bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phospho-ablation of cardiac sodium channel Nav1.5 mitigates susceptibility to atrial fibrillation and improves glucose homeostasis under conditions of diet-induced obesity
Authors: Dewal Revati S. , Greer-Short Amara , Lane Cemantha , Nirengi Shinsuke , Manzano Pedro Acosta , Hernández-Saavedra Diego , Wright Katherine R. , Nassal Drew , Baer Lisa A. , Mohler Peter J. , Hund Thomas J. , Stanford Kristin I. 
Published: January 2021

Abstract
Background
Atrial fibrillation (AF) is the most common sustained arrhythmia, with growing evidence identifying obesity as an important risk factor for the development of AF. Although defective atrial myocyte excitability due to stress-induced remodeling of ion channels is commonly observed in the setting of AF, little is known about the mechanistic link between obesity and AF. Recent studies have identified increased cardiac late sodium current (INa,L) downstream of calmodulin-dependent kinase II (CaMKII) activation as an important driver of AF susceptibility.

Methods
Here, we investigated a possible role for CaMKII-dependent INa,L in obesity-induced AF using wild-type (WT) and whole-body knock-in mice that ablates phosphorylation of the Nav1.5 sodium channel and prevents augmentation of the late sodium current (S571A; SA mice).

Results
A high-fat diet (HFD) increased susceptibility to arrhythmias in WT mice, while SA mice were protected from this effect. Unexpectedly, SA mice had improved glucose homeostasis and decreased body weight compared to WT mice. However, SA mice also had reduced food consumption compared to WT mice. Controlling for food consumption through pair feeding of WT and SA mice abrogated differences in weight gain and AF inducibility, but not atrial fibrosis, premature atrial contractions or metabolic capacity.

Conclusions
These data demonstrate a novel role for CaMKII-dependent regulation of Nav1.5 in mediating susceptibility to arrhythmias and whole-body metabolism under conditions of diet-induced obesity.
Strong internal resonance in a nonlinear, asymmetric microbeam resonator
Authors: Asadi Keivan , Yeom Junghoon , Cho Hanna 
Published: January 2021

AbstractExploiting nonlinear characteristics in micro/nanosystems has been a subject of increasing interest in the last decade. Among others, vigorous intermodal coupling through internal resonance (IR) has drawn much attention because it can suggest new strategies to steer energy within a micro/nanomechanical resonator. However, a challenge in utilizing IR in practical applications is imposing the required frequency commensurability between vibrational modes of a nonlinear micro/nanoresonator. Here, we experimentally and analytically investigate the 1:2 and 2:1 IR in a clamped–clamped beam resonator to provide insights into the detailed mechanism of IR. It is demonstrated that the intermodal coupling between the second and third flexural modes in an asymmetric structure (e.g., nonprismatic beam) provides an optimal condition to easily implement a strong IR with high energy transfer to the internally resonated mode. In this case, the quadratic coupling between these flexural modes, originating from the stretching effect, is the dominant nonlinear mechanism over other types of geometric nonlinearity. The design strategies proposed in this paper can be integrated into a typical micro/nanoelectromechanical system (M/NEMS) via a simple modification of the geometric parameters of resonators, and thus, we expect this study to stimulate further research and boost paradigm-shifting applications exploring the various benefits of IR in micro/nanosystems.
Replicable association between human cytomegalovirus infection and reduced white matter fractional anisotropy in major depressive disorder
Authors: Zheng Haixia , Bergamino Maurizio , Ford Bart N. , Kuplicki Rayus , Yeh Fang-Cheng , Bodurka Jerzy , Burrows Kaiping ,   Tulsa 1000 Investigators, Aupperle Robin , Bodurka Jerzy , Feinstein Justin , Khalsa Sahib S. , Paulus Martin P. , Savitz Jonathan , Victor Teresa A. , Hunt Peter W. , Teague T. Kent , Irwin Michael R. , Yolken Robert H. , Paulus Martin P. , Savitz Jonathan 
Published: January 2021

AbstractMajor depressive disorder (MDD) is associated with reductions in white matter microstructural integrity as measured by fractional anisotropy (FA), an index derived from diffusion tensor imaging (DTI). The neurotropic herpesvirus, human cytomegalovirus (HCMV), is a major cause of white matter pathology in immunosuppressed populations but its relationship with FA has never been tested in MDD despite the presence of inflammation and weakened antiviral immunity in a subset of depressed patients. We tested the relationship between FA and HCMV infection in two independent samples consisting of 176 individuals with MDD and 44 healthy controls (HC) (Discovery sample) and 88 participants with MDD and 48 HCs (Replication sample). Equal numbers of HCMV positive (HCMV+) and HCMV negative (HCMV−) groups within each sample were balanced on ten different clinical/demographic variables using propensity score matching. Anti-HCMV IgG antibodies were measured using a solid-phase ELISA. In the Discovery sample, significantly lower FA was observed in the right inferior fronto-occipital fasciculus (IFOF) in HCMV+ participants with MDD compared to HCMV− participants with MDD (cluster size 1316 mm3;pFWE < 0.05,d = −0.58). This association was confirmed in the replication sample by extracting the mean FA from this exact cluster and applying the identical statistical model (p < 0.05,d = −0.45). There was no significant effect of diagnosis or interaction between diagnosis and HCMV in either sample. The effect of chronic HCMV infection on white matter integrity may—in at-risk individuals—contribute to the psychopathology of depression. These findings may provide a novel target of intervention for a subgroup of patients with MDD.
MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis
Authors: Fan Huijie , Yuan Jing , Li Yaqing , Jia Yongxu , Li Jing , Wang Xiaofeng , Li Xingya 
Published: January 2021

AbstractMegakaryocytic leukemia 1 (MKL1) is a key transcription factor involved in non-small cell lung cancer (NSCLC) growth and metastasis. Yet, its downstream target genes, especially long non-coding RNA (lncRNA) targets, are poorly investigated. In this study, we employed lncRNA array technology to identify differentially expressed lncRNAs in NSCLC cells with or without overexpression of MKL1. Candidate lncRNAs were further explored for their clinical significance and function in NSCLC. The results showed that MKL1 promoted the expression of lncRNA SNHG18 in NSCLC cells. SNHG18 upregulation in NSCLC specimens correlated with lymph node metastasis and reduced overall survival of NSCLC patients. SNHG18 expression served as an independent prognostic factor for NSCLC. Knockdown of SNHG18 blocked MKL1-induced growth and invasion of NSCLC cells in vitro. Animal studies validated the requirement for SNHG18 in NSCLC growth and metastasis. Moreover, overexpression of SNHG18 promoted NSCLC cell proliferation and invasion. Mechanically, SNHG18 exerted its prometastatic effects on NSCLC cells through repression of miR-211-5p and induction of BRD4. Clinical evidence indicated that SNHG18 expression was negatively correlated with miR-211-5p expression in NSCLC tissues. Altogether, SNHG18 acts as a lncRNA mediator of MKL1 in NSCLC. SNHG18 facilitates NSCLC growth and metastasis by modulating the miR-211-5p/BRD4 axis. Therefore, SNHG18 may be a potential therapeutic target for the treatment of NSCLC.
The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks
Authors: Shorrocks Ann-Marie K. , Jones Samuel E. , Tsukada Kaima , Morrow Carl A. , Belblidia Zoulikha , Shen Johanna , Vendrell Iolanda , Fischer Roman , Kessler Benedikt M. , Blackford Andrew N. 
Published: January 2021

AbstractThe Bloom syndrome helicase BLM interacts with topoisomerase IIIα (TOP3A), RMI1 and RMI2 to form the BTR complex, which dissolves double Holliday junctions to produce non-crossover homologous recombination (HR) products. BLM also promotes DNA-end resection, restart of stalled replication forks, and processing of ultra-fine DNA bridges in mitosis. How these activities of the BTR complex are regulated in cells is still unclear. Here, we identify multiple conserved motifs within the BTR complex that interact cooperatively with the single-stranded DNA (ssDNA)-binding protein RPA. Furthermore, we demonstrate that RPA-binding is required for stable BLM recruitment to sites of DNA replication stress and for fork restart, but not for its roles in HR or mitosis. Our findings suggest a model in which the BTR complex contains the intrinsic ability to sense levels of RPA-ssDNA at replication forks, which controls BLM recruitment and activation in response to replication stress.
A new vector-based global river network dataset accounting for variable drainage density
Authors: Lin Peirong , Pan Ming , Wood Eric F. , Yamazaki Dai , Allen George H. 
Published: January 2021

AbstractSpatial variability of river network drainage density (Dd) is a key feature of river systems, yet few existing global hydrography datasets have properly accounted for it. Here, we present a new vector-based global hydrography that reasonably estimates the spatial variability ofDdworldwide. It is built by delineating channels from the latest 90-m Multi-Error-Removed Improved Terrain (MERIT) digital elevation model and flow direction/accumulation. A machine learning approach is developed to estimateDdbased on the global watershed-level climatic, topographic, hydrologic, and geologic conditions, where relationships between hydroclimate factors andDdare trained using the high-quality National Hydrography Dataset Plus (NHDPlusV2) data. By benchmarking our dataset against HydroSHEDS and several regional hydrography datasets, we show the new river flowlines are in much better agreement with Landsat-derived centerlines, and improvedDdpatterns of river networks (totaling ~75 million kilometers in length) are obtained. Basins and estimates of intermittent stream fraction are also delineated to support water resources management. This new dataset (MERIT Hydro–Vector) should enable full global modeling of river system processes at fine spatial resolutions.
Sensitivity to food and cocaine cues are independent traits in a large sample of heterogeneous stock rats
Authors: King Christopher P. , Tripi Jordan A. , Hughson Alesa R. , Horvath Aidan P. , Lamparelli Alexander C. , Holl Katie L. , Chitre Apurva S. , Polesskaya Oksana , Ishiwari Keita , Solberg Woods Leah C. , Palmer Abraham A. , Robinson Terry E. , Flagel Shelly B. , Meyer Paul J. 
Published: January 2021

AbstractSensitivity to cocaine and its associated stimuli (“cues”) are important factors in the development and maintenance of addiction. Rodent studies suggest that this sensitivity is related, in part, to the propensity to attribute incentive salience to food cues, which, in turn, contributes to the maintenance of cocaine self-administration, and cue-induced relapse of drug-seeking. Whereas each of these traits has established links to drug use, the relatedness between the individual traits themselves has not been well characterized in preclinical models. To this end, the propensity to attribute incentive salience to a food cue was first assessed in two distinct cohorts of 2716 outbred heterogeneous stock rats (HS; formerly N:NIH). We then determined whether each cohort was associated with performance in one of two paradigms (cocaine conditioned cue preference and cocaine contextual conditioning). These measure the unconditioned locomotor effects of cocaine, as well as conditioned approach and the locomotor response to a cocaine-paired floor or context. There was large individual variability and sex differences among all traits, but they were largely independent of one another in both males and females. These findings suggest that these traits may contribute to drug-use via independent underlying neuropsychological processes.
Measurement of hindered diffusion in complex geometries for high-speed studies of single-molecule forces
Authors: Bartsch Tobias F. , Villasante Camila M. , Hengel Felicitas E. , Touré Ahmed , Firester Daniel M. , Oswald Aaron , Hudspeth A. J. 
Published: January 2021

AbstractIn a high-speed single-molecule experiment with a force probe, a protein is tethered between two substrates that are manipulated to exert force on the system. To avoid nonspecific interactions between the protein and nearby substrates, the protein is usually attached to the substrates through long, flexible linkers. This approach precludes measurements of mechanical properties with high spatial and temporal resolution, for rapidly exerted forces are dissipated into the linkers. Because mammalian hearing operates at frequencies reaching tens to hundreds of kilohertz, the mechanical processes that occur during transduction are of very short duration. Single-molecule experiments on the relevant proteins therefore cannot involve long tethers. We previously characterized the mechanical properties of protocadherin 15 (PCDH15), a protein essential for human hearing, by tethering an individual monomer through very short linkers between a probe bead held in an optical trap and a pedestal bead immobilized on a glass coverslip. Because the two confining surfaces were separated by only the length of the tethered protein, hydrodynamic coupling between those surfaces complicated the interpretation of the data. To facilitate our experiments, we characterize here the anisotropic and position-dependent diffusion coefficient of a probe in the presence of an effectively infinite wall, the coverslip, and of the immobile pedestal.
Metal artefact reduction of different alloys with dual energy computed tomography (DECT)
Authors: Vellarackal Anand John , Kaim Achim Hermann 
Published: January 2021

AbstractTo evaluate the influence of dual-energy CT (DECT) and Virtual monochromatic spectral (VMS) imaging on: (1) the artefact size of geometrically identical orthopaedic implants consisting of three different compositions and (2) the image quality of the surrounding bone, three similar phantoms—each featuring one femoral stem composed of either titanium, chrome-cobalt or stainless steel surrounded by five calcium pellets (200 mg hydroxyapatite/calcium carbonate) to simulate bony tissue and one reference pellet located away from the femoral stem—were built. DECT with two sequential scans (80 kVp and 140 kVp; scan-to-scan technique) was performed, and VMS images were calculated between 40 and 190 keV. The artefact sizes were measured volumetrically by semiautomatic selection of regions of interest (ROIs), considering the VMS energies and the polychromatic spectres. Moreover, density and image noise within the pellets were measured. All three phantoms exhibit artefact size reduction as energy increases from 40 to 190 keV. Titanium exhibited a stronger reduction than chrome-cobalt and stainless steel. The artefacts were dependent on the diameter of the stem. Image quality increases with higher energies on VMS with a better depiction of surrounding structures. Monoenergetic energies 70 keV and 140 keV demonstrate superior image quality to those produced by spectral energies 80 kVp and 140 kVp.
Array of stacked leaky-wave antennas in groove gap waveguide technology
Authors: Memeletzoglou Nafsika , Rajo-Iglesias Eva 
Published: January 2021

AbstractThe design of an array of stacked leaky-wave antennas in groove gap waveguide technology is presented in this work. The proposed array is formed by simply stacking a number of leaky-wave antennas one on top of the other and feeding all of them with uniform amplitude and phase. The inter-element distance is studied in order to avoid grating lobes and to maximize the directivity. A feeding network based on vertical coupling is designed, where the input port feeds the bottom element, and then the energy is equally coupled to the other elements. To obtain maximum directivity the phase is corrected at each element separately. The central frequency of the proposed design is 28 GHz. With this technique of stacking the elements a pencil beam is achieved, i.e. the radiated energy is focalized in the two main planes. The designed array with four elements achieves an enhancement of + 5 dB, reaching 24.5 dBi of directivity in comparison to 19.6 dBi of directivity of the single leaky-wave antenna made in this technology. A prototype is manufactured and measured and its results are presented and compared with the simulations.
Nanoscale ordering of planar octupolar molecules for nonlinear optics at higher temperatures
Authors: Jarema Michał , Mituś Antoni C. , Zyss Joseph 
Published: January 2021

AbstractWe develop scenarios for orientational ordering of an in-plane system of small flat octupolar molecules at the low-concentration limit, aiming towards nonlinear-optical (NLO) applications at room temperatures. The octupoles interact with external electric poling fields and intermolecular interactions are neglected. Simple statistical-mechanics models are used to analyze the orientational order in the very weak poling limit, sufficient for retrieving the NLO signals owing to the high sensitivity of NLO detectors and measurement chains. Two scenarios are discussed. Firstly, the octupolar poling field is imparted by a system of point charges; the setup is subject to cell-related constraints imposed by mechanical strength and dielectric breakdown limit. The very weak octupolar order of benchmarking TATB molecules is shown to emerge at Helium temperatures. The second scenario addresses the dipoling of octupolar molecules with a small admixture of electric dipolar component. It requires a strong field regime to become effective at Nitrogen temperature range. An estimation of the nonlinear susceptibility coefficient matrix for both scenarios is done in the high-temperature (weak interaction) limit formalism. We argue that moderate modifications of the system like, e.g., an increase of the size of the octupole, accompanied by dipole-assisted octupoling, can increase the poling temperature above Nitrogen temperatures.
Recycling silver nanoparticle debris from laser ablation of silver nanowire in liquid media toward minimum material waste
Authors: Hwang June Sik , Park Jong-Eun , Kim Gun Woo , Nam Hyeono , Yu Sangseok , Jeon Jessie S. , Kim Sanha , Lee Huseung , Yang Minyang 
Published: January 2021

AbstractAs silver nanowires (Ag NWs) are usually manufactured by chemical synthesis, a patterning process is needed to use them as functional devices. Pulsed laser ablation is a promising Ag NW patterning process because it is a simple and inexpensive procedure. However, this process has a disadvantage in that target materials are wasted owing to the subtractive nature of the process involving the removal of unnecessary materials, and large quantities of raw materials are required. In this study, we report a minimum-waste laser patterning process utilizing silver nanoparticle (Ag NP) debris obtained through laser ablation of Ag NWs in liquid media. Since the generated Ag NPs can be used for several applications, wastage of Ag NWs, which is inevitable in conventional laser patterning processes, is dramatically reduced. In addition, electrophoretic deposition of the recycled Ag NPs onto non-ablated Ag NWs allows easy fabrication of junction-enhanced Ag NWs from the deposited Ag NPs. The unique advantage of this method lies in using recycled Ag NPs as building materials, eliminating the additional cost of junction welding Ag NWs. These fabricated Ag NW substrates could be utilized as transparent heaters and stretchable TCEs, thereby validating the effectiveness of the proposed process.
Alexithymia traits outweigh autism traits in the explanation of depression in adults with autism
Authors: Bloch Carola , Burghof Lana , Lehnhardt Fritz-Georg , Vogeley Kai , Falter-Wagner Christine 
Published: January 2021

AbstractWhen contemplating the alarming depression rates in adults with autism spectrum disorder (ASD), there is a need to find factors explaining heightened symptoms of depression. Beyond the impact of autism traits, markedly increased levels of alexithymia traits should be considered as a candidate for explaining why individuals with ASD report higher levels of depressive symptoms. Here, we aim to identify the extent to which autism or alexithymia traits indicate depressive symptoms in ASD and whether the pattern of association are specific to ASD. Data of a large (N = 400) representative clinical population of adults referred to autism diagnostics have been investigated and split by cases with a confirmed ASD diagnosis (N = 281) and cases with a ruled out ASD diagnosis (N = 119). Dominance analysis revealed the alexithymia factor,difficulties in identifying feelings,as the strongest predictor for depressive symptomatology in ASD, outweighing autism traits and other alexithymia factors. This pattern of prediction was not specific to ASD and was shared by clinical controls from the referral population with a ruled out ASD diagnosis. Thus, the association of alexithymia traits with depression is not unique to ASD and may constitute a general psychopathological mechanism in clinical samples.
Assessing the functional impact of PfRh5 genetic diversity on ex vivo erythrocyte invasion inhibition
Authors: Moore Adam J. , Mangou Khadidiatou , Diallo Fatoumata , Sene Seynabou D. , Pouye Mariama N. , Sadio Bacary D. , Faye Ousmane , Mbengue Alassane , Bei Amy K. 
Published: January 2021

AbstractThe PfRh5-Basigin ligand–receptor interaction is an essential step in the merozoite invasion process and represents an attractive vaccine target. To reveal genotype–phenotype associations between naturally occurring allelic variants of PfRh5 and invasion inhibition, we performed ex vivo invasion inhibition assays with monoclonal antibodies targeting basigin coupled with PfRh5 next-generation amplicon sequencing. We found dose-dependent inhibition of invasion across all isolates tested, and no statistically significant difference in invasion inhibition for any single nucleotide polymorphisms. This study demonstrates that PfRh5 remains highly conserved and functionally essential, even in a highly endemic setting, supporting continued development as a strain-transcendent malaria vaccine target.
CD8+ T cells predicted the conversion of common covid-19 to severe
Authors: Liu Li , Chen Zhiyong , Du Yingrong , Gao Jianpeng , Li Junyi , Deng Tiqin , Chen Chen , Wang Lin , Yang Yongrui , Liu Chunyun 
Published: January 2021

AbstractTo evaluate the predictive effect of T-lymphoid subsets on the conversion of common covid-19 to severe. The laboratory data were collected retrospectively from common covid-19 patients in the First People's Hospital of Zaoyang, Hubei Province, China and the Third People's Hospital of Kunming, Yunnan Province, China, between January 20, 2020 and March 15, 2020 and divided into training set and validation set. Univariate and multivariate logistic regression was performed to investigate the risk factors for the conversion of common covid-19 to severe in the training set, the prediction model was established and verified externally in the validation set. 60 (14.71%) of 408 patients with common covid-19 became severe in 6–10 days after diagnosis. Univariate and multiple logistic regression analysis revealed that lactate (P = 0.042, OR = 1097.983, 95% CI 1.303, 924,798.262) and CD8+ T cells (P = 0.010, OR = 0.903, 95% CI 0.835, 0.975) were independent risk factors for general type patients to turn to severe type. The area under ROC curve of lactate and CD8+ T cells was 0.754 (0.581, 0.928) and 0.842 (0.713, 0.970), respectively. The actual observation value was highly consistent with the prediction model value in curve fitting. The established prediction model was verified in 78 COVID-19 patients in the verification set, the area under the ROC curve was 0.906 (0.861, 0.981), and the calibration curve was consistent. CD8+ T cells, as an independent risk factor, could predict the transition from common covid-19 to severe.