bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AAA + ATPase valosin-containing protein (VCP)/p97/Cdc48 interaction network in Leishmania
Authors: Aguiar Bruno Guedes , Dumas Carole , Maaroufi Halim , Padmanabhan Prasad K. , Papadopoulou Barbara 
Published: August 2020

AbstractValosin‐containing protein (VCP)/p97/Cdc48 is an AAA + ATPase associated with many ubiquitin-dependent cellular pathways that are central to protein quality control. VCP binds various cofactors, which determine pathway selectivity and substrate processing. Here, we used co-immunoprecipitation and mass spectrometry studies coupled to in silico analyses to identify the Leishmania infantum VCP (LiVCP) interactome and to predict molecular interactions between LiVCP and its major cofactors. Our data support a largely conserved VCP protein network in Leishmania including known but also novel interaction partners. Network proteomics analysis confirmed LiVCP-cofactor interactions and provided novel insights into cofactor-specific partners and the diversity of LiVCP complexes, including the well-characterized VCP-UFD1-NPL4 complex. Gene Ontology analysis coupled with digitonin fractionation and immunofluorescence studies support cofactor subcellular compartmentalization with either cytoplasmic or organellar or vacuolar localization. Furthermore, in silico models based on 3D homology modeling and protein–protein docking indicated that the conserved binding modules of LiVCP cofactors, except for NPL4, interact with specific binding sites in the hexameric LiVCP protein, similarly to their eukaryotic orthologs. Altogether, these results allowed us to build the first VCP protein interaction network in parasitic protozoa through the identification of known and novel interacting partners potentially associated with distinct VCP complexes.
Optimisation of Tet-On inducible systems for Sleeping Beauty-based chimeric antigen receptor (CAR) applications
Authors: Ali Hosseini Rad S. M. , Poudel Aarati , Tan Grace Min Yi , McLellan Alexander D. 
Published: August 2020

AbstractRegulated expression of genetic elements that either encode polypeptides or various types of functional RNA is a fundamental goal for gene therapy. Inducible expression may be preferred over constitutive promoters to allow clinician-based control of gene expression. Existing Tet-On systems represent one of the tightest rheostats for control of gene expression in mammals. However, basal expression in absence of tetracycline compromises the widespread application of Tet-controlled systems in gene therapy. We demonstrate that the order of P2A-linked genes of interest was critical for maximal response and tightness of a chimeric antigen receptor (CAR)-based construct. The introduction of G72V mutation in the activation region of the TetR component of the rtTA further improved the fold response. Although the G72V mutation resulted in a removal of a cryptic splice site within rtTA, additional removal of this splice site led to only a modest improvement in the fold-response. Selective removal of key promoter elements (namely the BRE, TATA box, DPE and the four predicted Inr) confirmed the suitability of the minimal CMV promoter and its downstream sequences for supporting inducible expression. The results demonstrate marked improvement of the rtTA based Tet-On system in Sleeping Beauty for applications such as CAR T cell therapy.
High-mobility junction field-effect transistor via graphene/MoS2 heterointerface
Authors: Kim Taesoo , Fan Sidi , Lee Sanghyub , Joo Min-Kyu , Lee Young Hee 
Published: August 2020

AbstractMonolayer molybdenum disulfide (MoS2) possesses a desirable direct bandgap with moderate carrier mobility, whereas graphene (Gr) exhibits a zero bandgap and excellent carrier mobility. Numerous approaches have been suggested for concomitantly realizing high on/off current ratio and high carrier mobility in field-effect transistors, but little is known to date about the effect of two-dimensional layered materials. Herein, we propose a Gr/MoS2 heterojunction platform, i.e., junction field-effect transistor (JFET), that enhances the carrier mobility by a factor of ~ 10 (~ 100 cm2 V−1 s−1) compared to that of monolayer MoS2, while retaining a high on/off current ratio of ~ 108 at room temperature. The Fermi level of Gr can be tuned by the wide back-gate bias (VBG) to modulate the effective Schottky barrier height (SBH) at the Gr/MoS2 heterointerface from 528 meV (n-MoS2/p-Gr) to 116 meV (n-MoS2/n-Gr), consequently enhancing the carrier mobility. The double humps in the transconductance derivative profile clearly reveal the carrier transport mechanism of Gr/MoS2, where the barrier height is controlled by electrostatic doping.
Uncovering a possible role of reactive oxygen species in magnetogenetics
Authors: Brier Matthew I. , Mundell Jordan W. , Yu Xiaofei , Su Lichao , Holmann Alexander , Squeri Jessica , Zhang Baolin , Stanley Sarah A. , Friedman Jeffrey M. , Dordick Jonathan S. 
Published: August 2020

AbstractRecent reports have shown that intracellular, (super)paramagnetic ferritin nanoparticles can gate TRPV1, a non-selective cation channel, in a magnetic field. Here, we report the effects of differing field strength and frequency as well as chemical inhibitors on channel gating using a Ca2+-sensitive promoter to express a secreted embryonic alkaline phosphatase (SEAP) reporter. Exposure of TRPV1-ferritin-expressing HEK-293T cells at 30 °C to an alternating magnetic field of 501 kHz and 27.1 mT significantly increased SEAP secretion by ~ 82% relative to control cells, with lesser effects at other field strengths and frequencies. Between 30–32 °C, SEAP production was strongly potentiated 3.3-fold by the addition of the TRPV1 agonist capsaicin. This potentiation was eliminated by the competitive antagonist AMG-21629, the NADPH oxidase assembly inhibitor apocynin, and the reactive oxygen species (ROS) scavenger N-acetylcysteine, suggesting that ROS contributes to magnetogenetic TRPV1 activation. These results provide a rational basis to address the heretofore unknown mechanism of magnetogenetics.
Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model
Authors: Kanbara Shunsuke , Ohkawara Bisei , Nakashima Hiroaki , Ohta Kyotaro , Koshimizu Hiroyuki , Inoue Taro , Tomita Hiroyuki , Ito Mikako , Masuda Akio , Ishiguro Naoki , Imagama Shiro , Ohno Kinji 
Published: August 2020

AbstractCervical spondylotic myelopathy (CSM) is caused by chronic compression of the spinal cord and is the most common cause of myelopathy in adults. No drug is currently available to mitigate CSM. Herein, we made a rat model of CSM by epidurally implanting an expanding water-absorbent polymer underneath the laminae compress the spinal cord. The CSM rats exhibited progressive motor impairments recapitulating human CSM. CSM rats had loss of spinal motor neurons, and increased lipid peroxidation in the spinal cord. Zonisamide (ZNS) is clinically used for epilepsy and Parkinson's disease. We previously reported that ZNS protected primary spinal motor neurons against oxidative stress. We thus examined the effects of ZNS on our rat CSM model. CSM rats with daily intragastric administration of 0.5% methylcellulose (n = 11) and ZNS (30 mg/kg/day) in 0.5% methylcellulose (n = 11). Oral administration of ZNS ameliorated the progression of motor impairments, spared the number of spinal motor neurons, and preserved myelination of the pyramidal tracts. In addition, ZNS increased gene expressions of cystine/glutamate exchange transporter (xCT) and metallothionein 2A in the spinal cord in CSM rats, and also in the primary astrocytes. ZNS increased the glutathione (GSH) level in the spinal motor neurons of CSM rats. ZNS potentially ameliorates loss of the spinal motor neurons and demyelination of the pyramidal tracts in patients with CSM.
Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia
Authors: Leutner Michael , Matzhold Caspar , Bellach Luise , Deischinger Carola , Thurner Stefan , Klimek Peter , Kautzky-Willer Alexandra 
Published: August 2020

AbstractBetatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3–6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60′: 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60′ were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort.
Influence of flicker noise and nonlinearity on the frequency spectrum of spin torque nano-oscillators
Authors: Wittrock Steffen , Talatchian Philippe , Tsunegi Sumito , Crété Denis , Yakushiji Kay , Bortolotti Paolo , Ebels Ursula , Fukushima Akio , Kubota Hitoshi , Yuasa Shinji , Grollier Julie , Cibiel Gilles , Galliou Serge , Rubiola Enrico , Cros Vincent 
Published: August 2020

AbstractThe correlation of phase fluctuations in any type of oscillator fundamentally defines its spectral shape. However, in nonlinear oscillators, such as spin torque nano-oscillators, the frequency spectrum can become particularly complex. This is specifically true when not only considering thermal but also colored 1/f flicker noise processes, which are crucial in the context of the oscillator’s long term stability. In this study, we address the frequency spectrum of spin torque oscillators in the regime of large-amplitude steady oscillations experimentally and as well theoretically. We particularly take both thermal and flicker noise into account. We perform a series of measurements of the phase noise and the spectrum on spin torque vortex oscillators, notably varying the measurement time duration. Furthermore, we develop the modelling of thermal and flicker noise in Thiele equation based simulations. We also derive the complete phase variance in the framework of the nonlinear auto-oscillator theory and deduce the actual frequency spectrum. We investigate its dependence on the measurement time duration and compare with the experimental results. Long term stability is important in several of the recent applicative developments of spin torque oscillators. This study brings some insights on how to better address this issue.
Best period to replace or change plastic stents with self-expandable metallic stents using multivariate competing risk regression analysis
Authors: Chiba Masafumi , Kato Masayuki , Kinoshita Yuji , Shimamoto Nana , Tomita Youichi , Abe Takahiro , Kawahara Yosuke , Koyama Seita , Kanazawa Keisuke , Takakura Kazuki , Tsukinaga Shintaro , Nakano Masanori , Torisu Yuichi , Toyoizumi Hirobumi , Ikeda Keiichi , Arakawa Hiroshi , Sumiyama Kazuki 
Published: August 2020

AbstractIn endoscopic biliary drainage (EBD) for various benign and malignant biliary disorders, the appropriate timing to replace or change a plastic stent (PS) with a self-expandable metallic stent (SEMS) remains unclear. This study aimed to define the best period to replace or change a PS with a SEMS. Between January 1, 2012, and December 31, 2018, 1,887 consecutive EBD procedures, including 170 SEMS placements, were retrospectively identified. The period to recurrent biliary obstruction (PRBO) was estimated and compared between the malignant and benign groups and according to each disease using time to event analysis and competing risk analysis. Compared with the benign group, the malignant group had significantly shorter median PRBO with interquartile range (IQR) after PS placement [108 (39 – 270) vs. 613 (191 – 1,329) days, P < 0.001], even on multivariate analysis, with a subdistribution hazard ratio (SHR) of 3.58 (P < 0.001). The shortest PRBO distribution from the first quartile of the non-RBO period was seen in Mirizzi syndrome cases (25 days, P = 0.030, SHR = 3.32) in the benign group and in cases of pancreatic cancer (32 days, P = 0.041, SHR = 2.06); perihilar bile duct cancer (27 days, P = 0.006, SHR = 2.69); and ampullary cancer (22 days, P = 0.001, SHR = 3.78) in the malignant group. Our study supports that stent replacement for the benign group is feasible after 6 months, and the best period to replace or change a PS with a SEMS should be decided on the basis of the underlying disease to prevent RBO.
A novel Monte Carlo simulation procedure for modelling COVID-19 spread over time
Authors: Xie Gang 
Published: August 2020

AbstractThe coronavirus disease 2019 (COVID-19) has now spread throughout most countries in the world causing heavy life losses and damaging social-economic impacts. Following a stochastic point process modelling approach, a Monte Carlo simulation model was developed to represent the COVID-19 spread dynamics. First, we examined various expected performances (theoretical properties) of the simulation model assuming a number of arbitrarily defined scenarios. Simulation studies were then performed on the real COVID-19 data reported (over the period of 1 March to 1 May) for Australia and United Kingdom (UK). Given the initial number of COVID-19 infection active cases were around 10 for both countries, the model estimated that the number of active cases would peak around 29 March in Australia (≈ 1,700 cases) and around 22 April in UK (≈ 22,860 cases); ultimately the total confirmed cases could sum to 6,790 for Australia in about 75 days and 206,480 for UK in about 105 days. The results of the estimated COVID-19 reproduction numbers were consistent with what was reported in the literature. This simulation model was considered an effective and adaptable decision making/what-if analysis tool in battling COVID-19 in the immediate need, and for modelling any other infectious diseases in the future.
Development of digital breast tomosynthesis and diffuse optical tomography fusion imaging for breast cancer detection
Authors: Chae Eun Young , Kim Hak Hee , Sabir Sohail , Kim Yejin , Kim Hyeongseok , Yoon Sungho , Ye Jong Chul , Cho Seungryong , Heo Duchang , Kim Kee Hyun , Bae Young Min , Choi Young-Wook 
Published: August 2020

AbstractDiffuse optical tomography (DOT) non-invasively measures the functional characteristics of breast lesions using near infrared light to probe tissue optical properties. This study aimed to evaluate a new digital breast tomosynthesis (DBT)/DOT fusion imaging technique and obtain preliminary data for breast cancer detection. Twenty-eight women were prospectively enrolled and underwent both DBT and DOT examinations. DBT/DOT fusion imaging was created after acquisition of both examinations. Two breast radiologists analyzed DBT and DOT images independently, and then finally evaluated the fusion images. The diagnostic performance of each reading session was compared and interobserver agreement was assessed. The technical success rate was 96.4%, with one failure due to an error during DOT data storage. Among the 27 women finally included in the analysis, 13 had breast cancer. The areas under the receiver operating characteristic curve (AUCs) for DBT were 0.783 and 0.854 for readers 1 and 2, respectively. DOT showed comparable diagnostic performance to DBT for both readers. The AUCs were significantly improved (P = 0.004) when the DBT/DOT fusion images were used. Interobserver agreements were highest for the DBT/DOT fusion images. In conclusion, this study suggests that DBT/DOT fusion imaging technique appears to be a promising tool for breast cancer diagnosis.
Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried
Authors: Omeljaniuk Wioleta Justyna , Jabłońska Ewa , Garley Marzena , Pryczynicz Anna , Ratajczak-Wrona Wioletta , Socha Katarzyna , Borawska Maria Halina , Charkiewicz Angelika Edyta 
Published: August 2020

AbstractPregnancy loss is a multidisciplinary problem which concerns researchers from the fields of medicine, epidemiology, psychology, and public health. The primary objective of the present study was to explain the potential role of neutrophil extracellular traps (NETs) in the process of spontaneous miscarriage. Enzyme-linked immunosorbent assay to assess the levels of biomarkers of NETs in the serum of examined women was conducted. Furthermore, levels of nitric oxide (NO) and late markers of its action were measured in serum samples. Analyses results demonstrated the existence of NETs in the placental tissue of women who miscarried as well as a simultaneous increase in the levels of myeloperoxidase and pentraxin 3. This clearly confirms the participation of NETs in the course of pregnancy loss. Women who have had a miscarriage but did not show the presence of NETs in their placenta exhibited the highest contents of NO, nitrotyrosine, and malondialdehyde suggesting a different pathway leading to pregnancy loss associated with disturbed oxidative–antioxidative processes. Although study results demonstrate new aspects associated with the formation of NETs they are not, however, sufficient to unambiguously determine the role of NETs in the course of miscarriage.
The schizophrenia risk locus in SLC39A8 alters brain metal transport and plasma glycosylation
Authors: Mealer Robert G. , Jenkins Bruce G. , Chen Chia-Yen , Daly Mark J. , Ge Tian , Lehoux Sylvain , Marquardt Thorsten , Palmer Christopher D. , Park Julien H. , Parsons Patrick J. , Sackstein Robert , Williams Sarah E. , Cummings Richard D. , Scolnick Edward M. , Smoller Jordan W. 
Published: August 2020

AbstractA common missense variant in SLC39A8 is convincingly associated with schizophrenia and several additional phenotypes. Homozygous loss-of-function mutations in SLC39A8 result in undetectable serum manganese (Mn) and a Congenital Disorder of Glycosylation (CDG) due to the exquisite sensitivity of glycosyltransferases to Mn concentration. Here, we identified several Mn-related changes in human carriers of the common SLC39A8 missense allele. Analysis of structural brain MRI scans showed a dose-dependent change in the ratio of T2w to T1w signal in several regions. Comprehensive trace element analysis confirmed a specific reduction of only serum Mn, and plasma protein N-glycome profiling revealed reduced complexity and branching. N-glycome profiling from two individuals with SLC39A8-CDG showed similar but more severe alterations in branching that improved with Mn supplementation, suggesting that the common variant exists on a spectrum of hypofunction with potential for reversibility. Characterizing the functional impact of this variant will enhance our understanding of schizophrenia pathogenesis and identify novel therapeutic targets and biomarkers.
Transcriptomic profile of adverse neurodevelopmental outcomes after neonatal encephalopathy
Authors: Montaldo Paolo , Cunnington Aubrey , Oliveira Vania , Swamy Ravi , Bandya Prathik , Pant Stuti , Lally Peter J. , Ivain Phoebe , Mendoza Josephine , Atreja Gaurav , Padmesh Vadakepat , Baburaj Mythili , Sebastian Monica , Yasashwi Indiramma , Kamalarathnam Chinnathambi , Chandramohan Rema , Mangalabharathi Sundaram , Kumaraswami Kumutha , Kumar Shobha , Benakappa Naveen , Manerkar Swati , Mondhkar Jayashree , Prakash Vinayagam , Sajjid Mohammed , Seeralar Arasar , Jahan Ismat , Moni Sadeka Choudhury , Shahidullah Mohammod , Sujatha Radhika , Chandrasekaran Manigandan , Ramji Siddarth , Shankaran Seetha , Kaforou Myrsini , Herberg Jethro , Thayyil Sudhin 
Published: August 2020

AbstractA rapid and early diagnostic test to identify the encephalopathic babies at risk of adverse outcome may accelerate the development of neuroprotectants. We examined if a whole blood transcriptomic signature measured soon after birth, predicts adverse neurodevelopmental outcome eighteen months after neonatal encephalopathy. We performed next generation sequencing on whole blood ribonucleic acid obtained within six hours of birth from the first 47 encephalopathic babies recruited to the Hypothermia for Encephalopathy in Low and middle-income countries (HELIX) trial. Two infants with blood culture positive sepsis were excluded, and the data from remaining 45 were analysed. A total of 855 genes were significantly differentially expressed between the good and adverse outcome groups, of which RGS1 and SMC4 were the most significant. Biological pathway analysis adjusted for gender, trial randomisation allocation (cooling therapy versus usual care) and estimated blood leukocyte proportions revealed over-representation of genes from pathways related to melatonin and polo-like kinase in babies with adverse outcome. These preliminary data suggest that transcriptomic profiling may be a promising tool for rapid risk stratification in neonatal encephalopathy. It may provide insights into biological mechanisms and identify novel therapeutic targets for neuroprotection.
SpiFoG: an efficient supervised learning algorithm for the network of spiking neurons
Authors: Hussain Irshed , Thounaojam Dalton Meitei 
Published: August 2020

AbstractThere has been a lot of research on supervised learning in spiking neural network (SNN) for a couple of decades to improve computational efficiency. However, evolutionary algorithm based supervised learning for SNN has not been investigated thoroughly which is still in embryo stage. This paper introduce an efficient algorithm (SpiFoG) to train multilayer feed forward SNN in supervised manner that uses elitist floating point genetic algorithm with hybrid crossover. The evidence from neuroscience claims that the brain uses spike times with random synaptic delays for information processing. Therefore, leaky-integrate-and-fire spiking neuron is used in this research introducing random synaptic delays. The SpiFoG allows both excitatory and inhibitory neurons by allowing a mixture of positive and negative synaptic weights. In addition, random synaptic delays are also trained with synaptic weights in an efficient manner. Moreover, computational efficiency of SpiFoG was increased by reducing the total simulation time and increasing the time step since increasing time step within the total simulation time takes less iteration. The SpiFoG is benchmarked on Iris and WBC dataset drawn from the UCI machine learning repository and found better performance than state-of-the-art techniques.