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91.
Bob?JA?Schijvenaars Barend?Mons Marc?Weeber Martijn?J?Schuemie Erik?M?van Mulligen Hester?M?Wain Jan?A?KorsEmail author 《BMC bioinformatics》2005,6(1):149
Background
Massive text mining of the biological literature holds great promise of relating disparate information and discovering new knowledge. However, disambiguation of gene symbols is a major bottleneck. 相似文献92.
Miguel L Soares Seiki Haraguchi Maria-Elena Torres-Padilla Tibor Kalmar Lee Carpenter Graham Bell Alastair Morrison Christopher JA Ring Neil J Clarke David M Glover Magdalena Zernicka-Goetz 《BMC developmental biology》2005,5(1):1-11
Background
Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages.Results
We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages.Conclusion
Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo. 相似文献93.
Paola Lorena Smaldini María Lucía Orsini Delgado Carlos Alberto Fossati Guillermo Horacio Docena 《PloS one》2015,10(10)
The induction of peripheral tolerance may constitute a disease-modifying treatment for allergic patients. We studied how oral immunotherapy (OIT) with milk proteins controlled allergy in sensitized mice (cholera toxin plus milk proteins) upon exposure to the allergen. Symptoms were alleviated, skin test was negativized, serum specific IgE and IgG1 were abrogated, a substantial reduction in the secretion of IL-5 and IL-13 by antigen-stimulated spleen cells was observed, while IL-13 gene expression in jejunum was down-regulated, and IL-10 and TGF-β were increased. In addition, we observed an induction of CD4+CD25+FoxP3+ cells and IL-10- and TGF-β-producing regulatory T cells in the lamina propria. Finally, transfer experiments confirmed the central role of these cells in tolerance induction. We demonstrated that the oral administration of milk proteins pre- or post-sensitization controlled the Th2-immune response through the elicitation of mucosal IL-10- and TGF-β-producing Tregs that inhibited hypersensitivity symptoms and the allergic response. 相似文献
94.
Gomes JR Omar NF dos Santos Neves J Narvaes EA Novaes PD 《Journal of molecular histology》2011,42(2):153-159
MMP-9 and MMP-2 are metalloproteinases which degrade the denatured collagen fibers. However, there is no report about roles
of these MMPs in the odontogenic region of the adult rat incisor tooth under different eruption conditions. Male Wistar rats
were divided in a normofunctional group (NF) in which their lower teeth remained in a normal eruption. In a hypofunctional
group (HP) rats underwent shortening of their lower left incisor tooth every 2 days during 12 days. The eruption rate as well
as the expression and activities of MMP-9 and MMP-2 were evaluated using imunohistochemistry and zymography. Although the
shortening increased the eruption rate, no changes in the MMP-9 and MMP-2 were observed. We conclude that in adult rats, in
opposite to development of tooth, the MMP-9 and MMP-2 present in the odontogenic region does not seem to play a direct role
in the remodeling matrix, even after post-shortening procedures which to lead an acceleration of the eruption process in the
incisor. 相似文献
95.
In search for an alternative for nutritional antimicrobials in piglet feeding, the effects of adding whole Cuphea seeds, as a natural source of medium chain fatty acids (MCFA), with known antimicrobial effects, and an exogenous lipase to a weaner diet were studied. The foregut flora, the gut morphology, some digestive parameters and the zootechnical performance of weaned piglets were investigated. Thirty newly weaned piglets, initial weight 7.0 ± 0.4 kg, were divided according to litter, sex and weight in two groups (control diet; Cuphea+lipase diet). The Cuphea seeds (lanceolata and ignea) (50 g kg?1) were substituted for soybean oil (15 g kg?1), Alphacell (25 g kg?1) and soy protein isolate (10 g kg?1) in the control diet. Also 500 mg kg?1 microbial lipase was added to the Cuphea diet. The piglets were weighted individually on days 0, 3, 7, 14 and 16. Feed intake was recorded per pen during days 0 to 3, 3 to 7, 7 to 14 and 14 to 16. On day 7 five piglets of each experimental group were euthanized for counting the gastric and small intestinal gut flora and for gut morphology at two sites of the small intestine (proximal, distal). The results indicate a trend towards improved performances parameters by feeding Cuphea + lipase. The enzymic released MCFA (1.7 g kg?1 fresh gastric contents) tended to decrease the number of Coliforms in the proximal small intestine, but increased the number in the stomach and distal small intestine. With Cuphea, the number of Streptococci was significantly lower in small intestine, but not in the stomach, while the number of Lactobacilli was significantly lower in the distal small intestine and tended to be lower in the stomach and proximal small intestine. No differences between the diets were noted for the total anaerobic microbial load in the stomach or in the gut. Feeding Cuphea+lipase resulted in a significantly greater villus height (distal small intestine) and a lesser crypt depth (proximal and distal small intestine) and greater villus/crypt ratio depth (proximal and distal small intestine). The intra-epithelial lymphocyte (IEL) counts per 100 enterocytes were significantly decreased in the proximal small intestine and tended to decrease in the distal small intestine by feeding the Cuphea+lipase diet. Both phenomena are indicative for a more healthy and better functional state of the mucosa. Present results are in line with foregoing research, showing that manipulation of the gut ecosystem by the enzymic in situ released MCFA in the stomach and foregut can result in improved performances of the piglets, which makes the concept a potential alternative for in-feed nutritional antibiotics. 相似文献
96.
Tiziana Pascucci Giacomo Giacovazzo Diego Andolina Alessandra Accoto Elena Fiori Rossella Ventura Cristina Orsini David Conversi Claudia Carducci Vincenzo Leuzzi Stefano Puglisi-Allegra 《PloS one》2013,8(12)
Hyperphenylalaninemia (HPA) refers to all clinical conditions characterized by increased amounts of phenylalanine (PHE) in blood and other tissues. According to their blood PHE concentrations under a free diet, hyperphenylalaninemic patients are commonly classified into phenotypic subtypes: classical phenylketonuria (PKU) (PHE > 1200 µM/L), mild PKU (PHE 600-1200 µM/L) and persistent HPA (PHE 120-600 µM/L) (normal blood PHE < 120 µM/L). The current treatment for hyperphenylalaninemic patients is aimed to keep blood PHE levels within the safe range of 120-360 µM/L through a PHE-restricted diet, difficult to achieve. If untreated, classical PKU presents variable neurological and mental impairment. However, even mildly elevated blood PHE levels, due to a bad compliance to dietary treatment, produce cognitive deficits involving the prefrontal cortical areas, extremely sensible to PHE-induced disturbances. The development of animal models of different degrees of HPA is a useful tool for identifying the metabolic mechanisms underlying cognitive deficits induced by PHE. In this paper we analyzed the behavioral and biochemical phenotypes of different forms of HPA (control, mild-HPA, mild-PKU and classic-PKU), developed on the base of plasma PHE concentrations. Our results demonstrated that mice with different forms of HPA present different phenotypes, characterized by increasing severity of behavioral symptoms and brain aminergic deficits moving from mild HPA to classical PKU forms. In addition, our data identify preFrontal cortex and amygdala as the most affected brain areas and confirm the highest susceptibility of brain serotonin metabolism to mildly elevated blood PHE. 相似文献
97.
Luisa Orsini Joost Vanoverbeke Ine Swillen Joachim Mergeay Luc De Meester 《Molecular ecology》2013,22(24):5983-5999
Empirical population genetic studies have been dominated by a neutralist view, according to which gene flow and drift are the main forces driving population genetic structure in nature. The neutralist view in essence describes a process of isolation by dispersal limitation (IBDL) that generally leads to a pattern of isolation by distance (IBD). Recently, however, conceptual frameworks have been put forward that view local genetic adaptation as an important driver of population genetic structure. Isolation by adaptation (IBA) and monopolization (M) posit that gene flow among natural populations is reduced as a consequence of local genetic adaptation. IBA stresses that effective gene flow is reduced among habitats that show dissimilar ecological characteristics, leading to a pattern of isolation by environment. In monopolization, local genetic adaptation of initial colonizing genotypes results in a reduction in gene flow that fosters the persistence of founder effects. Here, we relate these different processes driving landscape genetic structure to patterns of IBD and isolation by environment (IBE). We propose a method to detect whether IBDL, IBA and M shape genetic differentiation in natural landscapes by studying patterns of variation at neutral and non‐neutral markers as well as at ecologically relevant traits. Finally, we reinterpret a representative number of studies from the recent literature by associating patterns to processes and identify patterns associated with local genetic adaptation to be as common as IBDL in structuring regional genetic variation of populations in the wild. Our results point to the importance of quantifying environmental gradients and incorporating ecology in the analysis of population genetics. 相似文献
98.
Spermiogenesis and ultrastructure of spermatozoon of Nicolla wisniewskii (Digenea, Opecoelidae), an intestinal parasite of Salmo trutta, were studied by electron microscopy. Spermiogenesis follows the general pattern found in the Digenea. It begins with the formation of a differentiation zone, including striated rootlets associated with 2 centrioles and an intercentriolar body. The flagella undergo a rotation of greater than 90 degrees. Then, their fusion with the median cytoplasmic process is proximodistal and asynchronous. A peculiarity was observed before the fusion of flagella, i.e., the attachment zones joined as 2 pairs by an electron-dense bridge. The mature spermatozoon is characterized by 2 axonemes, cortical microtubules, a nucleus, 2 mitochondria, external ornamentation, and spinelike bodies. At the posterior end of flagella, the spermatozoon is also characterized by the presence of a central element of the axoneme and without the 9 microtubule doublets. These results were compared with those of the other digeneans and, in particular, with other species of Opecoelidae. It appears that the number of cortical microtubules and their localization in the spermatozoon may be an interesting feature of their phylogeny. 相似文献
99.
Cassutt KJ Orsini MJ Abousleiman M Colone D Tang W 《Journal of biomolecular screening》2007,12(2):285-287
The authors used a homogeneous calcium dye kit with a cell line transfected using a recombinant protein construct to screen a 50,000 compound library for G-protein coupled receptor (GPCR) agonists. Only 1 of the 365 primary hits activated Gq-coupled GPCRs, as shown using IP-ONE HTRF. Furthermore, an agonist screen against the entire compound library and same heterologous cell line using AequoScreen technology generated no false positives and identified the same positive hit. Next, a multiplex assay composed of both Fluo-3 and Fura-2-loaded cells identified 1 false positive and the same true-positive hit out of the 365 primary hits. Finally, rescreening the 365 primary hits against the parental cell line loaded using the homogeneous calcium dye kit confirmed the specificity of the same true-positive hit only. In summary, the results suggest that AequoScreen technology, IP-ONE HTRF, and multiplex assays are unique, orthogonal technologies to identify nonspecific hits. 相似文献