bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subjective Beliefs In, Out, and About Control: A Quantitative Analysis
Authors: Mancinelli Federico , Roiser Jonathan , Dayan Peter 
Published: May 2020

AbstractA critical facet of adjusting one’s behaviour after succeeding or failing at a task is assigning responsibility for the ultimate outcome. Humans have trait- and state-like tendencies to implicate aspects of their own behaviour (called ‘internal’ ascriptions) or facets of the particular task or Lady Luck (‘chance’). However, how these tendencies interact with actual performance is unclear. We designed a novel task in which subjects had to learn the likelihood of achieving their goals, and the extent to which this depended on their efforts. High internality (Levenson I-score) was associated with decision making patterns that are less vulnerable to failure, and at the same time less oriented to more rewarding achievements. Our computational analyses suggested that this depended heavily on the adjustment in the perceived achievability of riskier goals following failure. We found beliefs about chance not to be explanatory of choice behaviour in our task. Beliefs about powerful others were strong predictors of behaviour, but only when subjects lacked substantial influence over the outcome. Our results provide an evidentiary basis for heuristics and learning differences that underlie the formation and maintenance of control expectations by the self.
Complexity analysis of heartbeat-related signals in Brain MRI time series as a potential biomarker for ageing and cognitive performance
Authors: López Pérez David , Bokde Arun L. W. , Kerskens Christian M. 
Published: May 2020

AbstractGetting older affects both the structure of the brain and some cognitive capabilities. Until now, magnetic resonance imaging (MRI) approaches have been unable to give a coherent reflection of the cognitive declines. It shows the limitation of the contrast mechanisms used in most MRI investigations, which are indirect measures of brain activities depending on multiple physiological and cognitive variables. However, MRI signals may contain information of brain activity beyond these commonly used signals caused by the neurovascular response. Here, we apply a zero-spin echo (ZSE) weighted MRI sequence, which can detect heartbeat evoked signals (HES). Remarkably, these MRI signals have properties only known from electrophysiology. We investigated the complexity of the HES arising from this sequence in two age groups; young (18-29 years) and old (over 65 years). While comparing young and old participants, we show that the complexity of the HES decreases with age, where the stability and chaoticity of these HES are particularly sensitive to age. However, we also found individual differences which were independent of age. Complexity measures were related to scores from different cognitive batteries and showed that higher complexity may be related to better cognitive performance. These findings underpin the affinity of the HES to electrophysiological signals. The profound sensitivity of these changes in complexity shows the potential of HES for understanding brain dynamics that need to be tested in more extensive and diverse populations with clinical relevance for all neurovascular diseases.
Host-dependent fungus-fungus competition suppresses fungal pathogenesis inArabidopsis thaliana
Authors: Pathompitaknukul Kuldanai , Hiruma Kei , Tanaka Hiroyuki , Kawamura Nanami , Toyoda Atsushi , Itoh Takehiko , Saijo Yusuke 
Published: May 2020

AbstractLike animals, plants accommodate a rich diversity of microbes, typically without discernible disease symptoms. How their pathogenesis is prevented in the host remains obscure. Here, we show that the root-infecting fungusColletotrichum fructicolaof theC.gloeosporioidesclade (CgE), isolated from field-grown healthy Brassicaceae plants, inhibits growth of pathogenic fungi inArabidopsis thaliana, in a phosphate status-dependent manner. Loss of host ethylene signaling or phytoalexins, camalexin or indole glucosinolates, however, allows CgE to display pathogenesis, suggesting host contributions to endophytic CgE colonization and benefit. Compared to a closely-relatedC. gloeosporioidespathogen (CgP), CgE is characterized by genome expansion and >700 fungal genes (4.34%) specifically induced in the host roots when co-inoculated with CgP, including genes related to fungal secondary metabolism. This may underlie antimicrobial tolerance of CgE and its dominance over pathogenic fungi within the host, pointing to a role for fungus-fungus competition in asymptomatic fungal colonization in plants.
STX18-AS1is a Long Noncoding RNA predisposing to Atrial Septal Defect via downregulation ofNKX2-5in differentiating cardiomyocytes
Authors: Liu Yingjuan , Choy Mun-kit , Abraham Sabu , Tenin Gennadiy , Black Graeme C. , Keavney Bernard D. 
Published: May 2020

AbstractPrevious genome-wide association studies (GWAS) have identified a region of chromosome 4p16 associated with the risk of Atrial Septal Defect (ASD), which is among the commonest Congenital Heart Disease (CHD) phenotypes. Here, we identify the responsible gene in the region and elucidate disease mechanisms. Linkage disequilibrium in the region, eQTL analyses in human atrial tissues, and spatio-temporal gene expression studies in human embryonic hearts concordantly suggested the long noncoding RNA (lncRNA)STX18-AS1as the causative gene in the region. Using CRISPR/Cas9 knockdown in HepG2 cells,STX18-AS1was shown to regulate the expression of the key cardiac transcription factorNKX2-5via atrans-acting effect on promoter histone methylation. Furthermore,STX18-AS1knockdown depleted the potential of human embryonic stem cells (H9) to differentiate into cardiomyocytes, without affecting their viability and pluripotency, providing a mechanistic explanation for the clinical association.
A genomic footprint of a moving hybrid zone in marbled newts
Authors: Arntzen Jan W. , López-Delgado Julia , van Riemsdijk Isolde , Wielstra Ben 
Published: May 2020

AbstractWe developed a panel of 44 nuclear genetic markers and applied this to two species of marbled newts in the north (Triturus marmoratus) and the south (T. pygmaeus) of the Iberian Peninsula, to document pattern and process of interspecific gene flow. The northernmost occurrence ofT. pygmaeusgenetic material was in aT. marmoratuspopulation north of the Vouga river estuary. This suggested the past presence of a hybrid zone, possibly coinciding with a natural river outlet at ca. 1200 A.D. Since 1808, the species contact has moved back south to a by then completed, man-made Vouga channel. We also found evidence for aT. marmoratusgenomic footprint inT. pygmaeusfrom the Serra de Sintra, near Lisbon. In combination with a previously reported southern, relic occurrence ofT. marmoratusin between both areas, the data point to the superseding with hybridization ofT. marmoratusbyT. pygmaeus. We estimate that the species hybrid zone has moved over a distance of ca. 215 km.
Pharmacologically modified pluripotent stem cell-based cancer vaccines with anti-metastatic potential
Authors: Heront-Kishi Masae , Asgarova Afag , Desterke Christophe , Chaker Diana , de Goër de Herve Marie-Ghislaine , Turhan Ali G , Bennaceur-Griscelli Annelise , Griscelli Frank 
Published: May 2020

ABSTRACTCancer is maintained by the activity of a rare population of self-renewing “cancer stem cells” (CSCs), which are resistant to conventional therapies. CSCs share several antigenic determinants with pluripotent stem cells (PSCs). We show here that PSCs, combined with a histone deacetylase inhibitor (HDACi), are able to elicit major anti-tumor responses in a model of highly aggressive breast cancer. This immunotherapy strategy was effective in preventing tumor establishment and efficiently targeted CSCs by inducing extensive modifications of the tumor microenvironment. The anti-tumor effect was correlated with a reduction in regulatory T and myeloid-derived suppressor cell populations and an increase in cytotoxic CD8+T cells within the tumor and the spleen along with a drastic reduction in metastatic dissemination and an improvement in the survival rate. These results demonstrate for the first time the possibility of using PSCs and HDACi as an allogeneic anticancer vaccine, in future universal immunotherapy strategies.
Phenotypes to remember: Evolutionary developmental memory capacity and robustness
Authors: Szilágyi András , Szabó Péter , Santos Mauro , Szathmáry Eörs 
Published: May 2020

AbstractThere is increased awareness of the possibility of developmental memories resulting from evolutionary learning. Genetic regulatory and neural networks can be modelled by analogous formalism raising the important question of productive analogies in principles, processes and performance. We investigate the formation and persistence of various developmental memories of past phenotypes asking how the number of remembered past phenotypes scales with network size, to what extent memories stored form by Hebbian-like rules, and how robust these developmental “devo-engrams” are against networks perturbations (graceful degradation). The analogy between neural and genetic regulatory networks is not superficial in that it allows knowledge transfer between fields that used to be developed separately from each other. Known examples of spectacular phenotypic radiations could partly be accounted for in such terms.
Multimodal immersive trail making – virtual reality paradigm to study cognitive-motor interactions
Authors: Plotnik Meir , Ben-Gal Oran , Doniger Glen M. , Gottlieb Amihai , Bahat Yotam , Cohen Maya , Kimel-Naor Shani , Zeilig Gabi , Beeri Michal Schnaider 
Published: May 2020

ABSTRACTBackgroundNeuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention - one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test-retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function.MethodsHealthy adults (n=147) in three age groups (young:n=50; middle-aged:n=80; older:n=17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance.ResultsConstruct validity was substantiated by moderate correlations between the ‘gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA0.58, tB0.71; HMD-CTT: tA0.62, tB0.69). VR versions showed relatively high test-retest reliability (intraclass correlation; VR: tA0.60-0.75, tB0.59-0.89; original: tA0.75-0.85, tB0.77-0.80) and discriminant validity (area under the curve; VR: tA0.70-0.92, tB0.71-0.92; original: tA0.73-0.95, tB0.77-0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants.ConclusionsThe present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.
Rapid toxin sequestration modifies poison frog physiology
Authors: O’Connell Lauren A. ,   LS50: Integrated Science Laboratory Course, O’Connell Jeremy D. , Paulo Joao A. , Trauger Sunia A. , Gygi Steven P. , Murray Andrew W. 
Published: May 2020

AbstractPoison frogs sequester chemical defenses from their diet of leaf litter arthropods for defense against predation. Little is known about the physiological adaptations that confer this unusual bioaccumulation ability. We conducted an alkaloid-feeding experiment with the Diablito poison frog (Oophaga sylvatica) to determine how quickly alkaloids are accumulated and how toxins modify frog physiology using quantitative proteomics. Diablito frogs rapidly accumulated the alkaloid decahydroquinoline within four days, and dietary alkaloid exposure altered protein abundance in the intestines, liver, and skin. Many proteins that increased in abundance with decahydroquinoline accumulation are plasma glycoproteins, including the complement system and the toxin-binding protein saxiphilin. Other protein classes that change in abundance with decahydroquinoline accumulation are membrane proteins involved in small molecule transport and metabolism. Overall, this work shows poison frogs can rapidly accumulate alkaloids, which alter carrier protein abundance, initiate an immune response, and alter small molecule transport and metabolism dynamics across tissues.Summary StatementPoison frogs rapidly accumulate toxins, which changes abundance of proteins involved in the immune system and small molecule binding and metabolism across tissues.
Wnt Signalling Orchestrates the Immune Response and Cardiac Damage DuringTrypanosoma cruziInfection
Authors: Volpini Ximena , Ambrosio Laura Fernanda , Brajín Agustina , Brugo María Belen , Aoki María Pilar , Rivarola Hector Walter , Alfonso Fernando , Fozzatti Laura , Cervi Laura , Motran Claudia Cristina 
Published: May 2020

AbstractChagas’ cardiomyopathy is the consequence of a compromised electrical and mechanical cardiac function, with parasite persistence, unbalanced inflammation and pathological tissue remodelling, being intricately related to the myocardial aggression and the impaired function. Recent studies have shown that Wnt signalling pathways, which are important for developmental processes, play a critical role in the pathogenesis of cardiac and vascular diseases. In addition, we have reported thatTrypanosoma cruziinfection activates Wnt signalling pathways in macrophages to promote their intracellular replication, with treatment of mice with IWP-L6 (an inhibitor of the O-acyl-transferase, PORCN, responsible for the post-translational modifications necessary for Wnt proteins secretion) being able to diminish parasitaemia and tissue parasitism. Therefore, Wnt signalling may contribute to the development of Chagas’ cardiomyopathy. In this work we have evaluated the effectiveness of Wnt secretion inhibition to control the parasite replication, modulate the adaptive immune response, and prevent the development of cardiac lesions in an experimental model of chronic Chagas disease. The IWP-L6 treatment, administered toT. cruziinfected BALB/c mice in a time window during the acute phase of the infection, was able to control the parasitaemia and heart parasitism together with the amelioration of the electrical, mechanical and histopathological cardiac alterations observed in chronically infected mice. Moreover, we demonstrated that during the acute phase of the infection Wnt signalling activation contributes to promote specific Th2-type immune response and to maintain the suppressive activity of Treg cells. Our data provide evidence that inhibition of Wnt signalling during the acute phase ofT. cruziinfection controls the parasite replication, inhibits the development of parasite-prone and fibrosis-prone Th2-type immune response and prevents the development of cardiac lesions characteristics of chronic Chagas disease. Our study suggests that Wnt signalling pathway might be a potential target to prevent the development ofT. cruzi-induced cardiomyopathy.
Head-to-head comparison of four antigen-based rapid detection tests for the diagnosis of SARS-CoV-2 in respiratory samples
Authors: Weitzel Thomas , Legarraga Paulette , Iruretagoyena Mirentxu , Pizarro Gabriel , Vollrath Valeska , Araos Rafael , Munita José M. , Porte Lorena 
Published: May 2020

AbstractIn the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We compared the performance of four rapid antigen detection tests for SARS-CoV-2 in respiratory samples. Immunochromatographic SARS-CoV-2 assays from RapiGEN, Liming bio, Savant, and Bioeasy were evaluated using universal transport medium containing naso-oropharyngeal swabs from suspected Covid-19 cases. The diagnostic accuracy was determined in comparison to SARS-CoV-2 RT-PCR. A total of 111 samples were included; 80 were RT-PCR positive. Median patients’ age was 40 years, 55% were female, and 88% presented within the first week after symptom onset. The evaluation of the Liming bio assay was discontinued due to insufficient performance. The overall sensitivity values of RapiGEN, Liming bio, and Bioeasy tests were 62.0% (CI95% 51.0–71.9), 16.7% (CI95% 10.0–26.5), and 85.0% (CI95% 75.6–91.2), respectively, with specificities of 100%. Sensitivity was significantly higher in samples with high viral loads (RapiGEN, 84.9%; Bioeasy, 100%). The study highlighted the significant heterogeneity of test performance among evaluated assays, which might have been influenced by the use of a non-validated sample material. The high sensitivity of some tests demonstrated that rapid antigen detection has the potential to serve as an alternative diagnostic method, especially in patients presenting with high viral loads in early phases of infection. This is particularly important in situations with limited access to RT-PCR or prolonged turnaround time. Further comparative evaluations are necessary to select products with high performance among the growing market of diagnostic tests for SARS-CoV-2.
PRosettaC: Rosetta based modeling of PROTAC mediated ternary complexes
Authors: Zaidman Daniel , London Nir 
Published: May 2020

AbstractProteolysis-targeting chimeras (PROTACs), which induce degradation by recruitment of an E3 ligase to a target protein, are gaining much interest as a new pharmacological modality. However, designing PROTACs is challenging. Formation of a ternary complex between the protein target, the PROTAC and the recruited E3 ligase is considered paramount for successful degradation. A structural model of this ternary complex could in principle inform rational PROTAC design. Unfortunately, only a handful of structures are available for such complexes, necessitating tools for their modeling. We developed a combined protocol that alternates between sampling of the protein-protein interaction space and the PROTAC molecule conformational space. Application of this protocol - PRosettaC - to a benchmark of known PROTAC ternary complexes results in near-native predictions, with often atomic accuracy prediction of the protein chains, as well as the PROTAC binding moieties. It allowed the modeling of a CRBN/BTK complex that recapitulated experimental results for a series of PROTACs. PRosettaC generated models may be used to design PROTACs for new targets, as well as improve PROTACs for existing targets, potentially cutting down time and synthesis efforts.
The carboxyl-termini of RAN translated GGGGCC nucleotide repeat expansions modulate toxicity in models of ALS/FTD
Authors: He Fang , Flores Brittany N. , Krans Amy , Frazer Michelle , Natla Sam , Niraula Sarjina , Adefioye Olamide , Barmada Sami J. , Todd Peter K. 
Published: May 2020

AbstractAn intronic hexanucleotide repeat expansion inC9ORF72causes familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This repeat is thought to elicit toxicity through RNA mediated protein sequestration and repeat-associated non-AUG (RAN) translation of dipeptide repeat proteins (DPRs). We generated a series of transgenicDrosophilamodels expressing GGGGCC (G4C2) repeats either inside of an artificial intron within a GFP reporter or within the 5’ UTR of GFP placed in different downstream reading frames. Expression of 484 intronic repeats elicited minimal alterations in eye morphology, viability, longevity, or larval crawling but did trigger RNA foci formation, consistent with prior reports. In contrast, insertion of repeats into the 5’ UTR elicited differential toxicity that was dependent on the reading frame of GFP relative to the repeat. Greater toxicity correlated with a short and unstructured carboxyl terminus in the glycine-arginine (GR) RAN protein reading frame. This change in C-terminal sequence triggered nuclear accumulation of all three RAN DPRs. A similar differential toxicity and dependence on the GR carboxyl terminus was observed when repeats were expressed in rodent neurons. The presence of the native carboxyl-termini across all three reading frames was partly protective. Taken together, these findings suggest that carboxyl terminal sequences outside of the repeat region may alter the behavior and toxicity of dipeptide repeat proteins derived from GGGGCC repeats.
Clarifying the role of higher-level cortices in resolving perceptual ambiguity using Ultra High Field fMRI
Authors: Dowdle Logan , Ghose Geoffrey , Ugurbil Kamil , Yacoub Essa , Vizioli Luca 
Published: May 2020

AbstractThe brain is organized into distinct, flexible networks. Within these networks, cognitive variables such as attention can modulate sensory representations in accordance with moment-to-moment behavioral requirements. These modulations can be studied by varying task demands; however, the tasks employed are often incongruent with the postulated functions of a sensory system, limiting the characterization of the system in relation to natural behaviors. Here we combine domain-specific task manipulations and ultra-high field fMRI to study the nature of top-down modulations. We exploited faces, a visual category underpinned by a complex cortical network, and instructed participants to perform either a stimulus-relevant/domain-specific or a stimulus-irrelevant task in the scanner. We found that 1. perceptual ambiguity (i.e. difficulty of achieving a stable percept) is encoded in top-down modulations from higher-level cortices; 2. the right inferior-temporal lobe is active under challenging conditions and uniquely encodes trial-by-trial variability in face perception.