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91.
Pu Y Perry NA Yang D Lewin NE Kedei N Braun DC Choi SH Blumberg PM Garfield SH Stone JC Duan D Marquez VE 《The Journal of biological chemistry》2005,280(29):27329-27338
Although multiple natural products are potent ligands for the diacylglycerol binding C1 domain of protein kinase C (PKC), RasGRP, and related targets, the high conservation of C1 domains has impeded the development of selective ligands. We characterized here a diacylglycerol-lactone, 130C037, emerging from a combinatorial chemical synthetic strategy, which showed substantial selectivity. 130C037 gave shallow binding curves for PKC isoforms alpha, beta, gamma, delta, and epsilon, with apparent Ki values ranging from 340 nm for PKCalpha to 29 nm for PKCepsilon. When binding to isolated C1 domains of PKCalpha and -delta, 130C037 showed good affinity (Ki= 1.78 nm) only for deltaC1b, whereas phorbol 12,13-dibutyrate showed affinities within 10-fold for all. In LNCaP cells, 130C037 likewise selectively induced membrane translocation of deltaC1b. 130C037 bound intact RasGRP1 and RasGRP3 with Ki values of 3.5 and 3.8 nm, respectively, reflecting 8- and 90-fold selectivity relative to PKCepsilon and PKCalpha. By Western blot of Chinese hamster ovary cells, 130C037 selectively induced loss from the cytosol of RasGRP3 (ED50 = 286 nm), partial reduction of PKCepsilon (ED50 > 10 microm), and no effect on PKCalpha. As determined by confocal microscopy in LNCaP cells, 130C037 caused rapid translocation of RasGRP3, limited slow translocation of PKCepsilon, and no translocation of PKCalpha. Finally, 130C037 induced Erk phosphorylation in HEK-293 cells ectopically expressing RasGRP3 but not in control cells, whereas phorbol ester induced phosphorylation in both. The properties of 130C037 provide strong proof of principle for the feasibility of developing ligands with selectivity among C1 domain-containing therapeutic targets. 相似文献
92.
Barbuto N Almeida JR Pereira LM Mandarim-de-Lacerda CA 《Journal of cellular and molecular medicine》2004,8(1):102-108
The kidney NO synthase is one of the most important renal controlling systems. This paper aims the quantification of renal cortical components involved in blood pressure regulation under NOs blockade. Spontaneous hypertensive rats (SHRs) are submitted to chronic blockade of NOs by L-nitro-arginine-methyl-ester (L-NAME) and an ACE inhibitor (enalapril) in comparison with the normotensive Wistar rats. Twenty SHRs and 5 Wistar rats were divided in 5 groups and observed for 21 days for blood pressure (BP) and serum creatinine: control Wistar (5) (C-W), control SHR (5) (C-SHR), L-SHR (5) - received L-NAME 30 mg/kg/day, L+E-SHR (5) - received L-NAME and Enalapril maleate 15 mg/kg/day, E-SHR (5) - received Enalapril maleate. A quantitative morphometric study (glomerular density, QA [g1], interstitium volume density, Vv[i], tubular surface and length densities, Sv[t] and Lv[t]) were performed at the end. The BP reached 226±15 mmHg in L-SHR group. The BP difference between the L-SHR and the C-SHR groups was significant from the first week while the E-SHR group became significant from the second week. At the end of the experiment the BP of the E-SHR group was similar to the BP in the C-W group. The QA [g1] was similar among C-SHR, L-SHR and L+E-SHR groups and no difference was found between E-SHR and C-W groups. In the L-SHRs serum creatinine was greatly increased, and microscopy showed thickening of arteriolar tunica media with an increase of the wall-to-lumen ratio, perivascular fibrosis, inflammatory infiltrated, tubular atrophy and interstitial fibrosis with focal segmental glomerulosclerosis. The use of enalapril was not completely efficient in reducing BP and morphological injury when the hypertension of SHRs was increased with the NOs blockade suggesting that NO deficiency-induced hypertension is not entirely mediated by the RAAS. 相似文献
93.
Dezso Nemeth Karolina Janacsek Zsolt Turi Agnes Lukacs Don Peckham Szilvia Szanka Dorottya Gazso Noemi Lovassy Michael T. Ullman 《PloS one》2015,10(3)
The contrast between regular and irregular inflectional morphology has been useful in investigating the functional and neural architecture of language. However, most studies have examined the regular/irregular distinction in non-agglutinative Indo-European languages (primarily English) with relatively simple morphology. Additionally, the majority of research has focused on verbal rather than nominal inflectional morphology. The present study attempts to address these gaps by introducing both plural and past tense production tasks in Hungarian, an agglutinative non-Indo-European language with complex morphology. Here we report results on these tasks from healthy Hungarian native-speaking adults, in whom we examine regular and irregular nominal and verbal inflection in a within-subjects design. Regular and irregular nouns and verbs were stem on frequency, word length, and phonological structure, and both accuracy and response times were acquired. The results revealed that the regular/irregular contrast yields similar patterns in Hungarian, for both nominal and verbal inflection, as in previous studies of non-agglutinative Indo-European languages: the production of irregular inflected forms was both less accurate and slower than of regular forms, both for plural and past-tense inflection. The results replicate and extend previous findings to an agglutinative language with complex morphology. Together with previous studies, the evidence suggests that the regular/irregular distinction yields a basic behavioral pattern that holds across language families and linguistic typologies. Finally, the study sets the stage for further research examining the neurocognitive substrates of regular and irregular morphology in an agglutinative non-Indo-European language. 相似文献
94.
Irisin levels before and after physical activity among school‐age children with different BMI: A direct relation with leptin
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95.
Michelle L. Verant Noemi d’Ozouville Patricia G. Parker Karen Shapiro Elizabeth VanWormer Sharon L. Deem 《EcoHealth》2014,11(2):207-214
Toxoplasmosis is a health concern for wildlife and humans, particularly in island ecosystems. In the Galápagos Islands, exposure to Toxoplasma gondii has been found in marine avifauna on islands with and without domestic cats. To evaluate potential waterborne transmission of T. gondii, we attempted to use filtration and epifluorescent microscopy to detect autofluorescent T. gondii oocysts in fresh and estuarine surface water samples. T. gondii oocyst-like structures were microscopically visualized but were not confirmed by polymerase chain reaction and sequence analyses. Further research is needed to refine environmental pathogen screening techniques and to evaluate disease risk of waterborne zoonoses such as T. gondii for wildlife and humans, particularly in the Galápagos and other naive island ecosystems. 相似文献
96.
Sixteen tardigrade species have been identified from a total of 943 specimens isolated from 69 positive soil samples collected in southern Spain (Andalusia, Huelva). Three genera (Hexapodibius, Xerobiotus and the new genus Sarascon) and eight species are new records for the Iberian Peninsula, increasing Iberian tardigrade biodiversity by 6%, and 10 species are new records for soil habitats, increasing soil tardigrade biodiversity by 9% (from 96 to 108 species). A newly discovered species and genus are described, followed by an analysis and discussion of the species' phylogenetic position and synapomorphies, based on morphological and total evidence (morphology and molecular – 18S and 28S rRNA – data combined) phylogenetic analyses. The new genus is distinguished from other Itaquasconinae genera, to which it is phylogenetically related, by having a Parascon buccopharyngeal apparatus and Ramajendas claws. In contrast to general eutardigrade evolution, which is primarily determined by claw morphology, itaquasconid evolution is more related to buccopharyngeal apparatus morphology, which shows homoplastic evolution at superfamily, family and subfamily levels, and also defines functional trophic groups in soil-related environments.http://zoobank.org/urn:lsid:zoobank.org:pub:068B9D87-27E2-4B26-8920-FF03CEF9869A 相似文献
97.
98.
Noemi Tornadore Mariacristina Villani Mariano Brentan Antonio Todaro Silvano Marchiori 《Plant biosystems》2013,147(3):293-303
ABSTRACT The Euganean Hills are a volcanic mountainous complex, which rises from the eastern Po Plain, and consists of about one hundred hills, rising from 80 m to 604 m above sea level. In the studied area, 1158 taxa of Tracheophytes have been collected. The chorological and life-form analyses of this flora have shown the predominance of the Mediterranean s.l. elements and of the hemicryptophytes, followed by the therophytes. The chorological aspect of this floristic complex was analysed. A cross-spectrum was calculated to see how life-forms are represented in the different chorotypes. A comparison with the biological and chorological spectra of the Veneto Region and of Italy as a whole was also carried out. Several species of remarkable floristic and phytogeographical interest have been found, as well as some included in the national and Regional lists of protected species. 相似文献
99.
ABSTRACT Eight endangered species of the Veneto region were examined from the karyological and micromorphological points of view. Their geographical distribution, the exsiccata of Herbarium Venetum (HV-PAD) and conservation problems were also considered. These species are: Cortusa matthioli L., a taxon sporadically distributed in Veneto with 2n=24 chromosomes; Calianthemum kernerianum Freyn ex Kerner, only known on Mt. Baldo (Verona) and with 2n=4x=32; Scrophularia vernalis L. with 2n=28; Kosteletzkya pentacarpos (L.) Ledeb., an entity with no regional conservation regulations and with 2n=34; Athamanta vestina A.Kerner, endemic to Italy and with 2n=22; Hottonia palustris L. with 2n=20 and in danger because of the destruction of its habitat; Sagittaria sagttifolia L. with 2n=22; Trapa natans L., a protected species in Veneto with 2n=36 and 2n=48. 相似文献
100.
Marta Marques Maia Allecineia Bispo da Cruz Noemi Nosomi Taniwaki Gislene Mitsue Namiyama Ricardo Gava Aparecida Helena Souza Gomes Cristina Takami Kanamura Maria Lourdes Peris Barbo Vera Lucia Pereira-Chioccola 《International journal for parasitology》2021,51(7):559-569
The study aim was to analyze whether microvesicles and exosomes, named extracellular vesicles (EVs), purified from Toxoplasma gondii are able to stimulate the protective immunity of experimental mice when administered, as challenge, a highly virulent strain. EVs excreted from T. gondii tachyzoites (RH strain) were purified by chromatography and used for immunization assays in inbred mouse groups (EV-IM). Chronic infected (CHR) and naive (NI) mice were used as control groups, since the immune response is well known. After immunizations, experimental groups were challenged with 100 tachyzoites. Next, parasitemias were determined by real-time PCR (qPCR), and survival levels were evaluated daily. The humoral response was analyzed by detection of IgM, IgG, IgG1 and IgG2a, and opsonization experiments. The cellular response was evaluated in situ by immunohistochemistry on IFN-γ, IL-10, TNF-α and IL-17 expression in cells of five organs (brain, heart, liver, spleen and skeletal muscles). EV immunization reduced parasitemia and increased the survival index in two mouse lineages (A/Sn and BALB/c) infected with a lethal T. gondii strain. EV-IM mice had higher IgG1 levels than IgM or IgG2a. IgGs purified from sera of EV-IM mice were able to opsonize tachyzoites (RH strain), and mice that received these parasites had lower parasitemias, and mortality was delayed 48 h, compared with the same results from those receiving parasites opsonized with IgG purified from NI mice. Brain and spleen cells from EV-IM mice more highly expressed IFN-γ, IL-10 and TNF-α. In conclusion, EV-immunization was capable of inducing immune protection, eliciting high production of IgG1, IFN-γ, IL-10 and TNF-α. 相似文献