bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome reconstruction of the non-culturable spinach downy mildew Peronospora effusa by metagenome filtering
Authors: Klein Joël , Neilen Manon , van Verk Marcel , Van den Ackerveken Guido , Dutilh Bas E. 
Published: November 2019

Peronospora effusa (previously known as P. farinosa f. sp. spinaciae, and here referred to as Pfs) is an obligate biotrophic oomycete that causes downy mildew on spinach (Spinacia oleracea). To combat this destructive disease resistant cultivars are continually bred. However, new Pfs races rapidly break the employed resistance genes. To get insight into the gene repertoire of Pfs and identify infection-related genes, the genome of the first reference race, Pfs1, was sequenced, assembled, and annotated. Due to the obligate biotrophic nature of this pathogen, material for DNA isolation can only be collected from infected spinach leaves that, however, also contain many other microorganisms. The obtained sequences are, therefore, considered a metagenome. To filter and obtain Pfs sequences we utilized the CAT tool to taxonomically annotate ORFs residing on long sequences of a genome pre-assembly. This study is the first to show that CAT filtering performs well on eukaryotic contigs. Based on the taxonomy, determined on multiple ORFs, contaminating long sequences and corresponding reads were removed. Filtered reads were re-assembled to provide a clean and improved Pfs genome sequence of 32.40 Mbp consisting of 8,635 scaffolds. Transcript sequencing of a range of infection time points aided the prediction of a total of 13,277 gene models, including 99 RXLR(-like) effector, and 14 putative Crinkler genes. Comparative analysis identified common features in the secretomes of different obligate biotrophic oomycetes, regardless of their phylogenetic distance. Their secretomes are generally smaller, compared to hemibiotrophic and necrotrophic oomycete species. We observe a reduction in proteins involved cell wall degradation, in Nep1-like proteins (NLPs), proteins with PAN/apple domains, and host translocated effectors. The genome of Pfs1 will be instrumental in studying downy mildew virulence and for understanding the molecular adaptations by which new isolates break spinach resistance.
Strong information-limiting correlations in early visual areas
Authors: Montijn Jorrit S , Liu Rex G , Aschner Amir , Kohn Adam , Latham Peter E , Pouget Alexandre 
Published: November 2019

AbstractIf the brain processes incoming data efficiently, information should degrade little between early and later neural processing stages, and so information in early stages should match behavioral performance. For instance, if there is enough information in a visual cortical area to determine the orientation of a grating to within 1 degree, and the code is simple enough to be read out by downstream circuits, then animals should be able to achieve that performance behaviourally. Despite over 30 years of research, it is still not known how efficient the brain is. For tasks involving a large number of neurons, the amount of information encoded by neural circuits is limited by differential correlations. Therefore, determining how much information is encoded requires quantifying the strength of differential correlations. Detecting them, however, is difficult. We report here a new method, which requires on the order of 100s of neurons and trials. This method relies on computing the alignment of the neural stimulus encoding direction, f′, with the eigenvectors of the noise covariance matrix, Σ. In the presence of strong differential correlations, f′ must be spanned by a small number of the eigenvectors with largest eigenvalues. Using simulations with a leaky-integrate-and-fire neuron model of the LGN-V1 circuit, we confirmed that this method can indeed detect differential correlations consistent with those that would limit orientation discrimination thresholds to 0.5-3 degrees. We applied this technique to V1 recordings in awake monkeys and found signatures of differential correlations, consistent with a discrimination threshold of 0.47-1.20 degrees, which is not far from typical discrimination thresholds (1-2 deg). These results suggest that, at least in macaque monkeys, V1 contains about as much information as is seen in behaviour, implying that downstream circuits are efficient at extracting the information available in V1.
Specificity in auxin responses is not explained by the promoter preferences of activator ARFs
Authors: Lanctot Amy , Taylor-Teeples Mallorie , Oki Erika A. , Nemhauser Jennifer L. 
Published: November 2019

AbstractAuxin is essential for almost every developmental process within plants. How a single small molecule can lead to a plethora of downstream responses has puzzled researchers for decades. It has been hypothesized that one source for such diversity is distinct promoter-binding and activation preferences for different members of the AUXIN RESPONSE FACTOR (ARF) family of transcription factors. We systematically tested this hypothesis by engineering varied promoter sequences in a heterologous yeast system and quantifying transcriptional activation by ARFs from two species, Arabidopsis thaliana and Zea mays. By harnessing the user-defined and scalable nature of our synthetic system, we elucidated promoter design rules for optimal ARF function, discovered novel ARF-responsive promoters, and characterized the impact of ARF dimerization on their activation potential. We found no evidence for specificity in ARF-promoter interactions, suggesting that the diverse auxin responses observed in plants may be driven by factors outside the core auxin response machinery.
Encoding of social exploration by neural ensembles in the insular cortex
Authors: Miura Isamu , Sato Masaaki , Kunori Nobuo , Overton Eric T.N. , Nakai Junichi , Kawamata Takakazu , Nakai Nobuhiro , Takumi Toru 
Published: November 2019

SummaryThe insular cortex participates in diverse complex brain functions including sociality, yet little is known about their cellular bases. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely-moving and restrained social targets, we identified two subsets of AI neurons –a larger fraction of Social-ON cells and a smaller fraction of Social-OFF cells– that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which were preferentially active during exploration under particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons in encoding conjunctive information on social behavior and suggest that AI may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.
Effect of the divalent cations zinc and calcium on the structure and mechanics of reconstituted vimentin intermediate filaments
Authors: Wu Huayin , Shen Yinan , Wang Dianzhuo , Herrmann Harald , Goldman Robert D. , Weitz David A. 
Published: November 2019

AbstractDivalent cations in a concentration-dependent manner behave as effective crosslinkers of intermediate filaments (IFs) such as vimentin IF (VIF). These interactions have been mostly attributed to their multivalency. However, ion-protein interactions often depend on the ion species, and these effects have not been widely studied in IFs. Here we investigate the effects of two biologically important divalent cations, Zn2+ and Ca2+, on VIF network structure and mechanics in vitro. We find that the network structure is unperturbed at micromolar Zn2+ concentrations, but strong bundle formation is observed at a concentration of 100 μM. Microrheological measurements show that network stiffness increases with cation concentration. However, bundling of filaments softens the network. This trend also holds for VIF networks formed in the presence of Ca2+, but remarkably, a concentration of Ca2+ that is two orders higher is needed to achieve the same effect as with Zn2+, which suggests the importance of salt-protein interactions as described by the Hofmeister effect. Furthermore, we find evidence of competitive binding between the two divalent ion species. Hence, specific interactions between VIFs and divalent cations are likely to be an important mechanism by which cells can control their cytoplasmic mechanics.SignificanceIntermediate filaments are key structural elements within cells; they are known to form networks that can be crosslinked by divalent cations, but the interactions between the ions and the filaments are not well understood. By measuring the effects that two divalent cations, zinc and calcium, have on the structure and mechanics of vimentin intermediate filaments (VIFs), we show that although both have concentration-dependent effects on VIFs, much more calcium is needed to achieve the same effect as a small amount of zinc. Furthermore, when mixtures of the ions are present, the results suggest that there is binding competition. Thus, cells may use the presence of different cation species to precisely control their internal mechanical properties.
Emergence of opposite neurons in a decentralized firing-rate model of multisensory integration
Authors: Niu Xueyan , Chau Ho Yin , Lee Tai Sing , Zhang Wen-Hao 
Published: November 2019

AbstractMultisensory integration areas such as dorsal medial superior temporal (MSTd) and ventral intraparietal (VIP) areas in macaques combine visual and vestibular cues to produce better estimates of self-motion. Congruent and opposite neurons, two types of neurons found in these areas, prefer congruent inputs and opposite inputs from the two modalities, respectively. A recently proposed computational model of congruent and opposite neurons reproduces their tuning properties and shows that congruent neurons optimally integrate information while opposite neurons compute disparity information. However, the connections in the network are fixed rather than learned, and in fact the connections of opposite neurons, as we will show, cannot arise from Hebbian learning rules. We therefore propose a new model of multisensory integration in which congruent neurons and opposite neurons emerge through Hebbian and anti-Hebbian learning rules, and show that these neurons exhibit experimentally observed tuning properties.
Laminin-511 and α6 Integrins Regulate the Expression of CXCR4 to Promote Endothelial Morphogenesis
Authors: Xu Hao , Pumiglia Kevin , LaFlamme Susan E. 
Published: November 2019

AbstractDuring angiogenesis, endothelial cells engage components of the extracellular matrix through integrin-mediated adhesion. Endothelial expression of laminin-411 and laminin-511 are known to promote vessel stability. However, little is known about the contribution of these laminins to endothelial morphogenesis. We used two organotypic cell culture angiogenesis assays in conjunction with RNAi approaches to demonstrate that depletion of either the α4 chain of laminin-411 or the α5 chain of laminin-511 from endothelial cells inhibits sprouting and tube formation. Depletion of α6 integrins resulted in similar phenotypes. Gene expression analysis indicated that loss of either laminin-511 or α6 integrins inhibited the expression of CXCR4, a gene previously associated with angiogenic endothelial cells. Pharmacological or RNAi-dependent inhibition of CXCR4 suppressed endothelial sprouting and morphogenesis. Importantly, expression of recombinant CXCR4 rescued endothelial morphogenesis when the α6 integrin expression was inhibited. Additionally, the depletion of α6 integrins from established tubes resulted in the loss of tube integrity and laminin-511. Taken together, our results indicate that α6 integrins and laminin-511 can promote endothelial morphogenesis by regulating the expression of CXCR4 and suggest that the α6-dependent deposition of laminin-511 protects the integrity of established endothelial tubes.Summary statementEndothelial-secreted laminin-511 and α6 integrins promote endothelial morphogenesis by regulating the expression of the chemokine receptor, CXCR4. The depletion of α6 integrins from established tubes results in the loss of tube integrity and laminin-511.
Single cell multiomic analysis of T cell exhaustion in vitro
Authors: Corselli Mirko , Saksena Suraj , Nakamoto Margaret , Lomas Woodrow E. , Taylor Ian , Chattopadhyay Pratip K. 
Published: November 2019

AbstractA key step in the clinical production of CAR-T cells is the expansion of engineered T cells. To generate enough cells for a therapeutic product, cells must be chronically stimulated, which raises the risk of inducing T-cell exhaustion and reducing therapeutic efficacy. As protocols for T-cell expansion are being developed to optimize CAR T cell yield, function and persistence, fundamental questions about the impact of in vitro manipulation on T-cell identity are important to answer. Namely: 1) what types of cells are generated during chronic stimulation? 2) how many unique cell states can be defined during chronic stimulation? We sought to answer these fundamental questions by performing single-cell multiomic analysis to simultaneously measure expression of 39 proteins and 399 genes in human T cells expanded in vitro. This approach allowed us to study – with unprecedented depth - how T cells change over the course of chronic stimulation. Comprehensive immunophenotypic and transcriptomic analysis at day 0 enabled a refined characterization of T-cell maturational states (from naïve to TEMRA cells) and the identification of a donor-specific subset of terminally differentiated T-cells that would have been otherwise overlooked using canonical cell classification schema. As expected, T-cell activation induced downregulation of naïve-associated markers and upregulation of effector molecules, proliferation regulators, co-inhibitory and co-stimulatory receptors. Our deep kinetic analysis further revealed clusters of proteins and genes identifying unique states of activation defined by markers temporarily expressed upon 3 days of stimulation (PD-1, CD69, LTA), markers constitutively expressed throughout chronic activation (CD25, GITR, LGALS1), and markers uniquely up-regulated upon 14 days of stimulation (CD39, ENTPD1, TNFDF10). Notably, different ratios of cells expressing activation or exhaustion markers were measured at each time point. These data indicate high heterogeneity and plasticity of chronically stimulated T cells in response to different kinetics of activation. In this study, we demonstrate the power of a single-cell multiomic approach to comprehensively characterize T cells and to precisely monitor changes in differentiation, activation and exhaustion signatures in response to different activation protocols.
Chromosome painting does not support a sex chromosome turnover in Lacerta agilis Linnaeus, 1758
Authors: Lisachov Artem P. , Giovannotti Massimo , Pereira Jorge C. , Andreyushkova Daria A. , Romanenko Svetlana A. , Ferguson-Smith Malcolm A. , Borodin Pavel M. , Trifonov Vladimir A. 
Published: November 2019

AbstractReptiles show a remarkable diversity of sex determination mechanisms and sex chromosome systems, derived from different autosomal pairs. The origin of the ZW sex chromosomes of Lacerta agilis, a widespread Eurasian lizard species, is a matter of discussion: is it a small macrochromosome from the 11-18 group, common to all lacertids, or this species has unique ZW pair derived from the large chromosome 5. Using independent molecular cytogenetic methods, we investigated the karyotype of L. agilis exigua from Siberia, Russia, to identify the sex chromosomes. FISH with the flow-sorted chromosome painting probe, derived from L. strigata and specific to chromosomes 13, 14, and Z, confirmed that the Z chromosome of L. agilis is a small macrochromosome, the same as in L. strigata. FISH with the telomeric probe showed an extensive accumulation of the telomeric repeat on the W chromosome in agreement with previous studies, excluding the possibility that the lineages of L. agilis studied in different works could have different sex chromosome systems due to a putative intra-species polymorphism. Our results reinforce the idea of the stability of the sex chromosomes and lack of evidence for sex-chromosome turnovers in known species of Lacertidae.
Nonlinear mechanics of lamin filaments and the meshwork topology build an emergent nuclear lamina
Authors: Sapra K. Tanuj , Qin Zhao , Dubrovsky-Gaupp Anna , Aebi Ueli , Müller Daniel J. , Buehler Markus , Medalia Ohad 
Published: November 2019

AbstractThe nuclear lamina – a meshwork of intermediate filaments termed lamins – functions as a mechanotransduction interface between the extracellular matrix and the nucleusviathe cytoskeleton. Although lamins are primarily responsible for the mechanical stability of the nucleus in multicellular organisms,in situcharacterization of lamin filaments under tension has remained elusive. Here, we apply an integrative approach combining atomic force microscopy, cryo-electron tomography, network analysis, and molecular dynamics simulations to directly measure the mechanical response of single lamin filaments in its three-dimensional meshwork. Endogenous lamin filaments portray non-Hookean behavior – they deform reversibly under a force of a few hundred picoNewtons and stiffen at nanoNewton forces. The filaments are extensible, strong and tough, similar to natural silk and superior to the synthetic polymer Kevlar®. Graph theory analysis shows that the lamin meshwork is not a random arrangement of filaments but the meshwork topology follows ‘small world’ properties. Our results suggest that the lamin filaments arrange to form a robust, emergent meshwork that dictates the mechanical properties of individual lamin filaments. The combined approach provides quantitative insights into the structure-function organization of laminsin situ, and implies a role of meshwork topology in laminopathies.
Foreign direct investment and economic growth nexus in Africa
Authors: Hagan Edmond , Amoah Anthony 
Published: November 2019

Purpose
African countries are generally fragile. This and other related characteristics affect the potential for growth and development. The purpose of this paper is to investigate whether the effect of FDI on economic growth is contingent on a financial system that accounts for financial market fragility. An important point of departure from earlier studies is the adoption of a new measure of financial market fragility.

Design/methodology/approach
Given the uniqueness of the data set, the study uses a panel data and estimates an econometric model using an instrumental variable approach. For robustness purposes, a pooled ordinary least square is also estimated.

Findings
The study provides evidence that if the financial market is fragile as in the case of Africa, FDI inflows may have a marginally significant positive impact on economic growth. The findings suggest that fragility in the financial market is a key absorptive capacity and cannot be trivialised when exploring FDI–growth nexus in Africa.

Research limitations/implications
The uniqueness of the data set limited the time period of the study. Nonetheless, the findings are still crucial to policy makers in Africa and other developing countries with similar characteristics.

Originality/value
To the best of the authors’ knowledge, this is the first study in Africa to investigate the FDI–growth nexus which accounts for financial market fragility.
Audit committee chairman characteristics and earnings management
Authors: Al-Absy Mujeeb Saif Mohsen , Ku Ismail Ku Nor Izah , Chandren Sitraselvi 
Published: November 2019

PurposeThe purpose of this paper is to examine the influence of the characteristics of audit committee chairman (ACC) (tenure, age, gender, ethnicity, accounting expertise and directorship) on earnings management (EM) practices.Design/methodology/approachThe Jones model and modified Jones model by Dechowet al.(1995) were used to determine the discretionary accruals (DA) of 288 Malaysian listed firms with lowest positive earnings for the years 2013‒2015.FindingsThe results of the ordinary least squares regression indicate that only tenure, gender and ethnicity of the ACC are associated with DA. A further test was conducted by dividing firms into two groups: firms whose boards are chaired by a family member and firms whose boards are chaired by a non-family member. The results reveal that it is possible for firms whose boards are chaired by family members to cause the corporate governance (CG) mechanisms, particularly the audit committee, to lose their effectiveness in overcoming the EM problem. In addition, robustness tests were conducted by using panel data regression, where the results were found to be similar to the original regression results.Originality/valueThis study alerts policymakers, firms and their stakeholders, as well as researchers, regarding the importance of having an independent board chairman, who has no relationship with any directors or major shareholders, as this may hinder the effectiveness of CG mechanisms in curbing EM, especially in emerging countries, such as Malaysia, where it is very difficult to stop members of the family from becoming board directors.
Job preservation efforts: when does job insecurity prompt performance?
Authors: Koen Jessie , Low Jasmine T.H. , Van Vianen Annelies 
Published: November 2019

PurposeWhile job insecurity generally impedes performance, there may be circumstances under which it can prompt performance. The purpose of this paper is to examine a specific situation (reorganization) in which job insecurity may prompt task and contextual performance. The authors propose that performance can represent a job preservation strategy, to which employees may only resort when supervisor-issued ratings of performance are instrumental toward securing one’s job. The authors hypothesize that because of this instrumentality, job insecurity will motivate employees’ performance only when they have low intrinsic motivation, and only when they perceive high distributive justice.Design/methodology/approachIn a survey study among 103 permanent employees of a company in reorganization, the authors assessed perceived job insecurity, intrinsic motivation and perceived distributive justice. Supervisors rated employees’ overall performance (task performance and organizational citizenship behaviors).FindingsMultilevel analyses showed that job insecurity was only positively related to supervisor-rated overall performance among employees with low intrinsic motivation and, unexpectedly, among employees who experienced low distributive justice. Results were cross-validated using employees’ self-rated performance, replicating the findings on distributive justice but not the findings on intrinsic motivation.Research limitations/implicationsThe results can inform future research on the specific situations in which job insecurity may prompt job preservation efforts, and call for research to uncover the mechanisms underlying employees’ negative and positive responses to job insecurity. The results and associated implications of this study are largely based on conceptual evidence. In addition, the cross-sectional design warrants precaution about drawing causal inferences from the data.Originality/valueBy combining insights from coping responses and threat foci, this study advances the understanding of when and why job insecurity may prompt performance.