bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapamycin rejuvenates oral health in aging mice
Authors: An Jonathan Y. , Kerns Kristopher A. , Ouellette Andrew , Robinson Laura , Morris Doug , Kaczorowski Catherine , Park So-Il , Mekvanich Title , Kang Alex , McLean Jeffrey S. , Cox Timothy C. , Kaeberlein Matt
Published: December 2019

Periodontal disease is an age-associated disorder clinically defined by periodontal bone loss, inflammation of the specialized tissues that surround and support the tooth, and microbiome dysbiosis. Currently, there is no therapy for reversing periodontal disease, and treatment is generally restricted to preventive measures or tooth extraction. The FDA-approved drug rapamycin slows aging and extends lifespan in multiple organisms, including mice. Here we demonstrate that short-term treatment with rapamycin rejuvenates the aged oral cavity of elderly mice, including regeneration of periodontal bone, attenuation of gingival and periodontal bone inflammation, and revertive shift of the oral microbiome toward a more youthful composition. This provides a geroscience strategy to potentially rejuvenate oral health and reverse periodontal disease in the elderly.

Single Sentence Summary

Short-term treatment with rapamycin reverses periodontal bone loss, attenuates inflammation, and remodels the oral microbiome toward a more youthful state.
Presynaptic dysfunction inCASK-related neurodevelopmental disorders
Authors: Becker Martin , Mastropasqua Francesca , Reising Jan Philipp , Maier Simon , Ho Mai-Lan , Rabkina Ielyzaveta , Li Danyang , Neufeld Janina , Ballenberger Lea , Myers Lynnea , Moritz Viveka , Kele Malin , Wincent Josephine , Willfors Charlotte , Sitnikov Rouslan , Herlenius Eric , Anderlid Britt-Marie , Falk Anna , Bölte Sven , Tammimies Kristiina
Published: December 2019

CASK-related disorders are a genetically defined group of neurodevelopmental syndromes. There is limited information about the effects ofCASKmutations in human neurons. Therefore, we sought to delineateCASKmutation consequences and neuronal level effects using induced pluripotent stem cell-derived neurons from two mutation carriers; one male diagnosed with ASD and a female with MICPCH. We show a reduction of the CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of gene sets involved in presynaptic development and CASK protein interactors. Furthermore,CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory (E/I) balance in developing neural circuitries. Usingin vivomagnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validatein vitrocellular data in brain. Our data shows that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments forCASK-related disorders.

Highlights

Modelling of CASK-related disorders using iPSC-derived human neuronal cells

CASKmutations cause dysregulation of its protein interactor partners

Reduced CASK levels primarily affect inhibitory presynapse development

In vitroGABAergic phenotype predictsin vivoneurotransmitter levels
Genome variation and population structure among 1,142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii
Authors:   The Anopheles gambiae 1000 Genomes Consortium, Clarkson Chris S , Miles Alistair , Harding Nicholas J , Lucas Eric R , Battey C J , Amaya-Romero Jorge Edouardo , Cano Jorge , Diabate Abdoulaye , Constant Edi , Nwakanma Davis C , Jawara Musa , Essandoh John , Dinis Joao , Le Goff Gilbert , Robert Vincent , Troco Arlete D , Costantini Carlo , Rohatgi Kyanne R , Elissa Nohal , Coulibaly Boubacar , Midega Janet , Mbogo Charles , Mawejje Henry D , Stalker Jim , Rockett Kirk A , Drury Eleanor , Mead Daniel , Jeffreys Anna E , Hubbart Christina , Rowlands Kate , Isaacs Alison T , Jyothi Dushyanth , Malangone Cinzia , Kamali Maryam , Henrichs Christa , Simpson Victoria , Ayala Diego , Besansky Nora J , Burt Austin , Caputo Beniamino , della Torre Alessandra , Fontaine Michael , Godfray H. Charles J , Hahn Matthew W , Kern Andrew D , Lawniczak Mara K N , O’Loughlin Samantha , Pinto Joao , Riehle Michelle M , Sharakhov Igor , Schrider Daniel R , Vernick Kenneth D , White Bradley J , Donnelly Martin J , Kwiatkowski Dominic P
Published: December 2019

Mosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analysed whole genomes of 1,142 individual mosquitoes sampled from the wild in 13 African countries, and a further 234 individuals comprising parents and progeny of 11 lab crosses. The data resource includes high confidence single nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We used these data to analyse genetic population structure, and characterise genetic diversity within and between populations. We also illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance, and for accelerating research and development of new vector control tools.
Genome compartmentalization predates species divergence in the plant pathogen genus Zymoseptoria
Authors: Feurtey Alice , Lorrain Cécile , Croll Daniel , Eschenbrenner Christoph , Freitag Michael , Habig Michael , Haueisen Janine , Möller Mareike , Schotanus Klaas , Stukenbrock Eva H.
Published: December 2019

Background

Antagonistic co-evolution can drive rapid adaptation in pathogens and shape genome architecture. Comparative genome analyses of several fungal pathogens revealed highly variable genomes, for many species characterized by specific repeat-rich genome compartments with exceptionally high sequence variability. Dynamic genome architecture may enable fast adaptation to host genetics. The wheat pathogen Zymoseptoria tritici with its highly variable genome and has emerged as a model organism to study the genomic evolution of plant pathogens. Here, we compared genomes of Z. tritici isolates and genomes of sister species infecting wild grasses to address the evolution of genome composition and structure.

Results

Using long-read technology, we sequenced and assembled genomes of Z. ardabiliae, Z. brevis, Z. pseudotritici and Z. passerinii, together with two isolates of Z. tritici. We report a high extent of genome collinearity among Zymoseptoria species and high conservation of genomic, transcriptomic and epigenomic signatures of compartmentalization. We identify high gene content variability both within and between species. In addition, such variability is mainly limited to the accessory chromosomes and accessory compartments. Despite strong host specificity and non-overlapping host-range between species, effectors are mainly shared among Zymoseptoria species, yet exhibiting a high level of presence-absence polymorphism within Z. tritici. Using in planta transcriptomic data from Z. tritici, we suggest different roles for the shared orthologs and for the accessory genes during infection of their hosts.

Conclusion

Despite previous reports of high genomic plasticity in Z. tritici, we describe here a high level of conservation in genomic, epigenomic and transcriptomic signatures of genome architecture and compartmentalization across the genus Zymoseptoria. The compartmentalized genome may reflect purifying selection to retain a functional core genome and relaxed selection on the accessory genome allowing a higher extent of polymorphism.
Choroid-resident macrophages maintain local vasculature and RPE integrity and spontaneously regenerate following depletion
Authors: Yang Xiao , Zhao Lian , Campos Maria M. , Abu-Asab Mones , Ortolan Davide , Hotaling Nathan , Bharti Kapil , Wong Wai T.
Published: December 2019

The choroid of the eye provides necessary vascular supply to the outer retina across the retinal pigment epithelial (RPE) layer and is a locus of progressive degenerative change in aging and age-related macular degeneration (AMD). Cellular mechanisms that maintain or compromise choroidal vasculature homeostasis are not well understood, complicating therapeutic efforts. We discover here that pharmacological ablation of macrophages normally resident in the adult mouse choroid via blockade of the CSF1 receptor resulted in progressive thinning of the choroid layer and atrophy of the choriocapillaris. Concurrently, choroidal macrophage ablation also induced structural disorganization of the RPE cell layer, downregulation of RPE visual cycle genes, and altered RPE angiogenic factor expression. Suspension of CSF1R blockade following ablation conversely enabled spontaneous regeneration of the choroidal macrophage population, restoring original macrophage distribution and morphological features. Macrophage repopulation significantly ameliorated the ablation-induced changes in RPE structure and angiogenic factor expression and arrested choroidal vascular atrophy. These findings reveal a previously unsuspected trophic function of resident choroidal macrophages in the maintenance of choroidal vasculature and the RPE layer, suggesting that insufficiency of macrophage function may contribute to age- and AMD-associated pathology. Modulating choroidal macrophage support function can constitute a strategy for therapeutic preservation of the choroid and RPE in AMD prevention and treatment.

Significance Statement

Choroidal atrophy is associated with normal aging and progression in age-related macular degeneration (AMD), a leading cause of blindness. Herein, we identify the choroidal macrophage as a critical player in the homeostatic maintenance of choroid-RPE complex of the eye. Depletion of choroidal macrophages resulted in progressive vascular atrophy, altered structure of retinal pigment epithelial (RPE) cells, and dysregulated RPE expression of visual cycle protein and angiogenic factors, VEGF and PEDF. We discovered that choroidal macrophages can regenerate and repopulate the choroid following depletion, ameliorating RPE alterations and arresting vascular atrophy. Our results suggest that insufficiency of macrophage function may contribute to age- and AMD-associated pathology, and modulation of macrophage support functions may be therapeutically useful in AMD prevention and treatment.
Fast and flexible design of novel proteins using graph neural networks
Authors: Strokach Alexey , Becerra David , Corbi-Verge Carles , Perez-Riba Albert , Kim Philip M.
Published: December 2019

Protein structure and function is determined by the arrangement of the linear sequence of amino acids in 3D space. Despite substantial advances, precisely designing sequences that fold into a predetermined shape (the “protein design” problem) remains difficult. We show that a deep graph neural network, ProteinSolver, can solve protein design by phrasing it as a constraint satisfaction problem (CSP). To sidestep the considerable issue of optimizing the network architecture, we first develop a network that is accurately able to solve the related and straightforward problem of Sudoku puzzles. Recognizing that each protein design CSP has many solutions, we train this network on millions of real protein sequences corresponding to thousands of protein structures. We show that our method rapidly designs novel protein sequences and perform a variety ofin silicoandin vitrovalidations suggesting that our designed proteins adopt the predetermined structures.

One Sentence Summary

A neural network optimized using Sudoku puzzles designs protein sequences that adopt predetermined structures.
Dynamic relocalization of the cytosolic type III secretion system components prevents premature protein secretion at low external pH
Authors: Wimmi Stephan , Balinovic Alexander , Jeckel Hannah , Selinger Lisa , Lampaki Dimitrios , Eisemann Emma , Meuskens Ina , Linke Dirk , Drescher Knut , Endesfelder Ulrike , Diepold Andreas
Published: December 2019

Many bacterial pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature secretion is prevented during infection. We found that in gastrointestinal pathogens, cytosolic injectisome components are temporarily released from the proximal interface of the injectisome at low external pH, preventing protein secretion in acidic environments, such as the stomach. In Yersinia enterocolitica, low external pH is detected in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions.
Draft Genomes of two Artocarpus plants, Jackfruit (A. heterophyllus) and Breadfruit (A. altilis)
Authors: Sahu Sunil Kumar , Liu Min , Yssel Anna , Kariba Robert , Jiang Sanjie , Song Bo , Muthemba Samuel , Hendre Prasad S. , Jamnadass Ramni , Kao Shu-Min , Featherston Jonathan , Zerega Nyree J.C. , Xu Xun , Yang Huanming , Deynze Allen Van , Peer Yves Van de , Liu Xin , Liu Huan
Published: December 2019

Two of the most economically important plants in the Artocarpus genus are jackfruit (A. heterophyllus Lam.) and breadfruit (A. altilis (Parkinson) Fosberg). Both species are long-lived trees that have been cultivated for thousands of years in their native regions. Today they are grown throughout tropical to subtropical areas as an important source of starch and other valuable nutrients. There are hundreds of breadfruit varieties that are native to Oceania, of which the most commonly distributed types are seedless triploids. Jackfruit is likely native to the western Ghats of India and produces one of the largest tree-borne fruit structures (reaching up to 100 pounds). To date, there is limited genomic information for these two economically important species. Here, we generated 273 Gb and 227 Gb of raw data from jackfruit and breadfruit, respectively. The high-quality reads from jackfruit were assembled into 162,440 scaffolds totaling 982 Mb with 35,858 genes. Similarly, the breadfruit reads were assembled into 180,971 scaffolds totaling 833 Mb with 34,010 genes. A total of 2,822 and 2,034 expanded gene families were found in jackfruit and breadfruit, respectively, enriched in pathways including starch- and sucrose metabolism, photosynthesis and others. The copy number of several starch synthesis related genes were found increased in jackfruit and breadfruit compared to closely related species, and the tissue specific expression might imply their sugar-rich and starch-rich characteristics. Overall, the publication of high-quality genomes for jackfruit and breadfruit provides information about their specific composition and the underlying genes involved in sugar and starch metabolism.
Intranasal oxytocin administration rescues neonatal thermo-sensory deficit in mouse model of Autism
Authors: Da Prato Laura Caccialupi , Abdallah Dina , Point Vanessa , Schaller Fabienne , Pallesi-Pocachard Emilie , Montheil Aurélie , Canaan Stéphane , Gaiarsa Jean-Luc , Muscatelli Françoise , Matarazzo Valéry
Published: December 2019

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we identified that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool sensory stimuli, while autonomic thermoregulatory function is active. This neonatal deficit was mimicked in control neonates by chemogenetic inactivation of oxytocin neurons. Importantly, intranasal administration of oxytocin was able to rescue the phenotype and brain Erk signaling impairment in mutants. This preclinical study establishes for the first-time early life impairments in thermosensory integration and shows the therapeutic potential benefits of intranasal oxytocin treatment on neonatal atypical sensory reactivity.
Feature-specific patterns of attention and functional connectivity in human visual cortex
Authors: Wailes-Newson Kirstie , Morland Antony B , Vernon Richard J. W. , Wade Alex R.
Published: December 2019

Attending to different features of a scene can alter the responses of neurons in early- and mid- level visual areas but the nature of this change depends on both the (top down) attentional task and the (bottom up) visual stimulus. One outstanding question is the spatial scale at which cortex is modulated by attention to low-level stimulus features such as shape, contrast and orientation. It is unclear whether the recruitment of neurons to particular tasks occurs at an area level or at the level of intra-areal sub-populations, or whether the critical factor is a change in the way that areas communicate with each other. Here we use functional magnetic resonance imaging (fMRI) and psychophysics, to ask how areas known to be involved in processing different visual features (orientation, contrast and shape) are modulated as participants switch between tasks based on those features while the visual stimulus itself is effectively constant. At a univariate level, we find almost no feature-specific bottom-up or top-down responses in the areas we examine. However, multivariate analyses reveal a complex pattern of voxel-level modulation driven by attentional task. Connectivity analyses also demonstrate flexible and selective patterns of connectivity between early visual areas as a function of attentional focus. Overall, we find that attention alters the sensitivity and connectivity of neuronal subpopulations within individual early visual areas but, surprisingly, not the univariate response amplitudes of the areas themselves.
New observations on non-coding RNAs involved in the dual translation system in zebrafish development
Authors: Breit Timo M. , Pagano Johanna F. B. , van der Jagt Pjotr L. , Mittring Ellis , Ensink Wim A. , van Olst Marina , van Leeuwen Selina , de Leeuw Wim , Nehrdich Ulrike , Spaink Herman P. , Rauwerda Han , Dekker Rob J.
Published: December 2019

Cellular translation relies heavily on the involvements of several types of non-coding RNAs. In previous studies we have identified a dual translation system in zebrafish development, involving maternal-type and somatic-type rRNAs, snoRNAs, and snRNAs. In this study we focused on several remaining non-coding RNAs involved in the translation system; tRNAs, RNase P, and SRP RNA. Even though our studies have been limited in extent, for all three types of non-coding RNA we were able to identify a maternal-specific type, with substantial sequence differences as compared to the somatic-type variant. Hence, these RNA types complement the previously discovered RNA types in the unique dual translation system in zebrafish development.
Quantitative assessment of bovine serum albumin proteins for blocking applications
Authors: Ma Gamaliel Junren , Ferhan Abdul Rahim , Jackman Joshua A. , Cho Nam-Joon
Published: December 2019

Bovine serum albumin (BSA) is one of the most widely used protein reagents in the scientific community, especially for surface passivation (“blocking”) applications in various bioassays. Numerous BSA protein options are commercially available, however, there is scarce information about which ones are preferable for blocking applications. Herein, we conducted biophysical and bioassay measurements to quantitatively compare the conformational, adsorption, and blocking properties of BSA protein reagents that were obtained through six purification methods. Depending on the method, there were significant differences in the conformational and adsorption properties of BSA proteins, mainly due to the presence of fatty acid stabilizers. In turn, we discovered that fatty acid-free BSA proteins exhibit superior blocking performance to fatty acid-stabilized BSA proteins in surface- and nanoparticle-based bioassays. We critically discuss mechanistic factors behind these performance variations and our findings offer a practical framework to guide BSA selection for blocking applications.
A closer look at the timecourse of mind wandering: pupillary responses and behaviour
Authors: Pelagatti Claudia , Binda Paola , Vannucci Manila
Published: December 2019

Mind wandering (MW) refers to the shift of attention away from a primary task and/or external environment towards thoughts unrelated to the task. Recent evidence has shown that pupillometry can be used as an objective marker of the onset and maintenance of externally-driven MW episodes. In the present study we aimed to further investigate pupillary changes associated with the onset and duration of self-reported MW episodes.

We used a modified version of the joint behavioural-pupillometry paradigm we recently introduced. Participants were asked to perform a monotonous vigilance task which was intermixed with task-irrelevant cue-phrases (visually presented verbal cues); they were instructed to interrupt the task whenever a thought came to mind (self-caught method) and to indicate the trigger of their thought, if any. We found systematic pupil dilation after the presentation of verbal cues reported to have triggered MW, compared with other verbal cues presented during a supposedly on-task period (i.e., the period immediately following the resuming of the task after a self-caught interruption and MW report). These results confirm that pupil diameter is sensitive to the changes associated with the onset of MW and its unfolding over time.

Moreover, by computing the latency between the trigger presentation and the task interruption (self-catch), we could also estimate the duration of MW episodes triggered by verbal cues. However, a high variability was found, implying very large inter-event variability, which could not be explained by any of the MW properties we acquired (including: temporal focus, specificity, emotional valence). Our behavioural and pupillometry findings stress the need for objective measures about the temporal unfolding of MW (while most studies focus on arbitrary time-window preceding self-reports of MW).
Worldwide occurrence records reflect a global decline in bee species richness
Authors: Zattara Eduardo E. , Aizen Marcelo A.
Published: December 2019

Wild and managed bees are key pollinators, providing ecosystem services to a large fraction of the world’s flowering plants, including ∼85% of all cultivated crops. Recent reports of wild bee decline and its potential consequences are thus worrisome. However, evidence is mostly based on local or regional studies; global status of bee decline has not been assessed yet. To fill this gap, we analyzed publicly available worldwide occurrence records from the Global Biodiversity Information Facility spanning more than a century of specimen collection. We found that after the 1980’s the number of collected bee species declines steeply, and approximately 25% fewer species were reported between 2006 and 2015 relative to the number of species counted before the 1990’s. These trends are alarming and encourage swift action to avoid further decline of these key pollinators.
Sequence-to-function deep learning frameworks for synthetic biology
Authors: Valeri Jacqueline , Collins Katherine M. , Lepe Bianca A. , Lu Timothy K. , Camacho Diogo M.
Published: December 2019

While synthetic biology has revolutionized our approaches to medicine, agriculture, and energy, the design of novel circuit components beyond nature-inspired templates can prove itself challenging without well-established design rules. Toehold switches — programmable nucleic acid sensors — face an analogous prediction and design bottleneck: our limited understanding of how sequence impacts functionality can require expensive, time-consuming screens for effective switches. Here, we introduce the Sequence-based Toehold Optimization and Redesign Model (STORM), a deep learning architecture that applies gradient ascent to re-engineer poorly-performing toeholds. Based on a dataset of 91,534 toehold switches, we examined convolutional filters and saliency maps of sequences to interpret our sequence-to-function model, identifying hot spots where mutations change toehold effectiveness and features unique to high-performing switches. Our modeling platform provides frameworks for future toehold selection, augmenting our ability to construct potent synthetic circuit components and precision diagnostics, and enabling straightforward translation of thisin silicoworkflow to other circuitries.
Reconciling author names in taxonomic and publication databases
Authors: Page Roderic D. M.
Published: December 2019

Taxonomic names remain fundamental to linking biodiversity data, but information on these names resides in separate silos. Despite often making their contents available in RDF, records in these taxonomic databases are rarely linked to identifiers in external databases, such as DOIs for publications, or ORCIDs for people. This paper explores how author names in publication databases such as CrossRef and ORCID can be reconciled with author names in a taxonomic database using existing vocabularies and SPARQL queries.
How tasks change whole-brain functional organization to reveal brain-phenotype relationships
Authors: Greene Abigail S. , Gao Siyuan , Noble Stephanie , Scheinost Dustin , Constable R. Todd
Published: December 2019

Functional connectivity (FC) calculated from task fMRI data better reveals brain-phenotype relationships than rest-based FC, but how tasks have this effect is unknown. In over 700 individuals performing 7 tasks, we use psychophysiological interaction (PPI) and predictive modeling analyses to demonstrate that task-induced changes in FC successfully predict phenotype, and these changes are not simply driven by task activation. Activation, however, is useful for prediction only if the in-scanner task is related to the predicted phenotype. Given this evidence that tasks change patterns of FC independent of activation to amplify brain-phenotype relationships, we develop and apply an inter-subject PPI analysis to further characterize these predictive FC changes. We find that task-induced consistency of FC patterns across individuals is useful for prediction—to a point; these results suggest that tasks improve FC-based prediction performance by de-noising the BOLD signal, revealing meaningful individual differences in brain functional organization. Together, these findings demonstrate that, when it comes to the effects of in-scanner tasks on the brain, focal activation is only the tip of the iceberg, and they offer a framework to best leverage both task activation and FC to reveal the neural bases of complex human traits, symptoms, and behaviors.
Ectoderm to mesoderm transition by downregulation of actomyosin contractility
Authors: Kashkooli Leily , Rozema David , Espejo-Ramirez Lina , Lasko Paul , Fagotto François
Published: December 2019

Collective migration of cohesive tissues is a fundamental process in morphogenesis, and is particularly well illustrated during gastrulation by the rapid and massive internalization of the mesoderm, which contrasts with the much more modest movements of the ectoderm. In the Xenopus embryo, the differences in morphogenetic capabilities of ectoderm and mesoderm can be connected to the intrinsic motility of individual cells, very low for ectoderm, highly for mesoderm. Surprisingly, we find these seemingly deep differences can be accounted for simply by differences in Rock-dependent actomyosin contractility. We show that Rock inhibition is sufficient to rapidly unleash motility in the ectoderm and confer it with mesoderm-like properties. In the mesoderm, this motility is dependent on two negative regulators of RhoA, the small GTPase Rnd1 and the RhoGAP Shirin/Dlc2/ArhGAP37. Both are absolutely essential for gastrulation. At the cellular and tissue level, the two regulators show overlapping yet distinct functions. They both contribute to decrease cortical tension and confer motility, but Shirin tends to increase tissue fluidity and stimulate dispersion, while Rnd1 tends to favour more compact collective migration. Thus, each is able to contribute to a specific property of the migratory behaviour of the mesoderm. We propose that the “ectoderm to mesoderm transition” is a prototypic case of collective migration driven by a downregulation of cellular tension, without the need for the complex changes traditionally associated with the epithelial to mesenchymal transition.
Rif1 functions in a tissue-specific manner to control replication timing through its PP1-binding motif
Authors: Armstrong Robin L. , Das Souradip , Hill Christina A. , Duronio Robert J. , Nordman Jared T.
Published: December 2019

Replication initiation in eukaryotic cells occurs asynchronously throughout S phase, yielding early and late replicating regions of the genome, a process known as replication timing (RT). RT changes during development to ensure accurate genome duplication and maintain genome stability. To understand the relative contributions that cell lineage, cell cycle, and replication initiation regulators have on RT, we utilized the powerful developmental systems available in Drosophila melanogaster. We generated and compared RT profiles from mitotic cells of different tissues and from mitotic and endocycling cells of the same tissue. Our results demonstrate that cell lineage has the largest effect on RT, whereas switching from a mitotic to an endoreplicative cell cycle has little to no effect on RT. Additionally, we demonstrate that the RT differences we observed in all cases are largely independent of transcriptional differences. We also employed a genetic approach in these same cell types to understand the relative contribution the eukaryotic RT control factor, Rif1, has on RT control. Our results demonstrate that Rif1 can function in a tissue-specific manner to control RT. Importantly, the Protein Phosphatase 1 (PP1) binding motif of Rif1 is essential for Rif1 to regulate RT. Together, our data support a model in which the RT program is primarily driven by cell lineage and is further refined by Rif1/PP1 to ultimately generate tissue-specific RT programs.
A novel cis regulatory element regulates human XIST in CTCF-dependent manner
Authors: Shah Rini , Sharma Ankita , Kelkar Ashwin , Sengupta Kundan , Galande Sanjeev
Published: December 2019

The long non-coding RNA XIST is the master regulator for the process of X chromosome inactivation (XCI) in mammalian females. Here we report the existence of a hitherto uncharacterized cis regulatory element (cRE) within the first exon of human XIST, which determines the transcriptional status of XIST during the initiation and maintenance phases of XCI. In the initiation phase, pluripotency factors bind to this cRE and keep XIST repressed. In the maintenance phase of XCI, the cRE is enriched for CTCF which activates XIST transcription. By employing a CRISPR-dCas9-KRAB based interference strategy, we demonstrate that binding of CTCF to the newly identified cRE is critical for regulating XIST in a YY1-dependent manner. Collectively, our study uncovers the combinatorial effect of multiple transcriptional regulators influencing XIST expression during the initiation and maintenance phases of XCI.
White beam diagnostics using X-ray back-scattering from a CVD diamond vacuum window
Authors: van Silfhout Roelof , Pothin Daniel , Martin Thierry
Published: December 2019

Collecting back-scattered X-rays from vacuum windows using a pinhole X-ray camera provides an efficient and reliable method of measuring the beam shape and position of the white synchrotron beam. In this paper, measurements are presented that were conducted at ESRF beamline ID6 which uses an in-vacuum cryogenically cooled permanent-magnet undulator (CPMU18) and a traditional U32 undulator as its radiation sources, allowing tests to be performed at very high power density levels that were adjusted by changing the gap of the undulators. These measurements show that it is possible to record beam shape and beam position using a simple geometry without having to place any further items in the beam path. With this simple test setup it was possible to record the beam position with a root-mean-square noise figure of 150 nm.
Characterizing the intrinsic properties of individual XFEL pulses via single-particle diffraction
Authors: Lee Heemin , Shin Jaeyong , Cho Do Hyung , Jung Chulho , Sung Daeho , Ahn Kangwoo , Nam Daewoong , Kim Sangsoo , Kim Kyung Sook , Park Sang-Yeon , Fan Jiadong , Jiang Huaidong , Kang Hyun Chol , Tono Kensuke , Yabashi Makina , Ishikawa Tetsuya , Noh Do Young , Song Changyong
Published: December 2019

With each single X-ray pulse having its own characteristics, understanding the individual property of each X-ray free-electron laser (XFEL) pulse is essential for its applications in probing and manipulating specimens as well as in diagnosing the lasing performance. Intensive research using XFEL radiation over the last several years has introduced techniques to characterize the femtosecond XFEL pulses, but a simple characterization scheme, while not requiring ad hoc assumptions, to address multiple aspects of XFEL radiation via a single data collection process is scant. Here, it is shown that single-particle diffraction patterns collected using single XFEL pulses can provide information about the incident photon flux and coherence property simultaneously, and the X-ray beam profile is inferred. The proposed scheme is highly adaptable to most experimental configurations, and will become an essential approach to understanding single X-ray pulses.
NASA electrified aircraft propulsion efforts
Authors: Jansen Ralph H. , Bowman Cheryl L. , Clarke Sean , Avanesian David , Dempsey Paula J. , Dyson Rodger W.
Published: December 2019

Purpose

This paper aims to review national aeronautics and space administration (NASA’s) broad investments in electrified aircraft propulsion (EAP). NASA investments are guided by an assessment of potential market impacts, technical key performance parameters, and technology readiness attained through a combination of studies, enabling fundamental research and flight research.

Design/methodology/approach

The impact of EAP varies by market and NASA is considering three markets as follows: national/international, on-demand mobility and short-haul regional air transport. Technical advances in key areas have been made that indicate EAP is a viable technology. Flight research is underway to demonstrate integrated solutions and inform standards and certification processes.

Findings

A key finding is that sufficient technical advances in key areas have been made, which indicate EAP is a viable technology for aircraft. Significant progress has been made to reduce EAP adoption barriers and further work is needed to transition the technology to a commercial product and improve the technology, so it is applicable to large transonic aircraft.

Practical implications

Significant progress has been made to reduce EAP adoption barriers and further work is needed to transition the technology to a commercial product and improve the technology, so it is applicable to large transonic aircraft.

Originality/value

This paper will review the activities of the hybrid gas-electric subproject of the Advanced Air Transport Technology Project, the Revolutionary Vertical Lift Technology Project and the X-57 Flight Demonstration Project, and discuss the potential EAP benefits for commercial and military applications. This paper focuses on the vehicle-related activities, however, there are related NASA activities in air space management and vehicle autonomy activities, as well as a breakthrough technology project called the Convergent Aeronautics Solutions Project. The target audience is people interested in EAP.
Financial development and agricultural performance in Nigeria: what role do institutions play?
Authors: Raifu Isiaka Akande , Aminu Alarudeen
Published: December 2019

Purpose

The centrality of agricultural sector to the economy, particularly in developing countries, has drawn the attention of researchers to critically examine different factors determining the performance of the sector. Given that massive investment is required to ensure maximum productivity in the sector, one of the factors identified is the issue of financing. However, financing agricultural sector in a poor institutional environment can be depressing. In the light of this, the purpose of this paper is to examine the nexus between financial development and agricultural performance in Nigeria with a view to investigating the role of institutions.

Design/methodology/approach

The study employed annual data spanning the period from 1981 to 2016. Three indicators of financial development and five institutional variables were used. Besides, for robust analysis, the study also computed an aggregate measure of financial development and institutions using principal component method. Autoregressive distributed lag method of estimation was used to examine the short-run and long-run effects of financial development on agricultural performance in Nigeria.

Findings

The findings showed that financial development has a positive impact on agricultural performance in Nigeria. However, this positive impact is being undermined by institutional variables.

Originality/value

To the best of the authors’ knowledge, this is the only study that examines the mediating role of institutional factors such as the rule of law, control of corruption, etc., in the financial development–agricultural performance nexus in Nigeria.
FactQA: question answering over domain knowledge graph based on two-level query expansion
Authors: Zhang Xiaoming , Meng Mingming , Sun Xiaoling , Bai Yu
Published: December 2019

Purpose

With the advent of the era of Big Data, the scale of knowledge graph (KG) in various domains is growing rapidly, which holds huge amount of knowledge surely benefiting the question answering (QA) research. However, the KG, which is always constituted of entities and relations, is structurally inconsistent with the natural language query. Thus, the QA system based on KG is still faced with difficulties. The purpose of this paper is to propose a method to answer the domain-specific questions based on KG, providing conveniences for the information query over domain KG.

Design/methodology/approach

The authors propose a method FactQA to answer the factual questions about specific domain. A series of logical rules are designed to transform the factual questions into the triples, in order to solve the structural inconsistency between the user’s question and the domain knowledge. Then, the query expansion strategies and filtering strategies are proposed from two levels (i.e. words and triples in the question). For matching the question with domain knowledge, not only the similarity values between the words in the question and the resources in the domain knowledge but also the tag information of these words is considered. And the tag information is obtained by parsing the question using Stanford CoreNLP. In this paper, the KG in metallic materials domain is used to illustrate the FactQA method.

Findings

The designed logical rules have time stability for transforming the factual questions into the triples. Additionally, after filtering the synonym expansion results of the words in the question, the expansion quality of the triple representation of the question is improved. The tag information of the words in the question is considered in the process of data matching, which could help to filter out the wrong matches.

Originality/value

Although the FactQA is proposed for domain-specific QA, it can also be applied to any other domain besides metallic materials domain. For a question that cannot be answered, FactQA would generate a new related question to answer, providing as much as possible the user with the information they probably need. The FactQA could facilitate the user’s information query based on the emerging KG.
Impact of AI regulation on intention to use robots
Authors: Chatterjee Sheshadri
Published: December 2019

Purpose

The purpose of this paper is to identify the factors influencing the citizens to use robots that would improve the quality of life of the citizens.

Design/methodology/approach

With the help of different adoption theories and models and with the support of background studies, some hypotheses have been formulated and a conceptual model has been developed with the consideration of the impact of artificial intelligence regulation (IAR) that controls the use of robots as a moderator. The model has been validated and the hypotheses have been tested by statistical analysis with the help of survey works involving consideration of feedbacks from 503 usable respondents.

Findings

The study reveals that the use of robots by the citizens would appreciably increase if government imposes strict artificial intelligence (AI) regulatory control concerning the use of robots, and in that case, it appears that the use of robots would improve the quality of life of the citizens.

Research limitations/implications

The duly validated model would help the authority to appropriately nurse and nurture the factors such as ethical dilemma, perceived risks and control beliefs for enhancing the intention of the citizens to use robots for many purposes including domestic usage in the context of appropriate restrictions imposed through AI regulation. Such use of robots would eventually improve the quality of life.

Originality/value

There are a few studies covering analysis of IAR as a moderator on the linkages of the predictors with the intention of the citizens to use robots. In this context, this study is claimed to have offered a novel contribution.
Impact of statutory regulation and key internal factors on firm’s corporate social responsibility
Authors: Chakraborty Ashok
Published: December 2019

Purpose

This study aims to examine the impact of statutory regulatory order by the government on the degree of corporate social responsibility (CSR) performance and disclosures. It also aims to empirically investigate the relationship of a firm’s key internal and governance factors with CSR performance and disclosures.

Design/methodology/approach

The study is based on empirical data from all banking firms listed in the Dhaka Stock Exchange (DSE) for a period of 2011-2015. The difference in difference analysis has been used to test the regulatory impact, where content analysis has been performed to find CSR disclosure scores. The multivariate regression analysis has been used to test hypotheses to find impact of firm’s internal factor on CSR disclosures.

Findings

The analysis and results of the study show that there is no significant impact of statutory regulatory impact on a firm’s level of CSR performance and disclosure. On the other hand, the study has found that board expertizes and board meetings have significant positive impact on firm’s CSR while no significant impact is found for firm networks to influence firm’s CSR disclosures.

Research limitations/implications

The main research limitation of the study is that it covers all listed firms of the banking industry in Bangladesh. Because of data inconsistency, other industries are not included in the data sample of this study.

Originality/value

The value of the study lies in its contribution to the empirical investigation of regulatory impact and key internal and governance factors in a developing country perspective, which will add value to the CSR literature.
School staff advice-seeking patterns regarding support for vulnerable students
Authors: Ortega Lorena , Thompson Ian , Daniels Harry
Published: December 2019

Purpose

Supporting the learning and wellbeing of vulnerable students is an important yet challenging part of school educators’ work. The purpose of this paper is to investigate advice-seeking patterns around the issue of supporting the learning and wellbeing of vulnerable students, among professional staff in six English secondary schools. The paper focuses on investigating variation in advice-seeking patterns among schools, exploring the association between these patterns and staff perceptions of the school climate for collaboration, and examining how these informal advice-seeking patterns relate to formal support arrangements in the schools.

Design/methodology/approach

A mixed-methods approach that combined findings from social network analysis with in-depth interviews was used.

Findings

It was found that advice-seeking patterns among staff vary substantively, even among similar schools. Furthermore, schools with more cohesive and reciprocal advice networks also showed a stronger climate for collaboration (i.e. mutual respect and distributed leadership). Also, formal organizational structures and informal advice-seeking structures showed coherence in the sample, as formally designated leaders, such as the Headteacher and the Special Educational Needs Coordinators, were generally highly central to their schools’ advice network.

Originality/value

This study advances the field as there is little research that examines the social networks of educators in England, and no previous studies that explore teacher advice-seeking networks in relation to supporting vulnerable students, internationally.
Entrepreneurs
Authors: Price Gregory
Published: December 2019

Purpose

The purpose of this paper is to consider if self-employed entrepreneurs, a class of individuals who require enforceable property rights to create new firms and ideas that could increase a society’s material living standards, constitute an individual property rights enforcement mechanism.

Design/methodology/approach

With data from the General Social Survey, the authors estimate the parameters of mixed-effects categorical regression specifications to measure the effect of self-employment on confidence in the US Supreme Court, raising and donating funds for social or political activities, and on trying to persuade others to share political views.

Findings

The findings suggest that self-employed entrepreneurs are one of the guarantors of a constitutional democracy based on an ethic of individual property rights, and public policies that are pro-entrepreneurship help mitigate the risk of constitutional failure, and maximize society’s material living and ethical standards.

Research limitations/implications

The results are based on cross-sectional data, which do not account for dynamic changes in preferences.

Practical implications

The findings suggest that self-employed entrepreneurs are a enforcement mechanism and a guarantor of an ethic of private property rights necessary for the ongoing success and viability of a constitutional democracy based on individual property rights.

Social implications

The findings suggest that as entrepreneurs constitute an enforcement mechanism for individual property rights, to the extent that entrepreneurialism also cultivates individual virtue entrepreneurs also serve as guarantors of a moral and ethical society that is based on virtue, which results in a constitutional democracy with high material living and ethical/moral standards.

Originality/value

This paper is among the first to empirically test whether entrepreneurs are an enforcement mechanism for individual property rights.