944 resultados para Localization and tracking
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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The correct identification of all human genes, and their derived transcripts, has not yet been achieved, and it remains one of the major aims of the worldwide genomics community. Computational programs suggest the existence of 30,000 to 40,000 human genes. However, definitive gene identification can only be achieved by experimental approaches. We used two distinct methodologies, one based on the alignment of mouse orthologous sequences to the human genome, and another based on the construction of a high-quality human testis cDNA library, in an attempt to identify new human transcripts within the human genome sequence. We generated 47 complete human transcript sequences, comprising 27 unannotated and 20 annotated sequences. Eight of these transcripts are variants of previously known genes. These transcripts were characterized according to size, number of exons, and chromosomal localization, and a search for protein domains was undertaken based on their putative open reading frames. In silico expression analysis suggests that some of these transcripts are expressed at low levels and in a restricted set of tissues.
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Includes bibliography
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Includes bibliography
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Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features include mild to severe intellectual disability with speech delay, growth failure, brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is typically caused by a large deletion on 17p11.2 that encompasses multiple genes including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene. Here we have evaluated 30 patients with suspected SMS and identified SMS-associated classical 17p11.2 deletions in six patients, an atypical deletion of ∼139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene nonsynonymous alterations of unknown significance in two unrelated patients. The RAI1 mutant proteins showed no significant alterations in molecular weight, subcellular localization and transcriptional activity. Clinical features of patients with or without 17p11.2 deletions and mutations involving the RAI1 gene were compared to identify phenotypes that may be useful in diagnosing patients with SMS. © 2012 Macmillan Publishers Limited All rights reserved.
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Background: The relationship between normal and tangential force components (grip force - GF and load force - LF, respectively) acting on the digits-object interface during object manipulation reveals neural mechanisms involved in movement control. Here, we examined whether the feedback type provided to the participants during exertion of LF would influence GF-LF coordination and task performance. Methods. Sixteen young (24.7 ±3.8 years-old) volunteers isometrically exerted continuously sinusoidal FZ (vertical component of LF) by pulling a fixed instrumented handle up and relaxing under two feedback conditions: targeting and tracking. In targeting condition, FZ exertion range was determined by horizontal lines representing the upper (10 N) and lower (1 N) targets, with frequency (0.77 or 1.53 Hz) dictated by a metronome. In tracking condition, a sinusoidal template set at similar frequencies and range was presented and should be superposed by the participants' exerted FZ. Task performance was assessed by absolute errors at peaks (AEPeak) and valleys (AEValley) and GF-LF coordination by GF-LF ratios, maximum cross-correlation coefficients (r max), and time lags. Results: The results revealed no effect of feedback and no feedback by frequency interaction on any variable. AE Peak and GF-LF ratio were higher and rmax lower at 1.53 Hz than at 0.77 Hz. Conclusion: These findings indicate that the type of feedback does not influence task performance and GF-LF coordination. Therefore, we recommend the use of tracking tasks when assessing GF-LF coordination during isometric LF exertion in externally fixed instrumented handles because they are easier to understand and provide additional indices (e.g., RMSE) of voluntary force control. © 2013 Pedão et al.; licensee BioMed Central Ltd.
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Background. Characterization of novel rodent models for prostate cancer studies requires evaluation of either spontaneous and carcinogen-induced tumors as well as tumor incidence in different prostatic lobes. We propose a new short-term rodent model of chemically induced prostate carcinogenesis in which prostate cancer progression occurs differentially in the dorsolateral and ventral lobes. Methods. Adult gerbils were treated with MNU alone or associated with testosterone for 3 or 6 months of treatment. Tumor incidence, latency, localization, and immunohistochemistry (AR, PCNA, smooth muscle α-actin, p63, MGMT, and E-cadherin) were studied in both lobes. Results. Comparisons between both lobes revealed that lesions developed first in the DL while the VL presented longer tumor latency. However, after 6 months, there was a dramatic increase in tumor multiplicity in the VL, mainly in MNU-treated groups. Lesions clearly progressed from a premalignant to a malignant phenotype over time and tumor latency was decreased by MNU + testosterone administration. Three-dimensional reconstruction of the prostatic complex showed that the DL developed tumors exclusively in the periurethral area and showed intense AR, PCNA, and MGMT immunostaining. Moreover, VL lesions emerged throughout the entire lobe. MNU-induced lesions presented markers indicative of an aggressive phenotype: lack of basal cells, rupture of the smooth muscle cell layer, loss of E-cadherin, and high MGMT staining. Conclusions. There are distinct pathways involved in tumor progression in gerbil prostate lobes. This animal provides a good model for prostate cancer since it allows the investigation of advanced steps of carcinogenesis with shorter latency periods in both lobes. Copyright © 2013 Wiley Periodicals, Inc.
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Introduction: The aim of this study was to characterize the formation and progression of experimentally induced periapical lesions in TLR2 knockout (TLR2 KO) mice. Methods: Periapical lesions were induced in molars of 28 wild type (WT) and 27 TLR2 KO mice. After 7, 21, and 42 days, the animals were euthanized, and the mandibles were subjected to histotechnical processing. Hematoxylin-eosin-stained sections were examined under conventional light microscopy for the description of pulpal, apical, and periapical features and under fluorescence microscopy for the determination of the periapical lesion size. The subsequent sections were evaluated by tartrate resistant acid phosphatase histoenzymology (osteoclasts), Brown and Brenn staining (bacteria), and immunohistochemistry (RANK, RANKL, and OPG). Data were analyzed by the Mann-Whitney U and Kruskal-Wallis tests (alpha = 0.05), Results: The WT group showed significant differences (P < .05) in the periapical lesion size and the osteoclast number between 7 and 42 days and between 21 and 42 days. In the TLR2 KO group, significant differences (P < .05) in the periapical lesion size and the osteoclast number were found between 7 days and the other periods. There was a significant difference (P < .05) between the 2 types of animal regarding the periapical lesion size, which was larger in the TLR2 KO animals. No significant differences (P > .05) were found between WT and TLR2 KO mice related to the pulpal, apical, and periapical features; bacteria localization; and immunohistochemical results (except for RANK expression). Conclusions: TLR2 KO animals developed larger periapical lesions with a greater number of osteoclasts, indicating the important role of this receptor in the host's immune and inflammatory response to root canal and periradicular infection. (J Endod 2012;38:803-813)
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Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.
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Objective: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease. Methods: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations. Results: Serum levels Of CA-125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups. Conclusion: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.
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This study aims to analyse the degree of completeness of world inventory of the mite family Phytoseiidae and the factors that might determine the process of species description. The world data set includes 2,122 valid species described from 1839 to 2010. Species accumulation curves were analysed. The effect of localisation (latitude ranges) and body size on the species description patterns over space and time was assessed. A low proportion of species seems remain to be described, but this trend could be explained by a critical reduction in the number of specialists dedicated to the study of those mites. In addition, this trend refers to the areas where phytoseiids have been well studied around the world, and it may change considerably if the study of these mites would be intensified in some areas. The number of newly described species is lower near the tropics, and their body size is also smaller. Differences in body size were noted between the three sub-families of Phytoseiidae, the highest mean body lengths of adult females being observed for Amblyseiinae, the most diverse family. In the future, collections would have certainly to take into consideration such conclusions for instance in using more adequate optical equipment especially for field collections. The decrease in the number of phytoseiid mite described was confirmed and the factors that could explain such a trend are discussed. Information for improving further inventories is provided and discussed, especially in relation to sampling localization and study methods.
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The down-regulation of the tumor-suppressor gene RASSF1A has been shown to increase cell proliferation in several tumors. RASSF1A expression is regulated through epigenetic events involving the polycomb repressive complex 2 (PRC2); however, the molecular mechanisms modulating the recruitment of this epigenetic modifier to the RASSF1 locus remain largely unknown. Here, we identify and characterize ANRASSF1, an endogenous unspliced long noncoding RNA (lncRNA) that is transcribed from the opposite strand on the RASSF1 gene locus in several cell lines and tissues and binds PRC2. ANRASSF1 is transcribed through RNA polymerase II and is 5'-capped and polyadenylated; it exhibits nuclear localization and has a shorter half-life compared with other lncRNAs that bind PRC2. ANRASSF1 endogenous expression is higher in breast and prostate tumor cell lines compared with non-tumor, and an opposite pattern is observed for RASSF1A. ANRASSF1 ectopic overexpression reduces RASSF1A abundance and increases the proliferation of HeLa cells, whereas ANRASSF1 silencing causes the opposite effects. These changes in ANRASSF1 levels do not affect the RASSF1C isoform abundance. ANRASSF1 overexpression causes a marked increase in both PRC2 occupancy and histone H3K27me3 repressive marks, specifically at the RASSF1A promoter region. No effect of ANRASSF1 overexpression was detected on PRC2 occupancy and histone H3K27me3 at the promoter regions of RASSF1C and the four other neighboring genes, including two well-characterized tumor suppressor genes. Additionally, we demonstrated that ANRASSF1 forms an RNA/DNA hybrid and recruits PRC2 to the RASSF1A promoter. Together, these results demonstrate a novel mechanism of epigenetic repression of the RASSF1A tumor suppressor gene involving antisense unspliced lncRNA, in which ANRASSF1 selectively represses the expression of the RASSF1 isoform overlapping the antisense transcript in a location-specific manner. In a broader perspective, our findings suggest that other non-characterized unspliced intronic lncRNAs transcribed in the human genome might contribute to a location-specific epigenetic modulation of genes.
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Rodent gastric mucosa grows and differentiates during suckling-weaning transition. Among the molecules in rat milk, EGF and TGFβ are important peptides in the control of cell proliferation, and together with TGFα, they are also produced by submandibular glands. We aimed to determine the effect of saliva and milk on epithelial cell proliferation in the stomach of rat pups. We also examined the distribution of TGFα in the gastric mucosa after sialoadenectomy (SIALO) and fasting in order to determine whether this growth factor is affected by the deprivation of molecules derived from saliva and milk. SIALO was performed at 14 days and fasting was induced 3 days later. Cell proliferation was evaluated through metaphasic index and TGFα was detected by immunohistochemistry. We observed that whereas SIALO did not alter cell division, since the metaphasic index (MI) was unchanged, fasting stimulated cell proliferation (P < 0.05). After SIALO and fasting, MI was reduced when compared to the fasted group (P < 0.05). We found that TGFα is distributed along gastric gland and SIALO did not interfere in the localization and number of immunolabeled cells, but fasting increased their density when compared to the control (P < 0.05). The association of SIALO and fasting reduced TGFα immunostaining (P < 0.05). Therefore, during fasting, high MI was parallel to increased TGFα in gastric epithelium, but interestingly, this effect was found only in the presence of submandibular glands. We suggest that during suckling, peptides derived from saliva and milk are important to regulate gastric growth.