Pathways of genetic adaptation: multistep origin of mutants under selection without induced mutagenesis in Salmonella enterica.

In several bacterial systems, mutant cell populations plated on growth-restricting medium give rise to revertant colonies that accumulate over several days. One model suggests that nongrowing parent cells mutagenize their own genome and thereby create beneficial mutations (stress-induced mutagenesis). By this model, the first-order induction of new mutations in a nongrowing parent cell population leads to the delayed accumulation of visible colonies. In an alternative model (selection only), selective conditions allow preexisting small-effect mutants to initiate clones that grow and give rise to faster-growing mutants. By the selection-only model, the delay in appearance of revertant colonies reflects (1) the time required for initial clones to reach a size sufficient to allow the second mutation plus (2) the time required for growth of the improved subclone. We previously characterized a system in which revertant colonies accumulate slowly and contain cells with two mutations, one formed before plating and one after. This left open the question of whether mutation rates increase under selection. Here we measure the unselected formation rate and the growth contribution of each mutant type. When these parameters are used in a graphic model of revertant colony development, they demonstrate that no increase in mutation rate is required to explain the number and delayed appearance of two of the revertant types

Semidefiniteness Without Hermiticity

Let A is an element of M(n)(C). We provode a rank characterization of the semidefiniteness of Hermitian A in two ways. We show that A is semidefinite if and only of rank [X* AX] = rank [AX], for all X is an element of M(n)(C), and that A is ssemidefinite if and only if rank [AXX*], for all X is an element of Mn(C). We show that, if A has semidefinite Hermitian part and A(2) has positive semidefinite Hermitian part, then A satisfies row and column inclusion. Let B is an element of M(n)(C), and let kappa be an integer with k \u3e= 2. If B*BA, B* BA(2), ..., N* BA(k) each has positive semidefinite Hermitian part; we show that rank [NAX} = rank [X*B*BAX] = ... = rank [X*B*BA(kappa-1)X], for all X is an element of M(n)(C) These results generalize or strengthen facts about real matrices known earlier

Sufficient conditions to be exceptional

A copositive matrix A is said to be exceptional if it is not the sum of a positive semidefinite matrix and a nonnegative matrix. We show that with certain assumptions on A(-1), especially on the diagonal entries, we can guarantee that a copositive matrix A is exceptional. We also show that the only 5-by-5 exceptional matrix with a hollow nonnegative inverse is the Horn matrix (up to positive diagonal congruence and permutation similarity)

The copositive completion problem

An n × n real symmetric matrix A is called (strictly) copositive if xTAx ⩾ 0 (\u3e0) whenever x ∈ Rn satisfies x ⩾ 0 (x ⩾ 0 and x ≠ 0). The (strictly) copositive matrix completion problem asks which partial (strictly) copositive matrices have a completion to a (strictly) copositive matrix. We prove that every partial (strictly) copositive matrix has a (strictly) copositive matrix completion and give a lower bound on the values used in the completion. We answer affirmatively an open question whether an n × n copositive matrix A = (aij) with all diagonal entries aii = 1 stays copositive if each off-diagonal entry of A is replaced by min{aij, 1}

Addressing emerging risks: Scientific and regulatory challenges associated with environmentally persistent free radicals

© 2016 by the authors; licensee MDPI, Basel, Switzerland. Airborne fine and ultrafine particulate matter (PM) are often generated through widely-used thermal processes such as the combustion of fuels or the thermal decomposition of waste. Residents near Superfund sites are exposed to PM through the inhalation of windblown dust, ingestion of soil and sediments, and inhalation of emissions from the on-site thermal treatment of contaminated soils. Epidemiological evidence supports a link between exposure to airborne PM and an increased risk of cardiovascular and pulmonary diseases. It is well-known that during combustion processes, incomplete combustion can lead to the production of organic pollutants that can adsorb to the surface of PM. Recent studies have demonstrated that their interaction with metal centers can lead to the generation of a surface stabilized metal-radical complex capable of redox cycling to produce ROS. Moreover, these free radicals can persist in the environment, hence their designation as Environmentally Persistent Free Radicals (EPFR). EPFR has been demonstrated in both ambient air PM2.5 (diameter \u3c 2.5 μm) and in PM from a variety of combustion sources. Thus, low-temperature, thermal treatment of soils can potentially increase the concentration of EPFR in areas in and around Superfund sites. In this review, we will outline the evidence to date supporting EPFR formation and its environmental significance. Furthermore, we will address the lack of methodologies for specifically addressing its risk assessment and challenges associated with regulating this new, emerging contaminant

Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study

African American Men are 65% more likely to develop prostate cancer and are twice as likely to die of prostate cancer, than are Caucasian American Males. The explanation for this glaring health disparity is still unknown; although a number of different plausible factors have been offered including genetic susceptibility and gene-environment interactions. We favor the hypothesis that altered gene expression plays a major role in the disparity observed in prostate cancer incidence and mortality between African American and Caucasian American Males. To discover genes or gene expression pattern(s) unique to African American or to Caucasian American Males that explain the observed prostate cancer health disparity in African American males, we conducted a micro array pilot project study that used prostate tumors with a Gleason score of 6. We compared gene expression profiling in tumors from African-American Males to prostate tumors in Caucasian American Males. A comparison of case-matched ratios revealed at least 67 statistically significant genes that met filtering criteria of at least +/- 4.0 fold change and p < 0.0001. Gene ontology terms prevalent in African American prostate tumor/normal ratios relative to Caucasian American prostate tumor/normal ratios included interleukins, progesterone signaling, Chromatin-mediated maintenance and myeloid dendritic cell proliferation. Functional in vitro assays are underway to determine roles that selected genes in these onotologies play in contributing to prostate cancer development and health disparity

A Structural Split in the Human Genome

Background: Promoter-associated CpG islands (PCIs) mediate methylation-dependent gene silencing, yet tend to co-locate to transcriptionally active genes. To address this paradox, we used data mining to assess the behavior of PCI-positive (PCI+) genes in the human genome. Results: PCI+ genes exhibit a bimodal distribution: (1) a 'housekeeping-like' subset characterized by higher GC content and lower intron length/number, and (2) a 'pseudogene paralog' subset characterized by lower GC content and higher intron length/number (p<0.001). These subsets are functionally distinguishable, with the former gene group characterized by higher expression levels and lower evolutionary rate (p<0.001). PCI-negative (PCI-) genes exhibit higher evolutionary rate and narrower expression breadth than PCI+ genes (p<0.001), consistent with more frequent tissue-specific inactivation. Conclusions: Adaptive evolution of the human genome appears driven in part by declining transcription of a subset of PCI+ genes, predisposing to both CpG→TpA mutation and intron insertion. We propose a model of evolving biological complexity in which environmentally-selected gains or losses of PCI methylation respectively favor positive or negative selection, thus polarizing PCI+ gene structures around a genomic core of ancestral PCI- genes. © 2007 Tang, Epstein.published_or_final_versio

Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection

How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data