Inhibitory effect of a short Z-DNA forming sequence on transcription elongation by T7 RNA polymerase

DNA sequences capable of forming unusual secondary structures can be a source of genomic instability. In some cases that instability might be affected by transcription, as recently shown for the Z-DNA forming sequence (CG)14, which causes genomic instability both in mammalian cells and in bacteria, and this effect increases with its transcription. We have investigated the effect of this (CG)14 sequence on transcription with T7 RNA polymerase in vitro. We detected partial transcription blockage within the sequence; the blockage increased with negative supercoiling of the template DNA. This effect was not observed in a control self-complementary sequence of identical length and base composition as the (CG)14 sequence, when the purine–pyrimidine alternation required for Z-DNA formation was disrupted. These findings suggest that the inhibitory effect on T7 transcription results from Z-DNA formation in the (CG)14 sequence rather than from an effect of the sequence composition or from hairpin formation in either the DNA or the RNA product

DNA slip-outs cause RNA polymerase II arrest in vitro: potential implications for genetic instability

The abnormal number of repeats found in triplet repeat diseases arises from ‘repeat instability’, in which the repetitive section of DNA is subject to a change in copy number. Recent studies implicate transcription in a mechanism for repeat instability proposed to involve RNA polymerase II (RNAPII) arrest caused by a CTG slip-out, triggering transcription-coupled repair (TCR), futile cycles of which may lead to repeat expansion or contraction. In the present study, we use defined DNA constructs to directly test whether the structures formed by CAG and CTG repeat slip-outs can cause transcription arrest in vitro. We found that a slip-out of (CAG)20 or (CTG)20 repeats on either strand causes RNAPII arrest in HeLa cell nuclear extracts. Perfect hairpins and loops on either strand also cause RNAPII arrest. These findings are consistent with a transcription-induced repeat instability model in which transcription arrest in mammalian cells may initiate a ‘gratuitous’ TCR event leading to a change in repeat copy number. An understanding of the underlying mechanism of repeat instability could lead to intervention to slow down expansion and delay the onset of many neurodegenerative diseases in which triplet repeat expansion is implicated

Early Warning Signals of Social Transformation: A Case Study from the US Southwest

abstract: Recent research in ecology suggests that generic indicators, referred to as early warning signals (EWS), may occur before significant transformations, both critical and non-critical, in complex systems. Up to this point, research on EWS has largely focused on simple models and controlled experiments in ecology and climate science. When humans are considered in these arenas they are invariably seen as external sources of disturbance or management. In this article we explore ways to include societal components of socio-ecological systems directly in EWS analysis. Given the growing archaeological literature on ‘collapses,’ or transformations, in social systems, we investigate whether any early warning signals are apparent in the archaeological records of the build-up to two contemporaneous cases of social transformation in the prehistoric US Southwest, Mesa Verde and Zuni. The social transformations in these two cases differ in scope and severity, thus allowing us to explore the contexts under which warning signals may (or may not) emerge. In both cases our results show increasing variance in settlement size before the transformation, but increasing variance in social institutions only before the critical transformation in Mesa Verde. In the Zuni case, social institutions appear to have managed the process of significant social change. We conclude that variance is of broad relevance in anticipating social change, and the capacity of social institutions to mitigate transformation is critical to consider in EWS research on socio-ecological systems.The article is published at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.016368

Air base defense different times call for different methods

As the United States Air Force air base defense doctrine evolved over the years, implementation and execution errors were occasionally exploited by insurgent forces operating in the areas adjacent to U.S. occupied air bases. Executing unconventional attack methodologies, primarily via stand-off weapons, these insurgents were able to wreak havoc on U.S. and allied air bases, causing massive destruction and the loss of American lives. An examination of the literature from air base (ground) attacks in Korea, Vietnam and at Khobar Towers indicated several problematic areas resonating in all three cases. These common areas include: inadequate intelligence (both organic and external), lack of proper focus on critical infrastructure and insufficient or absent force protection technologies. Many of today[alpha]s security experts are predicting future attacks on military infrastructure to include stateside and forwarddeployed air bases. Today[alpha]s slightly diverse, yet consistent insurgent enemy, with attack methodologies mirroring those of Korea, Vietnam and Khobar Towers, remains a constant and formidable threat. As the Air Force moves forward with its newly implemented Integrated Base Defense doctrine, specific attention must be paid to improving upon the problem areas from the past. This thesis focuses on the specific problematic areas, and provides policy recommendations for force protection planners.http://archive.org/details/airbasedefensedi109452508Approved for public release; distribution is unlimited

Social justice and spirituality in Rebecca Harding Davis’s early Atlantic Monthly writings.

This thesis examines three of Rebecca Harding Davis’s writings published by the Atlantic Monthly from 1860 to 1862. Davis begins with questioning capitalist claims of building a middle class in “Life in the Iron Mills.” In less than two years, the censure of Davis’s first work softens in a more merciful tone in her first novel Margret Howth. By the time Davis publishes the short story “David Gaunt” in 1862, her message of tolerance becomes more overtly political as it questions the necessity of the Civil War and foreshadows the trials of Reconstruction. The sole character type that escapes harsh reproach in these stories manifests in the plain female who is not merely tolerant but without prejudice regardless of race, class, gender, or politics on the basis of attempting to follow the teachings of Jesus. Followers of Jesus, Davis posits, can practice social justice without turning into zealots or Pharisees.M.A

T7 RNA polymerase

sequence on transcription elongation b