Human papillomavirus (HPV) types 16 and 18 are known to play a major role in cervical carcinogenesis. However, additional genetic alterations are required for the development and progression of ...cervical cancer. Our aim was to identify genes which are consistently down-regulated in cervical cancers (CxCa) and which are likely to contribute to malignant transformation. Microarray analyses of RNA from high-grade cervical precancers (CIN2/3) and CxCa were performed to screen for putative tumour suppressor genes (TSG) in predefined regions on chromosomes 4 and 10. Validation of the candidate genes was done by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in 16 normal cervical tissues, 14 CIN2/3 and 16 CxCa. The two most promising genes, SORBS2 and CALML5, were expressed ectopically in various cell lines in order to analyse their functional activity. Reconstitution of SORBS2 expression resulted in a significant reduction in cell proliferation, colony formation and anchorage-independent growth in CaSki, HPKII and HaCaT cells, whereby anchorage-independent growth could only be investigated for CaSki cells. SORBS2 had no effect on cell migration. In contrast, reconstitution of CALML5 expression did not influence the phenotype of all cell lines tested. None of the genes could induce senescence or apoptosis. Our results underline a possible role of SORBS2 as a TSG in cervical carcinogenesis.
Summary
Bread wheat derives from a grass ancestor structured in seven protochromosomes followed by a paleotetraploidization to reach a 12 chromosomes intermediate and a neohexaploidization (involving ...subgenomes A, B and D) event that finally shaped the 21 modern chromosomes. Insights into wheat syntenome in sequencing conserved orthologous set (COS) genes unravelled differences in genomic structure (such as gene conservation and diversity) and genetical landscape (such as recombination pattern) between ancestral as well as recent duplicated blocks. Contrasted evolutionary plasticity is observed where the B subgenome appears more sensitive (i.e. plastic) in contrast to A as dominant (i.e. stable) in response to the neotetraploidization and D subgenome as supra‐dominant (i.e. pivotal) in response to the neohexaploidization event. Finally, the wheat syntenome, delivered through a public web interface PlantSyntenyViewer at http://urgi.versailles.inra.fr/synteny-wheat, can be considered as a guide for accelerated dissection of major agronomical traits in wheat.
Spectrally shaped forms of random frequency modulation (RFM) radar waveforms have been experimentally demonstrated for a variety of implementation approaches and applications. Of these, the ...continuous-wave (CW) perspective is particularly interesting because it enables the prospect of very high signal dimensionality and arbitrary receive processing from a range/Doppler perspective, while also mitigating range ambiguities by avoiding repetition. Here we leverage a modification to the constant-envelope orthogonal frequency division multiplexing (CE-OFDM) framework, which was originally proposed for power-efficient communications, to realize a nonrepeating FMCW radar signal that can be represented with a compact parameterization, thereby circumventing memory constraints that could arise for some applications. Experimental loopback and open-air measurements are used to demonstrate this waveform type.
The family of multidrug resistance-associated proteins (MRPs) belongs to the superfamily of adenosine triphosphate-binding-cassette (ABC) transporters, which have the ability to function as outward ...pumps for chemotherapeutic drugs and therefore might be involved in drug resistance. In this study the expression of the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time polymerase chain reaction (PCR) in 103 children with previously untreated acute lymphoblastic leukemia (ALL) (precursor B-cell ALL B-ALL, n = 71; T-cell ALL T-ALL, n = 32). All 5 genes were expressed with a great variability. Only MRP3 expression was associated with a significantly worse prognosis (P= .008). The median expression of MRP3 was 10-fold higher in T-ALL than in precursor B-ALL (P< .001) and 4-fold higher in male patients than in female patients (P< .001). The prognostic impact of MRP3 was independent of immunophenotype or sex. Higher levels of MRP3 were found in patients with a poor in vivo response to prednisone, but this could not be confirmed in an independent case-control study (40 patients) for prednisone response. In healthy donors, the median expression of MRP4 was 4-fold higher in bone marrow and 8-fold higher in CD34+stem cells compared with peripheral blood (P= .002). Our results suggest that MRP3 is involved in drug resistance in childhood ALL. It therefore represents an interesting target to overcome multidrug resistance. High levels of MRP3 could possibly be the reason for the poorer prognosis of male patients or patients who have T-ALL. Similar to other members of the family of ABC transporters, MRP4 seems to be a marker for immature stem cells. (Blood. 2003;102:4493-4498)
The breast cancer resistance protein (BCRP), also known as mitoxantrone resistance protein (MXR) or placenta ABC protein (ABC‐P), is the second member of the ABCG subfamily of ABC transport proteins ...(gene symbol ABCG2). BCRP has been detected in acute myeloid leukaemia and in breast, colon and gastric cancer but there has been no reports regarding BCRP expression in acute lymphoblastic leukaemia (ALL). We report the first results of BCRP expression in childhood ALL. Sixty‐seven children (47 initial stage, 20 relapses) with ALL were analysed for BCRP gene expression by TaqMan real‐time polymerase chain reaction. The expression of BCRP in mononuclear cells obtained from the bone marrow (BM) and peripheral blood (PB) of healthy donors was also investigated. There was no relationship between BCRP expression and age, sex, initial blast cell count, prednisolone response or BM response on d 15 and 33. Patients with T‐lineage ALL showed a lower expression of BCRP (P = 0·044). Kaplan–Meier analysis of the relapse‐free interval showed no prognostic significance of BCRP expression when different levels of BCRP expression were used as cut‐off points. No significant difference in expression of BCRP mRNA was measured between initial‐stage and relapsed‐stage ALL or between normal MNC obtained from BM and ALL patients. The results indicate a low expression of BCRP in childhood ALL. Relationships between BCRP and clinical, molecular or in vivo resistance characteristics of the patients were not observed.
RNA-seq experiments are now routinely used for the large scale sequencing of transcripts. In bacteria or archaea, such deep sequencing experiments typically produce 10–50million fragments that cover ...most of the genome, including intergenic regions. In this context, the precise delineation of the non-coding elements is challenging. Non-coding elements include untranslated regions (UTRs) of mRNAs, independent small RNA genes (sRNAs) and transcripts produced from the antisense strand of genes (asRNA). Here we present a computational pipeline (DETR’PROK: detection of ncRNAs in prokaryotes) based on the Galaxy framework that takes as input a mapping of deep sequencing reads and performs successive steps of clustering, comparison with existing annotation and identification of transcribed non-coding fragments classified into putative 5′ UTRs, sRNAs and asRNAs. We provide a step-by-step description of the protocol using real-life example data sets from Vibrio splendidus and Escherichia coli.
The family of multidrug resistance-associated proteins (MRPs) belongs to the ATP-binding cassette superfamily of transporters, which have the ability to function as outward pumps for chemotherapeutic ...drugs. Their structure, function, and substrate specificity have been studied intensively, but little is known about their clinical relevance in malignant diseases.
In this study, the expression of the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time PCR in 53 children with de novo acute myeloid leukemia. Nine patients were also analyzed in relapse.
MRP3 gene expression was higher in patients who did not achieve remission (P = 0.023). Expression of MRP2 (P = 0.09) or MRP3 (P = 0.041) was associated with a lower rate of survival, and patients who expressed high levels of both genes had a particularly poor prognosis (P < 0.01). No significant association was found for overall survival or remission rate and the expression of MRP4, MRP5, and SMRP.
This study provides first data on the clinical relevance of five MRPs in acute myeloid leukemia patients. The results strongly suggest that MRP3 and possibly also MRP2 are involved in drug resistance in this disease. Those two proteins therefore represent interesting markers for risk-adapted therapy and possible targets for the development of specific drugs to overcome multidrug resistance.
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