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991.
Sònia Tugues Satoshi Honjo Christian K?nig Narendra Padhan Jeffrey Kroon Laura Gualandi Xiujuan Li Irmeli Barkefors Victor L. Thijssen Arjan W. Griffioen Lena Claesson-Welsh 《The Journal of biological chemistry》2013,288(26):19060-19071
CD63 is a member of the transmembrane-4 glycoprotein superfamily (tetraspanins) implicated in the regulation of membrane protein trafficking, leukocyte recruitment, and adhesion processes. We have investigated the involvement of CD63 in endothelial cell (EC) signaling downstream of β1 integrin and VEGF. We report that silencing of CD63 in primary ECs arrested capillary sprouting and tube formation in vitro because of impaired adhesion and migration of ECs. Mechanistically, CD63 associated with both β1 integrin and the main VEGF receptor on ECs, VEGFR2. Our data suggest that CD63 serves to bridge between β1 integrin and VEGFR2 because CD63 silencing disrupted VEGFR2-β1 integrin complex formation identified using proximity ligation assays. Signaling downstream of β1 integrin and VEGFR2 was attenuated in CD63-silenced cells, although their cell surface expression levels remained unaffected. CD63 was furthermore required for efficient internalization of VEGFR2 in response to VEGF. Importantly, systemic delivery of VEGF failed to potently induce VEGFR2 phosphorylation and downstream signaling in CD63-deficient mouse lungs. Taken together, our findings demonstrate a previously unrecognized role for CD63 in coordinated integrin and receptor tyrosine kinase signaling in vitro and in vivo. 相似文献
992.
Zsolt Kasza Peder Fredlund Fuchs Christoffer Tamm Anna S. Eriksson Paul O'Callaghan Femke Heindryckx Dorothe Spillmann Erik Larsson Sébastien Le Jan Inger Eriksson P?r Gerwins Lena Kjellén Johan Kreuger 《The Journal of biological chemistry》2013,288(36):25956-25963
Heparan sulfate (HS) proteoglycans, present at the plasma membrane of vascular endothelial cells, bind to the angiogenic growth factor VEGFA to modulate its signaling through VEGFR2. The interactions between VEGFA and proteoglycan co-receptors require sulfated domains in the HS chains. To date, it is essentially unknown how the formation of sulfated protein-binding domains in HS can be regulated by microRNAs. In the present study, we show that microRNA-24 (miR-24) targets NDST1 to reduce HS sulfation and thereby the binding affinity of HS for VEGFA. Elevated levels of miR-24 also resulted in reduced levels of VEGFR2 and blunted VEGFA signaling. Similarly, suppression of NDST1 using siRNA led to a reduction in VEGFR2 expression. Consequently, not only VEGFA binding, but also VEGFR2 protein expression is dependent on NDST1 function. Furthermore, overexpression of miR-24, or siRNA-mediated reduction of NDST1, reduced endothelial cell chemotaxis in response to VEGFA. These findings establish NDST1 as a target of miR-24 and demonstrate how such NDST1 suppression in endothelial cells results in reduced responsiveness to VEGFA. 相似文献
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Luiz Francisco Rocha e Silva Emerson Silva Lima Marne Carvalho de Vasconcellos Ellen Suzany Pereira Aranha David Siqueira Costa Elba Vieira Mustafa Sabrina Kelly Reis de Morais Maria das Gra?as Costa Alecrim Sergio Massayoshi Nunomura Lena Struwe Valter Ferreira de Andrade-Neto Adrian Martin Pohlit 《Memórias do Instituto Oswaldo Cruz》2013,108(4):501-507
Tachia sp. are used as antimalarials in the Amazon Region and
in vivo antimalarial activity of a Tachia sp. has been
previously reported. Tachia grandiflora Maguire and Weaver is
an Amazonian antimalarial plant and herein its cytotoxicity and antimalarial
activity were investigated. Spectral analysis of the tetraoxygenated xanthone
decussatin and the iridoid aglyone amplexine isolated, respectively, from the
chloroform fractions of root methanol and leaf ethanol extracts was performed.
In vitro inhibition of the growth of Plasmodium falciparum
Welch was evaluated using optical microscopy on blood smears. Crude extracts of
leaves and roots were inactive in vitro. However, chloroform fractions of the
root and leaf extracts [half-maximal inhibitory concentration (IC50) = 10.5 and
35.8 µg/mL, respectively] and amplexine (IC50= 7.1 µg/mL) were active in vitro.
Extracts and fractions were not toxic to type MRC-5 human fibroblasts (IC50>
50 µg/mL). Water extracts of the roots of T. grandiflora
administered by mouth were the most active extracts in the Peters 4-day
suppression test in Plasmodium berghei-infected mice. At 500
mg/kg/day, these extracts exhibited 45-59% inhibition five to seven days after
infection. T. grandiflora infusions, fractions and isolated
substance have potential as antimalarials. 相似文献
997.
The diet of the brown four-eyed opossum (Metachirus nudicaudatus) at a riparian savanna in Brazil was analyzed using 22 fecal samples collected monthly from November 2009 to October 2011. A comparison was established between samples from rainy and dry seasons. Diet composition varied seasonally. Arthropods and fruits were consumed in different frequencies of occurrence, in both seasons, but small vertebrates were only found in the dry season. Diet differences among biomes (Atlantic Forest and Cerrado) were also assessed by comparing the frequency of food items in the fecal sample in our study with data from the literature. Invertebrates (100%) were the most frequent food category found, followed by fruits (59%) and vertebrates (13.6%). Small differences in the consumption of invertebrates were found among the biomes. Nevertheless, seed frequency was significantly higher in samples from the Cerrado than in those from the Atlantic Forest. In our study site, Metachirus nudicaudatus is opportunistic and has an omnivorous diet, tending to include more fruits in its natural diet than has been previously described. 相似文献
998.
Olfaction is an important sensory modality that regulates a plethora of behavioural expressions in insects. Processing of olfactory information takes place in the primary olfactory centres of the brain, namely the antennal lobes (ALs). Neuropeptides have been shown to be present in the olfactory system of various insect species. In the present study, we analyse the distribution of tachykinin, FMRFamide-related peptides, allatotropin, allatostatin, myoinhibitory peptides and SIFamide in the AL of the male Egyptian cotton leafworm, Spodoptera littoralis. Immunocytochemical analyses revealed that most neuropeptides were expressed in different subpopulations of AL neurons. Their arborisation patterns within the AL suggest a significant role of neuropeptide signalling in the modulation of AL processing. In addition to local interneurons, our analysis also revealed a diversity of extrinsic peptidergic neurons that connected the antennal lobe with other brain centres. Their distributions suggest that extrinsic neurons perform various types of context-related modulation. 相似文献
999.
Lena Nyberg Fredrik Persson Bj?rn ?kerman Fredrik Westerlund 《Nucleic acids research》2013,41(19):e184
The commonly used fluorescent dye YOYO-1 (YOYO) has, using bulk techniques, been demonstrated to stain DNA heterogeneously at substoichiometric concentrations. We here, using nanofluidic channels and fluorescence microscopy, investigate the heterogeneous staining on the single DNA molecule level and demonstrate that the dye distribution is continuous. The equilibration of YOYO on DNA is extremely slow but can be accelerated by increasing the ionic strength and/or the temperature. Furthermore, we demonstrate how to use the heterogeneous staining as a tool for detailed and time-efficient studies of how fluorescent dyes affect the physical properties of DNA. We show that the relative increase in extension of DNA with increasing amount of YOYO bound is higher at low ionic strengths and also extrapolate the extension of native DNA. Our study reveals important information on how YOYO affects the physical properties of DNA, but it also has broader applications. First, it reveals how cationic intercalators, such as potential DNA drugs, affect DNA under strong confinement. Second, the strategy of using heterogeneous staining is of general use for single molecule studies of DNA interacting with proteins or ligands. 相似文献
1000.