| 1. |
- Al-Eryani, Yusra, et al.
(författare)
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Exploring structure and interactions of the bacterial adaptor protein YjbH by crosslinking mass spectrometry
- 2016
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Ingår i: Proteins: Structure, Function and Genetics. - : Wiley. - 0887-3585. ; 84:9, s. 1234-1245
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Tidskriftsartikel (refereegranskat)abstract
- Adaptor proteins assist proteases in degrading specific proteins under appropriate conditions. The adaptor protein YjbH promotes the degradation of an important global transcriptional regulator Spx, which controls the expression of hundreds of genes and operons in response to thiol-specific oxidative stress in Bacillus subtilis. Under normal growth conditions, the transcription factor is bound to the adaptor protein and therefore degraded by the AAA+ protease ClpXP. If this binding is alleviated during stress, the transcription factor accumulates and turns on genes encoding stress-alleviating proteins. The adaptor protein YjbH is thus a key player involved in these interactions but its structure is unknown. To gain insight into its structure and interactions we have used chemical crosslinking mass spectrometry. Distance constraints obtained from the crosslinked monomer were used to select and validate a structure model of YjbH and then to probe its interactions with other proteins. The core structure of YjbH is reminiscent of DsbA family proteins. One lysine residue in YjbH (K177), located in one of the α-helices outside the thioredoxin fold, crosslinked to both Spx K99 and Spx K117, thereby suggesting one side of the YjbH for the interaction with Spx. Another lysine residue that crosslinked to Spx was YjbH K5, located in the long and presumably very flexible N-terminal arm of YjbH. Our crosslinking data lend support to a model proposed based on site-directed mutagenesis where the YjbH interaction with Spx can stabilize and present the C-terminal region of Spx for protease recognition and proteolysis. Proteins 2016; 84:1234–1245.
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| 2. |
- Billings, LK, et al.
(författare)
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Impact of common variation in bone-related genes on type 2 diabetes and related traits
- 2012
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 61:8, s. 2176-2186
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Tidskriftsartikel (refereegranskat)abstract
- Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r2 > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post–oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations.
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| 3. |
- Boelt, Sanne Grundvad, et al.
(författare)
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Mapping the Ca2 + induced structural change in calreticulin
- 2016
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 142, s. 138-148
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Tidskriftsartikel (refereegranskat)abstract
- Calreticulin is a highly conserved multifunctional protein implicated in many different biological systems and has therefore been the subject of intensive research. It is primarily present in the endoplasmatic reticulum where its main functions are to regulate Ca2 + homeostasis, act as a chaperone and stabilize the MHC class I peptide-loading complex. Although several high-resolution structures of calreticulin exist, these only cover three-quarters of the entire protein leaving the extended structures unsolved. Additionally, the structure of calreticulin is influenced by the presence of Ca2 +. The conformational changes induced by Ca2 + have not been determined yet as they are hard to study with traditional approaches. Here, we investigated the Ca2 +-induced conformational changes with a combination of chemical cross-linking, mass spectrometry, bioinformatics analysis and modelling in Rosetta. Using a bifunctional linker, we found a large Ca2 +-induced change to the cross-linking pattern in calreticulin. Our results are consistent with a high flexibility in the P-loop, a stabilization of the acidic C-terminal and a relatively close interaction of the P-loop and the acidic C-terminal. Biological significance The function of calreticulin, an endoplasmatic reticulin chaperone, is affected by fluctuations in Ca2 + concentration, but the structural mechanism is unknown. The present work suggests that Ca2 +-dependent regulation is caused by different conformations of a long proline-rich loop that changes the accessibility to the peptide/lectin-binding site. Our results indicate that the binding of Ca2 + to calreticulin may thus not only just be a question of Ca2 + storage but is likely to have an impact on the chaperone activity.
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| 4. |
- Buch-Rasmussen, Thomas
(creator_code:cre_t)
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Coating system providing low friction
- 1999
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Patent (övrigt vetenskapligt/konstnärligt)abstract
- The present invention relates to a coating system, in particular to a coating system for articles where plastic materials slide against flexible rubber materials. The coating system is a silicone oil based coating having a viscosity of at least 200,000 centistokes, i.e. a high viscosity coating. The coating comprises in a preferred embodiment a silicone oil based block or graft copolymer, or segmented copolymer. Further the invention relates to a process of producing a component of an article coated as described above, comprising adding the coating material to the component material prior to molding and subsequently molding the component from the mixture, or molding the component from the component material and subsequently applying the coating material to the at least one surface of the component, as well as an article coated with a silicone oil based coating as defined above. Such an article is preferably a medical article, such as a container or an injection cylinder and a stopper. The coatings according to the present invention are especially suited to use for permanently coating internal surfaces of containers equipped with stoppers for storage and administration of liquid protein preparations. The coatings providing low friction between the two components, such as a container wall and a rubber stopper, result in high-precision dosing. The described coatings are particularly useful for coating containers for storage and administration of liquid protein solutions, such as insulin formulations.
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| 5. |
- Dahlstrand, Ursula, et al.
(författare)
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Primary patency of percutaneously inserted self-expanding metallic stents in patients with malignant biliary obstruction
- 2009
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Ingår i: HPB : the official journal of the International Hepato Pancreato Biliary Association. - : Elsevier BV. - 1365-182X. ; 11:4, s. 358-63
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Effective bile duct drainage is crucial to the health-related quality of life of patients with jaundice caused by obstruction of the bile duct by inoperable malignant tumours. METHODS: All patients who were treated at Uppsala University Hospital, Sweden with percutaneous stenting between 2000 and 2005 were identified retrospectively. Data on the location of the obstruction and type of stent used, date and cause of death and date of stent failure were abstracted from the patients' notes. Stent patency was defined as the duration from the insertion of the stent to the date of failure. In cases in which the cause of death was directly related to failure of the stent, the date of death was defined as the patency endpoint. RESULTS: A total of 64 patients (34 women, 30 men) were identified. Their mean age was 71 years (standard deviation 11 years). The median length of patency was 11.4 months. Stent diameter >10 mm and distal stricture were found to be associated with significantly longer patency time in univariate Cox proportional hazard analysis. In multivariate Cox proportional hazard analysis, only location of the stricture was found to be independently and significantly associated with patency time. DISCUSSION: Percutaneous stenting is a good alternative for patients with obstructive jaundice and a life expectancy /=10 mm. However, patency time was found to be lower for hilar tumours.
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| 6. |
- Darkahi, Bahman, et al.
(författare)
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Biliary Microflora in Patients Undergoing Cholecystectomy
- 2014
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Ingår i: Surgical Infections. - : Mary Ann Liebert Inc. - 1096-2964 .- 1557-8674. ; 15:3, s. 262-265
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Tidskriftsartikel (refereegranskat)abstract
- Background: The management of acute cholecystitis requires a sound knowledge of the biliary microflora. Methods: Bile samples were taken for culture according to a standard routine during all cholecystectomies performed from April 2007 to February 2009 in the Department of Surgery at Enkoping Hospital. The use of antibiotics within the 3-mo period before surgery, indication for surgery, prophylactic antibiotics, and post-operative complications were recorded prospectively. Results: Altogether, 246 procedures were performed during the study period, of which 149 (62%) were done on women. The mean (SD) age of the study subjects was 49 +/- 16y. Bacterial growth was seen in cultures from 34 (14%) of the subjects. The mean age of subjects with positive cultures was 64y and that of subjects with negative cultures was 47y (p<0.001). Positive culture was seen in 16 (31%) of the 51 patients who underwent operations for acute cholecystitis, whereas positive cultures were obtained in 18 of 195 patients without acute cholecystitis (9%) (p<0.001). Resistance to ampicillin was recorded in three of 34 (9%) of the cultures with bacterial growth, to co-trimoxazole in one of the 34 (3%) cultures, to fluoroquinolones in one of the 34 (3%) cultures, and to cephalosporins in one of the 34 (3%) cultures. Resistance to piperacillin-tazobactam was not observed in any of the cultures. In multivariable logistic regression analysis, a positive culture was the only factor significantly associated with risk for post-operative infectious complications (p<0.05). Discussion: Bacterial growth in the bile is observed more often in patients undergoing surgery for acute cholecystitis. The microflora of the bile is probably important for the outcome of surgery, but further studies are required for assessing the effectiveness of measures for preventing infectious post-operative complications.
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| 7. |
- Darkahi, Bahman, et al.
(författare)
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Effectiveness of antibiotic prophylaxis in cholecystectomy : a prospective population-based study of 1171 cholecystectomies
- 2012
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 47:10, s. 1242-1246
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Tidskriftsartikel (refereegranskat)abstract
- Background.The aim of this study was to assess the benefit from antibiotic prophylaxis (AP) during cholecystectomy in a population-based cohort study.Methods.All cholecystectomies performed in Uppsala County, 2003-2005, were registered prospectively according to a standardized protocol. High-risk procedures (HP) were defined as operations for acute cholecystitis and procedures including exploration of the common bile duct. Infections requiring surgical or percutaneous drainage and non-surgical infections that prolonged hospital stay were defined as major infectious complications (IC).Results. Altogether 1171 patients underwent cholecystectomy. AP was given to 130 of 867 (15%) of the patients undergoing low-risk procedures (LP) and 205 of 304 (67%) of those undergoing H-R P. Major IC were seen in 6 of 205 (3%) of the patients undergoing H-R P with AP and 1 of 99 of the patients undergoing H-R P without AP. No major IC was seen after L-R P. Minor IC were seen after 5 of 205 (2%) HP with AP, 1 of 99 (1%) HP without AP, 0 of 130 (0%) LP with AP, and 2 of 737 (0.3%) LP without AP. In univariate logistic analysis, the overall risk for IC was found to be higher with AP (p < 0.05), but the increase did not remain significant if adjusting for age, gender, ASA class, H-R P/L-R P and surgical approach or limiting the analysis to major IC.Conclusion. There is no benefit from AP in uncomplicated procedures. The effectiveness of antibiotic prophylaxis in complicated cholecystectomy must be evaluated in randomized controlled trials.
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| 8. |
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| 9. |
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| 10. |
- Eklund, Arne, 1957-, et al.
(författare)
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Low Recurrence Rate After Laparoscopic (TEP) and Open(Lichtenstein) Inguinal Hernia RepairA Randomized, Multicenter Trial With 5-Year Follow-Up
- 2009
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 249:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare a laparoscopic (totally extraperitoneal patch (TEP)) and an open technique (Lichtenstein) for inguinal hernia repair regarding recurrence rate and possible risk factors for recurrence. Summary Background Data: Laparoscopic hernia repair has been introduced as an alternative to open repair. Short-term follow-up suggests benefits for those patients operated with a laparoscopic approach compared with open techniques; ie, less postoperative pain and a shorter convalescence period. Long-term results, however, are less well known. Methods: The study was conducted as a multicenter randomized trial with a 5-year follow-up. A total of 1512 men aged 30 to 70 years, with a primary unilateral inguinal hernia, were randomized to either TEP or Lichtenstein repair. Results: Overall, 665 patients in the TEP group and 705 patients in the Lichtenstein group were evaluable. The cumulative recurrence rate was 3.5% in the TEP group and 1.2% in the Lichtenstein group (P = 0.008). Test for heterogeneity revealed significant differences between individual surgeons. The exclusion of 1 surgeon, who was responsible for 33% (7 of 21) of all recurrences in the TEP group, lowered the cumulative recurrence rate to 2.4% in this group, which was not statistically different from that of the Lichtenstein group. Conclusions: The recurrence rate for both TEP and Lichtenstein repair was low. A higher cumulative recurrence rate in the TEP group was seen at 5 years. Further analysis revealed that this could be attributable to incorrect surgical technique.
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