A comparative study of Tam3 and Ac transposition in transgenic tobacco and petunia plants

Transposition of the Anthirrinum majus Tam3 element and the Zea mays Ac element has been monitored in petunia and tobacco plants. Plant vectors were constructed with the transposable elements cloned into the leader sequence of a marker gene. Agrobacterium tumefaciens-mediated leaf disc transformation was used to introduce the transposable element constructs into plant cells. In transgenic plants, excision of the transposable element restores gene expression and results in a clearly distinguishable phenotype. Based on restored expression of the hygromycin phosphotransferase II (HPTII) gene, we established that Tam3 excises in 30% of the transformed petunia plants and in 60% of the transformed tobacco plants. Ac excises from the HPTII gene with comparable frequencies (30%) in both plant species. When the β-glucuronidase (GUS) gene was used to detect transposition of Tam3, a significantly lower excision frequency (13%) was found in both plant species. It could be shown that deletion of parts of the transposable elements Tam3 and Ac, removing either one of the terminal inverted repeats (TIR) or part of the presumptive transposase coding region, abolished the excision from the marker genes. This demonstrates that excision of the transposable element Tam3 in heterologous plant species, as documented for the autonomous element Ac, also depends on both properties. Southern blot hybridization shows the expected excision pattern and the reintegration of Tam3 and Ac elements into the genome of tobacco plants.

Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos

Phobos Laser Ranging (PLR) is a concept for a space mission designed to advance tests of relativistic gravity in the solar system. PLR's primary objective is to measure the curvature of space around the Sun, represented by the Eddington parameter $\gamma$, with an accuracy of two parts in $10^7$, thereby improving today's best result by two orders of magnitude. Other mission goals include measurements of the time-rate-of-change of the gravitational constant, $G$ and of the gravitational inverse square law at 1.5 AU distances--with up to two orders-of-magnitude improvement for each. The science parameters will be estimated using laser ranging measurements of the distance between an Earth station and an active laser transponder on Phobos capable of reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10 ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12 cm aperture will permit links that even at maximum range will exceed a photon per second. A total measurement precision of 50 ps demands a few hundred photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser ranging (SLR) facilities--with appropriate augmentation--may be able to participate in PLR. Since Phobos' orbital period is about 8 hours, each observatory is guaranteed visibility of the Phobos instrument every Earth day. Given the current technology readiness level, PLR could be started in 2011 for launch in 2016 for 3 years of science operations. We discuss the PLR's science objectives, instrument, and mission design. We also present the details of science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table

The extraordinary evolutionary history of the reticuloendotheliosis viruses

The reticuloendotheliosis viruses (REVs) comprise several closely related amphotropic retroviruses isolated from birds. These viruses exhibit several highly unusual characteristics that have not so far been adequately explained, including their extremely close relationship to mammalian retroviruses, and their presence as endogenous sequences within the genomes of certain large DNA viruses. We present evidence for an iatrogenic origin of REVs that accounts for these phenomena. Firstly, we identify endogenous retroviral fossils in mammalian genomes that share a unique recombinant structure with REVs—unequivocally demonstrating that REVs derive directly from mammalian retroviruses. Secondly, through sequencing of archived REV isolates, we confirm that contaminated Plasmodium lophurae stocks have been the source of multiple REV outbreaks in experimentally infected birds. Finally, we show that both phylogenetic and historical evidence support a scenario wherein REVs originated as mammalian retroviruses that were accidentally introduced into avian hosts in the late 1930s, during experimental studies of P. lophurae, and subsequently integrated into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes, generating recombinant DNA viruses that now circulate in wild birds and poultry. Our findings provide a novel perspective on the origin and evolution of REV, and indicate that horizontal gene transfer between virus families can expand the impact of iatrogenic transmission events

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients

10.1371/journal.pone.0054522PLoS ONE81

Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interac- tions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin g1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Prions are proteins that can access multiple conformations, at least one of which is beta-sheet rich, infectious and self-perpetuating in nature. These infectious proteins show several remarkable biological activities, including the ability to form multiple infectious prion conformations, also known as strains or variants, encoding unique biological phenotypes, and to establish and overcome prion species (transmission) barriers. In this Perspective, we highlight recent studies of the yeast prion [PSI+], using various biochemical and structural methods, that have begun to illuminate the molecular mechanisms by which self-perpetuating prions encipher such biological activities. We also discuss several aspects of prion conformational change and structure that remain either unknown or controversial, and we propose approaches to accelerate the understanding of these enigmatic, infectious conformers

Racism as a determinant of health: a systematic review and meta-analysis

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants.<br /

Hypoxia-Induced Down-Regulation of Neprilysin by Histone Modification in Mouse Primary Cortical and Hippocampal Neurons

Amyloid β-peptide (Aβ) accumulation leads to neurodegeneration and Alzheimer's disease (AD). Aβ metabolism is a dynamic process in the Aβ production and clearance that requires neprilysin (NEP) and other enzymes to degrade Aβ. It has been reported that NEP expression is significantly decreased in the brain of AD patients. Previously we have documented hypoxia is a risk factor for Aβ generation in vivo and in vitro through increasing Aβ generation by altering β-cleavage and γ-cleavage of APP and down-regulating NEP, and causing tau hyperphosphorylation. Here, we investigated the molecular mechanisms of hypoxia-induced down-regulation of NEP. We found a significant decrease in NEP expression at the mRNA and protein levels after hypoxic treatment in mouse primary cortical and hippocampal neurons. Chromatin immunoprecipitation (ChIP) assays and relative quantitative PCR (q-PCR) revealed an increase of histone H3-lysine9 demethylation (H3K9me2) and a decrease of H3 acetylation (H3-Ace) in the NEP promoter regions following hypoxia. In addition, we found that hypoxia caused up-regulation of histone methyl transferase (HMT) G9a and histone deacetylases (HDACs) HDAC-1. Decreased expression of NEP during hypoxia can be prevented by application with the epigenetic regulators 5-Aza-2′-deoxycytidine (5-Aza), HDACs inhibitor sodium valproate (VA), and siRNA-mediated knockdown of G9a or HDAC1. DNA methylation PCR data do not support that hypoxia affects the methylation of NEP promoters. This study suggests that hypoxia may down-regulate NEP by increasing H3K9me2 and decreasing H3-Ace modulation