| 1. |
|
|
| 2. |
- Lu, Lingyi, et al.
(författare)
-
Chromosomes 4 and 8 implicated in a genome wide SNP linkage scan of 762 prostate cancer families collected by the ICPCG
- 2012
-
Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 72:4, s. 410-426
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer (PC) remains largely incomplete. In a previous microsatellite-based linkage scan of 1,233 PC families, we identified suggestive evidence for linkage (i.e., LOD?=?1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. METHODS. In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 International Consortium for Prostate Cancer Genetics (ICPCG) groups. RESULTS. Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD cores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. CONCLUSIONS. These results will be useful in prioritizing future susceptibility gene discovery efforts in thiscommon cancer. Prostate 72: 410-426, 2012. (C) 2011 Wiley Periodicals, Inc.
|
|
| 3. |
- Teerlink, Craig C., et al.
(författare)
-
Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease
- 2014
-
Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 133:3, s. 347-356
-
Tidskriftsartikel (refereegranskat)abstract
- Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p a parts per thousand currency sign 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Carra, Serena, et al.
(författare)
-
The growing world of small heat shock proteins : from structure to functions
- 2017
-
Ingår i: Cell Stress and Chaperones. - : Springer Science and Business Media LLC. - 1355-8145 .- 1466-1268. ; 22:4, s. 601-611
-
Tidskriftsartikel (refereegranskat)abstract
- Small heat shock proteins (sHSPs) are present in all kingdoms of life and play fundamental roles in cell biology. sHSPs are key components of the cellular protein quality control system, acting as the first line of defense against conditions that affect protein homeostasis and proteome stability, from bacteria to plants to humans. sHSPs have the ability to bind to a large subset of substrates and to maintain them in a state competent for refolding or clearance with the assistance of the HSP70 machinery. sHSPs participate in a number of biological processes, from the cell cycle, to cell differentiation, from adaptation to stressful conditions, to apoptosis, and, even, to the transformation of a cell into a malignant state. As a consequence, sHSP malfunction has been implicated in abnormal placental development and preterm deliveries, in the prognosis of several types of cancer, and in the development of neurological diseases. Moreover, mutations in the genes encoding several mammalian sHSPs result in neurological, muscular, or cardiac age-related diseases in humans. Loss of protein homeostasis due to protein aggregation is typical of many age-related neurodegenerative and neuromuscular diseases. In light of the role of sHSPs in the clearance of un/misfolded aggregation-prone substrates, pharmacological modulation of sHSP expression or function and rescue of defective sHSPs represent possible routes to alleviate or cure protein conformation diseases. Here, we report the latest news and views on sHSPs discussed by many of the world’s experts in the sHSP field during a dedicated workshop organized in Italy (Bertinoro, CEUB, October 12–15, 2016).
|
|
| 7. |
- Kakkar, Vaishali, et al.
(författare)
-
The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model
- 2016
-
Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765. ; 62:2, s. 272-283
-
Tidskriftsartikel (refereegranskat)abstract
- Expanded CAG repeats lead to debilitating neurodegenerative disorders characterized by aggregation of proteins with expanded polyglutamine (polyQ) tracts. The mechanism of aggregation involves primary and secondary nucleation steps. We show how a noncanonical member of the DNAJ-chaperone family, DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by suppressing primary nucleation. This inhibition is mediated by a serine/threonine-rich region that provides an array of surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bonds essential for the stability of amyloid fibrils. Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and leads to delayed neurite retraction even before aggregates are visible. In a mouse model, brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifespan, pointing to DNAJB6 as a potential target for disease therapy and tool for unraveling early events in the onset of polyQ diseases. Kakkar et al. show that DNAJB6 is a chaperone that inhibits early steps in the formation of polyQ amyloid fibrils. An S/T-rich region in DNAJB6 is crucial for this function. In a polyQ mouse model, the inhibitory effects of DNAJB6 delay disease onset and increase lifespan.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Palmquist, Anders, 1977, et al.
(författare)
-
Calcium Aluminate Coated and Uncoated Free Form Fabricated CoCr Implants : A Comparative Study in Rabbit
- 2009
-
Ingår i: Journal of Biomedical Materials Research - Part B Applied Biomaterials. - : Wiley. - 1552-4973 .- 1552-4981. ; 91B:1, s. 122-127
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to compare the integration in bone of uncoated free form fabricated cobalt chromium (CoCr) implants to the same implant with a calcium aluminate coating. The implants of cylindrical design with a pyramidal surface structure were press-fit into the limbs of New Zealand white rabbits. After 6 weeks, the rabbits were sacrificed, and samples were retrieved and embedded. Ground sections were subjected to histological analysis and histomorphometry. The section counter part was used for preparing an electron transparent transmission electron microscopy sample by focused ion beam milling. Calcium aluminate dip coating provided a significantly greater degree of bone contact than that of the native CoCr. The gibbsite hydrate formed in the hardening reaction of the calcium aluminate was found to be the exclusive crystalline phase material in direct contact with bone.
|
|
