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- Andersson, Jan O, 1971-, et al.
(författare)
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Phylogenetic analyses of diplomonad genes reveal frequent lateral gene transfers affecting eukaryotes
- 2003
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Ingår i: Current Biology. - 0960-9822 .- 1879-0445. ; 13:2, s. 94-104
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lateral gene transfer (LGT) is an important evolutionary mechanism among prokaryotes. The situation in eukaryotes is less clear; the human genome sequence failed to give strong support for any recent transfers from prokaryotes to vertebrates, yet a number of LGTs from prokaryotes to protists (unicellular eukaryotes) have been documented. Here, we perform a systematic analysis to investigate the impact of LGT on the evolution of diplomonads, a group of anaerobic protists.RESULTS: Phylogenetic analyses of 15 genes present in the genome of the Atlantic Salmon parasite Spironucleus barkhanus and/or the intestinal parasite Giardia lamblia show that most of these genes originated via LGT. Half of the genes are putatively involved in processes related to an anaerobic lifestyle, and this finding suggests that a common ancestor, which most probably was aerobic, of Spironucleus and Giardia adapted to an anaerobic environment in part by acquiring genes via LGT from prokaryotes. The sources of the transferred diplomonad genes are found among all three domains of life, including other eukaryotes. Many of the phylogenetic reconstructions show eukaryotes emerging in several distinct regions of the tree, strongly suggesting that LGT not only involved diplomonads, but also involved other eukaryotic groups.CONCLUSIONS: Our study shows that LGT is a significant evolutionary mechanism among diplomonads in particular and protists in general. These findings provide insights into the evolution of biochemical pathways in early eukaryote evolution and have important implications for studies of eukaryotic genome evolution and organismal relationships. Furthermore, "fusion" hypotheses for the origin of eukaryotes need to be rigorously reexamined in the light of these results.
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- Chamberlain, Aaron K, et al.
(författare)
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Ultrastructural organization of amyloid fibrils by atomic force microscopy
- 2000
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Ingår i: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 79:6, s. 3282-3293
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Tidskriftsartikel (refereegranskat)abstract
- Atomic force microscopy has been employed to investigate the structural organization of amyloid fibrils produced in vitro from three very different polypeptide sequences. The systems investigated are a 10-residue peptide derived from the sequence of transthyretin, the 90-residue SH3 domain of bovine phosphatidylinositol-3'-kinase, and human wild-type lysozyme, a 130-residue protein containing four disulfide bridges. The results demonstrate distinct similarities between the structures formed by the different classes of fibrils despite the contrasting nature of the polypeptide species involved. SH3 and lysozyme fibrils consist typically of four protofilaments, exhibiting a left-handed twist along the fibril axis. The substructure of TTR(10-19) fibrils is not resolved by atomic force microscopy and their uniform appearance is suggestive of a regular self-association of very thin filaments. We propose that the exact number and orientation of protofilaments within amyloid fibrils is dictated by packing of the regions of the polypeptide chains that are not directly involved in formation of the cross-beta core of the fibrils. The results obtained for these proteins, none of which is directly associated with any human disease, are closely similar to those of disease-related amyloid fibrils, supporting the concept that amyloid is a generic structure of polypeptide chains. The detailed architecture of an individual fibril, however, depends on the manner in which the protofilaments assemble into the fibrillar structure, which in turn is dependent on the sequence of the polypeptide and the conditions under which the fibril is formed.
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- Dacks, JB, et al.
(författare)
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Evidence for cryptic Golgi in putatively ‘Golgi-lacking’ lineages
- 2003
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - 0962-8452 .- 1471-2954. ; 270, s. S168-71
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Tidskriftsartikel (refereegranskat)abstract
- Golgi bodies are nearly ubiquitous in eukaryotic cells. The apparent lack of such structures in certain eukaryotic lineages might be taken to mean that these protists evolved prior to the acquisition of the Golgi, and it raises questions of how these orga
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- Danielsson, Erik, et al.
(författare)
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Dry etching and metallization schemes in a GaN/SiC heterojunction device process
- 2000
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 338-342, s. 1049-1052
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Tidskriftsartikel (refereegranskat)abstract
- Dry etching and metallization schemes are described for a GaN/SiC heterojunction. GaN was reactive ion etched in a chlorine based chemistry (Cl2/Ar), and an ICP etch was used on 4H-SiC using a fluorine based chemistry (SF6/Ar/O2). The etch rates obtained on GaN was above 400 nm/min. High sample temperature from self heating and large dc-bias was the probable cause for the high etch rate. The ICP etch rate on SiC approached 320 nm/min, and the etch selectivity to GaN was >100. The metallization was based on Ti for both n-GaN and p-SiC. TLM and Kelvin structures were used to extract the specific contact resistivity, ÏC. After a 950 °C anneal in N2 ÏC on the GaN samples were below 1·10-6 Ωcm2 for sputtered contacts in room temperature, and an order of magnitude higher with evaporation. On p-SiC no ohmic behavior was found with a doping of 4·1018 cm-3, but the same contact metallization on highly doped areas (>1020 cm-3) showed ohmic behavior with ÏC below 10-4 Ωcm2.
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| 7. |
- Danielsson, E., et al.
(författare)
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The influence of band offsets on the IV characteristics for GaN/SiC heterojunctions
- 2002
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Ingår i: Solid-State Electronics. - 0038-1101 .- 1879-2405. ; 46:6, s. 827-835
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Tidskriftsartikel (refereegranskat)abstract
- GaN/SiC heterojunctions can improve the performance considerably for bipolar transistors based on SiC technology. In order to fabricate such devices with a high current gain, the origin of the low turn-on voltage for the heterojunction has to be investigated, which is believed to decrease the minority carrier injection considerably. In this work heterojunction diodes are compared and characterized. For the investigated diodes, the GaN layers have been grown by molecular beam epitaxy (MBE), metal organic chemical vapor deposition, and hydride vapor phase epitaxy. A diode structure fabricated with MBE is presented here, whereas others are collected from previous publications. The layers were grown either with a low temperature buffer, AIN buffer, or without buffer layer. The extracted band offsets are compared and included in a model for a recombination process assisted by tunneling, which is proposed as explanation for the low turn-on voltage. This model was implemented in a device simulator and compared to the measured structures, with good agreement for the diodes with a GaN layer grown without buffer layer. In addition the band offset has been calculated from Schottky barrier measurements, resulting in a type II band alignment with a conduction band offset in the range 0.6-0.9 eV. This range agrees well with the values extracted from capacitance-voltage measurements.
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- Trainer, P J, et al.
(författare)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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| 9. |
- van der Lely, A J, et al.
(författare)
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Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- 2001
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Ingår i: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
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Tidskriftsartikel (refereegranskat)abstract
- Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days.Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis.Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353).Pegvisomant is an effective medical treatment for acromegaly.
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