bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain natriuretic peptide improves heart regeneration after infarction by stimulating cardiomyocyte renewal
Authors: Bon-Mathier Anne-Charlotte , Déglise Tamara , Rignault-Clerc Stéphanie , Bielmann Christelle , Mazzolai Lucia , Rosenblatt-Velin Nathalie
Published: July 2022

Aim

Brain Natriuretic Peptide (BNP) supplementation after infarction increases heart function and decreases heart remodeling. BNP receptors, NPR-A and NPR-B, are expressed on adult cardiomyocytes (CMs). We thus investigated whether a part of the BNP cardioprotective effect in infarcted and unmanipulated hearts is due to modulation of the CM fate.

Methods and Results

BNP was injected in infarcted adult mice and in unmanipulated neonatal and adult mice. CMs were isolated, counted and characterized.

Increased number of CMs was detected in the hypoxic area of infarcted hearts, and in unmanipulated neonatal and adult hearts after BNP treatment. Accordingly, Troponin T plasma concentration was significantly reduced 1 and 3 days after infarction in BNP-treated mice, demonstrating less CM death. Furthermore, higher number of small, dedifferentiated and mononucleated CMs were identified in adult BNP-treated hearts when compared to saline-treated hearts. BNP-treated CMs express higher levels of mRNAs coding forhif1 alphaand for the different cyclins than CMs isolated from saline-treated hearts. Higher percentages of CMs undergoing DNA synthesis, expressing Ki67, phospho histone3 and Aurora B were detected in all BNP-treated hearts, which suggests that BNP stimulates CMs to re-enter to the cell cycle. Resultsin vitroconfirmed that BNP stimulates the proliferation of the neonatal CMs and the dedifferentiation of the adult CMs.

BNP effect on adult CMsin vivois mediated by NPR-A binding and activation of the ERK MAP kinase pathway. Interestingly, increased number of CMs was also detected in adult infarcted hearts treated with LCZ696, which inhibits all natriuretic peptide degradations.

Conclusions

Altogether, our results identified BNP and all therapies aimed to increase BNP’s bioavailability (such as LCZ696 treatment) as new targets to increase heart regeneration. By protecting CMs from cell death, and by stimulating their proliferation, BNP treatment leads to increased number of CMs in neonatal, adult unmanipulated and infarcted hearts.
Establishment of a novel fetal ovine heart cell line by spontaneous cell fusion
Authors: Suleiman Khalid M. , Aljulidan Mutaib M. , Hussein Gamal eldin M. , Alkhalaf Habib N.
Published: July 2022

We established a unique immortal cell line designated, FOH-SA, by serial passage of fetal ovine heart cells. In a novel phenomenon in cell biology, we demonstrated that the immortalization of the line supervened as a result of spontaneous cellular and nuclear fusion of two morphologically distinct cardiocytes in passage 29. Fused cells gave progeny cells which grew into multicellular filaments. Trypsinization of the filamentous multicellular growth gave the immortal heart cell line.

Comparative single nucleotide polymorphism (SNP) genotyping of the cell line before and after cell fusion revealed a large scale genetic conversion resulting in 96% homozygosity in SNPs genotypes in the progeny cells. Partial sequencing of the mitochondrial (mt) genome of the cell line revealed the occurrence of large mutational events in the control region, thetRNA-Pheand12S rRNAgenes of the mt genome of progeny cells. The cell line was found permissive to sheep pox, peste des petits ruminants (PPR), lumpy skin disease (LSD), rift valley fever (RVF), and camel pox viruses.

This study would resolve the over half a century mystery of how the African Green Monkey cell line (VERO) had evolved. We authenticated the cell line at the European Collection of Authenticated Cell Cultures (ECACC) and deposited it at the American Type Culture Collection (ATCC) for the purpose of patenting under the Budapest Treaty.
Diagnostic tool to identify and treat DNA repair deficient gastroesophageal adenocarcinomas
Authors: Prosz Aurel , Sahgal Pranshu , Morris Clare X. , Sztupinszki Zsofia , Börcsök Judit , Diossy Miklos , Tisza Viktoria , Spisak Sandor , Rusz Orsolya , Csabai Istvan , Huffman Brandon M. , Singh Harshabad , Lazaro Jean-Bernard , Cecchini Michael , Cleary James M. , Szallasi Zoltan , Sethi Nilay S.
Published: July 2022

Background and aims

DNA repair deficiency is a common feature of cancer. Homologous recombination (HR) and nucleotide excision repair (NER) are the two most frequently disabled DNA repair pathways in solid tumors. HR deficient breast, ovarian, pancreatic and prostate cancers respond well to platinum chemotherapy and PARP inhibitors. However, the frequency of DNA repair pathway deficiency in gastric and esophageal adenocarcinoma (GEA) still lacks diagnostic and functional validation. Furthermore, whether DNA repair deficient GEA have enhanced responsiveness to platinum chemotherapy and sensitivity to PARP inhibitors is not well characterized.

Methods

Using whole exome and genome sequencing data, we measured various HR deficiency-associated mutational signatures in patient specimen of gastric, esophageal and colorectal cancer specimens and gastric cancer cell lines. Gold-standard immunofluorescence assays were used to confirm HR and NER deficiency in cancer cell lines. The relationship between PARP inhibitor treatment and tumor response was evaluated in patients with gastric cancer. Drug sensitivity was determined using standard in vitro cell culture assays. Single-cell RNA-sequencing was performed to evaluate gastric cancer response to commonly used chemotherapeutics.

Results

We found that a significant subset of GEA, but very few colorectal tumors, show evidence of HR deficiency by mutational signature analysis (HRD score). Gastric cancer cell lines with high HRD mutational signature scores demonstrated functional HR deficiency by RAD51 assay and increased sensitivity to platinum and PARP inhibitors. There was a positive association between HRD scores and tumor response in patients with gastric cancer treated with a PARP inhibitor on a clinical trial. A gastric cancer cell line with strong sensitivity to cisplatin showed HR proficiency but exhibited NER deficiency by DDB2 proteo-probe assay. Single-cell RNA-sequencing revealed that, in addition to inducing general apoptosis, cisplatin treatment triggered ferroptosis in a NER-deficient gastric cancer, which may explain the outlier sensitivity.

Conclusion

A subset of upper gastrointestinal tumors have genomic features of HR and NER deficiency and therefore may be more likely to benefit from platinum chemotherapy and PARP inhibition.
Expanding the scope of bacterial CRISPR activation with PAM-flexible dCas9 variants
Authors: Kiattisewee Cholpisit , Karanjia Ava V. , Legut Mateusz , Daniloski Zharko , Koplik Samantha E. , Nelson Joely , Kleinstiver Benjamin P. , Sanjana Neville E. , Carothers James M. , Zalatan Jesse G.
Published: July 2022

CRISPR-Cas transcriptional tools have been widely applied for programmable regulation of complex biological networks. In comparison to eukaryotic systems, bacterial CRISPR activation (CRISPRa) has stringent target site requirements for effective gene activation. While genes may not always have an NGG PAM at the appropriate position, PAM-flexible dCas9 variants can expand the range of targetable sites. Here we systematically evaluate a panel of PAM-flexible dCas9 variants for their ability to activate bacterial genes. We observe that dxCas9-NG provides a high dynamic range of gene activation for sites with NGN PAMs while dSpRY permits modest activity across almost any PAM. Similar trends were observed for heterologous and endogenous promoters. For all variants tested, improved PAM-flexibility comes with the tradeoff that CRISPRi-mediated gene repression becomes less effective. Weaker CRISPRi gene repression can be partially rescued by expressing multiple sgRNAs to target many sites in the gene of interest. Our work provides a framework to choose the most effective dCas9 variant for a given set of gene targets, which will further expand the utility of CRISPRa/i gene regulation in bacterial systems.
Aberrant extracellular matrix and cardiac development in models lacking the PR-DUB component ASXL3
Authors: McGrath BT , Tsan YC , Salvi S , Ghali N , Martin DM , Hannibal M , Keegan CE , Helms A , Srivastava A , Bielas SL
Published: July 2022

Background

Clinical and research based genetic testing has uncovered genes that encode chromatin modifying complex components required for organogenesis. Covalent histone modifications play a key role in establishing transcriptional plasticity during development, required for cell fate specification, and have been implicated as a developmental mechanism that accounts for autism spectrum disorder (ASD) and CHD co-occurrence. ASXL3 has been identified as a high confidence ASD gene. ASXL3 is a component of the Polycomb Repressive Deubiquitination (PR-DUB) complex, which deubiquitinates histone H2A. However, the role of ASXL3 in cardiac development remains unknown.

Methods

We used CRISPR/Cas9 gene editing to generate clinically relevant Asxl3 frameshift alleles in a mouse model and human embryonic stem cells (hESCs). To evaluate ASXL3 function in developing hearts, we performed structural, molecular, immunostaining and histological analyses. Transcriptomic and cellular compositional changes were assessed with bulk RNA sequencing of mouse hearts and single-cell RNA sequencing (scRNA-seq) of human cardiac tissue differentiated from isogenic hESC lines.

Results

Biallelic genetic inactivation of Asxl3 leads to perinatal lethality and increased levels of histone H2A mono-ubiquitination, which are regulated by PR-DUB. Asxl3+/fs and Asxl3fs/fs mice display cardiac abnormalities including ventricular hypoplasia, septal defects, and bifid cardiac apex with variable penetrance. The presence of underdeveloped ventricles is preceded by increased progenitor proliferation in the ventricles, as determined by EdU incorporation. Differential gene expression, assessed by bulk RNA sequencing implicates extracellular matrix dysfunction as a pathogenic mechanism. This correlates with a reduction in vimentin-positive cardiac fibroblasts. scRNA-seq of cardiac cultures differentiated from human ASXL3fs/fs ESC lines exhibit altered ratios of cardiac fibroblasts and cardiomyocytes. Similar to the mouse data, genes essential for extracellular matrix composition and signaling are differentially expressed between ASXL3+/+ and ASXL3fs/fs human in vitro differentiated cardiac tissue. The observed transcriptomic changes predict diminished cell-cell signaling interactions between cardiac fibroblasts and cardiomyocyte progenitors in ASXL3 cultures.

Conclusions

Collectively, our data implicates species-specific roles for ASXL3 in both human and mouse cardiac development. These results highlight the role of extracellular matrix gene programs by cardiac fibroblast during cardiomyocyte development and provide insight into mechanisms of altered cardiogenesis by autism risk genes.
Crossmodal reorganization in deaf auditory cortices compensates for the impaired body-centered visuomotor transformation after early deafness
Authors: Song Li , Wang Pengfei , Li Hui , Weiss Peter H. , Fink Gereon R. , Zhou Xiaolin , Chen Qi
Published: July 2022

Early deafness leads to the reorganization of large-scale brain networks, involving and extending beyond the auditory system. Body-centered visuomotor transformation is impaired after early auditory deprivation, associated with a hyper-crosstalk between the task-critical frontoparietal network (FPN) and the default-mode network (DMN). It remains to be elucidated, how the reorganized functional connectivity between the auditory system, the FPN, and the DMN contributes to the impaired visuomotor transformation after early deafness. In this fMRI study, we asked early deaf participants and hearing controls to judge the spatial location of a visual target, either about the middle-sagittal line of their own body (the egocentric task) or another background object (the allocentric task). The bilateral superior temporal gyrus (STG) in the deaf group exhibited cross-modal reorganization, with generally enhanced neural activity during the visual tasks, compared to hearing controls. Moreover, the STG showed significantly increased functional connectivity with both the FPN and the DMN in the deaf group compared to hearing controls, specifically during the egocentric task. The increased STG-FPN and STG-DMN coupling, however, showed antagonistic effects on the egocentric performance of the deaf participants. The increased STG-FPN connectivity was associated with improved (i.e., a beneficial role) while the increased STG-DMN with deteriorated (i.e., a detrimental role) egocentric performance in the deaf participants. No such effect was observed in hearing controls. Therefore, the auditory cortex is reorganized to functionally resemble the FPN in the deaf brain, representing compensatory neuroplasticity to mitigate the impaired visuomotor transformation after early deafness.

Significance Statement

Our brain constantly plans vision-guided actions, transforming visuospatial representations of external visual targets into visuomotor representations. The frontoparietal network (FPN) critically supports this visuomotor transformation process, which is impaired after early deafness. To mitigate the impaired visuomotor transformation, the ‘deaf’ auditory cortex in the bilateral superior temporal gyrus (STG) shows compensatory cross-modal reorganization that functionally resembles the FPN regions. Specifically, the deaf auditory cortex becomes functionally coupled with the dorsal FPN regions. The stronger the STG-FPN coupling, the more improved the deaf adults’ visuomotor transformation performance, indicating the reorganized STG as a critical node of the task-critical network. Correspondingly, increased coupling between the task-critical deaf STG and the default-mode network impairs the visuomotor transformation.
A case of mycobacteriosis associated with Mycobacterium pseudoshottsii in aquarium-reared fish in Japan
Authors: Komine Takeshi , Hyogo Ihara , Kentaro Ono , Yoshida Mitsumi , Sugimoto Yuma , Inohana Mari , Fukano Hanako , Kurata Osamu , Wada Shinpei
Published: July 2022

In 2019, several aquarium-reared fish died at a sea life park in Japan. Necropsy revealed micronodules on the spleen in the dotted gizzard shad (Konosirus punctatus). Seven of 16 fish exhibited microscopic multifocal granulomas associated with acid-fast bacilli in the spleen, kidney, liver, alimentary tract, mesentery, gills, and/or heart. Bacterial cultures yielded isolates from the dotted gizzard shad and a Japanese sardine (Sardinops melanostictus). Microbiological examination, multilocus sequence typing analysis, and variable number of tandem repeats analysis with a newly proposed 6-loci set revealed the isolates as Mycobacterium pseudoshottsii. To our knowledge, this is the first isolation of M. pseudoshottsii from aquarium-reared fish.
Bridging the gap between in vitro and in silico single-molecule force spectroscopy
Authors: Gomes Diego E. B. , Melo Marcelo C. R. , Gomes Priscila S. F. C. , Bernardi Rafael C.
Published: July 2022

Staphylococci bacteria use an arsenal of virulence factors, mainly composed of proteins such as adhesins, to target and adhere to their host. Adhesins play critical roles during infection, mainly during the early steps of adhesion when cells are exposed to high mechanical stress. S. epidermidis SdrG:Fgβ force resilience has been investigated using AFM-based single molecule force spectroscopy experiments paired with steered molecular dynamics (SMD) simulations. However, there is still a gap between both kinds of experiments at high force-loading rates. Here, we leveraged the high-speed of coarse-grained (CG) SMD simulations to bridge the gap between the data obtained in vitro and in silico with all-atom SMD. We used the DHS theory to connect the two types of SMD simulations and the predictions are consistent with theory and experimentation. We believe that, when associated with all-atom SMD, course-grained SMD can be a powerful ally to help explain and complement the results of single-molecule force spectroscopy experiments.
WNT4 regulates cellular metabolism via intracellular activity at the mitochondria in breast and gynecologic cancers
Authors: Sottnik Joseph L. , Shackleford Madeleine T. , Villagomez Fabian R. , Bahnassy Shaymaa , Oesterreich Steffi , Hu Junxiao , Madak-Erdogan Zeynep , Riggins Rebecca B. , Corr Bradley R. , Cook Linda S. , Treviño Lindsey S. , Bitler Benjamin G. , Sikora Matthew J.
Published: July 2022

Wnt ligand WNT4 is critical in female reproductive tissue development, with WNT4 dysregulation linked to related pathologies including breast cancer (invasive lobular carcinoma, ILC) and gynecologic cancers. WNT4 signaling in these contexts is distinct from canonical Wnt signaling yet inadequately understood. We previously identified atypical intracellular activity of WNT4 (independent of Wnt secretion) regulating mitochondrial function, and herein examine intracellular functions of WNT4. We further examine how convergent mechanisms ofWNT4dysregulation impact cancer metabolism. In ILC,WNT4is co-opted by estrogen receptor α (ER) via genomic binding inWNT4intron 1, while in gynecologic cancers, a common genetic polymorphism (rs3820282) at this ER binding site altersWNT4regulation. Using proximity biotinylation (BioID), we show canonical Wnt ligand WNT3A is trafficked for secretion, but WNT4 is localized to the cytosol and mitochondria. We identified DHRS2, mTOR, and STAT1 as putative WNT4 cytosolic/mitochondrial signaling partners. Whole metabolite profiling, and integrated transcriptomic data, support that WNT4 mediates metabolic reprogramming via fatty acid and amino acid metabolism. Further, ovarian cancer cell lines with rs3820282 variant genotype are WNT4-dependent and have active WNT4 metabolic signaling. In protein array analyses of a cohort of 103 human gynecologic tumors enriched for patient diversity, germline rs3820282 genotype is associated with metabolic remodeling. Variant genotype tumors show increased AMPK activation and downstream signaling, with the highest AMPK signaling activity in variant genotype tumors from non-White patients. Taken together, atypical intracellular WNT4 signaling, in part via genetic dysregulation, regulate the distinct metabolic phenotypes of ILC and gynecologic cancers.

Significance

WNT4 regulates breast and gynecologic cancer metabolism via a previously unappreciated intracellular signaling mechanism at the mitochondria, with WNT4 mediating metabolic remodeling. Understanding WNT4 dysregulation by estrogen and genetic polymorphism offers new opportunities for defining tumor biology, precision therapeutics, and personalized cancer risk assessment.
mdciao: Accessible Analysis and Visualization of Molecular Dynamics Simulation Data
Authors: Pérez-Hernández Guillermo , Hildebrand Peter. W.
Published: July 2022

We present mdciao, an open-source command line tool and Python Application-Programmers-Interface (API) for easy, one-shot analysis and representation of molecular dynamics (MD) simulation data. Building upon the widely used concept of residue-residue contact-frequencies, mdciao offers a wide spectrum of further analysis and representations, enriched with domain specific annotations when possible. It tries offer a user-friendly interface, which simplifies most decisions for non-expert users, while keeping customizability for expert ones. Emphasis has been put into automatically producing annotated, paper-ready figures and tables. Furthermore, seamless on-the-fly query and inclusion of consensus nomenclatures for GPCR, G-proteins, and kinases is made possible through the respective online databases, which allows for bulk selection and comparison across different systems. Finally, the fully documented Python API allows users to include the basic or advanced mdciao functions in their analysis workflows, and provides numerous examples and Jupyter Notebook Tutorials. The source code is published under the GNU Lesser General Public License v3.0 or later and hosted on https://github.com/gph82/mdciao.
A fluorescently labelled quaternary ammonium compound (NBD-DDA) to study mode-of-action and resistance mechanisms in bacteria
Authors: Nordholt Niclas , O’Hara Kate , Resch-Genger Ute , Blaskovich Mark A. T. , Rühle Bastian , Schreiber Frank
Published: July 2022

Quaternary ammonium compounds (QACs) are widely used as active agents in disinfectants, antiseptics, and preservatives. Despite being in use since the 1940s, there remain multiple open questions regarding their detailed mode-of-action and the mechanisms, including phenotypic heterogeneity, that can make bacteria less susceptible to QACs. To facilitate mode-of-action studies, we synthesized a fluorescent analogue of the quaternary ammonium compound benzalkonium chloride, namely N-dodecyl-N,N-dimethyl-[2-[(4-nitro-2,1,3-benzoxadiazol-7-yl)amino]ethyl]azanium-iodide (NBD-DDA). NBD-DDA is readily detected by flow cytometry and fluorescence microscopy with standard GFP/FITC-settings, making it suitable for molecular and single-cell studies. NBD-DDA was then used to investigate resistance mechanisms which can be heterogeneous among individual bacterial cells. Our results reveal that the antimicrobial activity of NBD-DDA against E. coli, S. aureus and P. aeruginosa is comparable to that of benzalkonium chloride (BAC), a widely used QAC. Characteristic time-kill kinetics and increased tolerance of a BAC tolerant E. coli strain against NBD-DDA suggest that the mode of action of NBD-DDA is similar to that of BAC. Leveraging these findings and NBD-DDA’s fluorescent properties, we show that reduced cellular adsorption is responsible for the evolved BAC tolerance in the BAC tolerant E. coli strain. As revealed by confocal laser scanning microscopy (CLSM), NBD-DDA is preferentially localized in the cell envelope of E. coli, which is a primary target of BAC and other QACs. Overall, NBD-DDA’s antimicrobial activity, its fluorescent properties, and its ease of detection render it a powerful tool to study the mode-of-action and the resistance mechanisms of QACs in bacteria.
HMGN5, an RNA or Nucleosome binding protein - potentially switching between the substrates to regulate gene expression
Authors: Araya Ingrid , Nardocci Gino , Schwartz Uwe , Babl Sabrina , Barros Miriam , Carrasco-Wong Ivo , Imhof Axel , Montecino Martín , Längst Gernot
Published: July 2022

The packaging of DNA into chromatin and its compaction within cells renders the underlying DNA template un-accessible for processes like transcription, replication and repair. Active mechanisms as chromatin modifying activities or the association with non-coding RNAs can de-condense chromatin, rendering it accessible for the DNA dependent processes. High mobility group proteins (HMG) are small architectural chromatin proteins that were shown to contribute to the regulation of chromatin accessibility and condensation. Here we show that HMGN5, a member of the HMGN family that is capable to de-compact chromatin exhibits a novel RNA binding domain that overlaps with its nucleosome binding domain (NBD). HMGN5 binds exclusively to nucleosomes or RNA, suggesting that molecular function relies on switching between these two substrates. We show the specific binding of HMGN5 to regulatory regions and at the same time to bind the RNA of the genes it tends to activate. Furthermore, HMGN5 co-localizes and directly interacts with CTCF, suggesting a cooperative role of both proteins in organizing higher order structures of chromatin and active chromatin domains.
Imp is required for timely exit from quiescence in Drosophila type II neuroblasts
Authors: Munroe Jordan A. , Syed Mubarak H. , Doe Chris Q.
Published: July 2022

Stem cells must balance proliferation and quiescence, with excess proliferation favoring tumor formation, and premature quiescence preventing proper organogenesis. Drosophila brain neuroblasts are a model for investigating neural stem cell entry and exit from quiescence. Neuroblasts begin proliferating during embryogenesis, enter quiescence prior to larval hatching, and resume proliferation 12-30h after larval hatching. Here we focus on the mechanism used to exit quiescence, focusing on the “type II” neuroblasts. There are 16 type II neuroblasts in the brain, and they undergo the same cycle of embryonic proliferation, quiescence, and proliferation as do most other brain neuroblasts. We focus on type II neuroblasts due to their similar lineage as outer radial glia in primates (both have extended lineages with intermediate neural progenitors) and because of the availability of specific markers for type II neuroblasts and their progeny. Here we characterize the role of Insulin-like growth factor II mRNA-binding protein (Imp) in type II neuroblast proliferation and quiescence. Imp has previously been shown to promote proliferation in type II neuroblasts, in part by acting antagonistically to another RNA-binding protein called Syncrip (Syp). Here we show that reducing Imp levels delays neuroblast exit from quiescence in type II neuroblasts, acting independently of Syp, with Syp levels remaining low in both quiescent and newly proliferating type II neuroblasts. We conclude that Imp promotes exit from quiescence, a function closely related to its known role in promoting neuroblast proliferation.
Toward sustainable jet fuels: bioconversion of cellulose into isoprenoid biojet candidates using rumen bacteria and non-conventional yeast
Authors: Walls Laura E. , Otoupal Peter , Ledesma-Amaro Rodrigo , Velasquez-Orta Sharon B. , Gladden John M. , Rios-Solis Leonardo
Published: July 2022

In this study, organic acids were demonstrated as a promising carbon source for bisabolene production by the non-conventional yeast, Rhodosporidium toruloides, at microscale with a maximum titre of 1055 ± 7 mg/L. A 125-fold scale-up of the optimal process, enhanced bisabolene titres 2.5-fold to 2606 mg/L. Implementation of a pH controlled organic acid feeding strategy at this scale lead to a further threefold improvement in bisabolene titre to 7758 mg/L, the highest reported microbial titre. Finally, a proof-of-concept sequential bioreactor approach was investigated. Firstly, the cellulolytic bacterium Ruminococcus flavefaciens was employed to ferment cellulose, yielding 4.2 g/L of organic acids. R. toruloides was subsequently cultivated in the resulting supernatant, producing 318 ± 22 mg/L of bisabolene. This highlights the feasibility of a sequential bioprocess for the bioconversion of cellulose, into biojet fuel candidates. Future work will focus on enhancing organic acid yields and the use of real lignocellulosic feedstocks to further enhance bisabolene production.

Graphical Abstract
Evolution and spread of multi-adapted pathogens in a spatially heterogeneous environment
Authors: Griette Quentin , Alfaro Matthieu , Raoul Gaël , Gandon Sylvain
Published: July 2022

The emergence and the spread of multi-adapted pathogens is often viewed as a slow process resulting from the incremental accumulation of single adaptations. In bacteria, for instance, multidrug resistance to antibiotics may result from the sequential acquisition of single drug resistance to different antibiotics. In phytopathogens, the ability to infect different resistant varieties of crops may also result from the accumulation of distinct virulence genes. Here we use a general epidemiological model to analyse the evolution of pathogen adaptations throughout an epidemic spreading in a heterogeneous host population where selection varies periodically in space. This spatially heterogeneous selection may result from the use of different drugs, different vaccines or different crop varieties in agriculture. We study both the transient evolution of pathogen adaptation at the front of the epidemic and the long-term evolution far behind the epidemic front. We identify five different types of epidemic profiles that may arise from different combinations of spatial heterogeneity and the cost of multi-adaptation. In particular, we show that multi-adaptation can drive epidemic spread, while the evolution of single-adaptation may only occur in a second phase, when the pathogen specializes on local selective pressures. Indeed, a generalist pathogen with multiple adaptations can outpace the spread of a coalition of specialist pathogens when selection varies frequently in space. This result is amplified in finite host populations because demographic stochasticty can lead to the extinction of maladapted pathogens specialised to a local selective pressure. Our work has important implications for the management of multiple drugs and vaccines against pathogens but also for the optimal deployment of resistant varieties in agriculture.
GRMI4.0: a guide for representing and modeling Industry 4.0 business processes
Authors: Mosser Jérémie , Pellerin Robert , Bourgault Mario , Danjou Christophe , Perrier Nathalie
Published: July 2022

Purpose

The purpose of this paper is to propose a new business process representation adapted to the needs of Industry 4.0 to facilitate the implementation of technological solutions in the construction sector.

Design/methodology/approach

This work is based on the Design Research Methodology approach and includes four phases: (1) a literature review on the main business process modeling standards and their ability to take into account the specificities of Industry 4.0; (2) the identification of the attributes to be considered to model Industry 4.0 processes; (3) the development of a mapping model for Industry 4.0; and (4) the validation of the model using a case study from the construction sector.

Findings

To the authors’ knowledge, current business process modeling standards do not effectively represent business processes in the context of Industry 4.0.

Originality/value

The proposed model can represent not only the 4.0 solutions that can be implemented in the construction sector, particularly from a technology and data perspective but also measures, with the help of performance indicators, the impacts of successive process changes in terms of skills, cost and time for a true 4.0 transformation.
Transforming unstructured digital clinical notes for improved health literacy
Authors: Doppalapudi Shreyesh , Wang Tingyan , Qiu Robin
Published: July 2022

Purpose

Clinical notes typically contain medical jargons and specialized words and phrases that are complicated and technical to most people, which is one of the most challenging obstacles in health information dissemination to consumers by healthcare providers. The authors aim to investigate how to leverage machine learning techniques to transform clinical notes of interest into understandable expressions.

Design/methodology/approach

The authors propose a natural language processing pipeline that is capable of extracting relevant information from long unstructured clinical notes and simplifying lexicons by replacing medical jargons and technical terms. Particularly, the authors develop an unsupervised keywords matching method to extract relevant information from clinical notes. To automatically evaluate completeness of the extracted information, the authors perform a multi-label classification task on the relevant texts. To simplify lexicons in the relevant text, the authors identify complex words using a sequence labeler and leverage transformer models to generate candidate words for substitution. The authors validate the proposed pipeline using 58,167 discharge summaries from critical care services.

Findings

The results show that the proposed pipeline can identify relevant information with high completeness and simplify complex expressions in clinical notes so that the converted notes have a high level of readability but a low degree of meaning change.

Social implications

The proposed pipeline can help healthcare consumers well understand their medical information and therefore strengthen communications between healthcare providers and consumers for better care.

Originality/value

An innovative pipeline approach is developed to address the health literacy problem confronted by healthcare providers and consumers in the ongoing digital transformation process in the healthcare industry.
An opportunity to build back better? COVID-19 and environmental sustainability of Australian events
Authors: Hutte Gerard Jan , Markwell Kevin , Wilson Erica
Published: July 2022

Purpose

This study explores (1) the impacts of COVID-19 on the environmental sustainability of Australian events; (2) the measures undertaken to minimise the impacts of COVID-19 on environmental sustainability; (3) the key impediments to incorporating COVID-Safe measures in an environmentally sustainable way; and (4) the expected long-term impact of the COVID-19 situation on the development of the environmental sustainability of the Australian events industry.

Design/methodology/approach

The study follows a qualitative approach by undertaking semi-structured interviews with (N = 23) event industry professionals. The data collection phase took place between November 2020 and May 2021 and the study was completed in February 2022.

Findings

Adverse environmental impacts included increased waste output and the stagnation of planned or existing environmental practices. The study reveals positive effects such as reduced carbon emission outputs and increased environmental awareness of event participants. Financial costs, time pressure, uncertainty and sourcing issues are significant impediments to organising events in an environmentally sustainable manner during a global pandemic situation.

Practical implications

Understanding how COVID-19 impacts the environmental sustainability of events will help the industry to preserve previous progress made, overcome similar obstacles during future crises, and capitalise on opportunities for positive environmental change.

Originality/value

This is the first study to examine the impact of the COVID-19 pandemic on the environmental sustainability practices of Australian events.
Why should I let them know? Effects of workplace incivility and cynicism on employee knowledge hiding behavior under the control of ethical leadership
Authors: Anand Amitabh , Agarwal Upasna A. , Offergelt Florian
Published: July 2022

Purpose

The purpose of this study is to examine if individual cynicism mediates the relationship between workplace incivility (WI) and knowledge hiding (KH). Additionally, it is examined whether ethical leadership has a moderating role regarding the effect of WI on KH.

Design/methodology/approach

The authors conducted two multi-wave studies, each with two times of data collection. Study 1 included data from 390 members of 30 teams from knowledge-intensive organizations. In study 2, data was collected from 437 software professionals working in diverse organizations.

Findings

Results showed that cynicism mediated the impact of WI on KH. Furthermore, the positive direct and indirect effect of WI on KH was shown to be moderated by perceived ethical leadership such that high ethical leadership mitigates the effects.

Originality/value

This study extends the research on knowledge management by explaining a new mechanism and framework in which KH can occur and provides important practical recommendations for human resource managers to contribute to the overall organization's success.
Vibrations of a vertical 90° pipe bend under two-phase flow conditions
Authors: Shah Reza Shah Danial , Rasani Mohammad Rasidi
Published: July 2022

Purpose

A simulation framework that includes a finite element analysis (FEA) and computational fluid dynamics (CFD) model is generated to study the effect of unstable two-phase flow-induced vibrations at a vertical 90° pipe bend. The corresponding fluid-structure interaction (FSI) of an unstable flow may pose danger to the piping structure. This paper intends to discuss this interaction.

Design/methodology/approach

Four cases of flows under the slug flow and churn flow regimes were investigated. The flow regimes vary in superficial gas velocities with velocities from 0.978 m/s to 9.04 m/s, while the superficial liquid velocity is kept constant at 0.61 m/s. The pipe model consists of an internal diameter of 0.0525 m, a bend radius of 0.0762 m, and a stainless-steel pipe structure.

Findings

Results show that the average unstable void fractions increase with the superficial gas velocities, but the peak frequencies were constant at 13 Hz for three of the cases. The total displacement and von Mises stress increase with a declining rate in each subsequent case, while the RMS of von Mises stress begins to stall at superficial gas velocities between 5 m/s and 9.04 m/s. The peak frequencies of von Mises stress decrease in each subsequent case.

Originality/value

The proposed model can be used to investigate the FSI effect of unstable void fractions at pipe bends and could assist in the development of piping systems in which the use of piping elements arranged close together are unavoidable.
Influence of fire-resistant coating on the physical characteristics and residual mechanical properties of E350 steel section exposed to elevated temperature
Authors: Jaya Kumar G. , Kiran Tattukolla , Anand N. , Al-Jabri Khalifa
Published: July 2022

Purpose

Most of the industrial buildings which are designed to moderate loads are constructed using light gauge cold-formed steel (CFS) sections. Residual mechanical properties of CFS sections exposed to elevated temperature need to be investigated as it is necessary to predict the deterioration of elements to avoid failure of the structure or its elements. Also, it would be helpful to decide whether the structural elements need to be replaced or reused. The use of fire-resistant coatings in steel structures significantly reduces the cost of repairing structural elements and also the probability of collapse. This study investigates the effect of fire-resistant coating on post-fire residual mechanical properties of E350 steel grade.

Design/methodology/approach

In this study, an attempt has been made to evaluate the residual mechanical properties of E350 steel. A tensile coupon test was performed for the extracted specimens from the exposed CFS section to determine the mechanical properties. Four different fire-resistant coatings were selected and the sections were coated and heated as per ISO 834 fire temperature curve in the transient state for time durations of 30 minutes (821°C), 60 minutes (925°C), 90 minutes (986°C), and 120 minutes (1,029°C). After the exposure, all the coupon specimens were cooled by either ambient conditions (natural air) or water spraying before conducting the tension test on these specimens.

Findings

At 30 min exposure, the reduction in yield and ultimate strength of heated specimens was about 20 and 25% for air and water-cooled specimens compared with reference specimens. Specimens coated with vermiculite and perlite exhibited higher residual mechanical property up to 60 minutes than other coated specimens for both cooling conditions. Generally, water-cooled specimens had shown higher strength loss than air-cooled specimens. Specimens coated with vermiculite and perlite showed an excellent performance than other specimens coated with zinc and gypsum for all heating durations.

Originality/value

As CFS structures are widely used in construction practices, it is crucial to study the mechanical properties of CFS under post-fire conditions. This investigation provides detailed information about the physical and mechanical characteristics of E350 steel coated with different types of fire protection materials after exposure to elevated temperatures. An attempt has been made to improve the residual properties of CFS using the appropriate coatings. The outcome of the present study may enable the practicing engineers to select the appropriate coating for protecting and enhancing the service life of CFS structures under extreme fire conditions.
An interdisciplinary reflective approach to promote architectural design pedagogy: animating basic design principles by music visualizer
Authors: Abusafieh Shaden Fakhri
Published: July 2022

Purpose

The study investigates the effectiveness of an adaptive reflective framework that shifts the learning process toward a student-centered approach within an interdisciplinary learning environment. It aims to promote the learning process within an interdisciplinary learning environment that could promote the students’ design competencies.

Design/methodology/approach

The experiment was conducted at Basic Design studio, investigating three concepts of basic design principles: harmony, repetition and rhythm. A total of 80 first-year architectural students were enrolled in this study and placed into two equal groups: the “control group” received the traditional learning method and in contrast, the “experimental group” received an interdisciplinary reflective learning method using music as a relevant discipline.

Findings

The results showed that utilizing “Music Animation Machine” in the learning process significantly promoted students’ cognitive skills, engagement and design competencies. In addition, there was obvious evidence of excellent progress in learning basic design principles using the proposed reflective approach within a student-centered learning environment.

Originality/value

Many researchers focus on the importance of using music as a design tool. However, there is a crucial demand for investigating it as a learning tool. This research raised music effectiveness in the learning process of design principles. Thus, it incites to test more disciplines interconnected with architectural design. Other researchers could utilize this approach to ensure its effect on enhancing design competencies in the basic design and other architectural design courses.
Can disease resistance evolve independently at different ages? Genetic variation in age‐dependent resistance to disease in three wild plant species
Authors: Bruns Emily B. , Hood Michael E. , Antonovics Janis , Ballister Indigo H. , Troy Sarah E. , Cho Jae‐Hoon
Published: July 2022

Juveniles are typically less resistant (more susceptible) to infectious disease than adults, and this difference in susceptibility can help fuel the spread of pathogens in age‐structured populations. However, evolutionary explanations for this variation in resistance across age remain to be tested.

One hypothesis is that natural selection has optimized resistance to peak at ages where disease exposure is greatest. A central assumption of this hypothesis is that hosts have the capacity to evolve resistance independently at different ages. This would mean that host populations have (a) standing genetic variation in resistance at both juvenile and adult stages, and (b) that this variation is not strongly correlated between age classes so that selection acting at one age does not produce a correlated response at the other age.

Here we evaluated the capacity of three wild plant species (Silene latifolia, S. vulgaris and Dianthus pavonius) to evolve resistance to their anther‐smut pathogens (Microbotryum fungi), independently at different ages. The pathogen is pollinator transmitted, and thus exposure risk is considered to be highest at the adult flowering stage.

Within each species we grew families to different ages, inoculated individuals with anther smut, and evaluated the effects of age, family and their interaction on infection.

In two of the plant species, S. latifolia and D. pavonius, resistance to smut at the juvenile stage was not correlated with resistance to smut at the adult stage. In all three species, we show there are significant age × family interaction effects, indicating that age specificity of resistance varies among the plant families.

Synthesis. These results indicate that different mechanisms likely underlie resistance at juvenile and adult stages and support the hypothesis that resistance can evolve independently in response to differing selection pressures as hosts age. Taken together our results provide new insight into the structure of genetic variation in age‐dependent resistance in three well‐studied wild host–pathogen systems.
The Commission Knocked Out Cold: Laura Serrano and the End of the Mexico City Prohibition of Women's Boxing in the 1990s
Authors: Van Bavel Marjolein
Published: July 2022

This article examines the conflict over the legalisation of women's boxing in Mexico City in the 1990s. In 1995, Laura Serrano's Women's International Boxing Federation world boxing title put pressure on the legal system that had banned women from professional boxing in the Mexican capital since 1946. As the visibility of women's boxing grew in Mexico, Serrano publicly fought to end the ban in her home city. The Mexico City Boxing Commission's moral arguments and medical discourses about the female body became increasingly untenable as politics of gender equality won in importance. Using a range of sources, including Mexican newspapers and magazines, government gazettes, congress proceedings, and an autobiographical text by Serrano, this article illustrates the interplay of gender ideologies and institutional structures during an important period in Mexican political history. After seven decades of uninterrupted Institutional Revolutionary Party rule, power of the Mexican capital shifted to the Party of the Democratic Revolution (PRD) when Cuauhtémoc Cárdenas became the city's first elected governor in 1997. Although the PRD politically claimed the end of the prohibition in 1998, the shift in power cost Serrano the best paid boxing event of her career. It took another legal reform that outlawed discrimination in sports to force the Commission to finally regulate women's boxing in 1999.
Racism is a motivator and a barrier for people of color aspiring to become midwives in the United States
Authors: Mehra Renee , Alspaugh Amy , Joseph Jennie , Golden Bethany , Lanshaw Nikki , McLemore Monica R. , Franck Linda S.
Published: July 2022

Objective

To understand motivators and barriers of aspiring midwives of color.

Data Sources and Study Setting

Primary data were collected via a national online survey among people of color in the United States interested in pursuing midwifery education and careers between February 22 and May 2, 2021.

Study Design

Cross‐sectional survey consisted of 76 questions (75 closed‐ended and 1 open‐ended questions) including personal, familial, community, and societal motivators and barriers to pursuing midwifery.

Data Collection/Extraction Methods

We recruited respondents 18 years and older who identified as persons of color by posting the survey link on midwifery, childbirth, and reproductive justice listservs, social media platforms, and through emails to relevant midwifery and doula networks. We conducted descriptive and bivariate analyses by demographic characteristics and used exemplar quotes from the open‐ended question to illustrate findings from the descriptive data.

Principal Findings

The strongest motivating factors for the 799 respondents were providing racially concordant care for community members (87.7 percent), reducing racial disparities in health (67.2 percent), and personal experiences related to midwifery care (55.4 percent) and health care more broadly (54.6 percent). Main barriers to entering midwifery were direct (58.2 percent) and related (27.5 to 52.8 percent) costs of midwifery education, and lack of racial concordance in midwifery education and the midwifery profession (31.5 percent) that may contribute to racially motivated exclusion of people of color. Financial and educational barriers were strongest among those with lower levels of income or education.

Conclusions

Structural and interpersonal racisms are both motivators and barriers for aspiring midwives of color. Expanding and diversifying the perinatal workforce by addressing the financial and educational barriers of aspiring midwives of color, such as providing funding and culturally‐competent midwifery education, creating a robust pipeline, and opening more midwifery schools, is a matter of urgency to address the maternal health crisis.