bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laminin regulates PDGFRβ+ cell stemness and muscle development
Authors: Yao Yao , Norris Erin H. , E. Mason Christopher , Strickland Sidney 
Published: May 2016

AbstractMuscle-resident PDGFRβ+ cells, which include pericytes and PW1+ interstitial cells (PICs), play a dual role in muscular dystrophy. They can either undergo myogenesis to promote muscle regeneration or differentiate into adipocytes and other cells to compromise regeneration. How the differentiation and fate determination of PDGFRβ+ cells are regulated, however, remains unclear. Here, by utilizing a conditional knockout mouse line, we report that PDGFRβ+ cell-derived laminin inhibits their proliferation and adipogenesis, but is indispensable for their myogenesis. In addition, we show that laminin alone is able to partially reverse the muscle dystrophic phenotype in these mice at the molecular, structural and functional levels. Further RNAseq analysis reveals that laminin regulates PDGFRβ+ cell differentiation/fate determination via gpihbp1. These data support a critical role of laminin in the regulation of PDGFRβ+ cell stemness, identify an innovative target for future drug development and may provide an effective treatment for muscular dystrophy.
Wnt pathway activation by ADP-ribosylation
Authors: Yang Eungi , Tacchelly-Benites Ofelia , Wang Zhenghan , Randall Michael P. , Tian Ai , Benchabane Hassina , Freemantle Sarah , Pikielny Claudio , Tolwinski Nicholas S. , Lee Ethan , Ahmed Yashi 
Published: May 2016

AbstractWnt/β-catenin signalling directs fundamental processes during metazoan development and can be aberrantly activated in cancer. Wnt stimulation induces the recruitment of the scaffold protein Axin from an inhibitory destruction complex to a stimulatory signalosome. Here we analyse the early effects of Wnt on Axin and find that the ADP-ribose polymerase Tankyrase (Tnks)—known to target Axin for proteolysis—regulates Axin’s rapid transition following Wnt stimulation. We demonstrate that the pool of ADP-ribosylated Axin, which is degraded under basal conditions, increases immediately following Wnt stimulation in both Drosophila and human cells. ADP-ribosylation of Axin enhances its interaction with the Wnt co-receptor LRP6, an essential step in signalosome assembly. We suggest that in addition to controlling Axin levels, Tnks-dependent ADP-ribosylation promotes the reprogramming of Axin following Wnt stimulation; and propose that Tnks inhibition blocks Wnt signalling not only by increasing destruction complex activity, but also by impeding signalosome assembly.
Contributions of historical and contemporary geographic and environmental factors to phylogeographic structure in a Tertiary relict species, Emmenopterys henryi (Rubiaceae)
Authors: Zhang Yong-Hua , Wang Ian J. , Comes Hans Peter , Peng Hua , Qiu Ying-Xiong 
Published: May 2016

AbstractExamining how historical and contemporary geographic and environmental factors contribute to genetic divergence at different evolutionary scales is a central yet largely unexplored question in ecology and evolution. Here, we examine this key question by investigating how environmental and geographic factors across different epochs have driven genetic divergence at deeper (phylogeographic) and shallower (landscape genetic) evolutionary scales in the Chinese Tertiary relict treeEmmenopterys henryi. We found that geography played a predominant role at all levels – phylogeographic clades are broadly geographically structured, the deepest levels of divergence are associated with major geological or pre-Quaternary climatic events and isolation by distance (IBD) primarily explained population genetic structure. However, environmental factors are clearly also important – climatic fluctuations since the Last Interglacial (LIG) have likely contributed to phylogeographic structure and the population genetic structure (in our AFLP dataset) was partly explained by isolation by environment (IBE), which may have resulted from natural selection in environments with divergent climates. Thus, historical and contemporary geography and historical and contemporary environments have all shaped patterns of genetic structure inE. henryi, and, in fact, changes in the landscape through time have also been critical factors.
Children’s altruistic behavior in context: The role of emotional responsiveness and culture
Authors: Rajhans Purva , Altvater-Mackensen Nicole , Vaish Amrisha , Grossmann Tobias 
Published: May 2016

AbstractAltruistic behavior in humans is thought to have deep biological roots. Nonetheless, there is also evidence for considerable variation in altruistic behaviors among individuals and across cultures. Variability in altruistic behavior in adults has recently been related to individual differences in emotional responsiveness to fear in others. The current study examined the relation between emotional responsiveness (using eye-tracking) and altruistic behavior (using the Dictator Game) in 4 to 5-year-old children (N = 96) across cultures (India and Germany). The results revealed that increased altruistic behavior was associated with a greater responsiveness to fear faces (faster fixation), but not happy faces, in both cultures. This suggests that altruistic behavior is linked to our responsiveness to others in distress across cultures. Additionally, only among Indian children greater altruistic behavior was associated with greater sensitivity to context when responding to fearful faces. These findings further our understanding of the origins of altruism in humans by highlighting the importance of emotional processes and cultural context in the development of altruism.
Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues
Authors: Kosti Idit , Jain Nishant , Aran Dvir , Butte Atul J. , Sirota Marina 
Published: May 2016

AbstractThe central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.
Diffraction-limited ultrabroadband terahertz spectroscopy
Authors: Baillergeau M. , Maussang K. , Nirrengarten T. , Palomo J. , Li L. H. , Linfield E. H. , Davies A. G. , Dhillon S. , Tignon J. , Mangeney J. 
Published: May 2016

AbstractDiffraction is the ultimate limit at which details of objects can be resolved in conventional optical spectroscopy and imaging systems. In the THz spectral range, spectroscopy systems increasingly rely on ultra-broadband radiation (extending over more 5 octaves) making a great challenge to reach resolution limited by diffraction. Here, we propose an original easy-to-implement wavefront manipulation concept to achieve ultrabroadband THz spectroscopy system with diffraction-limited resolution. Applying this concept to a large-area photoconductive emitter, we demonstrate diffraction-limited ultra-broadband spectroscopy system up to 14.5 THz with a dynamic range of 103. The strong focusing of ultrabroadband THz radiation provided by our approach is essential for investigating single micrometer-scale objects such as graphene flakes or living cells and besides for achieving intense ultra-broadband THz electric fields.
Contrasting global genetic patterns in two biologically similar, widespread and invasive Ciona species (Tunicata, Ascidiacea)
Authors: Bouchemousse Sarah , Bishop John D. D. , Viard Frédérique 
Published: May 2016

AbstractHuman-mediated dispersal interplays with natural processes and complicates understanding of the biogeographical history of species. This is exemplified by two invasive tunicates, Ciona robusta (formerly Ciona intestinalis type A) and C. intestinalis (formerly Ciona intestinalis type B), globally distributed and sympatric in Europe. By gathering new mitochondrial sequences that were merged with published datasets, we analysed genetic patterns in different regions, with a focus on 1) their sympatric range and 2) allopatric populations in N and S America and southern Europe. In the sympatric range, the two species display contrasting genetic diversity patterns, with low polymorphism in C. robusta supporting the prevalent view of its recent introduction. In the E Pacific, several genetic traits support the non-native status of C. robusta. However, in the NE Pacific, this appraisal requires a complex scenario of introduction and should be further examined supported by extensive sampling efforts in the NW Pacific (putative native range). For C. intestinalis, Bayesian analysis suggested a natural amphi-North Atlantic distribution, casting doubt on its non-native status in the NW Atlantic. This study shows that both natural and human-mediated dispersal have influenced genetic patterns at broad scales; this interaction lessens our ability to confidently ascertain native vs. non-native status of populations, particularly of those species that are globally distributed.
New recombinant cyclohexylamine oxidase variants for deracemization of secondary amines by orthogonally assaying designed mutants with structurally diverse substrates
Authors: Li Guangyue , Yao Peiyuan , Cong Peiqian , Ren Jie , Wang Lei , Feng Jinhui , Lau Peter C.K. , Wu Qiaqing , Zhu Dunming 
Published: May 2016

AbstractTo further expand the substrate range of the cyclohexylamine oxidase (CHAO) fromBrevibacterium oxydans, a library of diverse mutants was created and assayed toward a group of structurally diverse substrates. Among them, mutants T198A and M226A exhibited enhanced activity relative to wt CHAO for most (S)-enantiomers of primary amines and some secondary amines. While mutants T198I, L199I, L199F, M226I and M226T were more active than wt CHAO toward the primary amines, mutants T198F, L199T, Y321A, Y321T, Y321I and Y321F enhanced the enzyme activity toward the secondary amines. In particular, mutant Y321I displayed an enhanced catalytic efficiency toward 1-(4-methoxybenzyl)-1, 2, 3, 4, 5, 6, 7, 8-octahydroisoquinoline (13). Whereas a double mutant, Y321I/M226T, acted on (S)-N-(prop-2-yn-1-yl)-2, 3-dihydro-1H-inden-1-amine [(S)-8]. Since (R)-8is an irreversible inhibitor of monoamine oxidase and (S)-13is an intermediate of dextromethorphan, a cough suppressant drug, deracemizations of8and13were carried out with crude enzyme extracts of the respective mutants. This resulted in 51% and 78% isolated yields of (R)-8and (S)-13, respectively, each with high enantiomeric excess (93% and 99% ee). The results demonstrated the application potential of the evolved CHAO mutants in drug synthesis requiring chiral secondary amines.
Stationary bubble formation and cavity collapse in wedge-shaped hoppers
Authors: Yagisawa Yui , Then Hui Zee , Okumura Ko 
Published: May 2016

AbstractThe hourglass is one of the apparatuses familiar to everyone, but reveals intriguing behaviors peculiar to granular materials, and many issues are remained to be explored. In this study, we examined the dynamics of falling sand in a special form of hourglass, i.e., a wedge-shaped hopper, when a suspended granular layer is stabilized to a certain degree. As a result, we found remarkably different dynamic regimes of bubbling and cavity. In the bubbling regime, bubbles of nearly equal size are created in the sand at a regular time interval. In the cavity regime, a cavity grows as sand beads fall before a sudden collapse of the cavity. Bubbling found here is quite visible to a level never discussed in the physics literature and the cavity regime is a novel phase, which is neither continuous, intermittent nor completely blocked phase. We elucidate the physical conditions necessary for the bubbling and cavity regimes and develop simple theories for the regimes to successfully explain the observed phenomena by considering the stability of a suspended granular layer and clogging of granular flow at the outlet of the hopper. The bubbling and cavity regimes could be useful for mixing a fluid with granular materials.
Charge collection kinetics on ferroelectric polymer surface using charge gradient microscopy
Authors: Choi Yoon-Young , Tong Sheng , Ducharme Stephen , Roelofs Andreas , Hong Seungbum 
Published: May 2016

AbstractA charge gradient microscopy (CGM) probe was used to collect surface screening charges on poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] thin films. These charges are naturally formed on unscreened ferroelectric domains in ambient condition. The CGM data were used to map the local electric current originating from the collected surface charges on the poled ferroelectric domains in the P(VDF-TrFE) thin films. Both the direction and amount of the collected current were controlled by changing the polarity and area of the poled domains. The endurance of charge collection by rubbing the CGM tip on the polymer film was limited to 20 scan cycles, after which the current reduced to almost zero. This degradation was attributed to the increase of the chemical bonding strength between the external screening charges and the polarization charges. Once this degradation mechanism is mitigated, the CGM technique can be applied to efficient energy harvesting devices using polymer ferroelectrics.
pGlyco: a pipeline for the identification of intact N-glycopeptides by using HCD- and CID-MS/MS and MS3
Authors: Zeng Wen-Feng , Liu Ming-Qi , Zhang Yang , Wu Jian-Qiang , Fang Pan , Peng Chao , Nie Aiying , Yan Guoquan , Cao Weiqian , Liu Chao , Chi Hao , Sun Rui-Xiang , Wong Catherine C. L. , He Si-Min , Yang Pengyuan 
Published: May 2016

AbstractConfident characterization of the microheterogeneity of protein glycosylation through identification of intact glycopeptides remains one of the toughest analytical challenges for glycoproteomics. Recently proposed mass spectrometry (MS)-based methods still have some defects such as lack of the false discovery rate (FDR) analysis for the glycan identification and lack of sufficient fragmentation information for the peptide identification. Here we proposed pGlyco, a novel pipeline for the identification of intact glycopeptides by using complementary MS techniques: 1) HCD-MS/MS followed by product-dependent CID-MS/MS was used to provide complementary fragments to identify the glycans and a novel target-decoy method was developed to estimate the false discovery rate of the glycan identification; 2) data-dependent acquisition of MS3 for some most intense peaks of HCD-MS/MS was used to provide fragments to identify the peptide backbones. By integrating HCD-MS/MS, CID-MS/MS and MS3, intact glycopeptides could be confidently identified. With pGlyco, a standard glycoprotein mixture was analyzed in the Orbitrap Fusion and 309 non-redundant intact glycopeptides were identified with detailed spectral information of both glycans and peptides.
Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production
Authors: Bailey Andy M. , Alberti Fabrizio , Kilaru Sreedhar , Collins Catherine M. , de Mattos-Shipley Kate , Hartley Amanda J. , Hayes Patrick , Griffin Alison , Lazarus Colin M. , Cox Russell J. , Willis Christine L. , O’Dwyer Karen , Spence David W. , Foster Gary D. 
Published: May 2016

AbstractSemi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi.
The arachidonic acid metabolite 11β-ProstaglandinF2α controls intestinal epithelial healing: deficiency in patients with Crohn’s disease
Authors: Coquenlorge Sabrina , Van Landeghem Laurianne , Jaulin Julie , Cenac Nicolas , Vergnolle Nathalie , Duchalais Emilie , Neunlist Michel , Rolli-Derkinderen Malvyne 
Published: May 2016

AbstractIn healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn’s Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression of glial markers and EGC-derived soluble factors (IL6, TGF-β, proEGF, GSH) but CD EGC failed to increase IEB resistance and healing. Lipid profiling showed that CD EGC produced decreased amounts of 15-HETE, 18-HEPE, 15dPGJ2 and 11βPGF2α as compared to healthy EGC. They also had reduced expression of the L-PGDS and AKR1C3 enzymes. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway.
Unimodal and cross-modal prediction is enhanced in musicians
Authors: Vassena Eliana , Kochman Katty , Latomme Julie , Verguts Tom 
Published: May 2016

AbstractMusical training involves exposure to complex auditory and visual stimuli, memorization of elaborate sequences and extensive motor rehearsal. It has been hypothesized that such multifaceted training may be associated with differences in basic cognitive functions, such as prediction, potentially translating to a facilitation in expert musicians. Moreover, such differences might generalize to non-auditory stimuli. This study was designed to test both hypotheses. We implemented a cross-modal attentional cueing task with auditory and visual stimuli, where a target was preceded by compatible or incompatible cues in mainly compatible (80% compatible, predictable) or random blocks (50% compatible, unpredictable). This allowed for the testing of prediction skills in musicians and controls. Musicians showed increased sensitivity to the statistical structure of the block, expressed as advantage for compatible trials (disadvantage for incompatible trials), but only in the mainly compatible (predictable) blocks. Controls did not show this pattern. The effect held within modalities (auditory, visual), across modalities and when controlling for short-term memory capacity. These results reveal a striking enhancement in cross-modal prediction in musicians in a very basic cognitive task.
Sequencing proteins with transverse ionic transport in nanochannels
Authors: Boynton Paul , Di Ventra Massimiliano 
Published: May 2016

AbstractDe novo protein sequencing is essential for understanding cellular processes that govern the function of living organisms and all sequence modifications that occur after a protein has been constructed from its corresponding DNA code. By obtaining the order of the amino acids that compose a given protein one can then determine both its secondary and tertiary structures through structure prediction, which is used to create models for protein aggregation diseases such as Alzheimer’s Disease. Here, we propose a new technique for de novo protein sequencing that involves translocating a polypeptide through a synthetic nanochannel and measuring the ionic current of each amino acid through an intersecting perpendicular nanochannel. We find that the distribution of ionic currents for each of the 20 proteinogenic amino acids encoded by eukaryotic genes is statistically distinct, showing this technique’s potential for de novo protein sequencing.
Elucidation of molecular and functional heterogeneity through differential expression network analyses of discrete tumor subsets
Authors: Naik Rutika R. , Gardi Nilesh L. , Bapat Sharmila A. 
Published: May 2016

AbstractIntratumor heterogeneity presents a major hurdle in cancer therapy. Most current research studies consider tumors as single entities and overlook molecular diversity between heterogeneous state(s) of different cells assumed to be homogenous. The present approach was designed for fluorescence-activated cell sorting-based resolution of heterogeneity arising from cancer stem cell (CSC) hierarchies and genetic instability in ovarian tumors, followed by microarray-based expression profiling of sorted fractions. Through weighted gene correlation network analyses, we could assign enriched modules of co-regulated genes to each fraction. Such gene modules often correlate with biological functions; one such specific association was the enrichment of CD53 expression in CSCs, functional validation indicated CD53 to be a tumor-initiating cell- rather than quiescent CSC-marker. Another association defined a state of poise for stress-induced metastases in aneuploid cells. Our results thus emphasize the need for studying cell-specific functionalities relevant to regeneration, drug resistance and disease progression in discrete tumor cell fractions.
Changes in variation at the MHC class II DQA locus during the final demise of the woolly mammoth
Authors: Pečnerová Patrícia , Díez-del-Molino David , Vartanyan Sergey , Dalén Love 
Published: May 2016

AbstractAccording to the nearly-neutral theory of evolution, the relative strengths of selection and drift shift in favour of drift at small population sizes. Numerous studies have analysed the effect of bottlenecks and small population sizes on genetic diversity in the MHC, which plays a central role in pathogen recognition and immune defense and is thus considered a model example for the study of adaptive evolution. However, to understand changes in genetic diversity at loci under selection, it is necessary to compare the genetic diversity of a population before and after the bottleneck. In this study, we analyse three fragments of the MHC DQA gene in woolly mammoth samples radiocarbon dated to before and after a well-documented bottleneck that took place about ten thousand years ago. Our results indicate a decrease in observed heterozygosity and number of alleles, suggesting that genetic drift had an impact on the variation on MHC. Based on coalescent simulations, we found no evidence of balancing selection maintaining MHC diversity during the Holocene. However, strong trans-species polymorphism among mammoths and elephants points to historical effects of balancing selection on the woolly mammoth lineage.