bluuebunny/crossref_metadata_2025_split huggingface dataset:
Similar levels of emotional contagion in male and female rats
Authors: Han Yingying , Sichterman Bo , Carrillo Maria , Gazzola Valeria , Keysers Christian 
Published: December 2019

AbstractEmotional contagion, the ability to feel what other individuals feel, is thought to be an important element of social life. In humans, emotional contagion has been shown to be stronger in women than men. Emotional contagion has been shown to exist also in rodents, and a growing number of studies explore the neural basis of emotional contagion in male rats and mice. These studies promise to shed light on the mechanisms that might go astray in psychiatric disorders characterized by dysfunctions of emotional contagion and empathy. Here we explore whether there are sex differences in emotional contagion in rats. We use an established paradigm in which a demonstrator rat receives footshocks while freezing is measured in both the demonstrator and an observer rat, which can hear, smell and see each other. By comparing pairs of male rats with pairs of female rats, we find (i) that female demonstrators freeze less when submitted to footshocks, but that (ii) the emotional contagion response, i.e. the degree of influence across the rats, does not depend on the sex of the rats. This was true whether emotional contagion was quantified based on the slope of a regression linking demonstrator and observer average freezing, or on Granger causality estimates of moment-to-moment freezing. The lack of sex differences in emotional contagion is compatible with an interpretation of emotional contagion as serving selfish danger detection.
Spontaneous generation of face recognition in untrained deep neural networks
Authors: Baek Seungdae , Song Min , Jang Jaeson , Kim Gwangsu , Paik Se-Bum 
Published: December 2019

AbstractFace-selective neurons are observed in the primate visual pathway and are considered the basis of facial recognition in the brain. However, it is debated whether this neuronal selectivity can arise spontaneously, or requires training from visual experience. Here, we show that face-selective neurons arise spontaneously in random feedforward networks in the absence of learning. Using biologically inspired deep neural networks, we found that face-selective neurons arise under three different network conditions: one trained using non-face natural images, one randomized after being trained, and one never trained. We confirmed that spontaneously emerged face-selective neurons show the biological view-point-invariant characteristics observed in monkeys. Such neurons suddenly vanished when feedforward weight variation declined to a certain level. Our results suggest that innate face-selectivity originates from statistical variation of the feedforward projections in hierarchical neural networks.
Interactions between the neural correlates of dispositional internally directed thought and visual imagery
Authors: Karapanagiotidis Theodoros , Jefferies Elizabeth , Smallwood Jonathan 
Published: December 2019

AbstractCognition is not always directed to the events in the here and now and we often self-generate thoughts and images in imagination. Important aspects of these self-generated experiences are associated with various dispositional traits. In this study, we explored whether these psychological associations relate to a common underlying neurocognitive mechanism. We acquired resting state functional magnetic resonance imaging data from a large cohort of participants and asked them to retrospectively report their experience during the scan. Participants also completed questionnaires reflecting a range of dispositional traits. We found thoughts emphasising visual imagery at rest were associated with dispositional tendency towards internally directed attention (self-consciousness and attentional problems) and linked to a stronger correlation between a posterior parietal network and a lateral fronto-temporal network. Furthermore, decoupling between the brainstem and a lateral visual network was associated with dispositional internally directed attention. Critically, these brain-cognition associations were related: the correlation between parietal-frontal regions and reports of visual imagery was stronger for individuals with increased connectivity between brainstem and visual cortex. Our results highlight neural mechanisms linked to the dispositional basis for patterns of self-generated thought, and suggest that accounting for dispositional traits is important when exploring the neural substrates of self-generated experience (and vice versa).
Glycan-dependent two-step cell adhesion mechanism of Tc toxins
Authors: Roderer Daniel , Bröcker Felix , Sitsel Oleg , Kaplonek Paulina , Leidreiter Franziska , Seeberger Peter H. , Raunser Stefan 
Published: December 2019

AbstractToxin complex (Tc) toxins are virulence factors widespread in insect and human bacterial pathogens. Tcs are composed of three subunits: TcA, TcB and TcC. TcA facilitates receptor-toxin interaction and membrane permeation, TcB and TcC form a toxin-encapsulating cocoon. While the mechanisms of holotoxin assembly and prepore-to-pore transition have been well-described, little is known about receptor binding and cellular uptake of Tcs. Here, we identify two classes of glycans, heparins/heparan sulfates and Lewis antigens, that act as receptors for different TcAs from insect- and human pathogenic bacteria. Glycan array screening and electron cryo microscopy (cryo-EM) structures reveal that all tested TcAs bind unexpectedly with their α-helical part of the shell domain to negatively charged heparins. In addition, TcdA1 from the insect-pathogen Photorhabdus luminescens binds to Lewis antigens with micromolar affinity. A cryo-EM structure of the TcdA1-Lewis X complex reveals that the glycan interacts with the receptor-binding domain D of the toxin. Our results suggest a two-step association mechanism of Tc toxins involving glycans on the surface of host cells.
Microscale Collagen and Fibroblast Interactions Enhance Primary Human Hepatocyte Functions in 3-Dimensional Models
Authors: Kukla David A. , Crampton Alexandra L. , Wood David K. , Khetani Salman R. 
Published: December 2019

ABSTRACTHuman liver models that are 3-dimensional (3D) in architecture are proving to be indispensable for diverse applications, including compound metabolism and toxicity screening during preclinical drug development, to model human liver diseases for the discovery of novel therapeutics, and for cell-based therapies in the clinic; however, further development of such models is needed to maintain high levels of primary human hepatocyte (PHH) functions for weeks to months in vitro. Therefore, here we determined how microscale 3D collagen-I presentation and fibroblast interaction could affect the long-term functions of PHHs. High-throughput droplet microfluidics was utilized to rapidly generate reproducibly-sized (~300 μm diameter) microtissues containing PHHs encapsulated in collagen-I +/− supportive fibroblasts, namely 3T3-J2 murine embryonic fibroblasts or primary human hepatic stellate cells (HSCs); self-assembled spheroids and bulk collagen gels (macrogels) containing PHHs served as gold-standard controls. Hepatic functions (e.g. albumin and cytochrome-P450 or CYP activities) and gene expression were subsequently measured for up to 6 weeks. We found that collagen-based 3D microtissues rescued PHH functions within static multi-well plates at 2- to 30-fold higher levels than self-assembled spheroids or macrogels. Further coating of PHH microtissues with 3T3-J2s led to higher hepatic functions than when the two cell types were either coencapsulated together or when HSCs were used for the coating instead. Additionally, the 3T3-J2-coated PHH microtissues displayed 6+ weeks of relatively stable hepatic gene expression and function at levels similar to freshly thawed PHHs. Lastly, microtissues responded in a clinically-relevant manner to drug-mediated CYP induction or hepatotoxicity. In conclusion, fibroblast-coated collagen microtissues containing PHHs display hepatic functions for 6+ weeks without any fluid perfusion at higher levels than spheroids and macrogels, and such microtissues can be used to assess drug-mediated CYP induction and hepatotoxicity. Ultimately, microtissues may find broader utility for modeling liver diseases and as building blocks for cell-based therapies.
Neural Arbitration between Social and Individual Learning Systems
Authors: Diaconescu Andreea O. , Stecy Madeline , Kasper Lars , Burke Christopher J. , Nagy Zoltan , Mathys Christoph , Tobler Philippe N. 
Published: December 2019

AbstractDecision making often requires integrating self-gathered information with information acquired from observing others. Depending on the situation, it may be beneficial to rely more on one than the other source, taking into account that either information may be imprecise or deceiving. The process by which one source is selected over the other based on perceived reliability, here defined as arbitration, has not been fully elucidated. In this study, we formalised arbitration as the relative reliability (precision) of predictions afforded by each learning system using hierarchical Bayesian models. In a probabilistic learning task, participants predicted the outcome of a lottery using recommendations from a more informed advisor and self-sampled outcomes. The number of points participants wagered on their predictions reflected arbitration: The higher the relative precision of one learning system over the other and the lower the intention volatility, the more points participants wagered on a given trial. Functional neuroimaging demonstrated that the arbitration signal was independent of decision confidence and involved modalityspecific brain regions. Arbitrating in favour of self-gathered information activated the dorsolateral prefrontal cortex and the midbrain whereas arbitrating in favour of social information engaged ventromedial prefrontal cortex and the temporoparietal junction. These findings are in line with domain specificity and indicate that relative precision captures arbitration between social and individual learning systems at both the behavioural and neural level.
A cross–nearest neighbor/Monte Carlo algorithm for single-molecule localization microscopy defines interactions between p53, Mdm2, and MEG3
Authors: Bauer Nicholas C. , Yang Anli , Wang Xin , Zhou Yunli , Klibanski Anne , Soberman Roy J. 
Published: December 2019

AbstractThe functions of long noncoding (lnc)RNAs such as MEG3 are defined by their interactions with other RNAs and proteins. These interactions, in turn, are shaped by their subcellular localization and temporal context. Therefore, it is important to be able to analyze the relationships of lncRNAs while preserving cellular architecture. The ability of MEG3 to suppress cell proliferation led to its recognition as a tumor suppressor. MEG3 has been proposed to activate p53 by disrupting the interaction of p53 with Mdm2. To test this mechanism in the native cellular context, we employed two-color direct stochastic optical reconstruction microscopy (dSTORM), a single-molecule localization microscopy (SMLM) technique to detect and quantify the localizations of p53, Mdm2, and MEG3 in U2OS cells. We developed a new cross-nearest neighbor/Monte Carlo algorithm to quantify the association of these molecules. Proof of concept for our method was obtained by examining the association between FKBP1A and mTOR, MEG3 and p53, and Mdm2 and p53. In contrast to previous models, our data support a model in which MEG3 modulates p53 independently of the interaction with Mdm2.
Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) Model
Authors: Khadka Niranjan , Liu Xijie , Zander Hans , Swami Jaiti , Rogers Evan , Lempka Scott F. , Bikson Marom 
Published: December 2019

AbstractObjectiveComputational current flow models of spinal cord stimulation (SCS) are widely used in device development, clinical trial design, and patient programming. Proprietary models of varied sophistication have been developed. An open-source model with state-of-the-art precision would serve as a standard for SCS simulation.ApproachWe developed a sophisticated SCS modeling platform, named Realistic Anatomically Detailed Open-Source Spinal Cord Stimulation (RADO-SCS) model. This platform consists of realistic and detailed spinal cord and ancillary tissues anatomy derived based on prior imaging and cadaveric studies. Represented tissues within the T9-T11 spine levels include vertebrae, intravertebral discs, epidural space, dura, CSF, white-matter, gray-matter, dorsal and ventral roots and rootlets, dorsal root ganglion, sympathetic chain, thoracic aorta, epidural space vasculature, white-matter vasculature, and thorax. As an exemplary, a bipolar SCS montage was simulated to illustrate the model workflow from the electric field calculated from a finite element model (FEM) to activation thresholds predicted for individual axons populating the spinal cord.Main ResultsCompared to prior models, RADO-SCS meets or exceeds detail for every tissue compartment. The resulting electric fields in white and gray-matter, and axon model activation thresholds are broadly consistent with prior stimulations.SignificanceThe RADO-SCS can be used to simulate any SCS approach with both unprecedented resolution (precision) and transparency (reproducibility). Freely available online, the RADO-SCS will be updated continuously with version control.
Morphine differentially alters the synaptic and intrinsic properties of D1R- and D2R-expressing medium spiny neurons in the nucleus accumbens
Authors: McDevitt Dillon S. , Jonik Benjamin , Graziane Nicholas M. 
Published: December 2019

AbstractExposure to opioids reshapes future reward and motivated behaviors partially by altering the functional output of medium spiny neurons (MSNs) in the nucleus accumbens shell. Here, we investigated how morphine, a highly addictive opioid, alters synaptic transmission and intrinsic excitability on dopamine D1-receptor (D1R) expressing and dopamine D2-receptor (D2R) expressing MSNs, the two main output neurons in the nucleus accumbens shell. Using whole-cell electrophysiology recordings, we show, that 24 h abstinence following repeated non-contingent administration of morphine (10 mg/kg, i.p.) in mice reduces miniature excitatory postsynaptic current (mEPSC) frequency and miniature inhibitory postsynaptic current (mIPSC) frequency on D2R-MSNs, with concomitant increases in D2R-MSN intrinsic membrane excitability. We did not observe any changes on synaptic or intrinsic changes on D1R-MSNs. Lastly, in an attempt to determine the integrated effect of the synaptic and intrinsic alterations on the overall functional output of D2R-MSNs, we measured the input-output efficacy by measuring synaptically-driven action potential firing. We found that both D1R-MSN and D2R-MSN output was unchanged following morphine treatment.
Integrity of the Uncinate Fasciculus Predicts Emotional Pattern Separation-Related fMRI Signals in the Hippocampal Dentate and CA3
Authors: Granger Steven J. , Leal Stephanie L. , Janecek John T. , McMillan Liv , Stern Hal , Yassa Michael A. 
Published: December 2019

AbstractAlterations in white matter integrity have been demonstrated in a number of psychiatric disorders that involve disruptions in emotional processing. One such pathway – the uncinate fasciculus (UF) – connects the orbitofrontal cortex (OFC) to the medial temporal lobes (MTL) and has been associated with early life adversity, maltreatment, anxiety, and depression. While it is purported to play a role in episodic memory and discrimination, its exact function remains poorly understood. We have previously described the role of the amygdala and dentate (DG)/CA3 fields of the hippocampus in the mnemonic discrimination of emotional experiences (i.e. emotional pattern separation). However, how this computation may be modulated by connectivity between the medial temporal lobes and the orbitofrontal cortex remains unknown. Here we ask the question of whether the uncinate fasciculus plays a role in influencing MTL subregional activity during emotional pattern separation. By combining diffusion imaging with high-resolution functional MRI, we found that reduced integrity of the UF is related to higher activation in the DG/CA3 subregions of the hippocampus during an emotional pattern separation task. We additionally report that higher levels of DG/CA3 activity are associated with poorer memory performance, suggesting that hyperexcitability in this network (which may be driven by CA3 recurrent collaterals) is associated with memory errors and that the UF may allow the OFC to exert inhibitory control on this network and improve discrimination of emotional experiences. This work provides novel mechanistic insight into the role of prefrontal interactions with the MTL, particularly in the context of emotional memory.
Effect of Sequence Depth and Length in Long-read Assembly of the Maize Inbred NC358
Authors: Ou Shujun , Liu Jianing , Chougule Kapeel M. , Fungtammasan Arkarachai , Seetharam Arun , Stein Joshua , Llaca Victor , Manchanda Nancy , Gilbert Amanda M. , Wei Xuehong , Chin Chen-Shan , Hufnagel David E. , Pedersen Sarah , Snodgrass Samantha , Fengler Kevin , Woodhouse Margaret , Walenz Brian P. , Koren Sergey , Phillippy Adam M. , Hannigan Brett , Kelly Dawe R. , Hirsch Candice N. , Hufford Matthew B. , Ware Doreen 
Published: December 2019

AbstractRecent improvements in the quality and yield of long-read data and scaffolding technology have made it possible to rapidly generate reference-quality assemblies for complex genomes. Still, generating these assemblies is costly, and an assessment of critical sequence depth and read length to obtain high-quality assemblies is important for allocating limited resources. To this end, we have generated eight independent assemblies for the complex genome of the maize inbred line NC358 using PacBio datasets ranging from 20-75x genomic depth and N50 read lengths of 11-21 kb. Assemblies with 30x or less depth and N50 read length of 11 kb were highly fragmented, with even the low-copy genic fraction of the genome showing degradation at 20x depth. Distinct sequence-quality thresholds were observed for complete assembly of genes, transposable elements, and highly repetitive genomic features such as telomeres, heterochromatic knobs and centromeres. This study provides a useful resource allocation reference to the community as long-read technologies continue to mature.
Charting the metabolic landscape of the facultative methylotroph Bacillus methanolicus
Authors: Delépine Baudoin , López Marina Gil , Carnicer Marc , Vicente Cláudia M. , Wendisch Volker F. , Heux Stéphanie 
Published: December 2019

ABSTRACTBacillus methanolicus MGA3 is a thermotolerant and relatively fast-growing methylotroph able to secrete large quantities of glutamate and lysine. These natural characteristics make B. methanolicus a good candidate to become a new industrial chassis organism, especially in a methanol-based economy. This has motivated a number of omics studies of B. methanolicus at the genome, transcript, protein and metabolic levels. Intriguingly, the only substrates known to support B. methanolicus growth as sole source of carbon and energy are methanol, mannitol, and to a lesser extent glucose and arabitol. We hypothesized that comparing methylotrophic and non-methylotrophic metabolic states at the flux level would yield new insights into MGA3 metabolism. 13C metabolic flux analysis (13C-MFA) is a powerful computational method to estimate carbon flows from substrate to biomass (i.e. the in vivo reaction rates of the central metabolic pathways) from experimental labeling data. In this study, we designed and performed a 13C-MFA of the facultative methylotroph B. methanolicus MGA3 growing on methanol, mannitol and arabitol to compare the associated metabolic states. The results obtained validate previous findings on the methylotrophy of B. methanolicus, allowed us to characterize the assimilation pathway of one of the studied carbon sources, and provide a better overall understanding of this strain.IMPORTANCEMethanol is cheap, easy to transport and can be produced both from renewable and fossil resources without mobilizing arable lands. As such, it is regarded as a potential carbon source to transition toward a greener industrial chemistry. Metabolic engineering of bacteria and yeast able to efficiently consume methanol is expected to provide cell factories that will transform methanol into higher-value chemicals in the so-called methanol economy. Toward that goal, the study of natural methylotrophs such as B. methanolicus is critical to understand the origin of their efficient methylotrophy. This knowledge will then be leveraged to transform such natural strains into new cell factories, or to design methylotrophic capability in other strains already used by the industry.
Highly diverse Asgard archaea participate in organic matter degradation in coastal sediments
Authors: Cai Mingwei , Liu Yang , Yin Xiuran , Zhou Zhichao , Friedrich Michael W. , Richter-Heitmann Tim , Nimzyk Rolf , Kulkarni Ajinkya , Wang Xiaowen , Li Wenjin , Pan Jie , Yang Yuchun , Gu Ji-Dong , Li Meng 
Published: December 2019

ABSTRACTAsgard is an archaeal superphylum that might hold the key to understand the origin of eukaryotes, but its diversity and ecological roles remain poorly understood. Here, we reconstructed 15 metagenomic-assembled genomes (MAGs) from coastal sediments covering most known Asgard archaea and a novel group, which is proposed as a new Asgard phylum named as the “Gerdarchaeota”. Genomic analyses predict that Gerdarchaeota are facultative anaerobes in utilizing both organic and inorganic carbon. Unlike their closest relatives Heimdallarchaeota, Gerdarchaeota have genes encoding for cellulase and enzymes involving in the tetrahydromethanopterin-based Wood–Ljungdahl pathway. Transcriptomic evidence showed that all known Asgard archaea are capable of degrading organic matter, including peptides, amino acids and fatty acids, in different ecological niches in sediments. Overall, this study broadens the diversity of the mysterious Asgard archaea and provides evidence for their ecological roles in coastal sediments.
Gorlin syndrome-induced pluripotent stem cells form medulloblastoma with loss of heterozygosity in PTCH1
Authors: Ikemoto Yu , Miyashita Toshiyuki , Nasu Michiyo , Hatsuse Hiromi , Kajiwara Kazuhiro , Fujii Katsunori , Motojima Toshino , Toyoda Masashi , Umezawa Akihiro 
Published: December 2019

AbstractGorlin syndrome is a rare autosomal dominant hereditary disease with high incidence of tumors such as basal cell carcinoma and medulloblastoma. Disease-specific induced pluripotent stem cells (iPSCs) have now been used as a model to analyze disease pathogenesis as well as an animal model. In this study, we generated iPSCs derived from fibroblasts of four patients with Gorlin syndrome (Gln-iPSCs) with a heterozygous mutation of the PTCH1 gene. Gln-iPSCs from the four patients developed medulloblastoma in 100% (four out of four), a manifestation of Gorlin syndrome, in the teratomas after implantation into immunodeficient mice, but none (0/584) of the other iPSC-teratomas. One of the medulloblastomas had loss of heterozygosity in the PTCH1 gene while benign teratoma, i.e. non-medulloblastoma part, did not, indicating a close clinical correlation between tumorigenesis in Gorlin syndrome patients and Gln-iPSCs.