Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets.

Pairing homologous chromosomes is required for recombination. However, in nonmeiotic stages it can lead to detrimental consequences, such as allelic misregulation and genome instability, and is rare in human somatic cells. How mitotic recombination is prevented-and how genetic stability is maintained across daughter cells-is a fundamental, unanswered question. Here, we report that both human and mouse cells impede homologous chromosome pairing by keeping two haploid chromosome sets apart throughout mitosis. Four-dimensional analysis of chromosomes during cell division revealed that a haploid chromosome set resides on either side of a meridional plane, crossing two centrosomes. Simultaneous tracking of chromosome oscillation and the spindle axis, using fluorescent CENP-A and centrin1, respectively, demonstrates collective genome behavior/segregation of two haploid sets throughout mitosis. Using 3D chromosome imaging of a translocation mouse with a supernumerary chromosome, we found that this maternally derived chromosome is positioned by parental origin. These data, taken together, support the identity of haploid sets by parental origin. This haploid set-based antipairing motif is shared by multiple cell types, doubles in tetraploid cells, and is lost in a carcinoma cell line. The data support a mechanism of nuclear polarity that sequesters two haploid sets along a subcellular axis. This topological segregation of haploid sets revisits an old model/paradigm and provides implications for maintaining mitotic fidelity

Seven-fluorochrome mouse M-FISH for high-resolution analysis of interchromosomal rearrangements

The mouse has evolved to be the primary mammalian genetic model organism. Important applications include the modeling of human cancer and cloning experiments. In both settings, a detailed analysis of the mouse genome is essential. Multicolor karyotyping technologies have emerged to be invaluable tools for the identification of mouse chromosomes and for the deciphering of complex rearrangements. With the increasing use of these multicolor technologies resolution limits are critical. However, the traditionally used probe sets, which employ 5 different fluorochromes, have significant limitations. Here, we introduce an improved labeling strategy. Using 7 fluorochromes we increased the sensitivity for the detection of small interchromosomal rearrangements (700 kb or less) to virtually 100%. Our approach should be important to unravel small interchromosomal rearrangements in mouse models for DNA repair defects and chromosomal instability. Copyright (C) 2003 S. Karger AG, Basel

Intrusion Detection Using Mouse Dynamics

Compared to other behavioural biometrics, mouse dynamics is a less explored area. General purpose data sets containing unrestricted mouse usage data are usually not available. The Balabit data set was released in 2016 for a data science competition, which against the few subjects, can be considered the first adequate publicly available one. This paper presents a performance evaluation study on this data set for impostor detection. The existence of very short test sessions makes this data set challenging. Raw data were segmented into mouse move, point and click and drag and drop types of mouse actions, then several features were extracted. In contrast to keystroke dynamics, mouse data is not sensitive, therefore it is possible to collect negative mouse dynamics data and to use two-class classifiers for impostor detection. Both action- and set of actions-based evaluations were performed. Set of actions-based evaluation achieves 0.92 AUC on the test part of the data set. However, the same type of evaluation conducted on the training part of the data set resulted in maximal AUC (1) using only 13 actions. Drag and drop mouse actions proved to be the best actions for impostor detection.Comment: Submitted to IET Biometrics on 23 May 201

Highly Variable Genomic Landscape of Endogenous Retroviruses in the C57BL/6J Inbred Strain, Depending on Individual Mouse, Gender, Organ Type, and Organ Location.

Transposable repetitive elements, named the "TREome," represent ~40% of the mouse genome. We postulate that the germ line genome undergoes temporal and spatial diversification into somatic genomes in conjunction with the TREome activity. C57BL/6J inbred mice were subjected to genomic landscape analyses using a TREome probe from murine leukemia virus-type endogenous retroviruses (MLV-ERVs). None shared the same MLV-ERV landscape within each comparison group: (1) sperm and 18 tissues from one mouse, (2) six brain compartments from two females, (3) spleen and thymus samples from four age groups, (4) three spatial tissue sets from two females, and (5) kidney and liver samples from three females and three males. Interestingly, males had more genomic MLV-ERV copies than females; moreover, only in the males, the kidneys had higher MLV-ERV copies than the livers. Perhaps, the mouse-, gender-, and tissue/cell-dependent MLV-ERV landscapes are linked to the individual-specific and dynamic phenotypes of the C57BL/6J inbred population

Roles of tumor suppressors in regulating tumor-associated inflammation.

Loss or silencing of tumor suppressors (TSs) promotes neoplastic transformation and malignant progression. To date, most work on TS has focused on their cell autonomous effects. Recent evidence, however, demonstrates an important noncell autonomous role for TS in the control of tumor-associated inflammation. We review evidence from clinical data sets and mouse model studies demonstrating enhanced inflammation and altered tumor microenvironment (TME) upon TS inactivation. We discuss clinical correlations between tumor-associated inflammation and inactivation of TS, and their therapeutic implications. This review sets forth the concept that TS can also suppress tumor-associated inflammation, a concept that provides new insights into tumor-host interactions. We also propose that in some cases the loss of TS function in cancer can be overcome through inhibition of the resulting inflammatory response, regardless whether it is a direct or an indirect consequence of TS loss

Mixing times and moving targets

We consider irreducible Markov chains on a finite state space. We show that the mixing time of any such chain is equivalent to the maximum, over initial states $x$ and moving large sets $(A_s)_s$, of the hitting time of $(A_s)_s$ starting from $x$. We prove that in the case of the $d$-dimensional torus the maximum hitting time of moving targets is equal to the maximum hitting time of stationary targets. Nevertheless, we construct a transitive graph where these two quantities are not equal, resolving an open question of Aldous and Fill on a "cat and mouse" game