AmFm and lithium gap stars: Stellar evolution models with mass loss

A thorough study of the effects of mass loss on internal and surface abundances of A and F stars is carried out in order to constrain mass loss rates for these stars, as well as further elucidate some of the processes which compete with atomic diffusion. Self-consistent stellar evolution models of 1.3 to 2.5 M_sun stars including atomic diffusion and radiative accelerations for all species within the OPAL opacity database were computed with mass loss and compared to observations as well as previous calculations with turbulent mixing. Models with unseparated mass loss rates between 5 x 10^-14 and 10^-13 M_sun/yr reproduce observations for many cluster AmFm stars as well as Sirius A and o Leonis. These models also explain cool Fm stars, but not the Hyades lithium gap. Like turbulent mixing, these mass loss rates reduce surface abundance anomalies; however, their effects are very different with respect to internal abundances. For most of the main sequence lifetime of an A or F star, surface abundances in the presence of such mass loss depend on separation which takes place between log(Delta M/M_star)= -6 and -5. The current observational constraints do not allow us to conclude that mass loss is to be preferred over turbulent mixing (induced by rotation or otherwise) in order to explain the AmFm phenomenon. Internal concentration variations which could be detectable through asteroseismic tests should provide further information. If atomic diffusion coupled with mass loss are to explain the Hyades Li gap, the wind would need to be separated.Comment: 27 pages, 25 figures, accepted for publication in A&

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Orthogonal surface functionalization through bioactive vapor‐based polymer coatings

Reactive chemical vapor deposition (CVD) polymerization provides a substrate‐independent platform for effective functionalization of virtually any solid substrates, flat, or curved, even with complex geometries. This article reviews bioactive surface functionalization strategies based on CVD polymerization and highlights commonly used surface chemistries. These reactions include alkyne–azide “click” chemistry, reactions of active esters with amine, aldehydes/ketones with hydrazides and alkoxyamines, thiols with alkenes and alkynes and surface‐initiated atom transfer radical polymerization. The resulting biofunctional surface coatings can facilitate orthogonal immobilization of more than one type of ligand on a substrate. CVD polymer coatings with nanoscale thicknesses are widely applicable in biomedical applications and can be easily integrated into micro‐ and nanodevice fabrication. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131 , 40315.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106951/1/app40315.pd

White-to-brown metabolic conversion of human adipocytes by JAK inhibition

The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of novel therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus Kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a novel role for the JAK/STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity

TDP2 suppresses chromosomal translocations induced by DNA topoisomerase II during gene transcription

© The Author(s) 2017. DNA double-strand breaks (DSBs) induced by abortive topoisomerase II (TOP2) activity are a potential source of genome instability and chromosome translocation. TOP2-induced DNA double-strand breaks are rejoined in part by tyrosyl-DNA phosphodiesterase 2 (TDP2)-dependent non-homologous end-joining (NHEJ), but whether this process suppresses or promotes TOP2-induced translocations is unclear. Here, we show that TDP2 rejoins DSBs induced during transcription-dependent TOP2 activity in breast cancer cells and at the translocation ‘hotspot’, MLL. Moreover, we find that TDP2 suppresses chromosome rearrangements induced by TOP2 and reduces TOP2-induced chromosome translocations that arise during gene transcription. Interestingly, however, we implicate TDP2-dependent NHEJ in the formation of a rare subclass of translocations associated previously with therapy-related leukemia and characterized by junction sequences with 4-bp of perfect homology. Collectively, these data highlight the threat posed by TOP2-induced DSBs during transcription and demonstrate the importance of TDP2-dependent non-homologous end-joining in protecting both gene transcription and genome stability

Antibody-Based Sensors: Principles, Problems and Potential for Detection of Pathogens and Associated Toxins

Antibody-based sensors permit the rapid and sensitive analysis of a range of pathogens and associated toxins. A critical assessment of the implementation of such formats is provided, with reference to their principles, problems and potential for ‘on-site’ analysis. Particular emphasis is placed on the detection of foodborne bacterial pathogens, such as Escherichia coli and Listeria monocytogenes, and additional examples relating to the monitoring of fungal pathogens, viruses, mycotoxins, marine toxins and parasites are also provided

Three-dimensional cathodoluminescence imaging and electron backscatter diffraction: tools for studying the genetic nature of diamond inclusions

As a step towards resolving the genesis of inclusions in diamonds, a new technique is presented. This technique combines cathodoluminescence (CL) and electron backscatter diffraction (EBSD) using a focused ion beam-scanning electron microscope (FIB-SEM) instrument with the aim of determining, in detail, the three-dimensional diamond zonation adjacent to a diamond inclusion. EBSD reveals that mineral inclusions in a single diamond have similar crystallographic orientations to the host, within ±0. 4°. The chromite inclusions record a systematic change in Mg# and Cr# from core to the rim of the diamond that corresponds with a ~80°C decrease of their formation temperature as established by zinc thermometry. A chromite inclusion, positioned adjacent to a boundary between two major diamond growth zones, is multi-faceted with preferred octahedral and cubic faces. The chromite is surrounded by a volume of non-luminescent diamond (CL halo) that partially obscures any diamond growth structures. The CL halo has apparent crystallographic morphology with symmetrically oriented pointed features. The CL halo is enriched in ~200 ppm Cr and ~80 ppm Fe and is interpreted to have a secondary origin as it overprints a major primary diamond growth structure. The diamond zonation adjacent to the chromite is complex and records both syngenetic and protogenetic features based on current inclusion entrapment models. In this specific case, a syngenetic origin is favoured with the complex form of the inclusion and growth layers indicating changes of growth rates at the diamond-chromite interface. Combined EBSD and 3D-CL imaging appears an extremely useful tool in resolving the ongoing discussion about the timing of inclusion growth and the significance of diamond inclusion studies. © 2010 The Author(s)

Recombinase technology: applications and possibilities

The use of recombinases for genomic engineering is no longer a new technology. In fact, this technology has entered its third decade since the initial discovery that recombinases function in heterologous systems (Sauer in Mol Cell Biol 7(6):2087–2096, 1987). The random insertion of a transgene into a plant genome by traditional methods generates unpredictable expression patterns. This feature of transgenesis makes screening for functional lines with predictable expression labor intensive and time consuming. Furthermore, an antibiotic resistance gene is often left in the final product and the potential escape of such resistance markers into the environment and their potential consumption raises consumer concern. The use of site-specific recombination technology in plant genome manipulation has been demonstrated to effectively resolve complex transgene insertions to single copy, remove unwanted DNA, and precisely insert DNA into known genomic target sites. Recombinases have also been demonstrated capable of site-specific recombination within non-nuclear targets, such as the plastid genome of tobacco. Here, we review multiple uses of site-specific recombination and their application toward plant genomic engineering. We also provide alternative strategies for the combined use of multiple site-specific recombinase systems for genome engineering to precisely insert transgenes into a pre-determined locus, and removal of unwanted selectable marker genes

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead