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51.

Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais – Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention.

  相似文献   
52.
This article introduces a simulation model of rat behavior in the elevated plus-maze, designed through a Decision trees approach using Classification and Regression algorithms. Starting from the analysis of the behavior performed by a sample of 18 Sprague-Dawley male rats, probabilistic rules describing behavioral patterns of the animals were extracted, and were used as the basis of the model computations. The model adequacy was tested by contrasting a simulated sample against an independent sample of real animals. Statistical tests showed that the simulated sample exhibits similar behaviors to those displayed by the real animals, both in terms of the number of entries to open and close arms as well as in terms of the time spent by the animals in those arms. However, the performance of the model in parameters related to the behavioral patterns was partially satisfactory. Given that previous attempts in the literature have neither include this kind of patterns nor the time as a crucial model parameter, the present model offers a suitable alternative for the computational simulation of this paradigm. Compared with antecedent models, the present simulation produced similar or better results in all the considered parameters. Beyond the goal of establish an appropriate simulational model, extracted rules also reveal important regularities associated to the rat behavior previously ignored by other models, i.e. that specific rat behaviors in the elevated plus-maze are time dependent. These and other important considerations to improve the model performance are discussed.  相似文献   
53.
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Genetic polymorphisms in the 3′UTR region of the CXCL12 (rs1801157) and TP53 codon 72 (rs1042522) genes may contribute to susceptibility to childhood ALL because they affect some important processes, such as metastasis regulation and tumor suppression. Thus the objective of the present study was to detect the frequency of two genetic polymorphisms in ALL patients and controls and to add information their impact on genetic susceptibility and prognosis. The CXCL12 and TP53 polymorphisms were tested in 54 ALL child patients and in 58 controls by restriction fragment length polymerase chain reaction and allelic specific chain reaction techniques, respectively. The frequencies of both allelic variants were higher in ALL patients than in the controls and indicated a positive association: OR = 2.44; 95 % CI 1.05–5.64 for CXCL12 and OR = 2.20; 95 % CI 1.03–4.70 for TP53. Furthermore, when the two genetic variants were analyzed together, they increased significantly more than fivefold the risk of this neoplasia development (OR = 5.24; 95 % CI 1.39–19.75), indicating their potential as susceptibility markers for ALL disease and the relevance of the allelic variant combination to increased risk of developing malignant tumors. Future studies may indicate a larger panel of genes involved in susceptibility of childhood ALL and other hematological neoplasias.  相似文献   
54.
Chromoblastomycosis is a chronic cutaneous and subcutaneous mycosis. The management of this infection continues to be challenging because there is no consensus on the therapeutic regimen. We report here a case of a 69-year-old male patient with cauliflower-like lesions on his left leg and foot. He had already been treated with itraconazole at a dose of 200 mg/day for 5 months, with mycological cure for all the affected areas. However, the lesions relapsed at both sites, and treatment with itraconazole was resumed at the dose previously used. Initially, direct mycological examination, cultural, and microculture slide observation were performed. Afterward, sequencing of the ITS1-5.8S rDNA-ITS2 region of the fungal DNA and evaluation of its susceptibility to antifungal agents alone and in combination were performed. In direct mycological examination, the presence of sclerotic cells was verified, and the fungus was identified as Fonsecaea based on cultural and microscopic examinations. Identification as Fonsecaea monophora was confirmed after sequencing of the ITS region and phylogenetic analysis. The isolate was susceptible to itraconazole and terbinafine. The combinations of amphotericin B and terbinafine and terbinafine and voriconazole were synergistic. The use of drugs for which the causative agent is susceptible to singly or in combination may be an alternative for the treatment of mycosis. Furthermore, the identification of the agent by molecular techniques is important for epidemiological purposes. To the best of our knowledge, this is the first case of relapsed chromoblastomycosis caused by F. monophora in Brazil.  相似文献   
55.
Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5′ phosphatase. Hence, our findings imply that Dok-3/Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency.  相似文献   
56.
57.
In this study a new species of Neralsia is described, N. incompleta n. sp. The radial cell shape allows to distinguish it clearly from the rest of species of the genus. The distribution of Neralsia incompleta n. sp. is probably the entire American continent, having been collected from Canada to Paraguay. In spite of its abundance, the associated biology is unknown, although it should be related with parasitism of Diptera Cyclorrhapha.  相似文献   
58.
The main objective of this study was to optimize a culture media for low scale biomass production of Pleurotus spp. Future applications of this optimization will be implemented for “in situ” rice straw degradation, increase soil nutrients availability, and lower residue and rice culture management costs. Soil samples were taken from different points in six important rice production cities in Colombia. For carbon and nitrogen source selection a factorial 42 design was carried out. The Plackett-Burman design permitted to detect carbon, nitrogen and inducer effects on fungus growth (response variable for all designs). This optimization was carried out by a Box-Behnken design. Finally a re-optimization assay for glucose concentration was performed by means of a One Factor design. Only 4/33 (12 %) isolates showed and important laccase or manganese peroxidase activity compared to Pleurotus ostreatus (HPB/P3). We obtained an increased biomass production in Pleurotus spp. (T1.1.) with glucose, followed by rice husk. Rice straw was considered an inducing agent for lignin degradation. Glucose was a significant component with positive effects, whereas Tween 80 and pH had negative effects. On the contrary, rice husk, yeast extract and CaCl2 were not significant components for increase the biomass production. Final media composition consisted of glucose 25 g L?1, yeast extract 5 g L?1, Tween 80 0.38 % (v/v), Rice husk 10 g L?1, CaCl2 1 g L?1, and pH 4.88 ± 0.2. The Box-Behnken polynomial prediction resulted to be lower than the experimental validation of the model (6.59 vs. 6.91 Log10 CFU ml?1 respectively).  相似文献   
59.
Leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, Mycobacterium leprae . The induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. The purpose of the present study was to evaluate the serum levels of tumour necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 and sTNF-R2) in leprosy patients at different stages of multidrug treatment (MDT) in comparison with non-infected individuals and to determine their role as putative biomarkers of the severity of leprosy or the treatment response. ELISA was used to measure the levels of these molecules in 30 healthy controls and 37 leprosy patients at the time of diagnosis and during and after MDT. Our results showed increases in the serum levels of TNF-α and sTNF-R2 in infected individuals in comparison with controls. The levels of TNF-α, but not sTNF-R2, decreased with treatment. The current results corroborate previous reports of elevated serum levels of TNF-α in leprosy and suggest a role for sTNF-R2 in the control of this cytokine during MDT.  相似文献   
60.
Several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases as well as nonneuropathic diseases such as type II diabetes and atrial amyloidosis are associated with aggregation of amyloid polypeptides into fibrillar structures, or plaques. In this study, we use molecular dynamics simulations to test the stability and orientation of membrane-embedded aggregates of the human islet amyloid polypeptide (hIAPP) implicated in type II diabetes. We find that in both monolayers and bilayers of dipalmitoylphosphatidylglycerol (DPPG) hIAPP trimers and tetramers remain inside the membranes and preserve their β-sheet secondary structure. Lipid bilayer-inserted hIAPP trimers and tetramers orient inside DPPG at 60° relative to the membrane/water interface and lead to water permeation and Na+ intrusion, consistent with ion-toxicity in islet β-cells. In particular, hIAPP trimers form a water-filled β-sandwich that induce water permeability comparable with channel-forming proteins, such as aquaporins and gramicidin-A. The predicted disruptive orientation is consistent with the amphiphilic properties of the hIAPP aggregates and could be probed by chiral sum frequency generation (SFG) spectroscopy, as predicted by the simulated SFG spectra.  相似文献   
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