bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why and how access consciousness can account for phenomenal consciousness
Authors: Naccache Lionel 
Published: July 2018

According to a popular distinction proposed by the philosopher Ned Block in 1995, our conscious experience would overflow the very limited set of what we can consciously report to ourselves and to others. He proposed to coin this limited consciousness ‘Access Consciousness' (A-Cs) and to define ‘Phenomenal Consciousness’ as a much richer subjective experience that is not accessed but that would still delineate the extent of consciousness. In this article, I review and develop five major problems raised by this theory, and show how a strict A-Cs theory can account for our conscious experience. I illustrate such an A-Cs account within the global workspace (GW) theoretical framework, and revisit some seminal empirical findings and neuropsychological syndromes. In this strict A-Cs perspective, subjective reports are not conceived as the mere passive broadcasting of information to the GW, but as resulting from a dynamic and active chain of internal processes that notably include interpretative and belief attribution stages. Finally, I list a set of testable predictions, of unsolved questions and of some counterintuitive hypotheses.
This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
COMPASS: An Open-Source, General-Purpose Software Toolkit for Computational Psychiatry
Authors: Yousefi Ali , Paulk Angelique C. , Basu Ishita , Dougherty Darin D. , Eskandar Emad N. , Eden Uri T. , Widge Alik S. 
Published: July 2018

AbstractMathematical modeling of behavior during psychophysical tasks, referred to as “computational psychiatry”, could greatly improve our understanding of mental disorders. One barrier to broader adoption of computational methods is that they often require advanced programming skills. We developed the Computational Psychiatry Adaptive State-Space (COMPASS) toolbox, an open-source MATLAB-based software package. After specifying a few parameters in a small set of user-friendly functions, COMPASS allows the user to efficiently fit of a wide range of computational behavioral models. The model output can be analyzed as an experimental outcome or used as a regressor for neural data, and can be tested using goodness-of-fit methods. Here, we demonstrate that COMPASS can replicate two computational behavior analyses from different groups. COMPASS replicates and, in one case, slightly improves on the original modeling results. This flexible, general-purpose toolkit should accelerate the use of computational modeling in psychiatric neuroscience.
The role of rare copy number variants in depression
Authors: Kendall Kimberley M , Rees Elliott , Bracher-Smith Matthew , Riglin Lucy , Zammit Stanley , O’Donovan Michael C , Owen Michael J , Jones Ian , Kirov George , Walters James T R 
Published: July 2018

AbstractThe role of large, rare copy number variants (CNVs) in neurodevelopmental disorders is well-established,1–5 but their contribution to common psychiatric disorders, such as depression, remains unclear. We have previously shown that a substantial proportion of CNV enrichment in schizophrenia is explained by CNVs associated with neurodevelopmental disorders.6, 7 Depression shares genetic risk with schizophrenia8, 9 and is frequently comorbid with neurodevelopmental disorders10, 11, suggesting to us the hypothesis that if CNVs play a role in depression, neurodevelopmental CNVs are those most likely to be associated. We confirmed this in UK Biobank by showing that neurodevelopmental CNVs were associated with depression (24,575 cases, 5.87%; OR=1.36, 95% CI 1.22-1.51, p=1.61×10-8), whilst finding no evidence implicating other CNVs. Four individual neurodevelopmental CNVs increased risk of depression (1q21.1 duplication, PWS duplication, 16p13.11 deletion, 16p11.2 duplication). The association between neurodevelopmental CNVs and depression was partially explained by social deprivation but not by education attainment or physical illness.
Mechanical Behavior of Axonal Microtubules; the Effect of Fluid on the Rupture of Axonal Microtubules
Authors: Manuchehrfar Farid , Shamloo Amir 
Published: July 2018

AbstractAxonal microtubules are dynamically instable bundles in the interior part of the axon. The dynamics of these bundles are of vital importance in the behavior of axon such as their degeneration. Each axon typically contains 10~100 microtubule bundles with average length of 4μm. These bundles are coated with cytoplasm and are cross linked with random number of tau proteins. In some circumstances such as acceleration or deceleration of head in space or during the strike, they are placed in tension which may cause rupture of these bundles or disconnection of tau protein cross links. Mechanical behavior and rupture modality of microtubule bundles are becoming more and more important recently. In our model, viscoelastic microtubule bundles constituted from several discrete masses connected to the neighboring mass with a standard linear solid (SLS), a spring damper model. In addition we take into account the effect of cytoplasm by Dissipative Particle Dynamic (DPD) to investigate the rupture nature and mechanical behavior of these bundles and the effect of cytoplasm on their mechanical behavior. We obtain these results for various amounts of suddenly applied end forces to the group of axonal microtubule bundles.
Haplotype-resolved and integrated genome analysis of the cancer cell line HepG2
Authors: Zhou Bo , Ho Steve S. , Greer Stephanie U. , Spies Noah , Bell John M. , Zhang Xianglong , Zhu Xiaowei , Arthur Joseph G. , Byeon Seunggyu , Pattni Reenal , Saha Ishan , Huang Yiling , Song Giltae , Perrin Dimitri , Wong Wing H. , Ji Hanlee P. , Abyzov Alexej , Urban Alexander E. 
Published: July 2018

SUMMARYThe HepG2 cancer cell line is one of the most widely-used biomedical research and one of the main cell lines of ENCODE. Vast numbers of functional genomics and epigenomics datasets have been produced to characterize its biology. However, the correct interpretation such data requires an understanding of the cell line’s genome sequence and genome structure. Using a variety of sequencing and analysis methods, we identified a wide spectrum of HepG2 genome characteristics: copy numbers of chromosomal segments, SNVs and Indels (corrected for aneuploidy), phased haplotypes extending to entire chromosome arms, loss of heterozygosity, retrotransposon insertions, structural variants (SVs) including complex and somatic genomic rearrangements. We also identified allele-specific expression and DNA methylation genome-wide and assembled an allele-specific CRISPR/Cas9 targeting map.SIGNIFICANCEHaplotype-resolved and comprehensive whole-genome analysis of a widely-used cell line for cancer research and ENCODE, HepG2, serves as an essential resource for unlocking complex cancer gene regulation using a genome-integrated framework and also provides genomic context for the analysis of ~1,000 functional datasets to date on ENCODE for biological discovery. We also demonstrate how deeper insights into genomic regulatory complexity are gained by adopting a genome-integrated framework.
Explore or reset? Pupil diameter transiently increases in self-chosen switches between cognitive labor and leisure in either direction
Authors: Algermissen Johannes , Bijleveld Erik , Jostmann Nils B. , Holland Rob W. 
Published: July 2018

AbstractWhen people invest effort in cognitive work, they often keep an eye open for rewarding alternative activities. Previous research suggests that the norepinephrine (NE) system regulates such trade-offs between exploitation of the current task and exploration of alternative possibilities. Here we examine the possibility that the NE-system is involved in a related trade-off, i.e., the trade-off between cognitive labor and leisure. We conducted two pre-registered studies (total N = 62) in which participants freely chose to perform either a paid 2-back task (labor) vs. a non-paid task (leisure), while we tracked their pupil diameter—which is an indicator of the state of the NE system. In both studies, consistent with prior work, we found (a) increases in pupil baseline and (b) decreases in pupil dilation when participants switched from labor to leisure. Unexpectedly, we found the same pattern when participants switched from leisure back to labor. Both increases in pupil baseline and decreases in pupil dilation were short-lived. Collectively, these results are more consistent with a role of norepinephrine in reorienting attention and task switching, as suggested by network reset theory, than with a role in motivation, as suggested by adaptive gain theory.
Perceptual grouping in the cocktail party: contributions of voice-feature continuity
Authors: Kreitewolf Jens , Mathias Samuel R. , Trapeau Régis , Obleser Jonas , Schönwiesner Marc 
Published: July 2018

AbstractCocktail parties pose a difficult yet solvable problem for the auditory system. Previous work has shown that the cocktail-party problem is considerably easier when all sounds in the target stream are spoken by the same talker (thevoice-continuity benefit).The present study investigated the contributions of two of the most salient voice features — glottal-pulse rate (GPR) and vocal-tract length (VTL) — to the voice-continuity benefit. Twenty young, normal-hearing listeners participated in two experiments. On each trial, listeners heard concurrent sequences of spoken digits from three different spatial locations and reported the digits coming from a target location. Critically, across conditions, GPR and VTL either remained constant or varied across target digits. Additionally, across experiments, the target location either remained constant (Experiment 1) or varied (Experiment 2) within a trial. In Experiment 1, listeners benefited from continuity in either voice feature, but VTL continuity was more helpful than GPR continuity. In Experiment 2, spatial discontinuity greatly hindered listeners’ abilities to exploit continuity in GPR and VTL. The present results suggest that selective attention benefits from continuity in target voice features, and that VTL and GPR play different roles for perceptual grouping and stream segregation in the cocktail party.
Genome-scale sequence disruption following biolistic transformation in rice and maize
Authors: Liu Jianing , Nannas Natalie J. , Fu Fang-fang , Shi Jinghua , Aspinwall Brooke , Parrott Wayne A. , Dawe R. Kelly 
Published: July 2018

ABSTRACTWe biolistically transformed linear 48 kb phage lambda and two different circular plasmids into rice and maize and analyzed the results by whole genome sequencing and optical mapping. While some transgenic events showed simple insertions, others showed extreme genome damage in the form of chromosome truncations, large deletions, partial trisomy, and evidence of chromothripsis and breakage-fusion bridge cycling. Several transgenic events contained megabase-scale arrays of introduced DNA mixed with genomic fragments assembled by non-homologous or microhomology-mediated joining. Damaged regions of the genome, assayed by the presence of small fragments displaced elsewhere, were often repaired without a trace, presumably by homology-dependent repair (HDR). The results suggest a model whereby successful biolistic transformation relies on a combination of end joining to insert foreign DNA and HDR to repair collateral damage caused by the microprojectiles. The differing levels of genome damage observed among transgenic events may reflect the stage of the cell cycle and the availability of templates for HDR.
Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography
Authors: Yoder Nate , Gouaux Eric 
Published: July 2018

AbstractAcid sensing ion channels (ASICs) are proton-gated ion channels that are members of the degenerin/epithelial sodium channel superfamily and are expressed throughout central and peripheral nervous systems. ASICs have been implicated in multiple physiological processes and are subject to numerous forms of endogenous and exogenous regulation that include modulation by Ca2+ and Cl− ions. However, the mapping of ion binding sites as well as a structure-based understanding of the mechanisms underlying ionic modulation of ASICs have remained elusive. Here we present ion binding sites of chicken ASIC1a in resting and desensitized states at high and low pH, respectively, determined by anomalous diffraction x-ray crystallography. The acidic pocket serves as a nexus for divalent cation binding at both low and high pH, while we observe divalent cation binding within the central vestibule on the resting channel at high pH only. Moreover, neutralization of residues positioned to coordinate divalent cations via individual and combined Glu to Gln substitutions reduced, but did not extinguish, modulation of proton-dependent gating by Ca2+. Additionally, we demonstrate that anion binding at the canonical thumb domain site is state-dependent and present a previously undetected anion site at the mouth of the extracellular fenestrations on the resting channel. Our results map anion and cation sites on ASICs across multiple functional states, informing possible mechanisms of modulation and providing a blueprint for the design of therapeutics targeting ASICs.
Evolution of neocortical folding: A phylogenetic comparative analysis of MRI from 34 primate species
Authors: Heuer Katja , Gulban Omer Faruk , Bazin Pierre-Louis , Osoianu Anastasia , Valabregue Romain , Santin Mathieu , Herbin Marc , Toro Roberto 
Published: July 2018

AbstractWe conducted a comparative analysis of primate cerebral size and neocortical folding using magnetic resonance imaging data from 65 individuals belonging to 34 different species. We measured several neocortical folding parameters and studied their evolution using phylogenetic comparative methods. Our results suggest that the most likely model for neuroanatomical evolution is one where differences appear randomly (the Brownian Motion model), however, alternative models cannot be completely ruled out. We present estimations of the ancestral primate phenotypes as well as estimations of the rates of phenotypic change. Based on the Brownian Motion model, the common ancestor of primates may have had a folded cerebrum similar to that of a small lemur such as the aye-aye. Finally, we observed a non-linear relationship between fold wavelength and fold depth with cerebral volume. In particular, gyrencephalic primate neocortices across different groups exhibited a strikingly stable fold wavelength of about 12 mm (± 20%), despite a 20-fold variation in cerebral volume. We discuss our results in the context of current theories of neocortical folding.
PBLR: an accurate single cell RNA-seq data imputation tool considering cell heterogeneity and prior expression level of dropouts
Authors: Zhang Lihua , Zhang Shihua 
Published: July 2018

AbstractSingle-cell RNA sequencing (scRNA-seq) provides a powerful tool to determine precise expression patterns of tens of thousands of individual cells, decipher cell heterogeneity and cell subpopulations and so on. However, scRNA-seq data analysis remains challenging due to various technical noise, e.g., the presence of dropout events (i.e., excess zero counts). Taking account of cell heterogeneity and structural effect of expression on dropout rate, we propose a novel method named PBLR to accurately impute the dropouts of scRNA-seq data. PBLR is an effective tool to recover dropout events on both simulated and real scRNA-seq datasets, and can dramatically improve low-dimensional representation and recovery of gene-gene relationship masked by dropout events compared to several state-of-the-art methods. Moreover, PBLR also detect accurate and robust cell subpopulations automatically, shedding light its flexibility and generality for scRNA-seq data analysis.
Association Between Rare Copy Number Variation and Response to Social Skills Training in Autism Spectrum Disorder
Authors: Tammimies Kristiina , Li Danyang , Rabkina Ielyzaveta , Stamouli Sofia , Becker Martin , Nicolaou Veronika , Berggren Steve , Coco Christina , Falkmer Torbjörn , Jonsson Ulf , Choque-Olsson Nora , Bölte Sven 
Published: July 2018

AbstractChallenges in social communication and interaction are core symptoms in autism spectrum disorder (ASD) for which social skills group training (SSGT) is a commonly used intervention. SSGT has shown modest but heterogeneous effects in clinical trials, and therefore identification of effect moderators could enable more precise intervention decisions. One of the major genetic risk factors in ASD are rare copy number variation (CNV). However, limited information exists whether rare CNVs profiles can be used to aid in intervention decisions. Therefore, we conducted the first study to date analyzing rare CNVs as genetic moderators in the outcome of SSGT in ASD. For this, we analyzed rare genic CNV carrier status of 207 children of which 105 received SSGT and 102 standard care as part of a recent randomized clinical trial for 12-weeks SSGT. We used mixed linear models to assess the association of being a CNV carrier, grouped by the effect and size of the CNVs and the primary response to SSGT, the parent-report Social Responsiveness Scale (SRS) measured at post-intervention and 3-months follow-up. Additionally, we analyzed the secondary outcome assessments included parent-rated adaptive behaviors (ABAS-II) and trainer-rated clinical global impression (CGI). We show that being a carrier of any size rare genic CNV did not impact on the SSGT outcome. However, when stratifying the groups by size of the CNVs, we identified that carriers of large CNVs (>500 kb) showed inferior SRS outcomes at post-intervention (β = 15.35, 95% CI 2.86-27.84, P=0.017) and follow-up (β = 14.19, 95% CI 1.68-26.70, P=0.028). Similar results were shown for the parent-rated secondary outcome. In contrast, the carriers of small CNVs had better outcome at post-intervention (β = −1.20, 95 % CI - 2.0 - −0.4 P = 0.003) but not at follow-up for the trainer-rated secondary outcome CGI. These results remained when we tested the specificity of the effect by including the standard care group and adjusting for IQ levels. While our study suggests that being a carrier of any size rare genic CNV did not impact the outcome, it provides preliminary evidence that carriers of high-risk CNVs might not benefit on SSGT as much as non-carriers. Our results indicate that genetic information eventually might help guide personalized intervention planning in ASD. We additionally highlight that more research is needed to understand the intervention needs of autistic individuals with specified molecular alterations.
Quantifying GC-biased gene conversion in great ape genomes using polymorphism-aware models
Authors: Borges Rui , Szöllősi Gergely , Kosiol Carolin 
Published: July 2018

AbstractAs multi-individual population-scale data is becoming available, more-complex modeling strategies are needed to quantify the genome-wide patterns of nucleotide usage and associated mechanisms of evolution. Recently, the multivariate neutral Moran model was proposed. However, it was shown insufficient to explain the distribution of alleles in great apes. Here, we propose a new model that includes allelic selection. Our theoretical results constitute the basis of a new Bayesian framework to estimate mutation rates and selection coefficients from population data. We employ the new framework to a great ape dataset at we found patterns of allelic selection that match those of genome-wide GC-biased gene conversion (gBCG). In particular, we show that great apes have patterns of allelic selection that vary in intensity, a feature that we correlated with the great apes’ distinct demographies. We also demonstrate that the AT/GC toggling effect decreases the probability of a substitution, promoting more polymorphisms in the base composition of great ape genomes. We further assess the impact of CG-bias in molecular analysis and we find that mutation rates and genetic distances are estimated under bias when gBGC is not properly accounted. Our results contribute to the discussion on the tempo and mode of gBGC evolution, while stressing the need for gBGC-aware models in population genetics and phylogenetics.
Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis
Authors: He Xiaojuan , Liu Jin , Liang Chao , Badshah Shaikh Atik , Zheng Kang , Dang Lei , Guo Baosheng , Li Defang , Lu Cheng , Guo Qingqing , Fan Danping , Bian Yanqin , Feng Hui , Xiao Lianbo , Pan Xiaohua , Xiao Cheng , Zhang BaoTing , Zhang Ge , Lu Aiping 
Published: July 2018

AbstractOsteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) was previously identified as a negative regulator of osteogenic lineage activity. Here we demonstrated that PLEKHO1 was highly expressed in osteoblasts of articular specimens from RA patients and inflammatory arthritis mice. Genetic deletion of osteoblastic Plekho1 ameliorated joint inflammation in mice with collagen-induced arthritis (CIA) and K/BxN serum-transfer arthritis (STA), whereas overexpressing Plekho1 only within osteoblasts in CIA and STA mice demonstrated exacerbated local inflammation. Furtherin vitrostudies indicated that PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-kB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition improved joint inflammation and attenuated bone formation reduction in CIA mice and non-human primate arthritis model. These data strongly suggest that highly expressed PLEKHO1 in osteoblast mediates joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.
Suppressor analysis uncovers that MAPs and microtubule dynamics balance with the Cut7/Kinesin-5 motor for mitotic spindle assembly inSchizosaccharomyces pombe
Authors: Yukawa Masashi , Yamada Yusuke , Toda Takashi 
Published: July 2018

ABSTRACTThe Kinesin-5 motor Cut7 inSchizosaccharomyces pombeplays essential roles in spindle pole separation, leading to the assembly of bipolar spindle. In many organisms, simultaneous inactivation of Kinesin-14s neutralizes Kinesin-5 deficiency. To uncover the molecular network that counteracts Kinesin-5, we have conducted a genetic screening for suppressors that rescue thecut7-22temperature sensitive mutation, and identified 10 loci. Next generation sequencing analysis reveals that causative mutations are mapped in genes encoding α-, β-tubulins and the microtubule plus-end tracking protein Mal3/EB1, in addition to the components of the Pkl1/Kinesin-14 complex. Moreover, the deletion of various genes required for microtubule nucleation/polymerization also suppresses thecut7mutant. Intriguingly, Klp2/Kinesin-14 levels on the spindles are significantly increased incut7mutants, whereas these increases are negated by suppressors, which may explain the suppression by these mutations/deletions. Consistent with this notion, mild overproduction of Klp2 confers temperature sensitivity. Surprisingly, treatment with a microtubule-destabilizing drug not only suppressescut7temperature sensitivity but also rescues the lethality resulting from the deletion ofcut7,though a singleklp2deletion per se cannot compensate for the loss of Cut7. We propose that microtubule assembly and/or dynamics antagonize Cut7 functions, and that the orchestration between these two factors is crucial for bipolar spindle assembly.