Rag mutations reveal robust alternative end joining

Mammalian cells repair DNA double-strand breaks (DSBs) through either homologous recombination or non-homologous end joining (NHEJ). V(D)J recombination, a cut-and-paste mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient. Nevertheless, DSB repair is not eliminated entirely in these animals: evidence of a third mechanism, 'alternative NHEJ', appears in the form of extremely rare V(D)J junctions and a higher rate of chromosomal translocations. The paucity of these V(D)J events has suggested that alternative NHEJ contributes little to a cell's overall repair capacity, being operative only (and inefficiently) when classical NHEJ fails. Here we find that removing certain portions of murine Rag proteins reveals robust alternative NHEJ activity in NHEJ-deficient cells and some alternative joining activity even in wild-type cells. We propose a two-tier model in which the Rag proteins collaborate with NHEJ factors to preserve genomic integrity during V(D)J recombination.     

功率谱的信息几何

利用信息几何的方法,给出了功率谱的信息几何结构. 将要研究的功率谱的集合看成一个微分流形,定义了分数阶功率谱,引入黎曼度量和对偶联络,并获得了三个随机过程模型的几何度量.      

The clonal and mutational evolution spectrum of primary triple-negative breast cancers

Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.     

L-模糊集的可数STARPLUS-紧性

研究了在L-拓扑空间中,利用L-拓扑的水平拓扑引入可数Starp lus-紧性的概念,获得了可数Starp lus-紧性的性质,并且对一般拓扑中可数Starp lus-紧性的推广.     

Structural and optical properties of Zn1−xNixTe thin films prepared by electron beam evaporation technique

Zn1-xNixTe thin films with different composition(x=0.0, 0.05, 0.10, 0.15 and 0.20) were deposited on glass substrate by electron beam evaporation technique followed by its characterization using advanced structural and optical analysis techniques. Structural properties of the prepared thin films were studied by X-ray diffraction(XRD). The XRD patterns revealed that the binary compounds transformed into a ternary compound with cubic structure having preferred orientation along the c-direction with(111) planes. Composition analysis of the films was determined by energy dispersive analysis of X-rays(EDAX) and found to be in agreement with the precursor composition. Optical properties such as extinction coefficient(k) and band gap energy of these films were examined by using a spectroscopic ellipsometer. It was found that the extinction coefficient(k) increased with the addition of Ni content in the alloy. In comparison, the band gap energy was also determined by using transmission spectra and found to be agreed with that of the ellipsometric results. These analyses confirm that the band gap energy decreases with the increase of Ni content in the alloy.     

An improved technique of preparing primary cultures of isolated cells from adult frog kidney

Zusammenfassung Eine verbesserte Technik zur Gewinnung der ersten Einzelschichtbildungen von Froschnierenzellen wurde entwickelt. Die Zellen werden in neuem auflösendem Nährboden isoliert und wachsen auf modifiziertem Eagle-Nährboden mit 13% Kalbsserum. Nach 10 Tagen zeigt sich stark aktives mitotisches Zellwachstum in der Kultur.     

Transition metals in an experimental tumour system.

In this report we present an analysis by atomic absorption spectrometry of some of the transition metals Fe, Zn, Cu, Mn, Co, and Ni in tissues and nuclear fractions in an experimental tumour system.