bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway
Authors: Morizawa Yosuke M. , Hirayama Yuri , Ohno Nobuhiko , Shibata Shinsuke , Shigetomi Eiji , Sui Yang , Nabekura Junichi , Sato Koichi , Okajima Fumikazu , Takebayashi Hirohide , Okano Hideyuki , Koizumi Schuichi 
Published: June 2017

AbstractAstrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia. Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis in vitro. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to remodeling of damaged tissues and penumbra networks.
MRI-derived diffusion parameters in the human optic nerve and its surrounding sheath during head-down tilt
Authors: Gerlach Darius A. , Marshall-Goebel Karina , Hasan Khader M. , Kramer Larry A. , Alperin Noam , Rittweger Joern 
Published: June 2017

AbstractMore than half of astronauts present with significant neuro-ophthalmic findings during 6-month missions onboard the International Space Station. Although the underlying cause of this Microgravity Ocular Syndrome is currently unknown, alterations in cerebrospinal fluid dynamics within the optic nerve sheath may play a role. In the presented study, diffusion tensor imaging was used to assess changes in diffusivity of the optic nerve and its surrounding sheath during head-down tilt, a ground-based model of microgravity. Nine healthy male subjects (mean age ± SD: 25 ± 2.4 years; mean body mass index ± SD: 24.1 ± 2.4 kg/m2) underwent 5 head-down tilt conditions: −6°,−12°, −18°,−12° and 1% CO2, and −12° and lower body negative pressure. Mean diffusivity, fractional anisotropy, axial diffusivity, radial diffusivity were quantified in the left and right optic nerves and surrounding sheaths at supine baseline and after 4.5 h head-down tilt for each condition. In the optic nerve sheath, mean diffusivity was increased with all head-down tilt conditions by (Best Linear Unbiased Predictors) 0.147 (SE: 0.04) × 10−3 mm2/s (P < 0.001), axial diffusivity by 0.188 (SE: 0.064) × 10−3 mm2/s (P < 0.001), and radial diffusivity by 0.126 (SE: 0.04) × 10−3 mm2/s (P = 0.0019). Within the optic nerve itself, fractional anisotropy was increased by 0.133 (SE: 0.047) (P = 0.0051) and axial diffusivity increased by 0.135 (SE: 0.08) × 10−3 mm2/s (P = 0.014) during head-down tilt, whilst mean diffusivity and radial diffusivity were unaffected (P > 0.3). These findings could be due to increased perioptic cerebral spinal fluid hydrodynamics during head-down tilt, as well as increased cerebral spinal fluid volume and movement within the optic nerve sheath.
Acute loss of the hepatic endo-lysosomal system in vivo causes compensatory changes in iron homeostasis
Authors: Metzendorf Christoph , Zeigerer Anja , Seifert Sarah , Sparla Richard , Najafi Bahar , Canonne-Hergaux François , Zerial Marino , Muckenthaler Martina U. 
Published: June 2017

AbstractLiver cells communicate with the extracellular environment to take up nutrients via endocytosis. Iron uptake is essential for metabolic activities and cell homeostasis. Here, we investigated the role of the endocytic system for maintaining iron homeostasis. We specifically depleted the small GTPase Rab5 in the mouse liver, causing a transient loss of the entire endo-lysosomal system. Strikingly, endosome depletion led to a fast reduction of hepatic iron levels, which was preceded by an increased abundance of the iron exporter ferroportin. Compensatory changes in livers of Rab5-depleted mice include increased expression of transferrin receptor 1 as well as reduced expression of the iron-regulatory hormone hepcidin. Serum iron indices (serum iron, free iron binding capacity and total iron binding capacity) in Rab5-KD mice were increased, consistent with an elevated splenic and hepatic iron export. Our data emphasize the critical importance of the endosomal compartments in hepatocytes to maintain hepatic and systemic iron homeostasis in vivo. The short time period (between day four and five) upon which these changes occur underscore the fast dynamics of the liver iron pool.
Conformational plasticity and evolutionary analysis of the myotilin tandem Ig domains
Authors: Puž Vid , Pavšič Miha , Lenarčič Brigita , Djinović-Carugo Kristina 
Published: June 2017

AbstractMyotilin is a component of the sarcomere where it plays an important role in organisation and maintenance of Z-disk integrity. This involves direct binding to F-actin and filamin C, a function mediated by its Ig domain pair. While the structures of these two individual domains are known, information about their relative orientation and flexibility remains limited. We set on to characterise the Ig domain pair of myotilin with emphasis on its molecular structure, dynamics and phylogeny. First, sequence conservation analysis of myotilin shed light on the molecular basis of myotilinopathies and revealed several motifs in Ig domains found also in I-band proteins. In particular, a highly conserved Glu344 mapping to Ig domain linker, was identified as a critical component of the inter-domain hinge mechanism. Next, SAXS and molecular dynamics revealed that Ig domain pair exists as a multi-conformation species with dynamic exchange between extended and compact orientations. Mutation of AKE motif to AAA further confirmed its impact on inter-domain flexibility. We hypothesise that the conformational plasticity of the Ig domain pair in its unbound form is part of the binding partner recognition mechanism.
Ocean acidification as a driver of community simplification via the collapse of higher-order and rise of lower-order consumers
Authors: Vizzini S. , Martínez-Crego B. , Andolina C. , Massa-Gallucci A. , Connell S. D. , Gambi M. C. 
Published: June 2017

AbstractIncreasing oceanic uptake of CO2 is predicted to drive ecological change as both a resource (i.e. CO2 enrichment on primary producers) and stressor (i.e. lower pH on consumers). We use the natural ecological complexity of a CO2 vent (i.e. a seagrass system) to assess the potential validity of conceptual models developed from laboratory and mesocosm research. Our observations suggest that the stressor-effect of CO2 enrichment combined with its resource-effect drives simplified food web structure of lower trophic diversity and shorter length. The transfer of CO2 enrichment from plants to herbivores through consumption (apparent resource-effect) was not compensated by predation, because carnivores failed to contain herbivore outbreaks. Instead, these higher-order consumers collapsed (apparent stressor-effect on carnivores) suggesting limited trophic propagation to predator populations. The dominance of primary producers and their lower-order consumers along with the loss of carnivores reflects the duality of intensifying ocean acidification acting both as resource-effect (i.e. bottom-up control) and stressor-effect (i.e. top-down control) to simplify community and trophic structure and function. This shifting balance between the propagation of resource enrichment and its consumption across trophic levels provides new insights into how the trophic dynamics might stabilize against or propagate future environmental change.
Naked singularity, firewall, and Hawking radiation
Authors: Zhang Hongsheng 
Published: June 2017

AbstractSpacetime singularity has always been of interest since the proof of the Penrose-Hawking singularity theorem. Naked singularity naturally emerges from reasonable initial conditions in the collapsing process. A recent interesting approach in black hole information problem implies that we need a firewall to break the surplus entanglements among the Hawking photons. Classically, the firewall becomes a naked singularity. We find some vacuum analytical solutions in R
n
-gravity of the firewall-type and use these solutions as concrete models to study the naked singularities. By using standard quantum theory, we investigate the Hawking radiation emitted from the black holes with naked singularities. Here we show that the singularity itself does not destroy information. A unitary quantum theory works well around a firewall-type singularity. We discuss the validity of our result in general relativity. Further our result demonstrates that the temperature of the Hawking radiation still can be expressed in the form of the surface gravity divided by 2π. This indicates that a naked singularity may not compromise the Hakwing evaporation process.
Global profiling of phytohormone dynamics during combined drought and pathogen stress in Arabidopsis thaliana reveals ABA and JA as major regulators
Authors: Gupta Aarti , Hisano Hiroshi , Hojo Yuko , Matsuura Takakazu , Ikeda Yoko , Mori Izumi C. , Senthil-Kumar Muthappa 
Published: June 2017

AbstractGlobal transcriptome studies demonstrated the existence of unique plant responses under combined stress which are otherwise not seen during individual stresses. In order to combat combined stress plants use signaling pathways and ‘cross talk’ mediated by hormones involved in stress and growth related processes. However, interactions among hormones’ pathways in combined stressed plants are not yet known. Here we studied dynamics of different hormones under individual and combined drought and pathogen infection in Arabidopsis thaliana by liquid chromatography-mass spectrometry (LC-MS) based profiling. Our results revealed abscisic acid (ABA) and salicylic acid (SA) as key regulators under individual drought and pathogen stress respectively. Under combined drought and host pathogen stress (DH) we observed non-induced levels of ABA with an upsurge in SA and jasmonic acid (JA) concentrations, underscoring their role in basal tolerance against host pathogen. Under a non-host pathogen interaction with drought (DNH) stressed plants, ABA, SA and JA profiles were similar to those under DH or non-host pathogen alone. We propose that plants use SA/JA dependent signaling during DH stress which antagonize ABA biosynthesis and signaling pathways during early stage of stress. The study provides insights into hormone modulation at different time points during combined stress.
Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid
Authors: Fujii Chikako , Miyashita Kazutoshi , Mitsuishi Masanori , Sato Masaaki , Fujii Kentaro , Inoue Hiroyuki , Hagiwara Aika , Endo Sho , Uto Asuka , Ryuzaki Masaki , Nakajima Motowo , Tanaka Tohru , Tamaki Masanori , Muraki Ayako , Kawai Toshihide , Itoh Hiroshi 
Published: June 2017

AbstractRecently, sarcopenia has attracted attention as therapeutic target because it constitutes a risk factor for metabolic and cardiovascular diseases. We focused 5-aminolevulinic acid (ALA) which act as electron carriers in the mitochondrial electron transport system. The mice that received ALA for 8 weeks gained muscle strength and endurance, and exhibited increased muscle mass and mitochondrial amount. Administration of ALA to sarcopenia mice aged 100 weeks and chronic kidney disease (CKD) model mice also increased muscle mass and improved physical performance. Metabolome analysis revealed increased branched-chain amino acids (BCAAs) levels in the skeletal muscle of ALA-treated mice. Quantitative PCR analysis revealed decreased expression levels in branched-chain amino acid transaminases (BCATs) that degrade BCAAs and other muscle-degrading factors, and increased levels of mitochondria-activating factors. We also studied in cultured myocytes and obtained compatible results. ALA-treated mice tended to increase body weight, but reduced blood glucose level. These suggested that ALA treatment not only activated muscle mitochondria but also enhanced muscle mass through an increase in BCAAs contents, as to improve muscle strength, endurance and glucose tolerance in mice. In these ways, muscle mitochondrial activation with ALA is suggested to be useful for the treatment of sarcopenia and glucose intolerance.
Vapour-Induced Liquid Crystallinity and Self-Recovery Mechanochromism of Helical Block Copolymer
Authors: Hayashi Hiroki , Iseki Tomokazu , Nimori Shigeki , Goto Hiromasa 
Published: June 2017

AbstractNew molecular design of conjugated polymer that possess high sensitivity to vapour and self-recovering property against pressure is proposed. We synthesised a rod-rod diblock copolymer, poly(3-((3S)-3,7-dimethyl-octyl)-thiophene)-block-poly(4-octyl phenylisocyanide) (PTh-b-PPI), composed of a π-conjugated polymer and a rod-type helical coiled polymer. Introduction of PPI block in the block copolymer architecture enabled PTh-b-PPI film to exhibit solid-to-liquid crystal phase transition by exposure to chloroform vapour, accompanied with colour change (purple-to-yellow), which is the first report on a new phenomenon of “vapour-induced liquid crystallinity”. In addition, PTh-b-PPI film showed colour change (purple-to-vermillion) during mechanical shearing, and spontaneously recovered under ambient conditions. We concluded that rod-type helical coiled polymer PPI block performs crucial roles as intrinsically vapour-induced liquid crystallinity and self-reassembling property in the architecture of PTh-b-PPI.
De novo yeast genome assemblies from MinION, PacBio and MiSeq platforms
Authors: Giordano Francesca , Aigrain Louise , Quail Michael A , Coupland Paul , Bonfield James K , Davies Robert M , Tischler German , Jackson David K , Keane Thomas M , Li Jing , Yue Jia-Xing , Liti Gianni , Durbin Richard , Ning Zemin 
Published: June 2017

AbstractLong-read sequencing technologies such as Pacific Biosciences and Oxford Nanopore MinION are capable of producing long sequencing reads with average fragment lengths of over 10,000 base-pairs and maximum lengths reaching 100,000 base- pairs. Compared with short reads, the assemblies obtained from long-read sequencing platforms have much higher contig continuity and genome completeness as long fragments are able to extend paths into problematic or repetitive regions. Many successful assembly applications of the Pacific Biosciences technology have been reported ranging from small bacterial genomes to large plant and animal genomes. Recently, genome assemblies using Oxford Nanopore MinION data have attracted much attention due to the portability and low cost of this novel sequencing instrument. In this paper, we re-sequenced a well characterized genome, the Saccharomyces cerevisiae S288C strain using three different platforms: MinION, PacBio and MiSeq. We present a comprehensive metric comparison of assemblies generated by various pipelines and discuss how the platform associated data characteristics affect the assembly quality. With a given read depth of 31X, the assemblies from both Pacific Biosciences and Oxford Nanopore MinION show excellent continuity and completeness for the 16 nuclear chromosomes, but not for the mitochondrial genome, whose reconstruction still represents a significant challenge.
Quantitative Phosphoproteomics Reveals a Role for Collapsin Response Mediator Protein 2 in PDGF-Induced Cell Migration
Authors: Sarhan Adil R. , Szyroka Justyna , Begum Shabana , Tomlinson Michael G. , Hotchin Neil A. , Heath John K. , Cunningham Debbie L. 
Published: June 2017

AbstractThe Platelet Derived Growth Factor (PDGF) family of ligands have well established functions in the induction of cell proliferation and migration during development, tissue homeostasis and interactions between tumours and stroma. However, the mechanisms by which these actions are executed are incompletely understood. Here we report a differential phosphoproteomics study, using a SILAC approach, of PDGF-stimulated mouse embryonic fibroblasts (MEFs). 116 phospho-sites were identified as up-regulated and 45 down-regulated in response to PDGF stimulation. These encompass proteins involved in cell adhesion, cytoskeleton regulation and vesicle-mediated transport, significantly expanding the range of proteins implicated in PDGF signalling pathways. Included in the down-regulated class was the microtubule bundling protein Collapsin Response Mediator Protein 2 (CRMP2). In response to stimulation with PDGF, CRMP2 was dephosphorylated on Thr514, an event known to increase CRMP2 activity. This was reversed in the presence of micromolar concentrations of the protein phosphatase inhibitor okadaic acid, implicating PDGF-induced activation of protein phosphatase 1 (PP1) in CRMP2 regulation. Depletion of CRMP2 resulted in impairment of PDGF-mediated cell migration in an in vitro wound healing assay. These results show that CRMP2 is required for PDGF-directed cell migration in vitro.
Disrupted functional connectivity between the periaqueductal gray and other brain regions in a rat model of recurrent headache
Authors: Jia Zhihua , Tang Wenjing , Zhao Dengfa , Yu Shengyuan 
Published: June 2017

AbstractFunctional connectivity (FC) has been used to investigate the pathophysiology of migraine. We aimed to identify atypical FC between the periaqueductal gray (PAG) and other brain areas in rats induced by repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Quiescent and face-grooming behaviors were observed to assess nociceptive behavior. FC analysis seeded on the PAG was performed on rats 21 days after IS infusion. The rats exhibited nociceptive behavior correlates of human behaviors associated with migraine after IS infusion. The PAG showed increased FC with the prefrontal cortex, cingulate gyrus, and motor cortex but decreased FC with the basal ganglia, dorsal lateral thalamus, internal capsule and prelimbic cortex in the rat model. The atypical FC of the PAG with brain regions in the rat model that are involved in nociception, somatosensory processing, emotional processing, and pain modulation are consistent with the clinical data from migraineurs, indicate that resting-state FC changes in migraine patients may be a consequence of headache attacks, and further validate this rat model of chronic migraine.
Transcriptome analyses of taste organoids reveal multiple pathways involved in taste cell generation
Authors: Ren Wenwen , Aihara Eitaro , Lei Weiwei , Gheewala Nishi , Uchiyama Hironobu , Margolskee Robert F. , Iwatsuki Ken , Jiang Peihua 
Published: June 2017

AbstractTaste cells undergo constant turnover throughout life; however, the molecular mechanisms governing taste cell generation are not well understood. Using RNA-Seq, we systematically surveyed the transcriptome landscape of taste organoids at different stages of growth. Our data show the staged expression of a variety of genes and identify multiple signaling pathways underlying taste cell differentiation and taste stem/progenitor cell proliferation. For example, transcripts of taste receptors appear only or predominantly in late-stage organoids. Prior to that, transcription factors and other signaling elements are upregulated. RNA-Seq identified a number of well-characterized signaling pathways in taste organoid cultures, such as those involving Wnt, bone morphogenetic proteins (BMPs), Notch, and Hedgehog (Hh). By pharmacological manipulation, we demonstrate that Wnt, BMPs, Notch, and Hh signaling pathways are necessary for taste cell proliferation, differentiation and cell fate determination. The temporal expression profiles displayed by taste organoids may also lead to the identification of currently unknown transducer elements underlying sour, salt, and other taste qualities, given the staged expression of taste receptor genes and taste transduction elements in cultured organoids.
Anti-proliferative therapy for HIV cure: a compound interest approach
Authors: Reeves Daniel B. , Duke Elizabeth R. , Hughes Sean M. , Prlic Martin , Hladik Florian , Schiffer Joshua T. 
Published: June 2017

AbstractIn the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4+ T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size. We frame this concept in terms of compounding interest: small changes in interest rate drastically improve returns over time. On ART, latent cell proliferation rates are orders of magnitude larger than activation and new infection rates. Contingent on subtypes of cells that may make up the reservoir and their respective proliferation rates, our model predicts that coupling clinically available, anti-proliferative therapies with ART could result in functional cure within 2–10 years rather than several decades on ART alone.
Geochemical constraints on the Hadean environment from mineral fingerprints of prokaryotes
Authors: Novoselov Alexey A. , Silva Dailto , Schneider Jerusa , Abrevaya Ximena Celeste , Chaffin Michael S. , Serrano Paloma , Navarro Margareth Sugano , Conti Maria Josiane , Souza Filho Carlos Roberto de 
Published: June 2017

AbstractThe environmental conditions on the Earth before 4 billion years ago are highly uncertain, largely because of the lack of a substantial rock record from this period. During this time interval, known as the Hadean, the young planet transformed from an uninhabited world to the one capable of supporting, and inhabited by the first living cells. These cells formed in a fluid environment they could not at first control, with homeostatic mechanisms developing only later. It is therefore possible that present-day organisms retain some record of the primordial fluid in which the first cells formed. Here we present new data on the elemental compositions and mineral fingerprints of both Bacteria and Archaea, using these data to constrain the environment in which life formed. The cradle solution that produced this elemental signature was saturated in barite, sphene, chalcedony, apatite, and clay minerals. The presence of these minerals, as well as other chemical features, suggests that the cradle environment of life may have been a weathering fluid interacting with dry-land silicate rocks. The specific mineral assemblage provides evidence for a moderate Hadean climate with dry and wet seasons and a lower atmospheric abundance of CO2than is present today.