| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 3. |
- Bajammal, Sohail S., et al.
(författare)
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The use of calcium phosphate bone cement in fracture treatment : A meta-analysis of randomized trials
- 2008
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Ingår i: Journal of Bone and Joint Surgery. American volume. - 0021-9355 .- 1535-1386. ; 90:6, s. 1186-96
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Available options to fill fracture voids include autogenous bone, allograft bone, and synthetic bone materials. The objective of this meta-analysis was to determine whether the use of calcium phosphate bone cement improves clinical and radiographic outcomes and reduces fracture complications as compared with conventional treatment (with or without autogenous bone graft) for the treatment of fractures of the appendicular skeleton in adult patients. METHODS: Multiple databases, online registers of randomized controlled trials, and the proceedings of the meetings of major national orthopaedic associations were searched. Published and unpublished randomized controlled trials were included, and data on methodological quality, population, intervention, and outcomes were abstracted in duplicate. Data were pooled across studies, and relative risks for categorical outcomes and weighted mean differences for continuous outcomes, weighted according to study sample size, were calculated. Heterogeneity across studies was determined, and sensitivity analyses were conducted. RESULTS: We identified eleven published and three unpublished randomized controlled trials. Of the fourteen studies, six involved distal radial fractures, two involved femoral neck fractures, two involved intertrochanteric femoral fractures, two involved tibial plateau fractures, one involved calcaneal fractures, and one involved multiple types of metaphyseal fractures. All of the studies evaluated the use of calcium phosphate cement for the treatment of metaphyseal fractures occurring primarily through trabecular, cancellous bone. Autogenous bone graft was used in the control group in three studies, and no graft material was used in the remaining studies. Patients managed with calcium phosphate had a significantly lower prevalence of loss of fracture reduction in comparison with patients managed with autograft (relative risk reduction, 68%; 95% confidence interval, 29% to 86%) and had less pain at the fracture site in comparison with controls managed with no graft (relative risk reduction, 56%; 95% confidence interval, 14% to 77%). We were unable to compare pain at the bone-graft donor site between the studies because of methodological reasons. Three studies independently demonstrated improved functional outcomes when the use of calcium phosphate was compared with the use of no grafting material. CONCLUSIONS: The use of calcium phosphate bone cement for the treatment of fractures in adult patients is associated with a lower prevalence of pain at the fracture site in comparison with the rate in controls (patients managed with no graft material). Loss of fracture reduction is also decreased in comparison with that in patients managed with autogenous bone graft.
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| 4. |
- Baniulis, Danas, et al.
(författare)
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Monoclonal antibody CL5 recognizes the amino terminal domain of human phagocyte flavocytochrome b558 large subunit, gp91phox
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 74:4, s. 337-347
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Tidskriftsartikel (refereegranskat)abstract
- Human phagocyte flavocytochrome b558 (Cytb) is a heterodimeric integral membrane protein that serves as the electron transferase of the β-nicotinamide adenine dinucleotidephosphate, reduced (NADPH)-oxidase, an enzyme complex important in the host defense function of phagocytic cells. In this study, we report the characterization of monoclonal antibody (mAb) CL5 that is specific for the large subunit, gp91phox, of the oxidase protein. This antibody recognizes gp91phox by immunoblot analysis of membrane extracts and samples of the immunopurified gp91phox/p22 phox heterodimer, prepared on anti-p22phox affinity matrices. Phage display analysis confirmed this specificity, indicating that the CL5 epitope contains the region 135-DPYSVALSELGDR of gp91phox. The antibody was used to probe for the presence of gp91phox in membrane preparations from neutrophils of patients with nine genetically distinct forms of X-linked chronic granulomatous disease (CGD). The causative mutations included missense errors as well as nonsense errors that result in premature termination of gp91phox synthesis. Analysis of the CGD samples by immunoblotting indicated that CL5 recognizes only the full-length wild-type and two missense mutations, consistent with the absence of stable short gp91 phox peptide expression in CGD neutrophils. Interestingly, CL5 was also shown to be cross-reactive with cytosolic and membrane-bound gelsolin, identified by purification, mass spectrometry and immunoblot analysis. CL5 probably cross-reacts with the sequence 771-DPLDRAMAEL in the C-terminus of gelsolin. We conclude that mAb CL5 is a useful probe for detection of full length and possibly truncated N-terminal fragments of gp91phox from membranes of Cytb-producing cells. © Blackwell Munksgaard 2005.
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| 5. |
- Baniulis, Danas, et al.
(författare)
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Unusual polyclonal anti-gp91phox peptide antibody interactions with X-linked chronic granulomatous disease-derived human neutrophils are not from compensatory expression of Nox proteins 1, 3, or 4
- 2005
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 74:3, s. 241-249
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Tidskriftsartikel (refereegranskat)abstract
- To obtain topological information about human phagocyte flavocytochrome b558 (Cytb), rabbit anti-peptide antibodies were raised against synthetic peptides mimicking gp91phox regions: 1-9 (MGN), 30-44 (YRV), 150-159 (ESY), 156-166 (ARK), 247-257 (KIS-1, KIS-2). Following affinity purification on immobilized peptide matrices, all antibodies but not prebleed controls recognized purified detergent-solubilized Cytb by enzyme-linked immunosorbent assay (ELISA). Affinity-purified antibodies recognizing KIS, ARK and ESY but not YRV, MGN or prebleed IgG specifically detected gp91phox in immunoblot analysis. Antibodies recognizing MGN, ESY, ARK and KIS but not YRV or the prebleed IgG fraction labeled intact normal neutrophils. Surprisingly, all antibodies, with the exception of YRV and pre-immune IgG controls, bound both normal and Cytb-negative neutrophils from the obligate heterozygous mother of a patient with X-linked chronic granulomatous disease (X-CGD) and all neutrophils from another patient lacking the gp91phox gene. Further immunochemical examination of membrane fractions derived from nine genetically unrelated patients with X-CGD, using an antibody that recognizes other Nox protein family members, suggests that the unusual reactivity observed does not reflect the compensatory expression of gp91phox homologs Nox1, 3 or 4. These results suggest that an unusual surface reactivity exists on neutrophils derived from X-linked chronic granulomatous disease patients that most likely extends to normal neutrophils as well. The study highlights the need for caution in interpreting the binding of rabbit polyclonal antipeptide antibodies to human neutrophils in general and, in the specific case of antibodies directed against Cytb, the need for Cytb-negative controls.
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| 6. |
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| 7. |
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| 8. |
- Stensdotter, Ann-Katrin, et al.
(författare)
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Quadriceps EMG in Open and Closed Kinetic Chain Tasks in Women With Patellofemoral Pain.
- 2007
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Ingår i: Journal of motor behavior. - 0022-2895 .- 1940-1027. ; 39:3, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated whether the discrepancy noted in the literature regarding delayed and decreased activity in vastus medialis obliquus (VMO) in people with patellofemoral pain (PFP) depends on the nature of the open kinetic chain (OKC) and the closed kinetic chain (CKC) in the experimental task. They hypothesized that activity in VMO would be more delayed and decreased in CKC tasks than in OKC tasks. Women with PFP (n = 17) and healthy controls (n = 17) performed isometric quadriceps contractions in CKC and OKC tasks. The authors manipulated only the application of resistance. Electromyographs (EMGs) showed that participants with PFP reacted later and activated the quadriceps more in the CKC task but had intramuscular quadriceps coordination similar to that of controls. The nature of the OKC task or the CKC task does not seem to explain contradictory findings regarding VMO activation.
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| 9. |
- Wall, Rebecca, 1979-, et al.
(författare)
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Genomic diversity of cultivable Lactobacillus populations residing in the neonatal and adult gastrointestinal tract
- 2007
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Ingår i: FEMS Microbiology Ecology. - Oxon, United Kingdom : Blackwell Publishing. - 0168-6496 .- 1574-6941. ; 59:1, s. 127-137
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to investigate the cultivable Lactobacillus population in adult and infant faecal material to identify strains shared across a number of individuals. A range of lactobacilli isolated on Lactobacillus-selective agar from faeces of 16 infants and 11 adults were genetically fingerprinted and further characterized by 16S rRNA gene sequencing. The relatedness of all the Lactobacillus strains isolated to known species was also determined both genetically and phenotypically. This study revealed that the human intestine is initially colonized by only a few (1-2) different cultivable strains whereas in adults the pattern becomes more complex with a higher diversity of strains. The adult samples contained three genetically distinct Lactobacillus strains in some cases, while infant samples generally harboured only one dominant Lactobacillus strain. Moreover, the species in general appeared to differ with Lactobacillus rhamnosus and Lactobacillus casei/paracasei found mainly in adults, whereas Lactobacillus gasseri and Lactobacillus salivarius were more commonly isolated in infant samples. The data reaffirm the differences in Lactobacillus populations both between individual subjects and between the infant and adult, with an overall change in the diversity and complexity from early stages of life to adulthood.
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| 10. |
- Wall, Rebecca, 1979-, et al.
(författare)
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Metabolic activity of the enteric microbiota influences the fatty acid composition of murine and porcine liver and adipose tissues
- 2009
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Ingår i: American Journal of Clinical Nutrition. - Bethesda, USA : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 89:5, s. 1393-1401
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent reports suggest that the metabolic activity of the gut microbiota may contribute to the pathogenesis of obesity and hepatic steatosis.Objective: The objective was to determine whether the fat composition of host tissues might be influenced by oral administration of commensal bifidobacteria previously shown by us to produce bioactive isomers of conjugated linoleic acid (CLA).Design: Murine trials were conducted in which linoleic acid-supplemented diets were fed with or without Bifidobacterium breve NCIMB 702258 (daily dose of 10(9) microorganisms) to healthy BALB/c mice and to severe combined immunodeficient mice for 8-10 wk. To ensure that the observations were not peculiar to mice, a similar trial was conducted in weanling pigs over 21 d. Tissue fatty acid composition was assessed by gas-liquid chromatography.Results: In comparison with controls, there was an increase in cis-9, trans-11 CLA in the livers of the mice and pigs after feeding with linoleic acid in combination with B. breve NCIMB 702258 (P < 0.05). In addition, an altered profile of polyunsaturated fatty acid composition was observed, including higher concentrations of the omega-3 (n-3) fatty acids eicosapentaenoic acid and docosahexaenoic acid in adipose tissue (P < 0.05). These changes were associated with reductions in the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma (P < 0.05).Conclusions: These results are consistent with the concept that the metabolome is a composite of host and microbe metabolic activity and that the influence of the microbiota on host fatty acid composition can be manipulated by oral administration of CLA-producing microorganisms.
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