bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transgenic overexpression of furin increases epileptic susceptibility
Authors: Yang Yi , He Miaoqing , Tian Xin , Guo Yi , Liu Feng , Li Yun , Zhang Haiqing , Lu Xi , Xu Demei , Zhou Ruijiao , Ma Yuanlin , Wang Wei , Chen Guojun , Hu Yida , Wang Xuefeng 
Published: October 2018

AbstractThe proprotein convertase Furin plays crucial roles in the pathology of many diseases. However, the specific role of furin in epilepsy remains unclear. In our study, furin protein was increased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. The furin transgenic (TG) mice showed increased susceptibility to epilepsy and heightened epileptic activity compared with wild-type (WT) mice. Conversely, lentivirus-mediated knockdown of furin restrained epileptic activity. Using whole-cell patch clamp, furin knockdown and overexpression influenced neuronal inhibitory by regulating postsynaptic gamma-aminobutyric acid A receptor (GABAAR)-mediated synaptic transmission. Importantly, furin influenced the expression of GABAAR β2/3 membrane and total protein in epileptic mice by changing transcription level of GABAAR β2/3, not the protein degradation. These results reveal that furin may regulate GABAAR-mediated inhibitory synaptic transmission by altering the transcription of GABAAR β2/3 subunits in epilepsy; this finding could provide new insight into epilepsy prevention and treatment.
Aberrant activation of non-coding RNA targets of transcriptional elongation complexes contributes to TDP-43 toxicity
Authors: Chung Chia-Yu , Berson Amit , Kennerdell Jason R. , Sartoris Ashley , Unger Travis , Porta Sílvia , Kim Hyung-Jun , Smith Edwin R. , Shilatifard Ali , Van Deerlin Vivianna , Lee Virginia M.-Y. , Chen-Plotkin Alice , Bonini Nancy M. 
Published: October 2018

AbstractTDP-43 is the major disease protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-TDP). Here we identify the transcriptional elongation factor Ell—a shared component of little elongation complex (LEC) and super elongation complex (SEC)—as a strong modifier of TDP-43-mediated neurodegeneration. Our data indicate select targets of LEC and SEC become upregulated in the fly ALS/FTLD-TDP model. Among them, U12 snRNA and a stress-induced long non-coding RNA Hsrω, functionally contribute to TDP-43-mediated degeneration. We extend the findings of Hsrω, which we identify as a chromosomal target of TDP-43, to show that the human orthologue Sat III is elevated in a human cellular disease model and FTLD-TDP patient tissue. We further demonstrate an interaction between TDP-43 and human ELL2 by co-immunoprecipitation from human cells. These findings reveal important roles of Ell-complexes LEC and SEC in TDP-43-associated toxicity, providing potential therapeutic insight for TDP-43-associated neurodegeneration.
Discovery of RNA-binding proteins and characterization of their dynamic responses by enhanced RNA interactome capture
Authors: Perez-Perri Joel I. , Rogell Birgit , Schwarzl Thomas , Stein Frank , Zhou Yang , Rettel Mandy , Brosig Annika , Hentze Matthias W. 
Published: October 2018

AbstractFollowing the realization that eukaryotic RNA-binding proteomes are substantially larger than anticipated, we must now understand their detailed composition and dynamics. Methods such as RNA interactome capture (RIC) have begun to address this need. However, limitations of RIC have been reported. Here we describe enhanced RNA interactome capture (eRIC), a method based on the use of an LNA-modified capture probe, which yields numerous advantages including greater specificity and increased signal-to-noise ratios compared to existing methods. In Jurkat cells, eRIC reduces the rRNA and DNA contamination by >10-fold compared to RIC and increases the detection of RNA-binding proteins. Due to its low background, eRIC also empowers comparative analyses of changes of RNA-bound proteomes missed by RIC. For example, in cells treated with dimethyloxalylglycine, which inhibits RNA demethylases, eRIC identifies m6A-responsive RNA-binding proteins that escape RIC. eRIC will facilitate the unbiased characterization of RBP dynamics in response to biological and pharmacological cues.
Diffusion-limited reactions in dynamic heterogeneous media
Authors: Lanoiselée Yann , Moutal Nicolas , Grebenkov Denis S. 
Published: October 2018

AbstractMost biochemical reactions in living cells rely on diffusive search for target molecules or regions in a heterogeneous overcrowded cytoplasmic medium. Rapid rearrangements of the medium constantly change the effective diffusivity felt locally by a diffusing particle and thus impact the distribution of the first-passage time to a reaction event. Here, we investigate the effect of these dynamic spatiotemporal heterogeneities onto diffusion-limited reactions. We describe a general mathematical framework to translate many results for ordinary homogeneous Brownian motion to heterogeneous diffusion. In particular, we derive the probability density of the first-passage time to a reaction event and show how the dynamic disorder broadens the distribution and increases the likelihood of both short and long trajectories to reactive targets. While the disorder slows down reaction kinetics on average, its dynamic character is beneficial for a faster search and realization of an individual reaction event triggered by a single molecule.
Dynamic coordination of two-metal-ions orchestrates λ-exonuclease catalysis
Authors: Hwang Wonseok , Yoo Jungmin , Lee Yuno , Park Suyeon , Hoang Phuong Lien , Cho HyeokJin , Yu Jeongmin , Hoa Vo Thi Minh , Shin Minsang , Jin Mi Sun , Park Daeho , Hyeon Changbong , Lee Gwangrog 
Published: October 2018

AbstractMetal ions at the active site of an enzyme act as cofactors, and their dynamic fluctuations can potentially influence enzyme activity. Here, we use λ-exonuclease as a model enzyme with two Mg2+ binding sites and probe activity at various concentrations of magnesium by single-molecule-FRET. We find that while MgA2+ and MgB2+ have similar binding constants, the dissociation rate of MgA2+ is two order of magnitude lower than that of MgB2+ due to a kinetic-barrier-difference. At physiological Mg2+ concentration, the MgB2+ ion near the 5’-terminal side of the scissile phosphate dissociates each-round of degradation, facilitating a series of DNA cleavages via fast product-release concomitant with enzyme-translocation. At a low magnesium concentration, occasional dissociation and slow re-coordination of MgA2+ result in pauses during processive degradation. Our study highlights the importance of metal-ion-coordination dynamics in correlation with the enzymatic reaction-steps, and offers insights into the origin of dynamic heterogeneity in enzymatic catalysis.
High-performance and scalable on-chip digital Fourier transform spectroscopy
Authors: Kita Derek M. , Miranda Brando , Favela David , Bono David , Michon Jérôme , Lin Hongtao , Gu Tian , Hu Juejun 
Published: October 2018

AbstractOn-chip spectrometers have the potential to offer dramatic size, weight, and power advantages over conventional benchtop instruments for many applications such as spectroscopic sensing, optical network performance monitoring, hyperspectral imaging, and radio-frequency spectrum analysis. Existing on-chip spectrometer designs, however, are limited in spectral channel count and signal-to-noise ratio. Here we demonstrate a transformative on-chip digital Fourier transform spectrometer that acquires high-resolution spectra via time-domain modulation of a reconfigurable Mach-Zehnder interferometer. The device, fabricated and packaged using industry-standard silicon photonics technology, claims the multiplex advantage to dramatically boost the signal-to-noise ratio and unprecedented scalability capable of addressing exponentially increasing numbers of spectral channels. We further explore and implement machine learning regularization techniques to spectrum reconstruction. Using an ‘elastic-D1’ regularized regression method that we develop, we achieved significant noise suppression for both broad (>600 GHz) and narrow (<25 GHz) spectral features, as well as spectral resolution enhancement beyond the classical Rayleigh criterion.
Defective transcription elongation in a subset of cancers confers immunotherapy resistance
Authors: Modur Vishnu , Singh Navneet , Mohanty Vakul , Chung Eunah , Muhammad Belal , Choi Kwangmin , Chen Xiaoting , Chetal Kashish , Ratner Nancy , Salomonis Nathan , Weirauch Matthew T. , Waltz Susan , Huang Gang , Privette-Vinnedge Lisa , Park Joo-Seop , Janssen Edith M. , Komurov Kakajan 
Published: October 2018

AbstractThe nature and role of global transcriptional deregulations in cancers are not fully understood. We report that a large proportion of cancers have widespread defects in mRNA transcription elongation (TE). Cancers with TE defects (TEdeff) display spurious transcription and defective mRNA processing of genes characterized by long genomic length, poised promoters and inducible expression. Signaling pathways regulated by such genes, such as pro-inflammatory response pathways, are consistently suppressed in TEdeff tumors. Remarkably, TEdeff correlates with the poor response and outcome in immunotherapy, but not chemo- or targeted therapy, -treated renal cell carcinoma and metastatic melanoma patients. Forced pharmacologic or genetic induction of TEdeff in tumor cells impairs pro-inflammatory response signaling, and imposes resistance to the innate and adaptive anti-tumor immune responses and checkpoint inhibitor therapy in vivo. Therefore, defective TE is a previously unknown mechanism of tumor immune resistance, and should be assessed in cancer patients undergoing immunotherapy.
A microfabricated nerve-on-a-chip platform for rapid assessment of neural conduction in explanted peripheral nerve fibers
Authors: Gribi Sandra , du Bois de Dunilac Sophie , Ghezzi Diego , Lacour Stéphanie P. 
Published: October 2018

AbstractPeripheral nerves are anisotropic and heterogeneous neural tissues. Their complex physiology restricts realistic in vitro models, and high resolution and selective probing of axonal activity. Here, we present a nerve-on-a-chip platform that enables rapid extracellular recording and axonal tracking of action potentials collected from tens of myelinated fibers. The platform consists of microfabricated stimulation and recording microchannel electrode arrays. First, we identify conduction velocities of action potentials traveling through the microchannel and propose a robust data-sorting algorithm using velocity selective recording. We optimize channel geometry and electrode spacing to enhance the algorithm reliability. Second, we demonstrate selective heat-induced neuro-inhibition of peripheral nerve activity upon local illumination of a conjugated polymer (P3HT) blended with a fullerene derivative (PCBM) coated on the floor of the microchannel. We demonstrate the nerve-on-a-chip platform is a versatile tool to optimize the design of implantable peripheral nerve interfaces and test selective neuromodulation techniques ex vivo.
Multipartite Entanglement at Finite Temperature
Authors: Gabbrielli Marco , Smerzi Augusto , Pezzè Luca 
Published: October 2018

AbstractThe interplay of quantum and thermal fluctuations in the vicinity of a quantum critical point characterizes the physics of strongly correlated systems. Here we investigate this interplay from a quantum information perspective presenting the universal phase diagram of the quantum Fisher information at a quantum phase transition. Different regions in the diagram are identified by characteristic scaling laws of the quantum Fisher information with respect to temperature. This feature has immediate consequences on the thermal robustness of quantum coherence and multipartite entanglement. We support the theoretical predictions with the analysis of paradigmatic spin systems showing symmetry-breaking quantum phase transitions and free-fermion models characterized by topological phases. In particular we show that topological systems are characterized by the survival of large multipartite entanglement, reaching the Heisenberg limit at finite temperature.
Spine-to-Dendrite Calcium Modeling Discloses Relevance for Precise Positioning of Ryanodine Receptor-Containing Spine Endoplasmic Reticulum
Authors: Breit Markus , Kessler Marcus , Stepniewski Martin , Vlachos Andreas , Queisser Gillian 
Published: October 2018

AbstractThe endoplasmic reticulum (ER) forms a complex endomembrane network that reaches into the cellular compartments of a neuron, including dendritic spines. Recent work discloses that the spine ER is a dynamic structure that enters and leaves spines. While evidence exists that ER Ca2+ release is involved in synaptic plasticity, the role of spine ER morphology remains unknown. Combining a new 3D spine generator with 3D Ca2+ modeling, we addressed the relevance of ER positioning on spine-to-dendrite Ca2+ signaling. Our simulations, which account for Ca2+ exchange on the plasma membrane and ER, show that spine ER needs to be present in distinct morphological conformations in order to overcome a barrier between the spine and dendritic shaft. We demonstrate that RyR-carrying spine ER promotes spine-to-dendrite Ca2+ signals in a position-dependent manner. Our simulations indicate that RyR-carrying ER can initiate time-delayed Ca2+ reverberation, depending on the precise position of the spine ER. Upon spine growth, structural reorganization of the ER restores spine-to-dendrite Ca2+ communication, while maintaining aspects of Ca2+ homeostasis in the spine head. Our work emphasizes the relevance of precise positioning of RyR-containing spine ER in regulating the strength and timing of spine Ca2+ signaling, which could play an important role in tuning spine-to-dendrite Ca2+ communication and homeostasis.
Intraventricular Vortex Interaction between Transmitral Flow and Paravalvular Leak
Authors: Morisawa Daisuke , Falahatpisheh Ahmad , Avenatti Eleonora , Little Stephen H. , Kheradvar Arash 
Published: October 2018

AbstractParavalvular leak (PVL) is a complication of transcatheter aortic valve replacement. Despite its marked clinical impact, no previous study has reported how PVL affects the intraventricular fluid dynamics. This study aims to delineate vortex interaction between PVL and transmitral flow and the influence of PVL orifice location on intraventricular fluid dynamics using Echocardiographic Particle Image Velocimetry. Three different conditions of no PVL, anterior PVL and posterior PVL were experimentally studied and clinically compared. Circulation, impulse, kinetic energy (KE) and change in KE (ΔKE) were calculated. As well, vortex formation analyses and streamline description were performed to study vortex interactions. The anterior PVL jet streamed into the LV and interfered with the transmitral flow. Posterior PVL jet formed a large clockwise vortex and collided with transmitral flow, which resulted in flow disturbance. Compared to no PVL condition, average circulation, impulse, KE and ΔKE increased in presence of PVL. In conclusion, we found that PVL jets lead to abnormal vortex formation that interfere with natural advancement of transmitral flow, and negatively affect the LV fluid dynamics parameters. PVL orifice location strongly affects the intraventricular vortex formation, and posterior PVL may have more negative effects compared to anterior PVL.
Sensory attenuation in Parkinson’s disease is related to disease severity and dopamine dose
Authors: Wolpe Noham , Zhang Jiaxiang , Nombela Cristina , Ingram James N. , Wolpert Daniel M. ,   Cam-CAN, Tyler Lorraine K. , Brayne Carol , Bullmore Edward T. , Calder Andrew C. , Cusack Rhodri , Dalgleish Tim , Duncan John , Matthews Fiona E. , Marslen-Wilson William D. , Shafto Meredith A. , Cheung Teresa , Geerligs Linda , McCarrey Anna , Mustafa Abdur , Price Darren , Samu David , Treder Matthias , Tsvetanov Kamen A. , van Belle Janna , Williams Nitin , Bates Lauren , Gadie Andrew , Gerbase Sofia , Georgieva Stanimira , Hanley Claire , Parkin Beth , Troy David , Auer Tibor , Correia Marta , Gao Lu , Green Emma , Henriques Rafael , Allen Jodie , Amery Gillian , Amunts Liana , Barcroft Anne , Castle Amanda , Dias Cheryl , Dowrick Jonathan , Fair Melissa , Fisher Hayley , Goulding Anna , Grewal Adarsh , Hale Geoff , Hilton Andrew , Johnson Frances , Johnston Patricia , Kavanagh-Williamson Thea , Kwasniewska Magdalena , McMinn Alison , Norman Kim , Penrose Jessica , Roby Fiona , Rowland Diane , Sargeant John , Squire Maggie , Stevens Beth , Stoddart Aldabra , Stone Cheryl , Thompson Tracy , Yazlik Ozlem , Dan Barnes  , Dixon Marie , Hillman Jaya , Mitchell Joanne , Villis Laura , Rowe James B. 
Published: October 2018

AbstractAbnormal initiation and control of voluntary movements are among the principal manifestations of Parkinson’s disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, reflected in a ‘sensory attenuation’. We examined this integration process and its relation to dopamine in PD, by measuring sensory attenuation. Patients with idiopathic PD (n = 18) and population-derived controls (n = 175) matched a set of target forces applied to their left index finger by a torque motor. To match the force, participants either pressed with their right index finger (‘Direct’ condition) or moved a knob that controlled a motor through a linear potentiometer (‘Slider’ condition). We found that despite changes in sensitivity to different forces, overall sensory attenuation did not differ between medicated PD patients and controls. Importantly, the degree of attenuation was negatively related to PD motor severity but positively related to individual patient dopamine dose, as measured by levodopa dose equivalent. The results suggest that dopamine could regulate the integration of sensorimotor prediction with sensory information to facilitate the control of voluntary movements.
c-Fos induces chondrogenic tumor formation in immortalized human mesenchymal progenitor cells
Authors: Abarrategi Ander , Gambera Stefano , Alfranca Arantzazu , Rodriguez-Milla Miguel A. , Perez-Tavarez Raquel , Rouault-Pierre Kevin , Waclawiczek Alexander , Chakravarty Probir , Mulero Francisca , Trigueros César , Navarro Samuel , Bonnet Dominique , García-Castro Javier 
Published: October 2018

AbstractMesenchymal progenitor cells (MPCs) have been hypothesized as cells of origin for sarcomas, and c-Fos transcription factor has been showed to act as an oncogene in bone tumors. In this study, we show c-Fos is present in most sarcomas with chondral phenotype, while multiple other genes are related to c-Fos expression pattern. To further define the role of c-Fos in sarcomagenesis, we expressed it in primary human MPCs (hMPCs), immortalized hMPCs and transformed murine MPCs (mMPCs). In immortalized hMPCs, c-Fos expression generated morphological changes, reduced mobility capacity and impaired adipogenic- and osteogenic-differentiation potentials. Remarkably, immortalized hMPCs or mMPCs expressing c-Fos generated tumors harboring a chondrogenic phenotype and morphology. Thus, here we show that c-Fos protein has a key role in sarcomas and that c-Fos expression in immortalized MPCs yields cell transformation and chondrogenic tumor formation.
Detecting long-lived autodependency changes in a multivariate system via change point detection and regime switching models
Authors: Cabrieto Jedelyn , Adolf Janne , Tuerlinckx Francis , Kuppens Peter , Ceulemans Eva 
Published: October 2018

AbstractLong-lived simultaneous changes in the autodependency of dynamic system variables characterize crucial events as epileptic seizures and volcanic eruptions and are expected to precede psychiatric conditions. To understand and predict such phenomena, methods are needed that detect such changes in multivariate time series. We put forward two methods: First, we propose KCP-AR, a novel adaptation of the general-purpose KCP (Kernel Change Point) method. Whereas KCP is implemented on the raw data and does not shed light on which parameter changed, KCP-AR is applied to the running autocorrelations, allowing to focus on changes in this parameter. Second, we revisit the regime switching AR(1) approach and propose to fit models wherein only the parameters capturing autodependency differ across the regimes. We perform a simulation study comparing both methods: KCP-AR outperforms regime switching AR(1) when variables are uncorrelated, while the latter is more reliable when multicolinearity is severe. Regime switching AR(1), however, may yield recurrent switches even when the change is long-lived. We discuss an application to psychopathology data where we investigate whether emotional inertia -the autodependency of affective states- changes before a relapse into depression.
Effect of therapy on Quantiferon-Plus response in patients with active and latent tuberculosis infection
Authors: Petruccioli Elisa , Chiacchio Teresa , Vanini Valentina , Cuzzi Gilda , Codecasa Luigi Ruffo , Ferrarese Maurizio , Schininà Vincenzo , Palmieri Fabrizio , Ippolito Giuseppe , Goletti Delia 
Published: October 2018

AbstractLack of biomarkers for treatment monitoring is listed among the main requirements for next generation assays, as identified globally among tuberculosis (TB) researchers. In this study, we evaluated in a low TB endemic country such as Italy, the effect of preventive therapy on the results obtained in the QuantiFERON TB Plus (QFT-Plus), in a cohort of subjects with latent TB infection (LTBI) and active TB. We found that TB therapy significantly decreased IFN-γ values and number of responders to TB1- and TB2- peptides stimulation in both LTBI and active TB patients. Stratifying LTBI subjects according to the type of preventive TB therapy used, we found that INH treatment but not INH and RIF significantly decreased IFN-γ production. Stratifying the active TB patients according the microbiological status, we found that TB therapy significantly decreased IFN-γ response to antigen present in QFT-Plus test in patients with clinical diagnosis compared to those with a microbiological diagnosis. In conclusions, we demonstrated that TB therapy decreases IFN-γ level in response to antigen present in QFT-Plus test in LTBI and active TB patients. Future studies are needed to better characterize Mtb-specifc response as a potential marker for monitoring TB therapy and preventive treatment effects.