bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking spatial gene expression patterns to sex-specific brain structural changes on a mouse model of 16p11.2 hemideletion
Authors: Kumar Vinod Jangir , Grissom Nicola M. , McKee Sarah E. , Schoch Hannah , Bowman Nicole , Havekes Robbert , Kumar Manoj , Pickup Stephen , Poptani Harish , Reyes Teresa M. , Hawrylycz Mike , Abel Ted , Nickl-Jockschat Thomas 
Published: May 2018

AbstractNeurodevelopmental disorders, such as ASD and ADHD, affect males about three to four times more often than females. 16p11.2 hemideletion is a copy number variation that is highly associated with neurodevelopmental disorders. Previous work from our lab has shown that a mouse model of 16p11.2 hemideletion (del/+) exhibits male-specific behavioral phenotypes. We, therefore, aimed to investigate with magnetic resonance imaging (MRI), whether del/+ animals also exhibited a sex-specific neuroanatomical endophenotype. Using the Allen Mouse Brain Atlas, we analyzed the expression patterns of the 27 genes within the 16p11.2 region to identify which gene expression patterns spatially overlapped with brain structural changes. MRI was performed ex vivo and the resulting images were analyzed using Voxel-based morphometry for T1-weighted sequences and tract-based spatial statistics for diffusion-weighted images. In a subsequent step, all available in situ hybridization (ISH) maps of the genes involved in the 16p11.2 hemideletion were aligned to Waxholm space and clusters obtained by sex-specific group comparisons were analyzed to determine which gene(s) showed the highest expression in these regions. We found pronounced sex-specific changes in male animals with increased fractional anisotropy in medial fiber tracts, especially in those proximate to the striatum. Moreover, we were able to identify gene expression patterns spatially overlapping with male-specific structural changes that were associated with neurite outgrowth and the MAPK pathway. Of note, previous molecular studies have found convergent changes that point to a sex-specific dysregulation of MAPK signaling. This convergent evidence supports the idea that ISH maps can be used to meaningfully analyze imaging data sets.
The hedgehog and Wnt/β-catenin system machinery mediate myofibroblast differentiation of LR-MSCs in pulmonary fibrogenesis
Authors: Chen Xiang , Shi Chaowen , Cao Honghui , Chen Ling , Hou Jiwei , Xiang Zou , Hu Kebin , Han Xiaodong 
Published: May 2018

AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal lung disease that is characterized by enhanced changes in stem cell differentiation and fibroblast proliferation. Resident mesenchymal stem cells (LR-MSCs) can undergo phenotype conversion to myofibroblasts to augment extracellular matrix production, impairing function and contributing to pulmonary fibrosis. Hedgehog and Wnt signaling are developmental signal cascades that play an essential role in regulating embryogenesis and tissue homeostasis. Recently, it has been reported that both hedgehog and Wnt signaling play important roles in pulmonary fibrogenesis. Thus, the identification of specific target regulators may yield new strategy for pulmonary fibrosis therapies. In our work, we demonstrated the critical role of Gli1, Wnt7b, Wnt10a and Fzd10 in the process of pulmonary fibrogenesis in vitro and in vivo. Gli1 was induced in LR-MSCs following TGF-β1 treatment and fibrotic lung tissues. Inhibition of Gli1 suppressed myofibroblast differentiation of LR-MSCs and pulmonary fibrosis, and decreased the expression of Wnt7b, Wnt10a and β-catenin. Gli1 bound to and increased promoter activity of the Wnt7b and Wnt10a genes, and Wnt7b and Wnt10a were critical activators of Wnt/β-catenin signaling. It was noteworthy that Fzd10 knockdown reduced Wnt7b and Wnt10a-induced activation of Wnt/β-catenin signaling, which imply that Wnt7b and Wnt10a may be the ligands for Fzd10. Moreover, siRNA-mediated inhibition of Fzd10 prevented TGF-β1-induced myofibroblast differentiation of LR-MSCs in vitro and impaired bleomycin-induced pulmonary fibrosis. We conclude that hedgehog and Wnt/β-catenin signaling play a critical role in promoting myofibroblast differentiation of LR-MSCs and development of pulmonary fibrosis. These findings elucidate a therapeutic approach to attenuate pulmonary fibrosis through targeted inhibition of Gli1 or Fzd10.
Profiling and functional analysis of circular RNAs in acute promyelocytic leukemia and their dynamic regulation during all-trans retinoic acid treatment
Authors: Li Shufen , Ma Yunlin , Tan Yun , Ma Xuefei , Zhao Ming , Chen Bing , Zhang Rongsheng , Chen Zhu , Wang Kankan 
Published: May 2018

AbstractCircular RNAs (circRNAs) are a novel class of powerful regulators in gene expression and participate in the pathogenesis of many diseases, including cancer. However, little is known about the roles of circRNAs in the development and treatment of acute promyelocytic leukemia (APL). Here we report the expression profiling and function of circRNAs in APL, including their dynamic regulation during all-trans retinoic acid (ATRA)-induced differentiation. We performed two independent ribosomal RNA-minus RNA-sequencing (Ribo-minus RNA-seq) experiments with and without RNase R treatment on APL patient-derived NB4 cells and identified a total of 4313 circRNAs, including 1098 newly identified circRNAs. Detailed analysis showed that circRNAs expressed in APL cells were mostly exon-derived, not by-products during splicing, and could be distinguished from hematopoietic stem cells, neutrophils and lymphocytes. The true presence and stability of circRNAs were verified both in NB4 cells and primary APL patient samples. Moreover, we conducted a time-series analysis of circRNAs on ATRA-treated NB4 cells and uncovered 508 circRNAs with dynamic expression during ATRA treatment, including 246 upregulated and 262 downregulated. Further evidence demonstrated that the majority of circRNAs were regulated independently of their host linear mRNAs. Detailed functional experiments demonstrated that circ-HIPK2, one of the differentially expressed circRNAs, significantly influenced ATRA-induced differentiation of APL cells. Further mechanistic studies revealed that circ-HIPK2 was located in cytoplasm and served as a sponge for differentiation-associated miR-124-3p. Finally, circ-HIPK2 expression in APL patients was significantly lower than that in normal peripheral mononuclear cells and other subtypes of AML, indicating its potential role as an APL biomarker. Our study indicates the biological functions of circRNAs in the development and treatment of APL, and provides a comprehensive circRNA resource for future studies.
A neuronal role of the Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) for glycine inhibitory transmission and respiratory pattern
Authors: Mesuret Guillaume , Khabbazzadeh Sepideh , Bischoff Anne M. , Safory Hazem , Wolosker Herman , Hülsmann Swen 
Published: May 2018

AbstractThe Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) has been shown to play a role in synaptic availability of glycine although the exact mechanism remains unclear. We used electrophysiological recordings and biochemical experiments to investigate the role of Asc-1 transporter in glycinergic transmission in the brainstem respiratory network. Using both the Asc-1 substrate and transportable inhibitor D-isoleucine (D-Ile), and the non-transportable Asc-1 blocker Lu AE00527 (Lu), we found that D-Ile reduces glycinergic transmission and increases glycine release via hetero-exchange, whereas Lu has no acute effect on glycinergic synaptic transmission. Furthermore, D-Ile increases the frequency and reduces amplitude of the phrenic nerve activity in the arterially-perfused working heart brainstem preparation. These results suggest a role of Asc-1 in modulating presynaptic glycine levels that can impact on the respiratory network.
Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts
Authors: Dongre Mitesh , Singh Bhupender , Aung Kyaw Min , Larsson Per , Miftakhova Regina , Persson Karina , Askarian Fatemeh , Johannessen Mona , von Hofsten Jonas , Persson Jenny L. , Erhardt Marc , Tuck Simon , Uhlin Bernt Eric , Wai Sun Nyunt 
Published: May 2018

AbstractUsing Caenorhabditis elegans as an infection host model for Vibrio cholerae predator interactions, we discovered a bacterial cytotoxin, MakA, whose function as a virulence factor relies on secretion via the flagellum channel in a proton motive force-dependent manner. The MakA protein is expressed from the polycistronic makDCBA (motility-associated killing factor) operon. Bacteria expressing makDCBA induced dramatic changes in intestinal morphology leading to a defecation defect, starvation and death in C. elegans. The Mak proteins also promoted V. cholerae colonization of the zebrafish gut causing lethal infection. A structural model of purified MakA at 1.9 Å resolution indicated similarities to members of a superfamily of bacterial toxins with unknown biological roles. Our findings reveal an unrecognized role for V. cholerae flagella in cytotoxin export that may contribute both to environmental spread of the bacteria by promoting survival and proliferation in encounters with predators, and to pathophysiological effects during infections.
High-resolution small RNA structures from exact nuclear Overhauser enhancement measurements without additional restraints
Authors: Nichols Parker J. , Henen Morkos A. , Born Alexandra , Strotz Dean , Güntert Peter , Vögeli Beat 
Published: May 2018

AbstractRNA not only translates the genetic code into proteins, but also carries out important cellular functions. Understanding such functions requires knowledge of the structure and dynamics at atomic resolution. Almost half of the published RNA structures have been solved by nuclear magnetic resonance (NMR). However, as a result of severe resonance overlap and low proton density, high-resolution RNA structures are rarely obtained from nuclear Overhauser enhancement (NOE) data alone. Instead, additional semi-empirical restraints and labor-intensive techniques are required for structural averages, while there are only a few experimentally derived ensembles representing dynamics. Here we show that our exact NOE (eNOE) based structure determination protocol is able to define a 14-mer UUCG tetraloop structure at high resolution without other restraints. Additionally, we use eNOEs to calculate a two-state structure, which samples its conformational space. The protocol may open an avenue to obtain high-resolution structures of small RNA of unprecedented accuracy with moderate experimental efforts.
A database of biological and geomorphological sea-level markers from the Last Glacial Maximum to present
Authors: Hibbert F.D. , Williams F.H. , Fallon S.J. , Rohling E.J. 
Published: May 2018

AbstractThe last deglacial was an interval of rapid climate and sea-level change, including the collapse of large continental ice sheets. This database collates carefully assessed sea-level data from peer-reviewed sources for the interval 0 to 25 thousand years ago (ka), from the Last Glacial Maximum to the present interglacial. In addition to facilitating site-specific reconstructions of past sea levels, the database provides a suite of data beyond the range of modern/instrumental variability that may help hone future sea-level projections. The database is global in scope, internally consistent, and contains U-series and radiocarbon dated indicators from both biological and geomorpohological archives. We focus on far-field data (i.e., away from the sites of the former continental ice sheets), but some key intermediate (i.e., from the Caribbean) data are also included. All primary fields (i.e., sample location, elevation, age and context) possess quantified uncertainties, which—in conjunction with available metadata—allows the reconstructed sea levels to be interpreted within both their uncertainties and geological context.
A Research Graph dataset for connecting research data repositories using RD-Switchboard
Authors: Aryani Amir , Poblet Marta , Unsworth Kathryn , Wang Jingbo , Evans Ben , Devaraju Anusuriya , Hausstein Brigitte , Klas Claus-Peter , Zapilko Benjamin , Kaplun Samuele 
Published: May 2018

AbstractThis paper describes the open access graph dataset that shows the connections between Dryad, CERN, ANDS and other international data repositories to publications and grants across multiple research data infrastructures. The graph dataset was created using the Research Graph data model and the Research Data Switchboard (RD-Switchboard), a collaborative project by the Research Data Alliance DDRI Working Group (DDRI WG) with the aim to discover and connect the related research datasets based on publication co-authorship or jointly funded grants. The graph dataset allows researchers to trace and follow the paths to understanding a body of work. By mapping the links between research datasets and related resources, the graph dataset improves both their discovery and visibility, while avoiding duplicate efforts in data creation. Ultimately, the linked datasets may spur novel ideas, facilitate reproducibility and re-use in new applications, stimulate combinatorial creativity, and foster collaborations across institutions.
Catching VY Sculptoris in a low state
Authors: Schmidtobreick L. , Mason E. , Howell S. B. , Long K. S. , Pala A. F. , Points S. , Walter F. M. 
Published: May 2018

Context. In the context of a large campaign to determine the system parameters of high mass transfer cataclysmic variables, we found VY Scl in a low state in 2008.
Aims. Making use of this low state, we study the stellar components of the binary with little influence of the normally dominating accretion disc.
Methods. Time-resolved spectroscopy and photometry of VY Scl taken during the low state are presented. We analysed the lightcurve and radial velocity curve and use time-resolved spectroscopy to calculate Doppler maps of the dominant emission lines.
Results. The spectra show narrow emission lines of Hα, Hβ, He I, Na I D, and Fe II, as well as faint TiO absorption bands that trace the motion of the irradiated secondary star, and Hα and He I emission line wings that trace the motion of the white dwarf. From these radial velocities, we find an orbital period of 3.84 h, and put constraints on binary parameters such as the mass ratio M2/M1 of 0.43 and the inclination of 15°. With a secondary’s mass between 0.3 and 0.35 M⊙, we derive the mass for the white dwarf as M1 = 0.6–1.1 M⊙.
Environmental effects on the ionisation of brown dwarf atmospheres
Authors: Rodríguez-Barrera M. I. , Helling Ch. , Wood K. 
Published: May 2018

Context. Brown dwarfs emit bursts of Hα, white-light flares, and show radio flares and quiescent radio emission. They are suggested to form aurorae, similar to planets in the solar system, but much more energetic. All these processes require a source gas with an appropriate degree of ionisation, which, so far, is mostly postulated to be sufficient.
Aims. We aim to demonstrate that the Galactic environment influences atmospheric ionisation, and that it hence amplifies or enables the magnetic coupling of the atmospheres of ultra-cool objects, like brown dwarfs and free-floating planets.
Methods. We build on our previous work on thermal ionisation of ultra-cool atmospheres and explore the effect of environmental high-energy radiation on the degree of ionisation in the atmosphere. We consider the effect of photoionisation by Lyman-continuum radiation in three different environments: in the interstellar radiation field (ISRF), O and B stars in star-forming regions, and in white dwarf companions in binary systems. We apply our Monte Carlo radiation transfer code to investigate the effect of Lyman-continuum photoionisation for prescribed atmosphere structures for very low-mass objects.
Results. The external radiation environment plays an important role for the atmospheric ionisation of very low-mass, ultra-cool objects. Lyman-continuum irradiation greatly increases the level of ionisation in the uppermost atmospheric regions. Our results suggest that a shell of an almost fully ionised atmospheric gas emerges for brown dwarfs in star-forming regions and brown dwarfs in white dwarf binary systems. As a consequence, brown dwarf atmospheres can be magnetically coupled, which is the presumption for chromospheric heating to occur and for aurorae to emerge. First tests for assumed chromosphere-like temperature values suggest that the resulting free-free X-ray luminosities are comparable with those observed from non-accreting brown dwarfs in star-forming regions.
Akute Bewusstseinsstörung
Authors: Madlener Marie , Onur Oezguer A. 
Published: May 2018

ZusammenfassungDie Akutversorgung eines bewusstlosen Patienten in der Notaufnahme ist komplex und sollte nach einem standardisierten Algorithmus erfolgen. Die Aufrechterhaltung der Vitalparameter, Ursachensuche und Behandlung erfolgen zum Teil parallel und erfordern eine interdisziplinäre Zusammenarbeit. Die Notfalldiagnostik steht unter einem hohen Zeitdruck, um lebensbedrohliche Erkrankungen rasch erkennen und spezifische Therapien einleiten zu können. Der Zeitpunkt der Therapieeinleitung bestimmt dabei oft das Behandlungsergebnis.
Sport und Bewegung mit und nach Krebs – wer profitiert, was ist gesichert?
Authors: Steindorf Karen , Schmidt Martina , Zimmer Philipp 
Published: May 2018

ZusammenfassungDie Diagnose „Krebs“ und die anschließende medizinische Therapie verleiten viele Patienten dazu ihre körperlichen Aktivitäten einzuschränken. Doch gerade Sport und bewegungstherapeutische Programme sind effektive supportive Maßnahmen im Kampf gegen den Krebs und manche Nebenwirkungen. Zudem haben die Betroffenen eine einzigartige Chance, selbst aktiv an ihrem Genesungsprozess mitzuarbeiten. Was zu berücksichtigen ist, zeigt dieser Beitrag.
Störung zirkadianer Rhythmen im Kontext depressiver Erkrankungen
Authors: Wittmann Markus , Schreiber Wolfgang , Landgrebe Michael , Hajak Göran 
Published: May 2018

ZusammenfassungDie Entstehung depressiver Erkrankungen wird im Allgemeinen als multifaktorielles Geschehen verstanden. In den letzten Jahren konnten vielfältige
neurobiologische Veränderungen beschrieben werden, die mit der Entstehung und dem Verlauf von depressiven Erkrankungen in Zusammenhang gebracht werden. Das
ursprüngliche Paradigma der Monoanminomangelhypothese wird dabei immer weiter relativiert, es resultiert somit mittlerweile ein komplexes, aber immer noch nicht
vollständiges Verständnis der Genese dieser Erkrankungen. Dabei greifen die verschiedenen physiologischen Erkrankungsmodelle mit wachsendem Wissensstand
zunehmend ineinander über.
An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics
Authors: Blanc Florian , Isabet Tatiana , Benisty Hannah , Sweeney H. Lee , Cecchini Marco , Houdusse Anne 
Published: May 2018

Significance
Myosins are motor proteins involved in the transport of cellular cargoes and muscle contraction. Upon interaction with actin, the motor domain undergoes a conformational transition, called powerstroke, in which the lever arm is swung to generate force and directional motion. The recovery stroke reprimes the motor by coupling the reverse swing of the lever arm to ATP hydrolysis. Using X-ray crystallography and molecular simulations, we characterize a putative intermediate along the recovery stroke of myosin VI, which challenges existing models of myosin chemomechanical transduction. Intriguingly, the new structure suggests that the repriming of the lever arm would be uncoupled from ATPase activity until the very end of the recovery stroke and mostly driven by thermal fluctuations.
Protein kinase Cα gain-of-function variant in Alzheimer’s disease displays enhanced catalysis by a mechanism that evades down-regulation
Authors: Callender Julia A. , Yang Yimin , Lordén Gema , Stephenson Natalie L. , Jones Alexander C. , Brognard John , Newton Alexandra C. 
Published: May 2018

Significance
This work unveils how an Alzheimer’s disease-associated mutation (M489V) in protein kinase Cα (PKCα) enhances catalytic activity without sensitizing the protein to the cell’s homeostatic degradation of aberrantly active PKCα. The active conformation of wild-type PKC is sensitive to degradation, and therefore constitutively activated PKC paradoxically manifests as loss of function. We show that PKCα-M489V enhances the intrinsic catalytic rate of the kinase without altering the equilibrium between the autoinhibited (protected) conformation and the activated (degradation-sensitive) conformation. Thus, the on/off dynamics are unchanged, but reactions are catalyzed at a faster rate when the enzyme is on. These findings are significant because they provide a mechanism through which a disease mutation in PKCα causes aberrant activation without resulting in paradoxical loss of function via degradation.
Response of brain‐derived neurotrophic factor to combining cognitive and physical exercise
Authors: Miyamoto Toshiaki , Hashimoto Saya , Yanamoto Hideya , Ikawa Mai , Nakano Yoshiki , Sekiyama Takashi , Kou Keihou , Kashiwamura Shin‐Ichiro , Takeda Chisako , Fujioka Hiroyuki 
Published: May 2018

AbstractPurpose: Brain‐derived neurotrophic factor (BDNF) is well known for its potential to promote brain plasticity. It has been proposed that combining cognitive and physical exercise (CCPE) may have the potential to generate more synergistic benefits in cognitive function than either cognitive exercise (CE) or physical exercise (PE) alone. The purpose of this study was to examine acute responses of peripheral BDNF levels and cognitive performance to CE, PE, and CCPE.Methods: Thirteen healthy adult men participated in four experimental sessions; a 30‐min CE, a 30‐min cycling PE at an intensity of 60% peak oxygen uptake, a 30‐min CCPE at the same intensity as PE, and a 30‐min session of complete rest. Plasma BDNF levels and cognitive performance were measured before and after each session.Results: Both PE and CCPE significantly increased plasma BDNF levels (p < .05). CE led to no significant increase (p ≥ .05), and there was no significant difference in peripheral BDNF levels between PE and CCPE (p ≥ .05). No session induced a significant change in cognitive performance (p ≥ .05).Conclusions: Our study suggests that CE and PE have different responses of peripheral BDNF levels and that CCPE had no additional or synergistic effect on peripheral BDNF levels compared with PE alone. This study offers further insights into the potential mechanisms underlying the respective roles of CE, PE, and CCPE for peripheral BDNF levels and cognitive performance.