bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice
Authors: Fields Jerel Adam , Swinton Mary K. , Carson Aliyah , Soontornniyomkij Benchawanna , Lindsay Charmaine , Han May Madi , Frizzi Katie , Sambhwani Shrey , Murphy Anne , Achim Cristian L. , Ellis Ronald J. , Calcutt Nigel A. 
Published: November 2019

AbstractMounting evidence suggests that antiretroviral therapy (ART) drugs may contribute to the prevalence of HIV-associated neurological dysfunction. The HIV envelope glycoprotein (gp120) is neurotoxic and has been linked to alterations in mitochondrial function and increased inflammatory gene expression, which are common neuropathological findings in HIV+ cases on ART with neurological disorders. Tenofovir disproxil fumarate (TDF) has been shown to affect neurogenesis in brains of mice and mitochondria in neurons. In this study, we hypothesized that TDF contributes to neurotoxicity by modulating mitochondrial biogenesis and inflammatory pathways. TDF administered to wild-type (wt) and GFAP-gp120 transgenic (tg) mice caused peripheral neuropathy, as indicated by nerve conduction slowing and thermal hyperalgesia. Conversely TDF protected gp120-tg mice from cognitive dysfunction. In the brains of wt and gp120-tg mice, TDF decreased expression of mitochondrial transcription factor A (TFAM). However, double immunolabelling revealed that TFAM was reduced in neurons and increased in astroglia in the hippocampi of TDF-treated wt and gp120-tg mice. TDF also increased expression of GFAP and decreased expression of IBA1 in the wt and gp120-tg mice. TDF increased tumor necrosis factor (TNF) α in wt mice. However, TDF reduced interleukin (IL) 1β and TNFα mRNA in gp120-tg mouse brains. Primary human astroglia were exposed to increasing doses of TDF for 24 hours and then analyzed for mitochondrial alterations and inflammatory gene expression. In astroglia, TDF caused a dose-dependent increase in oxygen consumption rate, extracellular acidification rate and spare respiratory capacity, changes consistent with increased metabolism. TDF also reduced IL-1β-mediated increases in IL-1β and TNFα mRNA. These data demonstrate that TDF causes peripheral neuropathy in mice and alterations in inflammatory signaling and mitochondrial activity in the brain.
A thrips vector of tomato spotted wilt virus responds to tomato acylsugar chemical diversity with reduced oviposition and virus inoculation
Authors: Ben-Mahmoud Sulley , Anderson Taylor , Chappell Thomas M. , Smeda John R. , Mutschler Martha A. , Kennedy George G. , De Jong Darlene M. , Ullman Diane E. 
Published: November 2019

AbstractThere is increasing evidence that acylsugars deter insect pests and plant virus vectors, including the western flower thrips (WFT), Frankliniella occidentalis (Pergande), vector of tomato spotted wilt virus (TSWV). Acylsugars are sugar-polyesters composed of saturated, un-saturated, and variously branched short and long chain fatty acids (FAs) esterified to a glucose (acylglucose) or sucrose (acylsucrose) moiety. We sought to understand how acylsucrose amount and composition of associated FA profiles interacted to mediate resistance to WFT oviposition and TSWV inoculation on tomato leaves. Towards this goal, we examined WFT oviposition and TSWV inoculation behavior on tomato lines bred to exude varying amounts of acylsucrose in association with diverse FA profiles. Our data show that as acylsucrose amounts increased, WFT egg-laying (oviposition) decreased and TSWV inoculation was suppressed. Western flower thrips also responded to FA profiles that included iC4, iC11, nC12 and nC10 FA. These findings support improving acylsugar-mediated resistance against WFT by breeding tomatoes exuding greater amounts of acylsucrose associated with specific FA profiles. We show that increasing acylsucrose amount output by type IV trichomes and selecting for particular FA profiles through advanced breeding profoundly affects WFT behavior in ways that benefit management of WFT as direct pests and as TSWV vectors.
The NATO project: nanoparticle-based countermeasures for microgravity-induced osteoporosis
Authors: Cristofaro F. , Pani G. , Pascucci B. , Mariani A. , Balsamo M. , Donati A. , Mascetti G. , Rea G. , Rizzo A. M. , Visai L. 
Published: November 2019

AbstractRecent advances in nanotechnology applied to medicine and regenerative medicine have an enormous and unexploited potential for future space and terrestrial medical applications. The Nanoparticles and Osteoporosis (NATO) project aimed to develop innovative countermeasures for secondary osteoporosis affecting astronauts after prolonged periods in space microgravity. Calcium- and Strontium-containing hydroxyapatite nanoparticles (nCa-HAP and nSr-HAP, respectively) were previously developed and chemically characterized. This study constitutes the first investigation of the effect of the exogenous addition of nCa-HAP and nSr-HAP on bone remodeling in gravity (1 g), Random Positioning Machine (RPM) and onboard International Space Station (ISS) using human bone marrow mesenchymal stem cells (hBMMSCs). In 1 g conditions, nSr-HAP accelerated and improved the commitment of cells to differentiate towards osteoblasts, as shown by the augmented alkaline phosphatase (ALP) activity and the up-regulation of the expression of bone marker genes, supporting the increased extracellular bone matrix deposition and mineralization. The nSr-HAP treatment exerted a protective effect on the microgravity-induced reduction of ALP activity in RPM samples, and a promoting effect on the deposition of hydroxyapatite crystals in either ISS or 1 g samples. The results indicate the exogenous addition of nSr-HAP could be potentially used to deliver Sr to bone tissue and promote its regeneration, as component of bone substitute synthetic materials and additive for pharmaceutical preparation or food supplementary for systemic distribution.
On the existence of a perennial river in the Harappan heartland
Authors: Chatterjee Anirban , Ray Jyotiranjan S. , Shukla Anil D. , Pande Kanchan 
Published: November 2019

AbstractThe legendary river Saraswati of Indian mythology has often been hypothesized to be an ancient perennial channel of the seasonal river Ghaggar that flowed through the heartland of the Bronze Age Harappan civilization in north-western India. Despite the discovery of abundant settlements along a major paleo-channel of the Ghaggar, many believed that the Harappans depended solely on monsoonal rains, because no proof existed for the river’s uninterrupted flow during the zenith of the civilization. Here, we present unequivocal evidence for the Ghaggar’s perennial past by studying temporal changes of sediment provenance along a 300 km stretch of the river basin. This is achieved using 40Ar/39Ar ages of detrital muscovite and Sr-Nd isotopic ratios of siliciclastic sediment in fluvial sequences, dated by radiocarbon and luminescence methods. We establish that during 80-20 ka and 9-4.5 ka the river was perennial and was receiving sediments from the Higher and Lesser Himalayas. The latter phase can be attributed to the reactivation of the river by the distributaries of the Sutlej. This revived perennial condition of the Ghaggar, which can be correlated with the Saraswati, likely facilitated development of the early Harappan settlements along its banks. The timing of the eventual decline of the river, which led to the collapse of the civilization, approximately coincides with the commencement of the Meghalayan Stage.
New Fair Multiparty Quantum Key Agreement Secure against Collusive Attacks
Authors: Sun Zhiwei , Cheng Rong , Wu Chunhui , Zhang Cai 
Published: November 2019

AbstractFairness is an important standard needed to be considered in a secure quantum key agreement (QKA) protocol. However, it found that most of the quantum key agreement protocols in the travelling model are not fair, i.e., some of the dishonest participants can collaborate to predetermine the final key without being detected. Thus, how to construct a fair and secure key agreement protocol has obtained much attention. In this paper, a new fair multiparty QKA protocol that can resist the collusive attack is proposed. More specifically, we show that in a client-server scenario, it is possible for the clients to share a key and reveal nothing about what key has been agreed upon to the server. The server prepares quantum states for clients to encode messages to avoid the participants’ collusive attack. This construction improves on previous work, which requires either preparing multiple quantum resources by clients or two-way quantum communication. It is proven that the protocol does not reveal to any eavesdropper, including the server, what key has been agreed upon, and the dishonest participants can be prevented from collaborating to predetermine the final key.
Intrinsic dimension estimation for locally undersampled data
Authors: Erba Vittorio , Gherardi Marco , Rotondo Pietro 
Published: November 2019

AbstractIdentifying the minimal number of parameters needed to describe a dataset is a challenging problem known in the literature as intrinsic dimension estimation. All the existing intrinsic dimension estimators are not reliable whenever the dataset is locally undersampled, and this is at the core of the so called curse of dimensionality. Here we introduce a new intrinsic dimension estimator that leverages on simple properties of the tangent space of a manifold and extends the usual correlation integral estimator to alleviate the extreme undersampling problem. Based on this insight, we explore a multiscale generalization of the algorithm that is capable of (i) identifying multiple dimensionalities in a dataset, and (ii) providing accurate estimates of the intrinsic dimension of extremely curved manifolds. We test the method on manifolds generated from global transformations of high-contrast images, relevant for invariant object recognition and considered a challenge for state-of-the-art intrinsic dimension estimators.
Early detection of enamel demineralization by optical coherence tomography
Authors: Tsai Meng-Tsan , Wang Yen-Li , Yeh Ting-Wei , Lee Hsiang-Chieh , Chen Wen-Ju , Ke Jia-Ling , Lee Ya-Ju 
Published: November 2019

AbstractEnamel is the outermost layer of the tooth that protects it from invasion. In general, an acidic environment accelerates tooth demineralization, leading to the formation of cavities. Scanning electron microscopy (SEM) is conventionally used as an in vitro tool for the observation of tooth morphology changes with acid attacks. Yet, SEM has intrinsic limitations for the potential application of in vivo detection in the early demineralization process. In this study, a high-resolution optical coherence tomography (OCT) system with the axial and transverse resolutions of 2.0 and 2.7 μm in teeth has been utilized for characterizing the effect of the acidic environment (simulated by phosphoric acid) on the enamel topology. The scattering coefficient and the surface roughness of enamel can be directly derived from the OCT results, enabling a quantitative evaluation of the topology changes with demineralization. The dynamic process induced by the acid application is also recorded and analyzed with OCT, depicting the evolution of the demineralization process on enamel. Notably, the estimated enamel scattering coefficient and surface roughness significantly increase with the application time of acid and the results illustrate that the values of both parameters after demineralization are significantly larger than those obtained before the demineralization, illustrating both parameters could be effective to differentiate the healthy and demineralized teeth and determine the severity. The obtained results unambiguously illustrate that demineralization of the tooth surface can be successfully detected by OCT and further used as an indicator of early-stage cavity formation.
Genome-wide CRISPR Screen to Identify Genes that Suppress Transformation in the Presence of Endogenous KrasG12D
Authors: Huang Jianguo , Chen Mark , Xu Eric S. , Luo Lixia , Ma Yan , Huang Wesley , Floyd Warren , Klann Tyler S. , Kim So Young , Gersbach Charles A. , Cardona Diana M. , Kirsch David G. 
Published: November 2019

AbstractCooperating gene mutations are typically required to transform normal cells enabling growth in soft agar or in immunodeficient mice. For example, mutations in Kras and transformation-related protein 53 (Trp53) are known to transform a variety of mesenchymal and epithelial cells in vitro and in vivo. Identifying other genes that can cooperate with oncogenic Kras and substitute for Trp53 mutation has the potential to lead to new insights into mechanisms of carcinogenesis. Here, we applied a genome-wide CRISPR/Cas9 knockout screen in KrasG12D immortalized mouse embryonic fibroblasts (MEFs) to search for genes that when mutated cooperate with oncogenic Kras to induce transformation. We also tested if mutation of the identified candidate genes could cooperate with KrasG12D to generate primary sarcomas in mice. In addition to identifying the well-known tumor suppressor cyclin dependent kinase inhibitor 2A (Cdkn2a), whose alternative reading frame product p19 activates Trp53, we also identified other putative tumor suppressors, such as F-box/WD repeat-containing protein 7 (Fbxw7) and solute carrier family 9 member 3 (Slc9a3). Remarkably, the TCGA database indicates that both FBXW7 and SLC9A3 are commonly co-mutated with KRAS in human cancers. However, we found that only mutation of Trp53 or Cdkn2a, but not Fbxw7 or Slc9a3 can cooperate with KrasG12D to generate primary sarcomas in mice. These results show that mutations in oncogenic Kras and either Fbxw7 or Slc9a3 are sufficient for transformation in vitro, but not for in vivo sarcomagenesis.
Negative frequency dependent selection on plasmid carriage and low fitness costs maintain extended spectrum β-lactamases in Escherichia coli
Authors: Dimitriu Tatiana , Medaney Frances , Amanatidou Elli , Forsyth Jessica , Ellis Richard J. , Raymond Ben 
Published: November 2019

AbstractPlasmids may maintain antibiotic resistance genes in bacterial populations through conjugation, in the absence of direct selection pressure. However, the costs and benefits of conjugation for plasmid and bacterial fitness are not well understood. Using invasion and competition experiments with plasmid mutants we explicitly tested how conjugation contributes to the maintenance of a plasmid bearing a single extended-spectrum ß-lactamase (ESBL) gene (blaCTX-M-14). Surprisingly, conjugation had little impact on overall frequencies, although it imposed a substantial fitness cost. Instead, stability resulted from the plasmid conferring fitness benefits when rare. Frequency dependent fitness did not require a functional blaCTX-M-14 gene, and was independent of culture media. Fitness benefits when rare are associated with the core plasmid backbone but are able to drive up frequencies of antibiotic resistance because fitness burden of the blaCTX-M-14 gene is very low. Negative frequency dependent fitness can contribute to maintaining a stable frequency of resistance genes in the absence of selection pressure from antimicrobials. In addition, persistent, low cost resistance has broad implications for antimicrobial stewardship.
Characterization of laser-driven proton acceleration from water microdroplets
Authors: Becker Georg A. , Schwab Matthew B. , Lötzsch Robert , Tietze Stefan , Klöpfel Diethard , Rehwald Martin , Schlenvoigt Hans-Peter , Sävert Alexander , Schramm Ulrich , Zepf Matt , Kaluza Malte C. 
Published: November 2019

AbstractWe report on a proton acceleration experiment in which high-intensity laser pulses with a wavelength of 0.4 μm and with varying temporal intensity contrast have been used to irradiate water droplets of 20 μm diameter. Such droplets are a reliable and easy-to-implement type of target for proton acceleration experiments with the potential to be used at very high repetition rates. We have investigated the influence of the laser’s angle of incidence by moving the droplet along the laser polarization axis. This position, which is coupled with the angle of incidence, has a crucial impact on the maximum proton energy. Central irradiation leads to an inefficient coupling of the laser energy into hot electrons, resulting in a low maximum proton energy. The introduction of a controlled pre-pulse produces an enhancement of hot electron generation in this geometry and therefore higher proton energies. However, two-dimensional particle-in-cell simulations support our experimental results confirming, that even slightly higher proton energies are achieved under grazing laser incidence when no additional pre-plasma is present. Illuminating a droplet under grazing incidence generates a stream of hot electrons that flows along the droplet’s surface due to self-generated electric and magnetic fields and ultimately generates a strong electric field responsible for proton acceleration. The interaction conditions were monitored with the help of an ultra-short optical probe laser, with which the plasma expansion could be observed.
Thymic precursor cells generate acute myeloid leukemia in NUP98-PHF23/NUP98-HOXD13 double transgenic mice
Authors: Kundu Subhadip , Park Eun Sil , Chung Yang Jo , Walker Robert L. , Zhu Yuelin J. , Negi Vijay , Meltzer Paul S. , Aplan Peter D. 
Published: November 2019

AbstractTransgenic mice that express either a NUP98–PHF23 (NP23) or NUP98-HOXD13 (NHD13) fusion in the hematopoietic compartment develop a wide spectrum of leukemias, including myeloid, erythroid, megakaryocytic and lymphoid, at age 9–14 months. NP23-NHD13 double transgenic mice were generated by interbreeding NP23 and NHD13 mice. Remarkably, 100% of the NP23-NHD13 double transgenic mice developed acute myeloid leukemia (AML) within three months, characterized by replacement of the thymus with leukemic myeloblasts. The marked infiltration of thymus led to the intriguing hypothesis that AML generated in NP23-NHD13 mice arose in the thymus, as opposed to the bone marrow (BM). Transplantation of CD4-CD8- double negative (DN) thymocytes (which were also negative for Mac1 and Gr1) from leukemic NHD13/NP23 mice demonstrated that DN thymocytes could transmit AML, and limiting dilution studies showed that leukemia initiating cells were increased 14-fold in the thymus compared to BM. Further thymocyte fractionation demonstrated that DN1 and DN2, but not DN3 or DN4 fractions transmitted AML, and a marked expansion (100-fold) of Lineage-Sca1 + Kit + (LSK) cells in the thymus of the NP23-NHD13 mice. Taken together, these results show that the thymus of NP23-NHD13 mice acts as a reservoir for AML initiating cells and that thymic progenitors can transmit AML.
Appetitive and aversive motivation in depression: The temporal dynamics of task-elicited asymmetries in alpha oscillations
Authors: Messerotti Benvenuti Simone , Buodo Giulia , Mennella Rocco , Dal Bò Elisa , Palomba Daniela 
Published: November 2019

AbstractThe capability model of alpha asymmetries posits that state emotional manipulations are a more powerful detector of depression-related motivational deficits than alpha activity at rest. The present study used a time-frequency approach to investigate the temporal dynamics of event-related changes in alpha power during passive viewing of emotional pictures in individuals with dysphoria (n = 23) and in individuals without dysphoria (n = 24). In the whole group, the processing of pleasant and unpleasant compared to neutral pictures was associated with a decrease in event-related alpha power (i.e., alpha desynchronization) at centro-parietal and parietal scalp sites in the 538–1400 ms post-stimulus. The group with dysphoria revealed a smaller alpha desynchronization than the group without dysphoria in response to pleasant, but not neutral and unpleasant, stimuli at frontal, fronto-central and centro-parietal sites. Interestingly, at central and centro-parietal scalp sites, the difference between groups in response to pleasant stimuli was lateralized to the right hemisphere, whereas no clear lateralization was observed at frontal and fronto-central scalp sites. These findings suggest that decreased cortical activity (i.e., reduced alpha desynchronization) in a network involving bilateral frontal and right-lateralized parietal regions may provide a specific measure of deficits in approach-related motivation in depression.
Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
Authors: Hyvärinen Tanja , Hyysalo Anu , Kapucu Fikret Emre , Aarnos Laura , Vinogradov Andrey , Eglen Stephen J. , Ylä-Outinen Laura , Narkilahti Susanna 
Published: November 2019

AbstractHuman pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.
Particle Mobility Analysis Using Deep Learning and the Moment Scaling Spectrum
Authors: Arts Marloes , Smal Ihor , Paul Maarten W. , Wyman Claire , Meijering Erik 
Published: November 2019

AbstractQuantitative analysis of dynamic processes in living cells using time-lapse microscopy requires not only accurate tracking of every particle in the images, but also reliable extraction of biologically relevant parameters from the resulting trajectories. Whereas many methods exist to perform the tracking task, there is still a lack of robust solutions for subsequent parameter extraction and analysis. Here a novel method is presented to address this need. It uses for the first time a deep learning approach to segment single particle trajectories into consistent tracklets (trajectory segments that exhibit one type of motion) and then performs moment scaling spectrum analysis of the tracklets to estimate the number of mobility classes and their associated parameters, providing rich fundamental knowledge about the behavior of the particles under study. Experiments on in-house datasets as well as publicly available particle tracking data for a wide range of proteins with different dynamic behavior demonstrate the broad applicability of the method.