bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bones hold the key to DNA virus history and epidemiology
Authors: Toppinen M. , Perdomo M. F. , Palo J. U. , Simmonds P. , Lycett S. J. , Söderlund-Venermo M. , Sajantila A. , Hedman K. 
Published: November 2015

AbstractDNA in human skeletal remains represents an important historical source of host genomic information and potentially of infecting viruses. However, little is known about viral persistence in bone. We searched ca. 70-year-old long bones of putative Finnish casualties from World War II for parvovirus B19 (B19V) DNA and found a remarkable prevalence of 45%. The viral sequences were exclusively of genotypes 2 (n = 41), which disappeared from circulation in 1970´s, or genotype 3 (n = 2), which has never been reported in Northern Europe. Based on mitochondrial and Y-chromosome profiling, the two individuals carrying B19V genotype 3 were likely from the Soviet Red Army. The most recent common ancestor for all genotypes was estimated at early 1800s. This work demonstrates the forms of B19V that circulated in the first half of the 20th century and provides the first evidence of the suitability of bone for exploration of DNA viruses.
Tandem Spinach Array for mRNA Imaging in Living Bacterial Cells
Authors: Zhang Jichuan , Fei Jingyi , Leslie Benjamin J. , Han Kyu Young , Kuhlman Thomas E. , Ha Taekjip 
Published: November 2015

AbstractLive cell RNA imaging using genetically encoded fluorescent labels is an important tool for monitoring RNA activities. A recently reported RNA aptamer-fluorogen system, the Spinach, in which an RNA aptamer binds and induces the fluorescence of a GFP-like 3,5-difluoro-4-hydroxybenzylidene imidazolinone (DFHBI) ligand, can be readily tagged to the RNA of interest. Although the aptamer–fluorogen system is sufficient for imaging highly abundant non-coding RNAs (tRNAs, rRNAs, etc.), it performs poorly for mRNA imaging due to low brightness. In addition, whether the aptamer-fluorogen system may perturb the native RNA characteristics has not been systematically characterized at the levels of RNA transcription, translation and degradation. To increase the brightness of these aptamer-fluorogen systems, we constructed and tested tandem arrays containing multiple Spinach aptamers (8–64 aptamer repeats). Such arrays enhanced the brightness of the tagged mRNA molecules by up to ~17 fold in living cells. Strong laser excitation with pulsed illumination further increased the imaging sensitivity of Spinach array-tagged RNAs. Moreover, transcriptional fusion to the Spinach array did not affect mRNA transcription, translation or degradation, indicating that aptamer arrays might be a generalizable labeling method for high-performance and low-perturbation live cell RNA imaging.
Structural delineation of stem-loop RNA binding by human TAF15 protein
Authors: Kashyap Maruthi , Ganguly Akshay Kumar , Bhavesh Neel Sarovar 
Published: November 2015

AbstractHuman TATA binding protein associated factor 2 N (TAF15) and Fused in sarcoma (FUS) are nucleic acid binding proteins belonging to the conserved FET family of proteins. They are involved in diverse processes such as pre-mRNA splicing, mRNA transport and DNA binding. The absence of information regarding the structural mechanism employed by the FET family in recognizing and discriminating their cognate and non-cognate RNA targets has hampered the attainment of consensus on modes of protein-RNA binding for this family. Our study provides a molecular basis of this RNA recognition using a combination of solution-state NMR spectroscopy, calorimetry, docking and molecular dynamics simulation. Analysis of TAF15-RRM solution structure and its binding with stem-loop RNA has yielded conclusive evidence of a non-canonical mode of RNA recognition. Rather than classical stacking interactions that occur across nitrogen bases and aromatic amino acids on ribonucleoprotein sites, moderate-affinity hydrogen bonding network between the nitrogen bases in the stem-loop RNA and a concave face on the RRM surface primarily mediate TAF15-RRM RNA interaction. We have compared the binding affinities across a set of single-stranded RNA oligonucleotides to conclusively establish that RNA binding is dependent upon structural elements in the RNA rather than sequence.
Severity of DSS-induced colitis is reduced in Ido1-deficient mice with down-regulation of TLR-MyD88-NF-kB transcriptional networks
Authors: Shon Woo-Jeong , Lee Young-Kwan , Shin Ji Hee , Choi Eun Young , Shin Dong-Mi 
Published: November 2015

AbstractIndoleamine 2,3 -dioxygenase 1 (IDO1) catalyzes L-tryptophan to kynurenine in the first and rate-limiting step of tryptophan metabolism. IDO1 is expressed widely throughout the body, with especially high expression in colonic intestinal tissues. To examine the role of IDO1 in the colon, transcriptome analysis was performed in both Ido1−/− and Ido1+/+ mice. Gene set enrichment analysis identified the Inflammatory Response as the most significant category modulated by the absence of IDO1. This observation prompted us to further investigate the function of IDO1 in the development of tissue inflammation. By using DSS-induced experimental colitis mice models, we found that the disease in Ido1−/− mice was less severe than in Ido1+/+ mice. Pharmacological inhibition of IDO1 by L-1MT attenuated the severity of DSS-colitis as well. Transcriptome analyses revealed that pathways involving TLR and NF-kB signaling were significantly down-regulated by the absence of IDO1. Furthermore, dramatic changes in TLR and NF-kB signaling resulted in substantial changes in the expression of many inflammatory cytokines and chemokines. Numbers of inflammatory cells in colon and peripheral blood were reduced in IDO1 deficiency. These findings suggest that IDO1 plays important roles in producing inflammatory responses and modulating transcriptional networks during the development of colitis.
Enhanced Charge Separation and FRET at Heterojunctions between Semiconductor Nanoparticles and Conducting Polymer Nanofibers for Efficient Solar Light Harvesting
Authors: Sardar Samim , Kar Prasenjit , Remita Hynd , Liu Bo , Lemmens Peter , Kumar Pal Samir , Ghosh Srabanti 
Published: November 2015

AbstractEnergy harvesting from solar light employing nanostructured materials offer an economic way to resolve energy and environmental issues. We have developed an efficient light harvesting heterostructure based on poly(diphenylbutadiyne) (PDPB) nanofibers and ZnO nanoparticles (NPs)viaa solution phase synthetic route. ZnO NPs (~20 nm) were homogeneously loaded onto the PDPB nanofibers as evident from several analytical and spectroscopic techniques. The photoinduced electron transfer from PDPB nanofibers to ZnO NPs has been confirmed by steady state and picosecond-resolved photoluminescence studies. The co-sensitization for multiple photon harvesting (with different energies) at the heterojunction has been achievedviaa systematic extension of conjugation from monomeric to polymeric diphenyl butadiyne moiety in the proximity of the ZnO NPs. On the other hand, energy transfer from the surface defects of ZnO NPs (~5 nm) to PDPB nanofibers through Förster Resonance Energy Transfer (FRET) confirms the close proximity with molecular resolution. The manifestation of efficient charge separation has been realized with ~5 fold increase in photocatalytic degradation of organic pollutants in comparison to polymer nanofibers counterpart under visible light irradiation. Our results provide a novel approach for the development of nanoheterojunctions for efficient light harvesting which will be helpful in designing future solar devices.
pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity
Authors: Jiang Wei , Strohman Michael J. , Somasundaram Sriram , Ayyangar Sashi , Hou Tieying , Wang Nan , Mellins Elizabeth D. 
Published: November 2015

AbstractThe peptide-exchange catalyst, HLA-DM and its inhibitor, HLA-DO control endosomal generation of peptide/class II major histocompatibility protein (MHC-II) complexes; these complexes traffic to the cell surface for inspection by CD4+ T cells. Some evidence suggests that pH influences DO regulation of DM function, but pH also affects the stability of polymorphic MHC-II proteins, spontaneous peptide loading, DM/MHC-II interactions and DM catalytic activity, imposing challenges on approaches to determine pH effects on DM-DO function and their mechanistic basis. Using optimized biochemical methods, we dissected pH-dependence of spontaneous and DM-DO-mediated class II peptide exchange and identified an MHC-II allele-independent relationship between pH, DO/DM ratio and efficient peptide exchange. We demonstrate that active, free DM is generated from DM-DO complexes at late endosomal/lysosomal pH due to irreversible, acid-promoted DO destruction rather than DO/DM molecular dissociation. Any soluble DM that remains in complex with DO stays inert. pH-exposure of DM-DO in cell lysates corroborates such a pH-regulated mechanism, suggesting acid-activated generation of functional DM in DO-expressing cells.
Functional analysis of the 11q23.3 glioma susceptibility locus implicates PHLDB1 and DDX6 in glioma susceptibility
Authors: Baskin Rebekah , Woods Nicholas T. , Mendoza-Fandiño Gustavo , Forsyth Peter , Egan Kathleen M. , Monteiro Alvaro N.A. 
Published: November 2015

AbstractGlioma is the most common malignant primary brain tumor and is associated with poor prognosis. Genetic factors contributing to glioma risk have recently been investigated through genome-wide association studies (GWAS), implicating seven independent glioma risk loci in six chromosomal regions. Here, we performed an in-depth functional analysis of the risk locus proximal to the PHLDB1 gene on 11q23.3. We retrieved all SNPs in linkage disequilibrium (r2 ≥ 0.2) with the glioma-associated SNP (rs498872) and performed a comprehensive bioinformatics and experimental functional analysis for the region. After testing candidate SNPs for allele-specific activity in a luciferase-based enhancer scanning assay, we established a subset of 10 functional SNPs in the promoters of PHLDB1 and DDX6, and in a putative enhancer element. Chromatin conformation capture (3C) identified a physical interaction between the enhancer element containing a functional SNP (rs73001406) and the promoter of the DDX6 gene. Knockdown experiments in cell culture and 3D assays to evaluate the role of PHLDB1 and DDX6 suggest that both genes may contribute to the phenotype. These studies reveal the functional landscape of the 11q23.3 glioma susceptibility locus and identify a network of functional SNPs in regulatory elements and two target genes as a possible mechanism driving glioma risk association.
Aminopeptidase T of M29 Family Acts as A Novel Intracellular Virulence Factor for Listeria monocytogenes Infection
Authors: Cheng Changyong , Wang Xiaowen , Dong Zhimei , Shao Chunyan , Yang Yongchun , Fang Weihuan , Fang Chun , Wang Hang , Yang Menghua , Jiang Lingli , Zhou Xiangyang , Song Houhui 
Published: November 2015

AbstractThe foodborne pathogen Listeria monocytogenes employs a number of virulence determinants including metalloproteases to infect hosts. Here for the first time, we identified an M29 family aminopeptidase T (encoded by lmo1603) from L. monocytogenes that possesses a typical feature to catalyze the cleavage of amino acids from peptide substrates, with a preference for arginine. The purified recombinant Lmo1603 was activated by Fe3+, Zn2+ and Mn2+, but strongly stimulated by Co2+, indicating that Lmo1603 is a cobalt-dependent aminopeptidase. Single mutation at any of the Glu216, Glu281, His308, Tyr315, His327 and Asp329 completely abolished the enzymatic activity of Lmo1603. More importantly, we showed that Lmo1603 was mainly involved in Listeria infection, but not required for growth in rich laboratory medium and minimal defined medium. Disruption of Lmo1603 resulted in almost complete attenuation of Listeria virulence in a mouse infection model. In addition, we demonstrated that Lmo1603 was mainly localized in the bacterial cytosol and required for invasion and survival inside human epithelial cells and murine macrophages. We conclude that Lmo1603 encodes a functional aminopeptidase T of M29 family, which acts as a novel intracellular virulence factor essential in the successful establishment of L. monocytogenes infections in a mouse model.
Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1
Authors: Sasaki Yuka , Kamiyama Shuhei , Kamiyama Azusa , Matsumoto Konomi , Akatsu Moe , Nakatani Yoshihito , Kuwata Hiroshi , Ishikawa Yukio , Ishii Toshiharu , Yokoyama Chieko , Hara Shuntaro 
Published: November 2015

AbstractProstacyclin synthase (PGIS) and microsomal prostaglandin E synthase-1 (mPGES-1) are prostaglandin (PG) terminal synthases that function downstream of inducible cyclooxygenase (COX)-2 in the PGI2 and PGE2 biosynthetic pathways, respectively. mPGES-1 has been shown to be involved in various COX-2-related diseases such as inflammatory diseases and cancers, but it is not yet known how PGIS is involved in these COX-2-related diseases. Here, to clarify the pathophysiological role of PGIS, we investigated the phenotypes of PGIS and mPGES-1 individual knockout (KO) or double KO (DKO) mice. The results indicate that a thioglycollate-induced exudation of leukocytes into the peritoneal cavity was suppressed by the genetic-deletion of PGIS. In the PGIS KO mice, lipopolysaccharide-primed pain nociception (as assessed by the acetic acid-induced writhing reaction) was also reduced. Both of these reactions were suppressed more effectively in the PGIS/mPGES-1 DKO mice than in the PGIS KO mice. On the other hand, unlike mPGES-1 deficiency (which suppressed azoxymethane-induced colon carcinogenesis), PGIS deficiency up-regulated both aberrant crypt foci formation at the early stage of carcinogenesis and polyp formation at the late stage. These results indicate that PGIS and mPGES-1 cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis and that PGIS-derived PGI2 has anti-carcinogenic effects.
Climate-induced mortality of spruce stands in Belarus
Authors: Kharuk Viacheslav I , Im Sergei T , Dvinskaya Maria L , Golukov Alexei S , Ranson Kenneth J 
Published: November 2015

Abstract
The aim of this work is an analysis of the causes of spruce (Picea abies L.) decline and mortality in Belarus. The analysis was based on forest inventory and Landsat satellite (land cover classification, climate variables (air temperature, precipitation, evaporation, vapor pressure deficit, SPEI drought index)), and GRACE-derived soil moisture estimation (equivalent of water thickness anomalies, EWTA). We found a difference in spatial patterns between dead stands and all stands (i.e., before mortality). Dead stands were located preferentially on relief features with higher water stress risk (i.e., higher elevations, steeper slopes, south and southwestern exposure). Spruce mortality followed a series of repeated droughts between 1990 and 2010. Mortality was negatively correlated with air humidity (r = –0.52), and precipitation (r = –0.57), and positively correlated with the prior year vapor pressure deficit (r = 0.47), and drought increase (r = 0.57). Mortality increased with the increase in occurrence of spring frosts (r = 0.5), and decreased with an increase in winter cloud cover (r = –0.37). Spruce mortality was negatively correlated with snow water accumulation (r = –0.81) and previous year anomalies in water soil content (r = –0.8). Weakened by water stress, spruce stands were attacked by pests and phytopathogens. Overall, spruce mortality in Belarussian forests was caused by drought episodes and drought increase in synergy with pest and phytopathogen attacks. Vast Picea abies mortality in Belarus and adjacent areas of Russia and Eastern Europe is a result of low adaptation of that species to increased drought. This indicates the necessity of spruce replacement by drought-tolerant indigenous (e.g., Pinus sylvestris, Querqus robur) or introduced (e.g., Larix sp. or Pseudotsuga menzieslii) species to obtain sustainable forest growth management.
Insights into the evolution of symbiotic recurrent novae from radio synchrotron emission: V745 Scorpii and RS Ophiuchi
Authors: Kantharia N. G. , Dutta Prasun , Roy Nirupam , Anupama G. C. , Ishwara-Chandra C. H. , Chitale A. , Prabhu T. P. , Banerjee D. P. K. , Ashok N. M. 
Published: November 2015

Abstract
We present observations at 610 and 235 MHz using the Giant Metrewave Radio Telescope (GMRT) of the recurrent nova V745 Scorpii which recorded its last outburst on 2014 February 6. This is the second symbiotic recurrent nova whose light curve at low frequencies has been followed in detail, the first being RS Ophiuchi in 2006. We fitted the 610 MHz light curve by a model of synchrotron emission from an expanding shell being modified by radiative transfer effects due to local absorbing gas consisting of a uniformly distributed and a clumpy component. Using our model parameters, we find that the emission at 235 MHz peaked around day 35 which is consistent with our GMRT observations. The two main results of our study are (1) The radio emission at a given frequency is visible sooner after the outburst in successive outbursts of both V745 Scorpii and RS Ophiuchi. The earlier detection of radio emission is interpreted to be caused by decreasing foreground densities. (2) The clumpy material, if exists, is close to the white dwarf and can be interpreted as being due to the material from the hot accretion disc. The uniform density gas is widespread and attributed to the winds blown by the white dwarf. We present implications of these results on the evolution of both novae. Such studies along with theoretical understanding have the potential of resolving several outstanding issues such as why all recurrent novae are not detectable in synchrotron radio and whether recurrent novae are progenitor systems of Type 1a supernova.
A timing constraint on the (total) mass of the Large Magellanic Cloud
Authors: Peñarrubia Jorge , Gómez Facundo A. , Besla Gurtina , Erkal Denis , Ma Yin-Zhe 
Published: November 2015

Abstract
This paper explores the effect of the Large Magellanic Cloud (LMC) on the mass estimates obtained from the timing argument. We show that accounting for the presence of the LMC systematically lowers the Local Group mass (MLG) derived from the relative motion of the Milky Way–Andromeda pair. Motivated by this result, we apply a Bayesian technique devised by Peñarrubia et al. to simultaneously fit (i) distances and velocities of galaxies within 3 Mpc and (ii) the relative motion between the Milky Way and Andromeda derived from HST observations, with the LMC mass (MLMC) as a free parameter. Our analysis returns a Local Group mass $M_{\rm LG}=2.64^{+0.42}_{-0.38}\times 10^{12}\,\mathrm{M}_{\odot }$ at a 68 per cent confidence level. The masses of the Milky Way, $M_{\rm MW}=1.04_{-0.23}^{+0.26}\times 10^{12}\,\mathrm{M}_{\odot }$, and Andromeda, $M_{{\rm M}31}=1.33_{-0.33}^{+0.39}\times 10^{12}\,\mathrm{M}_{\odot }$, are consistent with previous estimates that neglect the impact of the LMC on the observed Hubble flow. We find a (total) LMC mass $M_{\rm LMC}=0.25_{-0.08}^{+0.09}\times 10^{12}\,\mathrm{M}_{\odot }$, which is indicative of an extended dark matter halo and supports the scenario where this galaxy is just past its first pericentric approach. Consequently, these results suggest that the LMC may induce significant perturbations on the Galactic potential.
Increased avidity for Dpp/BMP2 maintains the proliferation of eye progenitors inDrosophila
Authors: Neto M. , Casares F. 
Published: November 2015

AbstractDuring normal organ development, the progenitor cell state is transient: it depends on specific combinations of transcription factors and extracellular signals, that cooperate to sustain the proliferative potential and undifferentiated status of organ progenitor cells. Not surprisingly, abnormal maintenance of progenitor transcription factors may lead to tissue overgrowth, and the concurrence of specific signals from the local environment is often critical to trigger this overgrowth. Therefore, the identification of the specific combinations of transcription factors and signals that promote or oppose proliferation in progenitor cells is essential to understand normal development and disease. We have investigated this issue by asking what signals may promote the proliferation of eye progenitors inDrosophila. Two transcription factors, the MEIS1 homologuehomothorax (hth)and the Zn-fingerteashirt (tsh)are transiently expressed in eye progenitors causing the expansion of the progenitor pool. However, if their co-expression is maintained experimentally, cell proliferation continues and differentiation is halted. Here we show that Hth+Tsh-induced tissue overgrowth requires the BMP2 ligand Dpp and the activation of its pathway. In Hth+Tsh cells, the Dpp pathway is abnormally hyperactivated. Rather than using autocrine Dpp expression, Hth+Tsh cells increase their avidity for Dpp, produced locally, by upregulating extracellular matrix components. During normal development, Dpp represses hth and tsh ensuring that the progenitor state is transient. However, cells in which Hth+Tsh expression is maintained use Dpp to enhance their proliferation.Summary StatementInDrosophila, homothorax, the Meis1 homologue, andteashirtjointly sustain the proliferation of eye progenitor cells by increasing their avidity for BMP produced by the local microenvironment.
A comprehensive analysis of 3’ end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogenous ribonucleoprotein C on cleavage and polyadenylation
Authors: Gruber Andreas J. , Schmidt Ralf , Gruber Andreas R. , Martin Georges , Ghosh Souvik , Belmadani Manuel , Keller Walter , Zavolan Mihaela 
Published: November 2015

AbstractAlternative polyadenylation (APA) is a general mechanism of transcript diversification in mammals, which has been recently linked to proliferative states and cancer. Different 3’ untranslated region (3’ UTR) isoforms interact with different RNA binding proteins (RBPs), which modify the stability, translation, and subcellular localization of the corresponding transcripts. Although the heterogeneity of pre-mRNA 3’ end processing has been established with high-throughput approaches, the mechanisms that underlie systematic changes in 3’ UTR lengths remain to be characterized. Through a uniform analysis of a large number of 3’ end sequencing data sets we have uncovered 18 signals, 6 of which novel, whose positioning with respect to pre-mRNA cleavage sites indicates a role in pre-mRNA 3’ end processing in both mouse and human. With 3’ end sequencing we have demonstrated that the heterogeneous ribonucleoprotein C (HNRNPC), which binds the poly(U) motif whose frequency also peaks in the vicinity of polyadenylation (poly(A)) sites, has a genome-wide effect on poly(A) site usage. HNRNPC-regulated 3’ UTRs are enriched in ELAV-like RNA binding protein 1 (ELAVL1) binding sites and include those of the CD47 molecule (CD47) gene, which participate in the recently discovered mechanism of 3’ UTR-dependent protein localization (UDPL). Our study thus establishes an up-to-date, high-confidence catalog of 3’ end processing sites and poly(A) signals and it uncovers an important role of HNRNPC in regulating 3’ end processing. It further suggests that U-rich elements mediate interactions with multiple RBPs that regulate different stages in a transcript’s life cycle.