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Train of thought Group

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Search Results For Adobe After Effects (192)



APP can be processed proteolytically via alternative pathways. In the α-secretase pathway, the cleavage occurs within Aβ domain and generates a large, secreted form of APP (APPs) and, therefore, precludes the formation of the amyloidogenic Aβ (20). Cleavages at the N and C termini of Aβ domain by β- and γ-secretase can yield Aβ (21, 22). Proteolytic processing of APP can be regulated by a variety of neurotransmitter receptors, including acetylcholine, serotonin, glutamate, vasopressin, and bradykinin (23). Nitsch et al. (24) found that agonist stimulation of muscarinic receptors by carbachol increased APPs release in transfected cells expressing only M1 and M3 receptor subtypes. Stimulated secretion of APPs by muscarinic receptor activation is accompanied by the reduction of Aβ levels, suggesting a reciprocal relationship between the processing of APP into either a nonamyloidogenic or amyloidogenic pathway (25). The effects of muscarinic M1 and M3 receptors on APP processing are mediated by the phosphoinositide secondary messenger system and protein kinase C (PKC) (26). Activation of PKC with phorbol esters or constitutive up-regulation of PKC in rats results in enhanced secretion of APPs (27, 28), whereas PKC inhibitors block this effect (29, 30). Elevated release of APPs by receptor stimulation is not affected by protein synthesis inhibitors, indicating that preexisting APP is cleaved (31). However, increased APP processing by PKC activation is independent of direct APP phosphorylation, indicating that other proteins are phosphorylated and may be involved in APP processing (32).




Search results for adobe after effects (192)



The role of IVIG sialylation in a mouse model of immune thrombocytopenia (ITP) was recently explored. No role for sialylation in the inhibitory effects of IVIG was found in that therapeutic model (28). In another study, contradictory results were reported in a prophylactic model for ITP (36). We therefore wanted to explore the role of sialylation in other animal models of Ab-driven inflammation, such as the K/BxN serum transfer (K/BxN) (37) and collagen Ab-induced arthritis (CAbIA) (38) models of RA. We examined the effect of IVIG in these two models and evaluated the proposed mechanisms of action. We found that IVIG was protective in a dose-dependent manner in both mouse models of Ab-induced arthritis and that the protective activity resided within the Fc fragment. Similar to our findings in mouse ITP (28), sialylation of IVIG was not required for efficacy. We also found that, in contrast to previous reports in Ab-driven arthritis (35), basophils were not required for the protective effect of IVIG.


Despite some differences between the CAbIA and K/BxN arthritis models, detailed above, we obtained comparable results for the effects of IVIG in the two models. Although we concur that IVIG and IgG Fc, but not Fab, can protect from Ab-induced arthritis, our findings do not support a role for Fc sialylation or basophil involvement in IVIG protection from disease in either model. The choice of model is therefore unlikely to explain our disagreement with the published findings of Ravetch and colleagues. Our data are also derived from multiple laboratories, reducing the chance of laboratory-specific outcomes. Other reasons should therefore be considered including IVIG source, route and time of administration, mouse strain, and experimental setup.


Extracellular vesicles (EVs), which contain microRNA (miRNA), constitute a novel means of cell communication that may contribute to the inevitable expansion of renal fibrosis during diabetic kidney disease (DKD). Exendin-4 is effective for treating DKD through its action on GLP-1R. However, the effect of exendin-4 on EVs miRNA expression and renal cell communication during the development of DKD remains unknown. In this study, we found that EVs derived from exendin-4 and high-glucose (Ex-HG)-pretreated HK-2 cells, which was taken up by normal HK-2 cells, resulted in decreased levels of FN and Col-I compared with those treated with HG pretreated HK-2 cells derived EVs. Furthermore, we found this may contribute to a decrease in miR-192 in both HK-2 cells and EVs after exendin-4 treatment in a p53-dependent manner. Besides, we found that the amelioration of renal fibrosis by exendin-4 occurs through a miR-192-GLP-1R pathway, indicating a new pathway by which exendin-4 regulates GLP-1R. The results of this study suggest that exendin-4 can inhibit the transfer of EVs miR-192 from HG-induced renal tubular epithelial cells to normal cells, thus inhibiting GLP-1R down-regulation and protecting renal cells. This study reports a new mechanism by which exendin-4 exerts a protective effect against DKD.


VAERS is a national passive vaccine safety surveillance system, jointly managed by CDC and FDA, that monitors adverse events after vaccination (7). VAERS accepts reports from anyone, including health care providers, vaccine manufacturers, and members of the public. Symptoms, signs, and diagnostic findings in VAERS reports are assigned Medical Dictionary for Regulatory Activities (MedDRA) preferred terms by VAERS staff members. VAERS reports are classified as serious if any of the following are reported: hospitalization, prolongation of hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death.** Reports of serious adverse events receive follow-up by VAERS staff members to obtain additional information, including medical records. For reports of death, death certificates and autopsy reports are obtained, if available. CDC physicians reviewed all available information for each decedent to form an impression about cause of death. Reports of myocarditis and pericarditis after receipt of COVID-19 vaccine were identified by a search for selected MedDRA preferred terms (7); CDC staff members attempted to collect information about clinical course and recovery related to myocarditis and pericarditis from patients and health care providers.


Using specific BLAST searches in genomic and EST libraries, we found that DAYSLEEPER-like genes (hereafter called SLEEPER genes) are unique to angiosperms. Basal angiosperms as well as grasses (Poaceae) and dicotyledonous plants possess such putative orthologous genes, but SLEEPER-family genes were not found in gymnosperms, mosses and algae. Most species contain more than one SLEEPER gene. All SLEEPERs contain a C2H2 type BED-zinc finger domain and a hATC dimerization domain. We designated 3 motifs, partly overlapping the BED-zinc finger and dimerization domain, which are hallmark features in the SLEEPER family. Although SLEEPER genes are structurally conserved between species, constructs with SLEEPER genes from grapevine and rice did not complement the daysleeper phenotype in Arabidopsis, when expressed under control of the DAYSLEEPER promoter. However these constructs did cause a dominant phenotype when expressed in Arabidopsis. Rice plant lines with an insertion in the RICESLEEPER1 or 2 locus displayed phenotypic abnormalities, indicating that these genes are functional and important for normal development in rice. We suggest a model in which we hypothesize that an ancestral hAT transposase was retrocopied and stably integrated in the genome during early angiosperm evolution. Evidence is also presented for more recent retroposition events of SLEEPER genes, such as an event in the rice genome, which gave rise to the RICESLEEPER1 and 2 genes. 041b061a72


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