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81.
Abel Viejo-Borbolla Nadia Martinez-Mart��n Hendrik J. Nel Patricia Rueda Roc��o Mart��n Soledad Blanco Fernando Arenzana-Seisdedos Marcus Thelen Padraic G. Fallon Antonio Alcam�� 《PLoS pathogens》2012,8(2)
Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell-binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses. 相似文献
82.
Mochida GH Ganesh VS Felie JM Gleason D Hill RS Clapham KR Rakiec D Tan WH Akawi N Al-Saffar M Partlow JN Tinschert S Barkovich AJ Ali B Al-Gazali L Walsh CA 《American journal of human genetics》2010,87(6):882-889
The tight junction, or zonula occludens, is a specialized cell-cell junction that regulates epithelial and endothelial permeability, and it is an essential component of the blood-brain barrier in the cerebrovascular endothelium. In addition to functioning as a diffusion barrier, tight junctions are also involved in signal transduction. In this study, we identified a homozygous mutation in the tight-junction protein gene JAM3 in a large consanguineous family from the United Arab Emirates. Some members of this family had a rare autosomal-recessive syndrome characterized by severe hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Their clinical presentation overlaps with some reported cases of pseudo-TORCH syndrome as well as with cases involving mutations in occludin, another component of the tight-junction complex. However, massive intracranial hemorrhage distinguishes these patients from others. Homozygosity mapping identified the disease locus in this family on chromosome 11q25 with a maximum multipoint LOD score of 6.15. Sequence analysis of genes in the candidate interval uncovered a mutation in the canonical splice-donor site of intron 5 of JAM3. RT-PCR analysis of a patient lymphoblast cell line confirmed abnormal splicing, leading to a frameshift mutation with early termination. JAM3 is known to be present in vascular endothelium, although its roles in cerebral vasculature have not been implicated. Our results suggest that JAM3 is essential for maintaining the integrity of the cerebrovascular endothelium as well as for normal lens development in humans. 相似文献
83.
Nadia Z. Dimetry A.M.E. Abd El-Salam F.M.A. El-Hawary 《Archives Of Phytopathology And Plant Protection》2013,46(7):700-711
Field evaluation of some botanical formulations like Neem Azal T/S, Neem Azal T/S + TS/fort and petroleum ether extract of Curcuma longa for the management of different pests attacking broad bean crop in a new reclaimed area at El- Noubaria and under storage conditions has been carried out. All tested formulations could be considered efficient in controlling Aphis craccivora infesting broad bean under field conditions. As to the leafminer, the number of living Liriomyza trifolii larvae decreased significantly compared to non-treated control. The number of living larvae continued to decrease until seven days post-treatment after which an increase in their number was noticed after 14 days post-treatment. Neem Azal T/S + additive (TS/fort) ranked first in comparison to other treatments for the control of aphids and leafminers attacking broad bean in the field either by killing, deterrent or antifeedant effect. The yield of treated crop increased significantly in comparison to the control. Another spray was used before harvesting the crop with the same formulations for protection of the stored crop. Neem Azal T/S with adjuvant (TS/fort) protected broad bean seeds from weevil attack for one year. Petroleum ether extract of C. longa could protect the stored crops for two months only. The percentage weight loss in one kg stored seeds treated in the field with Neem formulation + adjuvant was very small compared with those seeds treated with petroleum ether extract of C. longa and control. 相似文献
84.
Identification of interferon-stimulated gene 15 as an antiviral molecule during Sindbis virus infection in vivo 下载免费PDF全文
Lenschow DJ Giannakopoulos NV Gunn LJ Johnston C O'Guin AK Schmidt RE Levine B Virgin HW 《Journal of virology》2005,79(22):13974-13983
The innate immune response, and in particular the alpha/beta interferon (IFN-alpha/beta) system, plays a critical role in the control of viral infections. Interferons alpha and beta exert their antiviral effects through the induction of hundreds of interferon-induced (or -stimulated) genes (ISGs). While several of these ISGs have characterized antiviral functions, their actions alone do not explain all of the effects mediated by IFN-alpha/beta. To identify additional IFN-induced antiviral molecules, we utilized a recombinant chimeric Sindbis virus to express selected ISGs in IFN-alpha/beta receptor (IFN-alpha/betaR)(-/-) mice and looked for attenuation of Sindbis virus infection. Using this approach, we identified a ubiquitin homolog, interferon-stimulated gene 15 (ISG15), as having antiviral activity. ISG15 expression protected against Sindbis virus-induced lethality and decreased Sindbis virus replication in multiple organs without inhibiting the spread of virus throughout the host. We establish that, much like ubiquitin, ISG15 requires its C-terminal LRLRGG motif to form intracellular conjugates. Finally, we demonstrate that ISG15's LRLRGG motif is also required for its antiviral activity. We conclude that ISG15 can be directly antiviral. 相似文献
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Differential toxicity of TAR DNA‐binding protein 43 isoforms depends on their submitochondrial localization in neuronal cells 下载免费PDF全文
Illari Salvatori Alberto Ferri Silvia Scaricamazza Ilaria Giovannelli Alessia Serrano Simona Rossi Nadia D'Ambrosi Mauro Cozzolino Andrea Di Giulio Sandra Moreno Cristiana Valle Maria Teresa Carrì 《Journal of neurochemistry》2018,146(5):585-597
88.
Nadia Formicola Jeshlee Vijayakumar Florence Besse 《Traffic (Copenhagen, Denmark)》2019,20(9):639-649
Membrane‐less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing and rapid response to environmental fluctuations. These features are particularly important in the context of neuronal cells, where synapse‐specific activation, or localized extracellular cues, induce signaling events restricted to specialized axonal or dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, or granules, are nonmembrane bound macromolecular condensates that concentrate specific sets of mRNAs and regulatory proteins, promoting their long‐distance transport to axons or dendrites. Neuronal RNP granules also have a dual function in regulating the translation of associated mRNAs: while preventing mRNA translation at rest, they fuel local protein synthesis upon activation. As revealed by recent work, rapid and reversible switches between these two functional modes are triggered by modifications of the networks of interactions underlying RNP granule assembly. Such flexible properties also come with a cost, as neuronal RNP granules are prone to transition into pathological aggregates in response to mutations, aging, or cellular stresses, further emphasizing the need to better understand the mechanistic principles governing their dynamic assembly and regulation in living systems. 相似文献
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BackgroundThe main behaviour change intervention available for coronary heart disease (CHD) patients is cardiac rehabilitation. There is little recognition of what the active ingredients of behavioural interventions for CHD might be. Using a behaviour change technique (BCT) framework to code existing interventions may help to identify this. The objectives of this systematic review are to determine the effectiveness of CHD behaviour change interventions and how this may be explained by BCT content and structure.ConclusionsBehaviour change interventions for CHD patients appear to have a positive impact on a number of outcomes. Using an existing BCT taxonomy to code the interventions helped us to understand which were the most commonly used techniques, providing information and goal setting, but not the active components of these complex interventions. 相似文献