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81.
The promyelocytic leukemia (PML) tumor suppressor is a pleiotropic modulator of apoptosis. However, the molecular basis for such a diverse proapoptotic role is currently unknown. We show that extranuclear Pml was specifically enriched at the endoplasmic reticulum (ER) and at the mitochondria-associated membranes, signaling domains involved in ER-to-mitochondria calcium ion (Ca(2+)) transport and in induction of apoptosis. We found Pml in complexes of large molecular size with the inositol 1,4,5-trisphosphate receptor (IP(3)R), protein kinase Akt, and protein phosphatase 2a (PP2a). Pml was essential for Akt- and PP2a-dependent modulation of IP(3)R phosphorylation and in turn for IP(3)R-mediated Ca(2+) release from ER. Our findings provide a mechanistic explanation for the pleiotropic role of Pml in apoptosis and identify a pharmacological target for the modulation of Ca(2+) signals.  相似文献   
82.
We investigated for 2 years (1995–1996) the time course development of chlorosis and the variation of iron (Fe) content in vegetative and reproductive organs in two nectarine orchards planted with cv Spring Red and cv Stark Redgold on calcareous soils of the Po valley (Italy) with the final aim to evaluate possible tools for the early prognosis of Fe chlorosis and a more efficient fertilization management. Due to the withdrawal of Fe supply, floral Fe concentration significantly decreased in 1996 as compared with 1995 in cv Spring Red, but not in Stark Redgold. Correlation coefficients between Fe and chlorophyll (Chl) from the same leaves were always higher when Fe was considered as amount present per leaf or per unit of leaf area than as leaf dry weight. The fact that chlorotic and green leaves had similar Fe concentration could be explained by an overestimate of Fe in the chlorotic leaf as a consequence of a reduction of its size. However, the decrease of Chl concentration between 60 and 120 days after full bloom (DAFB) occurred while leaf Fe content generally increased, indicating that even during chlorosis development leaves were supplied with some iron. We therefore suggest that the development of chlorosis was associated with an inactivation of Fe in the leaf apoplast. In 1995, regardless the cultivar, floral Fe concentration and leaf Chl were never correlated. In 1996 floral Fe concentration was linearly related to leaf Chl recorded 60 and 120 DAFB in cv Spring Red only. Floral Fe concentration at full bloom 1996, regardless the variety, was linearly related to leaf Chl determined in spring of the previous year, suggesting that flower Fe concentration might be used for assessing the storage of iron during the previous season.  相似文献   
83.
84.
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides (Mmm) is a severe cattle disease, present in many countries in sub-Saharan Africa. The development of improved diagnostic tests and vaccines for CBPP control remains a research priority. Polyacrylamide gel electrophoresis and mass spectrometry were used to characterize the Triton X-114 soluble proteome of nine Mmm strains isolated from Europe or Africa. Of a total of 250 proteins detected, 67 were present in all strains investigated. Of these, 44 were predicted to be lipoproteins or cytoplasmic membrane-associated proteins and are thus likely to be members of the core in vitro surface membrane-associated proteome of Mmm. Moreover, the presence of all identified proteins in other ruminant Mycoplasma pathogens were investigated. Two proteins of the core proteome were identified only in other cattle pathogens of the genus Mycoplasma pointing towards a role in host–pathogen interactions. The data generated will facilitate the identification and prioritization of candidate Mycoplasma antigens for improved control measures, as it is likely that surface-exposed membrane proteins will include those that are involved in host–pathogen interactions.  相似文献   
85.
Canine pulmonary eosinophilic granulomatosis is a rare inflammatory pulmonary disease characterized by formation of eosinophilic granulomas that tend to obliterate the normal pulmonary architecture. The purpose of this retrospective study was to describe the CT characteristics of confirmed idiopathic pulmonary eosinophilic granulomatosis in a group of dogs. Five dogs met inclusion criteria. All patients were young adult dogs of variable breeds. No dog had concurrent occult heartworm disease. Computed tomographic characteristics most commonly included pulmonary masses and nodules of variable size, and lesions were most commonly located in the caudal lung lobes. Four dogs had large pulmonary masses with or without additional nodules and one dog had nodular lesions disseminated throughout the entire lung parenchyma. All large eosinophilic granulomas were smoothly margined, heterogeneous pulmonary masses displaying heterogeneous contrast enhancement. A honeycomb‐like enhancement pattern was observed in all but one mass and consisted of multiple hyperattenuating rims delineating central hypoattenuating areas, suggestive of bronchiectatic lung with peripheral enhancing airway walls and fluid‐filled, necrotic bronchial lumen. One dog had evidence of tracheobronchial lymphadenopathy. Findings indicated that canine eosinophilic pulmonary granulomatosis should be included as a differential diagnosis for dogs with CT characteristics of multiple pulmonary masses and/or nodules in caudal lung lobes, and a honeycomb‐like enhancement pattern in masses after intravenous administration of iodinated contrast medium.  相似文献   
86.
Checkpoint-mediated control of replicating chromosomes is essential for preventing cancer. In yeast, Rad53 kinase protects stalled replication forks from pathological rearrangements. To characterize the mechanisms controlling fork integrity, we analyzed replication intermediates formed in response to replication blocks using electron microscopy. At the forks, wild-type cells accumulate short single-stranded regions, which likely causes checkpoint activation, whereas rad53 mutants exhibit extensive single-stranded gaps and hemi-replicated intermediates, consistent with a lagging-strand synthesis defect. Further, rad53 cells accumulate Holliday junctions through fork reversal. We speculate that, in checkpoint mutants, abnormal replication intermediates begin to form because of uncoordinated replication and are further processed by unscheduled recombination pathways, causing genome instability.  相似文献   
87.
A femtosecond laser-based optical frequency synthesizer is referenced to an optical standard, and we use it to demonstrate the generation and control of the frequency of electromagnetic fields over 100 terahertz of bandwidth with fractional uncertainties approaching 1 part in 10(19). The reproducibility of this performance is verified by comparison of different types of femtosecond laser-based frequency synthesizers from three laboratories.  相似文献   
88.
89.
A degenerate gas of identical fermions is brought to collapse by the interaction with a Bose-Einstein condensate. We used an atomic mixture of fermionic potassium-40 and bosonic rubidium-87, in which the strong interspecies attraction leads to an instability above a critical number of particles. The observed phenomenon suggests a direction for manipulating fermion-fermion interactions on the route to superfluidity.  相似文献   
90.
Group B Streptococcus (GBS) is a multiserotype bacterial pathogen representing a major cause of life-threatening infections in newborns. To develop a broadly protective vaccine, we analyzed the genome sequences of eight GBS isolates and cloned and tested 312 surface proteins as vaccines. Four proteins elicited protection in mice, and their combination proved highly protective against a large panel of strains, including all circulating serotypes. Protection also correlated with antigen accessibility on the bacterial surface and with the induction of opsonophagocytic antibodies. Multigenome analysis and screening described here represent a powerful strategy for identifying potential vaccine candidates against highly variable pathogens.  相似文献   
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