Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status

Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.     

A cat cloned by nuclear transplantation

Sheep, mice, cattle, goats and pigs have all been cloned by transfer of a donor cell nucleus into an enucleated ovum, and now we add the successful cloning of a cat (Felis domesticus) to this list. However, this cloning technology may not be readily extendable to other mammalian species if our understanding of their reproductive processes is limited or if there are species-specific obstacles.     

Petrological implication of wagnerite-Ma5bc in the quartzofeldspathic gneiss, Larsemann Hills, East Antarctica

Mg dominantmineralsofwagnerite triplite group,i.e.(Mg,Fe,Mn)2(PO4)(F,OH),arerelativelyrare,buthavebeenfoundinawidevariety ofgeologicenvironments,includingmetamorphic rocksofallgrades[1]suchasquartz carbonateveinsof hydrothermalorigin,pegmatites,kyanite quartzite,micaschist,sillimanitegneiss,andmagnetiteores.Uptonow,wagneriteispresentmainlyasthe Ma2bcpolytype,anaccessorymineralincalcium poorrocks[2,5]inwhichapatite,ifpresent,oftenoc cursasretrograderimaroundwagnerite.Henriques[6]reportedasma…     

Study on molecular interaction between NifA and NifL of Pseudomonas stutzeri A1501 by using the yeast two-hybrid system

Pseudomonas stutzeri AI501 (formerly Alcaligenes faecalis A1501), which was isolated from rice paddies in South China in 1980, can colonize tightly on rhizoplane of the host plants or invade the roots of plants for growth and nitrogen fixation. But A1501 can fix nitrogen only under the micro-aerobic and nitrogen-free conditions. The oxygen concentration and the availability of fixed nitrogen are therefore important factors in the regulation of nitrogenase biosynthesis of associative nitrogen-fixing bacteria.     

Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice.

Pigmentary glaucoma is a significant cause of human blindness. Abnormally liberated iris pigment and cell debris enter the ocular drainage structures, leading to increased intraocular pressure (IOP) and glaucoma. DBA/2J (D2) mice develop a form of pigmentary glaucoma involving iris pigment dispersion (IPD) and iris stromal atrophy (ISA). Using high-resolution mapping techniques, sequencing and functional genetic tests, we show that IPD and ISA result from mutations in related genes encoding melanosomal proteins. IPD is caused by a premature stop codon mutation in the Gpnmb (GpnmbR150X) gene, as proved by the occurrence of IPD only in D2 mice that are homozygous with respect to GpnmbR150X; otherwise, similar D2 mice that are not homozygous for GpnmbR150X do not develop IPD. ISA is caused by the recessive Tyrp1b mutant allele and rescued by the transgenic introduction of wildtype Tyrp1. We hypothesize that IPD and ISA alter melanosomes, allowing toxic intermediates of pigment production to leak from melanosomes, causing iris disease and subsequent pigmentary glaucoma. This is supported by the rescue of IPD and ISA in D2 eyes with substantially decreased pigment production. These data indicate that pigment production and mutant melanosomal protein genes may contribute to human pigmentary glaucoma. The fact that hypopigmentation profoundly alleviates the D2 disease indicates that therapeutic strategies designed to decrease pigment production may be beneficial in human pigmentary glaucoma.