bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of transcranial magnetic stimulation of the medial prefrontal cortex on emotional memory schemas
Authors: Bovy Leonore , Berkers Ruud M.W.J. , Pottkämper Julia , Varatheesvaran Rathiga , Fernández Guillén , Tendolkar Indira , Dresler Martin 
Published: June 2019

AbstractMemory bias for negative information is a critical characteristic of major depression, but the underlying neural mechanisms are largely unknown. The recently revived concept of memory schemas may shed new light on memory bias in depression: negative schemas might enhance the encoding and consolidation of negative experiences, thereby contributing to the genesis and perpetuation of depressive pathology. To investigate this relationship, we aimed to transiently perturb processing in the medial prefrontal cortex (mPFC), a core region involved in schema memory, using neuronavigated transcranial magnetic stimulation (TMS) targeting the mPFC. Forty healthy volunteers first underwent a negative mood induction to activate negative schema processing after which they received either active inhibitory (N = 20) or control (N = 20) stimulation to the mPFC. Then, all participants performed the encoding of an emotional false memory task. Recall and recognition performance was tested the following morning. Polysomnographic data was recorded continuously during the night before and after encoding. Secondary measures included sleep and mood questionnaires. We observed a significantly lower number of false recognition of negative critical lures following mPFC perturbation compared to the control group, whereas no differences in veridical memory performance were observed. These findings were supported by reaction time data. No relation between REM sleep and (false) emotional memory performance was observed. These findings support previous causal evidence for a role of the mPFC in schema memory processing and further suggest a role of the mPFC in memory bias.
Enriched G-quadruplexes on the Drosophila Male X Chromosome Function as Insulators of Dosage Compensation Complex
Authors: Qian Sheng-Hu , Chen Lu , Chen Zhen-Xia 
Published: June 2019

AbstractThe evolution of sex chromosomes has resulted in half X chromosome dosage in males as females. Dosage compensation, or the two-fold upregulation in males, was thus evolved to balance the gene expression between sexes. However, the step-wise evolutionary trajectory of dosage compensation during Y chromosome degeneration is still unclear. Here, we show that the specific structured elements G-quadruplexes (G4s) are enriched on the X chromosome in Drosophila melanogaster. Meanwhile, on the X chromosome, the G4s are underrepresented on the H4K16 acetylated regions and the binding sites of dosage compensation complex male-specific lethal (MSL) complex. Peaks of G4 density and potential are observed at the flanking regions of MSL binding sites, suggesting G4s act as insulators to precisely up-regulate certain regions in males. Thus, G4s may be involved in the evolution of dosage compensation process through fine-tuning one-dose proto-X chromosome regions around MSL binding sites during the gradual Y chromosome degeneration.One Sentence SummaryG-quadruplexes act as insulators to precisely up-regulate X chromosome in males.
Genetic background modifies CNS-mediated sensorimotor decline in the AD-BXD mouse population
Authors: O’Connell Kristen M.S. , Ouellette Andrew R. , Neuner Sarah M. , Dunn Amy R. , Kaczorowski Catherine C. 
Published: June 2019

AbstractMany patients with Alzheimer’s dementia also exhibit non-cognitive symptoms such as sensorimotor deficits, which can precede the onset of the hallmark cognitive deficits and significantly impact daily activities and an individual’s ability to live independently. However, the mechanisms underlying sensorimotor dysfunction in AD and the relationship between sensorimotor and cognitive decline remain poorly understood, due in part to a lack of translationally relevant animal models. To address this, we recently developed a novel model of genetic diversity in Alzheimer’s disease, the AD-BXD genetic reference panel. In this study, we investigated sensorimotor deficits in the AD-BXDs and their relationship to cognitive decline in these mice. We found that both age- and AD-related declines in coordination, balance, and vestibular function vary significantly across the panel, indicating that genetic background strongly influences the expressivity of the familial AD mutations used in the AD-BXD panel and their impact on motor function. Further, we found that motor decline is not associated withcognitive decline in either AD or aging, suggesting that sensorimotor deficits in AD occur – in part - through distinct mechanisms. Overall, the results presented here suggest that AD-related sensorimotor decline is strongly dependent on background genetics and is independent of dementia and cognitive deficits, suggesting that effective therapeutics for the entire spectrum of AD symptoms will likely require interventions targeting each distinct domain involved in the disease.
Unconventional cell division cycles from marine-derived yeasts
Authors: Mitchison-Field Lorna M.Y. , Vargas-Muñiz José M. , Stormo Benjamin M. , Vogt Ellysa J.D. , Van Dierdonck Sarah , Ehrlich Christoph , Lew Daniel J. , Field Christine M. , Gladfelter Amy S. 
Published: June 2019

AbstractFungi have been found in every marine habitat that has been explored, however, the diversity and functions of fungi in the ocean are poorly understood. In this study, fungi were cultured from the marine environment in the vicinity of Woods Hole, MA, USA including from plankton, sponge and coral. Our sampling resulted in 36 unique species across 20 genera. We observed many isolates by time-lapse differential interference contrast (DIC) microscopy and analyzed modes of growth and division. Several black yeasts displayed highly unconventional cell division cycles compared to those of traditional model yeast systems. Black yeasts have been found in habitats inhospitable to other life and are known for halotolerance, virulence, and stress-resistance. We find that this group of yeasts also shows remarkable plasticity in terms of cell size control, modes of cell division, and cell polarity. Unexpected behaviors include division through a combination of fission and budding, production of multiple simultaneous buds, and cell division by sequential orthogonal septations. These marine-derived yeasts reveal alternative mechanisms for cell division cycles that seem likely to expand the repertoire of rules established from classic model system yeasts.
Toward computational design of protein crystals with improved resolution
Authors: Jeliazkov Jeliazko R. , Robinson Aaron C. , García-Moreno E. Bertrand , Berger James M. , Gray Jeffrey J. 
Published: June 2019

AbstractSubstantial advances have been made in the computational design of protein interfaces over the last 20 years. However, the interfaces targeted by design have typically been stable and high affinity. Here, we report the development of a generic computational design method to stabilize the weak interactions at crystallographic interfaces. Initially, we analyzed structures reported in the Protein Data Bank (PDB) to determine whether crystals with more stable interfaces result in higher resolution structures. We found that, for twenty-two variants of a single protein crystallized by a single individual, Rosetta score correlates with resolution. We next developed and tested a computational design protocol, seeking to identify point mutations that would improve resolution on a highly stable variant of staphylococcal nuclease (SNase Δ+PHS). Only one of eleven initial designs crystallized, forcing us to re-evaluate our strategy and base our designs on an ensemble of protein backbones. Using this strategy, four of the five designed proteins crystallized. Collecting diffraction data for multiple crystals per design and solving crystal structures, we found that designed crystals improved resolution modestly and in unpredictable ways, including altering crystal space group. Post-hoc, in silico analysis showed that crystal space groups could have been predicted for four of six variants (including WT), but that resolution did not correlate with interface stability, as it did in the preliminary results. Our results show that single point mutations can have significant effects on crystal resolution and space group, and that it is possible to computationally identify such mutations, suggesting a potential design strategy to generate high-resolution protein crystals from poorly diffracting ones.
Single Nanoparticle Tracking Reveals Efficient Long-Distance Undercurrent Transport above Swarming Bacteria
Authors: Feng Jingjing , Zhang Zexin , Wen Xiaodong , Xue Jianfeng , He Yan 
Published: June 2019

AbstractFlagellated bacteria move collectively in a swirling pattern on agar surfaces immersed in a thin layer of viscous “swarm fluid”, but the role of this fluid in mediating the cooperation of the bacterial population is not well understood. Herein, we use gold nanorods (AuNRs) as single particle tracers to explore the spatiotemporal structure of the swarm fluid. We observed that individual AuNRs are transported in a plane of ~2 μm above the motile cells. They can travel for long distances (>700 μm) in a 2D plane at high speed (often >50 μm2/s) without interferences from bacterial movements. The particles are apparently lifted up and transported by collective mixing of the small vortices around bacteria during localized clustering and de-clustering of the motile cells, exhibiting superdiffusive and non-Gaussian characteristics with alternating large-step jumps and confined lingering. Their motions are consistent with the Lévy walk (LW) model, revealing efficient transport flows above swarms. These flows provide obstacle-free highways for long-range material transportations, shed light on how swarming bacteria perform population-level communications, and reveal the essential role of the fluid phase on the emergence of large-scale synergy. This approach is promising for probing complex fluid dynamics and transports in other collective systems.
Automated Threshold Selection for Cryo-EM Density Maps
Authors: Pfab Jonas , Si Dong 
Published: June 2019

AbstractRecent advances in cryo-EM have made it possible to create protein density maps with a near-atomic resolution. This has contributed to its wide popularity, resulting in a rapidly growing number of available cryo-EM density maps. In order to computationally process them, an electron density threshold level is required which defines a lower bound for density values. In the context of this paper the threshold level is required in a pre-processing step of the backbone structure prediction project which predicts the location of Cα atoms of the backbone of a protein based on its cryo-EM density map using deep learning techniques. A custom threshold level has to be selected for each prediction in order to reduce noise that could irritate the deep learning model. Automatizing this threshold selection process makes it easier to run predictions as well as it removes the dependency of the prediction accuracy to the ability of someone to choose the right threshold value. This paper presents a method to automatize the threshold selection for the previously mentioned project as well as for other problems which require a density threshold level. The method uses the surface area to volume ratio and the ratio of voxels that lie above the threshold level to non-zero voxels as metrics to derive characteristics about suitable threshold levels based on a training dataset. The threshold level selection was tested by integrating it in the backbone prediction project and evaluating the accuracy of predictions using automatically as well as manually selected thresholds. We found that there was no loss in accuracy using the automatically selected threshold levels indicating that they are equally good as manually selected ones. The source code related to this paper can be found at https://github.com/DrDongSi/Auto-Thresholding.
Age-dependent changes in electrophysiology and calcium handling – implications for pediatric cardiac research
Authors: Swift Luther M. , Burke Morgan , Guerrelli Devon , Ramadan Manelle , Reilly Marissa , McCullough Damon , Chaluvadi Ashika , Mulvany Colm , Jaimes Rafael , Posnack Nikki Gillum 
Published: June 2019

ABSTRACTRationaleThe heart continues to develop and mature after birth and into adolescence. Accordingly, cardiac maturation is likely to include a progressive refinement in both organ morphology and function during the postnatal period. Yet, age-dependent changes in cardiac electrophysiology and calcium handling have not yet been fully characterized.ObjectiveThe objective of this study, was to examine the relationship between cardiac maturation, electrophysiology, and calcium handling throughout postnatal development in a rat model.MethodsPostnatal rat cardiac maturation was determined by measuring the expression of genes involved in cell-cell coupling, electrophysiology, and calcium handling. In vivo electrocardiograms were recorded from neonatal, juvenile, and adult animals. Simultaneous dual optical mapping of transmembrane voltage and calcium transients was performed on isolated, Langendorff-perfused rat hearts (postnatal day 0–3, 4-7, 8-14, adult).ResultsYounger, immature hearts displayed slowed electrical conduction, prolonged action potential duration and increased ventricular refractoriness. Slowed calcium handling in the immature heart increased the propensity for calcium transient alternans which corresponded to alterations in the expression of genes encoding calcium handling proteins. Developmental changes in cardiac electrophysiology were associated with the altered expression of genes encoding potassium channels and intercalated disc proteins.ConclusionUsing an intact whole heart model, this study highlights chronological changes in cardiac electrophysiology and calcium handling throughout postnatal development. Results of this study can serve as a comprehensive baseline for future studies focused on pediatric cardiac research, safety assessment and/or preclinical testing using rodent models.
Gap junctions in theC. elegansnervous system regulate ageing and lifespan
Authors: Vladis Nathalie Alexandra , Fischer Katharina Elisabeth , Digalaki Eva , Marcu Daniel-Cosmin , Bimpos Modestos Nakos , Greer Peta , Ayres Alice , Li Qiaochu , Busch Karl Emanuel 
Published: June 2019

AbstractThe nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits inCaenorhabditis eleganshave extensive and diverse impacts on lifespan. Loss of the neural innexinunc-9increases longevity by a third and also strongly benefits healthspan.Unc-9acts specifically in a glutamatergic circuit linked to mechanosensation. Absence ofunc-9depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal ofunc-9requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.
Microstructural plasticity in the bilingual brain
Authors: Luo Daiyi , Kwok Veronica P.Y. , Li Ping , Liu Qing , Li Wenlong , Yang Yang , Zhou Ke , Xu Min , Gao Jia-Hong , Tan Li Hai 
Published: June 2019

AbstractThe human brain has been uniquely equipped with the remarkable ability to acquire more than one language, as in bilingual individuals. Previous neuroimaging studies have indicated that learning a second language (L2) induced neuroplasticity at the macrostructural level. In this study, using the quantitative MRI (qMRI) combined with functional MRI (fMRI) techniques, we quantified the microstructural properties and tested whether second language learning modulates the microstructure in the bilingual brain. We found significant microstructural variations related to age of acquisition of second language in the left inferior frontal region and the left fusiform gyrus that are crucial for resolving lexical competition of bilinguals’ two languages. Early second language acquisition contributes to enhance cortical development at the microstructural level.Significant statementThe ability to communicate in two languages is becoming more and more important in the increasingly global community. Does learning a second language (L2) affect the human brain development? At the macrostructural level, there has been neuroimaging evidence revealing neuroplasticity induced by the acquisition of L2. Here, we employed the quantitative MRI technique to investigate the microstructural variations related to L2 learning, and found that age of acquisition of L2, but not its proficiency, is associated with cortical proliferation. Early second language acquisition seems to enhance cortical development at the microstructural level.
Tolerance of nonsynonymous variation is closely correlated between human and mouse orthologues
Authors: Powell George , Simon Michelle , Pulit Sara , Mallon Ann-Marie , Lindgren Cecilia M. 
Published: June 2019

ABSTRACTGenic constraint describes how tolerant a gene is of nonsynonymous variation before it is removed from the population by negative selection. Here, we provide the first estimates of intraspecific constraint for mouse genes genome-wide, and show constraint is positively correlated between human and mouse orthologues (r = 0.806). We assess the relationships between mouse gene constraint and knockout phenotypes, showing gene constraint is positively associated with pleiotropy (ie an increased number of phenotype associations (R2= 0.65)), in addition to an enrichment in lethal, developmental, and craniofacial knockout phenotypes amongst the most constrained genes. Finally, we show mouse constraint can be used to predict human genes associated with Mendelian disease, and is positively correlated with an increase in the number of known pathogenic variants in the human orthologue (R2= 0.23). Our metrics of mouse and human constraint are available to inform future research using mouse models.
Expectation pooling: An effective and interpretable pooling method for predicting DNA-protein binding
Authors: Luo Xiao , Tu Xinming , Ding Yang , Gao Ge , Deng Minghua 
Published: June 2019

AbstractMotivationConvolutional neural networks (CNNs) have outperformed conventional methods in modeling the sequence specificity of DNA-protein binding. While previous studies have built a connection between CNNs and probabilistic models, simple models of CNNs cannot achieve sufficient accuracy on this problem. Recently, some methods of neural networks have increased performance using complex neural networks whose results cannot be directly interpreted. However, it is difficult to combine probabilistic models and CNNs effectively to improve DNA-protein binding predictions.ResultsIn this paper, we present a novel global pooling method: expectation pooling for predicting DNA-protein binding. Our pooling method stems naturally from the EM algorithm, and its benefits can be interpreted both statistically and via deep learning theory. Through experiments, we demonstrate that our pooling method improves the prediction performance DNA-protein binding. Our interpretable pooling method combines probabilistic ideas with global pooling by taking the expectations of inputs without increasing the number of parameters. We also analyze the hyperparameters in our method and propose optional structures to help fit different datasets. We explore how to effectively utilize these novel pooling methods and show that combining statistical methods with deep learning is highly beneficial, which is promising and meaningful for future studies in this field.Contactdengmh@pku.edu.cn,gaog@mail.cbi.pku.edu.cnSupplementary informationAll code is public inhttps://github.com/gao-lab/ePooling
Metabolic Alterations in Human Peripheral Blood Mononuclear Cells Associate with Progression to Islet Autoimmunity and Type 1 Diabetes
Authors: Sen Partho , Dickens Alex M. , López-Bascón María Asunción , Lindeman Tuomas , Kemppainen Esko , Lamichhane Santosh , Rönkkö Tuukka , Ilonen Jorma , Toppari Jorma , Veijola Riitta , Hyöty Heikki , Hyötyläinen Tuulia , Knip Mikael , Orešič Matej 
Published: June 2019

ABSTRACTPrevious metabolomics studies suggest that type 1 diabetes (T1D) is preceded by specific metabolic disturbances. Here we asked whether distinct metabolic patterns occur in peripheral blood mononuclear cells (PBMCs) of children later developing pancreaticβ-cell autoimmunity or overt T1D. In a longitudinal cohort setting, PBMC metabolomic analysis was applied in children who either (1) progressed to T1D (PT1D, n=34), (2) seroconverted to ≥1 islet autoantibody without progressing to T1D (P1Ab, n=27), or (3) remained autoantibody negative during follow-up (CTRL, n=10). During the first year of life, levels of most lipids and polar metabolites were lower in PT1D and P1Ab, versus CTRLs. Pathway overrepresentation analysis suggested alanine, aspartate, glutamate, glycerophospholipid and sphingolipid metabolism were overrepresented in PT1D. Genome-scale metabolic models of PBMCs in T1D progression were developed using available transcriptomics data and constrained with metabolomics data from our study. Metabolic modeling confirmed altered ceramide pathways as specifically associated with T1D progression.
Diurnal.plant.tools: comparative transcriptomic and co-expression analyses of diurnal gene expression of the Archaeplastida kingdom
Authors: Xiong Ng Jonathan Wei , Tan Qiao Wen , Ferrari Camilla , Mutwil Marek 
Published: June 2019

ABSTRACTAlmost all organisms coordinate some aspects of their biology through the diurnal cycle. Photosynthetic organisms, and plants especially, have established complex programs that coordinate physiological, metabolic and developmental processes with the changing light. The diurnal regulation of the underlying transcriptional processes is observed when groups of functionally related genes (gene modules) are expressed at a specific time of the day. However, studying the diurnal regulation of these gene modules in the plant kingdom was hampered by the large amount of data required for the analyses. To meet this need, we used gene expression data from 17 diurnal studies spanning the whole Archaeplastida kingdom (Plantae kingdom in the broad sense) to make an online diurnal database. We have equipped the database with tools that allow user-friendly cross-species comparisons of gene expression profiles, entire co-expression networks, co-expressed clusters (involved in specific biological processes), time-specific gene expression, and others. We exemplify how these tools can be used by studying three important biological questions: (i) the evolution of cell division, (ii) the diurnal control of gene modules in algae and (iii) the conservation of diurnally-controlled modules across species. The database is freely available at http://diurnal.plant.tools/.