Adriamycin-induced chromosome damage: Elevated frequencies of isochromatid aberrations in G2 and S phases

Summary Analysis of chromosomes from cells treated with adriamycin during G₂ and S phases showed a high frequency of isochromatid-type of breaks, in addition to the expected chromatid breaks. These are interpreted as independent breaks on sister chromatids because of preferential effects of the drug in specific chromosome regions. The break points are likely to be different, but morphologically such breaks would be indistinguishable from isochromatid or chromosome breaks.Supported in part by NO1-CM-53773 Division of Cancer Treatment NCI, Bethesda, Maryland, and by Research Grant No. VC-21 from American Cancer Society.     

Robertsonian fusion between homologous chromosomes in a natural population of the least cotton rat,Sigmodon minimus (Rodentia,Cricetidae)

Zusammenfassung Die diploide Chromosomenzahl vonSigmodon minimus, einem Nager der Familie der Cricetiden ist 30. Im Karyotyp befindet sich kein grosses metazentrisches Chromosom. Bei Tieren aus einer Population von Silver City, New Mexico, wurden 29 Chromosomen gefunden. Eines davon war relativ gross und metazentrisch. Beim Paaren der Chromosomen in Meiose ist es evident, dass das metazentrische Chromosom das Fusionsprodukt von 2 homologen Chromosomen ist.

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The author wishes to thank Dr. J.Wright, Dr. J. S.Findley and Mr. J. T.Mascarello for their assistance in procuring the live specimens.     

Fe—27Mn—6Si—5Cr形状记忆合金丝材退火对显微组织与相变点的影响

对Ｆｅ－２７Ｍｎ－６Ｓｉ－５Ｃｒ（％,质量分数）形状记忆合金热拉丝经不同温度退火,观察其显微组织．发现７００°Ｃ时再结晶刚结束,此时晶粒最细小;低于７００°Ｃ退火,试样内存在变形晶粒;８００°Ｃ退火再结晶,呈现晶粒粗大．采用膨胀法和四端电阻法研究退火温度对试样热诱发ε－马氏体Ｍｓ的影响．Ｍｓ随退火温度的升高而升高,到７００°Ｃ达到最高,８００°Ｃ以上Ｍｓ复又降低,这可能与７００°Ｃ退火后变形结构的消除、再结晶晶粒十分细小和层错单一取向形成有关．     

Functional genomics reveal that the serine synthesis pathway is essential in breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.     

Selection and validation of differentially expressed genes in head and neck cancer

We applied a robust combinatorial (multi-test) approach to microarray data to identify genes consistently up- or down-regulated in head and neck squamous cell carcinoma (HNSCC). RNA was extracted from 22 paired samples of HNSCC and normal tissue from the same donors and hybridized to the Affymetrix U95A chip. Forty-two differentially expressed probe sets (representing 38 genes and one expressed sequence tag) satisfied all statistical tests of significance and were selected for further validation. Selected probe sets were validated by hierarchical clustering, multiple probe set concordance, and target-subunit agreement. In addition, real-time PCR analysis of 8 representative (randomly selected from 38) genes performed on both microarray-tested and independently obtained samples correlated well with the microarray data. The genes identified and validated by this method were in comparatively good agreement with other rigorous HNSCC microarray studies. From this study, we conclude that combinatorial analysis of microarray data is a promising technique for identifying differentially expressed genes with few false positives.Received 12 February 2004; received after revision 22 March 2004; accepted 14 April 2004     

Hydrogen isotope geochemistry of lherzolitic shergottite in Martian meteorite GRV99027 from the Grove Mountains in Antarctica

Whether life vestige existed in Martian meteorites or not has provoked a hot tide toward Mars exploration. Among the other things, whether water existed in Marsor not again becomes a hot point of contemporary sci- entific exploration. Analyzing the hydrog…     

Experimental investigation of geologically produced antineutrinos with KamLAND

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.