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961.
Villeneuve C Baricault L Canelle L Barboule N Racca C Monsarrat B Magnaldo T Larminat F 《Molecular biology of the cell》2011,22(7):999-1013
Although the anti-apoptotic activity of Bcl-2 has been extensively studied, its mode of action remains incompletely understood. Deciphering the network of Bcl-2 interacting factors is necessary to better understand the key function of Bcl-2 in apoptosis initiation. To identify novel Bcl-2 mitochondrial partners, we have combined a Bcl-2 immunocapture with a mass spectrometry analysis using highly pure mitochondrial fractions isolated from human cancer cells. We identified at high confidence 127 potential Bcl-2-interacting proteins. Gene ontology mining reveals enrichment for mitochondrial proteins, endoplasmic reticulum-associated proteins, and cytoskeleton-associated proteins. Importantly, we report the identification of galectin-7 (Gal7), a member of a family of β-galactoside-binding lectins that was already known to exhibit a pro-apoptotic function, as a new mitochondrial Bcl-2 interacting partner. Our data further show that endogenous Bcl-2 coimmunoprecipitates with Gal7 and that recombinant Gal7 directly interacts with recombinant Bcl-2. A fraction of Gal7 is constitutively localized at mitochondria in a Bcl-2-dependent manner and sensitizes the mitochondria to the apoptotic signal. In addition, we show that the Bcl-2/Gal7 interaction is abolished following genotoxic stress. Taken together, our findings suggest that the binding of Gal7 to Bcl-2 may constitute a new target for enhancing the intrinsic apoptosis pathway. 相似文献
962.
963.
Bessire M Borel S Fabre G Carraça L Efremova N Yephremov A Cao Y Jetter R Jacquat AC Métraux JP Nawrath C 《The Plant cell》2011,23(5):1958-1970
Although the multilayered structure of the plant cuticle was discovered many years ago, the molecular basis of its formation and the functional relevance of the layers are not understood. Here, we present the permeable cuticle1 (pec1) mutant of Arabidopsis thaliana, which displays features associated with a highly permeable cuticle in several organs. In pec1 flowers, typical cutin monomers, such as ω-hydroxylated fatty acids and 10,16-dihydroxypalmitate, are reduced to 40% of wild-type levels and are accompanied by the appearance of lipidic inclusions within the epidermal cell. The cuticular layer of the cell wall, rather than the cuticle proper, is structurally altered in pec1 petals. Therefore, a significant role for the formation of the diffusion barrier in petals can be attributed to this layer. Thus, pec1 defines a new class of mutants. The phenotypes of the pec1 mutant are caused by the knockout of ATP BINDING CASSETTEG32 (ABCG32), an ABC transporter from the PLEIOTROPIC DRUG RESISTANCE family that is localized at the plasma membrane of epidermal cells in a polar manner toward the surface of the organs. Our results suggest that ABCG32 is involved in the formation of the cuticular layer of the cell wall, most likely by exporting particular cutin precursors from the epidermal cell. 相似文献
964.
965.
Large scale international activities for systematic conditional mouse mutagenesis, exploiting advances in the sophisticated manipulation of the mouse genome, has established the mouse as the premier organism for developing models of human disease and drug action. Conditional mutagenesis is critical for the elucidation of the gene functions that exert pleiotropic effects in a variety of cell types and tissues throughout the life of the animal. The majority of new mouse mutants are therefore designed as conditional, activated only in a specific tissue (spatial control) and/or life stage (temporal control) through biogenic Cre/loxP technologies. The full power of conditional mutant mice can therefore only be exploited with the availability of well characterized mouse lines expressing Cre-recombinase in tissue, organ and cell type-specific patterns, to allow the creation of somatic mutations in defined genes. This chapter provides an update on the current state of Cre driver mouse lines worldwide, and reviews the available public databases and portals that capture critical details of Cre driver lines such as the efficiency of recombination, cell tissue specificity, or genetic background effects. The continuously changing landscape of these mouse resources reflects the rapid progression of research and development in conditional and inducible mouse mutagenesis. 相似文献
966.
Normah M. Noor Choo Wee Kean Yap Lip Vun Zeti Azura Mohamed-Hussein 《In vitro cellular & developmental biology. Plant》2011,47(1):26-36
Malaysia is fortunate and proud to contain some of the world’s richest biodiversity. In Malaysia, there are an estimated 185,000
species of fauna and 12,500 species of flowering plants, many of which are endemic to tropical forests in this region. Indeed,
such diversity is an important and invaluable national asset to safeguard both present and future generations. In vitro conservation offers possible techniques for the preservation of plant germplasm that at present is difficult to maintain
or is maintained with limited success. Research at the Universiti Kebangsaan Malaysia (The National University of Malaysia)
focuses on the cryopreservation of woody fruit species with seeds that cannot tolerate cryopreservation (recalcitrant or intermediate).
Among the plants with recalcitrant seeds are such traditionally important edible tropical fruits as mangosteen, langsat, and
rambai (Garcinia mangostana, Lansium domesticum, and Baccaurea motleyana). Citrus aurantifolia, Citrus suhuiensis, Citrus madurensis, Citrus hystrix, and Fortunella polyandra are among the Citrus and Citrus-related species studied. Cryopreservation studies include the Nepenthes species (pitcher plants) of Malaysia. Fundamental research on desiccation and low-temperature tolerance and on the physiology
of desiccation are used to understand seed behavior, a prerequisite for the development of successful conservation techniques.
At the same time, cryopreservation protocols for several Citrus and forestry species were developed for embryonic axes and adventitious shoots, mainly using rapid dehydration and PVS2 vitrification
techniques. There are no successful standard techniques or protocols for species with highly recalcitrant seeds such as Garcinia species. Modification of existing protocols or development of new methods is required, but this can be accomplished only
when a detailed understanding of the recalcitrant nature of the seeds or explants is achieved. While we have considerable
knowledge concerning the basics of biochemical processes and some molecular data from work on desiccation-tolerant seeds,
a great need remains for understanding the cause of the recalcitrance or desiccation sensitivity of these seeds. It may be
necessary to use a systems biology approach that exploits the “omics” technologies to generate global molecular data. In combination
with bioinformatics for data integration and analyses, this approach would move toward improved modeling of the biological
pathways associated with the development of recalcitrant seeds. 相似文献
967.
Everaert N Willemsen H Kamers B Decuypere E Bruggeman V 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2011,158(2):215-220
It has been shown that during embryonic chicken (Gallus gallus) development, the metabolism of broiler embryos differs from that of layers in terms of embryonic growth, pCO2/pO2 blood levels, heat production, and heart rate. Therefore, these strains might adapt differently on extreme environmental factors such as exposure to high CO2. The aim of this study was to compare broiler and layer embryos in their adaptation to 4% CO2 from embryonic days (ED) 12 to 18. Due to hypercapnia, blood pCO2 increased in both strains. Blood bicarbonate concentration was ~10 mmol/L higher in embryos exposed to high CO2 of both strains, while the bicarbonates of broilers had ~5 mmol/L higher values than layer embryos. In addition, the pH increased when embryos of both strains were exposed to CO2. Moreover, under CO2 conditions, the blood potassium concentration increased in both strains significantly, reaching a plateau at ED14. At ED12, the layer strain had a higher increase in CAII protein in red blood cells due to incubation under high CO2 compared to the broiler strain, whereas at ED14, the broiler strain had the highest increase. In conclusion, the most striking observation was the similar mechanism of broiler and layer embryos to cope with high CO2 levels. 相似文献
968.
Fugier C Klein AF Hammer C Vassilopoulos S Ivarsson Y Toussaint A Tosch V Vignaud A Ferry A Messaddeq N Kokunai Y Tsuburaya R de la Grange P Dembele D Francois V Precigout G Boulade-Ladame C Hummel MC Lopez de Munain A Sergeant N Laquerrière A Thibault C Deryckere F Auboeuf D Garcia L Zimmermann P Udd B Schoser B Takahashi MP Nishino I Bassez G Laporte J Furling D Charlet-Berguerand N 《Nature medicine》2011,17(6):720-725
Myotonic dystrophy is the most common muscular dystrophy in adults and the first recognized example of an RNA-mediated disease. Congenital myotonic dystrophy (CDM1) and myotonic dystrophy of type 1 (DM1) or of type 2 (DM2) are caused by the expression of mutant RNAs containing expanded CUG or CCUG repeats, respectively. These mutant RNAs sequester the splicing regulator Muscleblind-like-1 (MBNL1), resulting in specific misregulation of the alternative splicing of other pre-mRNAs. We found that alternative splicing of the bridging integrator-1 (BIN1) pre-mRNA is altered in skeletal muscle samples of people with CDM1, DM1 and DM2. BIN1 is involved in tubular invaginations of membranes and is required for the biogenesis of muscle T tubules, which are specialized skeletal muscle membrane structures essential for excitation-contraction coupling. Mutations in the BIN1 gene cause centronuclear myopathy, which shares some histopathological features with myotonic dystrophy. We found that MBNL1 binds the BIN1 pre-mRNA and regulates its alternative splicing. BIN1 missplicing results in expression of an inactive form of BIN1 lacking phosphatidylinositol 5-phosphate-binding and membrane-tubulating activities. Consistent with a defect of BIN1, muscle T tubules are altered in people with myotonic dystrophy, and membrane structures are restored upon expression of the normal splicing form of BIN1 in muscle cells of such individuals. Finally, reproducing BIN1 splicing alteration in mice is sufficient to promote T tubule alterations and muscle weakness, a predominant feature of myotonic dystrophy. 相似文献
969.
Megan Hardin Edwin K Silverman R Graham Barr Nadia N Hansel Joyce D Schroeder Barry J Make James D Crapo Craig P Hersh 《Respiratory research》2011,12(1):127
Background
The coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.Methods
We performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.Results
119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.Conclusion
Subjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.Trial registration
ClinicalTrials.gov: NCT00608764相似文献970.
Nadia Al-Zahery Maria Pala Vincenza Battaglia Viola Grugni Mohammed A Hamod Baharak Hooshiar Kashani Anna Olivieri Antonio Torroni Augusta S Santachiara-Benerecetti Ornella Semino 《BMC evolutionary biology》2011,11(1):1-16