bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oscillatory traveling waves reveal predictive coding abnormalities in schizophrenia
Authors: Alamia Andrea , Gordillo Dario , Chkonia Eka , Roinishvili Maya , Cappe Celine , Herzog Michael H. 
Published: October 2023

AbstractThe computational mechanisms underlying psychiatric disorders are hotly debated. One hypothesis, grounded in the Bayesian predictive coding framework, proposes that schizophrenia patients have abnormalities in encoding prior beliefs about the environment, resulting in abnormal sensory inference, which can explain core aspects of the psychopathology, such as some of its symptoms. Here, we tested this hypothesis by identifying oscillatory traveling waves as neural signatures of predictive coding. By analyzing a EEG dataset. comprising 146 schizophrenia patients and 96 age-matched healthy controls, we found that schizophrenia patients have stronger top-down alpha-band traveling waves compared to healthy controls during resting state, reflecting stronger precise priors at higher levels of the predictive processing hierarchy. Conversely, we found stronger bottom-up alpha-band waves in schizophrenia patients during a visual task reflecting an alteration of lower sensory priors. Our results yield a novel spatial-based characterization of oscillatory dynamics in schizophrenia, considering brain rhythms as traveling waves and providing a unique framework to study the different components involved in a predictive coding scheme. Altogether, our findings significantly advance our understanding of the mechanisms involved in fundamental pathophysiological aspects of schizophrenia, promoting a more comprehensive and hypothesis-driven approach to psychiatric disorders.SignificanceWe provide novel evidence favoring the Bayesian predictive coding interpretation of schizophrenia. Relying on computational and experimental works that characterized electrophysiological correlates of predictive processes, we investigate oscillatory traveling waves in EEG data of 146 schizophrenia patients and 96 age-matched healthy controls. Our results reveal stronger top-down alpha-band traveling waves in schizophrenia patients, reflecting an increase in the precision of high-level priors. On the other hand, we observed an increase in bottom-up alpha-band waves during a visual task, in line with the proposed reduction in precision of low-level sensory priors. Our findings suggest that traveling waves’ analysis is a versatile technique to probe predictive processing mechanisms in different cognitive processes. Impairments in this mechanism may underlie perceptual alterations as well as the pronounced clinical symptoms of schizophrenia. The strong hypothesis-driven nature of our results accentuates the relevance of our findings.
How did UGA codon translation as tryptophan evolve in certain ciliates? A critique of Kachale et al. 2023Nature
Authors: Swart Estienne Carl , Emmerich Christiane , Seah Kwee Boon Brandon , Singh Minakshi , Shulgina Yekaterina , Singh Aditi 
Published: October 2023

AbstractCiliates are a widespread clade of microbial eukaryotes with the greatest diversity of nuclear genetic codes (at least eight) following a recent addition1. All non-standard ciliate genetic codes involve stop codon reassignments1,2,3. Two of these codes are ambiguous1–3, with “stop” codons either translated or terminating translation depending on their context2,3. Ambiguous genetic codes have arisen not only in ciliates, but also independently in trypanosomatids from the genusBlastocrithidia4and an alveolate species from the genusAmoebophrya5. Two ambiguous genetic codes in ciliates share translation of UGA “stop” codons as tryptophan withBlastocrithidiaand theAmoebophryaspecies. tRNA genes with complementary anticodons to reassigned UAA and UAG stop codons have invariably been found in ciliate species that translate these codons1,2. Furthermore, though a UGA-cognate tRNACysUCAwas reported inEuplotes6, a ciliate genus that translates UGA as cysteine, vexingly, no nuclear genome-encoded tRNATrpUCAhas been found in ciliate species with UGA tryptophan codons. Recently, Kachale et al. provided evidence for UGA translation as tryptophan inBlastocrithidia nonstopand the ciliateCondylostoma magnumusing 4 base pair anticodon stem (AS) near-cognate tryptophan tRNATrpCCA’s, rather than the typical 5 base pair stem tRNAs7. New tRNA data we report from additional ciliates bolsters this hypothesis. Kachale et al. also hypothesised that a particular amino acid substitution in the key stop codon recognition protein, eRF1 (eukaryotic Release Factor 1), favours translation of UGA as tryptophan instead of termination7. Contrary to Kachale et al, we propose such substitutions favouring reduced eRF1 competition enhancing “stop” codon translation do not need to occur concomitantly with tRNA alterations or acquisitions to evolve new genetic codes via stop codon reassignment. We report multiple instances of the substitution investigated in Kachale et al. 2023 that have not led to UGA translation, and multiple ciliate species with UGA tryptophan translation but without the substitution, indicating it is not necessary. Consistent with the ambiguous intermediate hypothesis for genetic code evolution, experimental evidence and our observations suggest continued potential ciliate eRF1-tRNA competition.
Fexinidazole induced cytotoxicity is distinct from related anti-trypanosome nitroaromatic drugs
Authors: Rogers Indea , Berg Kenna , Ramirez Hayley , Hovel-Miner G A 
Published: October 2023

ABSTRACTNitroaromatic drugs are of critical importance for the treatment of trypanosome infections in Africa and the Americas. Fexinidazole recently joined benznidazole and nifurtimox in this family when it was approved as the first oral therapy against Human African trypanosomiasis (HAT). Nitroaromatic prodrugs are bioactivated by the trypanosome-specific type I nitroreductase (NTR) enzyme that renders the compounds trypanocidal. A caveat to the specificity of NTR activation is the potential for drug resistance and cross-resistance that can arise if NTR expression or functionality is altered through mutation. The outcomes of NTR bioactivation of nitroaromatic compounds is variable but can include the formation highly reactive open chain nitriles that can damage biomolecules including DNA. A proposed mechanism of action of nitroaromatic compounds is the formation of reactive oxygen species (ROS) resulting in the formation of trypanocidal levels of DNA damage. Fexinidazole made its way to clinical approval without a significant interrogation of its effects on trypanosome biology and a limited understanding of its mechanism of action. Early reports mentioned fexinidazole potentially affects DNA synthesis but without supporting data. In this study, we evaluated and compared the cytotoxic effects of nifurtimox, benznidazole, and fexinidazole onTrypanosoma bruceiusing in vitro analyses. Specifically, we sought to differentiate between the proposed effects of nitroaromatics on DNA damage and DNA synthesis. Toward this goal we generated a novel γH2A-based flow cytometry assay that reports DNA damage formation in conjunction with cell cycle progression. Here we report that fexinidazole’s cytotoxic outcomes are distinct from the related drugs nifurtimox and benznidazole. Specifically, we show that fexinidazole treatment results in a pronounced defect in DNA synthesis that reduces the population of parasites in S phase. In contrast, treatment with nifurtimox and benznidazole appear accumulate DNA damage early in cell cycle and result in a defective G2population. The findings presented here bring us closer to understanding the anti-trypanosomatid mechanisms of action of nitroaromatic compounds, which will promote improved drug design and help combat potential drug resistance in the future. Our findings also highlight DNA synthesis inhibition as a powerful anti-parasitic drug target.
Post-transcriptional control contributes to hypoxia-induced tumorigenic phenotypes in macrophages
Authors: Courvan Edward M.C. , Parker Roy R. 
Published: October 2023

AbstractMacrophages are effector immune cells that experience substantial changes to oxygenation when transiting through tissues, especially when entering tumors or infected wounds. How the transition to hypoxia alters gene expression and macrophage effector function remains poorly understood, especially at the post-transcriptional level. Here we use TimeLapse-seq to measure how hypoxia modifies inflammatory activation of primary macrophages. Nucleoside recoding sequencing allowed us to derive steady-state transcript levels, degradation rates, and transcriptional synthesis rates from the same dataset. We find that inflammatory activation of macrophages is altered by hypoxia due to increased mRNA decay. Destabilized transcripts encode for proteins associated with phagocytosis and proteolysis of the extracellular matrix. Consistent with differential gene expression, we observed hypoxia alters the specificity of macrophage phagocytosis and reduces their invasion of extracellular matrix. Hypoxic gene expression bears similarity to tumorigenic macrophages in solid tumor biopsies suggesting post-transcriptional control contributes to the macrophage transition from tumoricidal to tumorigenic.
Emergence ofAcinetobacter baumanniiInternational Clone 10 predominantly found in the Middle East
Authors: Karah Nabil , Faille Nathan , Grenier Frédéric , Abou-Fayad Antoine , Higgins Paul G. , Al-Hassan Leena , Evans Benjamin A. , Poirel Laurent , Bonnin Rémy , Hammerum Anette M. , Hansen Frank , Rafei Rayane , Hamze Monzer , Didelot Xavier , Castillo-Ramírez Santiago , Lévesque Simon , Rodrigue Sébastien , Uhlin Bernt Eric , Haraoui Louis-Patrick 
Published: October 2023

AbstractAcinetobacter baumanniiis a globally distributed human pathogen. Infections caused by carbapenem-resistant isolates ofA. baumannii(CRAB) are of great concern, as treatment options are very limited. Despite having among the highest rates reported worldwide, there exists limited genomic data from CRAB strains isolated in the Middle East. Here we report epidemiological, phenotypic, and genome sequencing data (short reads and long reads) on a set of 60A. baumanniiisolates belonging to Sequence Type ST158 (Pasteur MLST scheme). They represent a novel international clone (IC), designated IC10, with limited geographic spread beyond the Middle East. Specific antibiotic-resistance genes associated with this clone were identified and data on the plasmid content associated with this lineage are presented.
Ongoing evolution of theMycobacterium tuberculosislactate dehydrogenase reveals the pleiotropic effects of bacterial adaption to host pressure
Authors: Stanley Sydney , Wang Xin , Liu Qingyun , Kwon Young Yon , Frey Abigail M , Hicks Nathan D , Vickers Andrew J , Hui Sheng , Fortune Sarah M 
Published: October 2023

AbstractThe bacterial determinants that facilitateMycobacterium tuberculosis(Mtb) adaptation to the human host environment are poorly characterized. We have sought to decipher the pressures facing the bacteriumin vivoby assessing Mtb genes that are under positive selection in clinical isolates. One of the strongest targets of selection in the Mtb genome islldD2, which encodes a quinone-dependent L-lactate dehydrogenase (LldD2) that catalyzes the oxidation of lactate to pyruvate. Lactate accumulation is a salient feature of the intracellular environment during infection andlldD2is essential for Mtb growth in macrophages. We determined the extent oflldD2variation across a set of global clinical isolates and defined how prevalent mutations modulates Mtb fitness. We show the stepwise nature oflldD2evolution that occurs as a result of ongoinglldD2selection in the background of ancestral lineage defining mutations and demonstrate that the genetic evolution oflldD2additively augments Mtb growth in lactate. Using quinone-dependent antibiotic susceptibility as a functional reporter, we also find that the evolvedlldD2mutations functionally increase the quinone-dependent activity of LldD2. Using13C-lactate metabolic flux tracing, we find thatlldD2is necessary for robust incorporation of lactate into central carbon metabolism. In the absence oflldD2, label preferentially accumulates in methylglyoxal precursors dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P) and is associated with a discernible growth defect, providing experimental evidence for accumulated lactate toxicity via a methylglyoxal pathway that has been proposed previously. The evolvedlldD2variants increase lactate incorporation to pyruvate but also alter flux in the methylglyoxal pathway, suggesting both an anaplerotic and detoxification benefit tolldD2evolution. We further show that the mycobacterial cell is transcriptionally sensitive to the changes associated with alteredlldD2activity which affect the expression of genes involved in cell wall lipid metabolism and the ESX-1 virulence system. Together, these data illustrate a multifunctional role of LldD2 that provide context for the selective advantage oflldD2mutations in adapting to host stress.
Wild and cultivated rice host different populations of the blast fungus,Pyricularia oryzae, in Mali
Authors: Diagne Diariatou , Adreit Henri , Milazzo Joëlle , Koita Ousmane , Tharreau Didier 
Published: October 2023

ABSTRACTBlast is a devastating disease of rice caused by the fungusPyricularia oryzae. The role of infected straw and seed as sources of primary inoculum in blast disease epidemics is well known. The role of alternative hosts is yet to be confirmed. The current study sought to assess if wild rice is a major source of inoculum for cultivated rice by comparing the genetic structure ofP. oryzaepopulations from both hosts. Cross infectivity ofP. oryzaeisolates was also assessed using pathogenicity tests. Samples were collected from cultivated and wild rice organs with blast symptoms in irrigated and lowland areas of Mali in Koulikoro, Sikasso, and Ségou regions. Under controlled conditions,P. oryzaeisolates from wild rice were pathogenic to cultivated rice but, on average, had a narrower range of cultivar compatibility. Results of pathogenicity tests suggest thatP. oryzaeisolates from wild rice have the potential to attack cultivated rice in the field. However, populations ofP. oryzaeon cultivated and wild rice were genetically differentiated. Thus, although physically close, each host plant hosts a different population of the pathogen, and our results support the hypothesis that wild rice is not a major source of blast inoculum for cultivated rice.
Tim-1 and Tim-4 mediate entry of the human Kaposi’s sarcoma-associated herpesvirus and the related rhesus monkey rhadinovirus
Authors: Scribano Stefano , Schlagowski Sarah , Liu Shanchuan , Fricke Thomas , Yang Xiaoliang , Neipel Frank , Großkopf Anna K. , Hörnich Bojan F. , Backovic Marija , Ensser Armin , Hahn Alexander S. 
Published: October 2023

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) is a human tumor virus. It is associated with Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV is known to interact with several different receptors, among them heparan sulfate proteoglycans, Eph family receptors, and integrins. We mutated the closely related rhesus monkey rhadinovirus in the known receptor interaction sites for Eph family and Plexin domain containing proteins and found it to still replicate on certain cells. This lytic virus was then used as a selection agent in a genome-wide CRISPR knockout screen, which identified TIM1 and NRP1 as host dependency factors. NRP1 is also host factor for the related Epstein-Barr virus and was recently reported to promote KSHV infection, which we confirm even if it functions with low efficiency on most cells and became functional only after ablation of the Eph receptor interaction. Further analysis through overexpression demonstrated that Tim-1 and the related Tim-4 are strong mediators of RRV and KSHV infection, in particular in the absence of other receptor interactions and even more pronounced for a KSHV mutant deleted in glycoprotein K8.1. Both Tim-1 and Tim-4 are heavily O-glycosylated phosphatidylserine (PS) receptors. For KSHV in particular, experiments with mutated Tim-1 and comparison to Ebola virus glycoprotein-driven entry indicate that the interaction with Tim-1 occurs through PS-binding by Tim-1 and suggest additional interaction in a PS-independent manner. The mucin-like domain of Tim-1 is required for optimal receptor function. The use of Tim proteins for entry is a novelty for herpesviruses and underscores the unique biology of KSHV and RRV.
Micro-political strategies in negotiating the role of women's networks in organizations
Authors: Gremmen Ine , Benschop Yvonne W.M. 
Published: October 2023

PurposeThe authors aim to contribute to current knowledge on women's networks in organizations by exploring the strategies employed by members of women's networks, Human Resources (HR) management and senior line management to negotiate the role of these networks in their organizations.Design/methodology/approachThe authors employ the theoretical perspective of micro-politics to analyze qualitative data they collected in an action research project using open-ended interviews and participant observation. The interviews were conducted with network board and active members, and members of their organizations' HR departments and senior management. Participant observation of the interviewees' interactions took place during facilitated workshops.FindingsAdding to the literature, the authors find that members of the different parties employ different micro-political strategies. Many senior HR and management members demand that the networks' activities contribute to the organizations' diversity aims and bottom line. They largely avoid strategic cooperation with the networks. Most network members, in turn, resist the restricted role of the networks as an instrument to realize their organizations' business case. They claim some freedom to independently decide on the networks' strategies and activities. They resist being attributed tasks and responsibilities that they consider to reside with their organizations. Moreover, they try to sustain cooperative relationships with senior HR and management in an advisory role.Originality/valueThe action research approach enabled the authors to contribute to existing knowledge and extend the micro-politics theoretical perspective to include the collective agency of members of organizational groups and cooperation between these groups.
Serial multiple mediation of career adaptability and self-perceived employability in the relationship between career competencies and job search self-efficacy
Authors: Gerçek Merve 
Published: October 2023

PurposeThis study aims to explore the relationships between career competencies and job search self-efficacy via the serial multiple mediation effect of career adaptability and self-perceived employability within multiple theoretical frameworks.Design/methodology/approachThis study adopts a cross-sectional design to collect data at a specific point in time and employs self-report questionnaires to collect data from participants. In total, 302 students from the “management and organization department” in a vocational school of a public university completed the survey forms. To test the hypothesized model, a serial multiple mediation analysis was performed using structural equation modeling (SEM) via SPSS (Statistical Package for Social Sciences) AMOS (Analysis of Moment Structures).FindingsThe results indicated that career competencies, career adaptability, job search self-efficacy and self-perceived employability all had significant and positive relationships. Additionally, the relationship between career competencies and job search self-efficacy was serially mediated by career adaptability and self-perceived employability as anticipated.Practical implicationsConsidering the growing importance of the subject of how universities might better prepare their graduates for the job market, the study's findings have important policy implications. University students should also be provided with career management resources, specifically adaptation resources, to help them navigate their individual characteristics and transfer more successfully into the existing job market. This is the cause of the need for constant planning, adaptation, assessment and evaluation of career competencies in current labor markets.Originality/valueThe study contributes to international career development and vocational education research by filling a gap in the literature by demonstrating that job search self-efficacy, which is a predictor of job search behavior, can be promoted by career competencies, career adaptability and self-perceived employability. These findings are particularly significant because they highlight the importance of career-related knowledge, skills and abilities in engaging university students seeking employment in a developing country with a highly competitive labor market.
Do customers evaluate the competence of SME retailers and retail chains differently in the context of online product presentations?
Authors: Mennekes Theresia , Röding Tobias , Wagner Gerhard , Schramm-Klein Hanna 
Published: October 2023

PurposeThe purpose of this paper is to explore the extent to which customers evaluate inferior product presentations on a local shopping platform based on the retailer (small and medium-sized enterprise [SME] vs retail chain).Design/methodology/approachThe authors conducted a between-subject online study (N = 728) with a 2 (SME vs retail chain) x 2 (high vs low-quality product presentation) between-subject experimental design. The authors conducted several analyses of variance to analyze the hypotheses and analyses of covariance for a mediating effect.FindingsThis study's results show that customers tend to overlook inaccuracies from a retail chain more often than they overlook inaccuracies from SME retailers. The authors show that the perceived competence of the retailer mediates the impact of the retailer's quality on customer purchasing intentions, not only for the presented product but also for the retailer itself.Practical implicationsBased on this study's results, the authors give implications for retailer cross-channel strategies and hint at the importance of emphasizing the retail size.Originality/valueThis paper provides important contributions to the literature on resource-advantage theory by explaining that consumers perceive quality differences within product presentations on online shopping platforms differently with regard to retail chains vs SME retailers. Moreover, the information processing theory helps to provide a theoretical foundation concerning differences in online store quality (via engineered low- vs high-quality product presentations in this study).