bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Session Real-time fMRI Neurofeedback has a Lasting Impact on Cognitive Behavioral Therapy Strategies
Authors: MacDuffie Katherine E. , MacInnes Jeff , Dickerson Kathryn C. , Eddington Kari M. , Strauman Timothy J. , Adcock R. Alison 
Published: February 2018

AbstractTo benefit from cognitive behavioral therapy (CBT), individuals must not only learn new skills but also strategically implement them outside the session. Here, we tested a novel technique for personalizing CBT skills and facilitating their generalization to daily life. We hypothesized that showing participants the impact of specific CBT strategies on their own brain function using real-time functional magnetic imaging (rt-fMRI) neurofeedback would increase their metacognitive awareness, help them identify effective strategies, and motivate real-world use. In a within-subjects design, participants who had completed a clinical trial of a standardized course of CBT created a personal repertoire of negative autobiographical stimuli and mood regulation strategies. From each participant’s repertoire, a set of experimental and control strategies were identified; only experimental strategies were practiced in the scanner. During the rt-fMRI neurofeedback session, participants used negative stimuli and strategies from their repertoire to manipulate activation in the anterior cingulate cortex, a region implicated in emotional distress. The primary outcome measures were changes in participant ratings of strategy difficulty, efficacy, and frequency of use. As predicted, ratings for unscanned control strategies were stable across observations, whereas ratings for experimental strategies changed after neurofeedback. At follow-up one month after the session, efficacy and frequency ratings for scanned strategies were predicted by neurofeedback during the rt-fMRI session. These results suggest that rt-fMRI neurofeedback created a salient and durable learning experience for patients, extending beyond the clinic to guide and motivate CBT skill use weeks later. This metacognitive approach to neurofeedback offers a promising model for increasing clinical benefits from cognitive-behavioral therapy by personalizing skills and facilitating generalization.
Structure of Zip2:Spo16, a conserved XPF:ERCC1-like complex critical for meiotic crossover formation
Authors: Arora Kanika , Corbett Kevin D. 
Published: February 2018

AbstractIn eukaryotic meiosis, generation of haploid gametes depends on the formation of inter-homolog crossovers, which enable the pairing, physical linkage, and eventual segregation of homologs in the meiosis I division. A class of conserved meiosis-specific proteins, collectively termed ZMMs, are required for formation and spatial control of crossovers throughout eukaryotes. Here, we show that threeS. cerevisiaeZMM proteins – Zip2, Zip4, and Spo16 – interact with one another and form a DNA-binding complex critical for crossover formation and control. We determined the crystal structure of a Zip2:Spo16 subcomplex, revealing a heterodimer structurally related to the XPF:ERCC1 endonuclease complex. Zip2:Spo16 lacks an endonuclease active site, but binds specific DNA structures found in early meiotic recombination intermediates. Mutations in multiple DNA-binding surfaces on the Zip2:Spo16 complex severely compromise DNA binding, supporting a model in which the complex’s central and HhH domains cooperate to bind DNA. Overall, our data support a model in which the Zip2:Zip4:Spo16 complex binds and stabilizes early meiotic recombination intermediates, then coordinates additional factors to promote crossover formation and license downstream events including synaptonemal complex assembly.
Selection dynamics in transient compartmentalization
Authors: Blokhuis Alex , Lacoste David , Nghe Philippe , Peliti Luca 
Published: February 2018

Transient compartments have been recently shown to be able to maintain functional replicators in the context of prebiotic studies. Motivated by this experiment, we show that a broad class of selection dynamics is able to achieve this goal. We identify two key parameters, the relative amplification of non-active replicators (parasites) and the size of compartments. Since the basic ingredients of our model are the competition between a host and its parasite, and the diversity generated by small size compartments, our results are relevant to various phage-bacteria or virus-host ecology problems.PACS numbers: 05.40.-a, 87.14.G-, 87.23.Kg
Presenilin-mediated cleavage of APP regulates synaptotagmin-7 and presynaptic plasticity
Authors: Barthet Gaël , Jordà-Siquier Tomàs , Rumi-Masante Julie , Bernadou Fanny , Müller Ulrike , Mulle Christophe 
Published: February 2018

SUMMARYPresenilin (PS), the catalytic subunit of γ-secretase and its main substrate the amyloid precursor protein (APP) are mutated in a large majority of patients with familial Alzheimer disease. PS and APP interact with proteins of the neurotransmitter release machinery but the functional consequences of these interactions are unknown. Here we report that genetic deletion of presynaptic PS markedly decreases the axonal expression of the Ca2+sensor synaptotagmin-7 (Syt7), and impairs synaptic facilitation and replenishment of release-competent synaptic vesicles. These properties are fully restored by presynaptic re-expression of Syt7. The regulation of Syt7 expression occurs post-transcriptionally and depends on γ-secretase activity. In the combined absence of both APP and PS1, the loss of Syt7 is prevented, indicating that the action of γ-secretase on presynaptic mechanisms depends on its substrate APP. The molecular mechanism involves the substrate of PS, APP-βCterminal (APP-βCTF), which interacts with Syt7 and accumulates in synaptic terminals under conditions of pharmacological or genetic inhibition of γ-secretase. These results reveal a role of PS in presynaptic mechanisms through regulation of Syt7 by APP-dependent cleavage, and highlight aberrant synaptic vesicle processing as a possible new pathway in AD.
GEMC1 and CCNO are required for efferent duct development and male fertility
Authors: Terré Berta , Lewis Michael , Gil-Gómez Gabriel , Stracker Travis H. 
Published: February 2018

AbstractGEMC1 is a Geminin family protein that triggers the E2F4/5-mediated transcriptional activation of target genes, including many required for multiciliogenesis, such as Mcidas, FoxJ1 and Ccno. Male mice lacking either Gemc1 or Ccno were found to be infertile, but the origin of this defect has remained unclear. Here we show that mice lacking either Gemc1 or Ccno showed a nearly empty seminiferous tubule phenotype. While both genes were expressed in the testes, much higher levels were observed in the efferent ducts that mobilize sperm to the epididymis. We found that both GEMC1 and CCNO were required for the generation of multiciliated cells in the efferent ducts but that they differentially affect activation of FoxJ1 and Tp73. These data indicate that defective efferent duct development, rather than defects in testes development, are likely the primary origin of male infertility observed in the absence of GEMC1 and CCNO and this could extend to Reduced Generation of Multiple Motile Cilia patients with MCIDAS and CCNO mutations.Summary statementWe demonstrate that male mice lacking GEMC1 or CCNO are infertile due to defects in the formation of the efferent ducts.
Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin
Authors: Daane Jacob M , Lanni Jennifer , Rothenberg Ina , Seebohm Guiscard , Higdon Charles W , Johnson Stephen L , Harris Matthew P 
Published: February 2018

AbstractThe establishment of relative size of organs and structures is paramount for attaining final form and function of an organism. Importantly, variation in the proportions of structures frequently underlies adaptive change in morphology in evolution and maybe a common mechanism underlying selection. However, the mechanism by which growth is integrated within tissues during development to achieve proper proportionality is poorly understood. We have shown that signaling by potassium channels mediates coordinated size regulation in zebrafish fins. Recently, calcineurin inhibitors were shown to elicit changes in zebrafish fin allometry as well. Here, we identify the potassium channelkcnk5bas a key player in integrating calcineurin’s growth effects, in part through regulation of the cytoplasmic C-terminus of the channel. We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth. Importantly, we find that this regulation is epistatic to inherent mechanisms instructing overall size as inhibition of calcineurin is able to bypass genetic instruction of size as seen insofand wild-type fins, however, it is not sufficient to re-specify positional memory of size of the fin. These findings integrate classic signaling mediators such as calcineurin with ion channel function in the regulation of size and proportion during growth.
Neuregulin-1 exerts molecular control over axolotl lung regeneration through ErbB family receptors
Authors: Jensen Tyler B , Giunta Peter , Schulz Natalie Grace , Kyeremateng Yaa , Wong Hilary , Adesina Adeleso , Monaghan James R 
Published: February 2018

ABSTRACTThe induction of new lung tissue after disease or trauma has the potential to save lives and transform patient outcomes. Ambystoma mexicanum, the axolotl salamander, is a classic model organism used to study vertebrate regeneration, primarily after limb amputation. While it is hypothesized that axolotls regenerate all of their tissues, exploration of lung regeneration has not been performed until now. Proliferation after lung injury was observed to be a global response, suggesting that regeneration utilizes a compensatory mechanism, in contrast to limb regeneration’s epimorphic response. ErbB signaling is crucial for the proliferative response during lung regeneration, likely through the ErbB2:ErbB4 receptor heterodimer. ErbB4 mRNA was found to be highly upregulated at both one and three weeks post amputation. Neuregulin-1p (NRG1) can induce proliferation in the lung and likely exerts molecular control over lung regeneration. Inhibition of ErbB2 was sufficient to both block regeneration and the proliferative response observed after NRG1 treatment.
Identification of transcriptional signatures for cell types from single-cell RNA-Seq
Authors: Ntranos Vasilis , Yi Lynn , Melsted Páll , Pachter Lior 
Published: February 2018

AbstractSingle-cell RNA-Seq makes it possible to characterize the transcriptomes of cell types and identify their transcriptional signatures via differential analysis. We present a fast and accurate method for discriminating cell types that takes advantage of the large numbers of cells that are assayed. When applied to transcript compatibility counts obtained via pseudoalignment, our approach provides a quantification-free analysis of 3’ single-cell RNA-Seq that can identify previously undetectable marker genes.
Modulation of neuronal resilience during aging by Hsp70/Hsp90/STI1 chaperone system
Authors: Lackie Rachel E. , Razzaq Abdul R. , Farhan Sali M.K. , Moshitzky Gilli , Beraldo Flavio H. , Lopes Marilene H. , Maciejewski Andrzej , Gros Robert , Fan Jue , Choy Wing-Yiu , Greenberg David S. , Martins Vilma R. , Duennwald Martin L. , Soreq Hermona , Prado Vania F. , Prado Marco A.M. 
Published: February 2018

ABSTRACTChaperone networks are dysregulated with aging and neurodegenerative disease, but whether compromised Hsp70/Hsp90 chaperone function directly contributes to neuronal degeneration is unknown. Stress-inducible phosphoprotein-1 (STI1; STIP1; HOP) is a co-chaperone that simultaneously interacts with Hsp70 and Hsp90, but whose functionin vivoremains poorly understood. To investigate the requirement of STI1-mediated regulation of the chaperone machinery in aging we combined analysis of a mouse line with a hypomorphicStip1allele, with a neuronal cell line lacking STI1 and in-depth analyses of chaperone genes in human datasets. Loss of STI1 function severely disturbed the Hsp70/Hsp90 machineryin vivo, and all client proteins tested and a subset of cochaperones presented decreased levels. Importantly, mice expressing a hypomorphic STI1 allele showed spontaneous age-dependent hippocampal neurodegeneration, with consequent spatial memory deficits. STI1 is a critical node for the chaperone network and it can contribute to age-dependent hippocampal neurodegeneration.
SeqOthello: Query over RNA-seq experiments at scale
Authors: Yu Ye , Liu Jinpeng , Liu Xinan , Zhang Yi , Magner Eamonn , Qian Chen , Liu Jinze 
Published: February 2018

AbstractWe present SeqOthello, an ultra-fast and memory-efficient indexing structure to support arbitrary sequence query against large collections of RNA-seq experiments. SeqOthello requires only five minutes to conduct a global survey of 11,658 fusion events against 10,113 TCGA Pan-Cancer RNA-seq datasets on a standard computer with 19.1 GB memory space. The query recovers 92.7% of tier-1 fusions curated by TCGA Fusion Gene Database and further reveals 270 novel fusion occurrences, all of which present as tumor-specific. The entire index is only 76 GB, achieving a 700:1 compression ratio relative to the original sequencing data and making it extremely portable. This is the first sequence search index constructed on the scale of TCGA data. By providing a reference-free, alignment-free, and parameter-free sequence search system, SeqOthello will enable large-scale integrative studies using sequence-level data, an undertaking not previously practicable for many individual labs. SeqOthello is currently available at https://github.com/LiuBioinfo/SeqOthello.
Cortical networks for encoding near and far space in the non-human primate
Authors: Cléry Justine , Guipponi Olivier , Odouard Soline , Wardak Claire , Hamed Suliann Ben 
Published: February 2018

AbstractWhile extra-personal space is often erroneously considered as a unique entity, early neuropsychological studies report a dissociation between near and far space processing both in humans and in monkeys. Here, we use functional MRI in a naturalistic 3D environment to describe the non-human primate near and far space cortical networks. We describe the co-occurrence of two extended functional networks respectively dedicated to near and far space processing. Specifically, far space processing involves occipital, temporal, parietal, posterior cingulate as well as orbitofrontal regions not activated by near space, possibly subserving the processing of the shape and identity of objects. In contrast, near space processing involves temporal, parietal and prefrontal regions not activated by far space, possibly subserving the preparation of an arm/hand mediated action in this proximal space. Interestingly, this network also involves somatosensory regions, suggesting a cross-modal anticipation of touch by a nearby object. Last, we also describe cortical regions that process both far and near space with a preference for one or the other. This suggests a continuous encoding of relative distance to the body, in the form of a far-to-near gradient. We propose that these cortical gradients in space representation subserve the physically delineable peripersonal spaces described in numerous psychology and psychophysics studies.HighlightsNear space processing involves temporal, parietal and prefrontal regions.Far space activates occipital, temporal, parietal, cingulate & orbitofrontal areas.Most regions process both far & near space, with a preference for one or the other.Far-to-near gradient may subserve behavioral changes in peripersonal space size.
The evolution of ogres: cannibalistic growth in giant phagotrophs
Authors: Bloomfield Gareth 
Published: February 2018

AbstractEukaryotes span a very large size range, with macroscopic species most often formel in multicellular lifecycle stages, but sometimes as very large single cells containing many nuclei. The Mycetozoa are a group of amoebae that form macroscopic fruiting structures. However the structures formel by the two major mycetozoan groups are not homologous to each other. Here, it is proposel that the large size of mycetozoans frst arose after selection for cannibalistic feeling by zygotes. In one group, Myxogastria, these zygotes became omnivorous plasmolia; in Dictyostelia the evolution of aggregative multicellularity enablel zygotes to attract anl consume surrounling conspecifc cells. The cannibalism occurring in these protists strongly resembles the transfer of nutrients into metazoan oocytes. If oogamy evolvel early in holozoans, it is possible that aggregative multicellularity centrel on oocytes coull have precelel anl given rise to the clonal multicellularity of crown metazoa.
Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study
Authors: Knolle Franziska , Ermakova Anna O , Justicia Azucena , Fletcher Paul C , Bunzeck Nico , Düzel Emrah , Murray Graham K 
Published: February 2018

AbstractAbnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.
Cognitive Changes associated with Alzheimer’s disease in Down syndrome
Authors: Firth Nicholas C. , Startin Carla M. , Hithersay Rosalyn , Hamburg Sarah , Wijeratne Peter A. , Mok Kin Y. , Hardy John , Alexander Daniel C. ,   The LonDownS Consortium, Strydom André 
Published: February 2018

AbstractObjectiveIndividuals with Down syndrome (DS) have an extremely high genetic risk for Alzheimer’s disease (AD) however the course of cognitive decline associated with progression to dementia is ill-defined. Data-driven methods can estimate long-term trends from cross-sectional data while adjusting for variability in baseline ability, which complicates dementia assessment in those with DS.MethodsWe applied an event-based model to cognitive test data and informant-rated questionnaire data from 283 adults with DS (the largest study of cognitive functioning in DS to date) to estimate the sequence of cognitive decline and individuals’ disease stage.ResultsDecline in tests of memory, sustained attention / motor coordination, and verbal fluency occurred early, demonstrating that AD in DS follows a similar pattern of change to other forms of AD. Later decline was found for informant measures. Using the resulting staging model, we showed that adults with a clinical diagnosis of dementia and those with APOE 3:4 or 4:4 genotype were significantly more likely to be staged later, suggesting the model is valid.InterpretationOur results identify tests of memory and sustained attention may be particularly useful measures to track decline in the preclinical/prodromal stages of AD in DS whereas informant-measures may be useful in later stages (i.e. during conversion to dementia, or post-diagnosis). These results have implications for the selection of outcome measures of treatment trials to delay or prevent cognitive decline due to AD in DS. As clinical diagnoses are generally made late into AD progression, early assessment is essential.
Frequency and power of human alpha oscillations drift systematically with time-on-task
Authors: Benwell Christopher S.Y. , London Raquel E. , Tagliabue Chiara F. , Veniero Domenica , Gross Joachim , Keitel Christian , Thut Gregor 
Published: February 2018

AbstractOscillatory neural activity is a fundamental characteristic of the mammalian brain spanning multiple levels of spatial and temporal scale. Current theories of neural oscillations and analysis techniques employed to investigate their functional significance are based on an often implicit assumption: In the absence of experimental manipulation, the spectral content of any given EEG- or MEG-recorded neural oscillator remains approximately stationary over the course of a typical experimental session (~1 hour), spontaneously fluctuating only around its dominant frequency. Here, we examined this assumption for ongoing neural oscillations in the alpha-band (8:13 Hz). We found that alpha peak frequency systematically decreased over time, while alpha-power increased. Intriguingly, these systematic changes showed partial independence of each other: Statistical source separation (independent component analysis) revealed that while some alpha components displayed concomitant power increases and peak frequency decreases, other components showed either unique power increases or frequency decreases. Interestingly, we also found these components to differ in frequency. Components that showed mixed frequency/power changes oscillated primarily in the lower alpha-band (~8-10Hz), while components with unique changes oscillated primarily in the higher alpha-band (~9-13Hz). Our findings provide novel clues on the time-varying intrinsic properties of large-scale neural networks as measured by M/EEG, with implications for the analysis and interpretation of studies that aim at identifying functionally relevant oscillatory networks or at driving them through external stimulation.