bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau accumulation activates STAT1 triggering memory deficits via suppressing NMDA receptor expression
Authors: Li Xiao-Guang , Hong Xiao-Yue , Wang Ya-li , Zhang Shu-Juan , Zhang Jun-Fei , Li Xia-Chun , Liu Yan-Chao , Sun Dong-Shen , Feng Qiong , Ye Jin-Wang , Gao Yuan , Ke Dan , Wang Qun , Li Hong-lian , Ye Keqiang , Liu Gong-Ping , Wang Jian-Zhi 
Published: October 2018

ABSTRACTIntracellular tau accumulation forming neurofibrillary tangles is hallmark pathology of Alzheimer's disease (AD), but how tau accumulation induces synapse impairment is elusive. By overexpressing human full-length wildtype tau (termed hTau) to mimic tau abnormality as seen in the brain of sporadic AD patients, we found that hTau accumulation activated JAK2 to phosphorylate STAT1 (Signal Transducer and Activator of Transcription 1) at Tyr701 leading to STAT1 dimerization, nuclear translocation and its activation. STAT1 activation suppressed expression of N-methyl-D-aspartate receptors (NMDARs) through direct binding to the specific GAS element of GluN1, GluN2A and GluN2B promoters, while knockdown STAT1 by AAV-Cre in STAT1flox/floxmice or expressing dominant negative Y701F-STAT1 efficiently rescued hTau-induced suppression of NMDARs expression with amelioration of synaptic functions and memory performance. These findings indicate that hTau accumulation impairs synaptic plasticity through JAK2/STAT1-induced suppression of NMDARs expression, revealing a novel mechanism for hTau-associated synapse and memory deficits.
D-GPM: a deep learning method for gene promoter methylation inference
Authors: Pan Xingxin , Liu Biao , Wen Xingzhao , Liu Yulu , Zhang Xiuqing , Li Shengbin , Li Shuaicheng 
Published: October 2018

AbstractBackgroundGene promoter methylation plays a critical role in a wide range of biological processes, such as transcriptional expression, gene imprinting, X chromosome inactivation,etc. Whole-genome bisulfite sequencing generates a comprehensive profiling of the gene methylation levels but is limited by a high cost. Recent studies have partitioned the genes into landmark genes and target genes and suggested that the landmark gene expression levels capture adequate information to reconstruct the target gene expression levels. Moreover, the methylation level of the promoter is usually negatively correlated with its corresponding gene expression. This result inspired us to propose that the methylation level of the promoters might be adequate to reconstruct the promoter methylation level of target genes, which would eventually reduce the cost of promoter methylation profiling.ResultsHere, we developed a deep learning model (D-GPM) to predict the whole-genome promoter methylation level based on the methylation profile of the landmark genes. We benchmarked D-GPM against three machine learning methods, namely, linear regression (LR), regression tree (RT) and support vector machine (SVM), based on two criteria: the mean absolute deviation (MAE) and the Pearson correlation coefficient (PCC). After profiling the methylation beta value (MBV) dataset from the TCGA, with respect to MAE and PCC, we found that D-GPM outperforms LR by 9.59% and 4.34%, RT by 27.58% and 22.96% and SVM by 6.14% and 3.07% on average, respectively. For the number of better-predicted genes, D-GPM outperforms LR in 92.65% and 91.00%, RT in 95.66% and 98.25% and SVM in 85.49% and 81.56% of the target genes.ConclusionsD-GPM acquires the least overall MAE and the highest overall PCC on MBV-te compared to LR, RT, and SVM. For a genewise comparative analysis, D-GPM outperforms LR, RT, and SVM in an overwhelming majority of the target genes, with respect to the MAE and PCC. Most importantly, D-GPM predominates among the other models in predicting a majority of the target genes according to the model distribution of the least MAE and the highest PCC for the target genes.
Stereotyped Terminal Axon Branching of Leg Motor Neurons Mediated by IgSF Proteins DIP-α and Dpr10
Authors: Venkatasubramanian Lalanti , Guo Zhenhao , Xu Shuwa , Tan Liming , Xiao Qi , Nagarkar-Jaiswal Sonal , Mann Richard S. 
Published: October 2018

ABSTRACTThe ability of animals to perform coordinated movements depends on the precise organization of neural circuits controlling motor function. Motor neurons (MNs), which are key components of these circuits, must project their axons out of the central nervous system and form precise terminal branching patterns at specific muscles in the periphery. By focusing on theDrosophilaadult leg neuromuscular system we show that the stereotyped terminal branching of a subset of leg MNs is mediated by interacting transmembrane Ig superfamily (IgSF) proteins DIP-α and Dpr10, present in MNs and target muscles, respectively. Importantly, the DIP-α/Dpr10 interaction is needed only after MN axons reach the vicinity of their muscle targets. Live imaging of this process suggests that precise terminal branching patterns are gradually established by DIP-α/Dpr10-dependent interactions between fine axon filopodia and developing muscles. Further, different leg MNs depend on the DIP-α and Dpr10 interaction to varying degrees that correlate with the morphological complexity of the MNs and their muscle targets, suggesting that some MNs depend upon multiple sets of interacting proteins to establish terminal axon branching.
Aggression and discrimination among closely versus distantly related species of Drosophila
Authors: Gupta Tarun , Howe Sarah E. , Zorman Marlo L. , Lockwood Brent L. 
Published: October 2018

AbstractFighting between different species is widespread in the animal kingdom, yet this phenomenon has been relatively understudied in the field of aggression research. Particularly lacking are studies that test the effect of genetic distance, or relatedness, on aggressive behavior between species. Here we characterized male-male aggression within and between species of fruit flies across the Drosophila phylogeny. We show that male Drosophila discriminate between conspecifics and heterospecifics and show a bias for the target of aggression that depends on the genetic relatedness of opponent males. Specifically, males of closely related species treated conspecifics and heterospecifics equally, whereas males of distantly related species were overwhelmingly aggressive toward conspecifics. To our knowledge, this is the first study to quantify aggression between Drosophila species and to establish a behavioral bias for aggression against conspecifics versus heterospecifics. Our results suggest that future study of heterospecific aggression behavior in Drosophila is warranted to investigate the degree to which these trends in aggression among species extend to broader behavioral, ecological, and evolutionary contexts.
In vitro membrane remodelling by ESCRT-II/ESCRT-III is regulated by negative feedback from membrane tension
Authors: Booth Andrew , Marklew Christopher J. , Ciani Barbara , Beales Paul A. 
Published: October 2018

AbstractArtificial cells can shed new light on the molecular basis for life and hold potential for new chemical technologies. Inspired by how nature dynamically regulates its membrane compartments, we aim to repurpose the endosomal sorting complex required for transport (ESCRT) to generate complex membrane architectures as suitable scaffolds for artificial cells. Purified ESCRT-III components perform topological transformations on giant unilamellar vesicles (GUVs) to create complex “vesicles-within-a-vesicle” architectures resembling the compartmentalisation in eukaryotic cells. Thus far, the proposed mechanisms for this activity are based on how assembly and disassembly of ESCRT-III on the membrane drives deformation. Here we demonstrate the existence of a negative feedback mechanism from membrane mechanics that regulates ESCRT-III activity. ILV formation removes excess membrane area, increasing tension, which in turn suppresses downstream ILV formation. This mechanism for in vitro regulation of ESCRT-III activity may also have important implications for its in vivo functions.
The ataxin-1 interactome reveals direct connection with multiple disrupted nuclear transport pathways
Authors: Zhang Sunyuan , Williamson Nicholas A. , Jans David A. , Bogoyevitch Marie A. 
Published: October 2018

SummaryThe expanded polyglutamine (polyQ) tract form of ataxin-1 drives disease progression in spinocerebellar ataxia type 1 (SCA1). Although polyQ-ataxin-1 is known to form distinctive intranuclear bodies, the cellular pathways and functions it influences remain poorly understood. Here, we identify direct and proximal partners constituting the interactome of ataxin-1[85Q] in Neuro-2a cells. Pathways analyses indicate a significant enrichment of essential nuclear transporters in the interactome, pointing to disruptions in nuclear transport processes in the presence of polyQ-ataxin-1. Our direct assessments of nuclear transporters and their cargoes reinforce these observations, revealing disrupted trafficking often with relocalisation of transporters and/or cargoes to ataxin-1[85Q] nuclear bodies. Strikingly, the nucleoporin Nup98, dependent on its GLFG repeats, is recruited into polyQ-ataxin-1 nuclear bodies. Our results highlight a disruption of multiple essential nuclear protein trafficking pathways by polyQataxin-1, a key contribution to furthering understanding of pathogenic mechanisms initiated by polyQ tract proteins.
Quantitative Analysis of a Transient Dynamics of a Gene Regulatory Network
Authors: Lee JaeJun , Lee Julian 
Published: October 2018

AbstractIn a stochastic process, noise often modifies the picture offered by the mean field dynamics. In particular, when there is an absorbing state, the noise erases a stable fixed point of the mean field equation from the stationary distribution, and turns it into a transient peak. We make a quantitative analysis of this effect for a simple genetic regulatory network with positive feedback, where the proteins become extinct in the presence of stochastic noise, contrary to the prediction of the deterministic rate equation that the protein number converges to a non-zero value. We show that the transient peak appears near the stable fixed point of the rate equation, and the extinction time diverges exponentially as the stochastic noise approaches zero. We also show how the baseline production from the inactive gene ameliorates the effect of the stochastic noise, and interpret the opposite effects of the noise and the baseline production in terms of the position shift of the unstable fixed point. The order of magnitude estimates using biological parameters suggest that for a real gene regulatory network, the stochastic noise is sufficiently small so that not only is the extinction time much larger than biologically relevant time-scales, but also the effect of the baseline production dominates over that of the stochastic noise, leading to the protection from the catastrophic rare event of protein extinction.
Kinetochore protein depletion underlies cytokinesis failure and somatic polyploidization in the mossPhyscomitrella patens
Authors: Kozgunova Elena , Nishina Momoko , Goshima Gohta 
Published: October 2018

AbstractLagging chromosome is a hallmark of aneuploidy arising from errors in the kinetochore–spindle attachment in animal cells. However, kinetochore components and cellular phenotypes associated with kinetochore dysfunction are much less explored in plants. Here, we carried out a comprehensive characterization of conserved kinetochore components in the mossPhyscomitrella patensand uncovered a distinct scenario in plant cells regarding both the localization and cellular impact of the kinetochore proteins. Most surprisingly, knock-down of several kinetochore proteins led to polyploidy, not aneuploidy, through cytokinesis failure in >90% of the cells that exhibited lagging chromosomes for several minutes or longer. The resultant cells, containing two or more nuclei, proceeded to the next cell cycle and eventually developed into polyploid plants. As lagging chromosomes have been observed in various plant species in the wild, our observation raised a possibility that they could be one of the natural pathways to polyploidy in plants.
Light-evoked activity and BDNF regulate mitochondrial dynamics and mitochondrial localized translation
Authors: Kreymerman Alex , Weinstein Jessica E. , Shah Sahil H. , Buickians David N. , Faust Anne , Van Der Merwe Yolandi , Nahmou Michael M. , Cho In-Jae , Huynh Star K. , Verma Sonya , Xin Xiao-Lu , Steketee Michael B. , Goldberg Jeffrey L. 
Published: October 2018

AbstractMitochondria coordinate diverse functions within neurites, including signaling events for axonal maintenance, and degeneration. However, less is known about the role of mitochondria in axon development and maturation. Here we find that in maturing retinal ganglion cells (RGCs) in vivo, axonal mitochondria increase in size, number, and total area throughout development. We demonstrate through multiple approaches in vivo that the mechanism underlying these mitochondrial changes are dependent on eye opening and associated neuronal activity, which can be mimicked by brain derived neurotrophic factor (BDNF). We report downstream gene and protein expression changes consistent with mitochondrial biogenesis and energetics pathways, and present evidence that the associated transcripts are localized and translated at mitochondria within axons in an activity-dependent manner. Together these data support a novel model for mitochondrial-localized translation in support of intra-axonal mitochondrial dynamics and axonal maturation.
Patient-derivedphosphoribosyl pyrophosphate synthetasemutations inDrosophilaresult in autophagy and lysosome dysfunction
Authors: Santos Keemo Delos , Yergeau Christine , Moon Nam-Sung 
Published: October 2018

AbstractPhosphoribosyl pyrophosphate synthetase (PRPS) is a rate-limiting enzyme in nucleotide metabolism. While missense mutations ofPRPS1have been identified in neurological disorders such as Arts syndrome, little is known on how they contribute to pathogenesis. We engineeredDrosophila PRPS(dPRPS) alleles that carry patient-derived PRPS missense mutations. AlthoughdPRPSmutant flies develop normally, they have profound defects in autophagy induction and lysosome function. Consequently,dPRPSflies are sensitive to nutrient deprivation as they are unable to break down lipid storage by macroautophagy. In addition, we provide evidence showing thatdRPPSis required for proper cellular response to oxidative stress, providing a possible mechanism by which PRPS1 dysfunction contributes to neurological disorders.
The Novel Mnk1/2 Degrader VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis
Authors: Ramalingam Senthilmurugan , Ramamurthy Vidya P. , Gediya Lalji K. , Murigi Francis N. , Purushottamachar Puranik , Huang Weiliang , Choi Eun Yong , Zhang Yuji , Vasaitis Tadas S. , Kane Maureen A. , Lapidus Rena G. , Njar Vincent C. O. 
Published: October 2018

ABSTRACTCurrently, there are no effective therapies for patients with triple-negative breast cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development, progression and metastasis of TNBC. Herein, we undertook a comprehensive study to evaluate the activity of a first-in-class Mnk1/2 protein degraders, in clinically relevant models of TNBC. These studies enabled us to identify racemic VNLG-152R as the most efficacious Mnk1/2 degrader. By targeting Mnk1/2 protein degradation (activity), VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulated downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion, epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited remarkable antitumor and antimetastatic activities against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel therapeutic strategy that can be developed as monotherapy for effective treatment of patients with primary/metastatic TNBC.
To Overwrite or to Recall? Individual Differences in Motor Adaptation
Authors: Oh Youngmin , Schweighofer Nicolas 
Published: October 2018

AbstractThe central nervous system predicts the consequences of motor commands by leaning multiple internal models of external perturbations and of the body. It is not well understood, however, how new internal models are created. Here, we propose a novel computational model of motor adaptation in which a stochastic Bayesian decision-making process determines whether i) a previously updated expert perturbation model is recalled and updated, ii) a novice model is selected and is updated into a new expert, or iii) the “body” model is updated. Results from computer simulations provide insights into various and contradictory experimental data on savings and error-clamp, and predicts qualitative individual differences in adaptation. We verified these predictions in a visuomotor adaptation experiment in which we varied the perturbation amplitudes as well as the amount of noise added to perturbation, and added “trigger” trials in the error-clamp condition. Single trigger trials led to largely qualitatively different behavior and can therefore be used to probe individual differences in memory updates between “one-model” and “two-model” learners. “One-model” learners continuously update the body model, showing no savings during re-adaptation to the perturbation, and gradual decay during error clamp. In contrast, “two-model” learners switch between an updated expert model and the body model, showing large savings during re-adaptation and stochastic lags during error clamp. Our results thus support the view that motor adaptation belongs to the general class of human learning according to which new memories are created when no existing memories can account for discontinuities in sensory data.Short summary/significanceWhen movements are followed by unexpected outcomes, such as following the introduction of a visuomotor or force field perturbation, or the sudden removal of such perturbations, it is unclear whether the central nervous system updates existing memories or creates new memories. Here, we propose a novel model of adaptation, and investigate, via simulation and behavioral experiments, how the amplitude and schedule of the perturbation, as well as the characteristics of the learner, lead to updates of existing memories or creation of new memories. Our results provide insights into a number of puzzling and contradictory experimental data on savings and error-clamp, as well as large qualitative individual differences in adaptation.
Nutritional traffic light and self-regulatory consumption: the role of emotions
Authors: Sánchez-García Isabel , Rodríguez-Insuasti Homero , Martí-Parreño José , Sánchez-Mena Antonio 
Published: October 2018

Purpose
The purpose of this paper is to analyse how the nutritional traffic light can reduce consumers’ intention to purchase unhealthy food by eliciting negative emotions (i.e. fear and guilt). The work also examines the moderating role of income in the above-mentioned relationships.

Design/methodology/approach
The empirical study was conducted in Ecuador. In an initial phase, exploratory research was carried out with two focus groups. Then a quasi-experiment was conducted with 330 participants following a 3×2 design, in which the nutritional traffic light for a dairy product (green, yellow, red) and the variable income (high and low income) were manipulated.

Findings
Traffic light colours (red, yellow and green) significantly influence consumers’ levels of fear and guilt as well as their intention to purchase. Income has also been found to have a moderating effect on the above relationships.

Practical implications
Further understanding of how nutritional labels influence consumer behaviour may have beneficial effects for public authorities attempting to improve citizens’ health and for society as a whole. It may also help firms that produce and market packaged foods to be aware of what type of foods new consumers want and adapt their offering in consequence.

Originality/value
The main contribution of this work is the analysis of the influence of the nutritional traffic light on emotions, namely, fear and guilt and how these emotions lead consumers to control their consumption of unhealthy foods. In addition, the present work proposes the moderating effect of income on the influence of colour on emotions and purchase intention.
Performance landscape modeling in digital manufacturing firm
Authors: Kulkarni Sourabh , Verma Priyanka , Mukundan R. 
Published: October 2018

PurposeThe purpose of this paper is to update existing Kauffmann’s NK model to evaluate the manufacturing fitness of strategic business capabilities. The updated model is tested in a digital manufacturing (DM) setting to investigate the sequence for developing cumulative capabilities that can yield the maximum payoff.Design/methodology/approachThe authors develop a grey–DEMATEL–NK fitness model and show its application, through a case study, to a DM firm in India.FindingsThe grey–DEMATEL–NK model helps evaluate multiple manufacturing capabilities and indicates that quality–flexibility–cost–delivery is the sequence that yields the maximum manufacturing fitness (competitive payoff) for a DM firm. This sequence helps the firm reorganise its internal business processes and is different from that used to develop cumulative capabilities in a traditional manufacturing setting (quality–delivery–flexibility–cost).Originality/valueThis study presents a pilot model for computing the cumulative capabilities payoff and prescribes a sequence for developing cumulative capabilities within a DM context.
Developing Māori collections
Authors: Lilley Spencer 
Published: October 2018

PurposeThis paper aims to provide an introduction to Māori, the indigenous people of New Zealand, briefly describing their origin, population structure, language and knowledge structures. There is also a description of the process by which Māori knowledge systems were transformed into a written structure from predominantly oral and visual forms. In the latter part of the paper, there is a discussion about how the growing demand by Māori clients changed the delivery of resources and services in New Zealand libraries and led to the development of Māori collections in libraries.

Design/methodology/approachUsing a case study approach this paper outlines the impact that literacy and publishing had on Māori traditional knowledge transfer methods. The implication of these developments and their importance to libraries is considered as part of the Treaty of Waitangi reconciliation process and the growing consciousness of the need to be fulfilling the information needs of Māori clients.

FindingsThe development of Māori collection has been successful and plays a critical role in meeting the cultural, linguistic, research and recreational information needs of Māori clients.

Research limitations/implicationsThis case study provides a model for the development of indigenous collections in other countries.

Originality/valueThis paper makes a contribution to an area that has not had a significant amount of literature published on it.