| 1. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 2. |
- Aad, G., et al.
(författare)
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- 2013
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Khatib Shahidi, Roxana, et al.
(författare)
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Adult mice are unresponsive to AAV8-Gremlin1 gene therapy targeting the liver
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective Gremlin 1 (GREM1) is a secreted BMP2/4 inhibitor which regulates commitment and differentiation of human adipose precursor cells and prevents the browning effect of BMP4. GREM1 is an insulin antagonist and serum levels are high in type 2 diabetes (T2D). We here examined in vivo effects of AAV8 (Adeno-Associated Viral vectors of serotype eight) GREM 1 targeting the liver in mature mice to increase its systemic secretion and also, in a separate study, injected recombinant GREM 1 intraperitoneally. The objective was to characterize systemic effects of GREM 1 on insulin sensitivity, glucose tolerance, body weight, adipose cell browning and other local tissue effects. Methods Adult mice were injected with AAV8 vectors expressing GREM1 in the liver or receiving regular intra-peritoneal injections of recombinant GREM1 protein. The mice were fed with a low fat or high fat diet (HFD) and followed over time. Results Liver-targeted AAV8-GREM1 did not alter body weight, whole-body glucose and insulin tolerance, or adipose tissue gene expression. Although GREM1 protein accumulated in liver cells, GREM1 serum levels were not increased suggesting that it may not have been normally processed for secretion. Hepatic lipid accumulation, inflammation and fibrosis were also not changed. Repeated intraperitoneal rec-GREM1 injections for 5 weeks were also without effects on body weight and insulin sensitivity. UCP1 was slightly but significantly reduced in both white and brown adipose tissue but this was not of sufficient magnitude to alter body weight. We validated that recombinant GREM1 inhibited BMP4-induced pSMAD1/5/9 in murine cells in vitro, but saw no direct inhibitory effect on insulin signalling and pAkt (ser 473 and thr 308) activation. Conclusion GREM1 accumulates intracellularly when overexpressed in the liver cells of mature mice and is apparently not normally processed/secreted. However, also repeated intraperitoneal injections were without effects on body weight and insulin sensitivity and adipose tissue UCP1 levels were only marginally reduced. These results suggest that mature mice do not readily respond to GREMLIN 1 but treatment of murine cells with GREMLIN 1 protein in vitro validated its inhibitory effect on BMP4 signalling while insulin signalling was not altered.
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| 4. |
- Aad, G., et al.
(författare)
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- 2013
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :7
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Pinheiro, ET, et al.
(författare)
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Analysis of genotypic variation in genes associated with virulence in Aggregatibacter actinomycetemcomitans clinical isolates
- 2011
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Ingår i: Journal of Periodontal Research. - : Wiley. - 1600-0765 .- 0022-3484. ; 46:3, s. 310-317
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background and Objective: Although certain serotypes of Aggregatibacter actinomycetemcomitans are associated more with aggressive periodontitis than are other serotypes, the correlation between distinct lineages and virulence traits in this species is poorly understood. This study aimed to evaluate the polymorphism of genes encoding putative virulence factors of clinical isolates, and to correlate these findings with A. actinomycetemcomitans serotypes, genotypes and periodontal status of the hosts. Material and Methods: Twenty-six clinical isolates from diverse geographic populations with different periodontal conditions were evaluated. Genotyping was performed using pulse-field gel electrophoresis. Polymorphisms in the genes encoding leukotoxin, Aae, ApaH and determinants for serotype-specific O polysaccharide were investigated. Results: The isolates were classified into serotypes a–f, and exhibited three apaH genotypes, five aae alleles and 25 macrorestriction profiles. Two serotype b isolates (7.7%), obtained from Brazilian patients with aggressive periodontitis, were associated with the highly leukotoxic genotype; these isolates showed identical fingerprint patterns and aae and apaH genotypes. Serotype c, obtained from various periodontal conditions, was the most prevalent among Brazilian isolates, and isolates were distributed in two aae alleles, but formed a genetically distinct group based on apaH analysis. Cluster analysis showed a close relationship between fingerprinting genotypes and serotypes/apaH genotypes, but not with aae genotypes. Conclusion: Apart from the deletion in the ltx promoter region, no disease-associated markers were identified. Non-JP2-like strains recovered from individuals with periodontal disease exhibited considerable genetic variation regarding aae/apaH genotypes, serotypes and XhoI DNA fingerprints.
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| 6. |
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| 7. |
- Scuteri, Angelo, et al.
(författare)
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Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications.
- 2011
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Ingår i: Journal of Hypertension. - 1473-5598. ; 29, s. 1469-1477
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Tidskriftsartikel (refereegranskat)abstract
- Loss of cognitive function and hypertension are two common conditions in the elderly and both significantly contribute to loss of personal independency. Microvascular brain damage - the result of age-associated alteration in large arteries and the progressive mismatch of their cross-talk with small cerebral arteries - represents a potent risk factor for cognitive decline and for the onset of dementia in older individuals. The present review discusses the complexity of factors linking large artery to microvascular brain disease and to cognitive decline and the evidence for possible clinical markers useful for prevention of this phenomenon. The possibility of dementia prevention by cardiovascular risk factors control has not been demonstrated. In the absence of research clinical trials specifically and primarily designed to demonstrate the antihypertensive treatment efficacy for reducing the risk of dementia, further evidence demonstrating that it is possible to limit the progression of microvascular brain damage is needed.
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| 8. |
- Pinheiro de Lima, Edson, et al.
(författare)
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Understanding todays' operations performance measurement systems use
- 2011
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Ingår i: International Conference on Production Research (ICPR 21) : Innovation in Product and Production, July 31 - August 4, 2011 in Stuttgart, Germany; Conference Proceedings.
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Konferensbidrag (refereegranskat)abstract
- Contingency factors and globalization phenomena are forcing companies to revise the way theyconceive and manage their operations network. Operations strategic management systems shoulddevelop specific design requirements to deal with a complex and changing environment, that is,operations strategy plans should be continuously assed and updated. This paper frame a discussionbased on operations strategy and performance measurement framework. Performancemeasurement roles are revised in order to assess their alignment to new design requirements foroperations strategic management. Based on a set of updated performance measurement systemsroles, a case study protocol is developed and applied to manufacturing and service companies.Although classical roles as performance monitoring and control are still the main focus ofoperations performance measurement systems, evidences collected show a growing use of thesemanagement systems for continuous improvement and change management processes.
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| 9. |
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| 10. |
- Algaba Brazalez, Astrid, 1983, et al.
(författare)
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Improving microstrip filters with gap waveguide packaging
- 2011
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Ingår i: Proceedings of the 5th European Conference on Antennas and Propagation, EUCAP 2011. Rome, 11-15 April 2011. - 9781457702501 ; , s. 1080-1084
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Konferensbidrag (refereegranskat)abstract
- A study is presented of the performance of microstrip filters packaged with Perfect Magnetic Conductor (PMC) and realization of the PMC using a lid of nails. A 3rd order parallel coupled-line bandpass filter is designed and packaged with a lid of nails at the Ku-band. The study shows the PMC packaging technique is very efficient in improving the filter characteristics including the insertion loss in the bandpass region.
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