Identification of novel amplification gene targets in mouse and human breast cancer at a syntenic cluster mapping to mouse identification of novel amplification gene targets in mouse and human breast cancer at a syntenic cluster mapping to mouse ch8a1 and human ch13q34

Serial analysis of gene expression from aggressive mammary tumors derived from transplantable p53 null mouse mammary outgrowth lines revealed significant up-regulation of Tfdp1 (transcription factor Dp1), Lamp1 (lysosomal membrane glycoprotein 1) and Gas6 (growth arrest specific 6) transcripts. All of these genes belong to the same linkage cluster, mapping to mouse chromosome band 8A1. BAC-array comparative genomic hybridization and fluorescence in situ hybridization analyses revealed genomic amplification at mouse region ch8A1.1. The minimal region of amplification contained genes Cul4a, Lamp1, Tfdp1, and Gas6, highly overexpressed in the p53 null mammary outgrowth lines at preneoplastic stages, and in all its derived tumors. The same amplification was also observed in spontaneous p53 null mammary tumors. Interestingly, this region is homologous to human chromosome 13q34, and some of the same genes were previously observed amplified in human carcinomas. Thus, we further investigated the occurrence and frequency of gene amplification affecting genes mapping to ch13q34 in human breast cancer. TFDP1 showed the highest frequency of amplification affecting 31% of 74 breast carcinomas analyzed. Statistically significant positive correlation was observed for the amplification of CUL4A, LAMP1, TFDP1, and GAS6 genes (P < 0.001). Meta-analysis of publicly available gene expression data sets showed a strong association between the high expression of TFDP1 and decreased overall survival (P = 0.00004), relapse-free survival (P = 0.0119), and metastasis-free interval (P = 0.0064). In conclusion, our findings suggest that CUL4A, LAMP1, TFDP1, and GAS6 are targets for overexpression and amplification in breast cancers. Therefore, overexpression of these genes and, in particular, TFDP1 might be of relevance in the development and/or progression in a significant subset of human breastFil: Abba, Martín Carlos. University of Texas; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fabris, Victoria Teresa. University of Texas; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Hu, Yuhui. University of Texas; Estados UnidosFil: Kittrell, Frances S.. Baylor College of Medicine; Estados Unidos. University of Texas; Estados UnidosFil: Cai, Wei Wen. University of Texas; Estados Unidos. Baylor College of Medicine; Estados UnidosFil: Donehower, Lawrence A.. University of Texas; Estados UnidosFil: Sahin, Aysegui. University of Texas; Estados UnidosFil: Medina, Daniel. University of Texas; Estados Unidos. Baylor College of Medicine; Estados UnidosFil: Aldaz, Claudio Marcelo. University of Texas; Estados Unido

Improved Animal Model for Vibration Injury Study

Hand-Arm Vibration Syndrome is a debilitating condition that affects millions of power-tool users in the  U.S. Research into its etiology has been hampered by deficiencies in animal models used for vibration studies.  Our objective was to design an animal vibration injury model that: 1) vibrates only the studied limb, not  the body; and 2) avoids anaesthesia, thus allowing purer focus on physiological effects of vibration while  reducing pain and distress for the animals, thereby enhancing their well-being. We compared advantages  and disadvantages of several models, studying body temperature, body weight, tissue perfusion, vascular  pathohistology, and general animal condition. Our model uses an apparatus that limits vibration to one  body part and a specially designed cage that minimizes animal stress and suffering, eliminating the need for  anaesthesia. It is ideal for the study of vibration injury, providing tissue damaged purely by vibration that  can be used for pathohistology and biochemical study.

Coulomb impurity under magnetic field in graphene: a semiclassical approach

We address the problem of a Coulomb impurity in graphene in the presence of a perpendicular uniform magnetic field. We show that the problem can be solved below the supercritical impurity magnitude within the WKB approximation. Without impurity the semiclassical energies correctly reproduce the Landau level spectrum. For a given Landau level the WKB energy depends on the absolute value of angular momentum in a way which is consistent with the exact diagonalization result. Below the supercritical impurity magnitude, the WKB solution can be expanded as a convergent series in powers of the effective fine structure constant. Relevance of our results to validity of the widely used Landau level projection approximation is discussed.Comment: 10 pages, 5 figure