| 1. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
- Capela, J P, et al.
(author)
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Ecstasy-induced cell death in cortical neuronal cultures is serotonin 2A-receptor-dependent and potentiated under hyperthermia
- 2006
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In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 139:3, s. 1069-1081
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Journal article (peer-reviewed)abstract
- Studies on 3,4-methylenedioxymethamphetamine ("ecstasy")-induced neurotoxicity mainly focus on damage of serotonergic terminals. Less attention has been given to neuronal cell death produced by 3,4-methylenedioxymethamphetamine and other amphetamines in areas including the cortex, striatum and thalamus. In the present study we investigated 3,4-methylenedioxymethamphetamine-induced neurotoxicity in neuronal serum free cultures from rat cortex. Since 3,4-methylenedioxymethamphetamine intake induces hyperthermia in both animals and humans, the experiments were performed under normal (36.5 degrees C) and hyperthermic conditions (40 degrees C). Our findings showed a dose-, time- and temperature-dependent apoptotic cell death induced by 3,4-methylenedioxymethamphetamine in cortical neurons. 3,4-Methylenedioxymethamphetamine-induced damage was potentiated under hyperthermia. The neurotoxicity was reduced by the serotonin 2A-receptor antagonists, ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride, in both normothermic and hyperthermic conditions. (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride, a model agonist for the serotonin 2A-receptor, also induced a dose- and time-dependent apoptotic cell death. Again, protection was provided by ketanserin and (2R,4R)-5-[2-[2-[2-(3-methoxyphenyl)ethyl]phenoxy]ethyl]-1-methyl-3-pyrrol idinol hydrochloride against (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride-induced neurotoxicity, thereby indicating that the 3,4-methylenedioxymethamphetamine stimulation of the serotonin 2A-receptor leads to neurotoxicity. This study provides for the first time evidence that direct 3,4-methylenedioxymethamphetamine serotonin 2A-receptor stimulation leads to neuronal cortical death. alpha-Phenyl-N-tert-butyl nitrone a free radical scavenger and the nitric oxide synthase inhibitor Nomega-nitro-L-arginine as well as the NMDA-receptor antagonist MK-801 provided protection under normothermia and hyperthermia, thereby suggesting the participation of free radicals in 3,4-methylenedioxymethamphetamine-induced cell death. Since 3,4-methylenedioxymethamphetamine serotonin 2A-receptor agonistic properties lead to neuronal death, clinically available atypical antipsychotic drugs with serotonin 2A-antagonistic properties could be a valuable therapeutic tool against 3,4-methylenedioxymethamphetamine-induced neurodegeneration.
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| 3. |
- Belmont, Anne-Sophie, et al.
(author)
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Direct writing of molecularly imprinted microstructures using a nanofountain pen
- 2007
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 90:19
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Journal article (peer-reviewed)abstract
- Molecularly imprinted polymers (MIPs) constitute a very appealing avenue to parallel sensors of a multitude of small target molecules due to their stability, relative ease of preparation, and their ability to recognize targets for which natural capture molecules do not exist. The authors present here a way of arraying MIP structures with micrometer dimensions, using nanofountain pen, and demonstrate their functionality using a fluorescent template molecule. (C) 2007 American Institute of Physics.
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| 4. |
- Brage, Søren, et al.
(author)
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Hierarchy of individual calibration levels for heart rate and accelerometry to measure physical activity.
- 2007
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In: J Appl Physiol. - : American Physiological Society. - 8750-7587. ; 103:2, s. 682-92
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Journal article (peer-reviewed)abstract
- Combining accelerometry with heart rate (HR) monitoring may improve precision of physical activity measurement. Considerable variation exists in the relationships between physical activity intensity (PAI) and HR and accelerometry, which may be reduced by individual calibration. However, individual calibration limits feasibility of these techniques in population studies, and less burdensome, yet valid, methods of calibration are required. We aimed to evaluate the precision of different individual calibration procedures against a reference calibration procedure: a ramped treadmill walking-running test with continuous measurement of PAI by indirect calorimetry in 26 women and 25 men [mean (SD): 35 ( 9 ) yr, 1.69 (0.10) m, 70 ( 14 ) kg]. Acceleration (along the longitudinal axis of the trunk) and HR were measured simultaneously. Alternative calibration procedures included treadmill testing without calorimetry, submaximal step and walk tests with and without calorimetry, and nonexercise calibration using sleeping HR and gender. Reference accelerometry and HR models explained >95% of the between-individual variance in PAI ( P < 0.001). This fraction dropped to 73 and 81%, respectively, for accelerometry and HR models calibrated with treadmill tests without calorimetry. Step-test calibration captured 62–64% (accelerometry) and 68% (HR) of the variance between individuals. Corresponding values were 63–76% and 59–61% for walk-test calibration. There was only little benefit of including calorimetry during step and walk calibration for HR models. Nonexercise calibration procedures explained 54% (accelerometry) and 30% (HR) of the between-individual variance. In conclusion, a substantial proportion of the between-individual variance in relationships between PAI, accelerometry, and HR is captured with simple calibration procedures, feasible for use in epidemiological studies.
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| 5. |
- Brune, Mats, 1950, et al.
(author)
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Improved leukemia-free survival after postconsolidation immunotherapy with histamine dihydrochloride and interleukin-2 in acute myeloid leukemia: results of a randomized phase 3 trial
- 2006
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:1, s. 88-96
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Journal article (peer-reviewed)abstract
- The primary objective of this phase 3 study was to determine whether postconsolidation immunotherapy with interleukin-2 (IL-2) and histamine dihydrochloride (HDC) improved the leukemia-free survival (LFS) of adult patients with acute myeloid leukemia (AML) in complete remission (CR). Three hundred twenty patients with AML (median age, 57 years; range, 18-84 years) were stratified by CR1 or subsequent CR (CR > 1) and randomly assigned to treatment with HDC/IL-2 or no treatment (control). Treatment comprised 10 21-day cycles with IL-2 (16 400 U/kg) plus HDC (0.5 mg); both compounds were administered by subcutaneous injection twice daily. Study arms were balanced for age, sex, previous treatment, leukemic karyotypes, time from CR to inclusion, and frequency of secondary leukemia. Three years after enrollment of the last patient, treatment with HDC/IL-2 was found to improve LFS over control in the study population (CR1 + CR > 1, n = 320; P < .01, log-rank test). For patients in CR1 (n = 261), treatment significantly improved LFS (P = .01) with 3-year LFS estimates of 40% (HDC/IL-2) compared with 26% (control). Side effects were typically mild to moderate. These results indicate that HDC/IL-2 treatment offers an efficacious and tolerable treatment for patients with AML in remission.
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| 6. |
- Buschard, Karsten, et al.
(author)
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Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
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In: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
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Journal article (peer-reviewed)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
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| 7. |
- Durand, Caylib A, et al.
(author)
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Phosphoinositide 3-kinase p110 delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses.
- 2009
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In: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 183:9, s. 5673-84
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Journal article (peer-reviewed)abstract
- B-1 and marginal zone (MZ) B cells produce natural Abs, make Ab responses to microbial pathogens, and contribute to autoimmunity. Although the delta isoform of the PI3K p110 catalytic subunit is essential for development of these innate-like B cells, its role in the localization, activation, and function of normal B-1 and MZ B cells is not known. Using IC87114, a highly selective inhibitor of p110delta enzymatic activity, we show that p110delta is important for murine B-1 and MZ B cells to respond to BCR clustering, the TLR ligands LPS and CpG DNA, and the chemoattractants CXCL13 and sphingosine 1-phosphate. In these innate-like B cells, p110delta activity mediates BCR-, TLR- and chemoattractant-induced activation of the Akt prosurvival kinase, chemoattractant-induced migration, and TLR-induced proliferation. Moreover, we found that TLR-stimulated Ab responses by B-1 and MZ B cells, as well as the localization of MZ B cells in the spleen, depend on p110delta activity. Finally, we show that the in vivo production of natural Abs requires p110delta and that p110delta inhibitors can reduce in vivo autoantibody responses. Thus, targeting p110delta may be a novel approach for regulating innate-like B cells and for treating Ab-mediated autoimmune diseases.
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| 8. |
- Griffith, Simon C., et al.
(author)
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Fourteen polymorphic microsatellite loci characterized in the house sparrow Passer domesticus (Passeridae, Aves)
- 2007
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In: Molecular Ecology Notes. - : Wiley. - 1471-8278 .- 1471-8286. ; 7:2, s. 333-336
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Journal article (peer-reviewed)abstract
- We characterized 14 polymorphic microsatellite loci in the house sparrow Passer domesticus. Four loci were isolated from house sparrow genomic libraries and 10 loci were identified by testing 100 loci that had been originally isolated in other passerine species. Loci were characterized in 37-54 unrelated sparrows from British and Norwegian populations. Each locus displayed between two and 31 alleles, with the observed heterozygosity ranging between 0.30 and 0.91.
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| 9. |
- Hazlett, Karsten RO, et al.
(author)
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Adaptation of Francisella tularensis to the mammalian environment is governed by cues which can be mimicked in vitro
- 2008
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In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 76:10, s. 4479-4488
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Journal article (peer-reviewed)abstract
- The intracellular bacterium Francisella tularensis survives in mammals, arthropods, and freshwater amoeba. It was previously established that the conventional media used for in vitro propagation of this microbe do not yield bacteria that mimic those harvested from infected mammals; whether these in vitro-cultivated bacteria resemble arthropod- or amoeba-adapted Francisella is unknown. As a foundation for our goal of identifying F. tularensis outer membrane proteins which are expressed during mammalian infection, we first sought to identify in vitro cultivation conditions that induce the bacterium's infection-derived phenotype. We compared Francisella LVS grown in brain heart infusion broth (BHI; a standard microbiological medium rarely used in Francisella research) to that grown in Mueller-Hinton broth (MHB; the most widely used F. tularensis medium, used here as a negative control) and macrophages (a natural host cell, used here as a positive control). BHI- and macrophage-grown F. tularensis cells showed similar expression of MglA-dependent and MglA-independent proteins; expression of the MglA-dependent proteins was repressed by the supraphysiological levels of free amino acids present in MHB. We observed that during macrophage infection, protein expression by intracellular bacteria differed from that by extracellular bacteria; BHI-grown bacteria mirrored the latter, while MHB-grown bacteria resembled neither. Naïve macrophages responding to BHI- and macrophage-grown bacteria produced markedly lower levels of proinflammatory mediators than those in cells exposed to MHB-grown bacteria. In contrast to MHB-grown bacteria, BHI-grown bacteria showed minimal delay during intracellular replication. Cumulatively, our findings provide compelling evidence that growth in BHI yields bacteria which recapitulate the phenotype of Francisella organisms that have emerged from macrophages.
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| 10. |
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