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961.
962.
Although retinoic acid (RA) has been implicated as one of the diffusible signals regulating forebrain development, patterning of the forebrain has not been analyzed in detail in knockout mouse mutants deficient in embryonic RA synthesis. We show that the retinaldehyde dehydrogenase 2 (RALDH2) enzyme is responsible for RA synthesis in the mouse craniofacial region and forebrain between the 8- and 15-somite stages. Raldh2-/- knockout embryos exhibit defective morphogenesis of various forebrain derivatives, including the ventral diencephalon, the optic and telencephalic vesicles. These defects are preceded by regionally decreased cell proliferation in the neuroepithelium, correlating with abnormally low D-cyclin gene expression. Increases in cell death also contribute to the morphological deficiencies at later stages. Molecular analyses reveal abnormally low levels of FGF signaling in the craniofacial region, and impaired sonic hedgehog signaling in the ventral diencephalon. Expression levels of several regulators of diencephalic, telencephalic and optic development therefore cannot be maintained. These results unveil crucial roles of RA during early mouse forebrain development, which may involve the regulation of the expansion of neural progenitor cells through a crosstalk with FGF and sonic hedgehog signaling pathways. 相似文献
963.
Microfilaments and microtubules (MT) play a vital role in cellular endocytic processes. The present study evaluates the role of these cytoskeletal elements in the apical internalization and postendocytic fate of riboflavin (RF) in placental trophoblasts (BeWo cells). Biochemical modification of the actin and microtubule network by (1) okadaic acid (OA), which disrupts MT-based vesicular trafficking; (2) cytochalasin D and latrunculin B, which promote actin depolymerization; and (3) 2,3-butanedione monoxime (BDM), which inhibits myosin–actin interaction, was confirmed by immunofluorescence microscopy using actin- and tubulin-specific antibodies. Furthermore, involvement of the molecular motors dynein and kinesin was assessed in the presence of (1) sodium orthovanadate, which inhibits dynein-ATPase activity and (2) adenosine 5′-(β,γ-imido)triphosphate tetralithium salt hydrate, a non-hydrolyzable ATP analog, which results in defective kinesin-driven processes. RF internalization consequent to cytoskeletal alterations was compared with that of a clathrin-dependent endocytic marker ([125I]-transferrin [TF]), a caveolae-mediated endocytic substrate ([3H]-folic acid [FA]), and a fluid-phase endocytic marker ([125I]-horse radish peroxidase [HRP]). Apical recycling and bidirectional transport of RF and TF was measured following cytoskeletal alterations. Results indicate that uptake of RF, TF, FA and HRP are markedly reduced (~30–65%) in the presence OA and BDM, suggesting differential sensitivities to modification of kinesin-driven microtubules. However, actin depolymerization negatively affected HRP endocytosis alone, while RF, FA and TF internalization remained unchanged. Disturbances in protein phosphorylation cascades also influenced apical recycling while net ligand transport across monolayers remained unaffected. In conclusion, apical RF trafficking in placental cells is tightly regulated by microtubules and supported by accessory actin involvement. 相似文献
964.
Coro J Atherton R Little S Wharton H Yardley V Alvarez A Súarez M Pérez R Rodríguez H 《Bioorganic & medicinal chemistry letters》2006,16(5):1312-1315
The effect of several alkyl-linked bis tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) on Leishmania donovani, Trypanosoma brucei rhodesiense, and Plasmodium falciparum is reported. Most of the compounds exhibited a potent activity against the three parasitic strains but the best in vitro activity profiles were found against T. b. rhodesiense with IC(50) values ranging between 0.3 and 4 microM for the most active compounds. 相似文献
965.
Limited complementarity between U1 snRNA and a retroviral 5′ splice site permits its attenuation via RNA secondary structure 下载免费PDF全文
Daniela Zychlinski Steffen Erkelenz Vanessa Melhorn Christopher Baum Heiner Schaal Jens Bohne 《Nucleic acids research》2009,37(22):7429-7440
Multiple types of regulation are used by cells and viruses to control alternative splicing. In murine leukemia virus, accessibility of the 5′ splice site (ss) is regulated by an upstream region, which can fold into a complex RNA stem–loop structure. The underlying sequence of the structure itself is negligible, since most of it could be functionally replaced by a simple heterologous RNA stem–loop preserving the wild-type splicing pattern. Increasing the RNA duplex formation between U1 snRNA and the 5′ss by a compensatory mutation in position +6 led to enhanced splicing. Interestingly, this mutation affects splicing only in the context of the secondary structure, arguing for a dynamic interplay between structure and primary 5′ss sequence. The reduced 5′ss accessibility could also be counteracted by recruiting a splicing enhancer domain via a modified MS2 phage coat protein to a single binding site at the tip of the simple RNA stem–loop. The mechanism of 5′ss attenuation was revealed using hyperstable U1 snRNA mutants, showing that restricted U1 snRNP access is the cause of retroviral alternative splicing. 相似文献
966.
Siderophores are low molecular weight, high-affinity iron(III) ligands, produced by bacteria to solubilize and promote iron
uptake under low iron conditions. Two prominent structural features characterize the majority of the marine siderophores discovered
so far: (1) a predominance of suites of amphiphilic siderophores composed of an iron(III)-binding headgroup that is appended
by one or two of a series of fatty acids and (2) a prevalence of siderophores that contain α-hydroxycarboxylic acid moieties
(e.g., β-hydroxyaspartic acid or citric acid) which are photoreactive when coordinated to Fe(III). Variation of the fatty
acid chain length affects the relative amphiphilicity within a suite of siderophores. Catecholate sulfonation is another structural
variation that would affect the hydrophilicity of a siderophore. In addition to a review of the marine amphiphilic siderophores,
we report the production of petrobactin disulfonate by Marinobacter aquaeolei VT8.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
967.
Vanessa Cerantola Isabelle Guillas Carole Roubaty Christine Vionnet Danièle Uldry Jens Knudsen Andreas Conzelmann 《Molecular microbiology》2009,71(6):1523-1537
All mature Saccharomyces cerevisiae sphingolipids comprise inositolphosphorylceramides containing C26:0 or C24:0 fatty acids and either phytosphingosine or dihydrosphingosine. Here we analysed the lipid profile of lag1 Δ lac1 Δ mutants lacking acyl-CoA-dependent ceramide synthesis, which require the reverse ceramidase activity of overexpressed Ydc1p for sphingolipid biosynthesis and viability. These cells, termed 2Δ.YDC1, make sphingolipids containing exclusively dihydrosphingosine and an abnormally wide spectrum of fatty acids with between 18 and 26 carbon atoms. Like wild-type cells, 2Δ.YDC1 cells stop growing when exposed to Aureobasidin A (AbA), an inhibitor of the inositolphosphorylceramide synthase AUR1 , yet their ceramide levels remain very low. This finding argues against a current hypothesis saying that yeast cells do not require inositolphosphorylceramides and die in the presence of AbA only because ceramides build up to toxic concentrations. Moreover, W303 lag1 Δ lac1 Δ ypc1 Δ ydc1 Δ cells, reported to be AbA resistant, stop growing on AbA after a certain number of cell divisions, most likely because AbA blocks the biosynthesis of anomalous inositolphosphorylsphingosides. Thus, data argue that inositolphosphorylceramides of yeast, the equivalent of mammalian sphingomyelins, are essential for growth. Data also clearly confirm that wild-type strains, when exposed to AbA, immediately stop growing because of ceramide intoxication, long before inositolphosphorylceramide levels become subcritical. 相似文献
968.
Vanessa S.A. Barbosa Antônia C.J. Câmara Daniel P. Oliveira Aldo C. Medeiros 《Experimental parasitology》2009,123(4):309-312
With the aim of investigating the biodistribution of technetium-99 m pertechnetate () in rats infected with Y strain of Tripanosoma Cruzi, at the peak of parasitemia, (14th day of infection), we injected Wistar rats with 0.1 ml of (3.7 MBq). After 60 min, the percentage of radioactivity per gram was counted in several isolated organs and blood, using a gamma counter (1470 Wizard, PerkinElmer Finland). The uptake of increased significantly in blood and decreased in the colon of infected animals (p < 0.05). A significant reduction in serum iron and red blood cells and a significant increase in total proteins, leukocytes and lymphocytes in the infected rats were observed, compared with controls (p < 0.05). A reduction in muscle layer thickness of the colon and mononuclear inflammation were observed. These results conclusively demonstrate that T. cruzi infection would be associated with changes in the biodistribution of and in colon morphology, with potential clinical implications. 相似文献
969.
Ange-Marie Risterucci Isabelle Hippolyte Xavier Perrier Ling Xia Vanessa Caig Margaret Evers Eric Huttner Andrzej Kilian Jean-Christophe Glaszmann 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(6):1093-1103
Diversity Arrays Technology (DArT) is a DNA hybridisation-based molecular marker technique that can detect simultaneously
variation at numerous genomic loci without sequence information. This efficiency makes it a potential tool for a quick and
powerful assessment of the structure of germplasm collections. This article demonstrates the usefulness of DArT markers for
genetic diversity analyses of Musa spp. genotypes. We developed four complexity reduction methods to generate DArT genomic representations and we tested their
performance using 48 reference Musa genotypes. For these four complexity reduction methods, DArT markers displayed high polymorphism information content. We
selected the two methods which generated the most polymorphic genomic representations (PstI/BstNI 16.8%, PstI/TaqI 16.1%) to analyze a panel of 168 Musa genotypes from two of the most important field collections of Musa in the world: Cirad (Neufchateau, Guadeloupe), and IITA (Ibadan, Nigeria). Since most edible cultivars are derived from two
wild species, Musa acuminata (A genome) and Musa balbisiana (B genome), the study is restricted mostly to accessions of these two species and those derived from them. The genomic origin
of the markers can help resolving the pedigree of valuable genotypes of unknown origin. A total of 836 markers were identified
and used for genotyping. Ten percent of them were specific to the A genome and enabled targeting this genome portion in relatedness
analysis among diverse ploidy constitutions. DArT markers revealed genetic relationships among Musa genotype consistent with those provided by the other markers technologies, but at a significantly higher resolution and speed
and reduced cost. 相似文献
970.