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排序方式: 共有165条查询结果,搜索用时 15 毫秒
1.
Predisposition for breast cancer in carriers of constitutional translocation 11q;22q. 总被引:5,自引:1,他引:4
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A. Lindblom K. Sandelin L. Iselius J. Dumanski I. White M. Nordenskjld C. Larsson 《American journal of human genetics》1994,54(5):871-876
A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted us to study the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases was significantly higher than expected among the translocation carriers (P < .001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer. 相似文献
2.
Regulating retrotransposon activity through the use of alternative transcription start sites
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3.
Catrin S. Günther Sarah J. Knight Rory Jones Matthew R. Goddard 《Ecology and evolution》2019,9(14):8075-8086
Whether there are general mechanisms, driving interspecific chemical communication is uncertain. Saccharomycetaceae yeast and Drosophila fruit flies, both extensively studied research models, share the same fruit habitat, and it has been suggested their interaction comprises a facultative mutualism that is instigated and maintained by yeast volatiles. Using choice tests, experimental evolution, and volatile analyses, we investigate the maintenance of this relationship and reveal little consistency between behavioral responses of two isolates of sympatric Drosophila species. While D. melanogaster was attracted to a range of different Saccharomycetaceae yeasts and this was independent of fruit type, D. simulans preference appeared specific to a particular S. cerevisiae genotype isolated from a vineyard fly population. This response, however, was not consistent across fruit types and is therefore context‐dependent. In addition, D. simulans attraction to an individual S. cerevisiae isolate was pliable over ecological timescales. Volatile candidates were analyzed to identify a common signal for yeast attraction, and while D. melanogaster generally responded to fermentation profiles, D. simulans preference was more discerning and likely threshold‐dependent. Overall, there is no strong evidence to support the idea of bespoke interactions with specific yeasts for either of these Drosophila genotypes. Rather the data support the idea Drosophila are generally adapted to sense and locate fruits infested by a range of fungal microbes and/or that yeast–Drosophila interactions may evolve rapidly. 相似文献
4.
Chen Wu Cecilia Deng Elena Hilario Nick W. Albert Declan Lafferty Ella R. P. Grierson Blue J. Plunkett Caitlin Elborough Ali Saei Catrin S. Günther Hilary Ireland Alan Yocca Patrick P. Edger Laura Jaakola Katja Karppinen Adrian Grande Ritva Kylli Veli-Pekka Lehtola Andrew C. Allan Richard V. Espley David Chagn 《Molecular ecology resources》2022,22(1):345-360
Bilberry (Vaccinium myrtillus L.) belongs to the Vaccinium genus, which includes blueberries (Vaccinium spp.) and cranberry (V. macrocarpon). Unlike its cultivated relatives, bilberry remains largely undomesticated, with berry harvesting almost entirely from the wild. As such, it represents an ideal target for genomic analysis, providing comparisons with the domesticated Vaccinium species. Bilberry is prized for its taste and health properties and has provided essential nutrition for Northern European indigenous populations. It contains high concentrations of phytonutrients, with perhaps the most important being the purple colored anthocyanins, found in both skin and flesh. Here, we present the first bilberry genome assembly, comprising 12 pseudochromosomes assembled using Oxford Nanopore (ONT) and Hi-C Technologies. The pseudochromosomes represent 96.6% complete BUSCO genes with an assessed LAI score of 16.3, showing a high conservation of synteny against the blueberry genome. Kmer analysis showed an unusual third peak, indicating the sequenced samples may have been from two individuals. The alternate alleles were purged so that the final assembly represents only one haplotype. A total of 36,404 genes were annotated after nearly 48% of the assembly was masked to remove repeats. To illustrate the genome quality, we describe the complex MYBA locus, and identify the key regulating MYB genes that determine anthocyanin production. The new bilberry genome builds on the genomic resources and knowledge of Vaccinium species, to help understand the genetics underpinning some of the quality attributes that breeding programs aspire to improve. The high conservation of synteny between bilberry and blueberry genomes means that comparative genome mapping can be applied to transfer knowledge about marker-trait association between these two species, as the loci involved in key characters are orthologous. 相似文献
5.
Background
Previous trials of the RTS, S malaria candidate vaccine have shown that this vaccine is safe, tolerated and immunogenic. The development plan for this vaccine aims at administering it in the first year of life through the Expanded Program on Immunization (EPI). The objective was to evaluate the safety and reactogenicity of RTS, S/AS02D (0.5 ml dose), a pediatric formulation of GlaxoSmithKline Biologicals' current malaria candidate vaccine RTS, S/AS02A (0.25 ml dose). A 0.5 ml dose of AS02D is composed of the same active ingredients in the same quantities as in a 0.25 ml dose of AS02A and has been developed to be easily introduced into routine EPI practices.Methods
We performed a phase I/IIb randomized double-blind bridging study in a malaria-endemic region of Mozambique, to compare the safety and immunogenicity of both candidate vaccines with the aim of replacing RTS, S/AS02A with RTS, S/AS02D as the candidate pediatric vaccine. 200 Mozambican children aged 3 to 5 years were randomized 1:1 to receive one of the 2 vaccines according to a 0, 1, 2 month schedule.Results
Both vaccines were safe and had similar reactogenicity profiles. All subjects with paired pre and post-vaccination samples showed a vaccine response with respect to anti-circumsporozoite (CS) antibodies irrespective of initial anti-CS serostatus. Geometric mean titers (GMTs) were 191 EU/ml (95% CI 150–242) in recipients of RTS, S/AS02D compared to 180 EU/ml (95% CI 146–221) in recipients of RTS, S/AS02A. For the anti-hepatitis B surface antigen (HBsAg), all subjects were seroprotected at day 90, and the GMTs were 23978 mIU/ml (95% CI 17896–32127) in RTS, S/AS02D recipients and 17410 mIU/ml (95% CI 13322–22752) in RTS, S/AS02A recipients. There was a decrease in anti-CS GMTs between months 3 and 14 in both groups (191 vs 22 EU/mL in RTS, S/AS02D group and 180 vs 29 EU/mL in RTS, S/AS02A group).Conclusion
Our data show that the RTS, S/AS02D is safe, well tolerated, and demonstrates non-inferiority (defined as upper limit of the 95% confidence interval of the anti-CS GMT ratio of RTS, S/AS02A to RTS, S/AS02D below 3.0) of the antibody responses to circumsporozoite and HBsAg induced by the RTS, S/AS02D as compared to the RTS, S/AS02A. 相似文献6.
B-Raf acts via the ROCKII/LIMK/cofilin pathway to maintain actin stress fibers in fibroblasts
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Pritchard CA Hayes L Wojnowski L Zimmer A Marais RM Norman JC 《Molecular and cellular biology》2004,24(13):5937-5952
Recent data have shown that the BRAF gene is mutated at a high frequency in human malignancies. We have analyzed the migratory characteristics of B-raf(-/-) mouse embryonic fibroblasts (MEFs) and compared these with the organization of the actin cytoskeleton and the activity of signaling pathways that are known to influence this organization. Disruption of B-raf significantly reduced the levels of phospho-ERK1/2 and, surprisingly, induced an approximately 1.5-fold increase in cell migration. Consistent with these findings, the high level of actin stress fibers normally present in MEFs was considerably reduced following disruption of B-raf, and the F-actin content of B-raf(-/-) cells was less than half that of B-raf(+/+) cells. Phosphorylation of the myosin light chain on Thr18/Ser19 residues was not reduced in B-raf(-/-) cells. Rather, reduced ROCKII expression and attenuated phosphorylation of ADF/cofilin on serine 3 occurred. Normal stress fiber and phosphocofilin levels were restored by the expression of human B-Raf and catalytically active MEK and by the overexpression of LIM kinase (LIMK). These results have important implications for the role of the B-Raf/ERK signaling pathway in regulating cell motility in normal and malignant cells. They suggest that B-Raf is involved in invasiveness by regulating the proper assembly of actin stress fibers and contractility through a ROCKII/LIMK/cofilin signaling pathway. 相似文献
7.
Applied bioinformatics for the identification of regulatory elements 总被引:13,自引:0,他引:13
8.
Celis JE Gromov P Cabezón T Moreira JM Ambartsumian N Sandelin K Rank F Gromova I 《Molecular & cellular proteomics : MCP》2004,3(4):327-344
Clinical cancer proteomics aims at the identification of markers for early detection and predictive purposes, as well as to provide novel targets for drug discovery and therapeutic intervention. Proteomics-based analysis of traditional sources of biomarkers, such as serum, plasma, or tissue lyzates, has resulted in a wealth of information and the finding of several potential tumor biomarkers. However, many of these markers have shown limited usefulness in a clinical setting, underscoring the need for new clinically relevant sources. Here we present a novel and highly promising source of biomarkers, the tumor interstitial fluid (TIF) that perfuses the breast tumor microenvironment. We collected TIFs from small pieces of freshly dissected invasive breast carcinomas and analyzed them by two-dimensional polyacrylamide gel electrophoresis in combination with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Western immunoblotting, as well as by cytokine-specific antibody arrays. This approach provided for the first time a snapshot of the protein components of the TIF, which we show consists of more than one thousand proteins--either secreted, shed by membrane vesicles, or externalized due to cell death--produced by the complex network of cell types that make up the tumor microenvironment. So far, we have identified 267 primary translation products including, but not limited to, proteins involved in cell proliferation, invasion, angiogenesis, metastasis, inflammation, protein synthesis, energy metabolism, oxidative stress, the actin cytoskeleton assembly, protein folding, and transport. As expected, the TIF contained several classical serum proteins. Considering that the protein composition of the TIF reflects the physiological and pathological state of the tissue, it should provide a new and potentially rich resource for diagnostic biomarker discovery and for identifying more selective targets for therapeutic intervention. 相似文献
9.
Angharad E. Simpson Martin J. Stoddart Catrin M. Davies Katharina Jähn Pamela I. Furlong Jürg A. Gasser David B. Jones Brendon S. Noble Robert G. Richards 《Cell biochemistry and function》2009,27(1):23-29
The goal of this study was to assess the effect of the addition of TGFβ3, alone or in combination with loading, on the survival of osteocytes in 3D human explant cancellous bone during long-term culture in an ex vivo loading bioreactor. Human cancellous bone explants were cultured for up to 14 days with or without TGFβ3 (15 ng ml−1) and with or without loading (300 cycles, at 1 Hz, producing 4000 microstrain). Bone core response was visualized using undecalcified histology with morphological methods after embedding with Technovit 9100 New® resin. Histological examination revealed normal gross level bone structure with or without the application of load or the addition of TGFβ3. The viability of the osteocytes within the bone was assessed by lactate dehydrogenase (LDH) activity. We demonstrate that this ex vivo loading bioreactor is able to maintain a high percentage (over 50%) of viable osteocytes throughout the bone explants after 14 days in ex vivo culture. Further to this, the combination of daily loading and TGFβ3 administration produced superior osteocyte survival at the core centres when compared to loading or TGFβ alone. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
10.
Protein kinase C (PKC)-delta is a diacylglycerol-dependent, calcium-independent novel PKC isoform and has been demonstrated to exert negative regulatory functions in B lymphocytes as well as in mast cells. Whereas in mast cells PKC-delta functionally interacts with the high-affinity receptor for IgE, FcepsilonR1, no such association has been described for the B cell antigen receptor (BCR). In this report, for the first time, we demonstrate the interaction of PKC-delta with different classes of BCR by means of affinity purification and native protein complex analysis. Using a C-terminally truncated Ig-alpha as well as non-phosphorylated and phosphorylated peptides representing C-terminal regions of Ig-alpha, the dependence of this BCR/PKC-delta interaction on tyrosine-phosphorylated Ig-alpha is shown. Finally, splenocytes from PKC-delta-deficient mice are found to exert reduced phosphorylation of PKD (a.k.a. PKC-mu) in response to BCR engagement, suggesting the early, membrane-proximal activation of an attenuating kinase complex including PKC-delta and PKD. 相似文献