Rapid generation of chromosome-specific alphoid DNA probes using the polymerase chain reaction

Non-isotopic in situ hybridization of chromosome-specific alphoid DNA probes has become a potent tool in the study of numerical aberrations of specific human chromosomes at all stages of the cell cycle. In this paper, we describe approaches for the rapid generation of such probes using the polymerase chain reaction (PCR), and demonstrate their chromosome specificity by fluorescence in situ hybridization to normal human metaphase spreads and interphase nuclei. Oligonucleotide primers for conserved regions of the alpha satellite monomer were used to generate chromosome-specific DNA probes from somatic hybrid cells containing various human chromosomes, and from DNA libraries from sorted human chromosomes. Oligonucleotide primers for chromosome-specific regions of the alpha satellite monomer were used to generate specific DNA probes for the pericentromeric heterochromatin of human chromosomes 1, 6, 7, 17 and X directly from human genomic DNA

Water exchange at a hydrated platinum electrode is rare and collective

We use molecular dynamics simulations to study the exchange kinetics of water molecules at a model metal electrode surface -- exchange between water molecules in the bulk liquid and water molecules bound to the metal. This process is a rare event, with a mean residence time of a bound water of about 40 ns for the model we consider. With analysis borrowed from the techniques of rare-event sampling, we show how this exchange or desorption is controlled by (1) reorganization of the hydrogen bond network within the adlayer of bound water molecules, and by (2) interfacial density fluctuations of the bulk liquid adjacent to the adlayer. We define collective coordinates that describe the desorption mechanism. Spatial and temporal correlations associated with a single event extend over nanometers and tens of picoseconds.Comment: 10 pages, 9 figure

Note and Comment

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Composite repetition-aware data structures

In highly repetitive strings, like collections of genomes from the same species, distinct measures of repetition all grow sublinearly in the length of the text, and indexes targeted to such strings typically depend only on one of these measures. We describe two data structures whose size depends on multiple measures of repetition at once, and that provide competitive tradeoffs between the time for counting and reporting all the exact occurrences of a pattern, and the space taken by the structure. The key component of our constructions is the run-length encoded BWT (RLBWT), which takes space proportional to the number of BWT runs: rather than augmenting RLBWT with suffix array samples, we combine it with data structures from LZ77 indexes, which take space proportional to the number of LZ77 factors, and with the compact directed acyclic word graph (CDAWG), which takes space proportional to the number of extensions of maximal repeats. The combination of CDAWG and RLBWT enables also a new representation of the suffix tree, whose size depends again on the number of extensions of maximal repeats, and that is powerful enough to support matching statistics and constant-space traversal.Comment: (the name of the third co-author was inadvertently omitted from previous version

Fluctuations of water near extended hydrophobic and hydrophilic surfaces

We use molecular dynamics simulations of the SPC-E model of liquid water to derive probability distributions for water density fluctuations in probe volumes of different shapes and sizes, both in the bulk as well as near hydrophobic and hydrophilic surfaces. To obtain our results, we introduce a biased sampling of coarse-grained densities, which in turn biases the actual solvent density. The technique is easily combined with molecular dynamics integration algorithms. Our principal result is that the probability for density fluctuations of water near a hydrophobic surface, with or without surface-water attractions, is akin to density fluctuations at the water-vapor interface. Specifically, the probability of density depletion near the surface is significantly larger than that in bulk. In contrast, we find that the statistics of water density fluctuations near a model hydrophilic surface are similar to that in the bulk

Explanation of the Gibbs paradox within the framework of quantum thermodynamics

The issue of the Gibbs paradox is that when considering mixing of two gases within classical thermodynamics, the entropy of mixing appears to be a discontinuous function of the difference between the gases: it is finite for whatever small difference, but vanishes for identical gases. The resolution offered in the literature, with help of quantum mixing entropy, was later shown to be unsatisfactory precisely where it sought to resolve the paradox. Macroscopic thermodynamics, classical or quantum, is unsuitable for explaining the paradox, since it does not deal explicitly with the difference between the gases. The proper approach employs quantum thermodynamics, which deals with finite quantum systems coupled to a large bath and a macroscopic work source. Within quantum thermodynamics, entropy generally looses its dominant place and the target of the paradox is naturally shifted to the decrease of the maximally available work before and after mixing (mixing ergotropy). In contrast to entropy this is an unambiguous quantity. For almost identical gases the mixing ergotropy continuously goes to zero, thus resolving the paradox. In this approach the concept of ``difference between the gases'' gets a clear operational meaning related to the possibilities of controlling the involved quantum states. Difficulties which prevent resolutions of the paradox in its entropic formulation do not arise here. The mixing ergotropy has several counter-intuitive features. It can increase when less precise operations are allowed. In the quantum situation (in contrast to the classical one) the mixing ergotropy can also increase when decreasing the degree of mixing between the gases, or when decreasing their distinguishability. These points go against a direct association of physical irreversibility with lack of information.Comment: Published version. New title. 17 pages Revte

Detection of chromosome aberrations in the human interphase nucleus by visualization of specific target DNAs with radioactive and non-radioactive in situ hybridization techniques: diagnosis of trisomy 18 with probe L1.84

The localization of chromosome 18 in human interphase nuclei is demonstrated by use of radioactive and nonradioactive in situ hybridization techniques with a DNA clone designated L1.84. This clone represents a distinct subpopulation of the repetitive human alphoid DNA family, located in the centric region of chromosome 18. Under stringent hybridization conditions hybridization of L1.84 is restricted to chromosome 18 and reflects the number of these chromosomes present in the nuclei, namely, two in normal diploid human cells and three in nuclei from cells with trisomy 18. Under conditions of low stringency, cross-hybridization with other subpopulations of the alphoid DNA family occurs in the centromeric regions of the whole chromosome complement, and numerous hybridization sites are detected over interphase nuclei. Detection of chromosome-specific target DNAs by non-radioactive in situ hybridization with appropriate DNA probes cloned from individual chromosomal subregions presents a rapid means of identifying directly numerical or even structural chromosome aberrations in the interphase nucleus. Present limitations and future applications of interphase cytogenetics are discussed

Allele-specific distribution of RNA polymerase II on female X chromosomes

While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described genome wide; however, whether or not PolII binds at transcriptionally inactive sites remains uncertain. The two X chromosomes in female cells in mammals present an opportunity to examine each of the two alleles of a given locus in both active and inactive states, depending on which X chromosome is silenced by X chromosome inactivation. Here, we investigated PolII occupancy and expression of the associated genes across the active (Xa) and inactive (Xi) X chromosomes in human female cells to elucidate the relationship of gene expression and PolII binding. We find that, while PolII in the pseudoautosomal region occupies both chromosomes at similar levels, it is significantly biased toward the Xa throughout the rest of the chromosome. The general paucity of PolII on the Xi notwithstanding, detectable (albeit significantly reduced) binding can be observed, especially on the evolutionarily younger short arm of the X. PolII levels at genes that escape inactivation correlate with the levels of their expression; however, additional PolII sites can be found at apparently silenced regions, suggesting the possibility of a subset of genes on the Xi that are poised for expression. Consistent with this hypothesis, we show that a high proportion of genes associated with PolII-accessible sites, while silenced in GM12878, are expressed in other female cell lines