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21.
Knappskog PM Majewski J Livneh A Nilsen PT Bringsli JS Ott J Boman H 《American journal of human genetics》2003,72(2):375-383
In 1978, Sohar et al. described a strikingly peculiar syndrome in two Israeli sisters. These young women responded to environmental temperatures of 18 degrees C-7 degrees C with profuse sweating on large segments on their back and chest. Both had additional abnormalities, including a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend their elbows, and kyphoscoliosis. We have observed this disorder in two Norwegian brothers. Genome-wide screening in the two families, followed by saturation marker studies and linkage analysis, identified a 1.4-Mb homozygous candidate region on chromosome 19p12. The maximum multipoint LOD score was 4.22. In both families, DNA sequencing of 25 genes within the candidate region identified potentially deleterious CRLF1 sequence variants that were not found in unaffected control individuals. Our findings confirm that the cold-induced sweating syndrome is an autosomal recessive disorder that is probably caused by impaired function of the CRLF1 gene, and they suggest important developmental functions for human CRLF1. 相似文献
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Per M. Knappskog Hans Geir Eiken Aurora Martinez Torgeir Flatmark Jaran Apold 《Human genetics》1995,95(2):171-173
The mutation S349P in exon 10 of the phenylalanine hydroxylase (PAH) gene was identified in one Norwegian and one Polish phenylketonuria (PKU) allele on a haplotype 1.7 background. This missense mutation in PAH codon 349 is a T to C transition in cDNA position 1267. This mutation has been reported both on haplotype 1 and 4, suggesting recurrent mutation. In two different expression systems, the pET and the pMAL systems of Escherichia coli, it was shown that the S349P mutation, introduced by site directed mutagenesis, results in complete loss of enzymatic activity. Thus, protein instability alone does not seem to be the direct cause of the lack of activity of this PKU mutation as previously reported.We have identified mutations in the PAH gene of 118 PKU patients in Norway. To obtain information about how the different mutations affect the catalytic properties of the PAH enzyme we have used two prokaryotic expression systems.We detected the mutation S349P (Forrest et al. 1991) in one Norwegian patient and one of Polish ancestry. This mutation has previously been reported on haplotype 4 in North-African Jews (Weinstein et al. 1993), and on haplotype 1 in French-Canadians (John et al. 1992) and in Danes (Guldberg et al. 1993a). Here we present gene expression data showing that the recombinant mutant enzyme has no measurable residual catalytic activity. 相似文献
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Zhemin Zhou Inge Lundstrøm Alicia Tran-Dien Sebastián Duchêne Nabil-Fareed Alikhan Martin J. Sergeant Gemma Langridge Anna K. Fotakis Satheesh Nair Hans K. Stenøien Stian S. Hamre Sherwood Casjens Axel Christophersen Christopher Quince Nicholas R. Thomson François-Xavier Weill Simon Y.W. Ho M. Thomas P. Gilbert Mark Achtman 《Current biology : CB》2018,28(15):2420-2428.e10
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Ole-Gunnar Støen Per Wegge Stian Heid Olav Hjeljord Christian Nellemann 《European Journal of Wildlife Research》2010,56(5):789-795
The increasing development of recreational resorts and second homes in mountain regions worldwide require substantial infrastructure, and have large impact on habitats and ecosystems. We hypothesized that developed areas would attract predators and lead to higher predation on willow ptarmigan and lower their abundance. In a 500-km2 study area in south-central Norway, we sampled the density of territorial cocks in spring and the breeding success of willow ptarmigan along a 3-km gradient extending out from clusters of cabins. We also sampled red fox scats and corvid birds and measured nest predation on artificial nests across this gradient. Densities of cocks in the spring and of adults and brood sizes in August did not vary along the gradient. However, the density of chicks in August was higher beyond 1.5 km from cabin areas, presumably because more hens lost their clutches in the vicinity of cabins. This was supported by the results from the artificial nest experiment where significantly more nests were depredated near cabin areas than further away. The number of scats of red fox along trails increased with distance from cabins, whereas more corvid birds were observed near cabins. We conclude that corvid birds were the main cause of higher loss of ptarmigan nests near cabin areas, which led to lower production of chicks. Breeding density, however, did not seem to vary along the gradient, presumably because of suitable habitat for breeding and little human activity in these areas during the period of pair formation and nesting. 相似文献
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Stian Sjøli Ann Iren Solli Øyvind Akselsen Yang Jiang Eli Berg Trond Vidar Hansen Ingebrigt Sylte Jan-Olof Winberg 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Dysregulation of apoptotic cell death is observed in a large number of pathological conditions. As caspases are central enzymes in the regulation of apoptosis, a large number of procaspase-activating compounds (PAC-1 derivatives) and inhibitors (isatin derivatives) have been developed. Matrix metalloproteinases (MMPs) have been shown to have a dual role in apoptosis. Hence compounds that either activate or inhibit caspases should ideally not affect MMPs. As many PAC-1 derivatives contain a zinc chelating ortho-hydroxy N-acyl hydrazone moiety and isatin derivatives has two carbonyl groups on the indole core, it was of interest to determine to which extent these compounds can inhibit MMPs.Methods
Eight PAC-1 and five isatin derivatives were docked into MMP-9 and MMP-14. The same compounds were synthesized, characterized, purified and tested as inhibitors of MMP-9 and MMP-14, using fluorescence quenched peptide and biological substrates. Some of the compounds were also tested for fluorescence quenching.Results
Molecular docking suggested that the different compounds can bind to the MMP active sites. However, kinetic studies showed that neither of these compounds was a strong MMP inhibitor. IC50 values over 100 μM were obtained after the enzyme activities were corrected for quenching. These IC50 values are far above the concentrations needed to activate or inhibit the caspases.Conclusion
The use of PAC-1 and isatin derivatives against caspases should have little or no effect on the activity of MMPs.General significance
Activators and inhibitors of caspases are important potential therapeutic agents for several diseases such as cancer, diabetes and neurodegenerative disorders. 相似文献28.
Kine Marita Knudsen Sand Bj?rn Dalhus Gregory J. Christianson Malin Bern Stian Foss Jason Cameron Darrell Sleep Magnar Bj?r?s Derry C. Roopenian Inger Sandlie Jan Terje Andersen 《The Journal of biological chemistry》2014,289(24):17228-17239
Albumin is the most abundant protein in blood and plays a pivotal role as a multitransporter of a wide range of molecules such as fatty acids, metabolites, hormones, and toxins. In addition, it binds a variety of drugs. Its role as distributor is supported by its extraordinary serum half-life of 3 weeks. This is related to its size and binding to the cellular receptor FcRn, which rescues albumin from intracellular degradation. Furthermore, the long half-life has fostered a great and increasing interest in utilization of albumin as a carrier of protein therapeutics and chemical drugs. However, to fully understand how FcRn acts as a regulator of albumin homeostasis and to take advantage of the FcRn-albumin interaction in drug design, the interaction interface needs to be dissected. Here, we used a panel of monoclonal antibodies directed towards human FcRn in combination with site-directed mutagenesis and structural modeling to unmask the binding sites for albumin blocking antibodies and albumin on the receptor, which revealed that the interaction is not only strictly pH-dependent, but predominantly hydrophobic in nature. Specifically, we provide mechanistic evidence for a crucial role of a cluster of conserved tryptophan residues that expose a pH-sensitive loop of FcRn, and identify structural differences in proximity to these hot spot residues that explain divergent cross-species binding properties of FcRn. Our findings expand our knowledge of how FcRn is controlling albumin homeostasis at a molecular level, which will guide design and engineering of novel albumin variants with altered transport properties. 相似文献
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Frank T Bergmann Richard Adams Stuart Moodie Jonathan Cooper Mihai Glont Martin Golebiewski Michael Hucka Camille Laibe Andrew K Miller David P Nickerson Brett G Olivier Nicolas Rodriguez Herbert M Sauro Martin Scharm Stian Soiland-Reyes Dagmar Waltemath Florent Yvon Nicolas Le Novère 《BMC bioinformatics》2014,15(1)
Background
With the ever increasing use of computational models in the biosciences, the need to share models and reproduce the results of published studies efficiently and easily is becoming more important. To this end, various standards have been proposed that can be used to describe models, simulations, data or other essential information in a consistent fashion. These constitute various separate components required to reproduce a given published scientific result.Results
We describe the Open Modeling EXchange format (OMEX). Together with the use of other standard formats from the Computational Modeling in Biology Network (COMBINE), OMEX is the basis of the COMBINE Archive, a single file that supports the exchange of all the information necessary for a modeling and simulation experiment in biology. An OMEX file is a ZIP container that includes a manifest file, listing the content of the archive, an optional metadata file adding information about the archive and its content, and the files describing the model. The content of a COMBINE Archive consists of files encoded in COMBINE standards whenever possible, but may include additional files defined by an Internet Media Type. Several tools that support the COMBINE Archive are available, either as independent libraries or embedded in modeling software.Conclusions
The COMBINE Archive facilitates the reproduction of modeling and simulation experiments in biology by embedding all the relevant information in one file. Having all the information stored and exchanged at once also helps in building activity logs and audit trails. We anticipate that the COMBINE Archive will become a significant help for modellers, as the domain moves to larger, more complex experiments such as multi-scale models of organs, digital organisms, and bioengineering.Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0369-z) contains supplementary material, which is available to authorized users. 相似文献30.
Stian Ludvigsen Lars P. Folkow 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2009,195(11):1021-1030
Ducks are well-known to be more tolerant to asphyxia than non-diving birds, but it is not known if their defences include
enhanced neuronal hypoxia tolerance. To test this, we compared extracellular recordings of spontaneous activity in the Purkinje
cell layer of 400 μm thick isolated cerebellar slices from eider ducks, chickens and rats, before, during and after 60 min
hypoxia (95%N2–5%CO2) or chemical anoxia (hypoxia + 2 mM NaCN). Most slices rapidly lost activity in hypoxia, with or without recovery after rinse
and return to normoxia (95%O2–5%CO2), but some maintained spontaneous activity throughout the insult. Proportions of ‘surviving’ (i.e. recovering or active)
duck slices were significantly higher than for chickens in anoxia, and relative activity levels were higher for ducks than
for chickens during hypoxia, anoxia and recovery. Survival of rat slices was significantly poorer than for birds under all
conditions. Results suggest that (1) duck cerebellar neurons are intrinsically more hypoxia-tolerant than chicken neurons;
(2) avian neurons are more hypoxia-tolerant than rat neurons, and (3) the enhanced hypoxic tolerance of duck neurons largely
depended on efficient anaerobiosis since it mainly manifested itself in chemical anoxia. Mechanisms underlying the observed
differences in neuronal hypoxic responses remain to be elucidated. 相似文献