V-MitoSNP: visualization of human mitochondrial SNPs

BACKGROUND: Mitochondrial single nucleotide polymorphisms (mtSNPs) constitute important data when trying to shed some light on human diseases and cancers. Unfortunately, providing relevant mtSNP genotyping information in mtDNA databases in a neatly organized and transparent visual manner still remains a challenge. Amongst the many methods reported for SNP genotyping, determining the restriction fragment length polymorphisms (RFLPs) is still one of the most convenient and cost-saving methods. In this study, we prepared the visualization of the mtDNA genome in a way, which integrates the RFLP genotyping information with mitochondria related cancers and diseases in a user-friendly, intuitive and interactive manner. The inherent problem associated with mtDNA sequences in BLAST of the NCBI database was also solved. DESCRIPTION: V-MitoSNP provides complete mtSNP information for four different kinds of inputs: (1) color-coded visual input by selecting genes of interest on the genome graph, (2) keyword search by locus, disease and mtSNP rs# ID, (3) visualized input of nucleotide range by clicking the selected region of the mtDNA sequence, and (4) sequences mtBLAST. The V-MitoSNP output provides 500 bp (base pairs) flanking sequences for each SNP coupled with the RFLP enzyme and the corresponding natural or mismatched primer sets. The output format enables users to see the SNP genotype pattern of the RFLP by virtual electrophoresis of each mtSNP. The rate of successful design of enzymes and primers for RFLPs in all mtSNPs was 99.1%. The RFLP information was validated by actual agarose electrophoresis and showed successful results for all mtSNPs tested. The mtBLAST function in V-MitoSNP provides the gene information within the input sequence rather than providing the complete mitochondrial chromosome as in the NCBI BLAST database. All mtSNPs with rs number entries in NCBI are integrated in the corresponding SNP in V-MitoSNP. CONCLUSION: V-MitoSNP is a web-based software platform that provides a user-friendly and interactive interface for mtSNP information, especially with regard to RFLP genotyping. Visual input and output coupled with integrated mtSNP information from MITOMAP and NCBI make V-MitoSNP an ideal and complete visualization interface for human mtSNPs association studies

Inflammatory cytokines and biofilm production sustain Staphylococcus aureus outgrowth and persistence: A pivotal interplay in the pathogenesis of Atopic Dermatitis

Individuals with Atopic dermatitis (AD) are highly susceptible to Staphylococcus aureus colonization. However, the mechanisms driving this process as well as the impact of S. aureus in AD pathogenesis are still incompletely understood. In this study, we analysed the role of biofilm in sustaining S. aureus chronic persistence and its impact on AD severity. Further we explored whether key inflammatory cytokines overexpressed in AD might provide a selective advantage to S. aureus. Results show that the strength of biofilm production by S. aureus correlated with the severity of the skin lesion, being significantly higher (P < 0.01) in patients with a more severe form of the disease as compared to those individuals with mild AD. Additionally, interleukin (IL)-β and interferon γ (IFN-γ), but not interleukin (IL)-6, induced a concentration-dependent increase of S. aureus growth. This effect was not observed with coagulase-negative staphylococci isolated from the skin of AD patients. These findings indicate that inflammatory cytokines such as IL1-β and IFN-γ, can selectively promote S. aureus outgrowth, thus subverting the composition of the healthy skin microbiome. Moreover, biofilm production by S. aureus plays a relevant role in further supporting chronic colonization and disease severity, while providing an increased tolerance to antimicrobials

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Discrimination of Supramolecular Chirality using a Protein Nanopore

Supramolecular chirality may emerge from self-assembly processes to yield architectures that differ only in the topological arrangement of their constituent parts. Since the properties of the resulting enantiomeric assemblies are identical, purification and characterisation can be challenging. Here, we have examined the hypothesis that the intrinsic chirality of a protein nanopore can be exploited to detect supramolecular chirality. Transient blockages in the ion current flowing through a single membrane-spanning α-haemolysin nanopore were shown to discriminate between M4L6 tetrahedral coordination cages of opposing chiralities. The single-molecule nature of the approach facilitated direct access to the rates of association and dissociation with the nanopore, which allowed the concentrations of the enantiomeric supramolecular assemblies to be determined in situ. Thus, we have established that a protein nanopore can be used to discriminate the chiral topologies of supramolecular assemblies, even when they are too large to fully enter the nanopore

IGRhCellID: integrated genomic resources of human cell lines for identification

Cell line identification is emerging as an essential method for every cell line user in research community to avoid using misidentified cell lines for experiments and publications. IGRhCellID (http://igrcid.ibms.sinica.edu.tw) is designed to integrate eight cell identification methods including seven methods (STR profile, gender, immunotypes, karyotype, isoenzyme profile, TP53 mutation and mutations of cancer genes) available in various public databases and our method of profiling genome alterations of human cell lines. With data validation of 11 small deleted genes in human cancer cell lines, profiles of genomic alterations further allow users to search for human cell lines with deleted gene to serve as indigenous knock-out cell model (such as SMAD4 in gene view), with amplified gene to be the cell models for testing therapeutic efficacy (such as ERBB2 in gene view) and with overlapped aberrant chromosomal loci for revealing common cancer genes (such as 9p21.3 homozygous deletion with co-deleted CDKN2A, CDKN2B and MTAP in chromosome view). IGRhCellID provides not only available methods for cell identification to help eradicating concerns of using misidentified cells but also designated genetic features of human cell lines for experiments

Multi-Site N-glycan mapping study 1: Capillary electrophoresis – laser induced fluorescence

An international team that included 20 independent laboratories from biopharmaceutical companies, universities, analytical contract laboratories and national authorities in the United States, Europe and Asia was formed to evaluate the reproducibility of sample preparation and analysis of N-glycans using capillary electrophoresis of 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled glycans with laser induced fluorescence (CE-LIF) detection (16 sites) and ultra highperformance liquid chromatography (UHPLC, 12 sites; results to be reported in a subsequent publication). All participants used the same lot of chemicals, samples, reagents, and columns/capillaries to run their assays. Migration time, peak area and peak area percent values were determined for all peaks with >0.1% peak area. Our results demonstrated low variability and high reproducibility, both, within any given site as well across all sites, which indicates that a standard N-glycan analysis platform appropriate for general use (clone selection, process development, lot release, etc.) within the industry can be established

The genetic architecture of branched-chain amino acid accumulation in tomato fruits

Previous studies of the genetic architecture of fruit metabolic composition have allowed us to identify four strongly conserved co-ordinate quantitative trait loci (QTL) for the branched-chain amino acids (BCAAs). This study has been extended here to encompass the other 23 enzymes described to be involved in the pathways of BCAA synthesis and degradation. On coarse mapping the chromosomal location of these enzymes, it was possible to define the map position of 24 genes. Of these genes eight co-localized, or mapped close to BCAA QTL including those encoding ketol-acid reductoisomerase (KARI), dihydroxy-acid dehydratase (DHAD), and isopropylmalate dehydratase (IPMD). Quantitative evaluation of the expression levels of these genes revealed that the S. pennellii allele of IPMD demonstrated changes in the expression level of this gene, whereas those of KARI and DHAD were invariant across the genotypes. Whilst the antisense inhibition of IPMD resulted in increased BCAA, the antisense inhibition of neither KARI nor DHAD produced a clear effect in fruit BCAA contents. The results are discussed both with respect to the roles of these specific enzymes within plant amino acid metabolism and within the context of current understanding of the regulation of plant branched-chain amino acid metabolism

Proximity and Josephson effects in superconductor - antiferromagnetic Nb / \gamma-Fe50Mn50 heterostructures

We study the proximity effect in superconductor (S), antiferromagnetic (AF) bilayers, and report the fabrication and measurement of the first trilayer S/AF/S Josephson junctions. The disordered f.c.c. alloy \gamma-Fe50Mn50 was used as the AF, and the S is Nb. Micron and sub-micron scale junctions were measured, and the scaling of $J_C (d_AF)$ gives a coherence length in the AF of 2.4 nm, which correlates with the coherence length due to suppression of $T_C$ in the bilayer samples. The diffusion constant for FeMn was found to be 1.7 \times 10$^{-4}$ m$^2$ s$^-1$, and the density of states at the Fermi level was also obtained. An exchange biased FeMn/Co bilayer confirms the AF nature of the FeMn in this thickness regime.Comment: 6 pages, 5 figures, accepted for Phys. Rev.

A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay

We report a new measurement of electron antineutrino disappearance using the fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9$\times$10$^5$ GW$_{\rm th}$-ton-days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six $^{241}$Am-$^{13}$C radioactive calibration sources reduced the background by a factor of two for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of $\sin^{2}2\theta_{13}$ and $|\Delta m^2_{ee}|$ were halved as a result of these improvements. Analysis of the relative antineutrino rates and energy spectra between detectors gave $\sin^{2}2\theta_{13} = 0.084\pm0.005$ and $|\Delta m^{2}_{ee}|= (2.42\pm0.11) \times 10^{-3}$ eV$^2$ in the three-neutrino framework.Comment: Updated to match final published versio