The fate of the homoctenids (Tentaculitoidea) during the Frasnian-Famennian mass extinction (Late Devonian)

The homoctenids (Tentaculitoidea) are small, conical-shelled marine animals which are amongst the most abundant and widespread of all Late Devonian fossils. They were a principal casualty of the Frasnian-Famennian (F-F, Late Devonian) mass extinction, and thus provide an insight into the extinction dynamics. Despite their abundance during the Late Devonian, they have been largely neglected by extinction studies. A number of Frasnian-Famennian boundary sections have been studied, in Poland, Germany, France, and the United States. These sections have yielded homoctenids, which allow precise recognition of the timing of the mass extinction. It is clear that the homoctenids almost disappear from the fossil record during the latest Frasnian “Upper Kellwasser Event”. The coincident extinction of this pelagic group, and the widespread development of intense marine anoxia within the water column, provides a causal link between anoxia and the F-F extinction. Most notable is the sudden demise of a group, which had been present in rock-forming densities, during this anoxic event. One new species, belonging to Homoctenus is described, but is not formally named here

XUV digital in-line holography using high-order harmonics

A step towards a successful implementation of timeresolved digital in-line holography with extreme ultraviolet radiation is presented. Ultrashort XUV pulses are produced as high-order harmonics of a femtosecond laser and a Schwarzschild objective is used to focus harmonic radiation at 38 nm and to produce a strongly divergent reference beam for holographic recording. Experimental holograms of thin wires are recorded and the objects reconstructed. Descriptions of the simulation and reconstruction theory and algorithms are also given. Spatial resolution of few hundreds of nm is potentially achievable, and micrometer resolution range is demonstrated.Comment: 8 pages, 8 figure

Asiago eclipsing binaries program. II. V505 Per

The orbit and fundamental physical parameters of the double-lined eclipsing binary V505 Per are derived by means of Echelle high resolution, high S/N spectroscopy and B, V photometry. Effective temperatures, gravities, rotational velocities and metallicities are obtained from atmospheric chi^2 analysis. An E(B-V)<=0.01 mag reddening is derived from interstellar NaI and KI lines. The distance to the system computed from orbital parameters (60.6 +/- 1 pc) is identical to the newly re-reduced Hipparcos parallax (61.5 +/- 1.9 pc). The masses of the two components (M(1) = 1.2693 +/- 0.0011 and M(2) = 1.2514 +/- 0.0012 Msun) place them in the transition region between convective and radiative stellar cores of the HR diagram, with the more massive of the two showing already the effect of evolution within the Main Sequence band (T(1) = 6512 +/- 21 K, T(2) = 6462 +/- 12 K, R(1) = 1.287 +/- 0.014, R(2) = 1.266 +/- 0.013 Rsun). This makes this system of particular relevance to theoretical stellar models, as a test on the overshooting. We compare the firm observational results for V505 Per component stars with the predictions of various libraries of theoretical stellar models (BaSTI, Padova, Granada, Yonsei-Yale, Victoria-Regina) as well as BaSTI models computed specifically for the masses and chemical abundances of V505 Per. We found that the overshooting at the masses of V505 Per component stars is already pretty low, but not null, and described by efficiencies lambda(OV)=0.093 and 0.087 for the 1.27 and 1.25 Msun components, respectively. According to the computed BaSTI models, the age of the system is about 0.9 Gyr and the element diffusion during this time has reduced the surface metallicity from the initial [M/H]=-0.03 to the current [M/H]=-0.13, in excellent agreement with observed [M/H]=-0.12 +/- 0.03.Comment: accepted in press by A&

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia

Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy. Analysis of nonleukemic SCs from patients with CML also provided new insights into cell-extrinsic disruption of hematopoiesis in CML associated with clinical outcome. Furthermore, we used this single-cell approach to identify a blast-crisis-specific SC population, which was also present in a subclone of CML-SCs during the chronic phase in a patient who subsequently developed blast crisis. This approach, which might be broadly applied to any malignancy, illustrates how single-cell analysis can identify subpopulations of therapy-resistant SCs that are not apparent through cell-population analysis

Self-organized Emergence of Navigability on Small-World Networks

This paper mainly investigates why small-world networks are navigable and how to navigate small-world networks. We find that the navigability can naturally emerge from self-organization in the absence of prior knowledge about underlying reference frames of networks. Through a process of information exchange and accumulation on networks, a hidden metric space for navigation on networks is constructed. Navigation based on distances between vertices in the hidden metric space can efficiently deliver messages on small-world networks, in which long range connections play an important role. Numerical simulations further suggest that high cluster coefficient and low diameter are both necessary for navigability. These interesting results provide profound insights into scalable routing on the Internet due to its distributed and localized requirements.Comment: 3 figure

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

GenSeed-HMM: A tool for progressive assembly using profile HMMs as seeds and its application in Alpavirinae viral discovery from metagenomic data

This work reports the development of GenSeed-HMM, a program that implements seed-driven progressive assembly, an approach to reconstruct specific sequences from unassembled data, starting from short nucleotide or protein seed sequences or profile Hidden Markov Models (HMM). The program can use any one of a number of sequence assemblers. Assembly is performed in multiple steps and relatively few reads are used in each cycle, consequently the program demands low computational resources. As a proof-of-concept and to demonstrate the power of HMM-driven progressive assemblies, GenSeed-HMM was applied to metagenomic datasets in the search for diverse ssDNA bacteriophages from the recently described Alpavirinae subfamily. Profile HMMs were built using Alpavirinae-specific regions from multiple sequence alignments using either the viral protein 1 (VP1) (major capsid protein) or VP4 (genome replication initiation protein). These profile HMMs were used by GenSeed-HMM (running Newbler assembler) as seeds to reconstruct viral genomes from sequencing datasets of human fecal samples. All contigs obtained were annotated and taxonomically classified using similarity searches and phylogenetic analyses. The most specific profile HMM seed enabled the reconstruction of 45 partial or complete Alpavirinae genomic sequences. A comparison with conventional (global) assembly of the same original dataset, using Newbler in a standalone execution, revealed that GenSeed-HMM outperformed global genomic assembly in several metrics employed. This approach is capable of detecting organisms that have not been used in the construction of the profile HMM, which opens up the possibility of diagnosing novel viruses, without previous specific information, constituting a de novo diagnosis. Additional applications include, but are not limited to, the specific assembly of extrachromosomal elements such as plastid and mitochondrial genomes from metagenomic data. Profile HMM seeds can also be used to reconstruct specific protein coding genes for gene diversity studies, and to determine all possible gene variants present in a metagenomic sample. Such surveys could be useful to detect the emergence of drug-resistance variants in sensitive environments such as hospitals and animal production facilities, where antibiotics are regularly used. Finally, GenSeed-HMM can be used as an adjunct for gap closure on assembly finishing projects, by using multiple contig ends as anchored seeds

Iron bioavailability in two commercial cultivars of wheat: a comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.