The mechanisms by which deregulated nuclear factor erythroid-2-related factor 2 (NRF2) and kelch-like ECHassociated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and 13 C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (
So far we have identified 17 mutations in eastern India including five common mutations that account for 44% of patients. Comparative study on WD mutations between different regions of India suggests high genetic heterogeneity and the absence of a single or a limited number of common founder mutations. Genotype-phenotype correlation revealed that no particular phenotype could be assigned to a particular mutation and even same set of mutations in different patients showed different phenotypes.
Although organic matter may accumulate sometimes (e.g. lignocellulose in peat bog), most natural biodegradation processes are completed until full mineralization. Such transformations are often achieved by the concerted action of communities of interacting microbes, involving different species each performing specific tasks. These interactions can give rise to novel "community-intrinsic" properties, through e.g. activation of so-called "silent genetic pathways" or synergistic interplay between microbial activities and functions. Here we studied the microbial community-based degradation of keratin, a recalcitrant biological material, by four soil isolates, which have previously been shown to display synergistic interactions during biofilm formation; Stenotrophomonas rhizophila, Xanthomonas retroflexus, Microbacterium oxydans and Paenibacillus amylolyticus. We observed enhanced keratin weight loss in cultures with X. retroflexus, both in dual and four-species co-cultures, as compared to expected keratin degradation by X. retroflexus alone. Additional community intrinsic properties included accelerated keratin degradation rates and increased biofilm formation on keratin particles. Comparison of secretome profiles of X. retroflexus mono-cultures to cocultures revealed that certain proteases (e.g. serine protease S08) were significantly more abundant in mono-cultures, whereas co-cultures had an increased abundance of proteins related to maintaining the redox environment, e.g. glutathione peroxidase. Hence, one of the mechanisms related to the community intrinsic properties, leading to enhanced degradation from co-cultures, might be related to a switch from sulfitolytic to proteolytic functions between mono-and co-cultures, respectively.
, in a recent article in this journal (1 ), described the mechanisms leading to allele dropout in the PCR-based diagnosis of Wilson disease (WD) and reported potential solutions to this problem. We propose 2 strategies that would enable unequivocal and rapid identification of allele dropout in WD.In WD, an autosomal recessive disorder, mutations in the ATP7B gene lead to accumulation of copper in the liver and the brain (2 ). In PCR-based detection of WD carriers and presymptomatic individuals in affected families, the presence of numerous single-base variations in the ATP7B gene gives rise to allele dropout, the nonamplification of one of the alleles (1 ). In WD compound heterozygotes, if the wild-type allele corresponding to an identified mutation fails to amplify, the PCR product shows apparent homozygosity, leading to faulty diagnosis. Screening the entire ATP7B gene to exclude allele dropout, as recommended by Lam and Mak (1 ), is an arduous job because ATP7B is ϳ80 kb long with 21 exons and a coding length of more than 6.5 kb. The alternative suggestion, to design primers for PCR from intronic sequence-lacking nucleotide variants (1 ), can be hampered by lack of information on single-base variations, because HAPMAP project data (http://www.hapmap.org/) do not provide complete information on all the neutral nucleotide variants in different population groups.We suggest a much simpler and faster method for detection of allele dropout. Because WD is a simple Mendelian disorder that follows an autosomal recessive mode of inheritance, normal parents of a WD pa- Fig. 1. Flowchart to determine allele dropout in WD patient suspected to be homozygous for a mutation. D13S133, D13S316, D13S314 are dinucleotide repeat markers flanking WD locus with a large number of alleles. To ensure detection of any underlying heterogeneity between 2 WD-alleles in sporadic patient, genotyping for all 3 markers is recommended. Segregations of mutant alleles (m1, m2) and wild-type alleles (wt1, wt2) are shown.
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