bluuebunny/crossref_metadata_2025_split huggingface dataset:
From thoughtless awareness to effortful cognition: alpha - theta cross-frequency dynamics in experienced meditators during meditation, rest and arithmetic
Authors: Rodriguez-Larios Julio , Faber Pascal , Achermann Peter , Tei Shisei , Alaerts Kaat 
Published: January 2020

AbstractNeural activity is known to oscillate within discrete frequency bands and the synchronization between these rhythms is hypothesized to underlie information integration in the brain. Since strict synchronization is only possible for harmonic frequencies, a recent theory proposes that the interaction between different brain rhythms is facilitated by transient harmonic frequency arrangements. In this line, it has been recently shown that the transient occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms (i.e. falpha≈12 Hz; ftheta≈6 Hz) is enhanced during effortful cognition. In this study, we tested whether achieving a state of ‘mental emptiness’ during meditation is accompanied by a relative decrease in the occurrence of 2:1 harmonic cross-frequency relationships between alpha and theta rhythms. Continuous EEG recordings (19 electrodes) were obtained from 43 highly experienced meditators during meditation practice, rest and an arithmetic task. We show that the occurrence of transient alpha:theta 2:1 harmonic relationships increased linearly from a meditative to an active cognitive processing state (i.e. meditation< rest< arithmetic task). It is argued that transient EEG cross-frequency arrangements that prevent alpha:theta cross-frequency coupling could facilitate the experience of ‘mental emptiness’ by avoiding the interaction between the memory and executive components of cognition.
Evolutionary and ecological processes influencing chemical defense variation in an aposematic and mimeticHeliconiusbutterfly
Authors: Mattila Anniina L. K. , Jiggins Chris D. , Opedal Øystein H. , Montejo-Kovacevich Gabriela , de Castro Érika , McMillan William O. , Bacquet Caroline , Saastamoinen Marjo 
Published: January 2020

ABSTRACTChemical defences against predators underlie the evolution of aposematic coloration and mimicry, which are classic examples of adaptive evolution. Surprisingly little is known about the roles of ecological and evolutionary processes maintaining defence variation, and how they may feedback to shape the evolutionary dynamics of species. CyanogenicHeliconiusbutterflies exhibit diverse warning color patterns and mimicry, thus providing a useful framework for investigating these questions. We studied intraspecific variation inde novobiosynthesized cyanogenic toxicity and its potential ecological and evolutionary sources in wild populations ofHeliconius eratoalong environmental gradients, in common-garden broods and with feeding treatments. Our results demonstrate substantial intraspecific variation, including detectable variation among broods reared in a common garden. The latter estimate suggests considerable evolutionary potential in this trait, although predicting the response to selection is likely complicated due to the observed skewed distribution of toxicity values and the signatures of maternal contributions to the inheritance of toxicity. Larval diet contributed little to toxicity variation. Furthermore, toxicity profiles were similar along steep rainfall and altitudinal gradients, providing little evidence for these factors explaining variation in biosynthesized toxicity in natural populations. In contrast, there were striking differences in the chemical profiles ofH. eratofrom geographically distant populations, implying potential local adaptation in the acquisition mechanisms and levels of defensive compounds. The results highlight the extensive variation and potential for adaptive evolution in defense traits for aposematic and mimetic species, which may contribute to the high diversity often found in these systems.
Maternal genome dominance in early plant embryogenesis
Authors: Alaniz-Fabián Jaime , Xiang Daoquan , Toro-De León Gerardo Del , Orozco-Nieto Axel , Gao Peng , Sharpe Andrew , Kochian Leon V. , Selvaraj Gopalan , Springer Nathan , Abreu-Goodger Cei , Datla Raju , Gillmor C. Stewart 
Published: January 2020

AbstractPrevious studies have alternately supported and discounted the hypothesis that the maternal genome plays a predominant role in early embryogenesis in plants. We used 24embryo defective (emb)mutants ofArabidopsis thalianato test for maternal and paternal effects in early embryogenesis. 5embmutants had equal maternal and paternal effects, 5 showed maternal effects and weak paternal effects, and the remaining 14embmutants conditioned only maternal effects, demonstrating a more important role for the maternal allele for most of theseEMBgenes. To assess genome-wide maternal and paternal contributions to early embryos, we produced allele-specific transcriptomes from zygote to mature stage embryos derived from reciprocal crosses of Columbia-0 and Tsu-1, a hybrid combination we show to be a faithful proxy for isogenic Columbia-0. Parent-of-origin analysis of these transcriptomes revealed a reciprocal maternal bias in thousands of genes from the zygote to octant stage. This bias greatly diminished by the globular stage, and was absent at later stages. Comparison with egg cell transcriptomes revealed no correlation between transcript levels in the egg and maternal bias in pre-globular embryos, suggesting that the maternal bias observed in early embryos is due to preferential zygotic transcription of maternal alleles. Taken together, the functional and transcriptome data presented here support a predominant role for the maternal genome in early Arabidopsis embryogenesis.SignificanceIn both animals and plants, the zygote is produced by the union of the egg and sperm cells. In animals, it is well accepted that mRNAs and proteins from the egg direct the first steps of embryogenesis. Here we present genetic and genomic experiments that support a predominant role for the maternal genome in early embryogenesis of plants, as well. In contrast to animals, our data suggest that this maternal influence is primarily derived not from inheritance of egg transcripts, but from preferential transcription of maternal alleles in the zygote and early embryo. This transient maternal zygotic bias may reflect an ancestral condition to diminish paternal influence on early embryogenesis in outcrossing plants.
Development of Microstructural and Morphological Cortical Profiles in the Neonatal Brain
Authors: Fenchel Daphna , Dimitrova Ralica , Seidlitz Jakob , Robinson Emma C. , Batalle Dafnis , Hutter Jana , Christiaens Daan , Pietsch Maximilian , Brandon Jakki , Hughes Emer J. , Allsop Joanna , O’Keeffe Camilla , Price Anthony N. , Cordero-Grande Lucilio , Schuh Andreas , Makropoulos Antonios , Passerat-Palmbach Jonathan , Bozek Jelena , Rueckert Daniel , Hajnal Jo V. , Raznahan Armin , McAlonan Grainne , Edwards A. David , O’Muircheartaigh Jonathan 
Published: January 2020

AbstractIn the perinatal brain, regional cortical architecture and connectivity lay the foundations for functional circuits and emerging behaviour. Interruptions or atypical development during or before this period may therefore have long-lasting consequences. However, to be able to investigate these deviations, we need a measure of how this architecture evolves in the typically developing brain. To this end, in a large cohort of 241 term-born infants we used Magnetic Resonance Imaging to estimate cortical profiles based on morphometry and microstructure over the perinatal period (37-44 weeks post-menstrual age, PMA). Using the covariance of these profiles as a measure of inter-areal network similarity (Morphometric Similarity Networks; MSN), we clustered these networks into distinct modules. The resulting modules were consistent and symmetric, and corresponded to known functional distinctions, including sensory-motor, limbic and association regions and were spatially mapped onto known cytoarchitectonic tissue classes. Posterior (parietal, occipital) regions became more morphometrically similar with increasing PMA, while peri-cingulate and medial temporal regions became more dissimilar. Network strength was associated with PMA: Within-network similarity increased over PMA suggesting emerging network distinction. These changes in cortical network architecture over an eight-week period are consistent with, and likely underpin, the highly dynamic behavioural and cognitive development occurring during this critical period. The resulting cortical profiles might provide normative reference to investigate atypical early brain development.
Transcriptional profile of pyramidal neurons in chronic schizophrenia reveals lamina-specific dysfunction of neuronal immunity
Authors: Wu Xiaojun , Shukla Rammohan , Alganem Khaled , Depasquale Erica , Reigle James , Simmons Micah , Hahn Chang-Gyu , Haroutunian Vahram , Meller Jarek , Meador-Woodruff James , McCullumsmith Robert 
Published: January 2020

AbstractWhile the pathophysiology of schizophrenia has been extensively investigated using homogenized postmortem brain samples, few studies have examined changes in brain samples with techniques that may attribute perturbations to specific cell types. To fill this gap, we performed microarray assays on mRNA isolated from anterior cingulate cortex (ACC) superficial and deep pyramidal neurons from 12 schizophrenia and 12 control subjects using laser capture microdissection. Among all the annotated genes, we identified 134 significantly increased and 130 decreased genes in superficial pyramidal neurons, while 93 significantly increased and 101 decreased genes were found in deep pyramidal neurons, in schizophrenia compared to control subjects. In these differentially expressed genes, we detected lamina-specific changes of 55 and 31 genes in superficial and deep neurons in schizophrenia, respectively. Gene set enrichment analysis (GSEA) was applied to the entire pre-ranked differential expression gene lists to gain a complete pathway analysis throughout all annotated genes. Our analysis revealed over-represented groups of gene sets in schizophrenia, particularly in immunity and synapse related pathways in pyramidal neurons, suggesting the disruption of these pathways plays an important role in schizophrenia. We also detected pathways previously demonstrated in schizophrenia pathophysiology, including cytokine and chemotaxis, post-synaptic signaling, and glutamatergic synapses. In addition, we observed several novel pathways, including ubiquitin-independent protein catabolic process. By comparing our differential expression gene profiles with 51 antipsychotic treatment datasets, we demonstrated that our results were not influenced by antipsychotic treatment of our subjects. Taken together, we found pyramidal neuron-specific changes in neuronal immunity, synaptic dysfunction, and olfactory dysregulation in schizophrenia, providing new insights for the cell-subtype specific pathophysiology of chronic schizophrenia.
Interaction of 14-3-3I and CDPK1 mediates the growth of human malaria parasite
Authors: Jain Ravi , Dey Pinki , Gupta Sakshi , Pati Soumya , Bhattacherjee Arnab , Munde Manoj , Singh Shailja 
Published: January 2020

ABSTRACTScaffold proteins play pivotal role as modulators of cellular processes by operating as multipurpose conformation clamps. 14-3-3 proteins are gold-standard scaffold modules that recognize phosphoSer/Thr (pS/pT) containing conserved motifs of target proteins and confer conformational changes leading to modulation of their functional parameters. Modulation in functional activity of kinases has been attributed to their interaction with 14-3-3 proteins. Herein, we have characterizedPlasmodium falciparum14-3-3 and its interaction with key kinase of the parasite, Calcium-Dependent Protein Kinase 1 (CDPK1) by performing various analytical biochemistry and biophysical assays. Towards this, we annotated PF3D7_0818200 as 14-3-3 isoform I through extensive phylogenetic and comparative sequence analysis. Molecular dynamics simulation studies indicated that phosphoSer64present in CDPK1 polypeptide sequence (61KLGpS64) behaves as canonical Mode I-type (RXXpS/pT) consensus 14-3-3 binding motif, mediating the interaction. The protein-protein interaction was validatedin vitrowith ELISA and SPR, which confirmed that CDPK1 interacts with 14-3-3I in a phosphorylation dependent manner, with binding affinity constant of 670 ± 3.6 nM. The interaction of 14-3-3I with CDPK1 was validated with well characterized optimal 14-3-3 recognition motifs: ARSHpSYPA and RLYHpSLPA as CDPK1 mimetics, by simulation studies and ITC. Further, interaction antagonizing peptidomimetics showed growth inhibitory impact on the parasite indicating crucial physiological role of 14-3-3/CDPK1 interaction. Overall, this study characterizes 14-3-3I as a scaffold protein in the malaria parasite and unveils CDPK1 as its previously unidentified target. This sets a precedent for the rational design of 14-3-3 based PPI inhibitors by utilizing 14-3-3 recognition motif peptides, as a potential antimalarial strategy.
Atf-6regulates lifespan through ER-mitochondrial calcium homeostasis
Authors: Burkewitz Kristopher , Dutta Sneha , Kelley Charlotte A. , Steinbaugh Michael , Cram Erin J. , Mair William B. 
Published: January 2020

AbstractFunctional crosstalk between organelles is critical for maintaining cellular homeostasis. Individually, dysfunction of both endoplasmic reticulum (ER) and mitochondria have been linked to cellular and organismal aging, but little is known about how mechanisms of inter-organelle communication might be targeted to extended longevity. The metazoan unfolded protein response (UPR) maintains ER health through a variety of mechanisms beyond its canonical role in proteostasis, including calcium storage and lipid metabolism. Here we provide evidence that inC. elegans, inhibition of the conserved UPR mediator, activating transcription factor (atf)-6increases lifespan via modulation of calcium homeostasis and signaling to the mitochondria. Loss ofatf-6confers long life via downregulation of the ER calcium buffering protein, calreticulin. Function of the ER calcium release channel, the inositol triphosphate receptor (IP3R/itr-1), is required foratf-6mutant longevity while a gain-of-function IP3R/itr-1mutation is sufficient to extend lifespan. IP3R dysfunction leads to altered mitochondrial behavior and hyperfused morphology, which is sufficient to suppress long life inatf-6mutants. Highlighting a novel and direct role for this inter-organelle coordination of calcium in longevity, the mitochondrial calcium import channel,mcu-1, is also required foratf-6mutant longevity. Altogether this study reveals the importance of organellar coordination of calcium handling in determining the quality of aging, and highlights calcium homeostasis as a critical output for the UPR andatf-6in particular.
Neuronal LXR Regulates Neuregulin-1 Expression and Sciatic Nerve-Associated Cell signaling
Authors: Gavini Chaitanya K. , Bonomo Raiza , Mansuy-Aubert Virginie 
Published: January 2020

AbstractNeuropathic pain caused by peripheral nerve injury significantly affects sensory perception and quality of life. Accumulating evidence strongly link cholesterol and inflammation with development and progression of Obesity and Diabetes associated-neuropathies. However, the exact mechanisms of how lipid metabolism in peripheral nervous system (PNS) contributes to the pathogenesis of neuropathy remains poorly understood. Dysregulation of LXR pathways have been identified in many transcriptomic analyses in neuropathy models. LXR α/β expressed in sensory neurons are necessary for proper peripheral nerve function. Deletion of LXR α/β from sensory neurons lead to pain-like behaviors. In this study, we identified that LXR α/β expressed in sensory neurons regulates neuronal neuregulin-1 (Nrg1). Using in vivo cell-specific approaches, we observed that loss of LXR from sensory neurons altered genes regulating lipid metabolism in non-neuronal cells potentially representing Schwann cells (SC). Our data suggest that neuronal LXR may regulates SC function via a Nrg1-dependent mechanism. The decrease in Nrg1 expression in DRG neurons of WD-fed mice may suggest an altered Nrg1-dependent neuron-SC communication in Obesity. The communication between neurons and non-neuronal cell such as SC could be a new biological pathway to study and to treat Obesity-associated neuropathy and PNS dysfunction.
Pseudoreplication bias in single-cell studies; a practical solution
Authors: Zimmerman Kip D. , Espeland Mark A. , Langefeld Carl D. 
Published: January 2020

AbstractCells from the same individual share a common genetic and environmental background and are not independent, therefore they are subsamples or pseudoreplicates. Thus, single-cell data have a hierarchical structure that many current single-cell methods do not address, leading to biased inference, highly inflated type 1 error rates, and reduced robustness and reproducibility. This includes methods that use a batch effect correction for individual as a means of accounting for within sample correlation. Here, we document this dependence across a range of cell types and show that ‘pseudo-bulk’ aggregation methods are overly conservative and underpowered relative to mixed models. We propose applying two-part hurdle generalized linear mixed models with a random effect for individual to properly account for both zero inflation and the correlation structure among measures from cells within an individual. Finally, we provide power estimates across a range of experimental conditions to assist researchers in designing appropriately powered studies.
Reward modulates cortical representations of action
Authors: Adkins Tyler J. , Lee Taraz G. 
Published: January 2020

AbstractPeople are capable of rapid on-line improvements in performance when they are offered a reward. The neural mechanism by which this performance enhancement occurs remains unclear. We investigated this phenomenon by offering monetary reward to human participants, contingent on successful performance in a sequence production task. We found that people performed actions more quickly and accurately when they were offered large rewards. Increasing reward magnitude was associated with elevated activity throughout the brain prior to movement. Multivariate patterns of activity in these reward-responsive regions encoded information about the upcoming action. Follow-up analyses provided evidence that action decoding in pre-SMA and other motor planning areas was improved for large reward trials and successful action decoding was associated with improved performance. These results suggest that reward may enhance performance by enhancing neural representations of action used in motor planning.HighlightsReward enhances behavioral performance.Reward enhances action decoding in motor planning areas prior to movement.Enhanced action decoding coincides with improved behavioral performance.
Molecular packing structure of fibrin fibers resolved by X-ray scattering and molecular modeling
Authors: Jansen Karin A. , Zhmurov Artem , Vos Bart E. , Portale Giuseppe , Merino D. Hermida , Litvinov Rustem I. , Tutwiler Valerie , Kurniawan Nicholas A. , Bras Wim , Weisel John W. , Barsegov Valeri , Koenderink Gijsje H. 
Published: January 2020

ABSTRACTFibrin is the major extracellular component of blood clots and a proteinaceous hydrogel used as a versatile biomaterial. Fibrin forms branched networks of polymeric fibers, built of laterally associated double-stranded protofibrils. This multiscale hierarchical structure is crucial for the extraordinary mechanical resilience of blood clots. Yet, the structural basis of clot mechanical properties remains largely unclear due, in part, to the unresolved molecular packing structure of fibrin fibers. Here we quantitatively assess the packing structure of fibrin fibers by combining Small Angle X-ray Scattering (SAXS) measurements of fibrin networks reconstituted under a wide range of conditions with computational molecular modeling of fibrin oligomers. The number, positions, and intensities of the Bragg peaks observed in the SAXS experiments were reproduced computationally based on the all-atom molecular structure of reconstructed fibrin protofibrils. Specifically, the model correctly predicts the intensities of the reflections of the 22.5 nm axial repeat, corresponding to the half-staggered longitudinal arrangement of fibrin molecules. In addition, the SAXS measurements showed that protofibrils within fibrin fibers have a partially ordered lateral arrangement with a characteristic transverse repeat distance of 13 nm, irrespective of the fiber thickness. These findings provide fundamental insights into the molecular structure of fibrin clots that underlies their biological and physical properties.
A bead-based method for the removal of the amino acid lysine from cell-free transcription-translation systems
Authors: Finkler Marc , Kurt Ömer , Grimm Florent , Hartz Philip , Ott Albrecht 
Published: January 2020

AbstractCell-free transcription-translation systems are a versatile tool to study gene expression, enzymatic reactions and biochemical regulation mechanisms. Because cell-free transcription-translation systems are often derived from cell lysates, many different substances, among them amino acids, are present. However, experiments concerning the incorporation of non-canonical amino acids into proteins require a system with negligible amounts of canonical analogs. Here we propose a two-step method for the removal of residual free lysine in an allEscherichia coli-based cell-free expression system. The first step consists of the expression of a high-lysine dummy protein. The second step consists of direct removal via binding between lysine and DNA. The presented method is an efficient, fast and simple way to remove residual lysine without altering the system ability to perform gene expression.
Protein kinase Cε activation induces EHD-dependent degradation and downregulation of KATPchannels: Implications for glucose stimulated insulin secretion
Authors: Cockcroft Christopher J , Manna Paul , Karnik Rucha , Taneja Tarvinder K , Wrighton David , Mankouri Jamel , Rong Hong-Lin , Sivaprasadarao Asipu 
Published: January 2020

AbstractPancreatic β-cells have the unique ability to couple glucose metabolism to insulin secretion. This capacity is generally attributed to the ability of ATP to inhibit KATPchannels, and the consequent β-cell membrane depolarization and excitation. This notion has recently been challenged by a study which demonstrated that high glucose (HG) downregulates the cell surface KATPchannels, and thereby leads to β-cell depolarisation and excitation. The authors attributed the downregulation to HG-induced protein kinase C (PKC) activation and the consequent increase in channel endocytosis. This interpretation, however, is inconsistent with our previous findings that PKC activation does not affect endocytosis. To address this controversy, we revisited the problem: we have used cell biological and electrophysiological approaches combined with the pharmacological activator of PKC, PMA (phorbol 12-myristate 13-acetate). We first confirm that PKC does not play a role in KATPchannel endocytosis; instead, it downregulates the channel by promoting lysosomal degradation coupled with reduced recycling. We then show that (i) mutation of the dileucine motif (355LL356) in the C-terminal domain of the Kir6.2 subunit of the KATPchannel complex prevents lysosomal degradation; (ii) lysosomal targeting is mediated by the EHD (Eps15 homology domain– containing) proteins; and (iii) the PKC isoform responsible for channel degradation is PKCε. Taken together with the published data, we suggest that HG promotes β-cell excitability via two mechanisms: ATP-dependent channel inhibition and ATP-independent, PKCε-dependent channel degradation. The results likely have implications for glucose induced biphasic insulin secretion.