bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Emotions in Moral Judgments: Time-resolved evidence from event-related brain potentials
Authors: Demel Ronja , Waldmann Michael , Schacht Annekathrin 
Published: February 2019

AbstractThe influence of emotion on moral judgments has become increasingly prominent in recent years. While explicit normative measures are widely used to investigate this relationship, event-related potentials (ERPs) offer the advantage of a preconscious method to visualize the modulation of moral judgments. Based on Gray and Wegner’s (2009) Dimensional Moral Model, the present study investigated whether the processing of neutral faces is modulated by moral context information. We hypothesized that neutral faces gain emotional valence when presented in a moral context and thus elicit ERP responses comparable to those established for the processing of emotional faces. Participants (N= 26, 13 female) were tested with regard to their implicit (ERPs) and explicit (morality rating) responses to neutral faces, shown in either a morally positive, negative, or neutral context. Higher ERP amplitudes in early (P100, N170) and later (EPN, LPC) processing stages were expected for harmful/helpful scenarios compared to neutral scenarios. Agents and patients were expected to differ for moral compared to neutral scenarios. In the explicit ratings neutral scenarios were expected to differ from moral scenarios. In ERPs, we found indications for an early modulation of moral valence (harmful/helpful) and an interaction of agency and moral valence after 80-120 ms. Later time sequences showed no significant differences. Morally positive and negative scenarios were rated as significantly different from neutral scenarios. Overall, the results indicate that the relationship of emotion and moral judgments can be observed on a preconscious neural level at an early processing stage as well as in explicit judgments.
Traces of transposable elements in genome dark matter co-opted by flowering gene regulation networks
Authors: Baud Agnès , Wan Mariène , Nouaud Danielle , Francillonne Nicolas , Anxolabéhère Dominique , Quesneville Hadi 
Published: February 2019

AbstractTransposable elements (TEs) are mobile, repetitive DNA sequences that make the largest contribution to genome bulk. They thus contribute to the so-called “dark matter of the genome”, the part of the genome in which nothing is immediately recognizable as biologically functional.We developed a new method, based on k-mers, to identify degenerate TE sequences. With this new algorithm, we detect up to 10% of the A. thaliana genome as derived from as yet unidentified TEs, bringing the proportion of the genome known to be derived from TEs up to 50%. A significant proportion of these sequences overlapped conserved non-coding sequences identified in crucifers and rosids, and transcription factor binding sites. They are overrepresented in some gene regulation networks, such as the flowering gene network, suggesting a functional role for these sequences that have been conserved for more than 100 million years, since the spread of flowering plants in the Cretaceous.
Pathogen-induced pH changes regulate the growth-defense balance of plants
Authors: Kesten Christopher , Gámez-Arjona Francisco M. , Scholl Stefan , Menna Alexandra , Dora Susanne , Huerta Apolonio Ignacio , Huang Hsin-Yao , Tintor Nico , Kinoshita Toshinori , Rep Martijn , Krebs Melanie , Schumacher Karin , Sánchez-Rodríguez Clara 
Published: February 2019

AbstractEnvironmental adaptation of organisms relies on fast perception and response to external signals, which lead to developmental changes. Plant cell growth is strongly dependent on cell wall remodeling. However, little is known about cell wall-related sensing of biotic stimuli and the downstream mechanisms that coordinate growth and defense responses. We generated genetically encoded pH sensors to determine absolute pH changes across the plasma membrane in response to biotic stress. A rapid apoplastic acidification by phosphorylation-based proton pump activation was followed by an acidification of the cortical side of the plasma membrane in response to the fungus Fusarium oxysporum. The proton chemical gradient modulation immediately reduced cellulose synthesis and cell growth and, furthermore, had a direct influence on the pathogenicity of the fungus. All these effects were dependent on the COMPANION OF CELLULOSE SYNTHASE proteins that are thus at the nexus of plant growth and defense. Hence, our discoveries show a remarkable connection between plant biomass production, immunity, and pH control, and advance our ability to investigate the plant growth-defense balance.
A brain network supporting social influences in human decision-making
Authors: Zhang Lei , Gläscher Jan P. 
Published: February 2019

AbstractHumans learn from their own trial-and-error experience and from observing others. However, it remains unanswered how brain circuits compute expected values when direct learning and social learning coexist in an uncertain environment. Using a multi-player reward learning paradigm with 185 participants (39 being scanned) in real-time, we observed that individuals succumbed to the group when confronted with dissenting information, but increased their confidence when observing confirming information. Leveraging computational modeling and fMRI we tracked direct valuation through experience and vicarious valuation through observation, and their dissociable, but interacting neural representations in the ventromedial prefrontal cortex and the anterior cingulate cortex, respectively. Their functional coupling with the right temporoparietal junction representing instantaneous social information instantiated a hitherto uncharacterized social prediction error, rather than a reward prediction error, in the putamen. These findings suggest that an integrated network involving the brain’s reward hub and social hub supports social influence in human decision-making.
Paralog dependency indirectly affects the robustness of human cells
Authors: Dandage Rohan , Landry Christian R 
Published: February 2019

SummaryGene duplicates provide protection against loss-of-function mutations. This protective redundancy partly relies on the fact that paralogs carry their functions independently, i.e. the inactivation of one gene copy does not impair the function of the other copy. However, a significant fraction of paralogous proteins may form functionally dependent pairs, for instance through heteromerization. As a consequence, one could expect these heteromeric paralogs to be less protective against deleterious mutations. To test this hypothesis, we examined the fitness landscape of gene loss-of-function by CRISPR-Cas9 in more than 450 human cell lines. Our analysis revealed a robustness landscape of human cells showing regions of higher vulnerability to gene inactivation as a function of key paralog properties. We find that heteromerizing paralogs are indeed less protective than non-heteromeric ones, but this association is largely due to their higher abundance and their larger number of protein-protein interaction partners.
Motor cortex signals corresponding to the two arms are shared across hemispheres, mixed among neurons, yet partitioned within the population response
Authors: Cora Ames K. , Churchland Mark M. 
Published: February 2019

AbstractPrimary motor cortex (M1) has lateralized outputs, yet M1 neurons can be active during movements of either arm. What is the nature and role of activity in the two hemispheres? When one arm moves, are the contralateral and ipsilateral cortices performing similar or different computations? When both hemispheres are active, how does the brain avoid moving the “wrong” arm? We recorded muscle and neural activity bilaterally while two male monkeys (Macaca mulatta) performed a cycling task with one or the other arm. Neurons in both hemispheres were active during movements of either arm. Yet response patterns were arm-dependent, raising two possibilities. First, the nature of neural signals may differ (e.g., be high versus low-level) depending on whether the ipsilateral or contralateral arm is used. Second, the same population-level signals may be present regardless of the arm being used, but be reflected differently at the individual-neuron level. The data supported this second hypothesis. Muscle activity could be predicted by neural activity in either hemisphere. More broadly, we failed to find signals unique to the hemisphere contralateral to the moving arm. Yet if the same signals are shared across hemispheres, how do they avoid impacting the wrong arm? We found that activity related to the two arms occupied distinct, orthogonal subspaces of population activity. As a consequence, a linear decode of contralateral muscle activity naturally ignored signals related to the ipsilateral arm. Thus, information regarding the two arms is shared across hemispheres and neurons, but partitioned at the population level.
Comparing 3D genome organization in multiple species using Phylo-HMRF
Authors: Yang Yang , Zhang Yang , Ren Bing , Dixon Jesse , Ma Jian 
Published: February 2019

AbstractRecent developments in whole-genome mapping approaches for the chromatin interactome (such as Hi-C) have offered new insights into 3D genome organization. However, our knowledge of the evolutionary patterns of 3D genome structures in mammalian species remains surprisingly limited. In particular, there are no existing phylogenetic-model based methods to analyze chromatin interactions as continuous features across different species. Here we develop a new probabilistic model, named phylogenetic hidden Markov random field (Phylo-HMRF), to identify evolutionary patterns of 3D genome structures based on multi-species Hi-C data by jointly utilizing spatial constraints among genomic loci and continuous-trait evolutionary models. The effectiveness of Phylo-HMRF is demonstrated in both simulation evaluation and application to real Hi-C data. We used Phylo-HMRF to uncover cross-species 3D genome patterns based on Hi-C data from the same cell type in four primate species (human, chimpanzee, bonobo, and gorilla). The identified evolutionary patterns of 3D genome organization correlate with features of genome structure and function, including long-range interactions, topologically-associating domains (TADs), and replication timing patterns. This work provides a new framework that utilizes general types of spatial constraints to identify evolutionary patterns of continuous genomic features and has the potential to reveal the evolutionary principles of 3D genome organization.
The human non-visual opsin OPN3 regulates pigmentation of epidermal melanocytes through interaction with MC1R
Authors: Ozdeslik Rana N. , Olinski Lauren E. , Trieu Melissa M. , Oprian Daniel D. , Oancea Elena 
Published: February 2019

AbstractOpsins form a family of light-activated, retinal-dependent G-protein coupled receptors (GPCRs) that serve a multitude of visual and non-visual functions. Opsin3 (OPN3 or encephalopsin), initially identified in the brain, remains one of the few members of the mammalian opsin family with unknown function and ambiguous light-absorption properties. We recently discovered that OPN3 is highly expressed in human epidermal melanocytes—the skin cells that produce melanin. The melanin pigment is a critical defense against ultraviolet radiation and its production is mediated by the Gαs-coupled melanocortin-1 receptor (MC1R). The physiological function and light-sensitivity of OPN3 in melanocytes is yet to be determined. Here we show that in human epidermal melanocytes OPN3 acts as a negative regulator of melanin production by interacting with MC1R and modulating its cAMP signaling. OPN3 negatively regulates the cAMP response evoked by MC1R via activation of the Gαi subunit of G-proteins, thus decreasing cellular melanin levels. In addition to their functional relationship, OPN3 and MC1R colocalize at both the plasma membrane and in intracellular structures and form a physical complex. Remarkably, OPN3 can bind retinal, but does not mediate light-induced signaling in melanocytes. Our results identify a novel function for OPN3 in the regulation of the melanogenic pathway in epidermal melanocytes. Our results reveal a light-independent function for the poorly characterized OPN3 and a novel pathway that greatly expands our understanding of melanocyte and skin physiology.SignificanceOur data reveals a novel function for the non-visual opsin OPN3 in regulating the pigmentation of human melanocytes by interacting with and modulating the activity of MC1R.
PARAMO pipeline: reconstructing ancestral anatomies using ontologies and stochastic mapping
Authors: Tarasov Sergei , Mikó István , Yoder Matthew Jon , Uyeda Josef C. 
Published: February 2019

ABSTRACTComparative phylogenetics has been largely lacking a method for reconstructing the evolution of phenotypic entities that consist of ensembles of multiple discrete traits – entire organismal anatomies or organismal body regions. In this study, we provide a new approach namedPARAMO(PhylogeneticAncestralReconstruction ofAnatomy byMappingOntologies) that appropriately models anatomical dependencies and uses ontology-informed amalgamation of stochastic maps to reconstruct phenotypic evolution at different levels of anatomical hierarchy including entire phenotypes. This approach provides new opportunities for tracking phenotypic radiations and evolution of organismal anatomies.
QUANTIFYING CORAL MORPHOLOGY
Authors: Zawada Kyle J. A. , Dornelas Maria , Madin Joshua S. 
Published: February 2019

ABSTRACTThe morphology of coral colonies has important implications for their biological and ecological performance, including their role as ecosystem engineers. However, given that morphology is difficult to quantify across many taxa, morphological variation is typically shoehorned into coarse growth form categories (e.g., arborescent and digitate). In this study, we develop a quantitative schema for morphology by identifying three-dimensional shape variables that can describe coral morphology. We contrast six variables estimated from 152 laser scans of coral colonies that ranged across seven growth form categories and three orders of magnitude of size. We found that 88% of the variation in shape was captured by two axes of variation and three shape variables. The main axis was variation in volume compactness (cf. sphericity) and the second axis was the trade-off between surface complexity and the vertical distribution of volume (i.e., top heaviness). Variation in volume compactness also limited variation along the second axis, where surface complexity and vertical volume distribution ranged more freely when compactness was low. Traditional growth form categories occupied distinct regions within this morpho-space. However, these regions overlapped due to shape changes with colony size. Nonetheless, four of the shape variables were able to predict traditional growth form categories with 70 to 95% accuracy, suggesting that the continuous variables captured much of the qualitative variation inherently implied by these growth forms. Distilling coral morphology into geometric variables that capture shape variation will allow for better tests of the mechanisms that govern coral biology, ecology and ecosystem services such as reef building and provision of habitat.
Comprehensive Assessment of Sequence and Expression of Circular-RNAs in Progenitor Cell Types of the Developing Mammalian Cortex
Authors: Dori Martina , Alieh Leila Haj Abdullah , Cavalli Daniel , Massalini Simone , Lesche Mathias , Dahl Andreas , Calegari Federico 
Published: February 2019

ABSRTRACTCircular (circ) RNAs have recently emerged as a novel class of non coding transcripts whose identification and function remain elusive. Among many tissues and species, the mammalian brain is the organ in which circRNAs are more abundant and first evidence of their functional significance started to emerge. Yet, even within this well studied organ, annotation of circRNAs remains fragmentary, their sequence is unknown and their expression in specific cell types was never investigated. Overcoming these limitations, here we provide the fist comprehensive identification of circRNAs and their expression patterns in proliferating neural stem cells, neurogenic progenitors and newborn neurons of the developing mouse cortex. Extending the current knowledge about the diversity of this class of transcripts by the identification of nearly 4,000 new circRNAs, our study is the first to provide the full sequence information and expression patterns of circRNAs in cell types representing the lineage of neurogenic commitment. We further exploited our data by evaluating the coding potential, evolutionary conservation and biogenesis of circRNAs that we found to arise from a specific sub-class of linear mRNAs. Our study provides the arising field of circRNA biology with a powerful new resource to address the complexity and potential biological significance of this new class of transcripts.
Short-Term Plasticity Following Motor Sequence Learning Revealed by Diffusion MRI
Authors: Tavor Ido , Botvinik-Nezer Rotem , Bernstein-Eliav Michal , Tsarfaty Galia , Assaf Yaniv 
Published: February 2019

AbstractCurrent non-invasive methods to detect structural plasticity in humans are mainly used to study long-term changes. Diffusion MRI was recently proposed as a novel approach to reveal gray matter changes following spatial navigation learning and object-location memory tasks. In the present work we used diffusion MRI to investigate the short-term neuroplasticity that accompanies sequential motor learning. Following a 45-minutes training session in which participants learned to accurately play a short sequence on a piano keyboard, changes in diffusion properties were revealed mainly in motor system regions such as the premotor cortex and cerebellum. A second learning session taking place immediately afterwards shifted the attention of participants onto timing of key pressing instead of accuracy. This second session induced a different plasticity pattern, demonstrating the dynamic nature of this phenomenon, formerly thought to require months of training in order to be detectable. These results provide us with an important reminder that the brain is an extremely dynamic structure. Furthermore, diffusion MRI offers a novel measure to follow tissue plasticity particularly over short timescales, allowing new insights into the dynamics of structural brain plasticity.
The fog of genetics: Known unknowns and unknown unknowns in the genetics of complex traits and diseases
Authors: de Magalhães João Pedro , Wang Jingwei 
Published: February 2019

AbstractAssociating genetic variants with phenotypes is not only important to understand the underlying biology but also to identify potential drug targets for treating diseases. It is widely accepted that for most complex traits many associations remain to be discovered, the so-called “missing heritability.” Yet missing heritability can be estimated, it is a known unknown, and we argue is only a fraction of the unknowns in genetics. The majority of possible genetic variants in the genome space are either too rare to be detected or even entirely absent from populations, and therefore do not contribute to estimates of phenotypic or genetic variability. We call these unknown unknowns in genetics the “fog of genetics.” Using data from the 1000 Genomes Project we then show that larger genes with greater genetic diversity are more likely to be associated with human traits, demonstrating that genetic associations are biased towards particular types of genes and that the genetic information we are lacking about traits and diseases is potentially immense. Our results and model have multiple implications for how genetic variability is perceived to influence complex traits, provide insights on molecular mechanisms of disease and for drug discovery efforts based on genetic information.
Resident memory CD8 T cells persist for years in human small intestine
Authors: Bartolomé Casado Raquel , Landsverk Ole J.B. , Chauhan Sudhir Kumar , Richter Lisa , Phung Dang , Greiff Victor , Risnes Louise Fremgaard , Yao Ying , Neumann Ralf Stefan , Yaqub Sheraz , Øyen Ole , Horneland Rune , Aandahl Einar Martin , Paulsen Vemund , Sollid Ludvig M. , Qiao Shuo-Wang , Bækkevold Espen S. , Jahnsen Frode L. 
Published: February 2019

In human small intestine, most CD8 T cells in the lamina propria and epithelium express a resident memory (Trm) phenotype and persist for at least one year in transplanted tissue. Intestinal CD8 Trm cells have a clonally expanded immune repertoire that is stable over time and exhibit enhanced protective capabilities.Graphical abstractHighlightsThe vast majority of CD8 T cells in the human small intestine are Trm cellsCD8 Trm cells persist for >1 year in transplanted duodenumIntraepithelial and lamina propria CD8 Trm cells show highly similar TCR repertoireIntestinal CD8 Trm cells efficiently produce cytokines and cytotoxic mediators
Dimerization of human Rio2 kinase/ATPase locks its ATP-binding site in an apo state
Authors: Maurice Frédérique , Pérébaskine Natacha , Fribourg Sébastien 
Published: February 2019

ABSTRACTRio proteins form a conserved family of atypical protein kinases. Rio2 is a serine/threonine protein kinase/ATPase involved in pre-40S ribosomal maturation. Current crystal structures of archaeal and fungi Rio2 proteins report a monomeric form of the protein. Here, we describe three atomic structures of the human Rio2 kinase showing that it forms a homodimer. Upon self-association, the ATP-binding pocket is hidden from the solvent and the protein is locked in an apo state corresponding to an inactive form of the kinase. The homodimerization is mediated by key residues previously shown to be responsible for ATP binding and catalysis. This unusual protein kinase dimer reveals an intricate mechanism of mutually exclusive substrate binding and oligomeric state formation. We propose that this oligomeric state could serve a dual function in maintaining the protein in an inactive state and being a novel type of nuclear import signal.Significance StatementRio kinases form a family of atypical protein kinases that are believed to be ATPases rather than kinases. The three members of the Rio family are involved in ribosome biogenesis. We show here that contrarily to what was reported so far, Rio2 is able homodimerize in a conformation that locks it in an apo state, preventing its (re)association to pre-mature ribosomes. This unconventional self-association is not seen in any other protein kinase. This mechanism is likely to be transient and could used to efficiently re-import the protein to the nucleus.
Temporal regulation of cell polarity via the interaction of the Ras GTPase Rsr1 and the scaffold protein Bem1
Authors: Miller Kristi E. , Park Hay-Oak 
Published: February 2019

AbstractEstablishing cell polarity is critical for growth and development of most organisms. The Cdc42 GTPase plays a central role in polarity development in species ranging from yeast to humans. In budding yeast, a specific growth site (i.e. bud site) is selected in the G1 phase, which determines the axis of cell polarization. Rsr1, a Ras GTPase, interacts with Cdc42 and its associated proteins to promote polarized growth at the proper bud site. Yet the mechanism underlying spatial cue-directed cell polarization is not fully understood. Here, we show that Rsr1 associates with Bem1, a scaffold protein, preferentially in its GDP-bound state in early G1. This interaction involves a part of the Bem1 Phox homology (PX) domain, which overlaps with a region previously shown to interact with Exo70, an exocyst component. Furthermore, overexpression of the constitutively GDP-bound Rsr1 interferes with Bem1’s association with Exo70 and inhibits Bem1-dependent Exo70 polarization. We propose that Rsr1 plays a delicate role in coordination of spatial and temporal regulation of polarity establishment via its GTP- and GDP-bound states.