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- Hillier, Ladeana W, et al.
(author)
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Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
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In: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
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Journal article (peer-reviewed)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
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| 2. |
- Brown, George, et al.
(author)
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Culture, collegiality and collaborative learning
- 2003
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In: Effective teaching and learning in medical, dental and veterinary education. - : Kogan page. - 0749435623 ; , s. 18-35
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Book chapter (other academic/artistic)
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| 3. |
- Cobb, Christopher S., et al.
(author)
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Angiotensin I-converting enzyme-like activity in tissues from the Atlantic hagfish (Myxine glutinosa) and detection of immunoreactive plasma angiotensins
- 2004
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In: Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. - : Elsevier BV. - 1096-4959. ; 138,:4, s. 357-364
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Journal article (peer-reviewed)abstract
- Using a highly sensitive fluorimetric assay, significant levels of angiotensin I -converting enzyme-like activity (ACELA) were detected in a range of tissues (branchial heart, gill, kidney with associated vasculature and archinephric duct, liver, whole brain and gut) from the Atlantic hagfish (Myxine glutinosa). The highest ACELA occurred in heart and gill (1.8 and 1.5 nmol His–Leu min−1 mg protein−1, respectively). The mammalian angiotensin I-converting enzyme (ACE) inhibitor, captopril, at 10−5 M was a potent inhibitor of the ACELA found in all hagfish tissues. Radioimmunoassay showed that immunoreactive angiotensins (251.8±11.8 pM) were detectable in hagfish plasma. The validity of the assay for measurement of hagfish angiotensins was indicated by the parallelism of the angiotensin II standard curve against serially diluted hagfish plasma. Measurement of immunoreactive plasma angiotensins and detection of significant levels of ACELA in a wide range of tissues gives indirect evidence for the presence of a renin–angiotensin system in hagfishes, the earliest evolved group of craniates
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| 4. |
- Frayling, Timothy M., et al.
(author)
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A Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity.
- 2003
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 52:3, s. 872-881
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Journal article (peer-reviewed)abstract
- Maturity-onset diabetes of the young (MODY) is a heterogeneous single gene disorder characterized by non–insulin-dependent diabetes, an early onset and autosomal dominant inheritance. Mutations in six genes have been shown to cause MODY. Approximately 15–20% of families fitting MODY criteria do not have mutations in any of the known genes. These families provide a rich resource for the identification of new MODY genes. This will potentially enable further dissection of clinical heterogeneity and bring new insights into mechanisms of β-cell dysfunction. To facilitate the identification of novel MODY loci, we combined the results from three genome-wide scans on a total of 23 families fitting MODY criteria. We used both a strict parametric model of inheritance with heterogeneity and a model-free analysis. We did not identify any single novel locus but provided putative evidence for linkage to chromosomes 6 (nonparametric linkage [NPL]score 2.12 at 71 cM) and 10 (NPL score 1.88 at 169–175 cM), and to chromosomes 3 (heterogeneity LOD [HLOD] score 1.27 at 124 cM) and 5 (HLOD score 1.22 at 175 cM) in 14 more strictly defined families. Our results provide evidence for further heterogeneity in MODY.
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| 5. |
- Gabrielsson, Jon, 1973-
(author)
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Multivariate methods in tablet formulation
- 2004
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Doctoral thesis (other academic/artistic)abstract
- This thesis describes the application of multivariate methods in a novel approach to the formulation of tablets for direct compression. It begins with a brief historical review, followed by a basic introduction to key aspects of tablet formulation and multivariate data analysis. The bulk of the thesis is concerned with the novel approach, in which excipients were characterised in terms of multiple physical or (in most cases) spectral variables. By applying Principal Component Analysis (PCA) the descriptive variables are summarized into a few latent variables, usually termed scores or principal properties (PP’s). In this way the number of descriptive variables is dramatically reduced and the excipients are described by orthogonal continuous variables. This means that the PP’s can be used as ordinary variables in a statistical experimental design. The combination of latent variables and experimental design is termed multivariate design or experimental design in PP’s. Using multivariate design many excipients can be included in screening experiments with relatively few experiments. The outcome of experiments designed to evaluate the effects of differences in excipient composition of formulations for direct compression is, of course, tablets with various properties. Once these properties, e.g. disintegration time and tensile strength, have been determined with standardised tests, quantitative relationships between descriptive variables and tablet properties can be established using Partial Least Squares Projections to Latent Structures (PLS) analysis. The obtained models can then be used for different purposes, depending on the objective of the research, such as evaluating the influence of the constituents of the formulation or optimisation of a certain tablet property. Several examples of applications of the described methods are presented. Except in the first study, in which the feasibility of this approach was first tested, the disintegration time of the tablets has been studied more carefully than other responses. Additional experiments have been performed in order to obtain a specific disintegration time. Studies of mixtures of excipients with the same primary function have also been performed to obtain certain PP’s. Such mixture experiments also provide a straightforward approach to additional experiments where an interesting area of the PP space can be studied in more detail. The robustness of a formulation with respect to normal batch-to-batch variability has also been studied. The presented approach to tablet formulation offers several interesting alternatives, for both planning and evaluating experiments.
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| 10. |
- Loskog, Angelica, et al.
(author)
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Potent antitumor effects of CD154 transduced tumor cells in experimental bladder cancer
- 2001
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In: Journal of Urology. - 0022-5347 .- 1527-3792. ; 166:3, s. 1093-1097
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Journal article (peer-reviewed)abstract
- PURPOSE: Current intravesical immunotherapy for bladder cancer with bacillus Calmette-Guerin instillations is standard treatment for patients with high risk superficial tumors but relapses are common. We evaluated the tumor vaccine concept in murine bladder cancer by comparing tumor cell transduction with genes coding for the immunostimulatory molecules CD154, interleukin (IL)-12 and CD80 to design a novel vaccination strategy. MATERIALS AND METHODS: Adenoviral vectors were used to transduce murine bladder cancer MB-49 cells with genes coding for CD154, IL-12 and CD80. Parental or transduced MB-49 cells were injected subcutaneously into syngeneic mice. The effects of transgene expression on tumorigenicity and the generation of protective immunological memory against challenge with parental tumor were studied. RESULTS: All 76 animals injected with parental MB-49 cells had tumors within 8 to 12 days. Tumor cell expression of CD154 combined with IL-12 completely inhibited tumor outgrowth with all 21 mice tumor-free and CD154 transduction alone was almost as effective with 33 of 35 tumor-free. IL-12 production by tumor cells delayed tumor outgrowth and 4 of 10 mice remained tumor-free. Over expression of CD80 had no effect on tumorigenicity. CD154 expressing tumors were rapidly infiltrated with large numbers of CD4+ and CD8+ T cells. Mice vaccinated 4 times with adenoviral CD154 transduced MB-49 cells were completely protected against challenge with parental tumor. Co-injection of CD154 modified cells with parental MB-49 cells retarded tumor growth. CONCLUSIONS: Our experimental results suggest that the potent antitumor effects of CD154 gene transduction should be considered for immunostimulatory gene therapy for bladder cancer.
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| 13. |
- Tedengren, Michael, et al.
(author)
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Heat pretreatment increase cadmium resistance and HSP 70 levels in Baltic Sea mussels
- 2000
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In: Aquatic Toxicology. - 0166-445X .- 1879-1514. ; 48:1, s. 1-12
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Journal article (peer-reviewed)abstract
- The effects of heat treatment and cadmium exposure on the synthesis of a major stress inducible protein (hsp 70) and on the metabolism of the blue mussel Mytilus edulis L. from the Baltic Sea, were studied in a laboratory experiment. The mussels were kept in sea water of ambient salinity (6.3‰) and temperature (4°C). The effects of cadmium (20 μg l−1), measured as changes in physiological rates (oxygen consumption, ammonia excretion, clearance rates and scope for growth) and hsp 70 expression were studied at 4°C and in combination with a rapid rise in temperature to 20°C. Relatively low levels of hsp 70 were detected but the negative effect was reflected in a reduction of scope for growth of the exposed mussels compared to controls. This effect was more pronounced at 20°C. Mussels not exposed to cadmium in the first experiment were used in a second set of experiments. Heat shocked mussels were allowed to reacclimatise to 4°C for 5 days and then, along with the mussels already at 4°C, exposed to cadmium (20 μg l−1). The results clearly indicated that the mussels exposed to 20°C in the first experiment more rapidly induced synthesis of hsp 70 after cadmium exposure in the second experiment. Also the reacclimatised mussels exposed to heat shock but not to cadmium in the first experiment, induced some hsp 70 in the second experiment. This suggests that the rate of induction of heat shock or stress proteins in Baltic mussels is slower than what has been described for mussels from more marine environments. The mussels kept at 4°C throughout the experiment and exposed to cadmium showed low levels of hsp 70, again indicating a low rate of induction. The increasing levels of hsp 70 correlated well with a maintained level of physiological fitness, in terms of scope for growth, although the mussels showed increasing body burdens of cadmium.
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