bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene age predicts the transcriptional landscape of sexual morphogenesis in multicellular fungi
Authors: Merényi Zsolt , Virágh Máté , Gluck-Thaler Emile , Slot Jason C. , Kiss Brigitta , Varga Torda , Geösel András , Hegedüs Botond , Bálint Balázs , Nagy László G. 
Published: June 2021

AbstractMulticellularity has been one of the most important innovations in the history of life. The role of regulatory evolution in driving transitions to multicellularity is being increasingly recognized; however, patterns and drivers of transcriptome evolution are poorly known in many clades. We here reveal that allele-specific expression, natural antisense transcripts and developmental gene expression, but not RNA editing or a developmental hourglass act in concert to shape the transcriptome of complex multicellular fruiting bodies of fungi. We find that transcriptional patterns of genes are strongly predicted by their evolutionary age. Young genes showed more expression variation both in time and space, possibly because of weaker evolutionary constraint, calling for partially non-adaptive interpretations of evolutionary changes in the transcriptome of multicellular fungi. Gene age also correlated with function, allowing us to separate fruiting body gene expression related to simple sexual development from that potentially underlying complex morphogenesis. Our study highlighted a transcriptional complexity that provides multiple speeds for transcriptome evolution, but also that constraints associated with gene age shape transcriptomic patterns during transitions to complex multicellularity in fungi.
Nitrate reduction stimulates and is stimulated by phenazine-1-carboxylic acid oxidation by Citrobacter portucalensis MBL
Authors: Tsypin Lev M. , Newman Dianne K. 
Published: June 2021

ABSTRACTPhenazines are secreted metabolites that microbes use in diverse ways, from quorum sensing to antimicrobial warfare to energy conservation. Phenazines are able to contribute to these activities due to their redox activity. The physiological consequences of cellular phenazine reduction have been extensively studied, but the counterpart phenazine oxidation has been largely overlooked. Phenazine-1-carboxylic acid (PCA) is common in the environment and readily reduced by its producers. Here, we describe its anaerobic oxidation by Citrobacter portucalensis strain MBL, which was isolated from topsoil in Falmouth, MA, and which does not produce phenazines itself. This activity depends on the availability of a suitable terminal electron acceptor, specifically nitrate. When C. portucalensis MBL is provided reduced PCA and nitrate, it rapidly oxidizes the PCA. We compared this terminal electron acceptor-dependent PCA-oxidizing activity of C. portucalensis MBL to that of several other γ-proteobacteria with varying capacities to respire nitrate. We found that PCA oxidation by these strains in a nitrate-dependent manner is decoupled from growth and correlated with their possession of the periplasmic nitrate reductase Nap. We infer that bacterial PCA oxidation is widespread and propose that it may be genetically determined. Notably, oxidizing PCA enhances the rate of nitrate reduction to nitrite by C. portucalensis MBL beyond the stoichiometric exchange of electrons from PCA to nitrate, which we attribute to C. portucalensis MBL’s ability to also reduce oxidized PCA, thereby catalyzing a complete PCA redox cycle. This bidirectionality highlights the versatility of PCA as a biological redox agent.IMPORTANCEPhenazines are increasingly appreciated for their roles in structuring microbial communities. These tricyclic aromatic molecules have been found to regulate gene expression, be toxic, promote antibiotic tolerance, and promote survival under oxygen starvation. In all of these contexts, however, phenazines are studied as electron acceptors. Even if their utility arises primarily from being readily reduced, they need to be oxidized in order to be recycled. While oxygen and ferric iron can oxidize phenazines abiotically, biotic oxidation of phenazines has not been studied previously. We observed bacteria that readily oxidize phenazine-1-carboxylic acid (PCA) in a nitrate-dependent fashion, concomitantly increasing the rate of nitrate reduction to nitrite. Because nitrate is a prevalent terminal electron acceptor in diverse anoxic environments, including soils, and phenazine-producers are widespread, this observation of linked phenazine and nitrogen redox cycling suggests an underappreciated role for redox-active secreted metabolites in the environment.
Genomic differentiation within East Asian Helicobacter pylori
Authors: You Yuanhai , Thorell Kaisa , He Lihua , Yahara Koji , Yamaoka Yoshio , Cha Jeong-Heon , Murakami Kazunari , Katsura Yukako ,   TEAMHp, Kobayashi Ichizo , Falush Daniel , Zhang Jianzhong 
Published: June 2021

ABSTRACTThe East Asian region, including China, Japan and Korea, accounts for half of gastric cancer deaths. However, different areas have contrasting gastric cancer incidence and the population structure of Helicobacter pylori in this ethnically diverse region is yet unknown. We aimed to investigate genomic differences in H. pylori between these areas to identify sequence polymorphisms associated with increased cancer risk.We analysed 381 H. pylori genomes collected from different areas of the three countries using phylogenetic and population genetic tools to characterize population differentiation. The functional consequences of Single Nucleotide Polymorphisms (SNPs) with a highest fixation index (Fst) between subpopulations were examined by mapping amino-acid changes on 3D protein structure, solved or modelled.329/381 genomes belonged to the previously identified hspEAsia population indicating that import of bacteria from other regions of the world has been uncommon. Seven sub-regional clusters were found within hspEAsia, related to sub-populations with various ethnicities, geographies and gastric cancer risks. Sub-population-specific amino-acid changes were found in multi-drug exporters (hefC), transporters (frpB-4), outer membrane proteins (hopI), and several genes involved in host interaction, such as catalase, involved in H2O2 entrance, and a flagellin site mimicking host glycosylation. Several of the top hits including frpB-4, hefC, alpB/hopB, and hofC. were also differentiated within the Americas, indicating that a handful of genes may be key to local geographic adaptation.H. pylori within East Asia are not homogeneous but have become differentiated geographically at multiple loci that have facilitated adaptation to local conditions and hosts. This has important implications for further evaluation of these changes in relation to the varying gastric cancer incidence between geographical areas in this region.
Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations
Authors: Thorpe Harry A. , Tourrette Elise , Yahara Koji , Vale Filipa F. , Liu Siqi , Oleastro Mónica , Alarcon Teresa , Perets TsachiTsadok , Latifi-Navid Saeid , Yamaoka Yoshio , Martinez-Gonzalez Beatriz , Karayiannis Ioannis , Karamitros Timokratis , Sgouras Dionyssios N. , Elamin Wael , Pascoe Ben , Sheppard Samuel K. , Ronkainen Jukka , Aro Pertti , Engstrand Lars , Agreus Lars , Suerbaum Sebastian , Thorell Kaisa , Falush Daniel 
Published: June 2021

AbstractHelicobacter pylori lives in the human stomach and has a population structure which resembles that of its host. However, H. pylori from Europe and the Middle East trace a substantially higher fraction of ancestry from modern African populations than the humans that carry them. Here, we used a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations compared to either non-segregating or synonymous sites, implying selection to remove them. We used simulations to show that demographic bottlenecks can lead to long-term segregation of deleterious mutations, despite high rates of homologous recombination, but that population fitness can be restored by migration of small numbers of bacteria from non-bottlenecked populations, leading to mosaic patterns of ancestry like that seen for H. pylori. We conclude that H. pylori have been able to spread repeatedly from Africa by outcompeting strains that carried deleterious mutations accumulated during the original out-of-Africa bottleneck.
Differential yet integral contributions of Nrf1 and Nrf2 in the human antioxidant cytoprotective response against tert-butylhydroquinone as a pro-oxidative stressor
Authors: Wufur Reziyamu , Fan Zhuo , Liu Keli , Zhang Yiguo 
Published: June 2021

AbstractIn the past 25 years, Nrf2 had been preferentially parsed as a master hub of regulating antioxidant, detoxification and cytoprotective genes, albeit as a matter of fact that Nrf1, rather than Nrf2, is indispensable for cell homeostasis and organ integrity during normal growth and development. Here, distinct genotypic cell lines (Nrf1α−/−, Nrf2−/−ΔTA and caNrf2ΔN) are employed to determine differential yet integral roles of Nrf1 and Nrf2 in mediating antioxidant responsive genes to tBHQ as a pro-oxidative stressor. In Nrf1α−/− cells, Nrf2 was highly accumulated but also cannot fully compensate specific loss of Nrf1α’s function in its basal cytoprotective response against endogenous oxidative stress, though it exerted partially inducible antioxidant response, as the hormetic effect of tBHQ, against apoptotic damages. By contrast, Nrf2−/−ΔTA cells gave rise to a substantial reduction of Nrf1 in both basal and tBHQ-stimulated expression and hence resulted in obvious oxidative stress, but can still be allowed to mediate a potent antioxidant response, as accompanied by a significantly decreased ratio of GSSG to GSH. Conversely, a remarkable increase of Nrf1 expression was resulted from the constitutive active caNrf2ΔN cells, which were not manifested with oxidative stress, no matter if it was intervened with tBHQ. Such inter-regulatory effects of Nrf1 and Nrf2 on antioxidant and detoxification genes (encoding HO-1, NQO1, GCLC, GCLM, GSR, GPX1, TALDO, MT1E and MT2), as well on the ROS-scavenging activities of SOD and CAT, were further investigated. The collective results unraveled that Nrf1 and Nrf2 make distinctive yet cooperative contributions to finely tuning basal constitutive and/or tBHQ-inducible expression levels of antioxidant cytoprotective genes in the inter-regulatory networks. Overall, Nrf1 acts as a brake control for Nrf2’s functionality to be confined within a certain extent, whilst its transcription is regulated by Nrf2.
Mechanosensitive channel inhibition attenuates TGFβ2-induced actin cytoskeletal remodeling and reactivity in mouse optic nerve head astrocytes
Authors: Kirschner Alexander , Strat Ana N. , Yablonski John , Bagué Tyler , Li Haiyan , Herberg Samuel , Ganapathy Preethi S. 
Published: June 2021

AbstractAstrocytes within the optic nerve head undergo actin cytoskeletal rearrangement early in glaucoma, which coincides with astrocyte reactivity and extracellular matrix (ECM) deposition. Elevated transforming growth factor beta 2 (TGFβ2) levels within astrocytes have been described in glaucoma, and TGFβ signaling induces actin cytoskeletal remodeling and ECM deposition in many tissues. A key mechanism by which astrocytes sense and respond to external stimuli is via mechanosensitive ion channels. Here, we tested the hypothesis that inhibition of mechanosensitive channels will attenuate TGFβ2-mediated optic nerve head astrocyte actin cytoskeletal remodeling, reactivity, and ECM deposition. Primary optic nerve head astrocytes were isolated from C57BL/6J mice and cell purity was confirmed by immunostaining. Astrocytes were treated with vehicle control, TGFβ2 (5 ng/ml), GsMTx4 (a mechanosensitive channel inhibitor; 500 nM), or TGFβ2 (5 ng/ml) + GsMTx4 (500 nM) for 48 h. FITC-phalloidin staining was used to assess the formation of f-actin stress fibers and to quantify the presence of crosslinked actin networks (CLANs). Cell reactivity was determined by immunostaining for GFAP. Levels of fibronectin deposition were also quantified. Primary optic nerve head astrocytes were positive for the astrocyte marker GFAP and negative for markers for microglia (Iba1) and oligodendrocytes (OSP1). Significantly increased %CLAN-positive cells were observed after 48-h treatment with TGFβ2 vs. control in a dose-dependent manner. Co-treatment with GsMTx4 significantly decreased %CLAN-positive cells vs. TGFβ2 treatment and the presence of f-actin stress fibers. TGFβ2 treatment significantly increased GFAP and fibronectin fluorescence intensity, which were decreased with GsMTx4 treatment. Our data suggest inhibition of mechanosensitive channel activity as a potential therapeutic strategy to modulate actin cytoskeletal remodeling within the optic nerve head in glaucoma.
Anti-allergic and anti-inflammatory activities of black cumin extracts in in vitro and in vivo model systems
Authors: Shaheen Nazma , Azam Afiatul , Ganguly Amlan , Anwar Saeed , Parvez Md. Sorwer Alam , Punyamurtula Ujwal , Hasan Md. Kamrul 
Published: June 2021

AbstractBlack cumin (Nigella sativa) is a widely used ingredient of traditional medicine for its broad-spectrum pharmacological actions, including anti-allergic, bronchial asthma, and anti-inflammatory properties. We sought to evaluate BC extracts’ efficacy for their anti-allergic and anti-inflammatory properties using a comprehensive in vitro, in vivo, and silico experimental setup. To investigate whether BC extract has anti-inflammatory, anti-allergic, and analgesic therapeutic potentials in vitro and in vivo. The activity of BC was assessed through anti-allergic activity on rat basophilic leukemia-2H3 cell line, anti-inflammatory activity on J774.1A cell line, anti-inflammatory activity by carrageenan-induced rat paw edema, analgesic activity by acetic acid-induced writhing test, and ingenuity analysis of the BC extracts in inflammation control. BC exerted potent anti-allergic activity by inhibiting antigen-induced degranulation. An anti-inflammatory effect is shown by inhibiting TNF-α production. The acetic acid-induced writhing test shown a dose-dependent reduction of writhing number following BC administration. Rat paw edema test shown the dose-dependent reduction of paw edema volume following BC administration. Ingenuity Pathway Analysis (IPA) suggested BC extracts containing ferulic acid, p-coumaric acid, kaempferol, and quercetin can inhibit inflammation. This study suggests that bioactive compounds in BC extract act as an anti-allergic and anti-inflammatory agent by regulating several downstream and upstream inflammation pathways.
Phylogenetic Analysis of Crimean-Congo Hemorrhagic Fever Virus in Inner Mongolia, China
Authors: Kong Yunyi , Yan Chao , Liu Xiaodong , Jiang Lingling , Zhang Gang , He Biao , Li Yong 
Published: June 2021

AbstractCrimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne arbovirus that can cause bleeding and death in humans. The mortality rate in humans is between 5 to 30%. The pathogen is prevalent in more than 30 countries in the world. In China, reports of strains of CCHFV have been concentrated in Xinjiang province. However, the CCHFV strain has never been reported in Inner Mongolia, China. This study reports new CCHFV strains, HANM-18, from Hyalomma asiaticum and Hyalomma dromedarii collected in Alxa Left Banner and Alxa Right Banner in Inner Mongolia. Complete sequences of CCHFV were obtained by the nested PCR technique and used for analyzing the identity and evolutionary relationship with other CCHFV strains. Interestingly, our results showed that the S and L fragments of the HANM-18 strain had high degrees of identity with Xingjiang isolate strains, and the M fragment had significant identity with South African isolates. These analyses also indicate that the HANM-18 strain may have been prevalent in northwest Inner Mongolia for many years. This discovery will be helpful in CCHF prevention and control in Inner Mongolia, and it also adds new evidence to the epidemiology of CCHF in China.
Structural probing of Hsp26 activation and client binding by quantitative cross-linking mass spectrometry
Authors: Fürsch Julius , Voormann Carsten , Kammer Kai-Michael , Stengel Florian 
Published: June 2021

AbstractSmall heat-shock proteins (sHSP) are important members of the cellular stress response in all species. Their best described function is the binding of early unfolding states and the resulting prevention of protein aggregation. Most sHSPs exist as oligomers but vary in size and subunit organization. Many sHSPs exist as a polydisperse composition of oligomers which undergoes changes in subunit composition, folding status and relative distribution upon heat activation. To date only an incomplete picture of the mechanism of sHSP activation exists and in particularly the molecular basis of how sHSPs bind client proteins and mediate client specificity is not fully understood. In this study we have applied cross-linking mass spectrometry (XL-MS) to obtain detailed structural information on sHSP activation and client binding for yeast Hsp26. Our cross-linking data reveals the middle domain of Hsp26 as client-independent interface in multiple Hsp26::client complexes and indicates that client-specificity is likely mediated via additional binding sites within its αCD and CTE. Our quantitative XL-MS data underpins the middle domain as the main driver of heat-induced activation and client binding but shows that global rearrangements spanning all domains of Hsp26 are taking place simultaneously. We also investigated a Hsp26::client complex in the presence of Ssa1 (Hsp70) and Ydj1(Hsp40) at the initial stage of refolding and observe that the interaction between refolding chaperones is altered by the presence of a client protein, pointing to a mechanism where interaction of Ydj1 with the HSP::client complex initiates assembly of the active refolding machinery.
The information trust formation process for informal caregivers of people with dementia: a qualitative study
Authors: Sbaffi Laura , Hargreaves Sarah 
Published: June 2021

PurposeThis paper provides new insights on trust formation during information-seeking processes of informal caregivers of people with dementia and identifies the sources of information deemed as trustworthy by caregivers.Design/methodology/approachThe study adopts a phenomenological qualitative approach in the form of in-depth, semi-structured interviews with a sample of 20 informal caregivers.FindingsCaregivers trust sources that are perceived as authoritative and particularly value the information and advice provided by other caregivers. Trust in information can be divided into subjective and objective, but both are important precursors to the actual use of the information. The information available to caregivers is sufficient in quantity but inadequate in terms of ease of use, clarity and usefulness. Often, some key information needs remain unsatisfied due to the lack of timeliness, relevance and personalisation of the information.Practical implicationsThis paper provides recommendations for information and healthcare providers on how to improve communication and information relevance for informal caregivers of people with dementia.Originality/valueThis paper contributes to a more comprehensive perspective on caregivers’ information trust formation processes, which takes into account both the characteristics of the information and caregivers’ individual factors.
A measure of innovation performance: the Innovation Patent Index
Authors: Ponta Linda , Puliga Gloria , Manzini Raffaella 
Published: June 2021

PurposeThe measure of companies' Innovation Performance is fundamental for enhancing the value and decision-making processes of firms. The purpose of this paper is to present a new measure of Innovation Performance, called Innovation Patent Index (IPI), which makes it possible to quantitatively summarize different aspects of firms' innovation.Design/methodology/approachIn order to define the IPI, a secondary source, i.e. patent data, has been used. The five dimensions of IPI, i.e. efficiency, time, diversification, quality and internationalization have been defined both analyzing the literature and applying three different machine learning algorithms (regularized least squares, deep neural networks and decision trees), considering patent forward citations as a proxy of the innovation performance.FindingsResults show that the IPI index is a very useful tool, simple to use and very promptly. In fact, it is possible to get important results without making time consuming analysis with primary sources. It is a tool that can be used by managers, businessmen, policymakers, organizations, patent experts and financiers to evaluate and plan future activities, to enhance the innovation capability, to find financing and to support and improve innovation.Research limitations/implicationsPatent data are not widely used in all the sectors. Moreover, the pure number of forward citations is not the only forward looking indicator suggested by the literature.Originality/valueThe demand for a useable Innovation Performance tool, as well as the lack of tools able to grasp different aspects of the innovation, highlight the need to develop new instruments. In fact, although previous studies provide several measures of Innovation Performance, these are often difficult for managers to use, do not appreciate different aspects of the innovation and are not forward looking.