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61.
Rositsa Raikova Jan Celichowski Magdalena Pogrzebna Hristo Aladjov Piotr Krutki 《Journal of electromyography and kinesiology》2007,17(2):121-130
Repeated stimulation of motor units (MUs) causes an increase of the force output that cannot be explained by linear summation of equal twitches evoked by the same stimulation pattern. To explain this phenomenon, an algorithm for reconstructing the individual twitches, that summate into an unfused tetanus is described in the paper. The algorithm is based on an analytical function for the twitch course modeling. The input parameters of this twitch model are lead time, contraction and half-relaxation times and maximal force. The measured individual twitches and unfused tetani at 10, 20, 30 and 40 Hz stimulation frequency of three rat motor units (slow, fast resistant to fatigue and fast fatigable) are processed. It is concluded that: (1) the analytical function describes precisely the course of individual twitches; (2) the summation of equal twitches does not follow the results from the experimentally measured unfused tetani, the differences depend on the type of the MU and are bigger for higher values of stimulation frequency and fusion index; (3) the reconstruction of individual twitches from experimental tetanic records can be successful if the tetanus is feebly fused (fusion index up to 0.7); (4) both the maximal forces and time parameters of individual twitches subtracted from unfused tetani change and influence the course of each tetanus. A discrepancy with respect to the relaxation phase was observed between experimental results and model prediction for tetani with fusion index exceeding 0.7. This phase was predicted longer than the experimental one for better fused tetani. Therefore, a separate series of physiological experiments and then, more complex model are necessary for explanation of this distinction. 相似文献
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Background
Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers.Methodology/Principal Findings
Here we report amino acid residues responsible for stabilization of the structural and enzymatic integrity of the plasmodial PLP synthase, identified by using distinct mutational analysis and biochemical approaches. Residues R85, H88 and E91 (RHE) are located at the Pdx1:Pdx1 interface and play an important role in Pdx1 complex assembly. Mutation of these residues to alanine impedes both Pdx1 activity and Pdx2 binding. Furthermore, changing D26, K83 and K151 (DKK), amino acids from the active site of Pdx1, to alanine obstructs not only enzyme activity but also formation of the complex. In contrast to the monomeric appearance of the RHE mutant, alteration of the DKK residues results in a hexameric assembly, and does not affect Pdx2 binding or its activity. While the modelled position of K151 is distal to the Pdx1:Pdx1 interface, it affects the assembly of hexameric Pdx1 into a functional dodecamer, which is crucial for PLP synthesis.Conclusions/Significance
Taken together, our data suggest that the assembly of a functional Pdx1:Pdx2 complex follows a defined pathway and that inhibition of this assembly results in an inactive holoenzyme. 相似文献63.
A Founder Mutation in the GK1 Gene Is Responsible for Galactokinase Deficiency in Roma (Gypsies)
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Luba Kalaydjieva Anna Perez-Lezaun Dora Angelicheva Suna Onengut Danielle Dye Nils U. Bosshard Albena Jordanova Alexei Savov Peter Yanakiev Ivo Kremensky Brigitta Radeva Joachim Hallmayer Arseni Markov Vanya Nedkova Ivailo Tournev Lidia Aneva Richard Gitzelmann 《American journal of human genetics》1999,65(5):1299-1307
Galactokinase deficiency is an inborn error in the first step of galactose metabolism. Its major clinical manifestation is the development of cataracts in the first weeks of life. It has also been suggested that carriers of the deficiency are predisposed to presenile cataracts developing at age 20-50 years. Newborn screening data suggest that the gene frequency is very low worldwide but is higher among the Roma in Europe. Since the cloning of the galactokinase gene (GK1) in 1995, only two disease-causing mutations, both confined to single families, have been identified. Here we present the results of a study of six affected Romani families from Bulgaria, where index patients with galactokinase deficiency have been detected by the mass screening. Genetic linkage mapping placed the disease locus on 17q, and haplotype analysis revealed a small conserved region of homozygosity. Using radiation hybrid mapping, we have shown that GK1 is located in this region. The founder Romani mutation identified in this study is a single nucleotide substitution in GK1 resulting in the replacement of the conserved proline residue at amino acid position 28 with threonine (P28T). The P28T carrier rate in this endogamous population is approximately 5%, suggesting that the mutation may be an important cause of early childhood blindness in countries with a sizeable Roma minority. 相似文献
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Otto DM Campanero-Rhodes MA Karamanska R Powell AK Bovin N Turnbull JE Field RA Blackburn J Feizi T Crocker PR 《Analytical biochemistry》2011,(2):261-270
Here we describe a versatile high-throughput expression system that permits genome-wide screening of type 1 membrane and secreted proteins for interactions with glycans and proteins using both cell-expressed and soluble forms of the expressed proteins. Based on Gateway cloning methodology, we have engineered a destination vector that directs expression of enhanced green fluorescent protein (EGFP)-tagged proteins at the cell surface via a glycosylphosphatidylinositol tail. The EGFP fusion proteins can then be cleaved with PreScission protease to release soluble forms of proteins that can be optionally biotinylated. We demonstrate the utility of this cloning and expression system for selected low-affinity membrane lectins from the siglec family of sialic acid-binding immunoglobulin-like lectins, for the glycosaminoglycan-binding proteins FGF-1 and BACE, and for the heterotypic adhesion molecules JAM-B and JAM-C. Cell-expressed proteins can be evaluated for glycan interactions using polyvalent soluble glycan probes and for protein interactions using either cells or soluble proteins. Following cleavage from the cell surface, proteins were complexed in solution and sufficient avidity was achieved to measure weak protein–glycan and weak protein–protein interactions using glycan arrays and surface plasmon resonance, respectively. 相似文献
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Tsanova A Jordanova A Georgiev GA Pajpanova T Golovinsky E Lalchev Z 《Amino acids》2012,42(1):253-260
Using Langmuir’s monolayer technique, the surface behavior and the interaction of the synthetic neuropeptide methionine-enkephalin
(Met-enk) and its amidated derivate (Met-enk-NH2) with monolayers of the zwitterionic dimyristoylphosphatidylcholine (DMPC) and the negatively charged dimyristoylphosphatidylglycerol
(DMPG) were studied. The surface tension (γ, mN/m) of DMPG and DMPC monolayers as a function of time (after injection of the peptide under the interface) was detected.
The decrease in γ values showed that there was a strong penetration effect of both types of Met-enk molecules into the monolayers, being significantly
stronger for the amidated derivate, Met-enk-NH2. We suggest that the interaction between the neuropeptides and DMPC was predominantly determined by peptides amphiphilicity,
while the electrostatic forces play significant role for the insertion of the cationic Met-enk-NH2 in DMPG monolayers, especially at high packing densities. Our results demonstrate the potential of lipid monolayers formed
in Langmuir’s trough to be successfully used as an elegant and simple membrane models to study lipid–peptide interactions
at the air/water interface. 相似文献
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Rotthier A Auer-Grumbach M Janssens K Baets J Penno A Almeida-Souza L Van Hoof K Jacobs A De Vriendt E Schlotter-Weigel B Löscher W Vondráček P Seeman P De Jonghe P Van Dijck P Jordanova A Hornemann T Timmerman V 《American journal of human genetics》2010,87(4):513-4745
Hereditary sensory and autonomic neuropathy type I (HSAN-I) is an axonal peripheral neuropathy associated with progressive distal sensory loss and severe ulcerations. Mutations in the first subunit of the enzyme serine palmitoyltransferase (SPT) have been associated with HSAN-I. The SPT enzyme catalyzes the first and rate-limiting step in the de novo sphingolipid synthesis pathway. However, different studies suggest the implication of other genes in the pathology of HSAN-I. Therefore, we screened the two other known subunits of SPT, SPTLC2 and SPTLC3, in a cohort of 78 HSAN patients. No mutations were found in SPTLC3, but we identified three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families presenting with a typical HSAN-I phenotype. We demonstrate that these mutations result in a partial to complete loss of SPT activity in vitro and in vivo. Moreover, they cause the accumulation of the atypical and neurotoxic sphingoid metabolite 1-deoxy-sphinganine. Our findings extend the genetic heterogeneity in HSAN-I and enlarge the group of HSAN neuropathies associated with SPT defects. We further show that HSAN-I is consistently associated with an increased formation of the neurotoxic 1-deoxysphinganine, suggesting a common pathomechanism for HSAN-I. 相似文献
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Polystoma fuscus n. sp. (Polystomatidae, Polystomatinae) is described from the urinary bladder of Pelobates fuscus (Pelobatidae) in Bulgaria. Its general morphology is similar to that of other members of the genus but distinguished from them by the underdeveloped hamuli similar to the larval hamular primordia. The new species is also differentiated from the members of the genera of the subfamily Polystomatinae described without hamuli. 相似文献
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