bluuebunny/crossref_metadata_2025_split huggingface dataset:
A common framework for the problem of deriving estimates of dynamic functional brain connectivity
Authors: Thompson William Hedley , Fransson Peter 
Published: November 2017

AbstractThe research field of dynamic functional connectivity explores the temporal properties of brain connectivity. To date, many methods have been proposed, which are based on quite different assumptions. In order to understand in which way the results from different techniques can be compared to each other, it is useful to be able to formulate them within a common theoretical framework. In this study, we describe such a framework that is suitable for many of the dynamic functional connectivity methods that have been proposed. Our overall intention was to derive a theoretical framework that was constructed such that a wide variety of dynamic functional connectivity techniques could be expressed and evaluated within the same framework. At the same time, care was given to the fact that key features of each technique could be easily illustrated within the framework and thus highlighting critical assumptions that are made. We aimed to create a common framework which should serve to assist comparisons between different analytical methods for dynamic functional brain connectivity and promote an understanding of their methodological advantages as well as potential drawbacks.HighlightsDifferent approaches to compute dynamic functional brain connectivity have been proposed, each with their own assumptions.We present a theoretical framework that encompasses a large majority of proposed methods.Our common framework facilitates comparisons between different methods and illustrates their underlying assumptions.
A practical tool for Maximal Information Coefficient analysis
Authors: Albanese Davide , Riccadonna Samantha , Donati Claudio , Franceschi Pietro 
Published: November 2017

AbstractBackgroundThe ability of finding complex associations in large omics datasets, assessing their significance, and prioritizing them according to their strength can be of great help in the data exploration phase. Mutual Information based measures of association are particularly promising, in particular after the recent introduction of the TICeand MICeestimators, which combine computational efficiency with good bias/variance properties. Despite that, a complete software implementation of these two measures and of a statistical procedure to test the significance of each association is still missing.FindingsIn this paper we present MICtools, a comprehensive and effective pipeline which combines TICeand MICeinto a multi-step procedure that allows the identification of relationships of various degrees of complexity. MICtools calculates their strength assessing statistical significance using a permutation-based strategy. The performances of the proposed approach are assessed by an extensive investigation in synthetic datasets and an example of a potential application on a metagenomic dataset is also illustrated.ConclusionsWe show that MICtools, combining TICeand MICe, is able to highlight associations that would not be captured by conventional strategies. MICtools is implemented in Python, and is available for download athttps://github.com/minepy/mictools.
Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type
Authors: Boldog Eszter , Bakken Trygve , Hodge Rebecca D. , Novotny Mark , Aevermann Brian D. , Baka Judith , Bordé Sándor , Close Jennie L. , Diez-Fuertes Francisco , Ding Song-Lin , Faragó Nóra , Kocsis Ágnes K. , Kovács Balázs , McCorrison Jamison M. , Miller Jeremy A. , Molnár Gábor , Oláh Gáspár , Ozsvár Attila , Rózsa Márton , Shehata Soraya , Smith Kimberly A. , Sunkin Susan M. , Tran Danny N. , Venepally Pratap , Wall Abby , Puskás László G. , Barzó Pál , Steemers Frank J. , Schork Nicholas J. , Scheuermann Richard H. , Lasken Roger S. , Lein Ed S. , Tamás Gábor 
Published: November 2017

AbstractWe describe convergent evidence from transcriptomics, morphology and physiology for a specialized GABAergic neuron subtype in human cortex. Using unbiased single nucleus RNA sequencing, we identify ten GABAergic interneuron subtypes with combinatorial gene signatures in human cortical layer 1 and characterize a novel group of human interneurons with anatomical features never described in rodents having large, “rosehip”-like axonal boutons and compact arborization. These rosehip cells show an immunohistochemical profile (GAD1/CCK-positive, CNR1/SST/CALB2/PVALB-negative) matching a single transcriptomically-defined cell type whose molecular signature is not seen in mouse cortex. Rosehip cells make homotypic gap junctions, predominantly target apical dendritic shafts of layer 3 pyramidal neurons and inhibit backpropagating pyramidal action potentials in microdomains of the dendritic tuft. These cells are therefore positioned for potent local control of distal dendritic computation in cortical pyramidal neurons.
Divergent effects of healthy ageing on semantic knowledge and control: Evidence from novel comparisons with semantically-impaired patients
Authors: Hoffman Paul 
Published: November 2017

AbstractEffective use of semantic knowledge requires a set of conceptual representations and control processes which ensure that currently-relevant aspects of this knowledge are retrieved and selected. It is well-established that levels of semantic knowledge increase across the lifespan. However, the effects of ageing on semantic control processes have not been assessed. I addressed this issue by comparing the performance profiles of young and older people on a verbal comprehension test. Two sets of variables were used to predict accuracy and RT in each group: (a) the psycholinguistic properties of words probed in each trial, (b) the performance on each trial by two groups of semantically-impaired neuropsychological patients. Young people demonstrated poor performance for low frequency and abstract words, suggesting that they had difficulty processing words with intrinsically weak semantic representations. Indeed, performance in this group was strongly predicted by the performance of patients with semantic dementia, who suffer from degradation of semantic knowledge. In contrast, older adults performed poorly on trials where the target semantic relationship was weak and distractor relationships strong – conditions which require high levels of controlled processing. Their performance was not predicted by the performance of semantic dementia patients, but was predicted by the performance of patients with semantic control deficits. These findings indicate that the effects of ageing on semantic cognition are more complex than has previously been assumed. While older people have larger stores of knowledge than young people, they appear to be less skilled at exercising control over the activation of this knowledge.
Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes
Authors: Breen Michael S. , Wingo Aliza P. , Koen Nastassja , Donald Kirsten A. , Nicol Mark , Zar Heather J. , Ressler Kerry J. , Buxbaum Joseph D. , Stein Dan J. 
Published: November 2017

ABSTRACTPrenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We applied transcriptome-wide screens to 149 umbilical cord blood samples from neonates born to mothers with posttraumatic stress disorder (PTSD;n=20), depression (n=31) and PTSD with comorbid depression (n=13), compared to carefully matched trauma exposed controls (n=23) and healthy mothers (n=62). Analyses by maternal diagnoses revealed a clear pattern of gene expression signatures distinguishing neonates born to mothers with a history of psychopathology from those without. Co-expression network analysis identified distinct gene expression perturbations across maternal diagnoses, including two depression-related modules implicated in axon-guidance and mRNA stability, as well as two PTSD-related modules implicated in TNF signaling and cellular response to stress. Notably, these disease-related modules were enriched with brain-expressed genes and genetic risk loci for autism spectrum disorder and schizophrenia, which may imply a causal role for impaired developmental outcomes. These molecular alterations preceded changes in clinical measures at twenty-four months, including reductions in cognitive and socio-emotional outcomes in affected infants. Collectively, these findings indicate that prenatal exposure to maternal psychological distress induces neuronal, immunological and behavioral abnormalities in affected offspring and support the search for early biomarkers of exposures to adversein uteroenvironments and the classification of children at risk for impaired development.
Aquaporin-4 dependent glymphatic solute transport in rodent brain
Authors: Mestre Humberto , Kress Benjamin T. , Zou Wenyan , Pu Tinglin , Murlidharan Giridhar , Rivera Ruth M. Castellanos , Simon Matthew J. , Pike Martin M. , Plog Benjamin A , Xavier Anna L. R. , Thrane Alexander S. , Lundgaard Iben , Thomas John H. , Xiao Ming , Asokan Aravind , Miff Jeffrey J. , Nedergaard Maiken 
Published: November 2017

AbstractThe glymphatic system is a brain-wide metabolite clearance pathway, impairment of which in post-traumatic and ischemic brain or healthy aging is proposed to contribute to intracerebral accumulation of amyloid-β and tau proteins. Glymphatic perivascular influx of cerebrospinal fluid (CSF) depends upon the expression and perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Prompted by a recent publication that failed to find an effect of Aqp4 knockout on perivascular CSF tracer influx and interstitial fluid (ISF) tracer dispersion, four independent research groups have herein re-examined the importance of Aqp4 in glymphatic fluid transport. We concur in finding that CSF tracer influx, as well as fluorescently-tagged amyloid-β efflux, are significantly faster in wild-type mice than in three different transgenic lines featuring disruption of the Aqp4 gene and one line in which AQP4 expression lacks the critical perivascular localization (Snta1 knockout). These data validate the role of AQP4 in supporting fluid and solute transport and efflux in brain in accordance with the glymphatic system model.
Visual attention is not always spatially coupled to subsequent oculomotor program
Authors: Wollenberg Luca , Deubel Heiner , Szinte Martin 
Published: November 2017

AbstractThe premotor theory of attention postulates that spatial attention arises from the activation of saccade areas and that the deployment of attention is the consequence of motor programming. Yet, attentional and oculomotor processes have been shown to be dissociable at the neuronal level in covert attention tasks. To investigate a potential dissociation at the behavioral level, we instructed human participants to saccade towards one of two nearby, competing saccade cues. The spatial distribution of visual attention was determined using oriented Gabor stimuli presented either at the cue locations, between them or at several other equidistant locations. Results demonstrate that accurate saccades towards one of the cues were associated with presaccadic enhancement of visual sensitivity at the respective saccade endpoint compared to the non-saccaded cue location. In contrast, averaging saccades, landing between the two cues, were not associated with attentional facilitation at the saccade endpoint, ruling out an obligatory coupling of attentional deployment to the oculomotor program. Rather, attention before averaging saccades was equally distributed to the two cued locations. Taken together, our results reveal a spatial dissociation of visual attention and saccade programming. They suggest that the oculomotor program depends on the state of attentional selection before saccade onset, and that saccade averaging arises from unresolved attentional selection.
MRIQC Web-API: Crowdsourcing image quality metrics and expert quality ratings of structural and functional MRI
Authors: Esteban O. , Blair RW. , Nielson DM. , Varada JC. , Marrett S. , Thomas AG. , Poldrack RA. , Gorgolewski KJ. 
Published: November 2017

SynopsisThe MRIQC Web-API is a resource for scientists to train new automatic quality classifiers. The MRIQC Web-API has collected more than 30K sets of image quality measures automatically extracted from BOLD and T1-weighted scans using MRIQC. MRIQC is an automated MRI Quality Control tool, and here we present an extension to crowdsource these quality metrics along with anonymized metadata and manual quality ratings. This new resource will allow a better understanding of the normative values and distributions of these quality metrics, help determine the relationships between image quality and metadata such as acquisition parameters and finally, provide a cost-effective, easy way to annotate the quality of a large number of cross-site MR scans.
Failure of in vitro differentiation of Plasmodium falciparum gametocytes into ookinetes arises because of poor gamete fertilisation
Authors: Delves Michael J , Marques Sara R , Ruecker Andrea , Straschil Ursula , Miguel-Blanco Celia , López-Barragá María J , Lelièvre Joël , Molina Irene , Wree Melanie , Okitsu Shinji L , Winzeler Elizabeth , Li Fengwu , Vinetz Joseph , Sheppard Sam , Guedes Joana , Guerra Nadia , Herreros Esperanza , Sinden Robert E , Baum Jake 
Published: November 2017

ABSTRACTA critical step towards malaria elimination will be the interruption of Plasmodium transmission from the human host to the mosquito. At the core of the transmission cycle lies Plasmodium sexual reproduction leading to zygote formation and mosquito midgut colonisation by ookinetes. Whilst in vitro ookinete culture from the murine and avian malaria parasites, Plasmodium berghei and P. gallinaceum, has greatly increased our knowledge of transmission biology; efforts to mimic the process in the human parasite P. falciparum have, to date, had only limited success. Using fluorescence microscopy and flow cytometry with antibodies specific to the male gametocyte and developing ookinetes, we sought to evaluate P. falciparum ookinete production using previously published in vitro protocols. We then compared in vitro versus in vivo ookinete production in both P. falciparum and P. berghei parasites, exploring potential barriers to complete development. Finally, we sought to test a wide range of literature-led culture conditions towards further optimisation of in vitro P. falciparum ookinete production. Despite extensive testing, our efforts to replicate published methods did not produce appreciable quantities of fully formed P. falciparum ookinetes in vitro. In parallel, however, gametocyte cultures that failed to differentiate fully in vitro successfully developed into ookinetes in vivo with an efficiency approximating that of P. berghei. Flow cytometry analysis showed that this disparity likely lies with the poor fertilization of P. falciparum gametes in vitro. Attempts to improve gametocyte fertility or define conditions more permissive to fertilisation/ookinete survival in vitro were also unsuccessful. Current in vitro conditions for P. falciparum ookinete production are not optimal for gamete fertilisation either due to the lack of parasite-species-specific mosquito factors missing from in vitro culture, or non-permissive cues contaminating culture preparations.
The utility of mortality hazard rates in population analyses
Authors: Ergon Torbjørn , Borgan Ørnulf , Nater Chloé Rebecca , Vindenes Yngvild 
Published: November 2017

AbstractMortality is a key process in ecology and evolution, and much effort is spent on development and application of statistical and theoretical models involving mortality. Mortality takes place in continuous time, and a fundamental representation of mortality risks is the mortality hazard rate, which is the intensity of deadly events that an individual is exposed to at any point in time. In discrete-time population models, however, the mortality process is represented by survival or mortality probabilities, which are aggregate functions of the mortality hazard rates within given intervals. In this commentary, we argue that focussing on mortality hazard rates, also when using discrete-time models, aids the construction of biologically reasonable models and improves ecological inference.We discuss three topics in population ecology where hazard rates can be particularly useful for biological inference, but are nevertheless often not used: (i) modelling of covariate effects, (ii) modelling of multiple sources of mortality and competing risks, and (iii) elasticity analyses of population growth rate with respect to demographic parameters. To facilitate estimation of cause-specific mortality hazard rates, we provide extensions to the R package ‘marked’.Using mortality hazard rates sometimes makes it easier to formulate biologically reasonable models with more directly interpretable parameterizations and more explicit assumptions. In particular, interpretations about relative differences between mortality hazard rates, or effects of relative changes in mortality hazard rates on population growth (elasticities), are often more meaningful than interpretations involving relative differences in survival (or mortality) probabilities or odds.The concept of hazard rates is essential for understanding ecological and evolutionary processes and we give an intuitive explanation for this, using several examples. We provide some practical guidelines and suggestions for further methods developments.
Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore
Authors: Bao Xun X. , Spanos Christos , Kojidani Tomoko , Lynch Eric M. , Rappsilber Juri , Hiraoka Yasushi , Haraguchi Tokuko , Sawin Kenneth E. 
Published: November 2017

ABSTRACTNon-centrosomal microtubule organizing centers (MTOCs) are important for microtubule organization in many cell types. In fission yeastSchizosaccharomyces pombe, the protein Mto1, together with partner protein Mto2 (Mto1/2 complex), recruits the γ-tubulin complex to multiple non-centrosomal MTOCs, including the nuclear envelope (NE). Here, we develop a comparative-interactome mass spectrometry approach to determine how Mto1 localizes to the NE. Surprisingly, we find that Mto1, a constitutively cytoplasmic protein, docks at nuclear pore complexes (NPCs), via interaction with exportin Crm1 and cytoplasmic FG-nucleoporin Nup146. Although Mto1 is not a nuclear export cargo, it binds Crm1 via a nuclear export signal-like sequence, and docking requires both Ran in the GTP-bound state and Nup146 FG repeats. In addition to determining the mechanism of MTOC formation at the NE, our results reveal a novel role for Crm1 and the nuclear export machinery in the stable docking of a cytoplasmic protein complex at NPCs.
Auditory Figure-Ground Segregation is Impaired by High Visual Load
Authors: Molloy Katharine , Lavie Nilli , Chait Maria 
Published: November 2017

ABSTRACTFigure-ground segregation is fundamental to listening in complex acoustic environments. An ongoing debate pertains to whether segregation requires attention or is ‘automatic’ and pre-attentive. In this magnetoencephalography (MEG) study we tested a prediction derived from Load Theory of attention1 that segregation requires attention, but can benefit from the automatic allocation of any ‘leftover’ capacity under low load. Complex auditory scenes were modelled with Stochastic Figure Ground stimuli (SFG2) which occasionally contained repeated frequency component ‘figures’. Naive human subjects passively listened to these signals while performing a visual attention task of either low or high load. Whilst clear figure-related neural responses were observed under conditions of low load, high visual load essentially abolished the neural response to the figure in auditory cortex (Planum Temporale, Heschl’s gyrus). We conclude that fundamental figure-ground segregation in hearing is not automatic but draws on shared resources across vision and audition.
Stringency of synthetic promoter sequences inClostridiumrevealed and circumvented by tuning promoter library mutation rates
Authors: Mordaka Paweł M. , Heap John T. 
Published: November 2017

ABSTRACTCollections of characterized promoters of different strengths are key resources for synthetic biology, but are not well established for many important organisms, including industrially-relevantClostridiumspp. When generating promoters, reporter constructs are used to measure expression, but classical fluorescent reporter proteins are oxygen-dependent and hence inactive in anaerobic bacteria likeClostridium. We directly compared oxygen-independent reporters of different types inClostridium acetobutylicumand found that glucuronidase (GusA) fromE. coliperformed best. Using GusA, a library of synthetic promoters was first generated by a typical approach entailing complete randomization of a constitutive thiolase gene promoter (Pthl) except for the consensus -35 and -10 elements. In each synthetic promoter, the chance of each degenerate position matching Pthlwas 25%. Surprisingly, none of the synthetic promoters from this library were functional inC. acetobutylicum, even though they functioned as expected inE. coli. Next, instead of complete randomization, we specified lower promoter mutation rates using oligonucleotide primers synthesized using custom mixtures of nucleotides. Using these primers, two promoter libraries were constructed in which the chance of each degenerate position matching Pthlwas 79% or 58%, instead of 25% as before. Synthetic promoters from these ‘stringent’ libraries functioned well inC. acetobutylicum, covering a wide range of strengths. The promoters functioned similarly in the distantly-related speciesClostridium sporogenes, and allowed predictable metabolic engineering ofC. acetobutylicumfor acetoin production. Besides generating the desired promoters and demonstrating their useful properties, this work indicates an unexpected ‘stringency’ of promoter sequences inClostridium, not reported previously.GRAPHICAL ABSTRACT
Tumorcode - A framework to simulate vascularized tumors
Authors: Fredrich Thierry , Welter Michael , Rieger Heiko 
Published: November 2017

AbstractDuring the past years our group published several articles using computer simulations to address the complex interaction of tumors and the vasculature as underlying transport network. Advances in imaging and lab techniques pushed in vitro research of tumor spheroids forward and animal models as well as clinical studies provided more insights to single processes taking part in tumor growth, however, an overall picture is still missing. Computer simulations are a none-invasive option to cumulate current knowledge and form a quasi in vivo system. In our software, several known models were assembled into a multi-scale approach which allows to study length scales relevant for clinical applications.We release our code to the public domain, together with a detailed description of the implementation and several examples, with the hope of usage and futher development by the community. Justification for the included algorithms and the biological models was obtained in previous publications, here we summarize technical aspects following the workflow of a typical simulation procedure.