bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peripheral Blood Mononuclear Cell Oxytocin and Vasopressin Receptor Expression Positively Correlates with Social and Behavioral Function in Children with Autism
Authors: Voinsky Irena , Bennuri Sirish C. , Svigals Julie , Frye Richard E. , Rose Shannon , Gurwitz David 
Published: September 2019

AbstractThe peptide hormone oxytocin is an established regulator of social function in mammals, and dysregulated oxytocin signaling is implicated in autism spectrum disorder (ASD). Several clinical trials examining the effects of intranasal oxytocin for improving social and behavioral function in ASD have had mixed or inclusive outcomes. The heterogeneity in clinical trials outcomes may reflect large inter-individual expression variations of the oxytocin and/or vasopressin receptor genes OXTR and AVPR1A, respectively. To explore this hypothesis we examined the expression of both genes in peripheral blood mononuclear cells (PBMC) from ASD children, their non-ASD siblings, and age-matched neurotypical children aged 3 to 16 years of age as well as datamined published ASD datasets. Both genes were found to have large inter-individual variations. Higher OXTR and AVPR1A expression was associated with lower Aberrant Behavior Checklist (ABC) scores. OXTR expression was associated with less severe behavior and higher adaptive behavior on additional standardized measures. Combining the sum expression levels OXTR, AVPR1A, and IGF1 yielded the strongest correlation with ABC scores. We propose that future clinical trials in ASD children with oxytocin, oxytocin mimetics and additional tentative therapeutics should assess the prognostic value of their PBMC mRNA expression of OXTR, AVPR1A, and IGF1.
A Cortico- Basal Ganglia Model for choosing an optimal rehabilitation strategy in Hemiparetic Stroke
Authors: Narayanamurthy Rukhmani , Jayakumar Samyukta , Elango Sundari , Muralidharan Vignesh , Chakravarthy V. Srinivasa 
Published: September 2019

AbstractTo facilitate the selection of an optimal therapy for a stroke patient with upper extremity hemiparesis, we propose a cortico-basal ganglia model capable of performing reaching tasks under normal and stroke conditions. The model contains two hemispherical systems, each organized into an outer sensory-motor cortical loop and an inner basal ganglia (BG) loop, controlling their respective hands. The model is trained to simulate two therapeutic approaches: the constraint induced movement therapy (CIMT) in which the intact is arrested, and Bimanual Reaching in which the movements of the intact arm are found to aid the affected arm. Which of these apparently mutually conflicting approaches is right for a given patient? Based on our study on the effect of lesion size on arm performance, we hypothesize that the choice of the therapy depends on the lesion size. Whereas bimanual reaching is more suitable for smaller lesion size, CIMT is preferred in case of larger lesion sizes. By virtue of the model’s ability to capture the experimental results effectively, we believe that it can serve as a benchmark for the development and testing of various rehabilitation strategies for stroke.
Subsurface diffusion in crystals and effect of surface permeability on the atomic step motion
Authors: Kosolobov Sergey 
Published: September 2019

AbstractA new theoretical approach to characterize the diffusion of both surface and bulk point defects in crystals is presented. In our model, atomic steps are considered as sources and sinks not only for adatoms and advacancies but also for self-interstitials and bulk vacancies, providing a new mechanism for bulk point defect generation and annihilation. It is shown that the creation and annihilation of self-interstitials and vacancies occur at atomic steps and can be described by introducing a diffusive layer of the bulk point defects adsorbed just below the surface. The atomic step rate of advance is studied taking into account finite permeability of the surface for bulk and surface point defects. The surface permeability results in the appearance of the dependence of the total step rate of advance not only on the supersaturation in vapor phase but also on the supersaturation of point defects in the bulk.
Multifractal and entropy analysis of resting-state electroencephalography reveals spatial organization in local dynamic functional connectivity
Authors: Racz Frigyes Samuel , Stylianou Orestis , Mukli Peter , Eke Andras 
Published: September 2019

AbstractFunctional connectivity of the brain fluctuates even in resting-state condition. It has been reported recently that fluctuations of global functional network topology and those of individual connections between brain regions expressed multifractal scaling. To expand on these findings, in this study we investigated if multifractality was indeed an inherent property of dynamic functional connectivity (DFC) on the regional level as well. Furthermore, we explored if local DFC showed region-specific differences in its multifractal and entropy-related features. DFC analyses were performed on 62-channel, resting-state electroencephalography recordings of twelve young, healthy subjects. Surrogate data testing verified the true multifractal nature of regional DFC that could be attributed to the presumed nonlinear nature of the underlying processes. Moreover, we found a characteristic spatial distribution of local connectivity dynamics, in that frontal and occipital regions showed stronger long-range correlation and higher degree of multifractality, whereas the highest values of entropy were found over the central and temporal regions. The revealed topology reflected well the underlying resting-state network organization of the brain. The presented results and the proposed analysis framework could improve our understanding on how resting-state brain activity is spatio-temporally organized and may provide potential biomarkers for future clinical research.
Entanglement in a 20-Qubit Superconducting Quantum Computer
Authors: Mooney Gary J. , Hill Charles D. , Hollenberg Lloyd C. L. 
Published: September 2019

AbstractThe ability to prepare sizeable multi-qubit entangled states with full qubit control is a critical milestone for physical platforms upon which quantum computers are built. We investigate the extent to which entanglement is found within a prepared graph state on the 20-qubit superconducting quantum computer IBM Q Poughkeepsie. We prepared a graph state along a path consisting of all twenty qubits within the device and performed full quantum state tomography on all groups of four connected qubits along this path. We determined that each pair of connected qubits was inseparable and hence the prepared state was entangled. Additionally, a genuine multipartite entanglement witness was measured on all qubit subpaths of the graph state and we found genuine multipartite entanglement on chains of up to three qubits. These results represent a demonstration of entanglement in one of the largest solid-state qubit arrays to date and indicate the positive direction of progress towards the goal of implementing complex quantum algorithms relying on such effects.
A Functional Near-Infrared Spectroscopy Study on the Cortical Haemodynamic Responses During the Maastricht Acute Stress Test
Authors: Schaal N. K. , Hepp P. , Schweda A. , Wolf O. T. , Krampe C. 
Published: September 2019

AbstractIn order to better understand stress responses, neuroimaging studies have investigated the underlying neural correlates of stress. Amongst other brain regions, they highlight the involvement of the prefrontal cortex. The aim of the present study was to explore haemodynamic changes in the prefrontal cortex during the Maastricht Acute Stress Test (MAST) using mobile functional Near-Infrared Spectroscopy (fNIRS), examining the stress response in an ecological environment. The MAST includes a challenging mental arithmic task and a physically stressful ice-water task. In a between-subject design, participants either performed the MAST or a non-stress control condition. FNIRS data were recorded throughout the test. Additionally, subjective stress ratings, heart rate and salivary cortisol were evaluated, confirming a successful stress induction. The fNIRS data indicated significantly increased neural activity of brain regions of the dorsolateral prefrontal cortex (dlPFC) and the orbitofrontal cortex (OFC) in response to the MAST, compared to the control condition. Furthermore, the mental arithmetic task indicated an increase in neural activity in brain regions of the dlPFC and OFC; whereas the physically stressful hand immersion task indicated a lateral decrease of neural activity in the left dlPFC. The study highlights the potential use of mobile fNIRS in clinical and applied (stress) research.
Switching of Skyrmion chirality by local heating
Authors: Nakatani Yoshinobu , Yamada Keisuke , Hirohata Atsufumi 
Published: September 2019

AbstractMagnetic Skyrmions are energetically stable entities formed in a ferromagnet with a diameter of typically below 100 nm and are easily displaceable using an electrical current of 102 A/cm2, resulting the Skyrmions to be more advantageous than domain walls for spintronic memory applications. Here, we demonstrated switching of a chirality of magnetic Skyrmions formed in magnetic thin films by introducing a pulsed heat spot using micromagnetic simulation. Skyrmions are found to expand with a pulsed heat spot, which induces the magnetic moments surrounding the Skyrmion to rotate by this expansion, followed by the chirality switching of the Skyrmion. Such simple controllability can be used as a fundamental building block for memory and logic devices using the chirality of Skyrmions as a data bit.
Tumor Infiltrating Lymphocytes and Macrophages Improve Survival in Microsatellite Unstable Colorectal Cancer
Authors: Narayanan Sumana , Kawaguchi Tsutomu , Peng Xuan , Qi Qianya , Liu Song , Yan Li , Takabe Kazuaki 
Published: September 2019

AbstractDue to the loss of DNA repair mechanisms in colorectal cancer (CRC) with microsatellite instability (MSI), somatic mutations accumulate within DNA; making them more prone to attack by tumor infiltrating lymphocytes (TIL) and macrophages. We hypothesize that MSI-High (MSI-H) patients have favorable survival due to increased tumor immunogenicity. The Cancer Genome Atlas (TCGA) was used to evaluate gene expression from 283 patients with CRC, comparing MSI-H and microsatellite stable (MSS) patients. CIBERSORT algorithm estimated the fraction of immune cell types. We found that low expression of DNA repair genes (MLH1, MLH3, PMS1, PMS2, ATR, PRKDC, ATM, BRCA2) associated with MSI-H. MSI-H was directly associated with Helper T-cells (p = 0.034) and M1 macrophages (p < 0.0001). MSI-H tumors associated with diminished intra-tumoral heterogeneity as well as higher expression of checkpoint molecules PD-1, PD-L1, CTLA4, LAG3 and TIM3 (p < 0.0001). Improved OS was seen in patients with low ATM, PMS2 and MLH3. In the TCGA CRC cohort, decreased expression of DNA repair genes associated with MSI-H. MSI-H patients had improved survival, likely due to higher TIL and M1 macrophage infiltration as well as lower intra-tumoral heterogeneity. MSI-H also associates with expression of immune checkpoint molecules with potential for development of therapeutic targets.
The polymorphic variant rs1800734 influences methylation acquisition and allele-specific TFAP4 binding in the MLH1 promoter leading to differential mRNA expression
Authors: Thomas Rachael , Trapani Davide , Goodyer-Sait Lily , Tomkova Marketa , Fernandez-Rozadilla Ceres , Sahnane Nora , Woolley Connor , Davis Hayley , Chegwidden Laura , Kriaucionis Skirmantas , Maughan Timothy , Leedham Simon , Palles Claire , Furlan Daniela , Tomlinson Ian , Lewis Annabelle 
Published: September 2019

AbstractExpression of the mismatch repair gene MutL homolog 1 (MLH1) is silenced in a clinically important subgroup of sporadic colorectal cancers. These cancers exhibit hypermutability with microsatellite instability (MSI) and differ from microsatellite-stable (MSS) colorectal cancers in both prognosis and response to therapies. Loss of MLH1 is usually due to epigenetic silencing with associated promoter methylation; coding somatic mutations rarely occur. Here we use the presence of a colorectal cancer (CRC) risk variant (rs1800734) within the MLH1 promoter to investigate the poorly understood mechanisms of MLH1 promoter methylation and loss of expression. We confirm the association of rs1800734 with MSI+ but not MSS cancer risk in our own data and by meta-analysis. Using sensitive allele-specific detection methods, we demonstrate that MLH1 is the target gene for rs1800734 mediated cancer risk. In normal colon tissue, small allele-specific differences exist only in MLH1 promoter methylation, but not gene expression. In contrast, allele-specific differences in both MLH1 methylation and expression are present in MSI+ cancers. We show that MLH1 transcriptional repression is dependent on DNA methylation and can be reversed by a methylation inhibitor. The rs1800734 allele influences the rate of methylation loss and amount of re-expression. The transcription factor TFAP4 binds to the rs1800734 region but with much weaker binding to the risk than the protective allele. TFAP4 binding is absent on both alleles when promoter methylation is present. Thus we propose that TFAP4 binding shields the protective rs1800734 allele of the MLH1 promoter from BRAF induced DNA methylation more effectively than the risk allele.
Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen
Authors: Milcent B. , Josseaume N. , Petitprez F. , Riller Q. , Amorim S. , Loiseau P. , Toubert A. , Brice P. , Thieblemont C. , Teillaud J.-L. , Sibéril S. 
Published: September 2019

AbstractPreclinical models and clinical studies have shown that anti-CD20-based treatment has multifaceted consequences on T-cell immunity. We have performed a prospective study of peripheral T-cell compartment in FL patients, all exhibiting high tumor burden and receiving rituximab-chemotherapy-based regimen (R-CHOP). Before treatment, FL patients harbor low amounts of peripheral naive T cells, but high levels of CD4+ TEM, CD4+ Treg and CD8+ TEMRA subsets and significant amounts of CD38+ HLA-DR+ activated T cells. A portion of these activated/differentiated T cells also expressed PD-1 and/or TIGIT immune checkpoints. Hierarchical clustering of phenotyping data revealed that 5/8 patients with only a partial response to R-CHOP induction therapy or with disease progression segregate into a group exhibiting a highly activated/differentiated T cell profile and a markedly low proportion of naive T cells before treatment. Rituximab-based therapy induced a shift of CD4+ and CD8+ T cells toward a central memory phenotype and of CD8+ T cells to a naive phenotype. In parallel, a decrease in the number of peripheral T cells expressing both PD-1 and TIGIT was detected. These observations suggest that the standard rituximab-based therapy partially reverts the profound alterations observed in T-cell subsets in FL patients, and that blood T-cell phenotyping could provide a better understanding of the mechanisms of rituximab-based treatment.
Bright split red fluorescent proteins for the visualization of endogenous proteins and synapses
Authors: Feng Siyu , Varshney Aruna , Coto Villa Doris , Modavi Cyrus , Kohler John , Farah Fatima , Zhou Shuqin , Ali Nebat , Müller Joachim D. , Van Hoven Miri K. , Huang Bo 
Published: September 2019

AbstractSelf-associating split fluorescent proteins (FPs) are split FPs whose two fragments spontaneously associate to form a functional FP. They have been widely used for labeling proteins, scaffolding protein assembly and detecting cell-cell contacts. Recently developments have expanded the palette of self-associating split FPs beyond the original split GFP1-10/11. However, these new ones have suffered from suboptimal fluorescence signal after complementation. Here, by investigating the complementation process, we have demonstrated two approaches to improve split FPs: assistance through SpyTag/SpyCatcher interaction and directed evolution. The latter has yielded two split sfCherry3 variants with substantially enhanced overall brightness, facilitating the tagging of endogenous proteins by gene editing. Based on sfCherry3, we have further developed a new red-colored trans-synaptic marker called Neuroligin-1 sfCherry3 Linker Across Synaptic Partners (NLG-1 CLASP) for multiplexed visualization of neuronal synapses in living C. elegans, demonstrating its broad applications.
Dynamically tuned non-classical light emission from atomic defects in hexagonal boron nitride
Authors: Lazić Snežana , Espinha André , Pinilla Yanguas Sergio , Gibaja Carlos , Zamora Félix , Ares Pablo , Chhowalla Manish , Paz Wendel S. , Burgos Juan José Palacios , Hernández-Mínguez Alberto , Santos Paulo V. , van der Meulen Herko P. 
Published: September 2019

AbstractLuminescent defects in hexagonal boron nitride (h-BN) have recently emerged as a promising platform for non-classical light emission. On-chip solutions, however, require techniques for controllable in-situ manipulation of quantum light. Here, we demonstrate the dynamic spectral and temporal tuning of the optical emission from h-BN via moving acousto-mechanical modulation induced by stimulated phonons. When perturbed by the propagating acoustic phonon, the optically probed radiative h-BN defects are periodically strained and their sharp emission lines are modulated by the deformation potential coupling. This results in an acoustically driven spectral tuning within a 2.5-meV bandwidth. Our findings, supported by first-principles theoretical calculations, reveal exceptionally high elasto-optic coupling in h-BN of ~50 meV/%. Temporal control of the emitted photons is achieved by combining the acoustically mediated fine-spectral tuning with spectral detection filtering. This study opens the door to the use of sound for scalable integration of h-BN emitters in nanophotonic and quantum information technologies.
Kinetic analysis of the accumulation of a half-sandwich organo-osmium pro-drug in cancer cells
Authors: Ballesta Annabelle , Billy Frédérique , Coverdale James P C , Song Ji-Inn , Sanchez-Cano Carlos , Romero-Canelón Isolda , Sadler Peter J 
Published: September 2019

Abstract
The organo-osmium half-sandwich complex [(η6-p-cymene)Os(Ph-azopyridine-NMe2)I]+ (FY26) exhibits potent antiproliferative activity towards cancer cells and is active in vivo. The complex is relatively inert, but rapidly activated in cells by displacement of coordinated iodide. Here, we study time-dependent accumulation of FY26 in A2780 human ovarian cancer cells at various temperatures in comparison with the chlorido metabolite [(η6-p-cymene)Os(Ph-azopyridine-NMe2)Cl]+ (FY25). Mathematical models described the time evolution of FY26 and FY25 intracellular and extracellular concentrations taking into account both cellular transport (influx and efflux) and the intracellular conversion of FY26 to FY25. Uptake of iodide complex FY26 at 37 °C was 17× faster than that of chloride complex FY25, and efflux 1.4× faster. Osmium accumulation decreased markedly after 24 h of exposure. Modelling revealed that this phenomenon could be explained by complex-induced reduction of osmium uptake, rather than by a model involving enhanced osmium efflux. The intracellular osmium concentration threshold above which reduction in drug uptake was triggered was estimated as 20.8 μM (95% confidence interval [16.5, 30]). These studies provide important new insight into the dynamics of transport of this organometallic anticancer drug candidate.
Folate deficiency promotes differentiation of vascular smooth muscle cells without affecting the methylation status of regulated genes
Authors: Kolb Andreas F. , Petrie Linda , Mayer Claus D. , Pirie Lynn , Duthie Susan J. 
Published: September 2019

Abstract
Elevated serum homocysteine, an intermediate of cellular one-carbon metabolism, is an independent risk factor for cardiovascular disease (CVD). Folate deficiency increases serum homocysteine and may contribute to CVD progression. Vascular smooth muscle cells (VSMCs) regulate vascular contractility, but also contribute to repair processes in response to vascular injury. Nutritional deficiencies, like folate deficiency, are thought to impact on this phenotypic plasticity, possibly by epigenetic mechanisms. We have investigated the effect of folate deficiency on VSMCs in two cell culture systems representing early and late stages of smooth muscle cells differentiation. We find that folate deficiency promotes differentiation towards a more contractile phenotype as indicated by increased expression of respective marker genes. However, microarray analysis identified markers of striated muscle as the predominant gene expression change elicited by folate deficiency. These changes are not merely a reflection of cell cycle arrest, as foetal calf serum restriction or iron deficiency do not replicate the gene expression changes observed in response to folate deficiency. Folate deficiency only has a marginal effect on global DNA methylation. DNA methylation of CpG islands associated with genes regulated by folate deficiency remains unaffected. This supports our earlier findings in a mouse model system which also did not show any changes in global DNA methylation in response to folate and vitamin B6/B12 deficiency. These data suggest that folate deficiency enhances the expression of smooth muscle marker gene expression, promotes a shift towards a skeletal muscle phenotype, and does not regulate gene expression via DNA methylation.
Selective degradation of plasmid-derived mRNAs by MCPIP1 RNase
Authors: Qian Yisong , Li Xiuzhen , Miao Ruidong , Liu Shufeng , Xin Hong-Bo , Huang Xiaotian , Wang Tony T. , Fu Mingui 
Published: September 2019

Abstract
Detection and degradation of foreign nucleic acids is an ancient form of host defense. However, the underlying mechanisms are not completely clear. MCPIP1 is an endoribonuclease and an important regulator in both innate and adaptive immunity by targeting inflammatory mRNA degradation. Here we report that MCPIP1 RNase can also selectively detect and degrade the mRNAs encoded by transfected plasmids. In transient transfection, MCPIP1 expression potently degraded the mRNA from exogenously transfected vectors, which is independent on the vector, genes and cell types used. Conversely, the expression of transfected plasmids in MCPIP1-null cells is significantly higher than that in wild-type cells. Interestingly, overexpression of MCPIP1 or MCPIP1 deficiency does not affect the expression of the exogenous genes incorporated into the host genome in a stable cell line or the global gene expression of host genome. This ability is not associated with PKR/RNase L system, as PKR inhibitors does not block MCPIP1-mediated mRNA degradation of exogenously transfected genes. Lastly, expression of MCPIP1 suppressed replication of Zika virus in infected cells. The study may provide a model for understanding the antiviral mechanisms of MCPIP1, and a putative tool to increase the expression of transfected exogenous genes.