bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial, host and xenobiotic diversity in the cystic fibrosis sputum metabolome
Authors: Quinn Robert A , Phelan Vanessa V , Whiteson Katrine L , Garg Neha , Bailey Barbara A , Lim Yan Wei , Conrad Douglas J , Dorrestein Pieter C , Rohwer Forest L 
Published: December 2015

Abstract
Cystic fibrosis (CF) lungs are filled with thick mucus that obstructs airways and facilitates chronic infections. Pseudomonas aeruginosa is a significant pathogen of this disease that produces a variety of toxic small molecules. We used molecular networking-based metabolomics to investigate the chemistry of CF sputa and assess how the microbial molecules detected reflect the microbiome and clinical culture history of the patients. Metabolites detected included xenobiotics, P. aeruginosa specialized metabolites and host sphingolipids. The clinical culture and microbiome profiles did not correspond to the detection of P. aeruginosa metabolites in the same samples. The P. aeruginosa molecules that were detected in sputum did not match those from laboratory cultures. The pseudomonas quinolone signal (PQS) was readily detectable from cultured strains, but absent from sputum, even when its precursor molecules were present. The lack of PQS production in vivo is potentially due to the chemical nature of the CF lung environment, indicating that culture-based studies of this pathogen may not explain its behavior in the lung. The most differentially abundant molecules between CF and non-CF sputum were sphingolipids, including sphingomyelins, ceramides and lactosylceramide. As these highly abundant molecules contain the inflammatory mediator ceramide, they may have a significant role in CF hyperinflammation. This study demonstrates that the chemical makeup of CF sputum is a complex milieu of microbial, host and xenobiotic molecules. Detection of a bacterium by clinical culturing and 16S rRNA gene profiling do not necessarily reflect the active production of metabolites from that bacterium in a sputum sample.
Transcriptome dynamics of a broad host-range cyanophage and its hosts
Authors: Doron Shany , Fedida Ayalla , Hernández-Prieto Miguel A , Sabehi Gazalah , Karunker Iris , Stazic Damir , Feingersch Roi , Steglich Claudia , Futschik Matthias , Lindell Debbie , Sorek Rotem 
Published: December 2015

Abstract
Cyanobacteria are highly abundant in the oceans and are constantly exposed to lytic viruses. The T4-like cyanomyoviruses are abundant in the marine environment and have broad host-ranges relative to other cyanophages. It is currently unknown whether broad host-range phages specifically tailor their infection program for each host, or employ the same program irrespective of the host infected. Also unknown is how different hosts respond to infection by the same phage. Here we used microarray and RNA-seq analyses to investigate the interaction between the Syn9 T4-like cyanophage and three phylogenetically, ecologically and genomically distinct marine Synechococcus strains: WH7803, WH8102 and WH8109. Strikingly, Syn9 led a nearly identical infection and transcriptional program in all three hosts. Different to previous assumptions for T4-like cyanophages, three temporally regulated gene expression classes were observed. Furthermore, a novel regulatory element controlled early-gene transcription, and host-like promoters drove middle gene transcription, different to the regulatory paradigm for T4. Similar results were found for the P-TIM40 phage during infection of Prochlorococcus NATL2A. Moreover, genomic and metagenomic analyses indicate that these regulatory elements are abundant and conserved among T4-like cyanophages. In contrast to the near-identical transcriptional program employed by Syn9, host responses to infection involved host-specific genes primarily located in hypervariable genomic islands, substantiating islands as a major axis of phage–cyanobacteria interactions. Our findings suggest that the ability of broad host-range phages to infect multiple hosts is more likely dependent on the effectiveness of host defense strategies than on differential tailoring of the infection process by the phage.
Selective consumption and metabolic allocation of terrestrial and algal carbon determine allochthony in lake bacteria
Authors: Guillemette François , Leigh McCallister S , del Giorgio Paul A 
Published: December 2015

Abstract
Here we explore strategies of resource utilization and allocation of algal versus terrestrially derived carbon (C) by lake bacterioplankton. We quantified the consumption of terrestrial and algal dissolved organic carbon, and the subsequent allocation of these pools to bacterial growth and respiration, based on the δ13C isotopic signatures of bacterial biomass and respiratory carbon dioxide (CO2). Our results confirm that bacterial communities preferentially remove algal C from the terrestrially dominated organic C pool of lakes, but contrary to current assumptions, selectively allocate this autochthonous substrate to respiration, whereas terrestrial C was preferentially allocated to biosynthesis. The results provide further evidence of a mechanism whereby inputs of labile, algal-derived organic C may stimulate the incorporation of a more recalcitrant, terrestrial C pool. This mechanism resulted in a counterintuitive pattern of high and relatively constant levels of allochthony (~76%) in bacterial biomass across lakes that otherwise differ greatly in productivity and external inputs.
A molecular ruler regulates cytoskeletal remodelling by the Rho kinases
Authors: Truebestein Linda , Elsner Daniel J. , Fuchs Elisabeth , Leonard Thomas A. 
Published: December 2015

AbstractThe Rho-associated coiled-coil kinases (ROCK) are essential regulators of the actin cytoskeleton; however, the structure of a full-length ROCK is unknown and the mechanisms by which its kinase activity is controlled are not well understood. Here we determine the low-resolution structure of human ROCK2 using electron microscopy, revealing it to be a constitutive dimer, 120 nm in length, with a long coiled-coil tether linking the kinase and membrane-binding domains. We find, in contrast to previous reports, that ROCK2 activity does not appear to be directly regulated by binding to membranes, RhoA, or by phosphorylation. Instead, we show that changing the length of the tether modulates ROCK2 function in cells, suggesting that it acts as a molecular ruler. We present a model in which ROCK activity is restricted to a discrete region of the actin cytoskeleton, governed by the length of its coiled-coil. This represents a new type of spatial control, and hence a new paradigm for kinase regulation.
Branched-chain amino acid catabolism is a conserved regulator of physiological ageing
Authors: Mansfeld Johannes , Urban Nadine , Priebe Steffen , Groth Marco , Frahm Christiane , Hartmann Nils , Gebauer Juliane , Ravichandran Meenakshi , Dommaschk Anne , Schmeisser Sebastian , Kuhlow Doreen , Monajembashi Shamci , Bremer-Streck Sibylle , Hemmerich Peter , Kiehntopf Michael , Zamboni Nicola , Englert Christoph , Guthke Reinhard , Kaleta Christoph , Platzer Matthias , Sühnel Jürgen , Witte Otto W. , Zarse Kim , Ristow Michael 
Published: December 2015

AbstractAgeing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ageing in nematodes, zebrafish and mice. We observe the strongest extension of lifespan when impairing expression of the branched-chain amino acid transferase-1 (bcat-1) gene in C. elegans, which leads to excessive levels of branched-chain amino acids (BCAAs). We further show that BCAAs reduce a LET-363/mTOR-dependent neuro-endocrine signal, which we identify as DAF-7/TGFβ, and that impacts lifespan depending on its related receptors, DAF-1 and DAF-4, as well as ultimately on DAF-16/FoxO and HSF-1 in a cell-non-autonomous manner. The transcription factor HLH-15 controls and epistatically synergizes with BCAT-1 to modulate physiological ageing. Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.
MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity
Authors: Hou Qingming , Ruan Hongyu , Gilbert James , Wang Guan , Ma Qi , Yao Wei-Dong , Man Heng-Ye 
Published: December 2015

AbstractHomeostatic synaptic plasticity is a compensatory response to alterations in neuronal activity. Chronic deprivation of neuronal activity results in an increase in synaptic AMPA receptors (AMPARs) and postsynaptic currents. The biogenesis of GluA2-lacking, calcium-permeable AMPARs (CP-AMPARs) plays a crucial role in the homeostatic response; however, the mechanisms leading to CP-AMPAR formation remain unclear. Here we show that the microRNA, miR124, is required for the generation of CP-AMPARs and homeostatic plasticity. miR124 suppresses GluA2 expression via targeting its 3′-UTR, leading to the formation of CP-AMPARs. Blockade of miR124 function abolishes the homeostatic response, whereas miR124 overexpression leads to earlier induction of homeostatic plasticity. miR124 transcription is controlled by an inhibitory transcription factor EVI1, acting by association with the deacetylase HDAC1. Our data support a cellular cascade in which inactivity relieves EVI1/HDAC-mediated inhibition of miR124 gene transcription, resulting in enhanced miR124 expression, formation of CP-AMPARs and subsequent induction of homeostatic synaptic plasticity.
Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects
Authors: Zhang Hongkai , Sturchler Emmanuel , Zhu Jiang , Nieto Ainhoa , Cistrone Philip A. , Xie Jia , He LinLing , Yea Kyungmoo , Jones Teresa , Turn Rachel , Di Stefano Peter S. , Griffin Patrick R. , Dawson Philip E. , McDonald Patricia H. , Lerner Richard A. 
Published: December 2015

AbstractGlucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists have emerged as treatment options for type 2 diabetes mellitus (T2DM). GLP-1R signals through G-protein-dependent, and G-protein-independent pathways by engaging the scaffold protein β-arrestin; preferential signalling of ligands through one or the other of these branches is known as ‘ligand bias’. Here we report the discovery of the potent and selective GLP-1R G-protein-biased agonist, P5. We identified P5 in a high-throughput autocrine-based screening of large combinatorial peptide libraries, and show that P5 promotes G-protein signalling comparable to GLP-1 and Exendin-4, but exhibited a significantly reduced β-arrestin response. Preclinical studies using different mouse models of T2DM demonstrate that P5 is a weak insulin secretagogue. Nevertheless, chronic treatment of diabetic mice with P5 increased adipogenesis, reduced adipose tissue inflammation as well as hepatic steatosis and was more effective at correcting hyperglycaemia and lowering haemoglobin A1c levels than Exendin-4, suggesting that GLP-1R G-protein-biased agonists may provide a novel therapeutic approach to T2DM.
System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia
Authors: Zhu Yan , Guo Zhili , Zhang Liangxiao , Zhang Yingying , Chen Yinying , Nan Jingyi , Zhao Buchang , Xiao Hongbin , Wang Zhong , Wang Yongyan 
Published: December 2015

AbstractThe relationship between cerebral ischemia and metabolic disorders is poorly understood, which is partly due to the lack of comparative fusing data for larger complete systems and to the complexity of metabolic cascade reactions. Based on the fusing maps of comprehensive serum metabolome, fatty acid and amino acid profiling, we identified 35 potential metabolic biomarkers for ischemic stroke. Our analyses revealed 8 significantly altered pathways by MetPA (Metabolomics Pathway Analysis, impact score >0.10) and 15 significantly rewired modules in a complex ischemic network using the Markov clustering (MCL) method; all of these pathways became more homologous as the number of overlapping nodes was increased. We then detected 24 extensive pathways based on the total modular nodes from the network analysis, 12 of which were new discovery pathways. We provided a new perspective from the viewpoint of abnormal metabolites for the overall study of ischemic stroke as well as a new method to simplify the network analysis by selecting the more closely connected edges and nodes to build a module map of stroke.
Elasticity of Ferropericlase across the Spin Crossover in the Earth’s Lower Mantle
Authors: Yang Jing , Tong Xinyue , Lin Jung-Fu , Okuchi Takuo , Tomioka Naotaka 
Published: December 2015

AbstractKnowing the elasticity of ferropericlase across the spin transition can help explain seismic and mineralogical models of the lower-mantle including the origin of seismic heterogeneities in the middle to lowermost parts of the lower mantle1,2,3,4. However, the effects of spin transition on full elastic constants of ferropericlase remain experimentally controversial due to technical challenges in directly measuring sound velocities under lower-mantle conditions1,2,3,4,5. Here we have reliably measured both VP and VS of a single-crystal ferropericlase ((Mg0.92,Fe0.08)O) using complementary Brillouin Light Scattering and Impulsive Stimulated Light Scattering coupled with a diamond anvil cell up to 96 GPa. The derived elastic constants show drastically softened C11 and C12 within the spin transition at 40–60 GPa while C44 is not affected. The spin transition is associated with a significant reduction of the aggregate VP/VS via the aggregate VP softening because VS softening does not visibly occur within the transition. Based on thermoelastic modelling along an expected geotherm, the spin crossover in ferropericlase can contribute to 2% reduction in VP/VS in a pyrolite mineralogical model in mid lower-mantle. Our results imply that the middle to lowermost parts of the lower-mantle would exhibit enhanced seismic heterogeneities due to the occurrence of the mixed-spin and low-spin ferropericlase.
iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease
Authors: Martin-Rojas Tatiana , Mourino-Alvarez Laura , Alonso-Orgaz Sergio , Rosello-Lleti Esther , Calvo Enrique , Lopez-Almodovar Luis Fernando , Rivera Miguel , Padial Luis R. , Lopez Juan Antonio , Cuesta Fernando de la , Barderas Maria G. 
Published: December 2015

AbstractDegenerative aortic stenosis (AS) is the most common worldwide cause of valve replacement. The aortic valve is a thin, complex, layered connective tissue with compartmentalized extracellular matrix (ECM) produced by specialized cell types, which directs blood flow in one direction through the heart. There is evidence suggesting remodeling of such ECM during aortic stenosis development. Thus, a better characterization of the role of ECM proteins in this disease would increase our understanding of the underlying molecular mechanisms. Aortic valve samples were collected from 18 patients which underwent aortic valve replacement (50% males, mean age of 74 years) and 18 normal control valves were obtained from necropsies (40% males, mean age of 69 years). The proteome of the samples was analyzed by 2D-LC MS/MS iTRAQ methodology. The results showed an altered expression of 13 ECM proteins of which 3 (biglycan, periostin, prolargin) were validated by Western blotting and/or SRM analyses. These findings are substantiated by our previous results demonstrating differential ECM protein expression. The present study has demonstrated a differential ECM protein pattern in individuals with AS, therefore supporting previous evidence of a dynamic ECM remodeling in human aortic valves during AS development.
Exploring molecular variation in Schistosoma japonicum in China
Authors: Young Neil D. , Chan Kok-Gan , Korhonen Pasi K. , Min Chong Teik , Ee Robson , Mohandas Namitha , Koehler Anson V. , Lim Yan-Lue , Hofmann Andreas , Jex Aaron R. , Qian Baozhen , Chilton Neil B. , Gobert Geoffrey N. , McManus Donald P. , Tan Patrick , Webster Bonnie L. , Rollinson David , Gasser Robin B. 
Published: December 2015

AbstractSchistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.
Optogenetics-enabled assessment of viral gene and cell therapy for restoration of cardiac excitability
Authors: Ambrosi Christina M. , Boyle Patrick M. , Chen Kay , Trayanova Natalia A. , Entcheva Emilia 
Published: December 2015

AbstractMultiple cardiac pathologies are accompanied by loss of tissue excitability, which leads to a range of heart rhythm disorders (arrhythmias). In addition to electronic device therapy (i.e. implantable pacemakers and cardioverter/defibrillators), biological approaches have recently been explored to restore pacemaking ability and to correct conduction slowing in the heart by delivering excitatory ion channels or ion channel agonists. Using optogenetics as a tool to selectively interrogate only cells transduced to produce an exogenous excitatory ion current, we experimentally and computationally quantify the efficiency of such biological approaches in rescuing cardiac excitability as a function of the mode of application (viral gene delivery or cell delivery) and the geometry of the transduced region (focal or spatially-distributed). We demonstrate that for each configuration (delivery mode and spatial pattern), the optical energy needed to excite can be used to predict therapeutic efficiency of excitability restoration. Taken directly, these results can help guide optogenetic interventions for light-based control of cardiac excitation. More generally, our findings can help optimize gene therapy for restoration of cardiac excitability.
Origin of marine planktonic cyanobacteria
Authors: Sánchez-Baracaldo Patricia 
Published: December 2015

AbstractMarine planktonic cyanobacteria contributed to the widespread oxygenation of the oceans towards the end of the Pre-Cambrian and their evolutionary origin represents a key transition in the geochemical evolution of the Earth surface. Little is known, however, about the evolutionary events that led to the appearance of marine planktonic cyanobacteria. I present here phylogenomic (135 proteins and two ribosomal RNAs), Bayesian relaxed molecular clock (18 proteins, SSU and LSU) and Bayesian stochastic character mapping analyses from 131 cyanobacteria genomes with the aim to unravel key evolutionary steps involved in the origin of marine planktonic cyanobacteria. While filamentous cell types evolved early on at around 2,600–2,300 Mya and likely dominated microbial mats in benthic environments for most of the Proterozoic (2,500–542 Mya), marine planktonic cyanobacteria evolved towards the end of the Proterozoic and early Phanerozoic. Crown groups of modern terrestrial and/or benthic coastal cyanobacteria appeared during the late Paleoproterozoic to early Mesoproterozoic. Decrease in cell diameter and loss of filamentous forms contributed to the evolution of unicellular planktonic lineages during the middle of the Mesoproterozoic (1,600–1,000 Mya) in freshwater environments. This study shows that marine planktonic cyanobacteria evolved from benthic marine and some diverged from freshwater ancestors during the Neoproterozoic (1,000–542 Mya).
True and Perceived Synchrony are Preferentially Associated With Particular Sensory Pairings
Authors: Noel Jean-Paul , Wallace Mark T. , Orchard-Mills Emily , Alais David , Van der Burg Erik 
Published: December 2015

AbstractPerception and behavior are fundamentally shaped by the integration of different sensory modalities into unique multisensory representations, a process governed by spatio-temporal correspondence. Prior work has characterized temporal perception using the point in time at which subjects are most likely to judge multisensory stimuli to be simultaneous (PSS) and the temporal binding window (TBW) over which participants are likely to do so. Here we examine the relationship between the PSS and the TBW within and between individuals and within and between three sensory combinations: audiovisual, audiotactile and visuotactile. We demonstrate that TBWs correlate within individuals and across multisensory pairings, but PSSs do not. Further, we reveal that while the audiotactile and audiovisual pairings show tightly related TBWs, they also exhibit a differential relationship with respect to true and perceived multisensory synchrony. Thus, audiotactile and audiovisual temporal processing share mechanistic features yet are respectively functionally linked to objective and subjective synchrony.
Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin
Authors: Newland Ben , Leupelt Daniel , Zheng Yu , Thomas Laurent S. V. , Werner Carsten , Steinhart Martin , Wang Wenxin 
Published: December 2015

AbstractExternally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers and various therapeutics.