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| 4. |
- Pang, Jun-Feng, et al.
(författare)
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mtDNA data indicate a single origin for dogs south of Yangtze River, less than 16,300 years ago, from numerous wolves.
- 2009
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 26:12, s. 2849-64
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Tidskriftsartikel (refereegranskat)abstract
- There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.
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| 5. |
- Rydén, Lisa, et al.
(författare)
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Reproducibility of human epidermal growth factor receptor 2 analysis in primary breast cancer: a national survey performed at pathology departments in Sweden.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:6, s. 860-6
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Tidskriftsartikel (refereegranskat)abstract
- HER2 is a treatment predictive factor for the effect of trastuzumab and associated with poor prognosis in breast cancer. The analysis of HER2 must be performed with good quality, with regard to both the immunohistochemical (IHC) and in situ hybridization (ISH) analysis.A tissue microarray (TMA) including 11 breast cancer samples was sent twice (once in 2005 and again in 2006) to 24 pathology departments in Sweden. A questionnaire was also sent to the departments in 2006.With IHC, all departments reported the same results (0/1+ vs. 2+ vs. 3 + ) for three (2005) and six samples (2006). The mean kappa-value increased from 0.67 to 0.77, indicating a good reproducibility at both occasions. With fluorescence-ISH (FISH), the 11 departments using this technique reported the same results (amplified vs. normal) for nine (2005) and ten samples (2006). The mean kappa-value showed very good reproducibility both 2005 and 2006 (0.92 and 0.96, respectively). Based on the answers from the participating departments, the questionnaire revealed that 31% of primary breast cancer diagnosed in 2006 (n = 5 043) were 2 + /3+. FISH analysis of 2+ confirmed 12% of the samples to be amplified. The corresponding figure for 3 + was 90%. In total, 14.3% of the samples were HER2 positive (2+ and amplified, or 3 + ).The results obtained in this study indicate that the reproducibility for HER2 analysis is good (IHC) and very good (FISH) between the pathology departments in Sweden using TMA-based tumor samples. In 2006, 14.3% of invasive breast cancers were HER2 positive.
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- Pontoppidan, Katrine, 1976
(författare)
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Factors Influencing Phytate Degradation in Piglets. Feed phytate behaviour and degradation by microbial phytases
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Phytate, the main storage form of phosphorus (P) in plant feedstuffs, is indigestible for monogastric animals, and phytases are therefore used as feed additives to increase the digestibility of phytate-P and limit the inclusion of inorganic P. However, new and improved phytases are needed to obtain better phytate digestibility and allow for lower inclusions of inorganic P.The overall aim was to identify factors influencing phytate degradation in piglets as a means to develop improved phytases. The main part of the work therefore focussed on studying the in vitro and in vivo behaviour of feed phytate (soy/maize) and its degradation by microbial phytases (P. lycii and an experimental bacterial phytase).Pelleting and extrusion cooking only slightly affected the composition of inositol phosphates in feedstuffs. Phytate in soybean and maize meal precipitated with protein at pH below 4.0 and with minerals at pH above 4.5, and calcium critically increased the formation of phytate-mineral complexes. Both phytases demonstrated mainly 6-phytase activity when using Na-phytate as substrate in a simple buffered assay, but they showed different degradation pathways. Interestingly the bacterial phytase degraded InsP6 to InsP4 faster than the P. lycii phytase. During simulated digestion of a soybean-maize meal blend both phytases degraded phytate efficiently. The main difference also in this system was that the bacterial phytase was faster than the P. lycii phytase at degrading InsP6 to InsP4. In piglets, the bacterial phytase demonstrated double phytate degrading activity per unit of enzyme compared to the P. lycii phytase mainly due to superior survival during gastric digestion. Higher solubility of InsP4-InsP3 compared to InsP6-InsP5, together with the fact that InsP3-InsP5 was degraded in the small intestine, indicated that the bacterial phytase may also have an advantage of quickly producing InsP4. A high rate of gastric emptying was found to be limiting for phytate degradation in vivo, but supplying 50,000 FTU kg-1 DM partly overcame this limitation.Phosphorus was absorbed in the small intestine, but potential absorption of inositol phosphates measured as plasma InsP level could not be detected. Overall this work shows that in the search for new phytases, it is important to evaluate phytate degradation at the right conditions. In vitro assays should therefore carefully be adjusted with respect to e.g. substrate, pH, digestive proteases and mineral and protein content. Gastric stability and the speed at which certain inositol phosphates are degraded were found to be important factors for the efficacy of a phytase in vivo. However, a high rate of gastric emptying and the dosage of phytase seem to be the main determining factors for phytate degradation in piglets.
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| 8. |
- Sul, Young-Taeg, 1960, et al.
(författare)
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The role of surface chemistry and surface topography of osseointegrated titanium implant: strength and rate of osseointegration.
- 2009
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Ingår i: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 89A:4, s. 942-950
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Tidskriftsartikel (refereegranskat)abstract
- The present study investigated the effects of surface chemistry and topography on the strength and rate of osseointegration of titanium implants in bone. Three groups of implants were compared: (1) machine-turned implants (turned implants), (2) machine-turned and aluminum oxide-blasted implants (blasted implants), and (3) implants that were machine-turned, aluminum oxide-blasted, and processed with the micro-arc oxidation method (Mg implants). Three and six weeks after implant insertion in rabbit tibiae, the implant osseointegration strength and rate were evaluated. Surface chemistry revealed characteristic differences of nine at.% Mg for Mg implants and 11 at.% Al for blasted implants. In terms of surface roughness, there was no difference between Mg implants and blasted implants in developed surface ratio (Sdr; p = 0.69) or summit density (Sds; p = 0.96), but Mg implants had a significantly lower arithmetic average height deviation (Sa) value than blasted implants (p = 0.007). At both 3 and 6 weeks, Mg implants demonstrated significantly higher osseointegration strength compared with turned (p = 0.0001, p = 0.0001) and blasted (p = 0.0001, p = 0.035) implants, whereas blasted implants showed significantly higher osseointegration than turned implants at 6 weeks (p = 0.02) but not at 3 weeks (p = 0.199). The present results not only support the hypothesis that biochemical bonding facilitates rapid and strong integration of implants in bone, but also provide evidence for biochemical bonding theory previously proposed by Sul. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
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| 9. |
- Gyarmati, Peter, et al.
(författare)
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Implementation of molecular detection techniques in veterinary virology
- 2009
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Ingår i: Veterinary Sciences Tomorrow. - 1569-0830.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This article summarizes the research work of a recent PhD programme, which was a part of the international PhD training activities of the Veterinary Faculty of the SLU, the Collaborating Centre of the OIE. This PhD programme was focusing on the development and implementation of novel biotechnology-based techniques for the improved molecular diagnosis of infectious diseases of animals and man. In particular, it addressed diseases notifiable to the OIE, like the vesicular diseases complex and avian influenza, as well as Hepatitis E, an emerging zoonosis. With the worldwide introduction and use of polymerase chain reaction (PCR) methodologies, the detection of pathogens improved significantly - however, these systems have their weak points. Thus the simultaneous screening of multiple pathogens has not been satisfactorily solved, and the multiplexing capacity of most variants of the method is in general insufficient. The PhD programme did not intend to review the entire spectrum of molecular diagnostics or multiplex DNA detection; it was rather intended to highlight a specific area. The entire text can be downloaded from http://diss-epsilon.slu.se/archive/00001885/. Herewith, the results of this successful PhD programme are summarised by the new PhD holder (PG) and by the main supervisor (SB), in order to provide a brief review on this international training programme, focusing on new trends in molecular diagnostic virology, with special regards to the improved detection of zoonotic pathogens and/or viruses in food safety
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| 10. |
- Isoz, Isabelle, 1978-
(författare)
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Role of yeast DNA polymerase epsilon during DNA replication
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Each cell division, the nuclear DNA must be replicated efficiently and with high accuracy to avoid mutations which can have an effect on cell function. There are three replicative DNA polymerases essential for the synthesis of DNA during replication in eukaryotic cells. DNA polymerase α (Pol α) synthesize short primers required for DNA polymerase δ (Pol δ) and DNA polymerase ε (Pol ε) to carry out the bulk synthesis. The role of Pol δ and Pol ε at the replication fork has been unclear. The aim of this thesis was to examine what role Pol ε has at the replication fork, compare the biochemical properties of Pol δ and Pol ε, and to study the function of the second largest and essential subunit of Pol ε, Dpb2. To identify where Pol ε replicates DNA in vivo, a strategy was taken where the active site of Pol ε was altered to create a mutator polymerase leaving a unique error-signature. A series of mutant pol ε proteins were purified and analyzed for enzyme activity and fidelity of DNA synthesis. Two mutants, M644F and M644G, exhibited an increased mutation rate and close to normal polymerase activity. One of these, the M644G gave rise to a specific increase of mismatch mutations resulting from T-dTMP mis-pairing during DNA synthesis in vitro. The M644G mutant was introduced in yeast strains carrying a reporter gene, URA3, on either side of an origin in different orientations. Mutations which inactivated the URA3 gene in the M644G mutant strains were analyzed. A strand specific signature was found demonstrating that Pol ε participates in the synthesis of the leading strand. Pol δ and Pol ε are both stimulated by the processivity clamp, PCNA, in in vitro replication assays. To clarify any differences they were challenged side by side in biochemical assays. Pol ε was found to require that single-stranded template (ssDNA) was entirely coated with RPA, whereas Pol δ was much less sensitive to uncoated ssDNA. The processivity of Pol δ was stimulated to a much higher degree by PCNA than of Pol ε. In presence of PCNA the processivity of Pol δ and Pol ε was comparable. In contrast, Pol ε was approximately four times slower than Pol δ when replicating a single-primed circular template in the presence of all accessory proteins and an excess of polymerase. The biochemical characterization of the system suggests that Pol ε and Pol δ are loaded onto the PCNA-primer-ternary complex by separate mechanisms. A model is proposed where the loading of Pol ε onto the leading strand is independent of the PCNA interaction motif which is required by enzymes acting on the lagging strand. The essential gene DPB2 encodes for the second largest subunit of Pol ε. We carried out a genetic screen in S.cerevisiae and isolated a lethal mutant allele of dpb2 (dpb2-200). When over-expressed together with the remaining three subunits of Polε, Pol2, Dpb3 and Dpb4, the dpb2-201 did not copurify. The biochemical property of Pol2/Dpb3/Dpb4 complex was compared with wild-type four-subunit Pol ε (Pol2/Dpb2/Dpb3/Dpb4) and a Pol2/Dpb2 complex in replication assays. The absence of Dpb2 in the complex did not significantly affect the specific activity or the processivity, but gave a slightly reduced efficiency in holoenzyme assays when compared to wild-type four-subunit Pol ε. We propose that Dpb2 is not essential for the enzyme activity of Pol ε.
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| 11. |
- Lin, Jay
(författare)
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Enzymes in thymidylate synthesis in Ureaplasma parvum as medical targets
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The wall less bacterium Ureaplasma parvum (Up) is associated with ureathritis in adults and pneumonia in neonates. Up lack de novo nucleotide synthesis genes and has to import all DNA precursors. This thesis investigates known DNA biosynthesis pathways as targets for new antibiotics and concerns two enzymes in Up thymidylate synthesis; a thymidylate synthase (TS) and thymidine kinase (UpTK). TS activity was detected in Up-extracts and UU572 DNA could rescue a TS mutant E. coli. UU572 appeared to be proteolytic cleaved and cell cycle regulated in Up. Codon modified UU572 was cloned for expression in E. coli. However, no protein expression could be detected. A codon optimized synthesized UU572 homolog; MPN358 from Mycoplasma pneumonia was expressed in E. coli and showed TS activity. Low sequence homology to existing TSs suggests that UU572 and its homologs, belong to a new class of TS enzymes, which may contribute to future antibiotic development in human and veterinary medicine. Thirteen click chemistry-synthesized 3´-triazole thymidine analogs (1-13), using AZT as backbone, were evaluated with UpTK and hTK1. The bacterial TK exhibited a more open 3D structure than hTK1 explaining its substrate efficiency, while hTK1 seemed to have more closed structure as reflected by higher inhibition by the analogs. Docking models with 13 in TK1 structures revealed amino acid substitutions in the active site and most likely explain the different enzyme specificity. In addition, molecular docking could explain the 6-fold higher inhibition by the nucleoside analog 3´-azido-methyl-deoxythymidine (AZMT) with UpTK compared to hTK1. Nucleoside analogs have been used for fighting viruses with minimal side-effects. Why not use this strategy to control bacterial infections? The results presented in this thesis contribute towards attaining this goal.
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| 12. |
- Mascher, Henrik, et al.
(författare)
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Nya aspekter på aminosyrors roll i den muskulära anpassningen till träning
- 2006
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Ingår i: Svensk Idrottsforskning. - 1103-4629. ; 15:3, s. 56-60
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Sammanfattningsvis kan sägas att tillgängligheten av protein/aminosyror är nödvändig för den muskulära anpassningen till träning vid både styrke- och uthållighetsträning. Betydligt fler studier har undersökt effekterna på styrketräning, men vid båda typer av träning är dock kunskaperna om de bakomliggande mekanismerna ännu så länge små. Genom den omfattande forskning som pågår inom området kommer med all säkerhet de molekylära och cellulära förändringar som sker i samband med träning att kartläggas inom en relativt snar framtid. Därmed öppnas nya möjligheter att förbättra och optimera träningen, t.ex. genom kombination av olika typer av aktiviteter (uthållighet och styrketräning). Denna kunskap är också avgörande för att förstå och eventuellt kunna påverka träningseffekten genom förändringar i nutritionens sammansättning.
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| 13. |
- Pontoppidan, Katrine, 1976, et al.
(författare)
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Peniophora lycii phytase is stabile and degrades phytate and solubilises minerals in vitro during simulation of gastrointestinal digestion in the pig
- 2007
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Ingår i: Journal of the Science of Food and Agriculture. - : Wiley. - 1097-0010 .- 0022-5142. ; 87:14, s. 2700-2708
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Microbial phytases (EC 3.1.3) are widely used in diets for monogastric animals to hydrolyse phytate present in the feed and thereby increase phosphorus and mineral availability. Previous work has shown that phytate solubility is strongly affected by calcium in the feed and by pH in the gastrointestinal (GI) tract, which may have an effect on phytase efficacy. An in vitro model simulating the GI tract of pigs was used to study the survival of Peniophora lycii phytase and the effect of the phytase on phytate degradation, inositol phosphate formation and mineral solubilisation during in vitro digestion of a 30:70 soybean meal/maize meal blend with different calcium levels.RESULTS: The phytase retained 76 and 80% of its initial activity throughout the gastric in vitro digestion. Total phytate hydrolysis by P. lycii phytase was in the same range at total calcium levels of 1.2 and 6.2 mg g(-1) dry matter (DM), despite very large differences in phytate solubility at these calcium levels. However, at 11.2 and 21.2 mg Ca g(-1) DM, phytate hydrolysis was significantly lower. The amount of soluble mineral was generally increased by P. lycii phytase.CONCLUSION: Stability of P. lycii phytase during gastric digestion was not found to be critical for phytate hydrolysis. Furthermore, original phytate solubility was not an absolute requirement for phytate degradation; phytate solubility seemed to be in a steady state, allowing insoluble phytate to solubilise as soluble phytate was degraded. This is new and interesting knowledge that adds to the current understanding of phytate-phytase interaction.
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| 14. |
- Sahlin, Kent, et al.
(författare)
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Repeated static contractions increase mitochondrial vulnerability towards oxidative stress in human skeletal muscle
- 2007
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Ingår i: Journal of applied physiology. - 8750-7587 .- 1522-1601. ; 101, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- Repeated static contractions (RSC) induce large fluctuations in tissue oxygen tension and increase the generation of reactive oxygen species (ROS). This study investigated the effect of RSC on muscle contractility, mitochondrial respiratory function, and in vitro sarcoplasmatic reticulum (SR) Ca2+-kinetics in human muscle. Ten male subjects performed 5 bouts of static knee extension with 10 min rest in between. Each bout of RSC (target torque 66% of maximal voluntary contraction torque, MVC) was maintained to fatigue. Muscle biopsies were taken pre-exercise and 0.3 and 24 h post-exercise from vastus lateralis. Mitochondria were isolated and respiratory function measured after incubation with H2O2 (HPX) or control medium (CON). Mitochondrial function was not affected by RSC during CON. However, RSC exacerbated mitochondrial dysfunction during HPX resulting in decreased respiratory control index, decreased mitochondrial efficiency (P/O ratio) and increased non-coupled respiration (HPX/CON post vs. pre-exercise). SR Ca2+ uptake rate was lower 0.3 h vs. 24 h post-exercise, whereas SR Ca2+ release rate was unchanged. RSC resulted in long-lasting changes in muscle contractility including reduced maximal torque, low frequency fatigue (LFF) and faster torque relaxation. It is concluded that RSC increases mitochondrial vulnerability towards ROS, reduces SR Ca2+ uptake rate and causes LFF. Although conclusive evidence is lacking we suggest that these changes are related to increased formation of ROS during RSC.
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