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71.
Poornima Parameswaran Ella Sklan Courtney Wilkins Trever Burgon Melanie A. Samuel Rui Lu K. Mark Ansel Vigo Heissmeyer Shirit Einav William Jackson Tammy Doukas Suman Paranjape Charlotta Polacek Flavia Barreto dos Santos Roxana Jalili Farbod Babrzadeh Baback Gharizadeh Dirk Grimm Mark Kay Satoshi Koike Peter Sarnow Mostafa Ronaghi Shou-Wei Ding Eva Harris Marie Chow Michael S. Diamond Karla Kirkegaard Jeffrey S. Glenn Andrew Z. Fire 《PLoS pathogens》2010,6(2)
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts. 相似文献
72.
73.
A definitive role for chromogranin A (CGA)-derived fragments in the control of the gastrointestinal smooth muscle contractility has not been yet established. The purpose of the present study was to evaluate, in vitro, the effects of the recombinant vasostatin 1-78 (VS-1), CGA 7-57 and CGA 47-66 on the mouse gastric mechanical activity, recording the changes of intraluminal pressure. VS-1, CGA 7-57 and CGA 47-66 produced concentration-dependent relaxations. Mouse anti-vasostatin-1 monoclonal antibody 5A8, recognising the region 53-57, abolished the relaxation induced by VS-1, indicating the specificity of the effect. The relaxation was significantly reduced by tetrodotoxin (TTX), blocker of neuronal voltage-dependent Na(+) channels, l-NAME, inhibitor of nitric oxide (NO) synthase, or apamin, blocker of small conductance Ca(2+)-dependent K(+) channels. The joint application of TTX and l-NAME did not show any additive effects, whereas TTX plus apamin abolished the VS-1 response. The results suggest that the N-terminal CGA-derived peptides are able to relax mouse gastric muscle and, therefore, they point out an inhibitory role of vasostatin I in the gastrointestinal tract. The relaxation is mediated in part by neural mechanisms through NO production and in part by non-neural mechanisms involving the opening of small conductance Ca(2+)-dependent K(+) channels. 相似文献
74.
In a long-term experiment bean (Phaseolus vulgaris L.) seedlings were grown for 18 days in hydroponics in either phosphate-sufficient (+P) or phosphate-deficient (-P) nutrient solutions. Phosphate deprivation halved the phosphorous content of roots. In plasma membrane (PM) fractions isolated from -P roots the phospholipid (PL) level was reduced from 35 to 21 mol%, while PL composition and degree of unsaturation were hardly altered. Digalactosyldiacylglycerol (DGDG) accumulated up to 26% of total PM lipids, replacing PL to a large extent. Molecular species and fatty acid compositions of DGDG in root PM were different compared to DGDG present in the -P plastids. In a short-term study, bean seedlings were grown for 18 days in hydroponics with a complete nutrient solution containing phosphate and then incubated in a -P medium for increasing time ranging from 1 up to 96 h. At the end of the starvation period phosphorous content of -P roots was reduced by 30% compared to +P ones. An activation of phospholipase D and phospholipase C was observed after 1 and 2h of phosphate deprivation, respectively. Maximal phosphatidic acid accumulation was detected after 4h of phosphate deprivation, when also DGDG started to accumulate in PM of bean roots. The fatty acid composition of PLD-derived phosphatidylbutanol resembled that of phosphatidylcholine. 相似文献
75.
Giardina P Autore F Faraco V Festa G Palmieri G Piscitelli A Sannia G 《Applied microbiology and biotechnology》2007,75(6):1293-1300
The subfamily of POXA3 laccase isoenzymes produced by the fungus Pleurotus ostreatus has been characterized as an example of the complexity and heterogeneity of fungal isoenzyme patterns. Two isoenzymes, POXA3a
and POXA3b, were previously purified, exhibiting an unusual heterodimeric structure composed of a large (67 kDa) and a small
(18 or 16 kDa) subunit. A unique gene encodes the large subunit of both POXA3a and POXA3b, but alternative splicing produces
two variants—differing for an insertion of four amino acids—for each isoenzyme. Two genes encoding POXA3a and POXA3b small
subunits have been identified, and the corresponding amino acid sequences show only two amino acid substitutions. The 18-
and 16-kDa subunits of both POXA3a and POXA3b differ for N-glycosylation at Asn150 of the 16-kDa subunit. The POXA3 large subunit 3D model allows us to highlight peculiarities of this
molecule with respect to the laccases whose 3D structures are known. 相似文献
76.
Landa MS García SI Schuman ML Burgueño A Alvarez AL Saravia FE Gemma C Pirola CJ 《American journal of physiology. Endocrinology and metabolism》2007,292(5):E1388-E1394
We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect. Here, to study the role of TRH in obesity-induced hypertension (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) increased in HFD animals. Plasma leptin was correlated with peritoneal adipose tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and small interfering (si)RNA against the prepro-TRH. Antisense significantly decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. Similar effects were observed with siRNA against prepro-TRH but for up to 4 wk. Conversely, vehicle, an inverted antisense sequence and siRNA against green fluorescence protein, produced no changes. SABP decrease seems to be owing to an inhibition of the obesity-enhanced sympathetic outflow but not to an alteration in thyroid status. Using a simple OIH model we demonstrated, for the first time, that central TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity. Thus the TRH-leptin interaction may contribute to the strong association between hypertension and obesity. 相似文献
77.
Neutrophils activate macrophages for intracellular killing of Leishmania major through recruitment of TLR4 by neutrophil elastase 总被引:5,自引:0,他引:5
Ribeiro-Gomes FL Moniz-de-Souza MC Alexandre-Moreira MS Dias WB Lopes MF Nunes MP Lungarella G DosReis GA 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(6):3988-3994
We investigated the role of neutrophil elastase (NE) in interactions between murine inflammatory neutrophils and macrophages infected with the parasite Leishmania major. A blocker peptide specific for NE prevented the neutrophils from inducing microbicidal activity in macrophages. Inflammatory neutrophils from mutant pallid mice were defective in the spontaneous release of NE, failed to induce microbicidal activity in wild-type macrophages, and failed to reduce parasite loads upon transfer in vivo. Conversely, purified NE activated macrophages and induced microbicidal activity dependent on secretion of TNF-alpha. Induction of macrophage microbicidal activity by either neutrophils or purified NE required TLR4 expression by macrophages. Injection of purified NE shortly after infection in vivo reduced the burden of L. major in draining lymph nodes of TLR4-sufficient, but not TLR4-deficient mice. These results indicate that NE plays a previously unrecognized protective role in host responses to L. major infection. 相似文献
78.
Biogenesis and recycling of synaptic vesicles are accompanied by sorting processes that preserve the molecular composition of the compartments involved. In the present study, we have addressed the targeting of synaptobrevin 2/VAMP2 (vesicle-associated membrane protein 2), a critical component of the synaptic vesicle--fusion machinery, in a heterotypic context where its sorting is not confounded by the presence of other neuron-specific molecules. Ectopically expressed synaptophysin I interacts with VAMP2 and alters its default surface targeting to a prominent vesicular distribution, with no effect on the targeting of other membrane proteins. Protein-protein interaction is not sufficient for the control of VAMP2 sorting, which is mediated by the C-terminal domain of synaptophysin I. Synaptophysin I directs the sorting of VAMP2 to vesicles before surface delivery, without influencing VAMP2 endocytosis. Consistent with this, dynamin and alpha-SNAP (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein) mutants which block trafficking at the plasma membrane do not abrogate the effect of synaptophysin I on VAMP2 sorting. These results indicate that the sorting determinants of synaptic vesicle proteins can operate independently of a neuronal context and implicate the association of VAMP2 with synaptophysin I in the specification of the pathway of synaptic vesicle biogenesis. 相似文献
79.
Addessi E Chiarotti F Visalberghi E Anzenberger G 《American journal of primatology》2007,69(11):1210-1222
Neophobia, defined as showing caution toward novel features of the environment, is widespread in birds and mammals; it can be affected by ecology, early experience, and social context. In this study, we aimed to (i) investigate the response to novel food in adult common marmosets and Goeldi's monkeys and (ii) assess the role of social influences. We used an experimental paradigm employed previously with capuchin monkeys and children, in which a subject (observer) was presented with a novel food under three conditions: (i) Presence: group members did not have food; (ii) Different color: group members received familiar food whose color differed from that of the observer's novel food; (iii) Same color: group members received familiar food of the same color as the observer's novel food. Although most common marmosets tasted and/or ate the novel food, none of the Goeldi's monkeys ate it and only two sampled it. Differences in home range size and early social experience might explain the divergent behavior of the two species. Observers of both species similarly attended to group members and their visual attention increased with the number of group members eating, especially when the observer's and group members' foods were perceptually similar. However, we observed social influences on explorative behavior in Goeldi's monkeys but not on explorative or eating behavior in common marmosets. This result might be explained by the different pattern of response to novel food observed in the two species. Moreover, social influences on Goeldi's monkeys' behavior were nonspecific, i.e. they were not based on an appreciation that the food is safe because eaten by group members. 相似文献
80.
Martins-de-Souza D Martins D Astua-Monge G Coletta-Filho HD Winck FV Baldasso PA de Oliveira BM Marangoni S Machado MA Novello JC Smolka MB 《Current microbiology》2007,54(2):119-123
The fastidious bacterium Xylella fastidiosa is associated with important crop diseases worldwide. We have recently shown that X. fastidiosa is a peculiar organism having unusually low values of gene codon bias throughout its genome and, unexpectedly, in the group of the most abundant proteins. Here, we hypothesized that the lack of codon usage optimization in X. fastidiosa would incapacitate this organism to undergo quick and massive changes in protein expression as occurs in a classical stress response. Proteomic analysis of the response to heat stress in X. fastidiosa revealed that no changes in protein expression can be detected. Moreover, stress-inducible proteins identified in the closely related citrus pathogen Xanthomonas axonopodis pv citri were found to be constitutively expressed in X. fastidiosa. These proteins have extremely high codon bias values in the X. citri and other well-studied organisms, but low values in X. fastidiosa. Because biased codon usage is well known to correlate to the rate of protein synthesis, we speculate that the peculiar codon bias distribution in X. fastidiosa is related to the absence of a classical stress response, and, probably, alternative strategies for survival of X. fastidiosa under stressfull conditions. 相似文献