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51.
ABSTRACT: BACKGROUND: Understanding the pathogenesis of the chiari-like malformation in the Cavalier King Charles Spaniel (CKCS) is incomplete, and current hypotheses do not fully explain the development of syringomyelia (SM) in the spinal cords of affected dogs. This study investigates an unconventional pathogenetic theory for the development of cerebrospinal fluid (CSF) pressure waves in the subarachnoid space in CKCS with SM, by analogy with human diseases. In children with achondroplasia the shortening of the skull base can lead to a narrowing of the jugular foramina (JF) between the cranial base synchondroses. This in turn has been reported to cause a congestion of the major venous outflow tracts of the skull and consequently to an increase in the intracranial pressure (ICP). Amongst brachycephalic dog breeds the CKCS has been identified as having an extremely short and wide braincase. A stenosis of the JF and a consequential vascular compromise in this opening could contribute to venous hypertension, raising ICP and causing CSF jets in the spinal subarachnoid space of the CKCS. In this study, JF volumes in CKCSs with and without SM were compared to assess a possible role of this pathologic mechanism in the development of SM in this breed. RESULTS: Computed tomography (CT) scans of 40 CKCSs > 4 years of age were used to create three-dimensional (3D) models of the skull and the JF. Weight matched groups (7--10 kg) of 20 CKCSs with SM and 20 CKCSs without SM were compared. CKCSs without SM presented significantly larger JF -volumes (median left JF: 0.0633 cm3; median right JF: 0.0703 cm3; p < 0.0001) when compared with CKCSs with SM (median left JF: 0.0382 cm3; median right JF: 0.0434 cm3; p < 0.0001). There was no significant difference between the left and right JF within each group. Bland-Altman analysis revealed excellent reproducibility of all volume measurements. CONCLUSION: A stenosis of the JF and consecutive venous congestion may explain the aetiology of CSF pressure waves in the subarachnoid space, independent of cerebellar herniation, as an additional pathogenetic factor for the development of SM in this breed. 相似文献
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Laurent S Vander Elst L Thirifays C Muller RN 《European biophysics journal : EBJ》2008,37(6):1007-1014
Nuclear magnetic relaxation dispersion (NMRD) profiles of unilamellar DPPC liposomes incorporating Gd-DTPA-bisamides with alkyl chains of 12 to 18 C atoms in their external and internal layers were recorded in order to study the influence that the chain length and structure of Gd-bisamides incorporated in the liposomal membrane have on their proton relaxivity. The NMRD profiles recorded at 310 K show that the relaxivity reaches a minimum value when the carbon chain lengths of the phospholipid and of the Gd complex match and is at a maximum in the presence of a carbon-carbon double bond. For these DPPC paramagnetic liposomes, the longer the aliphatic chains of the complex, the larger will be its immobilization in the membrane. In addition, the presence of an unsaturated carbon-carbon bond in the alkyl chain of the Gd complex induces an increase of its mobility and of its water exchange rate with, as a result, a much greater efficiency as an MRI contrast agent. 相似文献
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Sylvie Séguier Eric Tartour Coralie Guérin Ludovic Couty Mathilde Lemitre Laetitia Lallement Marysette Folliguet Samah El Naderi Magali Terme Cécile Badoual Antoine Lafont Bernard Coulomb 《PloS one》2013,8(8)
We investigated whether gingival fibroblasts (GFs) can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs) and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM) from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05) inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism. 相似文献
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Nicole J. Lake Bryn D. Webb David A. Stroud Tara R. Richman Benedetta Ruzzenente Alison G. Compton Hayley S. Mountford Juliette Pulman Coralie Zangarelli Marlene Rio Nathalie Boddaert Zahra Assouline Mingma D. Sherpa Eric E. Schadt Sander M. Houten James Byrnes Elizabeth M. McCormick Zarazuela Zolkipli-Cunningham David R. Thorburn 《American journal of human genetics》2018,102(4):713
58.
Nicolas Brucato Veronica Fernandes Stéphane Mazières Pradiptajati Kusuma Murray P. Cox Joseph Wainaina Ng’ang’a Mohammed Omar Marie-Claude Simeone-Senelle Coralie Frassati Farida Alshamali Bertrand Fin Anne Boland Jean-Francois Deleuze Mark Stoneking Alexander Adelaar Alison Crowther Nicole Boivin Luisa Pereira François-Xavier Ricaut 《American journal of human genetics》2018,102(1):58-68
59.
Dawid G. Nowak Elianna Mohamed Amin Emma S. Rennel Coralie Hoareau-Aveilla Melissa Gammons Gopinath Damodoran Masatoshi Hagiwara Steven J. Harper Jeanette Woolard Michael R. Ladomery David O. Bates 《The Journal of biological chemistry》2010,285(8):5532-5540
Vascular endothelial growth factor (VEGF) is produced either as a pro-angiogenic or anti-angiogenic protein depending upon splice site choice in the terminal, eighth exon. Proximal splice site selection (PSS) in exon 8 generates pro-angiogenic isoforms such as VEGF165, and distal splice site selection (DSS) results in anti-angiogenic isoforms such as VEGF165b. Cellular decisions on splice site selection depend upon the activity of RNA-binding splice factors, such as ASF/SF2, which have previously been shown to regulate VEGF splice site choice. To determine the mechanism by which the pro-angiogenic splice site choice is mediated, we investigated the effect of inhibition of ASF/SF2 phosphorylation by SR protein kinases (SRPK1/2) on splice site choice in epithelial cells and in in vivo angiogenesis models. Epithelial cells treated with insulin-like growth factor-1 (IGF-1) increased PSS and produced more VEGF165 and less VEGF165b. This down-regulation of DSS and increased PSS was blocked by protein kinase C inhibition and SRPK1/2 inhibition. IGF-1 treatment resulted in nuclear localization of ASF/SF2, which was blocked by SPRK1/2 inhibition. Pull-down assay and RNA immunoprecipitation using VEGF mRNA sequences identified an 11-nucleotide sequence required for ASF/SF2 binding. Injection of an SRPK1/2 inhibitor reduced angiogenesis in a mouse model of retinal neovascularization, suggesting that regulation of alternative splicing could be a potential therapeutic strategy in angiogenic pathologies. 相似文献
60.
Coralie E. Salesse‐Smith Robert E. Sharwood Florian A. Busch David B. Stern 《Plant biotechnology journal》2020,18(6):1409-1420
Many C4 plants, including maize, perform poorly under chilling conditions. This phenomenon has been linked in part to decreased Rubisco abundance at lower temperatures. An exception to this is chilling‐tolerant Miscanthus, which is able to maintain Rubisco protein content under such conditions. The goal of this study was to investigate whether increasing Rubisco content in maize could improve performance during or following chilling stress. Here, we demonstrate that transgenic lines overexpressing Rubisco large and small subunits and the Rubisco assembly factor RAF1 (RAF1‐LSSS), which have increased Rubisco content and growth under control conditions, maintain increased Rubisco content and growth during chilling stress. RAF1‐LSSS plants exhibited 12% higher CO2 assimilation relative to nontransgenic controls under control growth conditions, and a 17% differential after 2 weeks of chilling stress, although assimilation rates of all genotypes were ~50% lower in chilling conditions. Chlorophyll fluorescence measurements showed RAF1‐LSSS and WT plants had similar rates of photochemical quenching during chilling, suggesting Rubisco may not be the primary limiting factor that leads to poor performance in maize under chilling conditions. In contrast, RAF1‐LSSS had improved photochemical quenching before and after chilling stress, suggesting that increased Rubisco may help plants recover faster from chilling conditions. Relatively increased leaf area, dry weight and plant height observed before chilling in RAF1‐LSSS were also maintained during chilling. Together, these results demonstrate that an increase in Rubisco content allows maize plants to better cope with chilling stress and also improves their subsequent recovery, yet additional modifications are required to engineer chilling tolerance in maize. 相似文献