bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Density EEG in Current Clinical Practice and Opportunities for the Future
Authors: Stoyell Sally M. , Wilmskoetter Janina , Dobrota Mary-Ann , Chinappen Dhinakaran M. , Bonilha Leonardo , Mintz Mark , Brinkmann Benjamin H. , Herman Susan T. , Peters Jurriaan M. , Vulliemoz Serge , Seeck Margitta , Hämäläinen Matti S. , Chu Catherine J. 
Published: March 2021

Summary:
High-density EEG (HD-EEG) recordings use a higher spatial sampling of scalp electrodes than a standard 10-20 low-density EEG montage. Although several studies have demonstrated improved localization of the epileptogenic cortex using HD-EEG, widespread implementation is impeded by cost, setup and interpretation time, and lack of specific or sufficient procedural billing codes. Despite these barriers, HD-EEG has been in use at several institutions for years. These centers have noted utility in a variety of clinical scenarios where increased spatial resolution from HD-EEG has been required, justifying the extra time and cost. We share select scenarios from several centers, using different recording techniques and software, where HD-EEG provided information above and beyond the standard low-density EEG. We include seven cases where HD-EEG contributed directly to current clinical care of epilepsy patients and highlight two novel techniques which suggest potential opportunities to improve future clinical care. Cases illustrate how HD-EEG allows clinicians to: case 1—lateralize falsely generalized interictal epileptiform discharges; case 2—improve localization of falsely generalized epileptic spasms; cases 3 and 4—improve localization of interictal epileptiform discharges in anatomic regions below the circumferential limit of standard low-density EEG coverage; case 5—improve noninvasive localization of the seizure onset zone in lesional epilepsy; cases 6 and 7—improve localization of the seizure onset zone to guide invasive investigation near eloquent cortex; case 8—identify epileptic fast oscillations; and case 9—map language cortex. Together, these nine cases illustrate that using both visual analysis and advanced techniques, HD-EEG can play an important role in clinical management.
Mechanisms Underlying Economic Revealed Preference Of Multi-Component Bundles In Primate Orbitofrontal Cortex
Authors: Pastor-Bernier Alexandre , Schultz Wolfram 
Published: March 2021

ABSTRACTClassic neuro-economic studies suggest that people and animals alike assign values to individual attributes arriving at a total summed valuation and therefore overall appraisal of the offer (Kahnt et al., 2011; Lak et al., 2014). However, further work is needed to determine whether such individual attribute appraisals can predict choice between multi-component bundles. In this paper we show the importance and applications of economic theory to decision neurophysiology concerning multi-component attribute options or bundles. We applied random utility modelling (McFadden, 1973) to choices amongst 10 different two-component bundles in non-human primates (Macacca mulatta). We found that behavioural random utility (RUM) complies well with revealed preference theory and recapitulates the fundamental properties of empirically obtained indifference curves (IC). Bundles positioned in the same IC display equal choice preference and similar utility whereas bundles positioned across different ICs display different choice preferences. RUM also captures the characteristic shape of IC on each bundle revealing the synergetic interactions between components. We extended RUM to neurophysiological data and focused our investigation to orbitofrontal cortex (OFC), area 13. Neuronal RUM complied with behavioural RUM at single neuron and population level (N: 54). Neural coding of utility was present at target onset, choice, and reward. However, a distinct and separate group of neurons (N: 26) showed partial compliance with utility in either the chosen or the unchosen bundle options and correlated with both utility and probability of choice. We show that relative chosen-utility coding constitutes a separate type of computation and suggest a role for this type of neuron in value-to-choice processing in OFC.
Murine deficiency of peroxisomal L-bifunctional protein (EHHADH) causes medium-chain 3-hydroxydicarboxylic aciduria and perturbs hepatic cholesterol homeostasis
Authors: Ranea-Robles Pablo , Violante Sara , Argmann Carmen , Dodatko Tetyana , Bhattacharya Dipankar , Chen Hongjie , Yu Chunli , Friedman Scott L. , Puchowicz Michelle , Houten Sander M. 
Published: March 2021

AbstractPeroxisomes play an essential role in the β-oxidation of dicarboxylic acids (DCAs), which are metabolites formed upon ω-oxidation of fatty acids. Genetic evidence linking transporters and enzymes to specific DCA β-oxidation steps is generally lacking. Moreover, the physiological functions of DCA metabolism remain largely unknown. In this study, we aimed to characterize the DCA β-oxidation pathway in human cells, and to evaluate the biological role of DCA metabolism using mice deficient in the peroxisomal L-bifunctional protein (EhhadhKO mice).In vitroexperiments using HEK-293 KO cell lines demonstrate that ABCD3 and ACOX1 are essential in DCA β-oxidation, whereas both the bifunctional proteins (EHHADH and HSD17B4) and the thiolases (ACAA1 and SCPx) have overlapping functions and their contribution may depend on expression level. We also show that medium-chain 3-hydroxydicarboxylic aciduria is a prominent feature of EHHADH deficiency in mice most notably upon inhibition of mitochondrial fatty acid oxidation. Using stable isotope tracing methodology, we confirmed that products of peroxisomal DCA β-oxidation can be transported to mitochondria for further metabolism. Finally, we show that, in liver,EhhadhKO mice have increased mRNA and protein expression of cholesterol biosynthesis enzymes with decreased (in females) or similar (in males) rate of cholesterol synthesis. We conclude that EHHADH plays an essential role in the metabolism of medium-chain DCAs and postulate that peroxisomal DCA β-oxidation is a regulator of hepatic cholesterol biosynthesis.
Liquid and vapor-phase antifungal activities of natural borneol against Candida albicans and its germ tube formation
Authors: Wang Yazhou , Liu Huiling 
Published: March 2021

AbstractCandida albicans infection mainly occurs in patients with suppressed immune function, and it is also the main pathogen of hospital infection. The new strategies are needed to treat the existing resistance of antifungal drugs. The use of natural products aimed at controlling fungal diseases is considered an interesting alternative to synthetic fungicides due to their lower adverse reactions, lower cost to plant preparations compared to modern conventional pharmaceuticals. Natural borneol has a long history of treating ulcers and local infections. In this study, the minimum inhibitory concentration of natural borneol on ATCC10231 and 10 clinically isolated Candida albicans was determined by vapor phase method and dilution method, and the influence of sub-minimum inhibitory concentration on the formation of Candida albicans hyphae was observed. We found that the minimum inhibitory concentration of ATCC10231 and 10 clinically the isolates in the vapor phase were both 0.4 mg/cm3, agar and broth dilution methods were 2 mg/mL. The vapor phase of natural borneol has a better inhibitory effect on Candida albicans, Sub-mic concentration of borneol (0.125-1mg/ml) in the liquid phase inhibits the 60%-99% formation of Candida albicans germ tube. Natural borneol is a potential natural medicine for the treatment and prevention of Candida albicans infection. It brings new insights into the development of novel effective antifungal drugs.
The transposable element-rich genome of the cereal pestSitophilus oryzae
Authors: Parisot Nicolas , Vargas-Chavez Carlos , Goubert Clément , Baa-Puyoulet Patrice , Balmand Séverine , Beranger Louis , Blanc Caroline , Bonnamour Aymeric , Boulesteix Matthieu , Burlet Nelly , Calevro Federica , Callaerts Patrick , Chancy Théo , Charles Hubert , Colella Stefano , Da Silva Barbosa André , Dell’Aglio Elisa , Di Genova Alex , Febvay Gérard , Gabaldon Toni , Galvão Ferrarini Mariana , Gerber Alexandra , Gillet Benjamin , Hubley Robert , Hughes Sandrine , Jacquin-Joly Emmanuelle , Maire Justin , Marcet-Houben Marina , Masson Florent , Meslin Camille , Montagne Nicolas , Moya Andrés , Ribeiro de Vasconcelos Ana Tereza , Richard Gautier , Rosen Jeb , Sagot Marie-France , Smit Arian F.A. , Storer Jessica M. , Vincent-Monegat Carole , Vallier Agnès , Vigneron Aurélien , Zaidman-Remy Anna , Zamoum Waël , Vieira Cristina , Rebollo Rita , Latorre Amparo , Heddi Abdelaziz 
Published: March 2021

AbstractBackgroundThe rice weevilSitophilus oryzaeis one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains.S. oryzaehas an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacteriumSodalis pierantoniusand is a valuable model to decipher host-symbiont molecular interactions.ResultsWe sequenced theSitophilus oryzaegenome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show thatS. oryzaehas undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state.S. oryzaehas undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 Kyear),S. pierantoniusrelies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino-acids required for insect development and cuticle biosynthesis.ConclusionsHere we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition,S. oryzaemay be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.
A Cultured Sensorimotor Organoid Model Forms Human Neuromuscular Junctions
Authors: Pereira João D. , DuBreuil Daniel M. , Devlin Anna-Claire , Held Aaron , Sapir Yechiam , Berezovski Eugene , Hawrot James , Dorfman Katherine , Chander Vignesh , Wainger Brian J. 
Published: March 2021

AbstractHuman induced pluripotent stem cells (iPSCs) hold promise for modeling diseases in individual human genetic backgrounds and thus for developing precision medicine. Here, we generate sensorimotor organoids containing physiologically functional neuromuscular junctions (NMJs) within a cultured organoid system and apply the model to different subgroups of amyotrophic lateral sclerosis (ALS). Using a range of molecular, genomic, and physiological techniques, we identify and characterize motor neurons and skeletal muscle, along with sensory neurons, astrocytes, microglia, and vasculature. Organoid cultures derived from ALS subject iPSC lines and isogenic lines edited to harbor familial ALS mutations all show impairment at the level of the NMJ, as detected by both contraction and immunocytochemical measurements. The physiological resolution of the human NMJ synapse, combined with the generation of major cellular cohorts exerting autonomous and non-cell autonomous effects in motor and sensory diseases, may prove valuable for more comprehensive disease modeling.
Ablating Ku70 phosphorylation results in defective DNA damage repair and spontaneous induction of hepatocellular carcinoma
Authors: Saha Janapriya , Bae Jinsung , Wang Shih-Ya , Chappell Lori J. , Gopal Purva , Davis Anthony J. 
Published: March 2021

SUMMARYMultiple pathways mediate the repair of DNA double-strand break (DSB), with numerous mechanisms responsible for driving choice between the pathways. Previously, we reported that phosphorylation of the non-homologous end joining (NHEJ) factor, Ku70, is required for the dissociation of the Ku heterodimer from DNA ends to allow DSB repair via homologous recombination (HR). A knock-in mouse, in which phosphorylation is ablated in the three conserved sites of Ku70 (Ku703A/3A), was generated in order to test the hypothesis that Ku70 phosphorylation is required for initiation of HR and that blocking this process results in enhanced genomic instability and tumorigenesis. Here, we show that Ku703A/3Amice develop spontaneous and have accelerated chemical-induced hepatocellular carcinoma (HCC) compared to wild-type (Ku70+/+) littermates. The HCC tumors from the Ku703A/3Amice have increased γH2AX and 8-oxo-G staining, suggesting DNA repair is decreased in these mice. Spontaneous transformed cell lines from Ku703A/3Amice are more radiosensitive, have a significant decrease in DNA end resection, and are more sensitive to the DNA cross-linking agent mitomycin C compared to cells from Ku70+/+littermates. Collectively, these findings demonstrate that phosphorylation-mediated dissociation of Ku heterodimer from DNA ends is required for efficient DNA damage repair and disruption of this process results in genomic instability and accelerated development of HCC.
Neuronal ROS-Induced Glial Lipid Droplet Formation is Altered by Loss of Alzheimer’s Disease-associated Genes
Authors: Moulton Matthew J. , Barish Scott , Ralhan Isha , Chang Jinlan , Goodman Lindsey D. , Harland Jake G. , Marcogliese Paul C. , Johansson Jan O. , Ioannou Maria S. , Bellen Hugo J. 
Published: March 2021

SummaryA growing list of Alzheimer’s disease (AD) genetic risk factors is being identified, but the contribution of these genetic mutations to disease remains largely unknown. Accumulating data support a role of lipid dysregulation and excessive ROS in the etiology of AD. Here, we identified cell-specific roles for eight AD risk-associated genes in ROS-induced glial lipid droplet (LD) formation. We demonstrate that ROS-induced glial LD formation requires two ABCA transporters (ABCA1andABCA7) in neurons, the APOE receptor (LRP1), endocytic genes (PICALM,CD2AP, andAP2A2) in glia, and retromer genes (VPS26andVPS35) in both neurons and glia. Moreover, ROS strongly enhances Aβ42-toxicity in flies and Aβ42-plaque formation in mice. Finally, an ABCA1-activating peptide restores glial LD formation in the APOE4-associated loss of LD. This study places AD risk factors in a neuron-to-glia lipid transfer pathway with a critical role in protecting neurons from ROS-induced toxicity.
SWI/SNF senses carbon starvation with a pH-sensitive low complexity sequence
Authors: Gutiérrez J. Ignacio , Brittingham Gregory P. , Karadeniz Yonca B. , Tran Kathleen D. , Dutta Arnob , Holehouse Alex S. , Peterson Craig L. , Holt Liam J. 
Published: March 2021

AbstractIt is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation inS. cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. We found that a glutamine-rich low complexity sequence (QLC) in theSNF5subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming during carbon starvation. Furthermore, theSNF5QLC mediated pH-dependent recruitment of SWI/SNF to a model promoterin vitro.Simulations showed that protonation of histidines within theSNF5QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that theSNF5QLC acts as a pH-sensor.
Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing
Authors: Marongiu Laura , Protti Giulia , Facchini Fabio A. , Valache Mihai , Mingozzi Francesca , Ranzani Valeria , Putignano Anna Rita , Salviati Lorenzo , Bevilacqua Valeria , Curti Serena , Crosti Mariacristina , D’Angiò Mariella , Bettini Laura Rachele , Biondi Andrea , Nespoli Luca , Tamini Nicolò , Clementi Nicola , Mancini Nicasio , Abrignani Sergio , Spreafico Roberto , Granucci Francesca 
Published: March 2021

AbstractGrowing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19 and this negatively affects T cell activation. The presence of functional effector T cells in mild patients and dysfunctional T cells in severely ill patients suggests that adequate T cell responses are needed to limit disease severity. Therefore, understanding how cDCs cope with SARS-CoV-2 infections can help elucidate the mechanism of generation of protective immune responses. Here, we report that cDC2 subtypes exhibit similar infection-induced gene signatures with the up-regulation of interferon-stimulated genes and IL-6 signaling pathways. The main difference observed between DC2s and DC3s is the up-regulation of anti-apoptotic genes in DC3s, which explains their accumulation during infection. Furthermore, comparing cDCs between severe and mild patients, we find in the former a profound down-regulation of genes encoding molecules involved in antigen presentation, such as major histocompatibility complex class II (MHCII) molecules, β2microglobulin, TAP and costimulatory proteins, while an opposite trend is observed for proinflammatory molecules, such as complement and coagulation factors. Therefore, as the severity of the disease increases, cDC2s enhance their inflammatory properties and lose their main function, which is the antigen presentation capacity. In vitro, direct exposure of cDC2s to the virus recapitulates the type of activation observed in vivo. Our findings provide evidence that SARS-CoV-2 can interact directly with cDC2s and, by inducing the down-regulation of crucial molecules required for T cell activation, implements an efficient immune escape mechanism that correlates with disease severity.
On-site genomic epidemiological analysis of antimicrobial-resistant bacteria in Cambodia with portable laboratory equipment
Authors: Hirabayashi Aki , Yanagisawa Hideji , Takahashi Hiromizu , Yahara Koji , Boeing Philipp , Wolfenden Bethan , Nov Vandarith , Lorn Vichet , Veng Mom , Ann Vuth , Darapheak Chau , Shibayama Keigo , Suzuki Masato 
Published: March 2021

AbstractThe rapid emergence of carbapenemase-producing Gram-negative bacteria (CPGNB) is a global threat due to the high mortality of infection and limited treatment options. Although there have been many reports of CPGNB isolated from Southeast Asian countries, to date there has been no genetic analysis of CPGNB isolated from Cambodia. Sequence-based molecular epidemiological analysis enables a better understanding of the genotypic characteristics and epidemiological significance of antimicrobial-resistant (AMR) bacteria in each country, and allows countries to enact measures related to AMR issues. In this study, we performed on-site genomic epidemiological analysis of CPGNB isolated in Cambodia using a portable laboratory equipment called Bento Lab, which combines a PCR thermal cycler, microcentrifuge, gel electrophoresis apparatus, and LED transilluminator, along with the MinION nanopore sequencer. PCR targeting of major carbapenemase genes using Bento Lab revealed that twoEscherichia coliisolates and oneAcinetobacter baumanniiisolate harbored carbapenemase genes:blaNDM,blaOXA-48, andblaOXA-23, respectively. The results of phenotypic diagnostic tests for CPGNB, such as the carbapenem inactivation method and double-disk diffusion test using a specific inhibitor of metallo-β-lactamases, were consistent with their AMR genotypes. Whole-genome sequencing analysis using MinION suggested thatblaNDM-5andblaOXA-181genes were carried on plasmids (93.9-kb plasmid with IncFIA, IncFIB, IncFII, and IncQ1 replicons, and 51.5-kb plasmid with the IncX3 replicon, respectively) inE. coli, and thatblaOXA-23was encoded in two locations on the chromosome ofA. baumannii. Plasmids carryingblaNDM-5orblaOXA-181inE. coliwere highly structurally identical to plasmids prevalent in Enterobacterales in China and other countries, suggesting that they disseminated from a common evolutionary origin. Our findings demonstrate the potential impact of portable laboratory equipment on AMR bacteria research in hospitals and research centers with limited research facilities, and provide the first glimpse into the genomic epidemiology of CPGNB in Cambodia.
Bayesian calibration of a stochastic, multiscale agent-based model for predicting in vitro tumor growth
Authors: Lima Ernesto A. B. F. , Faghihi Danial , Philley Russel , Yang Jianchen , Virostko John , Phillips Caleb M. , Yankeelov Thomas 
Published: March 2021

Hybrid multiscale agent-based models (ABMs) are unique in their ability to simulate individual cell interactions and microenvironmental dynamics. Unfortunately, the high computational cost of modeling individual cells, the inherent stochasticity due to probabilistic phenotypic transitions, and numerous model parameters that are difficult to measure directly are fundamental limitations of applying such models to predict tumor dynamics. To overcome these challenges, we have developed a coarse-grained two-scale ABM (cgABM) calibrated with a set of time-resolved microscopy measurements of cancer cells grown with different initial conditions. The multiscale model consists of a reaction-diffusion type model capturing the spatio-temporal evolution of glucose and growth factors in the tumor microenvironment (at tissue scale), coupled with a lattice-free ABM to simulate individual cell dynamics (at cellular scale). The experimental data consists of BT474 human breast carcinoma cells initialized with different glucose concentrations and tumor cell confluences. The confluence of live and dead cells was measured every three hours over four days. Given this model and data, we perform a global sensitivity analysis to identify the relative importance of the model parameters. The subsequent cgABM with a reduced parameter space is calibrated within a Bayesian framework to the experimental data to estimate model parameters, which are then used to predict the temporal evolution of the living and dead cell populations. To this end, a moment-based Bayesian inference is proposed to account for the stochasticity of the cgABM while quantifying uncertainties in model parameters and observational data. The results indicate that the cgABM can reliably predict the spatiotemporal evolution of breast cancer cells observed by the microscopy data with an average error and standard deviation for live and dead cells being 7.61 [[EQUATION]] 2.01 and 5.78 [[EQUATION]] 1.13, respectively.