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111.
TE Willnow C Antignac AW Br?ndli EI Christensen RD Cox D Davidson JA Davies O Devuyst G Eichele ND Hastie PJ Verroust A Schedl IC Meij 《Organogenesis》2005,2(2):42-47
Rapid progress in genome research creates a wealth of information on the functional annotation of mammalian genome sequences. However, as we accumulate large amounts of scientific information we are facing problems of how to integrate and relate the data produced by various genomic approaches. Here, we propose the novel concept of an organ atlas where diverse data from expression maps to histological findings to mutant phenotypes can be queried, compared and visualized in the context of a three-dimensional reconstruction of the organ. We will seek proof of concept for the organ atlas by elucidating genetic pathways involved in development and pathophysiology of the kidney. Such a kidney atlas may provide a paradigm for a new systems-biology approach in functional genome research aimed at understanding the genetic bases of organ development, physiology and disease.Key Words: EuReGene, kidney, genome, development, pathophysiology, genetics 相似文献
112.
Nellist M van Slegtenhorst MA Goedbloed M van den Ouweland AM Halley DJ van der Sluijs P 《The Journal of biological chemistry》1999,274(50):35647-35652
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by a broad phenotypic spectrum that includes seizures, mental retardation, renal dysfunction and dermatological abnormalities. Mutations to either the TSC1 or TSC2 gene are responsible for the disease. The TSC1 gene encodes hamartin, a 130-kDa protein without significant homology to other known mammalian proteins. Analysis of the amino acid sequence of tuberin, the 200-kDa product of the TSC2 gene, identified a region with limited homology to GTPase-activating proteins. Previously, we demonstrated direct binding between tuberin and hamartin. Here we investigate this interaction in more detail. We show that the complex is predominantly cytosolic and may contain additional, as yet uncharacterized components alongside tuberin and hamartin. Furthermore, because oligomerization of the hamartin carboxyl-terminal coiled coil domain was inhibited by the presence of tuberin, we propose that tuberin acts as a chaperone, preventing hamartin self-aggregation. 相似文献
113.
A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages 总被引:4,自引:13,他引:4
Lockhart PJ; Steel MA; Barbrook AC; Huson DH; Charleston MA; Howe CJ 《Molecular biology and evolution》1998,15(9):1183-1188
The aims of the work were (1) to develop statistical tests to identify
whether substitution takes place under a covariotide model in sequences
used for phylogenetic inference and (2) to determine the influence of
covariotide substitution on phylogenetic trees inferred for photosynthetic
and other organisms. (Covariotide and covarion models are ones in which
sites that are variable in some parts of the underlying tree are invariable
in others and vice versa.) Two tests were developed. The first was a
contingency test, and the second was an inequality test comparing the
expected number of variable sites in two groups with the observed number.
Application of these tests to 16S rDNA and tufA sequences from a range of
nonphotosynthetic prokaryotes and oxygenic photosynthetic prokaryotes and
eukaryotes suggests the occurrence of a covariotide mechanism. The degree
of support for partitioning of taxa in reconstructed trees involving these
organisms was determined in the presence or absence of sites showing
particular substitution patterns. This analysis showed that the support for
splits between (1) photosynthetic eukaryotes and prokaryotes and (2)
photosynthetic and nonphotosynthetic organisms could be accounted for by
patterns arising from covariotide substitution. We show that the additional
problem of compositional bias in sequence data needs to be considered in
the context of patterns of covariotide/covarion substitution. We argue that
while covariotide or covarion substitution may give rise to
phylogenetically informative patterns in sequence data, this may not always
be so.
相似文献
114.
Ans M. W. van den Ouweland Mieke N. van der Est Eveline Wesby-van Swaay Ton S. L. N. Tijmensen Frans J. Los Jan O. Van Hemel Raoul C. M. Hennekam Hanne J. Meijers-Heijboer Martinus F. Niermeijer Dicky J. J. Halley 《Human genetics》1995,95(5):562-567
Previously, 158 nuclear families with probands suspected of having either Prader Willi (PWS) or Angelman syndrome (AS) were analyzed with polymorphic DNA markers from the 15q11–13 region. These cases have been re-evaluated with the probe PW71 (D15S63), which detects parent-of-origin-specific alleles after digestion with a methylation-sensitive restriction enzyme (HpaII). Application of PW71 to DNA samples isolated from leucocytes, confirmed the deletions and uniparental disomies detected earlier by marker analysis, and resolved 50% of the previously uninformative (n=18) cases. PW71 and restriction fragment length polymorphism analysis indicated that, in all resolved cases, disomies of the 15q11–13 region were present. The use of PW71 increased the percentage of disomies detected in our PWS and AS patient groups. Almost 50% of our PWS patients and 17% of the AS patients showed a disomy of maternal or paternal origin, respectively. DNA of first trimester chorionic villi and of fibroblast cultures was not suitable for analysis with PW71 because of different methylation patterns. The application of PW71 is recommended for the diagnosis of the PWS and AS, with respect to DNA samples from blood. 相似文献
115.
F M Halley 《Biofeedback and self-regulation》1991,16(1):55-74
Increasing scientific study and attention is being directed to mind-body interactions, particularly to the interrelationships between the brain and the immune system. This effort has created a new interdisciplinary field, psychoneuroimmunology. An overview of this new field is provided, followed by a comprehensive survey of the growing evidence suggesting that measurable immune system parameters can be influenced by biobehavioral strategies involving self-regulation. Modalities included are relaxation and imagery techniques, biofeedback-assisted strategies, the use of humor, and affiliation to influence emotional states, hypnosis, and conditioning paradigms. The majority of studies have reported significant immune parameter changes. Additional well-designed research is needed to clarify and confirm these initial findings. Future research would benefit from investigating the clinical implications of these immune parameter changes. Knowledge of effects of the mind on the body is rapidly expanding and may be important for achieving improved immune system functioning and health. 相似文献
116.
Dispersal of Amazonian birds in continuous and fragmented forest 总被引:1,自引:0,他引:1
Many ecologists believe birds disappear from tropical forest fragments because they are poor dispersers. We test this idea using a spatially explicit capture data base from the Biological Dynamics of Forest Fragments Project near Manaus, Brazil. We measure bird movements directly, over relatively large scales of space and time, both before and after landscape fragmentation. We found that species which disappear from fragments move extensively between plots before isolation, but not after, and often disperse to longer distances in continuous forest than in fragmented forest. Such species also preferentially emigrate from smaller to larger fragments, showing no preference in continuous forest. In contrast, species that persist in fragments are generally less mobile, do not cross gaps as often, yet disperse further after fragmentation than before. 'Heavy tailed' probability models usually explain dispersal kernels better than exponential or Gaussian models, suggesting tropical forest birds may be better dispersers than assumed with some individuals moving very long distances. 相似文献
117.
K. Evangelou J. Bramis I. Peros P. Zacharatos D. Dasiou-Plakida N. Kalogeropoulos PJ Asimacopoulos C. Kittas E. Marinos VG Gorgoulis 《Biotechnic & histochemistry》2004,79(1):5-10
It is well established that p16INK4A protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 INK4A usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16INK4A immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16INK4 represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16INK4A staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16INK4A cytoplasmic expression. We observed p16 INK4A immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16INK4A immunoreactivity was detected only in the nuclei. We have demonstrated that p16INK4A cytoplasmic staining is specific and suggest that it represents a mechanism of p16INK4A inactivation similar to that observed in other tumor suppressor genes. 相似文献
118.
119.
120.
Tamar E. Carter Halley Malloy Alexandre Existe Gladys Memnon Yves St. Victor Bernard A. Okech Connie J. Mulligan 《PloS one》2015,10(10)
Hispaniola, comprising Haiti and the Dominican Republic, has been identified as a candidate for malaria elimination. However, incomplete surveillance data in Haiti hamper efforts to assess the impact of ongoing malaria control interventions. Characteristics of the genetic diversity of Plasmodium falciparum populations can be used to assess parasite transmission, which is information vital to evaluating malaria elimination efforts. Here we characterize the genetic diversity of P. falciparum samples collected from patients at seven sites in Haiti using 12 microsatellite markers previously employed in population genetic analyses of global P. falciparum populations. We measured multiplicity of infections, level of genetic diversity, degree of population geographic substructure, and linkage disequilibrium (defined as non-random association of alleles from different loci). For low transmission populations like Haiti, we expect to see few multiple infections, low levels of genetic diversity, high degree of population structure, and high linkage disequilibrium. In Haiti, we found low levels of multiple infections (12.9%), moderate to high levels of genetic diversity (mean number of alleles per locus = 4.9, heterozygosity = 0.61), low levels of population structure (highest pairwise Fst = 0.09 and no clustering in principal components analysis), and moderate linkage disequilibrium (ISA = 0.05, P<0.0001). In addition, population bottleneck analysis revealed no evidence for a reduction in the P. falciparum population size in Haiti. We conclude that the high level of genetic diversity and lack of evidence for a population bottleneck may suggest that Haiti’s P. falciparum population has been stable and discuss the implications of our results for understanding the impact of malaria control interventions. We also discuss the relevance of parasite population history and other host and vector factors when assessing transmission intensity from genetic diversity data. 相似文献