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81.
82.
Altering the expression kinetics of VP5 results in altered virulence and pathogenesis of herpes simplex virus type 1 in mice 下载免费PDF全文
While many herpes simplex virus (HSV) structural proteins are expressed with strict-late kinetics, the HSV virion protein 5 (VP5) is expressed as a "leaky-late" protein, such that appreciable amounts of VP5 are made prior to DNA replication. Our goal has been to determine if leaky-late expression of VP5 is a requirement for a normal HSV infection. It had been shown previously that recombinant viruses in which the VP5 promoter was replaced with promoters of other kinetic classes (including a strict late promoter) exhibited no alterations in replication kinetics or virus yields in vitro. In contrast, here we report that alterations in pathogenesis were observed when these recombinants were analyzed by experimental infection of mice. Following intracranial inoculation, a recombinant expressing VP5 from a strict-late promoter (U(L)38) exhibited an increased 50% lethal dose and a 10-fold decrease in virus yields in the central nervous system, while a recombinant expressing VP5 from an early (dUTPase) or another leaky-late (VP16) promoter exhibited wild-type neurovirulence. Moreover, following infection of the footpad, changing the expression kinetics of VP5 from leaky-late to strict-late resulted in 100-fold-less virus in the spinal ganglia during the acute infection than produced by either the parent virus or the rescued virus. These data indicate that the precise timing of appearance of the major capsid protein plays a role in the pathogenesis of HSV infections and that changing the expression kinetics has different effects in different cell types and tissues. 相似文献
83.
Hugo Cayuela Pierre Joly Benedikt R. Schmidt Julian Pichenot Eric Bonnaire Pauline Priol Olivier Peyronel Mathias Laville Aurélien Besnard 《Global Change Biology》2017,23(11):4620-4638
Over the last three decades, climate abnormalities have been reported to be involved in biodiversity decline by affecting population dynamics. A growing number of studies have shown that the North Atlantic Oscillation (NAO) influences the demographic parameters of a wide range of plant and animal taxa in different ways. Life history theory could help to understand these different demographic responses to the NAO. Indeed, theory states that the impact of weather variation on a species’ demographic traits should depend on its position along the fast–slow continuum. In particular, it is expected that NAO would have a higher impact on recruitment than on adult survival in slow species, while the opposite pattern is expected occur in fast species. To test these predictions, we used long‐term capture–recapture datasets (more than 15,000 individuals marked from 1965 to 2015) on different surveyed populations of three amphibian species in Western Europe: Triturus cristatus, Bombina variegata, and Salamandra salamandra. Despite substantial intraspecific variation, our study revealed that these three species differ in their position on a slow–fast gradient of pace of life. Our results also suggest that the differences in life history tactics influence amphibian responses to NAO fluctuations: Adult survival was most affected by the NAO in the species with the fastest pace of life (T. cristatus), whereas recruitment was most impacted in species with a slower pace of life (B. variegata and S. salamandra). In the context of climate change, our findings suggest that the capacity of organisms to deal with future changes in NAO values could be closely linked to their position on the fast–slow continuum. 相似文献
84.
Camille V. Chagneau Clmence Massip Nadge Bossuet-Greif Christophe Fremez Jean-Paul Motta Ayaka Shima Cline Besson Pauline Le Faouder Nicolas Cnac Marie-Paule Roth Hlne Coppin Maxime Fontani Patricia Martin Jean-Philippe Nougayrde Eric Oswald 《PLoS pathogens》2021,17(2)
Urinary tract infections (UTIs) are among the most common outpatient infections, with a lifetime incidence of around 60% in women. We analysed urine samples from 223 patients with community-acquired UTIs and report the presence of the cleavage product released during the synthesis of colibactin, a bacterial genotoxin, in 55 of the samples examined. Uropathogenic Escherichia coli strains isolated from these patients, as well as the archetypal E. coli strain UTI89, were found to produce colibactin. In a murine model of UTI, the machinery producing colibactin was expressed during the early hours of the infection, when intracellular bacterial communities form. We observed extensive DNA damage both in umbrella and bladder progenitor cells. To the best of our knowledge this is the first report of colibactin production in UTIs in humans and its genotoxicity in bladder cells. 相似文献
85.
Teresa Sadras Mickaël Martin Kohei Kume Mark E. Robinson Supraja Saravanakumar Gal Lenz Zhengshan Chen Joo Y. Song Tanya Siddiqi Laura Oksa Anne Marie Knapp Jevon Cutler Kadriye Nehir Cosgun Lars Klemm Veronika Ecker Janet Winchester Dana Ghergus Pauline Soulas-Sprauel Markus Müschen 《Molecular cell》2021,81(10):2094-2111.e9
86.
Yunpeng Su Louise Royle Catherine M. Radcliffe David J. Harvey Luisa Martinez-Pomares Pauline M. Rudd 《Biochemical and biophysical research communications》2009,384(4):436-727
The mannose receptor (MR) is a heavily glycosylated endocytic receptor that recognises both mannosylated and sulphated ligands through its C-type lectin domains (CTLDs) and cysteine-rich (CR) domain, respectively. It is widely expressed among different tissues and by certain cell types in vivo. Our previous study suggested that the glycosylation, especially terminal sialylation, regulated the functional specificities of MR. In the current investigation, the distribution of MR among various mouse tissues was studied and the N-linked glycosylation of spleen MR was analysed. Our results showed that spleen expressed the most abundant MR, consistent with its wide distribution in different cell types in this organ. Spleen MR was heterogeneously N-glycosylated. The majority of the glycans were sialylated in the α2 → 6-linkage and both Neu5Ac and Neu5Gc sialic acids were detected. Most glycans were bi-antennary (74%) with ∼22% tri-antennary and most were core fucosylated (68%). About 13% contained α-galactose. In the lung, MR exhibited more terminal sialic acids in the α2 → 3- rather than in the α2 → 6-configuration. Our study provides a profile of MR N-linked glycosylation that will facilitate our understanding of their physiological role on MR biology in vivo. 相似文献
87.
Exposure of HTC rat hepatoma cells to a 33% decrease in extracellular osmolality caused the cytosolic Ca(2+) concentration ([Ca(2+)](i)) to increase transiently by approximately 90 nm. This rise in [Ca(2+)](i) was inhibited strongly by apyrase, grade VII (which has a low ATP/ADPase ratio) but not by apyrase grade VI (which has a high ATP/ADPase ratio) or hexokinase, indicating that extracellular ADP and/or ATP play a role in the [Ca(2+)](i) increase. The hypotonically induced rise in [Ca(2+)](i) was prevented by the prior discharge of the intracellular Ca(2+) store of the cells by thapsigargin. Removal of extracellular Ca(2+) or inhibition of Ca(2+) influx by 1-10 microm Gd(3+) depleted the thapsigargin-sensitive Ca(2+) stores and thereby diminished the rise in [Ca(2+)](i). The hypotonically induced rise in [Ca(2+)](i) was prevented by adenosine 2'-phosphate-5'-phosphate (A2P5P) and pyridoxyl-5'-phosphate-6-azophenyl-2',4'-disulfonate, inhibitors of purinergic P2Y(1) receptors for which ADP is a major agonist. Both inhibitors also blocked the rise in [Ca(2+)](i) elicited by addition of ADP to cells in isotonic medium, whereas A2P5P had no effect on the rise in [Ca(2+)](i) elicited by the addition of the P2Y(2) and P2Y(4) receptor agonist, UTP. HTC cells were shown to express mRNA encoding for rat P2Y(1), P2Y(2), and P2Y(6) receptors. Inhibition of the hypotonically induced rise in [Ca(2+)](i) blocked hypotonically induced K(+) ((86)Rb(+)) efflux, modulated the hypotonically induced efflux of taurine, but had no significant effect on Cl(-) ((125)I-) efflux. The interaction of extracellular ATP and/or ADP with P2Y(1) purinergic receptors therefore plays a role in the response of HTC cells to osmotic swelling but does not account for activation of all the efflux pathways involved in the volume-regulatory response. 相似文献
88.
Leblond CS Heinrich J Delorme R Proepper C Betancur C Huguet G Konyukh M Chaste P Ey E Rastam M Anckarsäter H Nygren G Gillberg IC Melke J Toro R Regnault B Fauchereau F Mercati O Lemière N Skuse D Poot M Holt R Monaco AP Järvelä I Kantojärvi K Vanhala R Curran S Collier DA Bolton P Chiocchetti A Klauck SM Poustka F Freitag CM Waltes R Kopp M Duketis E Bacchelli E Minopoli F Ruta L Battaglia A Mazzone L Maestrini E Sequeira AF Oliveira B Vicente A Oliveira G Pinto D Scherer SW Zelenika D 《PLoS genetics》2012,8(2):e1002521
Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. 相似文献
89.
Summary The ultrastructure of the nerves forming the submucous plexus of cervical and thoracic parts of the trachea was studied in the guinea-pig. Specimens were obtained from 6 animals perfused with warm fixative and from 6 animals in which pieces of trachea were incubated in buffer containing 5-hydroxydopamine before being immersed in cold fixative. Of the two types of axonal terminal identified in the nerves, one contained mainly large dense-cored vesicles, and the second contained numerous small vesicles. In specimens incubated in 5-hydroxydopamine, the small vesicles of the latter terminals exhibited the electron-dense cores which are characteristic of adrenergic axonal terminals. Counts made on perfused specimens showed that, in both the thoracic and cervical parts of the trachea, the density of adrenergic terminals was higher than that of terminals containing mainly large dense-cored vesicles. Overall terminal density was, however, higher in the thoracic than in the cervical part of the trachea, and estimates of nerve size showed that this was associated with the presence in the thoracic plexus of a substantially greater proportion of nerves with less than 6 axons. The possible function of the nerves in the control of the calibre of the submucous blood vessels was discussed. 相似文献
90.
Issam Alamir Céline Niquet-Leridon Philippe Jacolot Camille Rodriguez Martine Orosco Pauline M. Anton Frédéric J. Tessier 《Amino acids》2013,44(6):1441-1449
Milk proteins are frequently used as supplements in fortified foods. However, processing produces chemical changes which likely affect the nutritional advantage. This study was intended to explore the possible difference in digestibility between extruded and non-extruded caseins and how the dietary N ε -carboxymethyllysine (CML) is metabolised. Normal rats were randomized into either an extruded protein diet (EP) or the same with unextruded proteins (UEP), for two periods of 2 weeks at 7 to 9 and 11 to 13 weeks of age. However, no difference in protein digestibility was detected between the two diets, either in young or in adult animals, despite a 9.4-fold higher level of CML and an 8.5-fold higher level of lysinoalanine in the EP than in the UEP. No diet-related changes were observed in plasma CML, either protein bound or free. Amounts of 38 and 48 % of the orally absorbed CML were excreted in urine and faeces, respectively, in UEP-fed rats. Lower rates of excretion were found in the EP-fed rats (23 and 37 %, respectively). A second animal study using a single oral dose of free CML (400 μg/rat) was set up to measure the systemic concentration of CML every hour from 0 to 4 h. It revealed that protein-bound CML was not affected by the oral dose of CML, and the highest free CML level found in the circulation was 600 ng/mL. Extruded proteins, therefore, appear to be well digested, and CML rapidly eliminated. Since its elimination is, however, incomplete, the question of its biodistribution and metabolism remains open. 相似文献