bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational burden of hepatoblastomas: a role for the CX3CL1/CX3CR1 chemokine signaling pathway
Authors: Marques Aguiar Talita Ferreira , Rivas Maria Prates , Costa Silvia , Rodrigues Tatiane , de Barros Juliana Sobral , Barbosa Anne Caroline , Maschietto Mariana , Valieris Renan , Fernandes Gustavo Ribeiro , Cypriano Monica , de Toledo Silvia Regina Caminada , Major Angela , Tojal Israel , de Pinho Apezzato Maria Lúcia , Carraro Dirce Maria , Rosenberg Carla , da Costa Cecilia Maria Lima , da Cunha Isabela Werneck , Sarabia Stephen Frederick , Terrada Dolores-López , Krepischi Ana Cristina Victorino 
Published: February 2019

ABSTRACTBackgroundHepatoblastoma is an embryonal liver tumor supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. CTNNB1 is the only recurrently mutated gene, and this relative paucity of somatic mutations poses a challenge to risk stratification and development of targeted therapies.MethodsIn this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case.ResultsOur data disclosed a low mutational background with only three recurrently mutated genes: CTNNB1 and two novel candidates, CX3CL1 and CEP164. The major finding was a recurrent mutation (A235G) identified in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed up-regulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas, with a predominance of these proteins in the cytoplasm of tumor cells. These proteins were not detected in the infiltrated lymphocytes of inflammatory regions of the tumors, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative tumor cells, but strongly positive infiltrated lymphocytes. Our data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, related only with tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations.ConclusionsOverall, we present here evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with hepatoblastoma tumorigenesis or progression, besides reporting a novel mutational signature specific to a hepatoblastoma subset.
Manipulating patterns of dynamic deformation elicits the impression of cloth with varying stiffness
Authors: Bi Wenyan , Jin Peiran , Nienborg Hendrikje , Xiao Bei 
Published: February 2019

AbstractCloth is a common material and humans can visually estimate its mechanical properties by observing how it deforms under external forces. Here we ask whether, and how, dynamic deformation can affect the perception of mechanical properties of cloth. In Experiment 1, we find that both intrinsic mechanical properties and optical properties affect stiffness perception when the stimuli are presented as images. By contrast, in videos, humans can partially discount the effect of optical appearances and exhibit higher sensitivity to stiffness. We further identified an idiosyncratic deformation pattern (i.e., movement uniformity) to differentiate stiffness, which can be reliably measured by six optical flow features. In Experiment 2, we isolate the deformation by creating dynamic dot stimuli from the 3D mesh of the cloth. We directly alter the movement pattern by manipulating the uniformity of the displacement vectors on the dot stimuli, and show that changing the pattern of dynamic deformation alone can alter the perceived stiffness of cloth in a variety of scene set-ups. Furthermore, by analyzing optical flow fields extracted from the manipulated dynamic dot stimuli, we confirmed the same six optical flow features can be diagnostic of the degree of stiffness of moving cloth across different scenes. Overall, our study demonstrates that manipulating patterns of dynamic deformation alone can elicit the impression of cloth with varying stiffness, suggesting that human visual system might rely on the idiosyncratic pattern of dynamic deformation for estimating stiffness.
The relationship of body condition, superoxide dismutase and superoxide with sperm performance
Authors: Friesen Christopher R. , de Graaf Simon P. , Olsson Mats 
Published: February 2019

AbstractSperm competition theory predicts a negative correlation between somatic investment in traits that aid in pre- and postcopulatory sexual selection. Sperm performance is critical for postcopulatory success but are susceptible to damage by free radicals such as superoxide radicals generated during mitochondrial respiration (mtSOx). Males can ameliorate damage to spermatozoa by investing in the production of antioxidants, like superoxide dismutase (SOD), which may act as a mechanistic link for pre and postcopulatory trade-offs. Some male Australian, colour-polymorphic painted dragon lizards (Ctenophorus pictus) possess a yellow throat patch (bib) that females prefer over non-bibbed males and are also more likely to win male-male contests indicating that males with bibs are better at monopolizing females. We tested whether the sperm performance in non-bibbed males was superior to that of bibbed males as predicted by sperm competition theory. We show that blood cell mtSOx levels are negatively correlated with SOD activity in the plasma in all males early in the breeding season but SOD was lower in bibbed males. Non-bibbed males maintain a positive correlation between body condition and SOD activity over time while bibbed males do not. Overall sperm performance was not different between the bib-morphs, however, higher mtSOx levels were negatively correlated with sperm performance in bibbed males, but not of non-bibbed males. Together these data suggest physiological associations between body condition, SOD activity and sperm performance are linked to the expression of a yellow gular patch, which may be related to intrinsic differences in metabolism of bibbed versus non-bibbed males.Lay summaryDamage-inducing reactive oxygen species (ROS) are a by-product of oxygen-based energy production that are quenched by energetically expensive antioxidants. Male sexual colouration requires investment of energy and resources, which may constrain allocation to other functions like antioxidant production or spermatogenesis. Here we explored whether the body condition of colourful male lizards reflected their investment in antioxidants and reduction of ROS, which may influence sperm performance. We found that drab males in better condition had more antioxidants. Colourful males had lower levels of antioxidants and their sperm performed poorly at higher ROS levels. These results suggest a trade-off between colour maintenance and sperm performance.
Spatiotemporal empirical mode decomposition of resting-state fMRI signals: application to global signal regression
Authors: Moradi Narges , Dousty Mehdy , Sotero Roberto C. 
Published: February 2019

AbstractResting-state functional connectivity MRI (rs-fcMRI) is a common method for mapping functional brain networks. However, estimation of these networks is affected by the presence of a common global systemic noise, or global signal (GS). Previous studies have shown that the common preprocessing steps of removing the GS may create spurious correlations between brain regions. In this paper, we decompose fMRI signals into 5 spatial and 3 temporal intrinsic mode functions (SIMF and TIMF, respectively) by means of the empirical mode decomposition (EMD), which is an adaptive data-driven method widely used to analyze nonlinear and nonstationary phenomena. For each SIMF, brain connectivity matrices were computed by means of the Pearson correlation between TIMFs of different brain areas. Thus, instead of a single connectivity matrix, we obtained 5 × 3 = 15 functional connectivity matrices. Given the high value obtained for large-scale topological measures such as transitivity, in the low spatial maps (SIMF3, SIMF4, and SIMF5), our results suggest that these maps can be considered as spatial global signal masks. Thus, the spatiotemporal EMD of fMRI signals automatically regressed out the GS, although, interestingly, the removed noisy component was voxel-specific. We compared the performance of our method with the conventional GS regression and to the results when the GS was not removed. While the correlation pattern identified by the other methods suffers from a low level of precision, our approach demonstrated a high level of accuracy in extracting the correct correlation between different brain regions.
Delta and theta neural entrainment during phonological and semantic processing in speech perception
Authors: Mai Guangting , Wang William S-Y. 
Published: February 2019

AbstractNeural entrainment of acoustic envelopes is important for speech intelligibility in spoken language processing. However, it is unclear how it contributes to processing at different linguistic hierarchical levels. The present EEG study investigated this issue when participants responded to stimuli that dissociated phonological and semantic processing (real-word, pseudo-word and backward utterances). Multivariate Temporal Response Function (mTRF) model was adopted to map speech envelopes from multiple spectral bands onto EEG signals, providing a direct approach to measure neural entrainment. We tested the hypothesis that entrainment at delta (supra-syllabic) and theta (syllabic and sub-syllabic) bands take distinct roles at different hierarchical levels. Results showed that both types of entrainment involve speech-specific processing, but their underlying mechanisms were different. Theta-band entrainment was modulated by phonological but not semantic contents, reflecting the possible mechanism of tracking syllabic- and sub-syllabic patterns during phonological processing. Delta-band entrainment, on the other hand, was modulated by semantic information, indexing more attention-demanding, effortful phonological encoding when higher-level (semantic) information is deficient. Interestingly, we further demonstrated that the statistical capacity of mTRFs at the delta band and theta band to classify utterances is affected by their semantic (real-word vs. pseudo-word) and phonological (real-word and pseudo-word vs. backward) contents, respectively. Moreover, analyses on the response weighting of mTRFs showed that delta-band entrainment sustained across neural processing stages up to higher-order timescales (~ 300 ms), while theta-band entrainment occurred mainly at early, perceptual processing stages (< 160 ms). This indicates that, compared to theta-band entrainment, delta-band entrainment may reflect increased involvement of higher-order cognitive functions during interactions between phonological and semantic processing. As such, we conclude that neural entrainment is not only associated with speech intelligibility, but also with the hierarchy of linguistic (phonological and semantic) content. The present study thus provide a new insight into cognitive mechanisms of neural entrainment for spoken language processing.HighlightsLow-frequency neural entrainment was examined via mTRF models in EEG during phonological and semantic processing.Delta entrainment take roles in effortful listening for phonological recognitionTheta entrainment take roles in tracking syllabic and subsyllabic patterns for phonological processingDelta and theta entrainment sustain at different timescales of neural processing
Novel polygenic risk score as a translational tool linking depression-related changes in the corticolimbic transcriptome with neural face processing and anhedonic symptoms
Authors: Mareckova Klara , Hawco Colin , Dos Santos Fernanda C. , Bakht Arin , Calarco Navona , Miles Amy E. , Voineskos Aristotle N. , Sibille Etienne , Hariri Ahmad R. , Nikolova Yuliya.S. 
Published: February 2019

ABSTRACTConvergent data from imaging and postmortem brain transcriptome studies implicate corticolimbic circuit (CLC) dysregulation in the pathophysiology of depression. To more directly bridge these lines of work, we generated a novel transcriptome-based polygenic risk score (T-PRS), capturing subtle shifts towards depression-like gene expression patterns in key CLC regions, and mapped this T-PRS onto brain function and related depressive symptoms in a non-clinical sample of 478 young adults (225 men; age 19.79+/−1.24) from the Duke Neurogenetics Study. First, T-PRS was generated based on common functional SNPs shifting CLC gene expression towards a depression-like state. Next, we used multivariate partial least squares regression to map T-PRS onto whole-brain activity patterns during perceptual processing of social stimuli (i.e., human faces). For validation, we conducted a comparative analysis with a PRS summarizing depression risk variants identified by the Psychiatric Genomics Consortium (PGC-PRS). Sex was modeled as moderating factor. We showed that T-PRS was associated with widespread reductions in neural response to neutral faces in women and to emotional faces and shapes in men (multivariate p<0.01). This female-specific reductions in neural response to neutral faces was also associated with PGC-PRS (multivariate p<0.03). Reduced reactivity to neutral faces was further associated with increased self-reported anhedonia. We conclude that women with functional alleles mimicking the postmortem transcriptomic CLC signature of depression have blunted neural activity to social stimuli, which may be expressed as higher anhedonia.
Marine deep biosphere microbial communities assemble in near-surface sediments in Aarhus Bay
Authors: Petro Caitlin , Zäncker Birthe , Starnawski Piotr , Jochum Lara M. , Ferdelman Timothy G. , Jørgensen Bo Barker , Røy Hans , Kjeldsen Kasper U. , Schramm Andreas 
Published: February 2019

AbstractAnalyses of microbial diversity in marine sediments have identified a core set of taxa unique to the marine deep biosphere. Previous studies have suggested that these specialized communities are shaped by processes in the surface seabed, in particular that their assembly is associated with the transition from the bioturbated upper zone to the nonbioturbated zone below. To test this hypothesis, we performed a fine-scale analysis of the distribution and activity of microbial populations within the upper 50 cm of sediment from Aarhus Bay (Denmark). Sequencing and qPCR were combined to determine the depth distributions of bacterial and archaeal taxa (16S rRNA genes) and sulfate-reducing microorganisms (dsrBgene). Mapping of radionuclides throughout the sediment revealed a region of intense bioturbation at 0-6 cm depth. The transition from bioturbated sediment to the subsurface below (7 cm depth) was marked by a shift from dominant surface populations to common deep biosphere taxa (e.g. Chloroflexi & Atribacteria). Changes in community composition occurred in parallel to drops in microbial activity and abundance caused by reduced energy availability below the mixed sediment surface. These results offer direct evidence for the hypothesis that deep subsurface microbial communities present in Aarhus Bay mainly assemble already centimeters below the sediment surface, below the bioturbation zone.
ILT7 activation and plasmacytoid dendritic cell response are governed by BST2 determinants that are structurally-distinct
Authors: Bego Mariana G. , Miguet Nolwenn , Laliberté Alexandre , Aschman Nicolas , Gerard Francine , Merakos Angelique A. , Weissenhorn Winfried , Cohen Éric A. 
Published: February 2019

AbstractThe interaction of the human pDC receptor ILT7 with its ligand, BST2, significantly regulates pDC’s TLR-induced innate immune responses. This interaction has critical biological consequences, yet, its structural requirements are not fully characterized. The BST2 ectodomain can be divided in structurally and functionally distinct regions; while the coiled-coil region contains a newly-defined ILT7 binding surface, the N-terminal region appears to negatively modulate ILT7 activation. A stable BST2 homodimer binds to ILT7 but post-binding events associated to the unique BST2 coiled-coil plasticity are required to trigger receptor signaling. Hence, BST2 with an unstable or with a rigid coiled-coil fails to activate ILT7, whereas mutations in the N-terminal region enhance activation. Importantly, the biological relevance of these newly defined domains of BST2 is underscored by the identification of mutations with opposed potential to activate ILT7, which are selected under pathological malignant conditions.
Combinatorial mutagenesis of rapidly-evolving residues yields super-restrictor antiviral proteins
Authors: Colón-Thillet Rossana , Hsieh Emily , Graf Laura , McLaughlin Richard N , Young Janet M. , Kochs Georg , Emerman Michael , Malik Harmit S. 
Published: February 2019

AbstractAntagonistic interactions drive host-virus evolutionary arms-races, which often manifest as recurrent amino acid changes (i.e., positive selection) at their protein-protein interaction interfaces. Here, we investigated whether combinatorial mutagenesis of positions under positive selection in a host antiviral protein could enhance its restrictive properties. We tested ~700 variants of human MxA, generated by combinatorial mutagenesis, for their ability to restrict Thogoto orthomyxovirus (THOV). We identified MxA super-restrictors with increased binding to THOV NP target protein and 10-fold higher anti-THOV restriction relative to wild-type human MxA, the most potent naturally-occurring anti-THOV restrictor identified. Our findings reveal a means to elicit super-restrictor antiviral proteins by leveraging signatures of positive selection. Although some MxA super-restrictors of THOV were impaired in their restriction of H5N1 influenza A virus (IAV), other super-restrictor variants increased THOV restriction without impairment of IAV restriction. Thus, broadly acting antiviral proteins such as MxA mitigate breadth-versus-specificity tradeoffs that could otherwise constrain their adaptive landscape.
Consciousness as a Concrete Physical Phenomenon
Authors: Jylkkä Jussi , Railo Henry 
Published: February 2019

AbstractWhy any type of neural activation is associated with subjective, conscious experience is a fundamental unsolved question in neuroscience. To bridge the gap between neural activity and conscious experience, one seemingly must tie together two very different entities. The paradigmatic view in consciousness science is that subjective experiences are private and cannot be scientifically observed or described: science can only discover correlations between subjective experiences and their neural realizers, but never observe or describe the experiences themselves. We present a metatheory of consciousness that explains how subjective experiences are related to empirical observations and models, and why the two appear so different from each other. We argue that consciousness is a concrete physical process that causally interacts with other physical phenomena. This entails that consciousness can be empirically observed and characterized. The reason why subjective experiences and empirical observations and models of them appear so different is explained by what we call the observer-observed distinction. Empirical observations are always distinct from the observer, but a subject and her experiences constitute a single physical-biological system. We argue that once science has completely described 1) the constitutive neural mechanisms that are isomorphic with experiences, 2) the etiological mechanisms that experiences are based on, and 3) their causal power, then science has provided an exhaustive description of phenomenology. Our conclusion is that, if we accept this framework we call Naturalistic Monism, consciousness collapses into a standard problem of science.
Dynamics of Sox2 expression during rat germ cell development and its relationship with emergence of spermatogonia
Authors: Oliveira Ticiana Volpato de , Tesser Renato Borges , Nunes Marina , Stumpp Taiza 
Published: February 2019

1.ABSTRACTThe gonocytes represent a specific phase of male gem cell development that precedes spermatogonial stem cell differentiation. Here, we describe the expression of Sox2, an OCT4 partner, during rat germ cell development. Our hypothesis is that SOX2 has a cytoplasmic role during gonocyte-to-spermatogonia transition. Male rat embryos and testes were submitted to the analysis of Sox2 expression. Sox2 was detected in germ cells from 14 days post-conception (dpc) to 8dpp. SOX2 was present in 14dpc and 15dpc embryos and absent at 17 and 19dpc; however, it did not show direct correlation with mRNA. SOX2 labelling was detected after birth and its expression increased from 1dpp to 5dpp. SOX2 was localized in the cytoplasm and showed a granulated pattern similar to P-bodies. Indeed, GW182/SOX2 and LIN28/SOX2 double-labelling showed that SOX2 partially co-localized with the P-bodies components GW182 and LIN28. At 8dpp SOX2 was detected in the nucleus and/or in the cytoplasm of spermatogonia, whereas at 25dpp it was detected in the nucleus of rare spermatogonia. This suggests that SOX2 localization changes during gonocytes to spermatogonia transition.
A comparative anatomy of protein crystals: lessons from the automatic processing of 56,000 samples
Authors: Svensson Olof , Gilski Maciej , Nurizzo Didier , Bowler Matthew W. 
Published: February 2019

SynopsisThe automatic processing of over 56,000 crystals by the autonomous ESRF beamline MASSIF-1 has provided a data set of crystal characteristics and properties that allows many theoretical proposals and assumptions to be evaluated experimentally.AbstractThe fully automatic processing of crystals of macromolecules has presented a unique opportunity to gather information on the samples that is not usually recorded. This has proved invaluable in improving the sample location, characterisation and data collection algorithms. After operating for four years, MASSIF-1 has now processed over 56,000 samples, gathering information at each stage, from the volume of the crystal to the unit cell dimensions, space group, quality of the data collected and the reasoning behind the decisions made in data collection. This provides an unprecedented opportunity to analyse these data together, providing a detailed landscape of macromolecular crystals and intimate details of their contents and, importantly, how the two are related. The data show that mosaic spread is unrelated to the size or shape of crystals and demonstrate experimentally that diffraction intensities scale in proportion to crystal volume and molecular weight. It is also shown that crystal volume scales inversely with molecular weight. The results set the scene for the development of X-ray crystallography in a changing environment for structural biology.