bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory B cells control SARS-CoV-2 variants upon mRNA vaccination of naive and COVID-19 recovered individuals
Authors: Sokal Aurélien , Barba-Spaeth Giovanna , Fernández Ignacio , Broketa Matteo , Azzaoui Imane , La Selle Andrea de , Vandenberghe Alexis , Fourati Slim , Roeser Anais , Meola Annalisa , Bouvier-Alias Magali , Crickx Etienne , Languille Laetitia , Michel Marc , Godeau Bertrand , Gallien Sébastien , Melica Giovanna , Nguyen Yann , Zarrouk Virginie , Canoui-Poitrine Florence , Noizat-Pirenne France , Megret Jérôme , Pawlotsky Jean-Michel , Fillatreau Simon , Bruhns Pierre , Rey Felix A. , Weill Jean-Claude , Reynaud Claude-Agnès , Chappert Pascal , Mahévas Matthieu
Published: June 2021

How a previous SARS-CoV-2 infection may amplify and model the memory B cell (MBC) response elicited by mRNA vaccines was addressed by a comparative longitudinal study of two cohorts, naive individuals and disease-recovered patients, up to 2 months after vaccination. The quality of the memory response was assessed by analysis of the VDJ repertoire, affinity and neutralization against variants of concerns (VOC), using unbiased cultures of 2452 MBCs. Upon boost, the MBC pool of recovered patients selectively expanded, further matured and harbored potent neutralizers against VOC. Maturation of the MBC response in naive individuals was much less pronounced. Nevertheless, and as opposed to their weaker neutralizing serum response, half of their RBD-specific MBCs displayed high affinity towards multiple VOC and one-third retained neutralizing potency against B.1.351. Thus, repeated vaccine challenges could reduce these differences by recall of affinity-matured MBCs and allow naive vaccinees to cope efficiently with VOC.
X-DPI: A structure-aware multi-modal deep learning model for drug-protein interactions prediction
Authors: Wang Penglei , Zheng Shuangjia , Jiang Yize , Li Chengtao , Liu Junhong , Wen Chang , Patronov Atanas , Qian Dahong , Chen Hongming , Yang Yuedong
Published: June 2021

Motivation

Identifying the drug-protein interactions (DPIs) is crucial in drug discovery, and a number of machine learning methods have been developed to predict DPIs. Existing methods usually use unrealistic datasets with hidden bias, which will limit the accuracy of virtual screening methods. Meanwhile, most DPIs prediction methods pay more attention to molecular representation but lack effective research on protein representation and high-level associations between different instances. To this end, we presented here a novel structure-aware multi-modal DPIs prediction model, X-DPI, performing on a curated industry-scale benchmark dataset.

Results

We built a high-quality benchmark dataset named GalaxyDB for DPIs prediction. This industry-scale dataset along with an unbiased training procedure resulted in a more robust benchmark study. For informative protein representation, we constructed a structure-aware graph neural network method from the protein sequence by combining predicted contact maps and graph neural networks. Through further integration of structure-based representation and high-level pre-trained embeddings for molecules and proteins, our model captured more effectively the feature representation of the interactions between them. As a result, X-DPI outperformed state-of-the-art DPIs prediction methods and obtained 5.30% Mean Square Error (MSE) improved in the DAVIS dataset and 8.89% area under the curve (AUC) improved in GalaxyDB dataset. Moreover, our model is an interpretable model with the transformer-based interaction mechanism, which can accurately reveal the binding sites between molecule and protein.
Universality of evolutionary trajectories under arbitrary competition dynamics
Authors: Mazzolini Andrea , Grilli Jacopo
Published: June 2021

The assumption of constant population size is central in population genetics. It led to a large body of results, that are robust to modeling choices and that have proven successful to understand evolutionary dynamics. In reality, allele frequencies and population size are both determined by the interaction between a population and the environment. Relaxing the constant-population assumption have two big drawbacks. It increases the technical difficulty of the analysis, and it requires specifying a mechanism for the saturation of the population size, possibly making the results contingent on model details. Here, we develop a framework that encompasses a great variety of systems with an arbitrary mechanism for population growth limitation. By using techniques based on scale separation for stochastic processes, we are able to calculate analytically properties of evolutionary trajectories, such as the fixation probability. Remarkably, these properties assume a universal form with respect to our framework, which depends on only three parameters related to the inter-generation timescale, the invasion fitness, and the carrying capacity of the strains. In other words, different systems, such as Lotka-Volterra or a chemostat model (contained in our framework), share the same evolutionary outcomes after a proper re-mapping of their parameters. An important and surprising consequence of our results is that the direction of selection can be inverted, with a population evolving to reach lower values of invasion fitness.
High heritabilities for antibiotic usage show potential to breed for disease resistance in finishing pigs
Authors: Gorssen Wim , Maes Dominiek , Meyermans Roel , Depuydt Jürgen , Janssens Steven , Buys Nadine
Published: June 2021

The use of antimicrobials in animal production is under public debate, mainly due to the risk of transfer of resistance to pathogenic bacteria in humans. Therefore, measures have been taken during the last decades to reduce antibiotic usage in animals, for instance by national monitoring programmes and by improving animal health management. Although some initiatives exist in molecular genetic selection, quantitative genetic selection of animals towards decreased antibiotic usage is an underexplored area to reduce antibiotic usage. However, this strategy could yield cumulative effects.

In this study we derived new phenotypes from on-farm parenteral antibiotic records from commercially grown crossbred finishing pigs used in the progeny test of Piétrain terminal sires to investigate the heritability of antibiotics usage. Parenteral antibiotic records, production parameters and pedigree records of 2238 fullsib pens from two experimental farms in Belgium between 2014 and 2020 were analysed. Heritability estimates were moderate (18-44%) for phenotypes derived from all antibiotic treatments, and low (1-15%) for phenotypes derived from treatments against respiratory diseases only. Moreover, genetic correlations between these new phenotypes and mortality were low to moderate (0.08-0.60) and no strong adverse genetic correlations with production traits were found.

The high heritabilities and favourable genetic correlations suggest these new phenotypes derived from on-farm antibiotics records to be promising for inclusion in future pig breeding programs to breed for a decrease in antibiotics usage.
Psychophysiological Evidence for Fear Extinction Learning via Mental Imagery
Authors: Jiang Xinrui , Greening Steven
Published: June 2021

Imagery-based extinction procedures have long been used in the treatments of fear-related conditions. The assumption is that imagery can substitute for the perceptual stimuli in the extinction process. Yet, experimental validations of this assumption have been limited in number and some have relied exclusively on measures of autonomic reactivity without consideration of conscious feelings of fear. The current investigation sought to assess whether imagery-based exposure could lead to extinction of conditioned fear to the corresponding perceptual stimulus. Conditioned fear responses were measured by both a physiological (i.e., skin conductance response/SCR) and a subjective (i.e., self-reported fear) measure. Participants (N= 56) first underwent perceptual differential fear conditioning, then imagery extinction, then perceptual extinction. SCR evidence was found for successful fear conditioning, generalization of fear from viewing to imagery, and most importantly, the absence of differential fear after imagery extinction upon re-exposure to the conditioned perceptual stimulus. Self-reported fear confirmed the acquisition and generalization of fear and provided evidence of a significant reduction in differential fear conditioning across extinction. Consistent with clinical evidence of the efficacy of imagery extinction and the existing limited experimental literature, the current study offers support for fear extinction to perceptual stimuli via imagery exposure.
Increased brain growth in escaped rainbow trout
Authors: Laberge Frédéric , Gutgesell Marie , McCann Kevin S.
Published: June 2021

Recent examples of rapid brain size plasticity in response to novel laboratory environments suggest that fish brain size is a flexible trait, allowing growth or shrinkage of brain tissue based on short term needs. Nevertheless, it remains to be seen if plasticity of fish brain size is relevant to natural environmental conditions. Here, using rainbow trout escaped from a farming operation as a natural experiment, we demonstrate that adult fish brain size can change rapidly in response to life in a natural lake environment. Specifically, escaped trout had on average 15% heavier brains relative to body size than captive trout after living for about 7 months in the lake. Because relative brain size of most escaped trout fell above the range of variation seen within the captive trout population, we conclude that increased brain size was achieved by plasticity after escape. Brain morphology analysis showed that the most anterior regions (olfactory bulbs and rest of telencephalon) contributed most to the increase in overall brain size in escaped trout. Relative size of the heart ventricle, another organ which can be subject to plastic changes under variable environmental conditions in fish, did not differ between escaped and captive trout. Massive and selective brain growth under the changed environmental conditions associated with escape from holding pens highlighted the plastic potential of fish brain size and suggests that a shift to increased complexity of life in the wild setting of a lake imposed greatly increased cognitive requirements on escaped trout.
IUCNN - deep learning approaches to approximate species’ extinction risk
Authors: Zizka Alexander , Andermann Tobias , Silvestro Daniele
Published: June 2021

Aim

The global Red List (RL) from the International Union for the Conservation of Nature is the most comprehensive global quantification of extinction risk, and widely used in applied conservation as well as in biogeographic and ecological research. Yet, due to the time- consuming assessment process, the RL is biased taxonomically and geographically, which limits its application on large scales, in particular for understudied areas such as the tropics, or understudied taxa, such as most plants and invertebrates. Here we present IUCNN, an R- package implementing deep learning models to predict species RL status from publicly available geographic occurrence records (and other traits if available).

Innovation

We implement a user-friendly workflow to train and validate neural network models, and subsequently use them to predict species RL status. IUCNN contains functions to address specific issues related to the RL framework, including a regression-based approach to account for the ordinal nature of RL categories and class imbalance in the training data, a Bayesian approach for improved uncertainty quantification, and a target accuracy threshold approach that limits predictions to only those species whose RL status can be predicted with high confidence. Most analyses can be run with few lines of code, without prior knowledge of neural network models. We demonstrate the use of IUCNN on an empirical dataset of ∼14,000 orchid species, for which IUCNN models can predict extinction risk within minutes, while outperforming comparable methods.

Main conclusions

IUCNN harnesses innovative methodology to estimate the RL status of large numbers of species. By providing estimates of the number and identity of threatened species in custom geographic or taxonomic datasets, IUCNN enables large-scale analyses on the extinction risk of species so far not well represented on the official RL.
Expression and function of SLC38A5, an amino acid-coupled Na+/H+ exchanger, in triple-negative breast cancer and its relevance to macropinocytosis
Authors: Ramachandran Sabarish , Sennoune Souad , Sharma Monica , Thangaraju Muthusamy , Suresh Varshini , Bhutia Yangzom D. , Pruitt Kevin , Ganapathy Vadivel
Published: June 2021

Metabolic reprogramming in cancer cells necessitates increased amino acid uptake, which is accomplished by upregulation of specific amino acid transporters. Since amino acid transporters differ in substrate selectivity, mode of transport, and driving forces, not all tumors rely on any single amino acid transporter for this purpose. Here we report on the differential upregulation of the amino acid transporter SLC38A5 in triple-negative breast cancer (TNBC). The upregulation is evident in primary TNBC tumors, conventional TNBC cell lines, patient-derived xenograft TNBC cell lines, and a mouse model of spontaneous mammary tumor representing TNBC. The upregulation is confirmed by functional assays. SLC38A5 is an amino acid-dependent Na+/H+ exchanger which transports Na+ and amino acids into cells coupled with H+ efflux. Since the traditional Na+/H+ exchanger is an established inducer of macropinocytosis, an endocytic process for cellular uptake of bulk fluid and its components, we examined the impact of SLC38A5 on macropinocytosis in TNBC cells. We found that the transport function of SLC38A5 is coupled to induction of macropinocytosis. Surprisingly, the transport function of SLC38A5 is inhibited by amilorides, the well-known inhibitors of Na+/H+ exchanger, possibly related to the amino acid-dependent Na+/H+ exchange function of SLC38A5. The Cancer Genome Atlas database corroborates SLC38A5 upregulation in TNBC. This represents the first report on the selective expression of SLC38A5 in TNBC and its role as an inducer of macropinocytosis, thus revealing a novel, hitherto unsuspected, function for an amino acid transporter that goes beyond amino acid delivery but is still relevant to cancer cell nutrition.

Summary Statement

SLC38A5 is an amino acid-coupled Na+/H+ exchanger that is upregulated in triple-negative breast cancer, and its function in cancer cells goes beyond amino acid delivery; it promotes macropinocytosis, a distinct form of endocytic process for cellular uptake of proteins and other nutrients present in extracellular fluid.
vWCluster: A Network Based Clustering of Multi-omics Breast Cancer Data Based on Vector-Valued Optimal Transport
Authors: Zhu Jiening , Oh Jung Hun , Deasy Joseph O. , Tannenbaum Allen
Published: June 2021

In this paper, we present a network-based clustering method based on the vector-valued Wasserstein distance derived from optimal mass transport (OMT) theory. This distance allows for the natural integration of multi-layer representations of data in a given network from which one derives clusters via a hierarchical clustering approach. In this study, we applied the methodology, called vector Wasserstein clustering (vW-cluster), to multi-omics data from the two largest breast cancer studies. The resultant clusters showed significantly different survival rates in Kaplan-Meier analysis in both datasets. CIBERSORT scores were compared among the identified clusters. Out of the 22 CIBERSORT immune cell types, 9 were commonly significantly different in both datasets, suggesting the difference of tumor immune microenvironment in the cluster. vWCluster can aggregate multi-omics data represented as a vectorial form in a network with multiple layers, taking into account the concordant effect of heterogeneous data, and further identify subtypes of tumors with different survival rates.
Post-Infection Entry Mechanism of Ricin A Chain-Pokeweed Antiviral Proteins (RTA-PAPs) Chimeras is Mediated by Viroporins
Authors: Hassan Yasser
Published: June 2021

The limitations of virus-specific antiviral drugs became apparent during the current COVID-19 pandemic. The search for broad range antiviral proteins of a new kind to answer current and future pandemics has become an even more pressing matter. Here, the author further describes the expected anti-SARS-CoV-2 mechanisms of a novel broad range antiviral chimeric protein constructed between ricin A chain and pokeweed antiviral proteins. The latest in protein-ligand docking software were used to determine binding affinity of RTA-PAPs to SARS-CoV-2 frameshift stimulation element and elucidate the preferential post-infection entry mechanisms of RTA-PAPs into virus infected cells over non-infected ones, by doing a comparative analysis between in vitro and in silico results on numerous viruses. The results obtained strongly suggest that the post-infection preferential entry of RTA-PAPs into infected cells is mediated by the presence of viroporins integrated into the host cell membrane. The discovery of this mechanism revealed RTA-PAPs, and proteins like them, to be a new class of broad range antivirals that target with high specificity viroporin producing viruses, and with gain of functions in antiviral activities, post-infection.
Demographic Inferences and Loci Under Selection in a Recently Expanded Coral Population
Authors: Fifer James E. , Yasuda Nina , Yamakita Takehisa , Davies Sarah W.
Published: June 2021

Coral poleward range expansions in response to warming oceans have been historically observed, however contemporary expansion rates of some coral species have become more rapid as global temperatures rise at unprecedented rates. Range expansion can lead to reduced genetic diversity and surfing of deleterious mutations in expanding populations, potentially limiting the ability for adaption and persistence in novel environments. Successful expansions that overcome these founder effects and colonize new habitat have been attributed to multiple introductions from different sources, hybridization with native populations, or rapid adaptive evolution. Here, we investigate population genomic patterns of the reef-building coralAcropora hyacinthusalong a latitudinal cline that includes a well-established range expansion front in Japan using 2b-RAD sequencing. A total of 184 coral samples were collected across seven sites spanning from ∼24°N to near its northern range front at ∼33°N. We uncover the presence of three cryptic lineages ofA. hyacinthus, which occupy discrete areas within this region. Only one lineage is present at the expansion front and we find evidence of its historical occupation of marginal habitats. Within this lineage we also find evidence of bottleneck pressures associated with expansion events including higher clonality, increased linkage disequilibrium, and lower genetic diversity in range edge populations compared to core populations. Asymmetric migration between populations was also detected with lower migration from edge sites. Lastly, we describe genomic signatures of local adaptation potentially attributed to lower winter temperatures experienced at the more recently expanded northern populations. Together these data illuminate the genomic consequences of range expansion in a coral and highlight how adaptation to colder temperatures along the expansion front may facilitate further range expansion in this coral lineage.
Habitat size, health and saturation do not alter movement decisions or the preference for familiarity in a social coral-reef fish
Authors: Froehlich Catheline Y.M. , Heatwole Siobhan J. , Klanten O. Selma , Wong Marian Y.L.
Published: June 2021

While habitat is often a limiting resource for group-living animals, we have yet to understand what aspects of habitat are particularly important for the maintenance of sociality. As anthropogenic disturbances rapidly degrade the quality of many habitats, site-attached animals are facing additional stressors that may alter the trade-offs of moving or remaining philopatric. Here we examined how habitat health, size and saturation affect movement decisions of a coral-dwelling goby, Gobiodon quinquestrigatus, that resides within bleaching-susceptible Acropora coral hosts. To assess effects of habitat health, we translocated individuals far from their home corals into dead corals with the choice of adjacent healthy corals. To assess effects of habitat size and saturation, we manipulated coral sizes and the number of residents in healthy corals. Remarkably, 55% of gobies returned home regardless of treatment, 7% stayed in the new coral, and the rest were not found. Contrary to expectations, habitat factors did not affect how costs of movement influence group-living decisions in this species. These site-attached fishes preferred to home instead of choosing alternative habitat, which suggests a surprising awareness of their ecological surroundings. However, disregarding alternative high-quality habitat is concerning as it may affect population persistence under conditions of rapid habitat degradation.
LmbU directly regulates SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780, which are located outside the lmb cluster and inhibit lincomycin biosynthesis in Streptomyces lincolnensis
Authors: Hou Bingbing , Zhang Xianyan , Mao Yue , Wang Ruida , Ye Jiang , Wu Haizhen , Zhang Huizhan
Published: June 2021

The productions of antibiotics are usually regulated by cluster-situated regulators (CSRs), which can directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). However, few studies have looked into the regulation of CSRs on the targets outside the BGC. Here, we screened the targets of LmbU in the whole genome of S. lincolnensis, and found 14 candidate targets, among of which, 8 targets can bind to LmbU by EMSAs. Reporter assays in vivo revealed that LmbU repressed transcription of SLINC_RS02575 and SLINC_RS05540, while activated transcription of SLINC_RS42780. In addition, disruptions of SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 promoted the production of lincomycin, and qRT-PCR showed that SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. What’s more, the homologues of LmbU and its targets SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 are widely found in actinomycetes, while the distributions of DNA-binding sites (DBS) of LmbU are diverse, indicating the regulatory mechanisms of LmbU homologues in various strains are different and complicated.

IMPORTANCE

Lincomycin is widely used in clinic treatment and animal husbandry. Our previous study firstly demonstrated that LmbU, a novel transcriptional regulator family, functions as a CSR and positively regulates lincomycin biosynthesis. Here, we revealed that LmbU may act as a pleiotropic transcriptional regulator, and directly regulates SLINC_RS02575, SLINC_RS05540 and SLINC_RS42780 which are located outside the lmb cluster and negatively regulate lincomycin biosynthesis. Interestingly, the homologues of LmbU and its targets are widely found in actinomycetes, indicating the regulatory patterns of LmbU to the targets may exist in a variety of strains. Collectively, our findings elucidated the molecular mechanism with which LmbU regulates the target genes outside the lmb culster, and draw a network diagram of LmbU regulation on lincomycin biosynthesis. This lays a solid foundation for the realization of high-yield of lincomycin in industry, and provides the theoretical basis for the functional research of LmbU family proteins.
Representational similarity scores of digits in the sensorimotor cortex are associated with behavioral performance
Authors: Gooijers J. , Chalavi S. , Roebroeck A. , Kaas A. , Swinnen S.P.
Published: June 2021

Previous studies aimed to unravel a digit-specific somatotopic organization in the primary sensorimotor (SM1) cortex. It is, however, yet to be determined whether such digit somatotopy is associated with motor performance (i.e., effector selection) and digit enslaving (unintentional co-contraction of fingers) during different types of motor tasks. Here, we adopted multivariate representational similarity analysis, applied to high-field (7T) MRI data, to explore digit activation patterns in response to online finger tapping. Sixteen young adults (7 males, mean age: 24.4 years) underwent MRI, and additionally performed an offline choice reaction time task (CRTT) to assess effector selection. During both the finger tapping task (FTT) and the CRTT, force sensor data of all digits were acquired. This allowed us to assess digit enslaving (obtained from CRTT & FTT), as well as digit interference (i.e., erroneous effector selection; obtained from CRTT) and determine the correlation between these variables and digit representational similarity scores of SM1. Digit enslaving during finger tapping was associated with contralateral SM1 representational similarity scores of both hands. During the CRTT, digit enslaving of the right hand only was associated with representational similarity scores of left SM1. Additionally, right hand digit interference was associated with representational similarity scores of left S1. In conclusion, we demonstrate a cortical origin of digit enslaving, and uniquely reveal that effector selection performance is predicted by digit representations in the somatosensory cortex.
Haplotype analyses reveal novel insights into tomato history and domestication including long-distance migrations and latitudinal adaptations
Authors: Blanca Jose , Sanchez-Matarredona David , Ziarsolo Peio , Montero-Pau J , van der Knaap Esther , Díez Maria José , Cañizares Joaquín
Published: June 2021

A novel haplotype-based approach that uses Procrustes analysis and automatic classification was used to provide further insights into tomato history and domestication. Agrarian societies domesticated species of interest by introducing complex genetic modifications. For tomatoes, two species, one of which had two botanical varieties, are thought to be involved in its domestication: the fully wildSolanum pimpinellifolium(SP), the wild and semi-domesticatedS. lycopersicumvar.cerasiforme(SLC) and the cultivatedS. l.var.lycopersicum(SLL). The Procrustes approach showed that SP evolved into SLC during a gradual migration from the Peruvian deserts to the Mexican rainforests and that Peruvian and Ecuadorian SLC populations were the result of more recent hybridizations. Our model was supported by independent evidence, including ecological data from the accession collection site and morphological data. Furthermore, we showed that photosynthesis-, and flowering time-related genes were selected during the latitudinal migrations.
Analysis of human brain tissue derived from DBS surgery
Authors: Kangas Salla M. , Teppo Jaakko , Lahtinen Maija J. , Suoranta Anu , Ghimire Bishwa , Mattila Pirkko , Uusimaa Johanna , Varjosalo Markku , Katisko Jani , Hinttala Reetta
Published: June 2021

Background

Transcriptomic and proteomic profiling of human brain tissue is hindered by availability of fresh samples from living patients. Postmortem samples usually represent the advanced disease stage of the patient. Furthermore, the postmortem interval affects the observed transcriptomic and proteomic profiles. Therefore, access to fresh brain tissue samples from living patients is valuable resource to obtain information on metabolically intact tissue. The implantation of deep brain stimulation (DBS) electrodes into the human brain is a neurosurgical treatment for, e.g., movement disorders. Here, we describe an improved approach to collect brain tissue from surgical instruments used in implantation of DBS device for transcriptomics and proteomics analyses.

Methods

Samples were extracted from guide tubes and recording electrodes used in routine DBS implantation procedure that was carried out to treat patients with Parkinson’s disease, genetic dystonia and tremor. RNA sequencing was carried out to tissue extracted from the recording microelectrodes and liquid chromatography-mass spectrometry was carried out to analyze tissue from guide tubes. To assess the performance of the current approach, obtained datasets were compared with previously published datasets representing brain tissue.

Results

In RNA sequencing, altogether 32,034 transcripts representing unique Ensembl gene identifiers were detected from eight samples representing both hemispheres of four patients. By using liquid chromatography-mass spectrometry, we identified 734 unique proteins from 31 samples collected from 14 patients. Comparison with previously published brain derived data indicated that both of our datasets reflected the expected brain tissue specific features. The datasets are available via BioStudies database (accession number S-BSST667).

Conclusions

Surgical instruments used in DBS installation retain enough brain material for protein and gene expression studies. Analysis of the datasets indicated that hemisphere-specific expression data can be obtained from individual patients without any sample pooling and without any modifications to the standard surgical protocol. Comparison with previously published datasets obtained with similar approach proved the robustness and reproducibility of the current improved protocol. This approach overcomes the issues that arise from using postmortem tissue, such as effect of postmortem interval, on proteomic and transcriptomic landscape of the brain and can be used for studying molecular aspects of DBS-treatable diseases.
N-terminal phosphorylation regulates the activity of Glycogen Synthase Kinase 3 from Plasmodium falciparum
Authors: Pazicky Samuel , Alder Arne , Mertens Haydyn , Svergun Dmitri , Gilberger Tim , Löw Christian
Published: June 2021

As the decline of malaria cases stalled over the last five years, novel targets in Plasmodium falciparum are necessary for the development of new drugs. Glycogen Synthase Kinase (PfGSK3) has been identified as a potential target, since its selective inhibitors were shown to disrupt the parasite’s life cycle. Here, we show that PfGSK3 exhibits autophosphorylation, leading to an extensive phosphorylation both in vitro and in the parasite. In the uncanonical N-terminal region of the parasite enzyme, we identified several autophosphorylation sites that regulate the activity of PfGSK3. By combining molecular modeling with experimental small-angle X-ray scattering data, we show that increased PfGSK3 activity is promoted by conformational changes in the PfGSK3 N-terminus, triggered by N-terminal phosphorylation. Our work provides novel insights into the structure and regulation of the malarial PfGSK3.
Pseudomonas syringae addresses distinct environmental challenges during plant infection through the coordinated deployment of polysaccharides
Authors: Krishna Pilla Sankara , Woodcock Stuart Daniel , Pfeilmeier Sebastian , Bornemann Stephen , Zipfel Cyril , Malone Jacob George
Published: June 2021

Prior to infection, phytopathogenic bacteria face a challenging environment on the plant surface, where they are exposed to nutrient starvation and abiotic stresses. Pathways enabling surface adhesion, stress tolerance and epiphytic survival are important for successful plant pathogenesis. Understanding the roles and regulation of these pathways is therefore crucial to fully understand bacterial plant infections. The phytopathogen Pseudomonas syringae pv. tomato (Pst) encodes multiple polysaccharides that are implicated in biofilm formation, stress survival and virulence in other microbes. To examine how these polysaccharides impact Pst epiphytic survival and pathogenesis, we analysed mutants in multiple polysaccharide loci to determine their intersecting contributions to epiphytic survival and infection. In parallel, we used qRT-PCR to analyse the regulation of each pathway. Pst polysaccharides are tightly coordinated by multiple environmental signals. Nutrient availability, temperature and surface association strongly affect the expression of different polysaccharides under the control of the signalling proteins ladS and cbrB and the second messenger cyclic-di-GMP. Furthermore, functionally redundant, combinatorial phenotypes were observed for several polysaccharides. Exopolysaccharides and WapQ-mediated lipopolysaccharide production are important for leaf adhesion, while α-glucan and alginate together confer desiccation tolerance. Our results suggest that polysaccharides play important roles in overcoming environmental challenges to Pst during plant infection.

Highlight

Pseudomonas syringae uses the coordinated deployment of polysaccharides to address environmental challenges during plant colonization. Functional redundancy renders individual polysaccharides dispensable during plant infection, but their combined loss impedes pathogenicity.
CCN2 activates ERK-signaling via integrin αv and enhances the interaction of ERK and DUSP6 in lymphatic endothelial cells
Authors: Hashiguchi Shiho , Tanaka Tomoko , Mano Ryosuke , Kondo Seiji , Kodama Shohta
Published: June 2021

Cellular communication network factor 2 (CCN2, also known as CTGF), is a modular and matricellular protein and a well-known angiogenic factor in physiological and pathological angiogenesis. However, its roles in lymphangiogenesis and intracellular signaling in lymphatic endothelial cells (LECs) remain unclear. Here, we investigated CCN2 signaling in LECs and its effects on lymphangiogenesis. In primary cultured LECs, gene expressions of lymphatic endothelial markers lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1), Podoplanin and prospero homeobox 1 (Prox1) and lymphangiogenic factors vascular endothelial cell growth factor c (Vegfc), vascular endothelial cell growth factor d (Vegfd) and fms-related tyrosine kinase 4 (Flt4, also known as Vegfr3) were upregulated by CCN2. Subsequently, we found that CCN2 induced phospho-ERK and that was decreased by suppression of integrin αv. CCN2 slightly decreased the growth of LECs due to enhancement of the interaction of ERK and dual specific protein phosphatase 6 (DUSP6), and knockdown of DUSP6 increased CCN2-induced phospho-ERK levels. In in vivo Matrigel plug assays, the number of Podoplanin-positive vessels was increased by exogenous CCN2, and phospho-ERK-positive LEC and DUSP6-positive LEC were detected in CCN2 plugs. These results suggest that CCN2-related lymphangiogenesis is regulated by DUSP6, which enables negative modulation of ERK-signaling.
Crystal structures of 9-[bis(benzylsulfanyl)methyl]anthracene and of cyclo-dodecakis(μ2-phenylmethanethiolato-κ2
S:S)hexapalladium(6 Pd—Pd)–anthracene-9,10-dione (1/1)
Authors: Raghuvanshi Abhinav , Krupp Anna , Viau Lydie , Knorr Michael , Strohmann Carsten
Published: June 2021

The first title compound, C29H24S2, L1, represents an example of an anthracene-based functionalized dithioether, which may be useful as a potential chelating or terminal ligand for coordination chemistry. This dithioacetal L1 crystallizes in the monoclinic space group P21/c. The phenyl rings of the benzyl groups and that of the anthracene unit form dihedral angles of 49.21 (4) and 58.79 (5)° and the crystal structure displays short C–H...π contacts. Surprisingly, when attempting to coordinate L1 to [PdCl2(PhCN)2], instead of the targeted chelate complex [PdCl2(κ2-L1)], a cleavage reaction leads to the formation of the centrosymmetric hexanuclear cyclic cluster of composition [Pd6(μ2-SCH2Ph)12] Pd6, or [Pd6(C7H7S)12]·C14H8O2. This tiara-shaped hexamer crystallizing in the triclinic space group P\overline{1} consists of six approximately square planar Pd(II)S4 centers, which are interconnected through twelve μ2-bridging benzyl thiolate groups. The Pd...Pd contacts range from 3.0892 (2) to 3.1609 (2) Å and can be considered as weakly bonding. The unit cell of Pd6 contains also a co-crystallized anthracene-9,10-dione molecule.
Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
Authors: Hatti Kaushik S. , McCoy Airlie J. , Read Randy J.
Published: June 2021

SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of the substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. Here, a likelihood-based target function is proposed to accurately estimate the strength of the anomalous scattering contribution directly from the measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of the intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprising one anomalous scatterer with a known value of f′′ and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer before the substructure is known. The maximum-likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log–log basis) of 0.72.
Structural insights into the interaction of papain-like protease 2 from the alphacoronavirus porcine epidemic diarrhea virus and ubiquitin
Authors: Durie Ian A. , Dzimianski John V. , Daczkowski Courtney M. , McGuire Jack , Faaberg Kay , Pegan Scott D.
Published: June 2021

Porcine epidemic diarrhea is a devastating porcine disease that is caused by the alphacoronavirus porcine epidemic diarrhea virus (PEDV). Like other members of the Coronaviridae family, PEDV encodes a multifunctional papain-like protease 2 (PLP2) that has the ability to process the coronavirus viral polyprotein to aid in RNA replication and antagonize the host innate immune response through cleavage of the regulatory proteins ubiquitin (Ub) and/or interferon-stimulated gene product 15 (ISG15) (deubiquitination and deISGylation, respectively). Because Betacoronavirus PLPs have been well characterized, it was sought to determine how PLP2 from the alphacoronavirus PEDV differentiates itself from its related counterparts. PEDV PLP2 was first biochemically characterized, and a 3.1 Å resolution crystal structure of PEDV PLP2 bound to Ub was then solved, providing insight into how Alphacoronavirus PLPs bind to their preferred substrate, Ub. It was found that PEDV PLP2 is a deubiquitinase and readily processes a variety of di-Ub linkages, in comparison with its Betacoronavirus counterparts, which have a narrower range of di-Ub activity but process both Ub and ISG15.
Crystallographic fragment screening-based study of a novel FAD-dependent oxidoreductase from Chaetomium thermophilum. Corrigendum
Authors: Švecová Leona , Østergaard Lars Henrik , Skálová Tereza , Schnorr Kirk Matthew , Koval' Tomáš , Kolenko Petr , Stránský Jan , Sedlák David , Dušková Jarmila , Trundová Mária , Hašek Jindřich , Dohnálek Jan
Published: June 2021

The synchrotron facilities used in collecting the data for the article by Švecová et al. [(2021), Acta Cryst. D77, 755–775] are acknowledged.
Understanding the luxury purchase intentions of young consumers: a qualitative analysis
Authors: Sharma Purva , Pradhan Sudeepta , Srivastava Ankur
Published: June 2021

Purpose

The study intends to investigate the key purchase drivers of luxury brands in India. Given that a major segment of this target audience is the young consumers, the study focuses on determining these antecedents of luxury purchase from a young Indian consumer lens.

Design/methodology/approach

The study uses an interpretive research position, employing qualitative techniques in the form of in-depth interviews. In total, 62 respondents were interviewed, and later the transcribed interviews were analyzed using content analysis.

Findings

The study identifies the three main value dimensions that contribute to the final purchase decision: functional, social and emotional. The study also highlights the importance of Internet and web for luxury brands and how young Indian consumer consumes luxury online.

Originality/value

Research on luxury brands is still at a nascent stage. Though variables such as economic value, brand origin, social identity, prestige, self-congruity and so on have been examined in the context of luxury brands in prior studies. However, these studies are restricted because either they were product-specific or actual users of luxury brands were not approached as the sample. Most importantly none of these studies reflect the purchase behavior of young consumers in an emerging market, especially India. Given the growth of luxury brands in India, it would be worthwhile to investigate the factors influencing the customer purchase intention of luxury brands in emerging markets.
Customer engagement on social media, brand equity and financial performance: a comparison of the US and Korea
Authors: Lee Jungwon , Park Cheol
Published: June 2021

Purpose

The purpose of this paper is to analyze the relationship between customer engagement in social media (CESM), brand equity and corporate performance and investigated whether these relationships differed according to cultural factors in the United States and South Korea.

Design/methodology/approach

We collected customer engagement on social media data on Facebook and brand equity data from Interbrand for listed companies in the United States and Korea. A total of 405 data sets were analyzed by partial least squares structural equation modeling (PLS-SEM).

Findings

Results revealed that CESM did not affect financial performance through a direct path but was found to have a positive indirect path via the mediation of brand equity. In addition, this relationship was found to differ between the United States and South Korea.

Originality/value

This study contributed to the literature on social media and international management by verifying the relationship between CESM, brand equity and financial performance, and by presenting exploratory research results to ascertain if these relationships differ according to the cultural dimension of the country.
The influence of ERP systems on organizational aspects of accounting: case studies in Portuguese companies
Authors: Martins José Luís , Santos Carlos
Published: June 2021

Purpose

This paper aims to investigate the changes caused by the use of the enterprise resource planning (ERP) systems in the accounting of organizations at different levels: organizational structure; processes; and employees.

Design/methodology/approach

The authors use a qualitative methodology with interpretative analysis through the study of five cases in Portuguese companies that implemented the Sage ERP X3. The data collection was carried out mainly through semi-structured interviews.

Findings

The results indicate that the successful implementation of the ERP system is associated with changes in the organizational structure, reengineering of processes and changes in the functions of employees. These changes interact and cause modifications among themselves, which makes it difficult to identify the origin and sequence of changes related to the implementation of the systems. It was possible to identify the direct impact of the ERP system on the change of processes, which is reflected in the functions of the employees, as well as to verify that the ERP system provides the opportunity for companies to change their organizational structure.

Originality/value

This paper contributes to the accounting literature by providing evidence on the influence of ERP systems on organizational aspects of accounting in the Portuguese reality, attesting that the successful implementation of the ERP system is associated with changes in the organizational structure, reengineering of processes and changes in the functions of employees.
Young consumers' purchase intention toward organic food: exploring the role of mindfulness
Authors: Tewari Alok , Srivastava Smriti , Gangwar Divya , Verma Vimal Chandra
Published: June 2021

Purpose

The role of mindfulness in influencing green behaviors has been recognized in literature though it has not been explored sufficiently in the context of organic food. This study makes an attempt to explore the role of mindfulness in influencing young consumers' purchase intention (PI) toward organic food in India.

Design/methodology/approach

A total of 348 useable responses were collected through an intercept survey at organic food stores using a purposive sampling approach. Data analysis was carried out through structural equation modeling.

Findings

Mindfulness emerged as a significant predictor of behavioral intention. Further, the specific indirect effects of mindfulness through attitude, perceived behavioral control (PBC), drive for environmental responsibility (DER) and label reference willingness (LRW) were also significant.

Originality/value

This research is one of the initial efforts to link mindfulness with PI for organic food. The results could help the government and marketers tap onto the potential of mindfulness with regard to environment-friendly products and frame appropriate strategies for stimulating the demand for organic food in India
Local government website usability on mobile devices: test results and recommendations
Authors: Król Karol , Zdonek Dariusz
Published: June 2021

Purpose

The range of official business that can be handled online has grown in the recent decade. In many cases, e-services are a must. At the same time, the economic impact and social importance of mobile technology have increased. Mobile devices are becoming more and more popular, and their applications diversify. It comes as no surprise that mobile users expect e-services and official information to be available through this channel. The purpose of this paper is to identify problems (difficulties) occurring when browsing websites of local government units (LGU) on mobile devices.

Design/methodology/approach

The comfort of website browsing depends mostly on the development technique, and the way content is published. Responsive websites are much easier to view on mobile devices than “static” ones. The study involves 400 websites of LGU in Poland. The websites were subjected to quantitative and qualitative analyses with selected techniques and computer tools.

Findings

The set of 400 websites contained 119 (29.75%) that were not responsive. It exhibited a substantial potential for the optimisation of websites for mobile devices. The study revealed the most common usability failures such as distorted images, “scattered icons”, partial responsiveness and bothersome messages in pop-ups.

Originality/value

The research identified the most widespread problems with the tested websites. The study yielded recommendations for local governments, which may be useful when managing content, upgrading the website or replacing it with a new one.