5B, CA9 and CLDN18 expression and any clinicopathological features. CONCLUSIONS: CLDN18 is a new metaplasia marker in gallbladder tissues, and is conserved in approximately half of GBC cases. MUC5B and CA9 are highly conserved during GBC histological progression. The three markers are potential theranostic markers, in particular CA9 and CLDN18, for which there are already targeted therapies available.


Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/análise , Anidrase Carbônica IX/biossíntese , Claudinas/biossíntese , Neoplasias da Vesícula Biliar/patologia , Mucina-5B/biossíntese , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanomedicina Teranóstica/métodos
15.
Tumour Biol ; 40(11): 1010428318810059, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30419802

RESUMO

A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor-node-metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman's test. Plasmatic levels of chemokines and inflammatory mediators' vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163+ cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL3/metabolismo , Quimiocina CCL4/metabolismo , Neoplasias Colorretais/patologia , Macrófagos/patologia , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico
16.
Environ Sci Pollut Res Int ; 25(36): 36671-36679, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30377965

RESUMO

A hundred nesting olive ridley turtles were sampled to determine biochemical parameters (ALP, AST, ALT, creatinine, albumin, cholesterol, glucose, proteins, triglycerides, urea, and P-nitrophenyl acetate esterase activity). Esterase activity (EA) is a new biomarker very sensitive to metals. Most of the samples showed detectable levels. We also analyzed the concentration of 11 inorganic elements (As, Cd, Cr, Cu, Mn, Ni, Pb, Sr, Ti, Se, and Zn), some of them previously reported with very high concentrations in this population (especially cadmium with 82 and 150 µg g-1 ww in liver and kidney, respectively). Cadmium presented two negative relationships with creatinine and glucose. Some other understudied elements, Sr and Ti, for instance, presented five and four significant relationships with some biochemical parameters, respectively (most of them positive). EA was the parameter with most negative relationships (with Pb, Ti, As, Cr, and Se), reinforcing the results of other researchers in humans regarding the possible inhibition of EA by metals.


Assuntos
Biomarcadores/sangue , Monitoramento Ambiental/métodos , Metais Pesados/sangue , Tartarugas/sangue , Poluentes Químicos da Água/sangue , Acetilesterase/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Hidrocortisona/sangue , Rim/metabolismo , Fígado/metabolismo , Tartarugas/metabolismo , Poluentes Químicos da Água/toxicidade
17.
Crit Rev Microbiol ; 44(6): 653-666, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30354913

RESUMO

Intense research has confirmed the formerly theoretical distribution of amyloids in nature, and studies on different systems have illustrated the role of these proteins in microbial adaptation and in interactions with the environment. Two lines of research are expanding our knowledge on functional amyloids: (i) structural studies providing insights into the molecular machineries responsible for the transition from monomer to fibers and (ii) studies showing the way in which these proteins might participate in the microbial fitness in natural settings. Much is known about how amyloids play a role in the social behavior of bacteria, or biofilm formation, and in the adhesion of bacteria to surfaces; however, we are still in the initial stages of understanding a complementary involvement of amyloids in bacteria-host interactions. This review will cover the following two topics: first, the key aspects of the microbial platforms dedicated to the assembly of the fibers, and second, the mechanisms by which bacteria utilize the morphological and biochemical variability of amyloids to modulate the immunological response of the host, plants and humans, contributing to (i) infection, in the case of pathogenic bacteria or (ii) promotion of the health of the host, in the case of beneficial bacteria.


Assuntos
Amiloide/química , Amiloide/metabolismo , Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Amiloide/genética , Bactérias/química , Bactérias/genética , Proteínas de Bactérias/genética
18.
Mol Plant Pathol ; 19(11): 2502-2515, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30073764

RESUMO

A major limitation of molecular studies in powdery mildew fungi (Erysiphales) is their genetic intractability. This is because they are obligate biotrophs. In these parasites, biotrophy is determined by the presence of haustoria, which are specialized structures of parasitism that play an essential role in the acquisition of nutrients and the deliverance of effectors. Podosphaera xanthii is the main causal agent of cucurbit powdery mildew and a major limitation for crop productivity. In a previous study using P. xanthii conidia, we showed, for the first time, the transformation of powdery mildew fungi by Agrobacterium tumefaciens. In this work, we hypothesized that the haustorium could also act as a natural route for the acquisition of DNA. To test our hypothesis, melon cotyledons were agro-infiltrated with A. tumefaciens that contained diverse transfer DNA (T-DNA) constructs harbouring different marker genes under the control of fungal promoters and, after elimination of the bacterium, the cotyledons were subsequently inoculated with P. xanthii conidia. Our results conclusively demonstrated the transfer of different T-DNAs from A. tumefaciens to P. xanthii, including two fungicide resistance markers (hph and tub2), a reporter gene (gfp) and a translational fusion (cfp-PxEC2). These results were further supported by the co-localization of translational fluorescent fusions of A. tumefaciens VirD2 and P. xanthii Rab5 proteins into small vesicles of haustorial and hyphal cells, suggesting endocytosis as the mechanism for T-DNA uptake, presumably by the haustorium. From our perspective, transformation by growth onto agro-infiltrated tissues (TGAT) is the easiest and most reliable method for the transient transformation of powdery mildew fungi.


Assuntos
Agrobacterium tumefaciens/crescimento & desenvolvimento , Ascomicetos/fisiologia , Cucurbita/genética , Cucurbita/microbiologia , Doenças das Plantas/microbiologia , Transformação Genética , Núcleo Celular/metabolismo , Endocitose , Endossomos/metabolismo , Proteínas Fúngicas/metabolismo , Fenótipo
19.
Immunol Res ; 66(5): 577-583, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30159862

RESUMO

Serological risk factors are the most important determinant in predicting unsuccessful pregnancy in obstetric antiphospholipid antibodies syndrome (OAPS) despite conventional treatment. It is not clear if changes in the profile of antiphospholipid antibodies (aPL) during pregnancy modify the risk associated with a poor response to conventional treatment. The aim of our study was to compare the value of a serological tag for aPL obtained before and during the first trimester of pregnancy to predict the response to conventional treatment. We carefully selected 97 pregnancies in women who were included in our study only if they were diagnosed with OAPS prior to a new pregnancy (basal serological risk), retested for aPL during the first trimester of pregnancy (serological risk during pregnancy), and treated with conventional therapy. High baseline serological risk was associated with pregnancy failure in 62.1% of cases (18/29) and predicted 82.5% of pregnancy outcomes with conventional treatment: OR = 16.9, CI = 5.5-52.1, p < 0.001. High serological risk during pregnancy was associated with pregnancy failure in 86.3% of cases (19/22) and predicted 91.8% of pregnancy outcomes with conventional treatment: OR = 88.7, CI = 19.4-404.8, p < 0.001. According to these results, we found that risk categorization performed during pregnancy was better in predicting pregnancy outcome (82.5 vs. 91.8%). Moreover, risk categorization during pregnancy had an increased specificity regarding the prediction: 84.9% at baseline and 95.9% during pregnancy (p = 0.024). Our findings suggest that it is important to perform aPL during the first trimester of pregnancy since that is the best time to establish the serological risk factors.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Complicações na Gravidez/diagnóstico , Adulto , Argentina/epidemiologia , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Prognóstico , Risco , Sensibilidade e Especificidade
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