Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expansion, branching of the subclones in parallel evolution, and neutral evolution. However, frequencie...

The Sox gene family constitutes transcription factors with a conserved high mobility group box (HMG) that regulate variety of developmental processes, including sex differentiation, neural, cartilage, and early embryonic development. In this study, we systematically analyzed characterized the 20 genes from whole buffalo genome, using comparative genomic evolutionary analyses. All were divided i...

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic disease, there is regression fibrosis and cirrhosis, improvement in clinical parameters (i.e. function hemodynamic markers, hepatic venous pressure gradient), survival rates, demonstrating that fibrolysis are a dynamic moving two directions. Microscopically, hepatocyte...

We present an innovative microfluidic-based system that automatizes the mutation accumulation culture in budding yeast. speed up by one order of magnitude time necessary for genome-wide measurements mutational profiles.

Extrahepatic biliary stenosis can be caused by benign and malignant disorders. In most cases, a tissue diagnosis is needed for optimal management of patients, but the sensitivity of biliary cytology for the diagnosis of a malignancy is relatively low. The additional diagnostic value of K-ras mutational analysis of endobiliary brush cytology was assessed. Endobiliary brush cytology specimens obt...

Background Recent studies have shown that KRAS mutations are negative predictors of benefit from both adjuvant chemotherapy and anti-EGFR directed therapies for non-small cell lung carcinoma (NSCLC). Needle core biopsy, cytology specimen and resected tissue have all been used for KRAS mutational analysis of malignant lung tumors. However, studies validating the correlation between needle core b...

There has been considerable recent interest in deciphering the adaptive properties underlying the structure and function of metabolic networks. Various features of metabolic networks such as the global topology, distribution of fluxes, and mutational robustness, have been proposed to have adaptive significance and hence reflect design principles. However, whether evolutionary processes alternat...

Nongenetic perturbations, such as environmental change or developmental noise, can induce novel phenotypes. If an induced phenotype appears recurrently and confers a fitness advantage, selection may promote its genetic stabilization. Nongenetic perturbations can thus initiate evolutionary innovation. Genetic variation that is not usually phenotypically visible may play an important role in this...

Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequenc...