bluuebunny/crossref_metadata_2025 huggingface dataset:
Model-driven characterization of functional diversity ofPseudomonas aeruginosaclinical isolates with broadly representative phenotypes
Authors: Islam Mohammad Mazharul , Kolling Glynis L. , Glass Emma M. , Goldberg Joanna B. , Papin Jason A.
Published: October 2023

Pseudomonas aeruginosais a leading cause of infections in immunocompromised individuals and in healthcare settings. This study aims to understand the relationships between phenotypic diversity and the functional metabolic landscape ofP. aeruginosaclinical isolates. To better understand the metabolic repertoire ofP. aeruginosain infection, we deeply profiled a representative set from a library of 971 clinicalP. aeruginosaisolates with corresponding patient metadata and bacterial phenotypes. The genotypic clustering based on whole-genome sequencing of the isolates, multi-locus sequence types, and the phenotypic clustering generated from a multi-parametric analysis were compared to each other to assess the genotype-phenotype correlation. Genome-scale metabolic network reconstructions were developed for each isolate through amendments to an existing PA14 network reconstruction. These network reconstructions show diverse metabolic functionalities and enhance the collectiveP. aeruginosapangenome metabolic repertoire. Characterizing this rich set of clinicalP. aeruginosaisolates allows for a deeper understanding of the genotypic and metabolic diversity of the pathogen in a clinical setting and lays a foundation for further investigation of the metabolic landscape of this pathogen and host-associated metabolic differences during infection.

Impact statement

Pseudomonas aeruginosais a leading cause of infections in immunocompromised individuals and in healthcare settings. The treatment of these infections is complicated by the presence of a variety of virulence mechanisms and metabolic uniqueness among clinically relevant strains. This study is an attempt to understand the relationships between isolate phenotypic diversity and the functional metabolic landscape within a representative group ofP. aeruginosaclinical isolates. Characterizing this rich set of clinicalP. aeruginosaisolates allows for a deeper understanding of genotypic and metabolic diversity of the pathogen in a clinical setting and lays a foundation for further investigation of the metabolic landscape of this pathogen and host-associated metabolic differences in infection.
Pindel-TD: a tandem duplication detector based on a pattern growth approach
Authors: Yang Xiaofei , Zheng Gaoyang , Jia Peng , Wang Songbo , Ye Kai
Published: October 2023

Tandem duplication(TD) is a major type ofstructural variation(SV), and plays an important role in novel gene formation and human diseases. However, TDs are often missed or incorrectly classified as insertions by most of modern SV detection methods due to the lacking of specialized operation on TD related mutational signals. Herein, we developed a TD detection module of Pindel referred as Pindel-TD based on a TD specificpattern growthapproach. Pindel-TD detects TDs with a wide size range at single nucleotide resolution. Using simulation and real read data of HG002, we demonstrate that Pindel-TD outperformed other leading methods in terms of precision, recall, F1-score and robustness. Further applying Pindel-TD on data generated from K562 cancer cell line, we identified a TD located at the seventh exon ofSAGE1, explaining its high expression. Pindel-TD is available athttps://github.com/xjtu-omics/pindeland free for non-commercial use.
Instant Assembly of Collagen for Scaffolding, Tissue Engineering, and Bioprinting
Authors: Gong Xiangyu , Wen Zhang , Liang Zixie , Xiao Hugh , Lee Sein , Wright Thomas , Nguyen Ryan Y. , Rossello Alejandro , Mak Michael
Published: October 2023

Controllable assembly of cells and tissues offers potential for advancing disease and development modeling and regenerative medicine. The body’s natural scaffolding material is the extracellular matrix, composed largely of collagen I. However, challenges in precisely controlling collagen assembly limit collagen’s applicability as a primary bioink or glue for biofabrication. Here, we introduce a set of biopatterning methods, termed Tunable Rapid Assembly of Collagenous Elements (TRACE), that enables instant gelation and rapid patterning of collagen I solutions with wide range of concentrations. Our methods are based on accelerating the gelation of collagen solutions to instantaneous speeds via macromolecular crowding, allowing versatile patterning of both cell-free and cell-laden collagen-based bioinks. We demonstrate notable applications, including macroscopic organoid engineering, rapid free-form 3D bioprinting, contractile cardiac ventricle model, and patterning of high-resolution (below 5 (m) collagen filament. Our findings enable more controllable and versatile applications for multi-scale collagen-based biofabrication.
Elucidating Compound Mechanism of Action and Polypharmacology with a Large-scale Perturbational Profile Compendium
Authors: Hu Lucas ZhongMing , Douglass Eugene , Turunen Mikko , Pampou Sergey , Grunn Adina , Realubit Ron , Antolin Albert A. , Wang Alexander L.E. , Li Hai , Subramaniam Prem , Mundi Prabhjot S , Karan Charles , Alvarez Mariano , Califano Andrea
Published: October 2023

The Mechanism of Action (MoA) of a drug is generally represented as a small, non-tissue-specific repertoire of high-affinity binding targets. Yet, drug activity and polypharmacology are increasingly associated with a broad range of off-target and tissue-specific effector proteins. To address this challenge, we have leveraged a microfluidics-based Plate-Seq technology to survey drug perturbational profiles representing >700 FDA-approved and experimental oncology drugs, in cell lines selected as high-fidelity models of 23 aggressive tumor subtypes. Built on this dataset, we implemented an efficient computational framework to define a tissue-specific protein activity landscape of these drugs and reported almost 50 million differential protein activities derived from drug perturbationsvs.vehicle controls. These analyses revealed thousands of highly reproducible and novel, drug-mediated modulation of tissue-specific targets, leading to generation of a proteome-wide drug functional network, characterization of MoA-related drug clusters and off-target effects, dramatical expansion of druggable human proteome, and identification and experimental validation of novel, tissue-specific inhibitors of undruggable oncoproteins, most never reported before. The drug perturbation profile resource described here represents the first, large-scale, whole-genome-wide, RNA-Seq based dataset assembled to date, with the proposed framework, which is easily extended to elucidating the MoA of novel small-molecule libraries, facilitates mechanistic exploration of drug functions, supports systematic and quantitative approaches to precision oncology, and serves as a rich data foundation for drug discovery.
Feasibility of Inferring Spatial Transcriptomics from Single-Cell Histological Patterns for Studying Colon Cancer Tumor Heterogeneity
Authors: Fatemi Michael Y. , Lu Yunrui , Sharma Cyril , Feng Eric , Azher Zarif L. , Diallo Alos B. , Srinivasan Gokul , Rosner Grace M. , Pointer Kelli B. , Christensen Brock C. , Salas Lucas A. , Tsongalis Gregory J. , Palisoul Scott M. , Perreard Laurent , Kolling Fred W. , Vaickus Louis J. , Levy Joshua J.
Published: October 2023

Background

Spatial transcriptomics involves studying the spatial organization of gene expression within tissues, offering insights into the molecular diversity of tumors. While spatial gene expression is commonly amalgamated from 1-10 cells across 50-micron spots, recent methods have demonstrated the capability to disaggregate this information at subspot resolution by leveraging both expression and histological patterns. However, elucidating such information from histology alone presents a significant challenge but if solved can better permit spatial molecular analysis at cellular resolution for instances where Visium data is not available, reducing study costs. This study explores integrating single-cell histological and transcriptomic data to infer spatial mRNA expression patterns in whole slide images collected from a cohort of stage pT3 colorectal cancer patients. A cell graph neural network algorithm was developed to align histological information extracted from detected cells with single cell RNA patterns through optimal transport methods, facilitating the analysis of cellular groupings and gene relationships. This approach leveraged spot-level expression as an intermediary to co-map histological and transcriptomic information at the single-cell level.

Results

Our study demonstrated that single-cell transcriptional heterogeneity within a spot could be predicted from histological markers extracted from cells detected within a spot. Furthermore, our model exhibited proficiency in delineating overarching gene expression patterns across whole-slide images. This approach compared favorably to traditional patch-based computer vision methods as well as other methods which did not incorporate single cell expression during the model fitting procedures. Topological nuances of single-cell expression within a Visium spot were preserved using the developed methodology.

Conclusion

This innovative approach augments the resolution of spatial molecular assays utilizing histology as a sole input through synergistic co-mapping of histological and transcriptomic datasets at the single-cell level, anchored by spatial transcriptomics. While initial results are promising, they warrant rigorous validation. This includes collaborating with pathologists for precise spatial identification of distinct cell types and utilizing sophisticated assays, such as Xenium, to attain deeper subcellular insights.
What are the mechanisms of effect of group antenatal care? A systematic realist review and synthesis of the literature
Authors: Mehay Anita , Da Motta Giordana , Hunter Louise , Rayment Juliet , Wiggins Meg , Haora Penny , McCourt Christine , Harden Angela
Published: October 2023

Background

There is growing interest in the benefits of group models of antenatal care. Although clinical reviews exist, there have been few reviews that focus on the mechanisms of effect of this model.

Methods

We conducted a realist review using a systematic approach incorporating all data types (including non-research and audiovisual media), with synthesis along Context-Intervention-Mechanism-Outcome (CIMO) configurations.

Results

A wide range of sources were identified, yielding 100 relevant sources in total (89 written and 11 audiovisual). Overall, there was no clear pattern of ‘what works for whom, in what circumstances’. Findings revealed six interlinking mechanisms, including: social support, peer learning, active participation in health, health education and satisfaction or engagement with care. A further, relatively under-developed theory related to impact on professional practice (but was relatively under-developed). An overarching mechanism of empowerment featured across most studies but there was variation in how this was collectively or individually conceptualised and applied.

Conclusions

Mechanisms of effect are amplified in contexts where inequalities in access and delivery of care exist, but poor reporting of populations and contexts limited fuller exploration. We recommend future studies provide detailed descriptions of the population groups involved and that they give full consideration to theoretical underpinnings and contextual factors.

Registration

The protocol for this realist review was registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42016036768)
TheEscherichia coliTolC efflux pump protein is immunogenic and elicits protective antibodies
Authors: Silva TO , Costa LVS , Chagas do Nascimento L , Barbosa LS , Fanticelli JGC , Rotilho C , Silva LS , dos Santos Abreu J , Rajsfus BF , Bulla ACS , Carneiro J , Allonso D , Salgado DR , da Silva ML , Echevarria-Lima J , Moreira LO , Olsen PC
Published: October 2023

Antimicrobial resistance is an increasing worldwide public health burden that threatens to make the existent antimicrobials obsolete. Among the mechanisms of antimicrobial resistance is the overexpression of efflux pumps, such as the AcrA–AcrB–TolC which extrude diverse compounds, reducing the intracellular concentration of antimicrobials. TolC is the outer membrane protein of this pump and has recently gained attention as a therapeutic target. However, little is known about the immune response generated against the TolC protein. Here we evaluated the cellular and humoral immune response against the TolC fromEscherichia coli. Anin silicoepitope prediction of theE. coliTolC showed several residues could bind to human antibodies, and we showed that human plasma presented anti-TolC IgG and IgA antibodies. Gram-negative infected patients presented a slight increase in anti-TolC IgM amounts, compared to controls. RecombinantE. coliTolC protein stimulated macrophagesin vitroto produce nitric oxide, as well as IL-6 and TNF-α, assessed by Griess assay and ELISA, respectively. Immunization of mice with TolC intraperitoneally and anin vitrore-stimulation of lymph node cells led to increased percentage of T cell proliferation and IFNγ production, evaluated by flow cytometry and ELISA, respectively. We observed that TolC mouse immunization stimulated anti-TolC IgM and IgG production, with a higher level of IgG1 and IgG2, amongst the IgG subclasses. Finally, TolC IgG from mouse immune serum could bind to liveE. coli,increase bacterial uptake by macrophagesin vitro. TolC immunized mice had a survival rate increased in 60% post infection withE. coli. Our results showed that TolC is immunogenic, activating macrophages, T and B cells, leading to the production of protective antibodies againstE. coli.
Predicting prime editing efficiency across diverse edit types and chromatin contexts with machine learning
Authors: Mathis Nicolas , Allam Ahmed , Tálas András , Benvenuto Elena , Schep Ruben , Damodharan Tanav , Balázs Zsolt , Janjuha Sharan , Schmidheini Lukas , Böck Desirée , van Steensel Bas , Krauthammer Michael , Schwank Gerald
Published: October 2023

Prime editing is a powerful genome editing technology, but its efficiency varies depending on the pegRNA design and target locus. Existing computational models for predicting prime editing rates are limited by their focus on specific edit types and by omitting the local chromatin environment. In our study, we developed machine learning models that predict prime editing efficiencies across a wide range of edit types up to 15 bp (’PRIDICT2.0’) and in different chromatin contexts (’ePRIDICT’). Both models can be accessed atwww.pridict.it.
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

The 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.

Significance

We 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

Ciliates 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

Nitroaromatic 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

Macrophages 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

Acinetobacter 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

The 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

Blast 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

Kaposi’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.
Managing Internal Growth at Vedanta Group
Authors: Agarwal Promila , Karna Amit
Published: October 2023

The case describes the internal growth workshop initiative at Vedanta Group. Anil Agarwal in 1976 founded Vedanta as a scrap-metal dealership in Mumbai (then Bombay). Over the years, Anil pursued a very aggressive growth journey with a vision to create a leading global natural resource company. The principal objective of discussing this case is to understand how Vedanta introduced this initiative and how it fits within the strategic human resource management at the group.
Micro-political strategies in negotiating the role of women's networks in organizations
Authors: Gremmen Ine , Benschop Yvonne W.M.
Published: October 2023

Purpose

The 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/approach

The 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.

Findings

Adding 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/value

The 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

Purpose

This 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/approach

This 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).

Findings

The 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 implications

Considering 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/value

The 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

Purpose

The 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/approach

The 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.

Findings

This 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 implications

Based 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/value

This 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).
Effect of different hydrolysis methods on composition and functional properties of fish protein hydrolysate obtained from Bigeye tuna waste
Authors: Abd El‐Rady Tasneem K. , Tahoun Al‐Azab M. , Abdin Mohamed , Amin Hesham F.
Published: October 2023

The objective of this research is to investigate the impact of different hydrolysis (chemical, enzymatic and microbiological) methods of Bigeye tuna waste (Thunnus obesus) on yield, degree of hydrolysis (DH), chemical composition, amino acid profile, functional properties and microbial quality of FPH produced. The enzymatic technique produced the highest yield (11.04%) and the greatest DH (39.04%) while it gave the lowest average peptide chain length (2.56) (P < 0.05). Also, protein and fat (76.37% and 10.82%, respectively) were the highest in the enzymatic hydrolyzed fish (FPH‐E) followed by microbial fermentation (FPH‐M) (P < 0.05). In FPH‐E, FPH‐M and chemical fish protein hydrolysates (FPH‐C), the essential to non‐essential amino acid ratios were 2.43, 1.79 and 0.51, respectively. They also had good functional properties, although they were less than FPH‐C in terms of water binding capacity (3.47 and 4.18 g g−1), oil binding capacity (9.84 and 7.38 g g−1) and foaming capacity (25% and 30%, respectively), and their foam stability rate was high. All FPHs products had a low range of microbial counts, with the FPH‐M exhibiting the greatest total count of bacteria, lactic acid bacteria and moulds and yeasts. Therefore, the biologically extracted FPH especially FPH‐E has the best compositions and qualities, making them an alternative ingredient for fish meal in fish feed formulation.
Economic production with Poisson demand, lost sales, fixed‐rate discrete replenishment, and a constant setup time
Authors: Schmitt Thomas , Faaland Bruce , McKay Mark
Published: October 2023

We address a production/inventory problem for a single product and machine where demand is Poisson distributed, and the times for unit production and setup are constant. Demand not in stock is lost. We derive a solution for a produce‐up‐to policy that minimizes average cost per unit time, including costs of setup, inventory carrying, and lost sales. The machine is stopped periodically, possibly rendered idle, set up for a fixed period, and then restarted. The average cost function, which we derive explicitly, is quasi‐convex sparately in the produce‐up‐to level Q, the low‐level R that prompts a setup, and jointly in R equals Q. We start by finding the minimizing value of Q where R equals 0, and then extend the search over larger R values. The discrete search may end with R less than Q, or on the matrix diagonal where R equals Q, depending on the problem parameters. Idle time disappears in the cycle when R equals Q, and the two‐parameter system folds into one. This hybrid policy is novel in make‐to‐stock problems with a setup time. The number of arithmetic operations to calculate costs in the ( Q, R) matrix depends on a vector search over Q. The computation of the algorithm is bounded by a quadratic function of the minimizing value of Q. The storage requirements and number of cells visited are proportional to it.
Association of the Arabidopsis oleoyl Δ12‐desaturase FAD2 with pre‐cis‐Golgi stacks at endoplasmic reticulum‐Golgi‐exit sites
Authors: Launhardt Larissa , Uhlenberg Johanna , Stellmach Hagen , Schomburg Marie , Hause Bettina , Heilmann Ingo , Heilmann Mareike
Published: October 2023

The unsaturation of phospholipids influences the function of membranes. In Arabidopsis thaliana, the oleoyl Δ12‐desaturase FAD2 converts oleic (18:1Δ9) to linoleic acid (18:2Δ9,12) and influences phospholipid unsaturation in different cellular membranes. Despite its importance, the precise localization of Arabidopsis FAD2 has not been unambiguously described. As FAD2 is thought to modify phospholipid‐associated fatty acids at the endoplasmic reticulum (ER), from where unsaturates are distributed to other cellular sites, we hypothesized that FAD2 locates to ER subdomains enabling trafficking of lipid intermediates through the secretory pathway. Fluorescent FAD2 fusions used to test this hypothesis were first assessed for functionality by heterologous expression in yeast (Saccharomyces cerevisiae), and in planta by Arabidopsis fad2 mutant rescue upon ectopic expression from an intrinsic FAD2 promoter fragment. Light sheet fluorescence, laser scanning confocal or spinning disc microscopy of roots, leaves, or mesophyll protoplasts showed the functional fluorescence‐tagged FAD2 variants in flattened donut‐shaped structures of ~0.5–1 μm diameter, in a pattern not resembling mere ER association. High‐resolution imaging of coexpressed organellar markers showed fluorescence‐tagged FAD2 in a ring‐shaped pattern surrounding ER‐proximal Golgi particles, colocalizing with pre‐cis‐Golgi markers. This localization required the unusual C‐terminal retention signal of FAD2, and deletion or substitutions in this protein region resulted in relaxed distribution and diffuse association with the ER. The distinct association of FAD2 with pre‐cis‐Golgi stacks in Arabidopsis root and leaf tissue is consistent with a contribution of FAD2 to membrane lipid homeostasis through the secretory pathway, as verified by an increased plasma membrane liquid phase order in the fad2 mutant.
Racial/Ethnic Differences in Physical Activity in a Low-Income Sample in Texas
Authors: Ranjit Nalini , Badillo David J. , Hoelscher Deanna M. , Macias Sarah , Gonzalez Alejandra , Wilkinson Anna V.
Published: October 2023

Introduction: National data reveal that the age-adjusted prevalence of leisure-time physical inactivity is higher among Blacks and Hispanics compared with Whites. However, these estimates do not consider nonleisure physical activity (PA). Also, race/ethnicity in these findings may by confounded by socioeconomic status disparities in PA. Here, we examine racial/ethnic differences in multiple measures of PA within a lower socioeconomic status sample. Methods: Participants in the current cross-sectional study (n = 1526 adults, aged ≥ 18 y) were recruited from Supplemental Nutrition Assistance Program-Education classes (nutrition education classes that target low-income people) in Texas. Self-report data were obtained using survey questionnaires in spring and fall 2018. PA outcomes of 4 different intensities were assessed: mean daily time spent walking, engaging in moderate and vigorous PA, and sitting. Additional PA-related measures included use and awareness of community PA resources. Linear regression models examined racial/ethnic differences in the 4 PA outcomes after adjusting for participant gender, age, household composition measures, and various socioeconomic status measures. Results: In this low-income sample, Hispanic and Black participants spent 6 to 9 more minutes per day walking and engaging in moderate and vigorous PA compared with White/other participants (P < .05 for each measure). Conversely, White/other participants reported spending 82 more minutes sitting per day than Black and Hispanic participants (P < .01). Overall, Black participants were most likely to utilize community PA resources and report ease of engaging in exercise. Discussion: Together, these results reveal greater engagement in PA by racial/ethnic minorities in low-income communities compared with Whites. Our results have implications for tailoring PA programming to these communities.
Wünderlich’s syndrome in a haemodialysis patient
Authors: Wood Anna , Ismail Ibrahim
Published: October 2023

Wünderlich’s syndrome, or spontaneous renal haemorrhages, are rare, atraumatic, intraparenchymal and perirenal haemorrhages, which are difficult to diagnose and can be potentially fatal.

Patients who are dialysis-dependent are at an increased risk of bleeding, due to an association between uraemia and platelet dysfunction; for this reason, the use of double antiplatelets is avoided in this cohort. Case studies exist demonstrating spontaneous bleeds in these patients.

Fish oil is used increasingly within medicine: however, it is known to interfere with platelet aggregation, therefore, theoretically increasing the tendency to bleed. The topic remains under debate, with systemic reviews refuting a correlation between intraoperative and postoperative bleeding and fish oil consumption. There is, however, an absence of literature on the adverse effects of fish oil when taken in large quantities.

This case study explores the case of a patient who had a spontaneous renal bleed following a large, self-medicated dose of fish oil.
THE ROLES OF PRODUCT INNOVATION CAPABILITY IN MARKETING PERFORMANCE
Authors: KHASANAH IMROATUL , SUKRESNA I. MADE
Published: October 2023

This study examines the role of product innovation capability in mediating the effect of market sensing capability on marketing performance. The sample data consist of 338 SMEs in the food product industry in Central Java, Indonesia. A model consisting of five hypotheses was proposed and tested. The statistical tests cover the following variables: market sensing capability, product innovation capability, competitive advantage and marketing performance. Structural Equation Modeling was used in the model and hypotheses testing. The results show that the five hypotheses have a positive and significant effect. Product innovation capability has the greatest influence on marketing performance, suggesting its important role in improving marketing performance. The results suggest that in increasing product innovation capability, SMEs must perpetually create and offer new ideas by considering market trends. Second, SMEs must be innovative in creating new food products in terms of both taste and packaging. Third, SMEs need to be the first to offer new products. Finally, SMEs must utilize the advancement of technology to develop food products and their variations.