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101.
Wang W Lohi H Skurat AV DePaoli-Roach AA Minassian BA Roach PJ 《Archives of biochemistry and biophysics》2007,457(2):264-269
Laforin, encoded by the EPM2A gene, by sequence is a member of the dual specificity protein phosphatase family. Mutations in the EPM2A gene account for around half of the cases of Lafora disease, an autosomal recessive neurodegenerative disorder, characterized by progressive myoclonus epilepsy. The hallmark of the disease is the presence of Lafora bodies, which contain polyglucosan, a poorly branched form of glycogen, in neurons, muscle and other tissues. Glycogen metabolizing enzymes were analyzed in a transgenic mouse over-expressing a dominant negative form of laforin that accumulates Lafora bodies in several tissues. Skeletal muscle glycogen was increased 2-fold as was the total glycogen synthase protein. However, the -/+glucose-6-P activity of glycogen synthase was decreased from 0.29 to 0.16. Branching enzyme activity was increased by 30%. Glycogen phosphorylase activity was unchanged. In whole brain, no differences in glycogen synthase or branching enzyme activities were found. Although there were significant differences in enzyme activities in muscle, the results do not support the hypothesis that Lafora body formation is caused by a major change in the balance between glycogen elongation and branching activities. 相似文献
102.
In order to compare gait patterns, a common procedure is to normalize strides both in time and magnitude. The stride duration is usually normalized to a time percentage before averaging curves. As the timing of event occurrences may shift across strides, the shape of the averaged curves is distorted and therefore the standard deviation is overvalued. Stride magnitude normalization is performed by means of dimensionless numbers. However, there is little agreement on which body size correction methods should be used. The Procrustes method describes curve shape and shape change in a mathematical and statistical framework, independently of time and size factors. The present study aims to explore how this technique may be used for time- and magnitude-stride normalization to reflect individual and group mean responses. The Procrustes method, which combines quantitative and visual features, is applied to the shape of the ankle and knee cyclograms. Superimposition of 25 cyclograms (10 for sprinters (SP) and 15 for middle-distance runners (MDR)) was supplemented by statistical procedures (principal component analysis, discriminant function) to extract the main key events, which vary according to the athletic specialities. In comparison with the MDR (poulaine-shaped cyclogram), the ovoid cyclogram of SP reveals the following gait indicators: a short braking phase, a rapid initial lower limb swing in the forward direction, a fast upward movement of the knee and ankle, and an active foot contact. The Procrustes approach could be used to describe other quasi-periodic movements through relative motion plots (e.g., cyclograms, angle-angle diagrams, phase plane portraits). 相似文献
103.
van der Kraan PM Goumans MJ Blaney Davidson E ten Dijke P 《Cell and tissue research》2012,347(1):257-265
Osteoarthritis (OA) is a disease of articular cartilage, with aging as the main risk factor. In OA, changes in chondrocytes
lead to the autolytic destruction of cartilage. Transforming growth factor-β has recently been demonstrated to signal not
only via activin receptor-like kinase 5 (ALK5)-induced Smad2/3 phosphorylation, but also via ALK1-induced Smad1/5/8 phosphorylation
in articular cartilage. In aging cartilage and experimental OA, the ratio ALK1/ALK5 has been found to be increased, and the
expression of ALK1 is correlated with matrix metalloproteinase-13 expression. The age-dependent shift towards Smad1/5/8 signalling
might trigger the differentiation of articular chondrocytes with an autolytic phenotype. 相似文献
104.
Bennett JA Prince LR Parker LC Stokes CA de Bruin HG van den Berge M Heijink IH Whyte MK Sabroe I 《Journal of virology》2012,86(12):6595-6604
Pellino-1 has recently been identified as a regulator of interleukin-1 (IL-1) signaling, but its roles in regulation of responses of human cells to human pathogens are unknown. We investigated the potential roles of Pellino-1 in the airways. We show for the first time that Pellino-1 regulates responses to a human pathogen, rhinovirus minor group serotype 1B (RV-1B). Knockdown of Pellino-1 by small interfering RNA (siRNA) was associated with impaired production of innate immune cytokines such as CXCL8 from human primary bronchial epithelial cells in response to RV-1B, without impairment in production of antiviral interferons (IFN), and without loss of control of viral replication. Pellino-1 actions were likely to be independent of interleukin-1 receptor-associated kinase-1 (IRAK-1) regulation, since Pellino-1 knockdown in primary epithelial cells did not alter responses to IL-1 but did inhibit responses to poly(I·C), a Toll-like receptor 3 (TLR3) activator that does not signal via IRAK-1 to engender a response. These data indicate that Pellino-1 represents a novel target that regulates responses of human airways to human viral pathogens, independently of IRAK signaling. Neutralization of Pellino-1 may therefore provide opportunities to inhibit potentially harmful neutrophilic inflammation of the airways induced by respiratory viruses, without loss of control of the underlying viral infection. 相似文献
105.
BMP signaling in vascular diseases 总被引:1,自引:0,他引:1
106.
William G. Ambrose Jr. Paul E. Renaud William L. Locke V Finlo R. Cottier J?rgen Berge Michael L. Carroll Benjamin Levin Stuart Ryan 《Polar Biology》2012,35(3):345-354
Growth patterns of two common circumpolar bivalves, the Greenland cockle (Serripes groenlandicus), and the hairy cockle (Clinocardium ciliatum) have been used in previous studies to reconstruct environmental conditions in the arctic. To date, there has been no direct
determination that growth lines in either species are deposited periodically, and there has been no examination of factors
affecting growth. We placed calcein-marked individuals of both species on oceanographic moorings in two fjords (Rijpfjord
and Kongsfjord) in the Svalbard archipelago for one and two (Kongsfjord only) years. Growth patterns were compared with concurrent
in situ temperature and fluorescence data in order to assess environmental controls on growth. Dark growth lines are evident
on the outer shell surface and internally in shell cross section in both S. groenlandicus and C. ciliatum, and both species deposited only one line per year, unequivocally confirming that internal lines are deposited annually. Growth
line deposition in both species began in late summer to early fall, before the seasonal decline in temperature. There was
no difference in growth of S. groenlandicus between the two fjords despite differences in water temperature (3°C), fluorescence (nearly threefold) and the onset and
duration of the winter season. C. ciliatum, however, grew approximately 2.8 times faster in the warmer, more food-rich Kongsfjord than in Rijpfjord. Subannual lines
were counted in two individuals of each species from each fjord, but deposition of these lines was not clearly related to
number of growing days estimated by temperature and fluorescence. 相似文献
107.
108.
109.
Carnicer M Canelas AB Ten Pierick A Zeng Z van Dam J Albiol J Ferrer P Heijnen JJ van Gulik W 《Metabolomics : Official journal of the Metabolomic Society》2012,8(2):284-298
Accurate, reliable and reproducible measurement of intracellular metabolite levels has become important for metabolic studies
of microbial cell factories. A first critical step for metabolomic studies is the establishment of an adequate quenching and
washing protocol, which ensures effective arrest of all metabolic activity and removal of extracellular metabolites, without
causing leakage of metabolites from the cells. Five different procedures based on cold methanol quenching and cell separation
by filtration were tested for metabolomics of Pichia pastoris regarding methanol content and temperature of the quenching solution as key parameters. Quantitative evaluation of these
protocols was carried out through mass balance analysis, based on metabolite measurements in all sample fractions, those are
whole broth, quenched and washed cells, culture filtrate and quenching and washing solution. Finally, the optimal method was
used to study the time profiles of free amino acid and central carbon metabolism intermediates in glucose-limited chemostat
cultures. Acceptable recoveries (>90%) were obtained for all quenching procedures tested. However, quenching at −27°C in 60%
v/v methanol performed slightly better in terms of leakage minimization. We could demonstrate that five residence times under
glucose limitation are enough to reach stable intracellular metabolite pools. Moreover, when comparing P. pastoris and S. cerevisiae metabolomes, under the same cultivation conditions, similar metabolite fingerprints were found in both yeasts, except for
the lower glycolysis, where the levels of these metabolites in P. pastoris suggested an enzymatic capacity limitation in that part of the metabolism. 相似文献
110.
Marta Laskowski Vernica A Grieneisen Hugo Hofhuis Colette A. ten Hove Paulien Hogeweg Athanasius F. M Mare Ben Scheres 《PLoS biology》2008,6(12)
Lateral organ position along roots and shoots largely determines plant architecture, and depends on auxin distribution patterns. Determination of the underlying patterning mechanisms has hitherto been complicated because they operate during growth and division. Here, we show by experiments and computational modeling that curvature of the Arabidopsis root influences cell sizes, which, together with tissue properties that determine auxin transport, induces higher auxin levels in the pericycle cells on the outside of the curve. The abundance and position of the auxin transporters restricts this response to the zone competent for lateral root formation. The auxin import facilitator, AUX1, is up-regulated by auxin, resulting in additional local auxin import, thus creating a new auxin maximum that triggers organ formation. Longitudinal spacing of lateral roots is modulated by PIN proteins that promote auxin efflux, and pin2,3,7 triple mutants show impaired lateral inhibition. Thus, lateral root patterning combines a trigger, such as cell size difference due to bending, with a self-organizing system that mediates alterations in auxin transport. 相似文献