bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the nucleosome histone core on the structure and dynamics of DNA containing pyrimidine-pyrimidone (6-4) photoproduct
Authors: Matoušková Eva , Bignon Emmanuelle , Claerbout Victor , Dršata Tomáš , Gillet Natacha , Monari Antonio , Dumont Elise , Lankaš Filip
Published: April 2020

The pyrimidine-pyrimidone (6-4) photoproduct (64-PP) is an important photoinduced DNA lesion, which constitutes a mutational signature for melanoma. The structural impact of 64-PP on DNA complexed with compaction proteins, and notably histones, affects the mechanism of its mutagenicity and repair but remains poorly understood. Here we investigate the conformational dynamics of DNA containing 64-PP lesions within the nucleosome core particle by atomic-resolution molecular dynamics simulations at the multi-microsecond time scale. We demonstrate that the histone core exerts important mechanical restraints that largely decrease global DNA structural fluctuations. However, we also show that local DNA flexibility at the damaged site is enhanced, due to imperfect structural adaptation to restraints imposed by the histone core. In particular, if 64-PP faces the histone core and is therefore not directly accessible by the repair protein, the complementary strand facing the solvent exhibits higher flexibility than the corresponding strand in a naked, undamaged DNA. This may serve as an initial recognition signal for repair. Our simulations also pinpoint the structural role of proximal residues from the truncated histone tails.
Chromosome-level and haplotype-resolved genome assembly enabled by high-throughput single-cell sequencing of gamete genomes
Authors: Campoy José A. , Sun Hequan , Goel Manish , Jiao Wen-Biao , Folz-Donahue Kat , Wang Nan , Rubio Manuel , Liu Chang , Kukat Christian , Ruiz David , Huettel Bruno , Schneeberger Korbinian
Published: April 2020

Generating chromosome-level, haplotype-resolved assemblies of heterozygous genomes remains challenging. To address this, we developed gamete binning, a method based on single-cell sequencing of haploid gametes enabling separation of the whole-genome sequencing reads into haplotype-specific reads sets. After assembling the reads of each haplotype, the contigs are scaffolded to chromosome-level using a genetic map derived from the gametes. As a proof-of-concept, we assembled the two genomes of a diploid apricot tree based on whole-genome sequencing of 445 individual pollen grains. The two haplotype assemblies (N50: 25.5 and 25.8 Mb) featured a haplotyping precision of >99% and were accurately scaffolded to chromosome-level.
Leveraging a WGS compression and indexing format with dynamic graph references to call structural variants
Authors: English Adam C. , McCarthy Nils , Flickenger Robert , Maheshwari Surabhi , Meed Lisa , Mangubat Alindrina , Shekar Sri Niranjan
Published: April 2020

We introduce a novel structural variant calling pipeline (BioGraph) that leverages a read compression and indexing format to discover alleles, assess their supporting coverage, and assign useful quality scores. To evaluate BioGraph’s performance, we run five sequencing replicates of the individual HG002 through the BioGraph variant calling pipeline, as well as two other short-read sv-calling pipelines. BioGraph detects the GIAB benchmark SVs at a peak sensitivity of ≈59% compared to ≈42% sensitivity from the other pipelines. The overall precision of BioGraph is lower than other pipelines (≈81% and ≈90%, respectively), however, adjusting for quality score, BioGraph calls were sensitive to a greater number of SV calls given the same false discovery rate compared to the other pipelines. Cumulatively ≈77% of GIAB benchmark SVs are discovered by BioGraph in at least one replicate. After merging discovered calls and running BioGraph Coverage to create a squared-off project-level VCF, we find ≈90% percent of discovered true positive alleles have at least 5x coverage in all replicates, thus increasing per-replicate recall of alleles having at least 1x coverage to ≈76.9%.
The direct and indirect effects of environmental toxicants on the health of bumble bees and their microbiomes
Authors: Rothman Jason A. , Russell Kaleigh A. , Leger Laura , McFrederick Quinn S. , Graystock Peter
Published: April 2020

Bumble bees (Bombusspp.) are important and widespread insect pollinators, but the act of foraging on flowers can expose them to harmful pesticides and environmental chemicals such as oxidizers and heavy metals. How these compounds directly influence bee survival and indirectly affect bee health via the gut microbiome is largely unknown. As the toxins and toxicants in floral nectar and pollen take many forms, we explored the genomes of core bumblebee microbes (Using RAST) for their potential to detoxify cadmium, copper, selenium, the neonicotinoid pesticide imidacloprid, and hydrogen peroxide - which have all been identified in floral nectar and pollen. We then exposedBombus impatiensworkers to varying concentrations of these chemicals spiked into their diet and identified the direct effects on bee survival. Using field realistic doses, we further explored indirect effects on bee microbiomes. We found multiple genes in core gut microbes that have the potential to aid in detoxifying harmful chemicals. We also found that while the chemicals are largely toxic at levels within and above field-realistic concentrations, the field-realistic concentrations - except for imidacloprid - altered the composition of the bee microbiome, potentially causing gut dysbiosis. Overall, our study shows that environmental chemicals found in floral nectar and pollen can directly cause bee mortality, and at field-realistic levels, likely have indirect, deleterious effects on bee health via their influence on the bee microbiome.
Control of ribosomal protein synthesis by Microprocessor complex
Authors: Jiang Xuan , Prabhakar Amit , Van der Voorn Stephanie M. , Ghatpande Prajakta , Celona Barbara , Venkataramanan Srivats , Calviello Lorenzo , Lin Chuwen , Wang Wanpeng , Black Brian L. , Floor Stephen N. , Lagna Giorgio , Hata Akiko
Published: April 2020

Ribosome biogenesis in eukaryotes requires stoichiometric production and assembly of 80 ribosomal proteins (RPs) and 4 ribosomal RNAs, and its rate must be coordinated with cellular growth. The indispensable regulator of RP biosynthesis is the 5’-terminal oligopyrimidine (TOP) motif, spanning the transcription start site of all RP genes. Here we show that the Microprocessor complex, previously linked to the first step of processing microRNAs (miRNAs), coregulates RP expression by binding the TOP motif of nascent RP mRNAs and stimulating transcription elongation via resolution of DNA/RNA hybrids. Cell growth arrest triggers nuclear export and degradation of the Microprocessor protein Drosha by the E3 ubiquitin ligase Nedd4, accumulation of DNA/RNA hybrids at RP gene loci, decreased RP synthesis, and ribosome deficiency, hence synchronizing ribosome production with cell growth. Conditional deletion ofDroshain erythroid progenitors phenocopies human ribosomopathies, in which ribosomal insufficiency leads to anemia. Outlining a miRNA-independent role of the Microprocessor complex at the interphase between cell growth and ribosome biogenesis offers a new paradigm by which cells alter their protein biosynthetic capacity and cellular metabolism.
Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7
Authors: Coppin Emilie , Sundarasetty Bala Sai , Rahmig Susann , Blume Jonas , Verheyden Nikita A. , Bahlmann Franz , Ravens Sarina , Schubert Undine , Schmid Janine , Ludwig Stefan , von Kaisenberg Constantin , Platz Alexander , Naumann Ronald , Ludwig Barbara , Prinz Immo , Waskow Claudia , Krueger Andreas
Published: April 2020

Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T cell differentiation remains inefficient. We generated mice expressing human interleukin (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T cell differentiationin vivoand to generate a human immune system with a better approximation of human lymphocyte ratios.
Coupling spectral and resource-use complementarity in experimental grassland and forest communities
Authors: Schweiger Anna K. , Cavender-Bares Jeannine , Kothari Shan , Townsend Philip A. , Madritch Michael D. , Grossman Jake J. , Gholizadeh Hamed , Wang Ran , Gamon John A.
Published: April 2020

Reflectance spectra provide integrative measures of plant phenotypes by capturing chemical, morphological, anatomical and architectural trait information. Here we investigate the linkages between plant spectral variation, spectral and resource-use complementarity that contribute to ecosystem productivity. In both a prairie grassland and a forest diversity experiment, we delineated N-dimensional hypervolumes using either wavelength-bands of reflectance spectra or foliar traits. First, we compared the hypervolume fraction unique to each species in either spectral or trait space with increasing dimensionality. Then, we investigated the association between the spectral space occupied by individual plants and their growth, as well as the spectral space occupied by plant communities and ecosystem productivity. We show that species are better distinguished in spectral space than in trait space, providing a conceptual basis for identifying plant taxa spectrally. In addition, the spectral space occupied by individuals increased with plant growth, and the spectral space occupied by plant communities increased with ecosystem productivity. Furthermore, ecosystem productivity was better explained by inter-individual spectral complementarity than by the large spectral space occupied by productive individuals. Our results indicate that spectral hypervolumes of plants can reflect ecological strategies that shape community composition and ecosystem function, and that spectral complementarity can reveal resource-use complementarity.
The Role of Rif1 in telomere length regulation is separable from its role in origin firing
Authors: Shubin Calla B. , Greider Carol W.
Published: April 2020

To examine the established link between DNA replication and telomere length, we tested whether firing of telomeric origins would cause telomere lengthening. We found thatRIF1mutants that block Protein Phosphatase 1 (PP1) binding activated telomeric origins but did not elongate telomeres. In a second approach, we found overexpression of ΔN-Dbf4 and Cdc7 increased DDK activity and activated telomeric origins, yet telomere length was unchanged. We tested a third mechanism to activate origins using thesld3-A mcm5-bob1mutant that deregulates the pre-replication complex, and again saw no change in telomere length. Finally, we tested whether mutations inRIF1that cause telomere elongation would affect origin firing. We found that neitherrif1-Δ1322norrif1HOOKaffected firing of telomeric origins. We conclude that telomeric origin firing does not cause telomere elongation, and the role of Rif1 in regulating origin firing is separable from its role in regulating telomere length.
Quantification of Mouse Reach Kinematics as a Foundation for Mechanistic Interrogation of Motor Control
Authors: Becker Matthew I. , Calame Dylan , Wrobel Julia , Person Abigail L.
Published: April 2020

Mice use reaching movements to grasp and manipulate objects in their environment, similar to primates. Thus, many recent studies use mouse reach to uncover neural control mechanisms, but quantification of mouse reach kinematics remains lacking, limiting understanding. Here we implement several analytical frameworks, from basic kinematic relationships to statistical machine learning, to quantify mouse reach kinematics across freely-behaving and head-fixed conditions. Overall, we find that many canonical features of primate reaches are conserved in mice, with some notable differences. Our results highlight the decelerative phase of reach as important in driving successful outcome. Late-phase kinematic adjustments are yoked to mid-flight position and velocity of the limb, allowing dynamic correction of initial variability, with head-fixed reaches being less dependent on position. Furthermore, consecutive reaches exhibit positional error-correction but not hot-handedness, implying opponent regulation of motor variability. Overall, our results establish foundational mouse reach kinematics in the context of neuroscientific investigation.
Sex-Specific Cross Tissue Meta-Analysis Identifies Immune Dysregulation in Women with Alzheimer’s Disease
Authors: Paranjpe Manish D , Belonwu Stella , Wang Jason K , Oskotsky Tomiko , Gupta Aarzu , Taubes Alice , Zalokusky Kelly , Paranjpe Ishan , Glicksberg Benjamin S , Huang Yadong , Sirota Marina ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2020

In spite of evidence of females having a greater lifetime risk of developing Alzheimer’s Disease (AD) and greater apolipoprotein E4-related (apoE4) AD risk compared to males, molecular signatures underlying these findings remain elusive. We took a meta-analysis approach to study gene expression in the brains of 1,084 AD patients and age-matched controls and whole blood from 645 AD patients and age-matched controls. Gene-expression, network-based analysis and cell type deconvolution approaches revealed a consistent immune signature in the brain and blood of female AD patients that was absent in males. Machine learning-based classification of AD using gene expression from whole blood in addition to clinical features revealed an improvement in classification accuracy upon stratifying by sex, achieving an AUROC of 0.91 for females and 0.80 for males. These results help identify sex and apoE4 genotype-specific transcriptomic signatures of AD and underscore the importance of considering sex in the development of biomarkers and therapeutic strategies for AD.
The genomes of invasive coral Tubastraea spp. (Dendrophylliidae) as tool for the development of biotechnological solutions
Authors: Soares-Souza Giordano Bruno , Amaral Danielle , Batista Daniela , Torres André Q. , Silva Serra Anna Carolini , Uliano-Silva Marcela , Leomil Luciana , Reis Aryane Camos , de Matos Elyabe Monteiro , Calderon Emiliano , Yu Vriko , Dondero Francesco , de Sousa Saulo Marçal , Baker David , Dumaresq Aline , Rebelo Mauro F.
Published: April 2020

Corals have been attracting huge attention due to the impact of climate change and ocean acidification on reef formation and resilience. Nevertheless, some species like Tubastraea coccinea and T. tagusensis have been spreading very fast replacing the native ones which affect the local environment and decrease biodiversity of corals and other organisms associated with them. Despite some focal efforts to understand the biology of these organisms, they remain understudied at the molecular level. This knowledge gap hinders the development of cost-effective strategies for both conservation and management of invasive species. In this circumstance, it is expected that genome sequencing would provide powerful insights that could lead to better strategies for prevention, management, and control of this and other invasive species. Here, we present three genomes of Tubastraea spp. in one of the most comprehensive biological studies of corals, that includes flow cytometry, karyotyping, transcriptomics, genomics, and phylogeny. The genome of T. tagusensis is organized in 23 chromosomes pairs and has 1.1 Gb, the T. coccinea genome is organized in 22 chromosome pairs and has 806 Mb, and the Tubastraea sp. genome is organized in 21 chromosome pairs and has 795 Mb. The hybrid assembly of T. tagusensis using short and long-reads has a N50 of 227,978 bp, 7,996 contigs and high completeness estimated as 91.6% of BUSCO complete genes, of T. coccinea has a N50 of 66,396 bp, 17,214 contigs and 88.1% of completeness, and of Tubastraea sp. has a N50 of 82,672 bp, 12,922 contigs and also 88.1% of completeness. We inferred that almost half of the genome consists of repetitive elements, mostly interspersed repeats. We provide evidence for exclusive Scleractinia and Tubastraea gene content related to adhesion and immunity. The Tubastraea spp. genomes are a fundamental study which promises to provide insights not only about the genetic basis for the extreme invasiveness of this particular coral genus, but to understand the adaptation flaws of some reef corals in the face of anthropic-induced environmental disturbances. We expect the data generated in this study will foster the development of efficient technologies for the management of coral species, whether invasive or threatened.
Functional Annotation of Human Cognitive States using Deep Graph Convolution
Authors: Zhang Yu , Tetrel Loïc , Thirion Bertrand , Bellec Pierre
Published: April 2020

A key goal in neuroscience is to understand brain mechanisms of cognitive functions. An emerging approach is “brain decoding”, which consists of inferring a set of experimental conditions performed by a participant, using pattern classification of brain activity. Few works so far have attempted to train a brain decoding model that would generalize across many different cognitive tasks drawn from multiple cognitive domains. To tackle this problem, we proposed amultidomainbrain decoder that automatically learns the spatiotemporal dynamics of brain response within a short time window using a deep learning approach. We evaluated the decoding model on a large population of 1200 participants, under 21 different experimental conditions spanning six different cognitive domains, acquired from the Human Connectome Project task-fMRI database. Using a 10s window of fMRI response, the 21 cognitive states were identified with a test accuracy of 90% (chance level 4.8%). Performance remained good when using a 6s window (82%). It was even feasible to decode cognitive states from a single fMRI volume (720ms), with the performance following the shape of the hemodynamic response. Moreover, a saliency map analysis demonstrated that the high decoding performance was driven by the response of biologically meaningful brain regions. Together, we provide an automated tool to annotate human brain activity with fine temporal resolution and fine cognitive granularity. Our model shows potential applications as a reference model for domain adaptation, possibly making contributions in a variety of domains, including neurological and psychiatric disorders.
Enhancer Remodeling Promotes Tumor-Initiating Activity in NRF2-Activated Non-Small Cell Lung Cancers
Authors: Okazaki Keito , Anzawa Hayato , Liu Zun , Ota Nao , Kitamura Hiroshi , Onodera Yoshiaki , Alam Md. Morshedul , Matsumaru Daisuke , Suzuki Takuma , Katsuoka Fumiki , Tadaka Shu , Motoike Ikuko , Watanabe Mika , Sakurada Akira , Okada Yoshinori , Yamamoto Masayuki , Suzuki Takashi , Kinoshita Kengo , Sekine Hiroki , Motohashi Hozumi
Published: April 2020

Transcriptional dysregulation, which can be caused by genetic and epigenetic alterations, is a fundamental feature of many cancers. A key cytoprotective transcriptional activator, NRF2, is often aberrantly activated in non-small cell lung cancers (NSCLCs) and supports both aggressive tumorigenesis and therapeutic resistance. Herein, we found that persistently activated NRF2 in NSCLCs generates enhancers at gene loci that are not normally regulated by transiently activated NRF2 under physiological conditions. Elevated accumulation of CEBPB in NRF2-activated NSCLCs was found to be one of the prerequisites for establishment of the unique NRF2-dependent enhancers, among whichNOTCH3enhancer was shown to be critical for the promotion of tumor-initiating activity. Enhancer remodeling mediated by NRF2-CEBPB cooperativity promotes tumor-initiating activity and drives malignancy of NRF2-activated NSCLCs via establishment of the NRF2-NOTCH3 regulatory axis.
Advanced computational and statistical multiparametric analysis of Susceptibility-Weighted Imaging to characterize gliomas and brain metastases
Authors: Ieva Antonio Di , Russo Carlo , Le Reste Pierre-Jean , Magnussen John S. , Heller Gillian
Published: April 2020

Susceptibility-weighted imaging (SWI) is a technique useful for evaluation of the internal structures of brain tumors, including microvasculature and microbleeds. Intratumoral patterns of magnetic susceptibility can be quantified by means of fractal analysis. Here, we propose a radiomics methodological pipeline to merge advanced fractal-based computational modelling with statistical analysis to objectively characterize the fingerprint of gliomas and brain metastases. Forty-seven patients with glioma (grades II-IV, according to the WHO 2016 classification system) and fourteen with brain metastases underwent 3 Tesla MRI using a SWI protocol. All images underwent computational analysis aimed to quantify three Euclidean parameters (related to tumor and SWI volume) and five fractal-based parameters (related to the pixel distribution and geometrical complexity of the SWI patterns). Principal components analysis, linear and quadratic discriminant analysis, K-nearest neighbor and support vector machine methods were used to discriminate between tumor types. The combination of parameters offered an objective evaluation of the SWI pattern in gliomas and brain metastases. The model accurately predicted 88% of glioblastoma, according to the quantification of intratumoral SWI features, failing to discriminate the other types. SWI is not normally used to classify brain tumors, however fractal-based multi-parametric computational analysis can be used to characterize intratumoral SWI patterns to objectively quantify tumors-related features. Specific parameters still have to be identified to provide completely automatic computerized differential diagnosis.
Chromosome-scale de novo diploid assembly of the apple cultivar ‘Gala Galaxy’
Authors: Broggini Giovanni A.L. , Schlathölter Ina , Russo Giancarlo , Copetti Dario , Yates Steven A. , Studer Bruno , Patocchi Andrea
Published: April 2020

Apple (Malus × domestica) is one of the most important fruit crops in terms of worldwide production. Due to its self-incompatibility system and the long juvenile period, breeding of new apple cultivars combining traits desired by growers (e.g. yield, pest and disease resistance) and consumers (e.g. fruit size, color, and flavor) is a long and complex process. Genomics-assisted breeding strategies can facilitate the selection of germplasm leading to new cultivars. While the most complete apple genome assemblies available to date are from anther-derived homozygous lines, de novo assembly of apple genomes encompassing the natural heterozygosity remains challenging. Using long- and short-read sequencing technologies in combination with optical mapping, we de novo assembled a diploid and heterozygous genome of the apple cultivar ‘Gala Galaxy’. This approach resulted in 154 hybrid scaffolds (N50 = 34.3 Mb) spanning 999.9 Mb and in 414.7 Mb of unscaffolded sequences. Anchoring 31 scaffolds with a genetic map was sufficient to represent an entire haploid genome of 17 pseudomolecules (719.4 Mb). The remaining sequences were assembled in a second set of 17 pseudomolecules, which spanned 601 Mb, leaving 80.6 Mb of unplaced sequences. A total of 41,264 genes were annotated using 74,900 transcripts derived from RNA sequencing of pooled leaf tissue samples. This study provides a high-quality diploid reference genome sequence encompassing the natural heterozygosity of the widely popular cultivar ‘Gala Galaxy’. The DNA sequence resources and the assembly described here will serve as a solid foundation for fundamental and applied apple breeding research.
Genome sequence of the banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae) and its symbionts
Authors: Mathers Thomas C. , Mugford Sam T. , Hogenhout Saskia A. , Tripathi Leena
Published: April 2020

The banana aphid, Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae), is a major pest of cultivated bananas (Musa spp., order Zingiberales), primarily due to its role as a vector of Banana bunchy top virus (BBTV), the most severe viral disease of banana worldwide. Here, we generated a highly complete genome assembly of P. nigronervosa using a single PCR-free Illumina sequencing library. Using the same sequence data, we also generated complete genome assemblies of the P. nigronervosa symbiotic bacteria Buchnera aphidicola and Wolbachia. To improve our initial assembly of P. nigronervos a we developed a k-mer based deduplication pipeline to remove genomic scaffolds derived from the assembly of haplotigs (allelic variants assembled as separate scaffolds). To demonstrate the usefulness of this pipeline, we applied it to the recently generated assembly of the aphid Myzus cerasi, reducing the duplication of conserved BUSCO genes by 25%. Phylogenomic analysis of P. nigronervos a, our improved M. cerasi assembly, and seven previously published aphid genomes, spanning three aphid tribes and two subfamilies, reveals that P. nigronervos a falls within the tribe Macrosiphini, but is an outgroup to other Macrosiphini sequenced so far. As such, the genomic resources reported here will be useful for understanding both the evolution of Macrosphini and for the study of P. nigronervosa. Furthermore, our approach using low cost, high-quality, Illumina short-reads to generate complete genome assemblies of understudied aphid species will help to fill in genomic black spots in the diverse aphid tree of life.
Genome-wide chromatin binding of transcriptional corepressor Topless-related 1 inArabidopsis
Authors: Griebel Thomas , Lapin Dmitry , Kracher Barbara , Concia Lorenzo , Benhamed Moussa , Parker Jane E.
Published: April 2020

Timely and specific regulation of gene expression is critical for plant responses to environmental and developmental cues. Transcriptional coregulators have emerged as important factors in gene expression control, although they lack DNA-binding domains and the mechanisms by which they are recruited to and function at the chromatin are poorly understood. Plant Topless-related 1 (TPR1), belonging to a family of transcriptional corepressors found across eukaryotes, contributes to immunity signaling inArabidopsis thalianaand wild tobacco. We performed chromatin immunoprecipitation and sequencing (ChIP-seq) on anArabidopsis TPR1-GFPexpressing transgenic line to characterize genome-wide TPR1-chromatin associations. The analysis revealed ∼1400 genes bound by TPR1, with the majority of binding sites located at gene upstream regions. Among the TPR1 bound genes, we find not only regulators of immunity but also genes controlling growth and development. To support further analysis of TPR1-chromatin complexes and other transcriptional corepressors in plants, we provide two ways to access the processed ChIP-seq data and enable their broader use by the research community.
The role of the meningeal lymphatic system in local inflammation and trigeminal nociception implicated in migraine pain
Authors: Mikhailov Nikita , Koroleva Kseniia , Abdollahzadeh Ali , Giniatullina Raisa , Gafurov Oleg , Malm Tarja , Sierra Alejandra , Tohka Jussi , Noe Francesco , Giniatullin Rashid
Published: April 2020

Background

A system of lymphatic vessels has been recently characterized in the meninges, with a postulated role in ‘cleaning’ the brain via cerebral fluid drainage. As meninges are the origin site of migraine pain, we hypothesized that malfunctioning of the lymphatic system should affect the local trigeminal nociception. To test this hypothesis, we studied nociceptive and inflammatory mechanisms in the meninges of K14-VEGFR3-Ig mice lacking the meningeal lymphatic system.

Methods

We recorded the spiking activity of meningeal afferents and estimated the local mast cells infiltration, calcitonin gene-related peptide (CGRP) and cytokine levels (basal and stimulated), as well as the dural trigeminal innervation in freshly-isolated hemiskull preparations from K14-VEGFR3-Ig (K14) or wild type C57BL/6 mice (WT).

Results

We found that the meningeal level of CGRP and of the pro-inflammatory cytokines IL12-p70 and TNFα (implicated in migraine) were reduced in the meninges of K14 mice. On the contrary, in the meninges of K14 mice, we found an increased level of the mast cell activator MCP-1 and, consistently, a larger number of dural mast cells. The other migraine-related pro-inflammatory cytokines did not differ between the two genotypes. The patterns of trigeminal innervation in meninges remained unchanged and we did not observe alterations in basal or ATP-induced nociceptive firing in the meningeal afferents.

Conclusions

In summary, the lack of meningeal lymphatic system does not induce migraine-like nociceptive stateper se, but leads to a new balance between pro- and antiinflammatory factors implicated in migraine mechanisms.
Novel class of OTU deubiquitinases regulate substrate ubiquitination uponLegionellainfection
Authors: Shin Donghyuk , Bhattacharya Anshu , Cheng Yi-Lin , Alonso Marta Campos , Mehdipour Ahmad Reza , van der Heden van Noort Gerbrand J. , Ovaa Huib , Hummer Gerhard , Dikic Ivan
Published: April 2020

Legionella pneumophilais a gram-negative pathogenic bacterium that causes Legionaries’ disease. TheLegionellagenome codes more than 300 effector proteins able to modulate host-pathogen interactions during infection. Among them are also enzymes altering the host-ubiquitination system including bacterial ligases and deubiquitinases. In this study, based on homology-detection screening on 305Legionellaeffector proteins, we identified twoLegionellaOTU-like deubiquitinases (LOT; LotB (Lpg1621/Ceg23) and LotC (Lpg2529), LotA (Lpg2248/Lem21) is already known). A crystal structure of LotC catalytic core (LotC14-310) was determined at 2.4 Å and compared with other OTU deubiquitinases, including LotB. Unlike the classical OTU-family, the structures ofLegionellaOTU-family (LotB and LotC) shows an extended helical lobe between the Cys-loop and the variable loop, which define a novel class of OTU-deubiquitinase. Despite structural differences in their helical lobes, both LotB and LotC interact with ubiquitin. LotB has an additional ubiquitin binding site (S1’) enabling specific cleavage of Lys63-linked poly-ubiquitin chains. By contrast, LotC only contains the S1 site and cleaves different species of ubiquitin chains. MS analysis of catalytically inactive LotB and LotC identified different categories of host-substrates for these two related DUBs. Together, our results provide new structural insights of bacterial OTU deubiquitinases and indicate distinct roles of bacterial deubiquitinases in host-pathogen interactions.
Binding Behavior of Microbial Functional Amyloids on Solid Surfaces
Authors: Yuca Esra , Kehribar Ebru Şahin , Şafak Şeker Urartu Özgür
Published: April 2020

Self-assembling protein subunits hold great potential as biomaterials with improved functions. Among the self-assembled protein structures functional amyloids are promising unique properties such as resistance to harsh physical and chemical conditions their mechanical strength, and ease of functionalization. Curli proteins, which are functional amyloids of bacterial biofilms can be programmed as intelligent biomaterials. In order to obtain controllable curli based biomaterials for biomedical applications, and to understand role of each of the curli forming monomeric proteins (namely CsgA and CsgB from Escherichia coli) we characterized their binding kinetics to gold, hydroxyapatite, and silica surfaces. We demonstrated that CsgA, CsgB, and their equimolar mixture have different binding strengths for different surfaces. On hydroxyapatite and silica surfaces, CsgB is the crucial element that determines the final adhesiveness of the CsgA-CsgB mixture. On the gold surface, on the other hand, CsgA controls the behavior of the mixture. Those findings uncover the binding behavior of curli proteins CsgA and CsgB on different biomedically valuable surfaces to obtain a more precise control on their adhesion to a targeted surface.
Joint epitope selection and spacer design for string-of-beads vaccines
Authors: Dorigatti Emilio , Schubert Benjamin
Published: April 2020

Motivation

Conceptually, epitope-based vaccine design poses two distinct problems: (1) selecting the best epitopes eliciting the strongest possible immune response, and (2) arranging and linking the selected epitopes through short spacer sequences to string-of-beads vaccines so as to increase the recovery likelihood of each epitope during antigen processing. Current state-of-the-art approaches solve this design problem sequentially. Consequently, such approaches are unable to capture the inter-dependencies between the two design steps, usually emphasizing theoretical immunogenicity over correct vaccine processing and resulting in vaccines with less effective immunogencity.

Results

In this work, we present a computational approach based on linear programming that solves both design steps simultaneously, allowing to weigh the selection of a set of epitopes that have great immunogenic potential against their assembly into a string-of-beads construct that provides a high chance of recovery. We conducted Monte-Carlo cleavage simulations to show that, indeed, a fixed set of epitopes often cannot be assembled adequately, whereas selecting epitopes to accommodate proper cleavage requirements substantially improves their recovery probability and thus the effective immunogenicity, pathogen, and population coverage of the resulting vaccines by at least two fold.

Availability

The software and the data analyzed are available athttps://github.com/SchubertLab/JessEV
Who are you? Inconsistent identity reporting in online labor markets
Authors: Kuselias Stephen
Published: April 2020

Purpose

Online labor pools continue to grow in popularity, serving as an inexpensive, readily available source of research data. Despite early skepticism, accounting research has generally found evidence that supports the use of these labor pools. However, one important distinction unique to online labor markets is the pre-screening process that qualifies participants for future studies. As the identity of online participants are generally unknown, researchers rely on participants’ self-reported identities to establish a pool of qualified respondents. This paper aims to provide evidence of the reliability of online participants’ answers to pre-screening questions.

Design/methodology/approach

Following the current literature’s recommendations on pre-screening candidates, I employ a multi-stage design using two similar surveys that are taken by each participant. I compare participants' answers on the first survey and the second survey to provide evidence on the consistency of their responses.

Findings

My results indicate that online participants are responding with substantial inconsistency to survey questions related to their social identity at a rate that may not be tolerable for many researchers. This has implications for researchers who use these online labor markets to represent a particular population of interest.

Originality/value

This study is the first to provide evidence on the consistency of online labor market participant responses. Additionally, it is the first to test the efficacy of current recommended guidelines for identifying populations of interest in the literature.
Innovation management in market-oriented SMEs: learning and internal arrangements for innovation
Authors: Didonet Simone , Diaz-Villavicencio Guillermo
Published: April 2020

Purpose

This study aims to investigate the role of market orientation (MO) in improving learning for innovation in small and medium-sized enterprises (SMEs) through the facilitation of the organisational structure and links to innovation.

Design/methodology/approach

The data for this research were collected through a survey that was applied to a sample of 169 SMEs in Ecuador. Existing scales were used to measure all the studied variables, i.e. MO, organisational structure for innovation, linkages and learning for innovation. The last three variables correspond to the characteristics of the innovation management process. Partial least square path modelling was used to analyse the data using the SmartPLS 2.0 software.

Findings

The results showed that MO enhances the learning for innovation in firms both directly and indirectly through improving organisational structure and linkages towards innovation. The research finding also showed that organisational structure for innovation is more important to enhance learning than linkages. Specifically, the mediation between MO and learning through linkages is smaller than the mediation through the organisational structure.

Practical implications

The study informs executives of the relevance of developing MO as a way of improving learning for innovation, which in turn, is favoured by an organisational structure that supports creativity and technological changes and by the internal and external linkages for innovation in market-oriented firms.

Originality/value

The findings of this study provide new insights regarding how MO can work together in an innovative context and highlight the importance of MO as an enabler of innovation characteristics in SMEs. This study also contributes to the existent innovation literature by shedding light on strategic questions regarding the development of innovation process in market-oriented SMEs. Specifically, it provides some evidence regarding the nature of innovation process in SMEs, which can orient future studies focused on the understanding of how successful innovation occurs.
Middle childhood vulnerability to drugs and alcohol
Authors: Ewin Rob , Reed Abi , Powell Lewis
Published: April 2020

Purpose

There are identified problems facing law enforcement in the correct approach to childhood drug and alcohol use at street level which can cause aggression, developmental, psychological problems and family conflict (Maher and Dixon, 1999). Childhood exposure to drugs and alcohol can encourage criminal activity, anti-social conduct and increased child-to-parent conflict (Brook et al., 1992; Reinherz et al., 2000; Coogan, 2011; McElhone, 2017).

Design/methodology/approach

The purpose of this study is to explore middle-childhood (11-15 years) experiences of drugs and alcohol through a survey to determine the earliest opportunity for the involvement of services based on the experiences of children.

Findings

The key findings are alcohol consumption in middle childhood is supported by parental alcohol provision; those in middle childhood are most likely to consume alcohol at home and drugs at street level (any place away from home including school, young clubs, open public space and parks); children in middle childhood use mainly cannabis to experience euphoria, minimize childhood problems and to fulfill acquisitive desire; and late childhood shows movement away from street-level drug use to drug use in private spaces with friends and increased levels of experiential or social drinking, within spaces shared by larger social groups.

Practical implications

The authors propose that a health-orientated early help model in middle childhood should be adopted, with support such as community- and school-based child and parental drug education; wider information sharing between schools, policing and health authorities at an early stage to support a contextual safeguarding approach; and recognition and recording practices around middle childhood which is an acute phase for children to become involved in drug and alcohol consumption.

Originality/value

Children’s drug use in middle childhood is often not recorded, and the problem can be associated with simple ill-parenting approaches. The authors believe that little was known about the spaces and occurrence of drug and alcohol use in middle childhood.
Older people's perspectives on living in integrated housing and care settings: the case of extra care housing
Authors: Cameron Ailsa , Johnson Eleanor K , Evans Simon
Published: April 2020

Purpose

This paper explores residents' perceptions and experiences of extra care housing as an integrated model of housing with care.

Design/methodology/approach

Data were collected in a longitudinal qualitative study based on four extra care housing schemes. Data from interviews with residents, care workers, managers and local commissioners were analysed thematically.

Findings

The integration of housing with care enabled many older people to manage their care proactively. However, the increasing number of residents with complex health and care needs, including chronic illness, led some residents to question the ability of the model to support residents to live independently.

Research limitations/implications

The study struggled to recruit sufficient residents from the specialist dementia setting who were able to communicate their consent to take part in the research. In addition, the quality of qualitative data collected in interviews with participants at this setting reduced over successive rounds of interviews.

Practical implications

The study suggests the need to ensure that residents are fully informed about levels of care and support is available when considering a move into extra care housing.

Originality/value

This paper provides a timely opportunity to consider extra care housing as an example of an integrated housing service, particularly in light of the current challenges facing the sector.
Entrepreneurial university ecosystems and graduates' career patterns: do entrepreneurship education programmes and university business incubators matter?
Authors: Guerrero Maribel , Urbano David , Gajón Eduardo
Published: April 2020

Purpose

This paper provides insights about how graduates' career patterns (i.e. academic entrepreneur, self-employed or paid employed) are influenced by entrepreneurial university ecosystems (i.e. incubators and entrepreneurship education programs).

Design/methodology/approach

By adopting Douglas and Shepherd's utility-maximising function, the influence of one entrepreneurial university ecosystem on graduates' career choices was tested using a sample of 11,512 graduates from the Monterrey Institute of Technology and Higher Education (ITESM) in Mexico.

Findings

Our results show the critical role of entrepreneurial universities ecosystems in facilitating employability options as academic entrepreneurship for ITESM's graduates. The study shows some insights about how graduates' risk aversion and work effort are positively influenced by the university business incubator and entrepreneurship education programs, respectively.

Practical implications

Diverse implications for stakeholders have emerged from our results. These implications are associated with potential benefits of implementing programmes oriented to engage academic entrepreneurship within Latin American universities.

Originality/value

Entrepreneurial universities provide a range of employability alternatives for their students, such as to be self-employed, academic entrepreneurs or paid employees. In this scenario, entrepreneurial universities have configured entrepreneurial ecosystems (educational programmes, business incubators and other infrastructures) to support potential entrepreneurs (students, academics, staff and alumni). Despite the relevance of the environmental conditions on individuals' occupational choices, few studies have explored the role of the entrepreneurial university ecosystems on graduates' employability. In this vein, our study contributes to some academic discussions: (1) the role of context on career choice models (Ilougaet al., 2014; Sieger and Monsen, 2015), (2) the role of incubators and entrepreneurship education on fostering academic entrepreneurship on the graduates' community (Nabiet al., 2017; Goodet al., 2019; Guerrero and Urbano, 2019a) and (3) the effectiveness of the entrepreneurial university ecosystems on graduates' employability (Herreraet al., 2018; Wrightet al., 2017).
Women's progress in the Arab world: classroom–boardroom pipeline
Authors: Kemp Linzi J
Published: April 2020

Purpose

The purpose of this conceptual paper was to investigate the contribution of the “Pipeline”, as a metaphor for building theory about Women-on-Boards (WoB) in the Arab world.

Design/methodology/approach

Narratives about women's progress in Arab countries were collected from a range of sources and content was analysed to identify emergent themes about pipeline.

Findings

Themes were identified of the pipeline metaphor that explained phenomena and generated solutions to employ, retain and advance women to board directorships; from higher education (“bulging”/“bursting” pipeline) through employment (“leaking” pipeline) to boardroom (“blocked” pipeline).

Research limitations/implications

Generalisation of these study results is limited by geographical context of this research. An implication is for further international studies on metaphor identification for women's progress.

Practical implications

Relevant metaphor-in-use required to generate company policy and praxis towards WoB in the Arab world.

Originality/value

The first academic study to investigate the value of metaphor for effect on women's progress in Arab countries. Novel metaphor identification is proposed to think and see women's experiences in cultural context.
Negative publicity and potential applicants' intention to apply amid a discrimination scandal: a moderated mediation model
Authors: Ouyang Zhe , Zhang Yuanyuan , Hu Xi
Published: April 2020

Purpose

The exposure of recruitment discrimination often leads to negative publicity, which can substantially affect organizational attractiveness and the behavioral intentions of stakeholders. Therefore, this study aims to examine the relationship between negative publicity and intention to pursue a job, with organizational attractiveness as a mediator and perceived corporate social responsibility (CSR) and corporate product quality (CPQ) as two moderators.

Design/methodology/approach

A survey completed by 382 college students in three universities in Nanjing, China, was used to empirically test the research hypotheses. The respondents were asked their intention to apply for a job at Meituan after the exposure of its recruitment discrimination scandal in 2017.

Findings

Perceived negative publicity negatively influences intention to pursue employment via organizational attractiveness. In addition, moderated path analysis indicated that perceived CSR strengthens and perceived CPQ weakens the direct effect of perceived negative publicity on organizational attractiveness and its indirect effect on intention to pursue employment.

Research limitations/implications

Future research should seek to replicate these findings in other contexts and populations, including people who are not new to the job market and to control additional firm-level and contextual variables.

Originality/value

This research confirms a moderated mediation model positioning organizational attractiveness as a mediator of negative publicity's effects on intention to pursue employment and organizational image as a moderator of such effects. This study also contributes to the debate concerning the effect of corporate image by demonstrating opposing effects of its different dimensions amid a discrimination scandal.