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41.
Lotta Mårtensson Beatriz Díez Ingvild Wartiainen Weiwen Zheng Rehab El-Shehawy Ulla Rasmussen 《Plant and Soil》2009,325(1-2):207-218
The diazotrophic communities in a rice paddy field were characterized by a molecular polyphasic approach including DNA/RNA-DGGE fingerprinting, real time RT-PCR analysis of nifH gene and the measurement of nitrogen fixation activities. The investigation was performed on a diurnal cycle and comparisons were made between bulk and rhizosphere / root soil as well as between fertilized / unfertilized soils. Real time RT-PCR showed no significant difference in the total quantity of nifH expression under the conditions investigated. The functional diversity and dynamics of the nifH gene expressing diazotroph community investigated using RT-PCR-DGGE revealed high diurnal variations, as well as variation between different soil types. Most of the sequence types recovered from the DGGE gels and clone libraries clustered within nifH Cluster I and III (65 different nifH sequences in total). Sequence types most similar to Azoarcus spp., Metylococcus spp., Rhizobium spp., Methylocystis spp., Desulfovibrio spp., Geobacter spp., Chlorobium spp., were abundant and indicate that these species may be responsible for the observed diurnal variation in the diazotrophic community structure in these rice field samples. Previously described diazotrophic cyanobacterial genera in rice fields, such as Nostoc and Cyanothece, were present in the samples but not detectable in RT-PCR assays. 相似文献
42.
Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen 《Immunogenetics》2009,61(4):247-256
Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune
and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the
DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional
genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging
single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to
validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were
genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy.
The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously
determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease
risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95%
to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk
effects. The method is transferable between populations and therefore suited for large-scale research studies and screening
of celiac disease among high-risk individuals or at the population level.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Lotta Koskinen and Jihane Romanos are authors with equal contribution. 相似文献
43.
Magnus Nilsson Anna Karin Belfrage Stefan Lindström Horst Wähling Charlotta Lindquist Susana Ayesa Pia Kahnberg Mikael Pelcman Kurt Benkestock Tatiana Agback Lotta Vrang Ylva Terelius Kristina Wikström Elizabeth Hamelink Christina Rydergård Michael Edlund Anders Eneroth Pierre Raboisson Tse-I Lin Herman de Kock Åsa Rosenquist 《Bioorganic & medicinal chemistry letters》2010,20(14):4004-4011
Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. 相似文献
44.
Katarina Kågedal Woojin Scott Kim Hanna Appelqvist Sharon Chan Danni Cheng Lotta Agholme Kevin Barnham Heather McCann Glenda Halliday Brett Garner 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(8):831-838
The Niemann-Pick type C1 (NPC1) protein mediates the trafficking of cholesterol from lysosomes to other organelles. Mutations in the NPC1 gene lead to the retention of cholesterol and other lipids in the lysosomal compartment, and such defects are the basis of NPC disease. Several parallels exist between NPC disease and Alzheimer's disease (AD), including altered cholesterol homeostasis, changes in the lysosomal system, neurofibrillary tangles, and increased amyloid-beta generation. How the expression of NPC1 in the human brain is affected in AD has not been investigated so far. In the present study, we measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and we revealed that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals. In the cerebellum, a brain region that is relatively spared in AD, no difference in NPC1 expression was detected. Similarly, murine NPC1 mRNA levels were increased in the hippocampus of 12-month-old transgenic mice expressing a familial AD form of human amyloid-beta precursor protein (APP) and presenilin-1 (APP/PS1tg) compared to 12-month-old wild type mice, whereas no change in NPC1 was detected in mouse cerebellum. Immunohistochemical analysis of human hippocampus indicated that NPC1 expression was strongest in neurons. However, in vitro studies revealed that NPC1 expression was not induced by transfecting SK-N-SH neurons with human APP or by treating them with oligomeric amyloid-beta peptide. Total cholesterol levels were reduced in hippocampus from AD patients compared to control individuals, and it is therefore possible that the increased expression of NPC1 is linked to perturbed cholesterol homeostasis in AD. 相似文献
45.
Boris Kartascheff Lotta Heckmann Barbara Drossel Christian Guill 《Theoretical Ecology》2010,3(3):195-208
It has recently been shown that the incorporation of allometric scaling into the dynamic equations of food web models enhances
network stability if predators are assigned a higher body mass than their prey. We investigate the underlying mechanisms leading
to this stability increase. The dynamic equations can be written such that allometric scaling influences these equations at
three places: the time scales of predator and prey dynamics become separated, the energy outflow to the predators is decreased,
and intraspecific competition is increased relative to metabolic rates. For five food web topologies and various network sizes
(i.e., species richness), we study the effect of each of these modifications on the percentage of surviving species separately
and find that the decreased interaction strengths and the increased intraspecific competition are responsible for the enhanced
stability. We also investigate the range of parameter values for which an enhanced stability is observed. 相似文献
46.
Håkansson G Gesslein B Gustafsson L Englund-Johansson U Malmsjö M 《Journal of ocular biology, diseases, and informatics》2010,3(1):20-29
Retinal ischemia arises from circulatory failure. As the retinal blood vessels are key organs in circulatory failure, our aim was to study the retinal vasculature separately from the neuroretina to elucidate the role of hypoxia-inducible factor (HIF) 1α and 1β and vascular endothelial growth factor (VEGF) in retinal ischemia. Retinal ischemia was induced in porcine eyes by applying an intraocular pressure, followed by 12 h of reperfusion. HIF-1α mRNA expression was not affected by ischemia, while immunofluorescence staining was higher after ischemia in the neuroretina. HIF-1β immunoreactivity and mRNA expression were unaffected. VEGF protein levels in the vitreous humor and VEGF staining in the neuroretina were more pronounced in eyes subjected to ischemia than in the sham eyes. VEGF may be activated downstream of HIF-1 and is known to stimulate retinal neovascularization, which causes sight-threatening complications. These results emphasize the need for pharmacological treatment to block the HIF and VEGF signaling pathways in retinal ischemia. 相似文献
47.
Human glutathione transferase (hGST) A1-1 and a lysine mutant (A216K) can both be rapidly and site-specifically acylated on Y9 and K216, respectively, using a range of thiolesters of glutathione (GS-thiolesters) as modifying reagents. The present investigation was aimed at developing a method with which to deliver a fluorescent acyl group from a solid support under conditions compatible with standard protein purification schemes. A number of fluorescent GS-thiolesters with modified peptide backbones were therefore prepared and tested for reactivity toward hGST A1-1 and the A216K mutant. Substitutions at the alpha-NH2 part of the glutathione backbone were not tolerated by the proteins. However, two fluorescent reagents that carry a biotin moiety at the C-terminal part of glutathione were found through MALDI-MS experiments to react in solution with Y9 of the wild-type protein and one reagent with K216 of A216K. The reaction can take place in the presence of glutathione and even in a crude E. coli lysate of cells expressing A216K. Delivery of the fluorescent group to Y9 or K216 was possible using NeutrAvidin (NA) beads that had been preincubated with biotinylated reagent. Alternatively, excess reagent can be removed by a brief incubation with NA beads. We have thus now developed a system for protein labeling with easy removal of excess and used up low-molecular weight reagent. This strategy can conceivably be utilized in future protein purification and labeling experiments. 相似文献
48.
49.
Ole Kilpinen 《Physiological Entomology》2005,30(3):232-240
Abstract. The behavioural responses of the poultry red mite, Dermanyssus gallinae , to three host-related stimuli, vibration, heat and CO2 , are studied in light and dark. Although D. gallinae usually feeds on host-blood at night, it can also be day active after a few days of starvation. However, the immediate response of the mites to CO2 in daylight is to freeze and remain motionless. Even with simultaneous presentation of an activating stimulus (heat), the mites freeze in response to CO2 . In the case of subsequent vibrations, they start moving but only for the duration of the vibrations. After 2 min, the freezing response disappears and the level of activity is significantly higher than for mites stimulated with vibrations alone. The freezing response is interpreted as a defence against being eaten by the host that apparently is close enough to breathe on the mites. At low-light intensities, where the birds are unable to see the mites, there is no freezing response, but only a synergistic effect of heat and vibration on the level of activity. The frequency of vibration most efficient in eliciting movement during the freezing response is found at 2 kHz with a threshold value of 35 µm s−1 peak-peak, suggesting that D. gallinae is more sensitive to substrate-borne vibrations than some insects (e.g. honeybees) known to use vibrations for intraspecific communication. 相似文献
50.
Muthas D Nöteberg D Sabnis YA Hamelink E Vrang L Samuelsson B Karlén A Hallberg A 《Bioorganic & medicinal chemistry》2005,13(18):5371-5390
The increasing resistance of the malarial parasite to antimalarial drugs is a major contributor to the reemergence of the disease and increases the need for new drug targets. The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets. In an effort to inhibit these hemoglobinases, a series of inhibitors encompassing a basic hydroxyethylamine transition state isostere as a central fragment were prepared. The synthesized compounds were varied in the P1' position and exhibited biological activities in the range of 31 to >2000 nM. To try to rationalize the results, molecular docking and 3D-QSAR analysis were used. 相似文献