bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of P2X7 receptors in a rodent PCP-induced schizophrenia model
Authors: Koványi Bence , Csölle Cecilia , Calovi Stefano , Hanuska Adrienn , Kató Erzsébet , Köles László , Bhattacharya Anindya , Haller József , Sperlágh Beáta 
Published: November 2016

AbstractP2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7−/−), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated. The selective P2X7 receptor antagonist JNJ-47965567 partly replicated the effect of gene deficiency on PCP-induced behavioral changes and counteracted PCP-induced social withdrawal. We also show that PCP treatment upregulates and increases the functional responsiveness of P2X7Rs in the prefrontal cortex of young adult animals. The amplitude of NMDA evoked currents recorded from layer V pyramidal neurons of cortical slices were slightly decreased by both genetic deletion of P2rx7 and by JNJ-47965567. PCP induced alterations in mRNA expression encoding schizophrenia-related genes, such as NR2A, NR2B, neuregulin 1, NR1 and GABA α1 subunit were absent in the PFC of young adult P2rx7−/− animals. Our findings point to P2X7R as a potential therapeutic target in schizophrenia.
Suppression of radiation-induced point defects by rhenium and osmium interstitials in tungsten
Authors: Suzudo Tomoaki , Hasegawa Akira 
Published: November 2016

AbstractModeling the evolution of radiation-induced defects is important for finding radiation-resistant materials, which would be greatly appreciated in nuclear applications. We apply the density functional theory combined with comprehensive analyses of massive experimental database to indicate a mechanism to mitigate the effect of radiation on W crystals by adding particular solute elements that change the migration property of interstitials. The resultant mechanism is applicable to any body-centered-cubic (BCC) metals whose self-interstitial atoms become a stable crowdion and is expected to provide a general guideline for computational design of radiation-resistant alloys in the field of nuclear applications.
Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance
Authors: Kadioglu Onat , Cao Jingming , Kosyakova Nadezda , Mrasek Kristin , Liehr Thomas , Efferth Thomas 
Published: November 2016

AbstractWe systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aberrations, including X-chromosome loss, 4q and 14q deletion, chromosome 7 inversion, balanced and unbalanced two and three way translocations: t(3;10), der(3)t(3;13), der(5)t(18;5;14), t(10;16), der(18)t(7;18), der(18)t(21;18;5), der(21;21;18;5) and der(22)t(9;22). CCRF-CEM consisted of two and CEM/ADR5000 of five major sub-clones, indicating genetic tumor heterogeneity. Loss of 3q27.1 in CEM/ADR5000 caused down-regulation of ABCC5 and ABCF3 expression, Xq28 loss down-regulated ABCD1 expression. ABCB1, the most well-known MDR gene, was 448-fold up-regulated due to 7q21.12 amplification. In addition to well-known drug resistance genes, numerous novel genes and genomic aberrations were identified. Transcriptomics and genetics in CEM/AD5000 cells unravelled a range of MDR mechanisms, which is much more complex than estimated thus far. This may have important implications for future treatment strategies.
Recurrence Quantification Analysis of Sentence-Level Speech Kinematics
Authors: Jackson Eric S. , Tiede Mark , Riley Michael A. , Whalen D. H. 
Published: November 2016

PurposeCurrent approaches to assessing sentence-level speech variability rely on measures that quantify variability across utterances and use normalization procedures that alter raw trajectory data. The current work tests the feasibility of a less restrictive nonlinear approach—recurrence quantification analysis (RQA)—via a procedural example and subsequent analysis of kinematic data.MethodTo test the feasibility of RQA, lip aperture (i.e., the Euclidean distance between lip-tracking sensors) was recorded for 21 typically developing adult speakers during production of a simple utterance. The utterance was produced in isolation and in carrier structures differing just in length or in length and complexity. Four RQA indices were calculated: percent recurrence (%REC), percent determinism (%DET), stability (MAXLINE), and stationarity (TREND).ResultsPercent determinism (%DET) decreased only for the most linguistically complex sentence; MAXLINE decreased as a function of linguistic complexity but increased for the longer-only sentence; TREND decreased as a function of both length and linguistic complexity.ConclusionsThis research note demonstrates the feasibility of using RQA as a tool to compare speech variability across speakers and groups. RQA offers promise as a technique to assess effects of potential stressors (e.g., linguistic or cognitive factors) on the speech production system.
Coastal sea level rise with warming above 2 °C
Authors: Jevrejeva Svetlana , Jackson Luke P. , Riva Riccardo E. M. , Grinsted Aslak , Moore John C. 
Published: November 2016

Significance
Warming of 2 °C will lead to an average global ocean rise of 20 cm, but more than 90% of coastal areas will experience greater rises. If warming continues above 2 °C, then, by 2100, sea level will be rising faster than at any time during human civilization, and 80% of the global coastline is expected to exceed the 95th percentile upper limit of 1.8 m for mean global ocean sea level rise. Coastal communities, notably rapidly expanding cities in the developing world; small island states; United Nations Educational, Scientific and Cultural Organization Cultural World Heritage sites; and vulnerable tropical coastal ecosystems will have a very limited time after midcentury to adapt to these rises.
Temporal coding of reward-guided choice in the posterior parietal cortex
Authors: Hawellek David J. , Wong Yan T. , Pesaran Bijan 
Published: November 2016

SignificanceA central question in systems neuroscience is how cognitive functions can arise from the interplay of many different brain areas. For example the cognitive act of forming a decision requires a concerted computation involving sensory, mnemonic, and executive information residing in neural circuits that have different anatomical locations, that operate on different temporal scales, and that extend over different spatial dimensions. We find that in a central cortical hub—the posterior parietal cortex—firing rate information about upcoming decisions is pulsed according to intrinsic temporal structure in the beta- and gamma-frequency ranges. The brain may use temporal structure at several time scales to support distributed computations that underlie reward-guided decisions.
For blacks in America, the gap in neighborhood poverty has declined faster than segregation
Authors: Firebaugh Glenn , Acciai Francesco 
Published: November 2016

SignificanceRacial inequality in America persists in part because of racial differences in exposure to adverse neighborhood environments. Blacks in particular are significantly more likely than other Americans to live in high-poverty neighborhoods—neighborhoods characterized by poor schools and limited access to healthcare, jobs, and beneficial social networks—resulting in inequality of opportunity, as life chances are diminished for residents of such neighborhoods. In addition, the greater exposure to crime, noise, and congestion implies a lower quality of life, on average, for black Americans. Because black neighborhood disadvantage results in inequality of life chances based on race, it is important to determine the direction, pace, and sources of change in black–nonblack differences in neighborhood poverty in America.
Gut microbiota induce IGF-1 and promote bone formation and growth
Authors: Yan Jing , Herzog Jeremy W. , Tsang Kelly , Brennan Caitlin A. , Bower Maureen A. , Garrett Wendy S. , Sartor Balfour R. , Aliprantis Antonios O. , Charles Julia F. 
Published: November 2016

Significance
New interventions are needed to improve bone health and reduce the risk for osteoporosis and fracture. Dysbiosis is increasingly linked to metabolic abnormalities, although the effect of the microbiota on skeletal health is poorly understood. Previous studies suggest microbiota are detrimental to bone by increasing resorption. In this report, we show that the gut resident microbiota promote bone formation, as well as resorption, with long-term exposure to microbiota resulting in net skeletal growth. Microbiota induce the hormone insulin-like growth factor 1 (IGF-1), which promotes bone growth and remodeling. Short-chain fatty acids (SCFAs), produced when microbiota ferment fiber, also induce IGF-1, suggesting a mechanism by which microbiota affect bone health. Manipulating the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition
Authors: Daitch Amy L. , Foster Brett L. , Schrouff Jessica , Rangarajan Vinitha , Kaşikçi Itır , Gattas Sandra , Parvizi Josef 
Published: November 2016

Significance
Humans have the unique ability to perform exact mental arithmetic, which derives from the association of symbols (e.g., “3”) with discrete quantities. Using direct intracranial recordings, we measured electrophysiological activity from neuronal populations in the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) that are known to be important for numerical processing as subjects performed various experiments. We observed functional heterogeneity within each region at the millimeter and millisecond scales and report empirical evidence of functional coupling between the LPC and VTC during mathematical cognition. Our results suggest the presence of an anatomically selective numerical cognition system that engages discrete neuronal populations of the ventral temporal and lateral parietal regions in different time windows of numerical processing.
Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks
Authors: Artemenko Yulia , Axiotakis Lucas , Borleis Jane , Iglesias Pablo A. , Devreotes Peter N. 
Published: November 2016

Significance
Cells directionally migrate in response to a variety of external cues, including chemical, electrical, and mechanical stimuli; however, only response to chemoattractants has been characterized at the molecular level. Binding of chemoattractants to specific surface receptors triggers rapid, transient activation of many signal transduction and cytoskeletal events. We discovered that brief application of shear stress to cells likely elicits activation of all of the same events. Responses to chemoattractants and shear stress are susceptible to many of the same perturbations, although that to mechanical stimulation uniquely is blocked by disruption of the actin cytoskeleton. Our finding provides insight into the molecular mechanism of cellular response to mechanical stimuli and has important implications for integration of chemical and mechanical inputs.
Quantitative determination of ribosome nascent chain stability
Authors: Samelson Avi J. , Jensen Madeleine K. , Soto Randy A. , Cate Jamie H. D. , Marqusee Susan 
Published: November 2016

Significance
A fundamental question in biology is how the biophysical parameters describing protein folding in vitro are altered during cotranslational folding. Because protein synthesis is slow, nascent chains can fold cotranslationally while still tethered to the ribosome and before the entire protein has emerged. Here we examine the effects of ribosomal tethering on protein stability and how that stability is modulated by the distance away from the ribosome’s active site. We develop a quantitative assay for measuring protein stability on stalled nascent chains and find that the ribosome destabilizes nascent chains. This destabilization may play a key role in ensuring folding fidelity by helping the nascent chain avoid partially folded kinetic traps before the entire chain has been synthesized.
The cholinergic forebrain arousal system acts directly on the circadian pacemaker
Authors: Yamakawa Glenn R. , Basu Priyoneel , Cortese Filomeno , MacDonnell Johanna , Whalley Danica , Smith Victoria M. , Antle Michael C. 
Published: November 2016

SignificanceSleep and wake states are regulated by a variety of mechanisms. One such important system is the circadian clock, which provides temporal structure to sleep and wake. Conversely, changes in behavioral state can influence the phase of the circadian clock. Here we demonstrate that the level of wakefulness is critical for arousal to reset circadian clock phase. We then show that treatments that produce arousal and reset the circadian clock activate the basal forebrain. Finally, we demonstrate that cholinergic input from the basal forebrain is both necessary and sufficient for eliciting this arousal-induced resetting of the circadian clock. These results establish a functional link between the major forebrain arousal center and the circadian system.
Engineering dynamical control of cell fate switching using synthetic phospho-regulons
Authors: Gordley Russell M. , Williams Reid E. , Bashor Caleb J. , Toettcher Jared E. , Yan Shude , Lim Wendell A. 
Published: November 2016

Significance
Many long-term cellular decisions in development, synaptic plasticity, and immunity require cells to recognize input dynamics such as pulse duration or frequency. In dynamically controlled cells, incoming stimuli are often processed and filtered by a rapid-acting signaling layer, and then passed to a downstream slow-acting layer that locks in a longer-term cellular response. Directly testing how such dual-timescale networks control dynamical regulation has been challenging because most tools in synthetic biology allow rewiring of slow gene expression circuits, but not of rapid signaling circuits. In this work, we developed modular peptide tags for engineering synthetic phosphorylation circuits. We used these phospho-regulons to build synthetic dual-timescale networks in which the dynamic responsiveness of a cell fate decision can be selectively tuned.
How social structures, space, and behaviors shape the spread of infectious diseases using chikungunya as a case study
Authors: Salje Henrik , Lessler Justin , Paul Kishor Kumar , Azman Andrew S. , Rahman M. Waliur , Rahman Mahmudur , Cummings Derek , Gurley Emily S. , Cauchemez Simon 
Published: November 2016

Significance
Although the determinants of infectious disease transmission have been extensively investigated in small social structures such as households or schools, the impact of the wider environment (e.g., neighborhood) on transmission has received less attention. Here we use an outbreak of chikungunya as a case study where detailed epidemiological data were collected and combine it with statistical approaches to characterize the multiple factors that influence the risk of infectious disease transmission and may depend on characteristics of the individual (e.g., age, sex), of his or her close relatives (e.g., household members), or of the wider neighborhood. Our findings highlight the role that integrating statistical approaches with in-depth information on the at-risk population can have on understanding pathogen spread.
X-ray and cryo-EM structures of monomeric and filamentous actin-like protein MamK reveal changes associated with polymerization
Authors: Löwe Jan , He Shaoda , Scheres Sjors H. W. , Savva Christos G. 
Published: November 2016

Significance
Some bacteria contain tiny magnets, so-called magnetosomes, that allow them to swim oriented by the Earth’s magnetic field. An intracellular filamentous protein, MamK, has previously been shown to align the magnetosomes along a straight line to combine their magnetic moments. Here we show the structure the MamK filaments have at the atomic level. We also show what happens when individual MamK molecules come together to form the filaments, because it is known that filament formation triggers the hydrolysis of the ATP molecule bound to MamK. The structure of monomeric MamK was determined by X-ray crystallography and of the filament by electron cryomicroscopy, image processing, and helical reconstruction.
Design of a molecular support for cryo-EM structure determination
Authors: Martin Thomas G. , Bharat Tanmay A. M. , Joerger Andreas C. , Bai Xiao-chen , Praetorius Florian , Fersht Alan R. , Dietz Hendrik , Scheres Sjors H. W. 
Published: November 2016

Significance
As the scope of macromolecular structure determination by cryo-electron microscopy (cryo-EM) is expanding rapidly, it is becoming increasingly clear that many biological complexes are too fragile to withstand the harsh conditions involved in making cryo-EM samples. We describe an original approach to protect proteins from harmful forces during cryo-EM sample preparation by enclosing them inside a three-dimensional support structure that we designed using DNA origami techniques. By binding the transcription cofactor p53 to a specific DNA sequence, and by modifying the position of this sequence in our support structure, we also sought to control the relative orientation of individual p53:DNA complexes.
Recent acceleration in coastal cliff retreat rates on the south coast of Great Britain
Authors: Hurst Martin D. , Rood Dylan H. , Ellis Michael A. , Anderson Robert S. , Dornbusch Uwe 
Published: November 2016

Significance
Cliffed coasts erode when attacked by energetic waves. Cliff retreat threatens coastal assets and livelihoods. Understanding rates of past erosion is vital to quantifying these risks, particularly when confronted with expected increases in storminess and sea level, and given continued human occupation and engineering of coastal regions. Historical observations of cliff retreat span 150 y at most. We derived past cliff retreat rates over millennial time scales for chalk cliffs on the south coast of Great Britain by interpreting measured cosmogenic nuclides with numerical models. Our results provide evidence for accelerated erosion in recent centuries, which we suggest is driven by reduced sediment supply and thinning of beaches in the face of environmental and anthropogenic changes.
Regulation of embryonic neurogenesis by germinal zone vasculature
Authors: Tata Mathew , Wall Ivan , Joyce Andy , Vieira Joaquim M. , Kessaris Nicoletta , Ruhrberg Christiana 
Published: November 2016

Significance
Neural progenitor cells (NPCs) proliferate to generate precursors for new neurons. To sustain this process, NPCs balance self-renewal with the generation of progeny committed to neuronal differentiation. In the adult mammalian brain, blood vessels and vessel-derived factors help regulate this balance by modulating NPC proliferation and quiescence, independently of vascular roles in providing oxygen and nutrients. In contrast, it has been proposed that vasculature regulates NPC behavior in the developing forebrain by alleviating tissue hypoxia. We show here that germinal zone vasculature in the embryonic hindbrain regulates the balance of NPC self-renewal with neuron production, independently of roles in tissue oxygenation. Information on how blood vessels regulate neurogenesis may aid in the design of therapies for brain regeneration in injury and disease.
Predators catalyze an increase in chloroviruses by foraging on the symbiotic hosts of zoochlorellae
Authors: DeLong John P. , Al-Ameeli Zeina , Duncan Garry , Van Etten James L. , Dunigan David D. 
Published: November 2016

Significance
Reproduction and growth of viruses depend on successful encounters with appropriate hosts. However, some hosts are difficult to encounter. In particular, chloroviruses cannot reach their target zoochlorellae hosts, because zoochlorellae are endosymbionts, living inside the cell of a protist that protects the zoochlorellae from the chlorovirus. The protist host is subject to predation, and we show that copepods foraging on zoochlorellae-bearing protists can disrupt the mutualism and pass endosymbiontic zoochlorellae through their guts, exposing them to chloroviruses. In this way, predators can catalyze the virus population growth by breaking down physical barriers between viruses and their endosymbiont hosts.
Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer
Authors: Xu George J. , Shah Ami A. , Li Mamie Z. , Xu Qikai , Rosen Antony , Casciola-Rosen Livia , Elledge Stephen J. 
Published: November 2016

Significance
In this study, we created a barcoded whole-genome ORF mRNA display library and combined it with phage-immunoprecipitation sequencing to look for autoantibodies in sera from patients with scleroderma who also had coincident cancer without a known autoantibody biomarker. Using these two technologies, we found that 25% of these patients had autoantibodies to RNA Binding Region Containing 3 (RNPC3) and multiple other components of the minor spliceosome. There was evidence of intra- and intermolecular epitope spreading within RNPC3 and the complex. These combined technologies are highly effective for rapidly discovering autoantibodies in patient subgroups, which will be useful tools for patient stratification and discovery of pathogenic pathways.
Reduced high-frequency motor neuron firing, EMG fractionation, and gait variability in awake walking ALS mice
Authors: Hadzipasic Muhamed , Ni Weiming , Nagy Maria , Steenrod Natalie , McGinley Matthew J. , Kaushal Adi , Thomas Eleanor , McCormick David A. , Horwich Arthur L. 
Published: November 2016

Significance
First recordings from awake walking symptomatic-stage amyotrophic lateral sclerosis (ALS) and control mice were made simultaneously from spinal cord motor pools and corresponding hindlimb flexor and extensor muscles. Spinal recordings revealed loss of high-frequency firing in ALS mice, and EMG showed an abnormal fractionated character with step-to-step variability and flexor/extensor coactivation, associated with step-to-step variability in kinematics and likely compensatory mechanisms that allow continued ability to walk in the face of motor neuron loss.
Learning and remembering real-world events after medial temporal lobe damage
Authors: Dede Adam J. O. , Frascino Jennifer C. , Wixted John T. , Squire Larry R. 
Published: November 2016

Significance
We explored the role of the medial temporal lobe (MTL) in remembering recent events. Patients with MTL damage and healthy controls were taken on a walk during which 11 planned events occurred. Patients remembered fewer details about the events than controls. Nevertheless, the details made reference to particular places and events from the walk. In addition, patients were similarly impaired across different kinds of content (spatial and nonspatial). Last, the patients were particularly impaired at remembering the temporal order in which the events occurred. The findings illuminate the role of the MTL in memory for real-world events and in the spatial and nonspatial aspects of recollection.