MRD is a database system to access the microsatellite repeats information of genomes such as archea, eubacteria, and other eukaryotic genomes whose sequence information is available in public ...domains. MRD stores information about simple tandemly repeated k-mer sequences where k= 1 to 6, i.e. monomer to hexamer. The web interface allows the users to search for the repeat of their interest and to know about the association of the repeat with genes and genomic regions in the specific organism. The data contains the abundance and distribution of microsatellites in the coding and non-coding regions of the genome. The exact location of repeats with respect to genomic regions of interest (such as UTR, exon, intron or intergenic regions) whichever is applicable to organism is highlighted. MRD is available on the World Wide Web at http://www.ccmb.res.in/mrd and/or http://www.ingenovis.com/mrd. The database is designed as an open-ended system to accommodate the microsatellite repeats information of other genomes whose complete sequences will be available in future through public domain.
Homeotic gene complexes determine the anterior-posterior body axis in animals. The expression pattern and function of hox genes along this axis is colinear with the order in which they are organized ...in the complex. This 'chromosomal organization and functional correspondence' is conserved in all bilaterians investigated. Although the molecular basis of this 'colinearity' in not yet understood, it is possible that there are control elements within or in the proximity of these complexes that establish and maintain the expression patterns of hox genes in a coordinated fashion. We report here an unprecedented conservation of non-coding DNA sequences adjacent to the HoxD complex of vertebrates. Stretches of hundreds of base pairs in a 7 kb region, upstream of HoxD complex, show 100% conservation from fish to human. Using primers designed from these sequences of human HoxD complex, we amplified the corresponding regions from different vertebrates, including mammals, aves, reptiles, amphibians and pisces. Such a high degree of conservation, where no variation was allowed during ~500 million years of evolution, suggests critical function for these sequences in the regulation of the HoxD complex. Furthermore, these sequences provide a molecular handle to gain insight into the mechanism of regulation of this complex.
KRAS mutations KRAS testing has long been a prerequisite to the treatment of advanced CRC, primarily due to its relationship with the EGFR (Epidermal Growth Factor Receptor), a protein, tyrosine ...kinase, that binds to the epidermal growth factor and is involved in cell signaling pathways for cell division. KRAS mutations are among the most common alterations found in CRC.3 Anti-EGFR antibodies, like cetuximab, have been shown to be effective in combination with chemotherapy in the treatment of advanced CRC.4 KRAS mutations in CRC tend to be constitutively activating; meaning, upstream EGFR inhibition has no effect on its signaling, rendering anti-EGFR antibodies ineffective in the treatment of KRAS mutant tumors. ...for over a decade, KRAS has played a key role as a predictive biomarker in colorectal cancer treatment. Multiple pre-clinical studies, along with early phase clinical trials, have demonstrated the efficacy of inhibitors of specific KRAS mutants in multiple solid tumor types.5 With the recent approvals by the U.S. Food and Drug Administration (FDA) of KRAS G12C mutant inhibitors, such as sotorasib, in lung cancer, and preliminary evidence of efficacy against this same mutation in CRC, targeted therapies for KRAS-mutant CRC may soon become the standard of care. ...complicating the picture, one recent study suggests that a subset of heavily pretreated metastatic micro satellite stable (MSS) colorectal cancer, without liver metastases, may also respond to ICB therapy.10 Given these conflicting data, and mediocre ICB response rate in MSI-high CRC, significant efforts are being made to understand what aspects of the tumor microenvironment may affect ICB treatment response.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Abstract Background Homeotic gene complexes determine the anterior-posterior body axis in animals. The expression pattern and function of hox genes along this axis is colinear with the order in which ...they are organized in the complex. This 'chromosomal organization and functional correspondence' is conserved in all bilaterians investigated. Genomic sequences covering the HoxD complex from several vertebrate species are now available. This offers a comparative genomics approach to identify conserved regions linked to this complex. Although the molecular basis of 'colinearity' of Hox complexes is not yet understood, it is possible that there are control elements within or in the proximity of these complexes that establish and maintain the expression patterns of hox genes in a coordinated fashion. Results We have compared DNA sequence flanking the HoxD complex of several primate, rodent and fish species. This analysis revealed an unprecedented conservation of non-coding DNA sequences adjacent to the HoxD complex from fish to human. Stretches of hundreds of base pairs in a 7 kb region, upstream of HoxD complex, show 100% conservation across the vertebrate species. Using PCR primers from the human sequence, these conserved regions could be amplified from other vertebrate species, including other mammals, birds, reptiles, amphibians and fish. Our analysis of these sequences also indicates that starting from the conserved core regions, more sequences have been added on and maintained during evolution from fish to human. Conclusion Such a high degree of conservation in the core regions of this 7 kb DNA, where no variation occurred during ~500 million years of evolution, suggests critical function for these sequences. We suggest that such sequences are likely to provide molecular handle to gain insight into the evolution and mechanism of regulation of associated gene complexes.
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