bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional asymmetry in the central brain regions in boys with Attention Deficit Hyperactivity Disorder detected by Event Related Potentials during performance of the Attentional Network Test
Authors: Abramov Dimitri Marques , Mourão Carlos Alberto , Cunha Carla Quero , Pontes Monique Castro , Galhanone Paulo Ricardo , deAzevedo Leonardo C. , Lazarev Vladimir V. 
Published: March 2017

AbstractBackgroundVarious functional asymmetries detected by different neurophysiological and neuroimaging methods have been reported in the literature on the Attention Deficit Hyperactivity Disorder (ADHD), some of them pointing to the right hemisphere activity. In our attempt to discriminate the ADHD patients from normal subjects by hierarchical clustering of behavioural, psychological and event related potential (ERP) variables, the late P3 component of potentials from the right central region (C4) proved to be one of the most informative parameters (in preparation for publication). Here, we have studied the differences in ERPs between the left (C3) and right (C4) central leads and relation of this asymmetry to ADHD diagnosed using DSM.Methods20 typically developing (TD) boys and 19 boys diagnosed with ADHD according to DSM-IV-TR, aged 10-13 years, were examined by the Attentional Network Test (ANT), with simultaneous recording of the respective ERPs. The intergroup differences in the ERP amplitude parameters in the left (C3) and right (C4) central channels and in the difference in these parameters between the two channels (C3 minus C4) were accessed. These characteristics were compared to the subjects DSM scores and ANT performance.ResultsThe target-related potentials late characteristics from the C4 and C3 did not shown significant difference between the groups. The difference between ERPs of the C3 and C4 channels inside the interval of 40-290 ms after target onset was larger in the ADHD group than in control, mainly for incongruent target condition. This asymmetry and right late component were correlated with DSM scores, mainly to hyperactive and impulsive criteria.ConclusionIn ADHD patients, the results suggest ERP pattern of right-side functional predominance in the motor control, which correlates to DSM scores, mainly to hyperactive and impulsive criteria.
Decision-related signals in the presence of nonzero signal stimuli, internal bias, and feedback
Authors: Chicharro Daniel , Panzeri Stefano , Haefner Ralf M. 
Published: March 2017

AbstractUnderstanding the nature of decision-related signals in sensory neurons promises to give insights into their role in perceptual decision-making. Those signals, traditionally quantified as choice probabilities (CP), are well-understood in a feedforward framework assuming zero-signal trials with no choice bias. Here, we extend this understanding by analytically solving models of choice-related signals that account for informative stimuli, choice bias, and importantly, feedback signals reflecting either internal states, such as attention or belief, or the outcome of the decision process. First, we relate CPs to Choice Triggered Averages (CTAs), which quantify choice-related average changes in neural responses, and show that both have general expressions valid for activity-choice covariations of both feedforward or feedback origin. These expressions allow a meaningful calculation of CPs across all trials, including non-zero signal trials. Second, we derive how CPs and CTAs depend on feedforward and feedback weights and on noise correlations under several plausible model architectures. Third, we examine different types of feedback signals, related to predictive coding, probabilistic inference, and attention, and we predict how CPs and CTAs depend in each case on the stimulus signal level and on the neural tuning properties. Finally, we show that measuring both CPs and CTAs offers complementary information about the origin of choice-related signals, especially when studying temporal changes of activity-choice covariations across the trial time. Overall, our work provides new analytical tools to better understand the link between sensory representations and perceptual decisions.
On the structure of cortical micro-circuits inferred from small sample sizes
Authors: Vegué Marina , Perin Rodrigo , Roxin Alex 
Published: March 2017

AbstractThe structure in cortical micro-circuits deviates from what would be expected in a purely random network, which has been seen as evidence of clustering. To address this issue we sought to reproduce the non-random features of cortical circuits by considering several distinct classes of network topology, including clustered networks, networks with distance-dependent connectivity and those with broad degree distributions. To our surprise we found that all these qualitatively distinct topologies could account equally well for all reported non-random features, despite being easily distinguishable from one another at the network level. This apparent paradox was a consequence of estimating network properties given only small sample sizes. In other words, networks which differ markedly in their global structure can look quite similar locally. This makes inferring network structure from small sample sizes, a necessity given the technical difficulty inherent in simultaneous intracellular recordings, problematic. We found that a network statistic called the sample degree correlation (SDC) overcomes this difficulty. The SDC depends only on parameters which can be reliably estimated given small sample sizes, and is an accurate fingerprint of every topological family. We applied the SDC criterion to data from rat visual and somatosensory cortex and discovered that the connectivity was not consistent with any of these main topological classes. However, we were able to fit the experimental data with a more general network class, of which all previous topologies were special cases. The resulting network topology could be interpreted as a combination of physical spatial dependence and non-spatial, hierarchical clustering.Significance StatementThe connectivity of cortical micro-circuits exhibits features which are inconsistent with a simple random network. Here we show that several classes of network models can account for this non-random structure despite qualitative differences in their global properties. This apparent paradox is a consequence of the small numbers of simultaneously recorded neurons in experiment: when inferred via small sample sizes many networks may be indistinguishable, despite being globally distinct. We develop a connectivity measure which successfully classifies networks even when estimated locally, with a few neurons at a time. We show that data from rat cortex is consistent with a network in which the likelihood of a connection between neurons depends on spatial distance and on non-spatial, asymmetric clustering.
Theta-modulation drives the emergence of network-wide connectivity patterns underlying replay in a model of hippocampal place cells
Authors: Theodoni Panagiota , Rovira Bernat , Wang Yingxue , Roxin Alex 
Published: March 2017

SummaryPlace cells of the rodent hippocampus fire action potentials when the animal traverses a particular spatial location in a given environment. Therefore, for any given trajectory one will observe a repeatable sequence of place cell activations as the animal explores. Interestingly, when the animal is quiescent or sleeping, one can observe similar sequences of activation, although at a highly compressed rate, known as “replays”. It is hypothesized that this replay underlies the process of memory consolidation whereby memories are “transferred” from hippocampus to cortex. However, it remains unclear how the memory of a particular environment is actually encoded in the place cell activity and what the mechanism for replay is. Here we study how plasticity during spatial exploration shapes the patterns of synaptic connectivity in model networks of place cells. Specifically, we show how plasticity leads to the emergence of patterns of activity which represent the spatial environment learned. These states become spontaneously active when the animal is quiescent, reproducing the phenomenology of replays. Interestingly, replay emerges most rapidly when place cell activity is modulated by an ongoing oscillation. The optimal oscillation frequency can be calculated analytically, is directly related to the plasticity rule, and for experimentally determined values of the plasticity window in rodent slices gives values in the theta range. A major prediction of this model is that the pairwise correlation of place cells which encode for neighboring locations should increase during initial exploration, leading up to the critical transition. We find such an increase in a population of simultaneously recorded CA1 pyramidal cells from a rat exploring a novel track. Furthermore, in a rat in which hippocampal theta is reduced through inactivation of the medial septum we find no such increase. Our model is the first to show how theta-modulation can speed up learning by facilitating the emergence of environment-specific network-wide patterns of synaptic connectivity in hippocampal circuits.
Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene targeted mice
Authors: Kanellopoulos Alexandros H. , Koenig Jennifer , Huang Honglei , Pyrski Martina , Millet Queensta , Lolignier Stephane , Morohashi Toru , Gossage Samuel J. , Jay Maude , Linley John , Baskozos Georgios , Kessler Benedikt , Cox James J. , Zufall Frank , Wood John N. , Zhao Jing 
Published: March 2017

AbstractThe voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways. Besides action potential propagation, NaV1.7 regulates neurotransmitter release, integrates depolarizing inputs over long periods and regulates transcription. In order to better understand these functions, we generated an epitope-tagged NaV1.7 mouse that showed normal pain behavior. Analysis of NaV1.7 complexes affinity-purified under native conditions by mass spectrometry revealed 267 NaV1.7 associated proteins including known interactors, such as the sodium channel β3 subunit (Scn3b) and collapsin response mediator protein (Crmp2), and novel interactors. Selected novel NaV1.7 protein interactors membrane-trafficking protein synapototagmin-2 (Syt2), G protein-regulated inducer of neurite outgrowth 1 (Gprin1), L-type amino acid transporter 1 (Lat1) and transmembrane P24 trafficking protein 10 (Tmed10) together with Scn3b and Crmp2 were validated using co-immunoprecipitation and functional assays. The information provided with this physiologically normal epitope-tagged mouse should provide useful insights into the pain mechanisms associated with NaV1.7 channel function.
On the feasibility of mining CD8+ T-cell receptor patterns underlying immunogenic peptide recognition
Authors: De Neuter Nicolas , Bittremieux Wout , Beirnaert Charlie , Cuypers Bart , Mrzic Aida , Moris Pieter , Suls Arvid , Van Tendeloo Viggo , Ogunjimi Benson , Laukens Kris , Meysman Pieter 
Published: March 2017

Abstract:Current T-cell epitope prediction tools are a valuable resource in designing targeted immunogenicity experiments. They typically focus on, and are able to, accurately predict peptide binding and presentation by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. However, recognition of the peptide-MHC complex by a T-cell receptor is often not included in these tools. We developed a classification approach based on random forest classifiers to predict recognition of a peptide by a T-cell and discover patterns that contribute to recognition. We considered two approaches to solve this problem: (1) distinguishing between two sets of T-cell receptors that each bind to a known peptide and (2) retrieving T-cell receptors that bind to a given peptide from a large pool of T-cell receptors. Evaluation of the models on two HIV-1, B*08-restricted epitopes reveals good performance and hints towards structural CDR3 features that can determine peptide immunogenicity. These results are of particularly importance as they show that prediction of T-cell epitope and T-cell epitope recognition based on sequence data is a feasible approach. In addition, the validity of our models not only serves as a proof of concept for the prediction of immunogenic T-cell epitopes but also paves the way for more general and high performing models.
Long-Term Imaging of Cellular Forces with High Precision by Elastic Resonator Interference Stress Microscopy
Authors: Kronenberg Nils M. , Liehm Philipp , Steude Anja , Knipper Johanna A. , Borger Jessica G. , Scarcelli Giuliano , Franze Kristian , Powis Simon J. , Gather Malte C. 
Published: March 2017

AbstractCellular forces are crucial for many biological processes but current methods to image them have limitations with respect to online analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell-substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic Resonator Interference Stress Microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity). This enables investigation of minute vertical stresses (<1 Pa) involved in podosome protrusion, protein specific cell-substrate interaction and amoeboid migration through spatial confinement in real time. ERISM requires no zero-force reference and avoids phototoxic effects, which facilitates force monitoring over multiple days and at high frame rates and eliminates the need to detach cells after measurements. This allows observation of slow processes like differentiation and further investigation of cells, e.g. by immunostaining.
Neuronal patterning of the tubular collar cord is highly conserved among enteropneusts but dissimilar to the chordate neural tube
Authors: Kaul-Strehlow Sabrina , Urata Makoto , Praher Daniela , Wanninger Andreas 
Published: March 2017

AbstractThe dorsal neural tube of chordates and the ventral nerve cord of annelids exhibit a similar molecular mediolateral architecture. Accordingly, the presence of such a complex nervous system (CNS) has been proposed for their last common ancestor. Members of Enteropneusta, a group of non-chordate deuterostomes, possess a less complex CNS including a hollow neural tube, whereby homology to its chordate counterpart remains elusive. Since the majority of data on enteropneusts stem fromSaccoglossus kowalevskii,a derived direct-developer, we investigated expression of key neuronal patterning genes in the indirect-developerBalanoglossus misakiensis.The collar cord ofB. misakiensisshows anteriorSix3/6and posteriorOtx+engrailedexpression, in a region corresponding to the chordate brain. NeuronalNk2.1/Nk2.2expression is absent. Interestingly, we found medianDlxand lateralPax6expression domains, i.e., a condition that is reversed compared to chordates.Comparative analyses reveal that CNS patterning is highly conserved among enteropneusts.BmiDlxandBmiPax6have no corresponding expression domains in the chordate brain, which may be indicative of independent acquisition of a tubular CNS in Enteropneusta and Chordata. Moreover, mediolateral architecture varies considerably among chordates and enteropneusts, questioning the presence of a vertebrate-like patterned nervous system in the last common deuterostome ancestor.
Insect behavioral evidence of spatial memories during environmental reconfiguration
Authors: Santos-Pata Diogo , Escuredo Alex , Mathews Zenon , Verschure Paul F.M.J. 
Published: March 2017

ABSTRACTInsects are great explorers, able to navigate through long-distance trajectories and successfully find their way back. Their navigational routes cross dynamic environments suggesting adaptation to novel configurations. Arthropods and vertebrates share neural organizational principles and it has been shown that rodents modulate their neural spatial representation accordingly with environmental changes. However, it is unclear whether insects reflexively adapt to environmental changes or retain memory traces of previously explored situations. We sought to disambiguate between insect behavior at environmental novel situations and reconfiguration conditions. An immersive mixed-reality multi-sensory setup was built to replicate multi-sensory cues. We have designed an experimental setup where female crickets Gryllus Bimaculatus were trained to move towards paired auditory and visual cues during primarily phonotactic driven behavior. We hypothesized that insects were capable of identifying sensory modifications in known environments. Our results show that, regardless of the animals history, novel situation conditions did not compromise the animals performance and navigational directionality towards a novel target location. However, in trials where visual and auditory stimuli were spatially decoupled, the animals heading variability towards a previously known location significantly increased. Our findings showed that crickets are able to behaviorally manifest environmental reconfiguration, suggesting the encoding for spatial representation.
Causes and consequences of nuclear gene positioning
Authors: Shachar Sigal , Misteli Tom 
Published: March 2017

AbstractThe eukaryotic genome is organized in a manner that allows folding of the genetic material in the confined space of the cell nucleus, while at the same time enabling its physiological function. A major principle of spatial genome organization is the non-random position of genomic loci relative to other loci and to nuclear bodies. The mechanisms that determine the spatial position of a locus, and how position affects function, are just beginning to be characterized. Initial results suggest multiple, gene-specific mechanisms and the involvement of a wide range of cellular machineries. In this Commentary, we review recent findings from candidate approaches and unbiased screening methods that provide initial insight into the cellular mechanisms of positioning and their functional consequences. We highlight several specific mechanisms including tethering to the nuclear periphery, passage through replication and histone modifications that contribute to gene positioning in yeast, plants and mammals.
Temporal fitness fluctuations in experimentalArabidopsis thalianapopulations
Authors: Hu Jinyong , Lei Li , de Meaux Juliette 
Published: March 2017

AbstractUnderstanding the genetics of lifetime fitness is crucial to understand a species’ ecological preferences and ultimately predict its ability to cope with novel environmental conditions. Yet, there is a dearth of information regarding the impact of the ecological variance experienced by natural populations on expressed phenotypic and fitness differences. Here, we follow the natural dynamics of experimentalA. thalianapopulations over 5 successive plantings whose timing was determined by the natural progression of the plant’s life cycle and disentangle the environmental and genetic factors that drive plant ecological performance at a given locality. We show that, at the intermediate latitude where the experiment was conducted, a given genotype can experience different life cycles across successive seasons. Lifetime fitness across these seasons varied strongly, with a fall planting yielding 36-fold higher fitness compared to a spring planting. In addition, the actual life-stage at which plant overwinter oscillated across years, depending on the timing of the end of the summer season. We observed a rare but severe fitness differential after inadequate early flowering in one of the five planting. Substrate variation played a comparatively minor role, but also contributed to modulate the magnitude of fitness differentials between genotypes. Finally, reciprocal introgressions on chromosome 4 demonstrated that the fitness effect of a specific chromosomal region is strongly contingent on micro-geographic and seasonal fluctuations. Our study contributes to emphasize the extent to which the fitness impact of phenotypic traits and the genes that encode them in the genome can fluctuate. Experiments aiming at dissecting the molecular basis of local adaptation must apprehend the complexity introduced by temporal fluctuations because they massively affect the expression of phenotype and fitness differences.
Intra- and Inter-individual genetic variation in human ribosomal RNAs
Authors: Babaian Artem 
Published: March 2017

AbstractThe ribosome is an ancient RNA-protein complex essential for translating DNA to protein. At its core are the ribosomal RNAs (rRNAs), the most abundant RNA in the cell. To support high levels of transcription, repetitive arrays of ribosomal DNA (rDNA) are necessary and the long-standing hypothesis is that they undergo sequence homogenization towards rDNA uniformity.Here I present evidence of the rich genetic diversity in human rDNA, both within and between individuals. Using state-of-the-art genome sequencing data revealed an average of 192.7 intra-individual variants, including some deeply penetrating the rDNA copies, such as the bi-allelically expressed 28S.59A>G. From 104 diverse genomes, 947 high-confidence variants were identified and unmask a hidden genetic diversity of humans.These findings support the emerging concept that ribosomes are heterogeneous within cells and extends the heterogeneity into the realm of population genetics. Fundamentally, do our ribosomal variants determine how our cells interpret the genome?
MTAG: Multi-Trait Analysis of GWAS
Authors: Turley Patrick , Walters Raymond K. , Maghzian Omeed , Okbay Aysu , Lee James J. , Fontana Mark Alan , Nguyen-Viet Tuan Anh , Wedow Robbee , Zacher Meghan , Furlotte Nicholas A. ,   23andMe Research Team,   Social Science Genetic Association Consortium, Magnusson Patrik , Oskarsson Sven , Johannesson Magnus , Visscher Peter M. , Laibson David , Cesarini David , Neale Benjamin M. , Benjamin Daniel J. 
Published: March 2017

ABSTRACTWe introduce Multi-Trait Analysis of GWAS (MTAG), a method for joint analysis of summary statistics from GWASs of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (Neff= 354,862), neuroticism (N= 168,105), and subjective well-being (N= 388,538). Compared to 32, 9, and 13 genome-wide significant loci in the single-trait GWASs (most of which are themselves novel), MTAG increases the number of loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase variance explained by polygenic scores by approximately 25%, matching theoretical expectations.