bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point-of-Use Detection of Environmental Fluoride via a Cell-Free Riboswitch-Based Biosensor
Authors: Thavarajah Walter , Silverman Adam D. , Verosloff Matthew S. , Kelley-Loughnane Nancy , Jewett Michael C. , Lucks Julius B. 
Published: July 2019

AbstractAdvances in biosensor engineering have enabled the design of programmable molecular systems to detect a range of pathogens, nucleic acids, and chemicals. Here, we engineer and field-test a biosensor for fluoride, a major groundwater contaminant of global concern. The sensor consists of a cell-free system containing a DNA template that encodes a fluoride-responsive riboswitch regulating genes that produce a fluorescent or colorimetric output. Individual reactions can be lyophilized for long-term storage and detect fluoride at levels above 2 parts per million, the EPA’s most stringent regulatory standard, in both laboratory and field conditions. Through onsite detection of fluoride in a real-world water source, this work provides a critical proof-of-principle for the future engineering of riboswitches and other biosensors to address challenges for global health and the environment.
Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis
Authors: Robinson Andrew P. , Zhang Joanne Zhongyan , Titus Haley E. , Karl Molly , Merzliakov Mikhail , Dorfman Adam R. , Karlik Stephen , Stewart Michael G. , Watt Richard K. , Facer Benjin D. , Facer Jon D. , Christian Noah D. , Ho Karen S. , Hotchkin Michael T. , Mortenson Mark G. , Miller Robert H. , Miller Stephen D. 
Published: July 2019

AbstractDevelopment of pharmacotherapies that promote remyelination are a high priority for multiple sclerosis (MS) due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of key myelin differentiation markers. Additional in vitro data demonstrated that these gold nanocrystals act via a novel energy metabolism pathway involving the enhancement of key indicators of aerobic glycolysis. In response to gold nanocrystals, co-cultured central nervous system cells exhibited elevated levels of the redox coenzyme nicotine adenine dinucleotide (NAD+), elevated total ATP levels, elevated extracellular lactate levels, and upregulation of myelin-synthesis related genes, collectively resulting in functional myelin generation. Based on these preclinical studies, clean-surfaced, faceted gold nanocrystals represent a novel remyelinating therapeutic for multiple sclerosis.One Sentence SummaryNanocatalytic activity of clean-surfaced, faceted gold nanocrystals results in robust remyelinating activity in demyelination animal models of multiple sclerosis.
Ribosomal stalk proteins RPLP1 and RPLP2 promote biogenesis of flaviviral and cellular multi-pass transmembrane proteins
Authors: Campos Rafael K. , Wijeratne Sagara , Shah Premal , Garcia-Blanco Mariano A. , Bradrick Shelton S. 
Published: July 2019

ABSTRACTDengue virus (DENV) and other mosquito-borne flaviviruses are highly dependent on the ribosomal stalk proteins, RPLP1 and RPLP2 (RPLP1/2), for efficient infection. Here, we show that RPLP1/2 function to relieve ribosome pausing within the DENV envelope coding sequence, leading to enhanced protein stability. We used ribosome profiling to evaluate viral and cellular translation in RPLP1/2-depleted cells. This revealed that ribosomes pause in the sequence coding for the N-terminus of the envelope protein, immediately downstream of sequences encoding two adjacent transmembrane domains (TMDs). RPLP1/2 function to enhance ribosome elongation at this position and increase viral protein stability, possibly by improving co-translational folding of DENV proteins. We also analyzed the effects of RPLP1/2 depletion on cellular translation. We find that RPLP1/2 affects ribosome density for a small subset of cellular mRNAs. However, meta-analysis of ribosome positions on all cellular mRNAs revealed slightly increased accumulation of ribosomes downstream of start codons in RPLP1/2-depleted cells, suggesting that RPLP1/2 enhance elongation efficiency. Importantly, we found that ribosome density on mRNAs encoding multiple TMDs was disproportionately affected by RPLP1/2 knockdown, implying a role for RPLP1/2 in transmembrane protein biogenesis. Together, our findings reveal insights into the function of RPLP1/2 in DENV and cellular translation.
Rab11is essential forlglmediated JNK–Dpp signaling in dorsal closure and epithelial morphogenesis inDrosophila
Authors: Nandy Nabarun , Roy Jagat Kumar 
Published: July 2019

AbstractDorsal closure inDrosophilaprovides a robust genetic platform providing deep insights into the basic cellular mechanisms that govern epithelial wound healing and morphogenesis. As dorsal closure proceeds, the adjacent epithelia advance contra-laterally involving coordinated cell shape changes in order to successfully accomplish the process. The JNK-Dpp signaling in these cells plays an instrumental role in guiding their fate as gastrulation completes. A huge number of genes have been reported to be involved in the regulation of this core signaling pathway, yet the mechanisms by which they do so is hitherto unclear, which forms the objective of our present study. Here we show thatlgl, which is a potent tumour suppressor gene, conserved across the phyla till humans, regulates the JNK–Dpp pathway in the dorsal closure and epithelial morphogenesis process where in ectopic knockdown of this gene results in the failure of dorsal closure. Interestingly, we also findRab11to be interacting withlglas they together regulate the core JNK-Dpp signaling pathway during dorsal closure and also during pupal thorax closure process. Using the robustGal4-UASsystem of targeted gene expression, we show here thatRab11andlglsynergize to successfully execute the dorsal closure and the similar thorax closure process, ensuring proper spatio-temporal JNK-Dpp signaling.
Fast and robust ancestry prediction using principal component analysis
Authors: Zhang Daiwei , Dey Rounak , Lee Seunggeun 
Published: July 2019

AbstractPopulation stratification (PS) is a major confounder in genome-wide association studies (GWAS) and can lead to false positive associations. To adjust for PS, principal component analysis (PCA)-based ancestry prediction has been widely used. Simple projection (SP) based on principal component loading and recently developed data augmentation-decomposition-transformation (ADP), such as LASER and TRACE, are popular methods for predicting PC scores. However, they are either biased or computationally expensive. The predicted PC scores from SP can be biased toward NULL. On the other hand, since ADP requires running PCA separately for each study sample on the augmented data set, its computational cost is high. To address these problems, we develop and propose two alternative approaches, bias-adjusted projection (AP) and online ADP (OADP). Using random matrix theory, AP asymptotically estimates and adjusts for the bias of SP. OADP uses computationally efficient online singular value decomposition, which can greatly reduce the computation cost of ADP. We carried out extensive simulation studies to show that these alternative approaches are unbiased and the computation times can be 10-100 times faster than ADP. We applied our approaches to UK-Biobank data of 488,366 study samples with 2,492 samples from the 1000 Genomes data as the reference. AP and OADP required 7 and 75 CPU hours, respectively, while the projected computation time of ADP is 2,534 CPU hours. Furthermore, when we only used the European reference samples in the 1000 Genomes to infer sub-European ancestry, SP clearly showed bias, unlike the proposed approaches. By using AP and OADP, we can infer ancestry and adjust for PS robustly and efficiently.
Disruption of aRAC1-centred protein interaction network is associated with Alzheimer’s disease pathology and causes age-dependent neurodegeneration
Authors: Kikuchi Masataka , Sekiya Michiko , Hara Norikazu , Miyashita Akinori , Kuwano Ryozo , Ikeuchi Takeshi , Iijima Koichi M. , Nakaya Akihiro 
Published: July 2019

AbstractThe molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated cross-talk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, includingRac1, as key players in PDN collapse. Using publicly available gene expression data, we confirmed that the mRNA expression level of theRAC1gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilizedDrosophilaas a genetic model and found that modest knockdown ofRac1in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator ofRAC1in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were upregulated specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y causedRAC1downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.
Evolutionary changes of phosphoenolpyruvate transporter (PPT) during the emergence of C4 photosynthesis
Authors: Lyu Ming-Ju Amy , Wang Yaling , Jiang Jianjun , Chen Genyun , Zhu Xin-Guang 
Published: July 2019

AbstractC4 photosynthesis is a complex trait, which evolved from its ancestral C3 photosynthesis by recruiting pre-existing genes. The evolutionary history of enzymes involved in the C4 shuttle has been extensively studied. Here we analyze the evolutionary changes of phosphoenolpyruvate (PEP) transporter (PPT) during its recruitment from C3 to C4 photosynthesis. Our analysis shows that 1) among the two PPT paralogs, i.e. PPT1 and PPT2, PPT1 is an ancestral copy while PPT2 is a derived copy; 2) during C4 evolution, PPT1 shifted its expression from predominantly in root to in leaf, and from bundle sheath cell to mesophyll cell, supporting that PPT1 was recruited into C4 photosynthesis; 3) PPT1 gained increased transcript abundance, gained more rapid and long-lasting responses to light during C3 to C4 evolution, while PPT2 lost its responsiveness to light; 4) PPT1 gained a number of new cis-elements during C4 evolution; 5) C4 PPT1 can complement the phenotype of Arabidopsis PPT1 loss-of-function mutant, suggesting that it is a bidirectional transporter and its transport direction did not alter during C4 evolution. We finally discuss mechanistic linkages between these observed changes in PPT1 and C4 photosynthesis evolution.High lightDuring the process of C4 photosynthesis evolution, PPT not only experienced changes in its expression location and transcript abundance, but also acquired new cis-elements in its promoter region and accumulated protein variations.
Measuring and Modelling the Emergence of Order in the Mouse Retinocollicular Projection
Authors: Lyngholm Daniel , Sterratt David C. , Hjorth J. J. Johannes , Willshaw David J. , Eglen Stephen J. , Thompson Ian D. 
Published: July 2019

AbstractIn the formation of retinotopic maps both experimental and theoretical work implicate guidance molecules and patterned neuronal activity. A common view is that molecular cues define and activity cues refine mappings. Important insights have come from studies of the retinocollicular projection in transgenic mice, in which cues have been modified either in isolation or in combination. Mostly these have generated descriptions of endpoint mappings. The dynamics of map formation remain under-explored experimentally and computationally. We have quantified changes in the ordering of the mouse retinocollicular projection with age after making local collicular injections of fluorescent microspheres. Contour analysis shows that, at birth (P0), cells from over 80% of the retina converge on a given collicular locus; this percentage falls gradually to P4 then rapidly approaches adult values by P12. Paired injections reveal how the segregation of labelled cells depends both on injection site separation and relative orientation and also age. At P0, large anterior-posterior separations failed to produce segregated label: segregation improved with a similar timecourse to convergence to reach near adult-values by P12. An implementation of a combined activity-molecular model captures these segregation dynamics.The developmental dynamics were then studied in the nAChR-β2−/− mouse, which has altered patterns of retinal activity in the first postnatal week that results in a more diffuse adult retinal projection. Surprisingly, both measures of map refinement (convergence and segregation) remain largely constant and imprecise in the first postnatal week – only subsequently does the projection begin to refine. Substituting nAChR-β2−/− activity patterns for wild-type patterns [5] into the model failed to capture the biology: refinement was initially faster. By reducing the relative importance of the gradients’ contribution to the model energy (to 15% of normal) we were able to mimic the delayed refinement observed in vivo. Our model therefore predicts the altered activity patterns may affect readout of guidance cues.
Emergence of the subapical domain is associated with the midblastula transition
Authors: Schmidt Anja , Großhans Jörg 
Published: July 2019

AbstractEpithelial domains and cell polarity are determined by polarity proteins which are associated with the cell cortex in a spatially restricted pattern. Early Drosophila embryos are characterized by a stereotypic dynamic and de novo formation of cortical domains. For example, the subapical domain emerges at the transition from syncytial to cellular development during the first few minutes of interphase 14. The dynamics in cortical patterning is revealed by the subapical markers Canoe/Afadin and ELMO-Sponge, which widely distributed in interphase 13 but subapically restricted in interphase 14. The factors and mechanism determining the timing for the emergence of the subapical domain have been unknown. In this study, we show, that the restricted localization of subapical markers depends on the onset of zygotic gene expression. In contrast to cell cycle remodeling, the emergence of the subapical domain does not depend on the nucleo-cytoplasmic ratio. Thus, we define cortical dynamics and specifically the emergence of the subapical domain as a feature of the midblastula transition.Author summaryMidblastula transition is a paradigm of a developmental transition. Multiple processes such as cell cycle, cell mobility, onset of zygotic gene expression, degradation of maternal RNA and chromatin structure are coordinated to lead to defined changes in visible morphology. The midblastula transition inDrosophilaembryos is associated with a change from fast nuclear cycles to a cell cycle mode with gap phase and slow replication, a strong increase in zygotic transcription and cellularization. The timing of the processes associated with the midblastula transition are controlled by the onset of zygotic gene expression or the nucleocytoplasmic ratio. Here we define the patterning of cortical domains, i. e. the emergence of a subapical domain as a novel feature of the midblastula transition whose appearance is controlled by the onset of zygotic transcription but not the nucleocytoplasmic ratio. Our findings will help to gain further understanding of the coordination of complex developmental processes during the midblastula transition.
Modern human changes in regulatory regions implicated in cortical development
Authors: Moriano Juan , Boeckx Cedric 
Published: July 2019

AbstractRecent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes that appeared after the split from the Neanderthal/Denisovan lineage. These regulatory regions exert their functions at early stages of cortical development and control a set of genes among which those related to chromatin regulation stand out. This functional category has not yet figured prominently in modern human evolution studies. Specifically, we find an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT-signaling for the generation and proliferation of intermediate progenitor cells.
Green patents: a way to guide the eco-innovation success process?
Authors: Scarpellini Sabina , Portillo-Tarragona Pilar , Marin-Vinuesa Luz Maria 
Published: July 2019

PurposeThe purpose of this paper is to explore the determinants of successful eco-innovation processes, using R&D intensity and green patents as metrics for eco-innovation measurement and analysis.Design/methodology/approachThe paper reports the results of a quantitative study based on a sample of 2,218 firms with proactive profiles in eco-innovation, 249 of which have green patents registered in Spain or in the European Union.FindingsThe results suggest positive relationships between the activity of eco-innovation of firms with both the innovation activity in firms and the R&D intensity. The findings also confirm the influence of implementing innovation in the financial performance of business.Research limitations/implicationsThe results will be useful for future studies on the subject and for practitioners making decisions on investments in collaborative R&D and its protection through industrial property in the form of green patents. The main determinants of eco-innovation analysed in this paper can be directly translated into practices because they provide information on how to strengthen these determinants in environmental R&D investments and the registration of green patents.Practical implicationsThe results will be useful for future studies on the subject and for practitioners making decisions on investments in collaborative R&D and its protection through industrial property in the form of green patents. The main determinants of eco-innovation analysed in this paper can be directly translated into practices because they provide information on how to strengthen these determinants in environmental R&D investments and the registration of green patents.Originality/valueDespite the popularity and potential impact of the eco-innovation on economy or society, it has fallen short in terms of its potential to improve financial performance in firms. This paper argues that the level of eco-innovation activity explains some variability in financial performance. In fact, those firms that have greater levels of innovation increase their performance.
Dispositional and situational factors at work
Authors: Pujol-Cols Lucas , Dabos Guillermo E. 
Published: July 2019

PurposeThe purpose of this paper is to examine the psychometric properties of the Spanish version of the Core Self-Evaluations Scale (CSES) and the Brief Index of Affective Job Satisfaction (BIAJS) in terms of internal consistency and factor structure and to, subsequently, analyze the influence of a set of dispositional factors (namely, core self-evaluations, CSEs) and situational factors (namely, psychosocial factors) on job satisfaction.Design/methodology/approachIn total, 209 academics from an Argentinian university completed online surveys at two stages, separated in time, to reduce the common method bias.FindingsThe Spanish version of the CSES and the BIAJS showed acceptable psychometric properties, which were similar to those previously reported in North-American, European and Asian settings. Hierarchical regression analyses revealed that both situational and dispositional factors are significant predictors of job satisfaction.Research limitations/implicationsThe CSES and the BIAJS seem to be valid and reliable instruments for assessing CSEs and job satisfaction, respectively, in Latin America. The adoption of an interactionist approach that includes both situational and dispositional factors is crucial in future research examining job satisfaction.Practical implicationsManagers should carefully evaluate the personality traits of candidates during personnel selection, as well as the working conditions they offer to their employees, since both factors seem to affect job satisfaction.Originality/valueThis paper contributes to the validation of two scales that may promote future organizational behavior/psychology research in Latin America. In addition, it provides empirical evidence on the relative influence of a set of situational and dispositional factors on job satisfaction, thus contributing to the resolution of the person-situation debate.
Understanding consumer’s motivations and behaviour in alternative food networks
Authors: Mastronardi Luigi , Romagnoli Luca , Mazzocchi Giampiero , Giaccio Vincenzo , Marino Davide 
Published: July 2019

Purpose
The purpose of this paper is to investigate the relationships in alternative food networks (AFNs) between the purchase of food, the motivations of consumers and their socio-demographic profiles.

Design/methodology/approach
The study includes a total sample of 1,200 individual questionnaires, administered to the customers of 34 AFNs in different urban areas. The methodology employed is multilevel regression analysis, which is useful for dealing with data with a nested structure.

Findings
The results allowed us to depict some findings: the most important motivations in purchasing decisions are the perceived quality as well as comfort with the location of the markets, shopping experience, variety of offered products and delivery methods. Other interesting results relate to the presence of children in the families and the role of women in the choice of quality food.

Practical implications
The observations could represent a basis for thinking about how to improve consumers’ behaviour and, at the same time, try to remove the obstacles to a greater recognition of the importance of AFNs by consumers.

Originality/value
The paper contributes to the debate on food policies. Indeed, the integration of the results into food policies could help to intercept the consumers’ trends and promote a transition of the food system towards a path of sustainability, in which the AFNs are the organisational expression of a change that concerns a wide geography and a large number of social and economic actors.