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21.
Changes in Human Immunodeficiency Virus Type 1 Populations after Treatment Interruption in Patients Failing Antiretroviral Therapy 总被引:7,自引:0,他引:7 下载免费PDF全文
22.
Evidence for Multidrug Resistance-1 P-Glycoprotein-dependent Regulation of Cellular ATP Permeability 总被引:8,自引:0,他引:8
R. M. Roman N. Lomri G. Braunstein A. P. Feranchak L. A. Simeoni A. K. Davison E. Mechetner E. M. Schwiebert J. G. Fitz 《The Journal of membrane biology》2001,183(3):165-173
The mechanisms responsible for regulating epithelial ATP permeability and purinergic signaling are not well defined. Based
on the observations that members of the ATP-binding cassette (ABC)1 family of proteins may contribute to ATP release, the purpose of these studies was to assess whether multidrug resistance-1
(MDR1) proteins are involved in ATP release from HTC hepatoma cells. Using a bioluminescence assay to detect extracellular
ATP, increases in cell volume increased ATP release ∼3-fold. The MDR1 inhibitors cyclosporine A (10 μm) and verapramil (10 μm) inhibited ATP release by 69% and 62%, respectively (p < 0.001). Similarly, in whole-cell patch-clamp recordings, intracellular dialysis with C219 antibodies to inhibit MDR1 decreased
ATP-dependent volume-sensitive Cl− current density from −33.1 ± 12.5 pA/pF to −2.0 ± 0.3 pA/pF (−80 mV, p≤ 0.02). In contrast, overexpression of MDR1 in NIH 3T3 cells increased ATP release rates. Inhibition of ATP release by Gd3+ had no effect on transport of the MDR1 substrate rhodamine-123; and alteration of MDR1-substrate selectivity by mutation
of G185 to V185 had no effect on ATP release. Since the effects of P-glycoproteins on ATP release can be dissociated from
P-glycoprotein substrate transport, MDR1 is not likely to function as an ATP channel, but instead serves as a potent regulator
of other cellular ATP transport pathways.
Received: 20 November 2000/Revised: 25 May 2001 相似文献
23.
Three sesterterpenes (1-3), one triterpene (4) and five diterpenes (5-9) were isolated from the aerial parts of Salvia palaestina Bentham (Lamiaceae), together with two sesquiterpenes, 10 known diterpenes, three triterpenes, and rosmarinic acid. Their structural elucidation was accomplished by extensive spectroscopic methods including 1D ((1)H, (13)C, (13)C DEPT, TOCSY, NOESY) and 2D NMR experiments (DQF-COSY, HSQC, HMBC, ROESY) as well as ESIMS analysis and chemical analysis. 相似文献
24.
Stphanie Sherpa Maya Guguen Julien Renaud Michael G. B. Blum Thierry Gaude Frdric Laporte Mustafa Akiner Bulent Alten Carles Aranda Hlne Barre‐Cardi Romeo Bellini Mikel Bengoa Paulis Xiao‐Guang Chen Roger Eritja Eleonora Flacio Cipriano Foxi Intan H. Ishak Katja Kalan Shinji Kasai Fabrizio Montarsi Igor Pajovi Duan Petri Rosa Termine Nataa Turi Gonzalo M. Vazquez‐Prokopec Enkelejda Velo Goran Vignjevi Xiaohong Zhou Laurence Desprs 《Ecology and evolution》2019,9(22):12658-12675
Invasive species can encounter environments different from their source populations, which may trigger rapid adaptive changes after introduction (niche shift hypothesis). To test this hypothesis, we investigated whether postintroduction evolution is correlated with contrasting environmental conditions between the European invasive and source ranges in the Asian tiger mosquito Aedes albopictus. The comparison of environmental niches occupied in European and source population ranges revealed more than 96% overlap between invasive and source niches, supporting niche conservatism. However, we found evidence for postintroduction genetic evolution by reanalyzing a published ddRADseq genomic dataset from 90 European invasive populations using genotype–environment association (GEA) methods and generalized dissimilarity modeling (GDM). Three loci, among which a putative heat‐shock protein, exhibited significant allelic turnover along the gradient of winter precipitation that could be associated with ongoing range expansion. Wing morphometric traits weakly correlated with environmental gradients within Europe, but wing size differed between invasive and source populations located in different climatic areas. Niche similarities between source and invasive ranges might have facilitated the establishment of populations. Nonetheless, we found evidence for environmental‐induced adaptive changes after introduction. The ability to rapidly evolve observed in invasive populations (genetic shift) together with a large proportion of unfilled potential suitable areas (80%) pave the way to further spread of Ae. albopictus in Europe. 相似文献
25.
Molecular Characterization of Subtype H11N9 Avian Influenza Virus Isolated from Shorebirds in Brazil
Renata Hurtado Thomas Fabrizio Ralph Eric Thijl Vanstreels Scott Krauss Richard J. Webby Robert G. Webster Edison Luiz Durigon 《PloS one》2015,10(12)
Migratory aquatic birds play an important role in the maintenance and spread of avian influenza viruses (AIV). Many species of aquatic migratory birds tend to use similar migration routes, also known as flyways, which serve as important circuits for the dissemination of AIV. In recent years there has been extensive surveillance of the virus in aquatic birds in the Northern Hemisphere; however in contrast only a few studies have been attempted to detect AIV in wild birds in South America. There are major flyways connecting South America to Central and North America, whereas avian migration routes between South America and the remaining continents are uncommon. As a result, it has been hypothesized that South American AIV strains would be most closely related to the strains from North America than to those from other regions in the world. We characterized the full genome of three AIV subtype H11N9 isolates obtained from ruddy turnstones (Arenaria interpres) on the Amazon coast of Brazil. For all gene segments, all three strains consistently clustered together within evolutionary lineages of AIV that had been previously described from aquatic birds in North America. In particular, the H11N9 isolates were remarkably closely related to AIV strains from shorebirds sampled at the Delaware Bay region, on the Northeastern coast of the USA, more than 5000 km away from where the isolates were retrieved. Additionally, there was also evidence of genetic similarity to AIV strains from ducks and teals from interior USA and Canada. These findings corroborate that migratory flyways of aquatic birds play an important role in determining the genetic structure of AIV in the Western hemisphere, with a strong epidemiological connectivity between North and South America. 相似文献
26.
Natalello A Prokorov VV Tagliavini F Morbin M Forloni G Beeg M Manzoni C Colombo L Gobbi M Salmona M Doglia SM 《Journal of molecular biology》2008,381(5):1349-1361
The existence of several prion strains and their capacity of overcoming species barriers seem to point to a high conformational adaptability of the prion protein. To investigate this structural plasticity, we studied here the aggregation pathways of the human prion peptide PrP82-146, a major component of the Gerstmann-Sträussler-Scheinker amyloid disease.By Fourier transform infrared (FT-IR) spectroscopy, electron microscopy, and atomic force microscopy (AFM), we monitored the time course of PrP82-146 fibril formation. After incubation at 37 °C, the unfolded peptide was found to aggregate into oligomers characterized by intermolecular β-sheet infrared bands. At a critical oligomer concentration, the emergence of a new FT-IR band allowed to detect fibril formation. A different intermolecular β-sheet interaction of the peptides in oligomers and in fibrils is, therefore, detected by FT-IR spectroscopy, which, in addition, suggests a parallel orientation of the cross β-sheet structures of PrP82-146 fibrils. By AFM, a wide distribution of PrP82-146 oligomer volumes—the smallest ones containing from 5 to 30 peptides—was observed. Interestingly, the statistical analysis of AFM data enabled us to detect a quantization in the oligomer height values differing by steps of ∼ 0.5 nm that could reflect an orientation of oligomer β-strands parallel with the sample surface. Different morphologies were also detected for fibrils that displayed high heterogeneity in their twisting periodicity and a complex hierarchical assembly.Thermal aggregation of PrP82-146 was also investigated by FT-IR spectroscopy, which indicated for these aggregates an intermolecular β-sheet interaction different from that observed for oligomers and fibrils. Unexpectedly, random aggregates, induced by solvent evaporation, were found to display a significant α-helical structure as well as several β-sheet components.All these results clearly point to a high plasticity of the PrP82-146 peptide, which was found to be capable of undergoing several aggregation pathways, with end products displaying different secondary structures and intermolecular interactions. 相似文献
27.
Pignatelli P Lenti L Sanguigni V Frati G Simeoni I Gazzaniga PP Pulcinelli FM Violi F 《American journal of physiology. Heart and circulatory physiology》2003,284(1):H41-H48
Carnitine is a physiological cellular constituent that favors intracellular fatty acid transport, whose role on platelet function and O(2) free radicals has not been fully investigated. The aim of this study was to seek whether carnitine interferes with arachidonic acid metabolism and platelet function. Carnitine (10-50 microM) was able to dose dependently inhibit arachidonic acid incorporation into platelet phospholipids and agonist-induced arachidonic acid release. Incubation of platelets with carnitine dose dependently inhibited collagen-induced platelet aggregation, thromboxane A(2) formation, and Ca(2+) mobilization, without affecting phospholipase A(2) activation. Furthermore, carnitine inhibited platelet superoxide anion (O(2)(-)) formation elicited by arachidonic acid and collagen. To explore the underlying mechanism, arachidonic acid-stimulated platelets were incubated with NADPH. This study showed an enhanced platelet O(2)(-) formation, suggesting a role for NADPH oxidase in arachidonic acid-mediated platelet O(2)(-) production. Incubation of platelets with carnitine significantly reduced arachidonic acid-mediated NADPH oxidase activation. Moreover, the activation of protein kinase C was inhibited by 50 microM carnitine. This study shows that carnitine inhibits arachidonic acid accumulation into platelet phospholipids and in turn platelet function and arachidonic acid release elicited by platelet agonists. 相似文献
28.
Monica Gomaraschi Alice Ossoli Silvia Pozzi Peter Nilsson Angelo B. Cefalù Maurizio Averna Jan Albert Kuivenhoven G. Kees Hovingh Fabrizio Veglia Guido Franceschini Laura Calabresi 《PloS one》2014,9(5)
Mutations in the CETP gene resulting in defective CETP activity have been shown to cause remarkable elevations of plasma HDL-C levels, with the accumulation in plasma of large, buoyant HDL particles enriched in apolipoprotein E. Genetic CETP deficiency thus represents a unique tool to evaluate how structural alterations of HDL impact on HDL atheroprotective functions. Aim of the present study was to assess the ability of HDL obtained from CETP-deficient subjects to protect endothelial cells from the development of endothelial dysfunction. HDL isolated from one homozygous and seven heterozygous carriers of CETP null mutations were evaluated for their ability to down-regulate cytokine-induced cell adhesion molecule expression and to promote NO production in cultured endothelial cells. When compared at the same protein concentration, HDL and HDL3 from carriers proved to be as effective as control HDL and HDL3 in down-regulating cytokine-induced VCAM-1, while carrier HDL2 were more effective than control HDL2 in inhibiting VCAM-1 expression. On the other hand, HDL and HDL fractions from carriers of CETP deficiency were significantly less effective than control HDL and HDL fractions in stimulating NO production, due to a reduced eNOS activating capacity, likely because of a reduced S1P content. In conclusion, the present findings support the notion that genetic CETP deficiency, by affecting HDL particle structure, impacts on HDL vasculoprotective functions. Understanding of these effects might be important for predicting the outcomes of pharmacological CETP inhibition. 相似文献
29.
Pavan S Schiavulli A Appiano M Marcotrigiano AR Cillo F Visser RG Bai Y Lotti C Ricciardi L 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2011,123(8):1425-1431
The powdery mildew disease affects several crop species and is also one of the major threats for pea (Pisum sativum L.) cultivation all over the world. The recessive gene er1, first described over 60 years ago, is well known in pea breeding, as it still maintains its efficiency as a powdery mildew
resistance source. Genetic and phytopathological features of er1 resistance are similar to those of barley, Arabidopsis, and tomato mlo powdery mildew resistance, which is caused by the loss of function of specific members of the MLO gene family. Here, we describe the obtainment of a novel er1 resistant line by experimental mutagenesis with the alkylating agent diethyl sulfate. This line was found to carry a single
nucleotide polymorphism in the PsMLO1 gene sequence, predicted to result in premature termination of translation and a non-functional protein. A cleaved amplified
polymorphic sequence (CAPS) marker was developed on the mutation site and shown to be fully co-segregating with resistance
in F2 individuals. Sequencing of PsMLO1 from three powdery mildew resistant cultivars also revealed the presence of loss-of-function mutations. Taken together, results
reported in this study strongly indicate the identity between er1 and mlo resistances and are expected to be of great breeding importance for the development of resistant cultivars via marker-assisted
selection. 相似文献
30.
Peripheral blood and tissue eosinophilia characterize trichinellosis in humans, and present in addition to the increased total IgE levels that occur in many helminth infections. Both processes are the consequence of T-helper 2 activation. Blood and tissue eosinophilia begins with eosinophilopoiesis in the bone marrow, which is followed by the migration of eosinophils through the circulatory system, the eosinophil infiltration of tissues at the inflammatory foci and, finally, degranulation and cell death. Recently, some aspects of eosinophilia caused by Trichinella spiralis infection have been elucidated; however, the protective role of this population of cells against Trichinella parasites remains controversial. Furthermore, when eosinophils are numerous, they can be toxic for host tissues. This review discusses these issues in both human and rodent infection models. 相似文献