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| Hypoxia stimulates the expression of ma... | Chiropractic and Osteopathy | |
| Background: Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells (VSMC) functions. Macrophage migration inhibitory factor (MIF) is a well known proinflammatory factor, and recent evidence suggests an important role of MIF in the progression of atherosclerosis and restenosis. However, the potential link between hypoxia and MIF in VSMC has not been investigated. The current study was designed to test whether hypoxia could regulate MIF expression in human VSMC. The effect of modulating MIF expression on hypoxia-induced VSMC proliferation and migration was also investigated at the same time. Results: Expression of MIF mRNA and protein was up-regulated as early as 2 hours in cultured human VSMCs after exposed to moderate hypoxia condition (3% O2). The up-regulation of MIF expression appears to be dependent on hypoxia-inducible transcription factor-1?(HIF-1?) since knockdown of HIF-1? inhibits the hypoxia induction of MIF gene and protein expression. The hypoxia induced expression of MIF was attenuated by antioxidant treatment as well as by inhibition of extracellular signal-regulated kinase (ERK). Under moderate hypoxia conditions (3% O2), both cell proliferation and cell migration were increased in VSMC cells. Blocking the MIF by specific small interference RNA to MIF (MIF-shRNA) resulted in the suppression of proliferation and migration of VSMCs. Conclusion: Our results demonstrated that in VSMCs, hypoxia increased MIF gene expression and protein production. The hypoxia-induced HIF-1? activation, reactive oxygen species (ROS) generation and ERK activation might be involved in this response. Both MIF and HIF-1? mediated the hypoxia response of vascular smooth muscle cells, including cell migration and proliferation. |
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| AlphaS1-casein, which is essential for ... | Chiropractic and Osteopathy | |
| Background: Caseins, the main milk proteins, aggregate in the secretory pathway of mammary epithelial cells into large supramolecular structures, casein micelles. The role of individual caseins in this process and the mesostructure of the casein micelle are poorly known. Results: In this study, we investigate primary steps of casein micelle formation in rough endoplasmic reticulum-derived vesicles prepared from rat or goat mammary tissues. The majority of both ?S1- and ?-casein which are cysteine-containing casein was dimeric in the endoplasmic reticulum. Saponin permeabilisation of microsomal membranes in physico-chemical conditions believed to conserve casein interactions demonstrated that rat immature ?-casein is weakly aggregated in the endoplasmic reticulum. In striking contrast, a large proportion of immature ?S1-casein was recovered in permeabilised microsomes when incubated in conservative conditions. Furthermore, a substantial amount of ?S1-casein remained associated with microsomal or post-ER membranes after saponin permeabilisation in non-conservative conditions or carbonate extraction at pH11, all in the presence of DTT. Finally, we show that protein dimerisation via disulfide bond is involved in the interaction of ?S1-casein with membranes. Conclusions: These experiments reveal for the first time the existence of a membrane-associated form of ?S1-casein in the endoplasmic reticulum and in more distal compartments of the secretory pathway of mammary epithelial cells. Our data suggest that ?S1-casein, which is required for efficient export of the other caseins from the endoplasmic reticulum, plays a key role in early steps of casein micelle biogenesis and casein transport in the secretory pathway. |
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| Karyopherin alpha7 (KPNA7), a divergent... | Chiropractic and Osteopathy | |
| Background: Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin ? and importin ?. NLS cargo is recognized by importin ?, which is bound by importin ?. Importin ? mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin ? triggers disassembly of the complex. To date, six importin ? family members, encoded by separate genes, have been described in humans. Results: We sequenced and characterized a seventh member of the importin ? family of transport factors, karyopherin ? 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin ? (IBB) is divergent, and shows stronger binding to importin ? than the IBB domains from of other importin ? family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. Conclusion: KPNA7 is a novel importin ? family member in humans that belongs to the importin ?2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin ? family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation. |
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| HMGA1 down-regulation is crucial for ch... | Chiropractic and Osteopathy | |
| Background: High mobility group A (HMGA) proteins regulate gene transcription through architectural modulation of chromatin and the formation of multi-protein complexes on promoter/enhancer regions. Differential expression of HMGA variants has been found to be important for distinct differentiation processes and deregulated expression was linked to several disorders. Here we used mouse C2C12 myoblasts and C2C12 cells stably over-expressing HMGA1a-eGFP to study the impact of deregulated HMGA1 expression levels on cellular differentiation. Results: We found that induction of the myogenic or osteogenic program of C2C12 cells caused an immediate down-regulation of HMGA1. In contrast to wild type C2C12 cells, an engineered cell line with stable over-expression of HMGA1a-eGFP failed to differentiate into myotubes. Immunolocalization studies demonstrated that sustained HMGA1a-eGFP expression prevented myotube formation and chromatin reorganization that normally accompanies differentiation. Western Blot analyses showed that elevated HMGA1a-eGFP levels affected chromatin composition through either down-regulation of histone H1 or premature expression of MeCP2. RT-PCR analyses further revealed that sustained HMGA1a expression also affected myogenic gene expression and caused either down-regulation of genes such as MyoD, myogenin, Igf1, Igf2, Igfbp1-3 or up-regulation of the transcriptional repressor Msx1. Interestingly, siRNA experiments demonstrated that knock-down of HMGA1a was required and sufficient to reactivate the myogenic program in induced HMGA1a over-expressing cells. Conclusions: Our data demonstrate that HMGA1 down-regulation after induction is required to initiate the myogenic program in C2C12 cells. Sustained HMGA1a expression after induction prevents expression of key myogenic factors. This may be due to specific gene regulation and/or global effects on chromatin. Our data further corroborate that altered HMGA1 levels influence the expression of other chromatin proteins. Thus, HMGA1 is able to establish a specific chromatin composition. This work contributes to the understanding of how differential HMGA1 expression is involved in chromatin organization during cellular differentiation processes and it may help to comprehend effects of HMGA1 over-expression occurring in malign or benign tumours. |
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| Lamellipodium extension and membrane ru... | Chiropractic and Osteopathy | |
| Background: Intracellular membrane traffic is an essential component of the membrane remodeling that supports lamellipodium extension during cell adhesion. The membrane trafficking pathways that contribute to cell adhesion have not been fully elucidated, but recent studies have implicated SNARE proteins. Here, the functions of several SNAREs (SNAP23, VAMP3, VAMP4 and syntaxin13) are characterized during the processes of cell spreading and membrane ruffling. Results: We report the first description of a SNARE complex, containing SNAP23, syntaxin13 and cellubrevin/VAMP3, that is induced by cell adhesion to an extracellular matrix. Impairing the function of the SNAREs in the complex using inhibitory SNARE domains disrupted the recycling endosome, impeded delivery of integrins to the cell surface, and reduced haptotactic cell migration and spreading. Blocking SNAP23 also inhibited the formation of PMA-stimulated, F-actin-rich membrane ruffles; however, membrane ruffle formation was not significantly altered by inhibition of VAMP3 or syntaxin13. In contrast, membrane ruffling, and not cell spreading, was sensitive to inhibition of two SNAREs within the biosynthetic secretory pathway, GS15 and VAMP4. Consistent with this, formation of a complex containing VAMP4 and SNAP23 was enhanced by treatment of cells with PMA. The results reveal a requirement for the function of a SNAP23-syntaxin13-VAMP3 complex in the formation of lamellipodia during cell adhesion and of a VAMP4-SNAP23-containing complex during PMA-induced membrane ruffling. Conclusions: Our findings suggest that different SNARE-mediated trafficking pathways support membrane remodeling during ECM-induced lamellipodium extension and PMA-induced ruffle formation, pointing to important mechanistic differences between these processes. |
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| Message d?intérêt public concernant le ... | Chiroblog | |
| Ne vous laissez pas séduire par un blanchiment de $99.00 offert dans les salons de coiffure ou d’esthétique, ou même dans des marchés aux puces. Ils utilisent du gel et une lampe fabriqués en Chine de très mauvaise qualité. Vous obtiendrez donc un résultat de blanchiment très décevant. voir la suite convert this post to pdf. |
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| Message d?intérêt public : Certaines cl... | Chiroblog | |
| J’ai récemment été étonné de constater que plusieurs cliniques, au Québec, offraient des soins de décompression neuro-vertébrale alors qu?en réalité, il s?agit de traitements de flexion-distraction. La technique « Cox » de flexion-distraction est très répandue en chiropratique et est réalisée grâce à un équipement très différent de celui utilisé en décompression neuro-vertébrale. Mais avant d?entrer dans le [...] |
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| La vérité concernant la décompression n... | Chiroblog | |
| D?abord, il faut que vous sachiez que je suis convaincu que la décompression neurovertébrale peut aider un très grand pourcentage de patients qui souffrent d?une hernie discale, d?un bombement du disque, d?une discopathie causé par la dégénérescence dû à l?arthrose (usure prématurée du disque ou amincissement du disque) et [...] | ||
| Les 7 étapes du blanchiment des dents p... | Chiroblog | |
| SOS Dents Blanches offre un service de blanchiment des dents est à la fine pointe de la technologie, utilisant le même appareil et les même gels blanchissant que les spécialistes utilisent dans leur clinique dentaire. Le blanchiment des dents en 7 étapes Voici comment se déroule le blanchiment des dents de base d’une durée de 15 minutes: Cliquez ici [...] |
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| La Cour de l?Alberta rejette un recours... | Chiroblog | |
| 13 janvier 2010, Edmonton, Alberta. – Dans les motifs de jugement rendu le 11 Janvier 2010, Monsieur le juge Paul Belzil de la Cour l’Alberta a refusé la certification du recours collectif lancé contre le Collège et l’Association des chiropraticiens de l’Alberta (ACAC). L?ACAC a été victorieux sur toutes les questions. L?Honorable Juge Belzil a trouvé [...] |
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| Nouvelle clinique de décompression neur... | Chiroblog | |
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| ACA and NWI Partner to Provide Wellness... | American Chiropractic Association | |
| Legislation Introduced to Include Docto... | American Chiropractic Association | |
| U.S. House Introduces Resolution to Rec... | American Chiropractic Association | |
| NACA Applauds Non-Discrimination in Hea... | American Chiropractic Association | |
| Future Health and the American Chiropra... | American Chiropractic Association | |
