Search results for "MUTATION"

A construction of Frobenius manifolds from stability conditions

2018

A finite quiver $Q$ without loops or 2-cycles defines a 3CY triangulated category $D(Q)$ and a finite heart $A(Q)$. We show that if $Q$ satisfies some (strong) conditions then the space of stability conditions $Stab(A(Q))$ supported on this heart admits a natural family of semisimple Frobenius manifold structures, constructed using the invariants counting semistable objects in $D(Q)$. In the case of $A_n$ evaluating the family at a special point we recover a branch of the Saito Frobenius structure of the $A_n$ singularity $y^2 = x^{n+1}$. We give examples where applying the construction to each mutation of $Q$ and evaluating the families at a special point yields a different branch of the m…

Mutant p53 gain of function can be at the root of dedifferentiation of human osteosarcoma MG63 cells into 3AB-OS cancer stem cells

2014

Osteosarcoma is a highly metastatic tumor affecting adolescents, for which there is no second-line chemotherapy. As suggested for most tumors, its capability to overgrow is probably driven by cancer stem cells (CSCs), and finding new targets to kill CSCs may be critical for improving patient survival. TP53 is the most frequently mutated tumor suppressor gene in cancers and mutant p53 protein (mutp53) can acquire gain of function (GOF) strongly contributing to malignancy. Studies thus far have not shown p53-GOF in osteosarcoma. Here, we investigated TP53 gene status/role in 3AB-OS cells-a highly aggressive CSC line previously selected from human osteosarcoma MG63 cells-to evaluate its involv…

Atypical Phacomatosis Pigmentokeratotica as the Expression of a Mosaic RASopathy With the BRAF-Glu586Lys Mutation

2016

Drosophila Enhancer of Zeste/ESC Complexes Have a Histone H3 Methyltransferase Activity that Marks Chromosomal Polycomb Sites

2002

AbstractEnhancer of Zeste is a Polycomb Group protein essential for the establishment and maintenance of repression of homeotic and other genes. In the early embryo it is found in a complex that includes ESC and is recruited to Polycomb Response Elements. We show that this complex contains a methyltransferase activity that methylates lysine 9 and lysine 27 of histone H3, but the activity is lost when the E(Z) SET domain is mutated. The lysine 9 position is trimethylated and this mark is closely associated with Polycomb binding sites on polytene chromosomes but is also found in centric heterochromatin, chromosome 4, and telomeric sites. Histone H3 methylated in vitro by the E(Z)/ESC complex …

Neutron cross section measurements at n_TOF for ADS related estudies

2005

A neutron Time-of-Flight facility (n_TOF) is available at CERN since 2001. The innovative features of the neutron beam, in particular the high instantaneous flux, the wide energy range, the high resolution and the low background, make this facility unique for measurements of neutron induced reactions relevant to the field of Emerging Nuclear Technologies, as well as to Nuclear Astrophysics and Fundamental Nuclear Physics. The scientific motivations that have led to the construction of this new facility are here presented. The main characteristics of the n_TOF neutron beam are described, together with the features of the experimental apparata used for cross-section measurements. The main res…

Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper fr…

2014

Item does not contain fulltext AIMS: Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH. METHODS AND RESULTS: Early diagn…

Extremely rapid acclimation of Escherichia coli to high temperature over a few generations of a fed-batch culture during slow warming

2014

This study aimed to demonstrate that adequate slow heating rate allows two strains of Escherichia coli rapid acclimation to higher temperature than upper growth and survival limits known to be strain-dependent. A laboratory (K12-TG1) and an environmental (DPD3084) strain of E. coli were subjected to rapid (few seconds) or slow warming (1 degrees C 12 h(-1)) in order to (re) evaluate upper survival and growth limits. The slow warming was applied from the ancestral temperature 37 degrees C to total cell death 46-54 degrees C: about 30 generations were propagated. Upper survival and growth limits for rapid warming (46 degrees C) were lower than for slow warming (46-54 degrees C). The thermal l…

Amino acid substitutions enhancing thermostability of Bacillus polymyxa beta-glucosidase A

1996

Mutations enhancing the thermostability of β-glucosidase A of Bacillus polymyxa, a family 1 glycosyl hydrolase, have been obtained after hydroxylamine mutagenesis of a plasmid containing the bglA gene, transformation of Escherichia coli with the mutagenized plasmid, and identification of transformant colonies that showed β-glucosidase activity after a thermal treatment that inactivated the wild-type enzyme. Two additive mutations have been characterized that cause replacement of glutamate at position 96 by lysine and of methionine at position 416 by isoleucine respectively. The thermoresistant mutant enzymes showed increased resistance to other denaturing agents, such as pH and urea, while …

The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex.

2013

Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not ab…

Genomics Meets Cancer Immunotherapy

2014

High-throughput cancer genomics and bioinformatics are revolutionizing our ability to profile tumor samples. With next-generation sequencing (NGS) and high-performance computing (HPC) platforms, we have developed the infrastructures to determine and characterize tumor genomes and transcriptomes within days. Now, we are integrating these platforms into both cancer immunology and patient therapy decision-making. Here, we briefly describe the technology platforms and highlight several emerging applications: profiling of tumor mutations and gene expression; determination of HLA type and tumor expression, enabling prediction of immunogenic tumor mutations; and identification of viruses present i…