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41.
Stephanie Lemaire Christian Derappe Valerie Pasqualetto Kristina Mrkoci Eric G Berger Michele Aubery Dominique Neel 《Glycoconjugate journal》1998,15(2):161-168
We previously showed that in vitro activated human T lymphocytes expressed increased amounts of -1,6-branched N-linked oligosaccharides (Lemaire S et al. (1994) J Biol Chem 269: 8069-74), which have been proposed to participate in the regulation of the immune process. In the present paper, we compared the activity and expression of -1,4-galactosyltransferase (GalT), one of the glycosyltransferases involved in the biosynthesis of these -1,6-branched N-linked oligosaccharides, before and after in vitro activation of T lymphocytes after a 40 h treatment with a mixture of phorbol 12-myristate 13-acetate and Phaseolus vulgaris lectin. After treatment, the enzymatic activity of the GalT was significantly increased and immunoblot experiments performed with a monoclonal antibody to human GalT showed an increased intensity of the GalT band at 49 kDa, attributable to an enhancement of GalT mRNA level, as shown by Northern blots. However, treatment of the same T-lymphocytes by phorbol ester alone, which is unable to induce mitosis, resulted in a comparable increase of the expression of GalT. Moreover, these phorbol ester-treated T lymphocytes, analysed by flow cytometry exhibited a two-fold increase in the expression of GalT. Finally, confocal fluorescence microscopy performed on all T lymphocytes (treated or not) showed that the flow cytometric signal of GalT originates from intracellular, Golgi-associated antigen only since no surface GalT was detected. 相似文献
42.
Icksoo Lee Alena Pecinova Petr Pecina Benjamin G. Neel Toshiyuki Araki Raju Kucherlapati Amy E. Roberts Maik Hüttemann 《生物化学与生物物理学报:疾病的分子基础》2010,1802(2):275-283
Noonan syndrome (NS) is an autosomal dominant disorder, and a main feature is congenital heart malformation. About 50% of cases are caused by gain-of-function mutations in the tyrosine phosphatase SHP2/PTPN11, a downstream regulator of ERK/MAPK. Recently it was reported that SHP2 also localizes to the mitochondrial intercristae/intermembrane space (IMS), but the role of SHP2 in mitochondria is unclear. The mitochondrial oxidative phosphorylation (OxPhos) system provides the vast majority of cellular energy and produces reactive oxygen species (ROS). Changes in ROS may interfere with organ development such as that observed in NS patients. Several phosphorylation sites have been found in OxPhos components including cytochrome c oxidase (CcO) and cytochrome c (Cytc), and we hypothesized that OxPhos complexes may be direct or indirect targets of SHP2. We analyzed mitochondrial function using mouse fibroblasts from wild-types, SHP2 knockdowns, and D61G SHP2 mutants leading to constitutively active SHP2, as found in NS patients. Levels of OxPhos complexes were similar except for CcO and Cytc, which were 37% and 28% reduced in the D61G cells. However, CcO activity was significantly increased, as we also found for two lymphoblast cell lines from NS patients with two independent mutations in PTPN11. D61G cells showed lower mitochondrial membrane potential and 30% lower ATP content compared to controls. ROS were significantly increased; aconitase activity, a marker for ROS-induced damage, was decreased; and catalase activity was increased in D61G cells. We propose that decreased energy levels and/or increased ROS may explain, at least in part, some of the clinical features in NS that overlap with children with mitochondrial disorders. 相似文献
43.
44.
The thorough screening of the MUTYH gene in a large French cohort of sporadic colorectal cancers 总被引:1,自引:0,他引:1
Küry S Buecher B Robiou-du-Pont S Scoul C Colman H Lelièvre B Olschwang S Le Houérou C Le Neel T Faroux R Ollivry J Lafraise B Chupin LD Bézieau S 《Genetic testing》2007,11(4):373-379
The MUTYH gene encodes a key glycosylase of the base-excision repair system that is involved in maintaining genomic DNA stability against oxidative damage. Biallelic germline MUTYH mutations have been proved to greatly predispose to non-familial adenomatous polyposis (FAP) and non-hereditary non-polyposis colorectal cancer (HNPCC) familial recessive forms of colorectal cancer with multiple adenomas. To date, there is still much debate over the impact of monoallelic germline MUTYH mutations on colorectal carcinogenesis. To evaluate their role in the susceptibility to sporadic colon and rectum cancers, we screened 1024 French sporadic colorectal cancer cases and 1121 French healthy controls for Caucasian MUTYH-associated polyposis mutations, including already known mutations p.Gly382Asp and p.Tyr165Cys, and new mutation p.Val479Phe. We observed a nonstatistically significant association between these MUTYH mutations at a heterozygous state and an increase in colorectal cancer risk (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.70-2.27). As a result, we conclude that heterozygous MUTYH mutations do not play a major role in sporadic colorectal carcinogenesis although a modest effect on this process cannot be ruled out. 相似文献
45.
Beste DJ Hooper T Stewart G Bonde B Avignone-Rossa C Bushell ME Wheeler P Klamt S Kierzek AM McFadden J 《Genome biology》2007,8(5):R89
Background
An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis. 相似文献46.
JI Priego AG Lucas-Cuevas I Aparicio JV Giménez JM Cortell-Tormo P Pérez-Soriano 《Biology of sport / Institute of Sport》2015,32(3):219-223
The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) – a 5-min maximal effort run in order to determine the participants’ maximal aerobic speed; and tests 2) and 3) – a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners. 相似文献
47.
3d interaction homology: The structurally known rotamers of tyrosine derive from a surprisingly limited set of information‐rich hydropathic interaction environments described by maps
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Mostafa H. Ahmed Vishal N. Koparde Martin K. Safo J. Neel Scarsdale Glen E. Kellogg 《Proteins》2015,83(6):1118-1136
Sidechain rotamer libraries are obtained through exhaustive statistical analysis of existing crystallographic structures of proteins and have been applied in multiple aspects of structural biology, for example, crystallography of relatively low‐resolution structures, in homology model building and in biomolecular NMR. Little is known, however, about the driving forces that lead to the preference or suitability of one rotamer over another. Construction of 3D hydropathic interaction maps for nearly 30,000 tyrosines reveals the environment around each, in terms of hydrophobic (π–π stacking, etc.) and polar (hydrogen bonding, etc.) interactions. After partitioning the tyrosines into backbone‐dependent (?, ψ) bins, a map similarity metric based on the correlation coefficient was applied to each map‐map pair to build matrices suitable for clustering with k‐means. The first bin (?200° ≤ ? < –155°; ?205° ≤ ψ < –160°), representing 631 tyrosines, reduced to 14 unique hydropathic environments, with most diversity arising from favorable hydrophobic interactions with many different residue partner types. Polar interactions for tyrosine include surprisingly ubiquitous hydrogen bonding with the phenolic OH and a handful of unique environments surrounding the tyrosine backbone. The memberships of all but one of the 14 environments are dominated (>50%) by a single χ1/χ2 rotamer. The last environment has weak or no interactions with the tyrosine ring and its χ1/χ2 rotamer is indeterminate, which is consistent with it being composed of mostly surface residues. Each tyrosine residue attempts to fulfill its hydropathic valence and thus, structural water molecules are seen in a variety of roles throughout protein structure. Proteins 2015; 83:1118–1136. © 2015 Wiley Periodicals, Inc. 相似文献
48.
M Montenegro S Llambí G Castro N Barlocco A Vadell V Landi JV Delgado A Martínez 《Genetics and molecular biology》2015,38(1):48-54
In this study, we genetically characterized the Uruguayan pig breed Pampa Rocha.
Genetic variability was assessed by analyzing a panel of 25 microsatellite markers
from a sample of 39 individuals. Pampa Rocha pigs showed high genetic variability
with observed and expected heterozygosities of 0.583 and 0.603, respectively. The
mean number of alleles was 5.72. Twenty-four markers were polymorphic, with 95.8% of
them in Hardy Weinberg equilibrium. The level of endogamy was low (FIS =
0.0475). A factorial analysis of correspondence was used to assess the genetic
differences between Pampa Rocha and other pig breeds; genetic distances were
calculated, and a tree was designed to reflect the distance matrix. Individuals were
also allocated into clusters. This analysis showed that the Pampa Rocha breed was
separated from the other breeds along the first and second axes. The
neighbour-joining tree generated by the genetic distances DA showed
clustering of Pampa Rocha with the Meishan breed. The allocation of individuals to
clusters showed a clear separation of Pampa Rocha pigs. These results provide
insights into the genetic variability of Pampa Rocha pigs and indicate that this
breed is a well-defined genetic entity. 相似文献
49.
Sara L. Zeigler Maile C. Neel Leonardo Oliveira Becky E. Raboy William F. Fagan 《Biodiversity and Conservation》2011,20(12):2779-2796
Functional connectivity is known to have an important, positive influence on species persistence. Measurements of functional
connectivity traditionally focus on structural attributes of landscapes such as the distance and matrix type between habitat
patches as well as on how species interact with those structural attributes. However, we propose that the social behavior
of a species, through conspecific and heterospecific attraction, will also impact connectivity by changing how dispersers
move with respect to each other and occupied patches. We analyzed functional connectivity patterns using circuit and graph
theory for golden-headed lion tamarins (Leontopithecus chrysomelas) in Brazil under three scenarios. In the first scenario, we looked at connectivity without the effects of attraction under
varying maximum dispersal distance and ecological movement cost thresholds. In the second scenario, we allowed dispersers
to travel over more hostile matrix than they normally would to reach an occupied patch. In the final scenario, we allowed
dispersers to move only to occupied patches. We found that, according to the first scenario, range-wide functional landscape
connectivity for golden-headed lion tamarins is low at realistic maximum dispersal distance and movement cost thresholds.
Incorporating the effects of conspecific or heterospecific attraction would increase functional connectivity, in the case
of scenario two, or decrease functional connectivity, in the case of scenario three. Because conspecific/heterospecific attraction
can have an impact on movement for some species, this factor should be incorporated in assessments of functional connectivity
patterns for social species and others where patch occupancy is likely to influence the movements of dispersers. 相似文献
50.