bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-immunoprecipitation with MYR1 identifies three additional proteins within theToxoplasmaparasitophorous vacuole required for translocation of dense granule effectors into host cells
Authors: Cygan Alicja M. , Theisen Terence C. , Mendoza Alma G. , Marino Nicole D. , Panas Michael W. , Boothroyd John C. 
Published: December 2019

AbstractToxoplasma gondiiis a ubiquitous, intracellular protozoan that extensively modifies infected host cells through secreted effector proteins. Many such effectors must be translocated across the parasitophorous vacuole (PV) in which the parasites replicate, ultimately ending up in the host cytosol or nucleus. This translocation has previously been shown to be dependent on five parasite proteins: MYR1, MYR2, MYR3, ROP17, and ASP5. We report here the identification of several MYR1-interacting and novel PV-localized proteins via affinity purification of MYR1, including TGGT1_211460 (dubbed MYR4), TGGT1_204340 (dubbed GRA54) and TGGT1_270320 (PPM3C). Further, we show that three of the MYR1-interacting proteins, GRA44, GRA45, and MYR4, are essential for the translocation of theToxoplasmaeffector protein GRA16, and for the upregulation of human c-Myc and cyclin E1 in infected cells. GRA44 and GRA45 contain ASP5-processing motifs, but like MYR1, processing at these sites appears to be nonessential for their role in protein translocation. These results expand our understanding of the mechanism of effector translocation inToxoplasmaand indicate that the process is highly complex and dependent on at least eight discrete proteins.ImportanceToxoplasmais an extremely successful intracellular parasite and important human pathogen. Upon infection of a new cell,Toxoplasmaestablishes a replicative vacuole and translocates parasite effectors across this vacuole to function from the host cytosol and nucleus. These effectors play a key role in parasite virulence. The work reported here newly identifies three parasite proteins that are necessary for protein translocation into the host cell. These results significantly increase our knowledge of the molecular players involved in protein translocation inToxoplasma-infected cells, and provide additional potential drug targets.
How community adaptation affects biodiversity-ecosystem functioning relationships
Authors: Aubree Flora , David Patrice , Jarne Philippe , Loreau Michel , Mouquet Nicolas , Calcagno Vincent 
Published: December 2019

SummaryEvidence is growing that evolutionary dynamics can impact biodiversity-ecosystem functioning (BEF) relationships. However the nature of such impacts remains poorly understood. Here we use a modelling approach to compare random communities, with no trait evolutionary fine-tuning, and co-adapted communities, where traits have co-evolved, in terms of emerging biodiversity-productivity, biodiversitystability, and biodiversity-invasion relationships. Community adaptation impacted most BEF relationships, sometimes inverting the slope of the relationship compared to random communities. Biodiversity-productivity relationships were generally less positive among co-adapted communities, with reduced contribution of sampling effects. The effect of community-adaptation, though modest regarding invasion resistance, was striking regarding invasion tolerance: co-adapted communities could remain very tolerant to invasions even at high diversity. BEF relationships are thus contingent on the history of ecosystems and their degree of community adaptation. Short-term experiments and observations following recent changes may not be safely extrapolated into the future, once eco-evolutionary feedbacks have taken place.
Mapping chromatin accessibility and active regulatory elements reveals new pathological mechanisms in human gliomas
Authors: Stępniak Karolina , Machnicka Magdalena A. , Mieczkowski Jakub , Macioszek Anna , Wojtaś Bartosz , Gielniewski Bartłomiej , Król Sylwia K. , Guzik Rafał , Dąbrowski Michał J. , Dramiński Michał , Jardanowska Marta , Grabowicz Ilona , Dziedzic Agata , Kranas Hanna , Sienkiewicz Karolina , Diamanti Klev , Kotulska Katarzyna , Grajkowska Wiesława , Roszkowski Marcin , Czernicki Tomasz , Marchel Andrzej , Komorowski Jan , Kaminska Bozena , Wilczyński Bartek 
Published: December 2019

SummaryChromatin structure and accessibility, and combinatorial binding of transcription factors to regulatory elements in genomic DNA control transcription. Genetic variations in genes encoding histones, epigenetics-related enzymes or modifiers affect chromatin structure/dynamics and result in alterations in gene expression contributing to cancer development or progression. Gliomas are brain tumors frequently associated with epigenetics-related gene deregulation. We performed whole-genome mapping of chromatin accessibility, histone modifications, DNA methylation patterns and transcriptome analysis simultaneously in multiple tumor samples to unravel novel epigenetic dysfunctions driving gliomagenesis. Based on the results of the integrative analysis of the acquired profiles, we created an atlas of active enhancers and promoters in benign and malignant gliomas. We explored these elements and intersected with Hi-C data to uncover molecular mechanisms instructing gene expression in gliomas.SignificanceEpigenetics-driven deregulation of gene expression accompanies cancer development, but its comprehensive characterization in cancer patients is fragmentary. We performed whole-genome profiling of gene expression, open chromatin, histone modifications and DNA-methylation profiles in the same samples from benign and malignant gliomas. Our study provides a first comprehensive atlas of active regulatory elements in gliomas, which allowed identification of the functional enhancers and promoters in patient samples. This comprehensive approach revealed epigenetic patterns influencing gene expression in benign gliomas and a new pathogenic mechanism involving FOXM1-driven network in glioblastomas. This atlas provides a common set of elements for cross-comparisons of existing and new datasets, prompting novel discoveries and better understanding of gliomagenesis.HighlightsWe provide an atlas of cis-regulatory elements active in human gliomasEnhancer-promoter contacts operating in gliomas are revealedDiverse enhancer activation is pronounced in malignant gliomasChromatin loop activates FOXM1-ANXA2R pathological network in glioblastomas.
Recovering individual haplotypes and a contiguous genome assembly from pooled long read sequencing of the diamondback moth (Lepidoptera: Plutellidae)
Authors: Whiteford Samuel , van’t Hof Arjen E. , Krishna Ritesh , Marubbi Thea , Widdison Stephanie , Saccheri Ilik J. , Guest Marcus , Morrison Neil I. , Darby Alistair C. 
Published: December 2019

AbstractBackgroundRecent advances in genomics have addressed the challenge that divergent haplotypes pose to the reconstruction of haploid genomes. However for many organisms, the sequencing of either field-caught individuals or a pool of heterogeneous individuals is still the only practical option. Here we present methodological approaches to achieve three outcomes from pooled long read sequencing: the generation of a contiguous haploid reference sequence, the sequences of heterozygous haplotypes; and reconstructed genomic sequences of individuals related to the pooled material.ResultsPacBio long read sequencing, Dovetail Hi-C scaffolding and linkage map integration yielded a haploid chromosome-level assembly for the diamondback moth (Plutella xylostella), a global pest of Brassica crops, from a pool of related individuals. The final assembly consisted of 573 scaffolds, with a total assembly size of 343.6Mbp a scaffold N50 value of 11.3Mbp (limited by chromosome size) and a maximum scaffold size of 14.4Mbp. This assembly was then integrated with an existing RAD-seq linkage map, anchoring 95% of the assembled sequence to defined chromosomal positions.ConclusionsWe describe an approach to resolve divergent haplotype sequences and describe multiple validation approaches. We also reconstruct individual genomes from pooled long-reads, by applying a recently developed k-mer binning method.
Genomic differentiation and intercontinental population structure of mosquito vectorsCulex pipiens pipiensandCulex pipiens molestus
Authors: Yurchenko Andrey A. , Masri Reem A. , Khrabrova Natalia V. , Sibataev Anuarbek K. , Fritz Megan L. , Sharakhova Maria V. 
Published: December 2019

AbstractUnderstanding the population structure and mechanisms of taxa diversification is important for organisms responsible for the transmission of human diseases. Two vectors of West Nile virus,Culex pipiens pipiensandCx. p. molestus, exhibit epidemiologically important behavioral and physiological differences, but the whole-genome divergence between them was unexplored. In this study, we re-sequenced and compared the whole genomes of 40 individual mosquitoes from four locations in Eurasia and North America: the Republic of Belarus, the Kyrgyz Republic, and the United States of America. Principal Component, ADMIXTURE, and neighbor joining analyses of the nuclear genomes identified two intercontinental, monophyletic clusters ofCx. p. pipiensandCx. p. molestus.The third cluster, having a polyphyletic origin, was formed byCx. p. pipiensandCx. quinquefasciatusfrom the USA. The level of genomic differentiation between the subspecies was uniform along chromosomes. The ADMIXTURE analysis determined signatures of admixture in allCx. p. pipenspopulations but not inCx. p. molestuspopulations. Comparison of mitochondrial genomes among the specimens showed a paraphyletic origin of the major haplogroups between the subspecies but a monophyletic structure between the continents. Thus, our study identified thatCx. p. molestusandCx. p. pipiensrepresent different evolutionary units with monophyletic origin that have undergone incipient ecological speciation.
Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC
Authors: Ventura Guilherme , Moreira Sofia , Barros-Carvalho André , Osswald Mariana , Morais-de-Sá Eurico 
Published: December 2019

AbstractApical-basal polarity underpins the formation of specialized epithelial barriers that are critical for metazoan physiology. Although apical-basal polarity is long known to require the basolateral determinants Lethal Giant Larvae (Lgl), Discs Large (Dlg) and Scribble (Scrib), mechanistic understanding of their function is limited. Lgl plays a role as an aPKC inhibitor, but it remains unclear whether Lgl also forms a complex with Dlg or Scrib. Using fluorescence recovery after photobleaching, we show that Lgl does not form immobile complexes at the lateral domain ofDrosophilafollicle cells. Optogenetic depletion of plasma membrane phosphatidylinositol 4,5-biphosphate (PIP2) or Dlg removal accelerate Lgl cortical dynamics. However, whereas Lgl turnover relies on PIP2binding, Dlg and Scrib are only required for Lgl localization and dynamic behavior in the presence of aPKC function. Furthermore, light-induced oligomerization of basolateral proteins indicate that Lgl is not part of the Scrib-Dlg complexin vivo. Thus, Scrib-Dlg are necessary to repress aPKC activity in the lateral domain but do not provide cortical binding sites for Lgl. Our work therefore highlights that Lgl does not act in a complex but in parallel with Scrib-Dlg to antagonize apical determinants.
Proteome-wide structural probing of low-abundant protein interactions by crosslinking
Authors: Fürsch Julius , Kammer Kai-Michael , Kreft Stefan G. , Beck Martin , Stengel Florian 
Published: December 2019

AbstractProteome-wide crosslinking studies have spurred great interest as they facilitate structural probing of protein interactions in living cells and organisms. However, current studies have a bias for high-abundant proteins. In a paradigm shift, we demonstrate both experimentally and by a kinetic model that this bias is caused by the propensity of crosslinks to preferentially form on high abundant proteins and not by the inability to detect crosslinks due to limitations in current technology. We further show, by using both an in-vitro mimic of a crowded cellular environment and eukaryotic cell lysates, that parameters optimized towards a pseudo 1storder kinetics model result in a significant 3 to 10-fold overall increase in the detection of lower-abundant proteins on a proteome-wide scale. Our study therefore explains the cause of a major limitation in current proteome-wide crosslinking studies and demonstrates how to address a larger part of the proteome by crosslinking.
Population-specific recombination maps from segments of identity by descent
Authors: Zhou Ying , Browning Brian L. , Browning Sharon R. 
Published: December 2019

ABSTRACTRecombination rates vary significantly across the genome, and estimates of recombination rates are needed for downstream analyses such as haplotype phasing and genotype imputation. Existing methods for recombination rate estimation are limited by insufficient amounts of informative genetic data or by high computational cost. We present a method for using segments of identity by descent to infer recombination rates. Our method can be applied to sequenced population cohorts to obtain high-resolution, population-specific recombination maps. We use our method to generate new recombination maps for European Americans and for African Americans from TOPMed sequence data from the Framingham Heart Study (1626 unrelated individuals) and the Jackson Heart Study (2046 unrelated individuals). We compare our maps to existing maps using the Pearson correlation between estimated recombination rates. In Europeans we use the deCODE map, which is based on a very large set of Icelandic family data (126,407 meioses), as a gold standard against which to compare other maps. Our European American map has higher accuracy at fine-scale resolution (1-10kb) than linkage disequilibrium maps from the HapMap and 1000 Genomes projects. Our African American map has much higher accuracy than an admixture-based map that is derived from a similar number individuals, and similar accuracy at fine scales (1-10kb) to an admixture-based map that is derived from 15 times as many individuals.
Cocaine memory reactivation induces functional adaptations of fast-spiking interneurons in the rat medial prefrontal cortex
Authors: Jorgensen Emily T. , Gonzalez Angela E. , Harkness John H. , Hegarty Deborah M. , Burchi Delta J. , Aadland Jake A. , Aicher Sue A. , Sorg Barbara A. , Brown Travis E. 
Published: December 2019

AbstractPerineuronal nets (PNNs) are specialized extracellular matrix structures that ensheathe parvalbumin-containing fast-spiking interneurons (PV FSIs) and play a key role in neuroplasticity. We previously showed that PNNs within the prelimbic prefrontal cortex (PL PFC) are required for the maintenance of cocaine-associated memories following cocaine memory reactivation. However, how cocaine memory reactivation affects PNNs, PV, and corresponding changes in PV FSI function are unknown. In this study, we characterized the electrophysiological properties of PV FSIs and corresponding changes in PNN and PV intensity within the PL PFC prior to and after cocaine memory reactivation. Adult male Sprague-Dawley rats were trained to acquire cocaine-conditioned place preference (CPP) and, following cocaine-CPP memory reactivation (30 m, 2 h, and 24 h post-reactivation), we measured PNN intensity (determined by Wisteria floribunda agglutinin [WFA] staining) as well as PV intensity using immunohistochemistry. The intensity of PV staining was reduced at all time points following memory reactivation with no changes in WFA intensity. Using whole-cell electrophysiology we found a reduction in the number of action potentials at 30 m and 2 h that returned to control levels by 24 h. The attenuation in firing was accompanied by a presumed compensatory increase in excitatory synaptic transmission, which was corroborated by an increase in VGluT1 puncta apposing PV/PNN neurons. Collectively, our results indicate that cocaine memory reactivation decreases PV intensity, which may play a role in decreasing excitation of PV FSIs. Thus, the inhibitory tone onto pyramidal neurons may be decreased following memory reactivation, resulting in an increase in PFC output to promote cocaine-seeking behaviors.
Architecture as an agency of resilience in urban armed conflicts
Authors: Kittana Abdalrahman M.G. , Meulder Bruno De 
Published: December 2019

PurposeContemporary wars are continuously striking population centres across the globe with devastating consequences of destruction and annihilation, and leading to mass casualties within civilians. The purpose of this paper is to question the role of architecture and urban tissue in packing up civilians’ resilience and survival practices during urban warfare.Design/methodology/approachThe investigation is based on critical spatial analysis of survival narratives obtained from an empirical study conducted in the city of Nablus in Palestine.FindingsThis paper shows that, due to its unique and highly complex socio-spatial entanglement, thekasbahof Nablus represents a paradigm in the (re)creation of community resilience. This paradigm is based on the interaction of three main elements: a multi-layered urban tissue accumulated along 2,000 years of urban evolution; a thick matrix of cultural and social constructs; and the lifting and switching of a lot of social conventions related to space during times of war.Originality/valueThe agency of architecture in supporting civilian survival practices during urban warfare is visited, nevertheless only partially unpacked by a number of prominent studies. This paper provides a deeper level of investigation and understanding of the interplay between the architecture of the city and resilience capacity.
Uncertainty and adaptation in the context of Brexit
Authors: Duarte Alonso Abel , Kok Seng , O'Brien Seamus 
Published: December 2019

PurposeThe purpose of this study is to propose a framework to understand firms’ adaptation to uncertainty and change, specifically, in regards to the perceived impacts of the Brexit phenomenon. In doing so, the study considers entrepreneurial action theory (EAT) and the dynamic capabilities approach (DCA).Design/methodology/approachFace-to-face interviews were conducted with owners and managers of 34 family-run firms operating in Italy’s Prosecco Superiore and Spain’s Cava industries.FindingsThe element of uncertainty because of the imminent Brexit decision clearly emerged and was demonstrated through various effects on firms including the falling British Pound. The findings revealed that combining the EAT and the DCA provides a stronger explanation in understanding adaptation to uncertainty. For example, sensing (DCA) was suggested to be a precursor of opportunity attention and evaluation (EAT) or recognising opportunities and was subsequently manifested by operators’ action or seizing (DCA), including through more involvement in exports and wine tourism.Originality/valueThe study is one of the few efforts to date to examine the potential impacts of an uncontrollable contemporary phenomenon, and ways to adapt from the perspective of entrepreneurs involved in a traditional and socioeconomically significant industry. The different adaptive strategies that emerged from the findings can provide practical insights. The proposed framework emphasises the theoretical and practical value of understanding adaptation through the lens of the adopted theoretical foundations.
Introducing the do-it-yourself concept in Egypt – the case of House Wonders
Authors: Ayman Ahmed , Shahin Mahitab Mohamed 
Published: December 2019

Learning outcomes
Firms that are selling a relatively new market offering have to create the need for that offering. House Wonders entered a market that was not that well-informed about their market offering, and thus, have experimented with several communication channels that had different cost, and naturally different results. The purpose of this case is to encourage the students to compare and contrast the different communication methods, discuss their usage by House Wonders and come up with the best communication strategy.

Case overview/synopsis
This case simulates the challenges faced by a department store that is specialized in home improvement and hardware that recently started operations in Egypt. The store heavily emphasizes the role of “do it yourself” products, which is relatively new to the Egyptian customers. The case study presents the current economic conditions in Egypt, the company profile of the store and its parent company. The following sections involve explaining the concept of “do it yourself,” and other competitive advantages the store, House Wonders, has and how the management team managed to make the best out of it. The case study is concluded by explaining that in spite of all their efforts, the team is still faced with a number of challenges that are yet to be resolved, the most important of which is how to better reach the targeted segment.

Complexity academic level
Undergraduate/ MBA.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS 8: Marketing.
Minimizing the influence of dynamic rumors based on community structure
Authors: Wu Qingqing , Zhao Xianguan , Zhou Lihua , Wang Yao , Yang Yudi 
Published: December 2019

PurposeWith the rapid development of internet technology, open online social networks provide a broader platform for information spreading. While dissemination of information provides convenience for life, it also brings many problems such as security risks and public opinion orientation. Various negative, malicious and false information spread across regions, which seriously affect social harmony and national security. Therefore, this paper aims to minimize negative information such as online rumors that has attracted extensive attention. The most existing algorithms for blocking rumors have prevented the spread of rumors to some extent, but these algorithms are designed based on entire social networks, mainly focusing on the microstructure of the network, i.e. the pairwise relationship or similarity between nodes. The blocking effect of these algorithms may be unsatisfactory in some networks because of the sparse data in the microstructure.Design/methodology/approachAn algorithm for minimizing the influence of dynamic rumor based on community structure is proposed in this paper. The algorithm first divides the network into communities, and integrates the influence of each node within communities and rumor influence probability to measure the influence of each node in the entire network, and then selects key nodes and bridge nodes in communities as blocked nodes. After that, a dynamic blocking strategy is adopted to improve the blocking effect of rumors.FindingsCommunity structure is one of the most prominent features of networks. It reveals the organizational structure and functional components of a network from a mesoscopic level. The utilization of community structure can provide effective and rich information to solve the problem of data sparsity in the microstructure, thus effectively improve the blocking effect. Extensive experiments on two real-world data sets have validated that the proposed algorithm has superior performance than the baseline algorithms.Originality/valueAs an important research direction of social network analysis, rumor minimization has a profound effect on the harmony and stability of society and the development of social media. However, because the rumor spread has the characteristics of multiple propagation paths, fast propagation speed, wide propagation area and time-varying, it is a huge challenge to improve the effectiveness of the rumor blocking algorithm.