bluuebunny/crossref_metadata_2025 huggingface dataset:
High diversity in the regulatory region of Stx-converting bacteriophage genomes
Authors: Fagerlund Annette , Aspholm Marina , Węgrzyn Grzegorz , Lindbäck Toril
Published: November 2021

Shiga toxin (Stx) is the major virulence factor of enterohemorrhagic Escherichia coli (EHEC), and the stx genes are carried by temperate bacteriophages (Stx phages). The switch between lysogenic and lytic life cycle of the phage, which is crucial for Stx production and for severity of the disease, is regulated by the CI repressor. CI maintain latency by preventing transcription of the replication proteins. Three EHEC phage replication units (Eru1-3) in addition to the classical lambdoid replication region have been described previously, and Stx phages carrying the Eru1 replication region were associated with highly virulent EHEC strains. In this study, we have classified the Eru replication region of 419 Stx phages. In addition to the lambdoid replication region and the three already described Erus, ten novel Erus (named Eru4 to Eru13) were detected. The lambdoid type, Eru1, Eru4 and Eru7 seem to be widely distributed in Western Europe. Notably, EHEC strains involved in severe outbreaks in England and Norway carry Stx phages with Eru1, Eru2, Eru5 and Eru7 replication regions. Phylogenetic analysis of CI repressors from Stx phages revealed eight major clades that largely separate according to Eru type. The classification of replication regions and CI proteins of Stx phages provides an important platform for further studies aimed to assess how characteristics of the replication region influence the regulation of phage life cycle and, consequently, the virulence potential of the host EHEC strain.

IMPORTANCE

EHEC is an emerging health challenge worldwide and outbreaks caused by this pathogen tend to be more frequent and severe. Increased knowledge on how characteristics of the replication region influence the virulence of E. coli may be used for more precise identification of high-risk EHEC strains.
High prevalence ofKlebsiella pneumoniaein European food products: a multicentric study comparing culture and molecular detection methods
Authors: Rodrigues Carla , Hauser Kathrin , Cahill Niamh , Ligowska-Marzęta Małgorzata , Centorotola Gabriella , Cornacchia Alessandra , Garcia Fierro Raquel , Haenni Marisa , Møller Nielsen Eva , Piveteau Pascal , Barbier Elodie , Morris Dearbháile , Pomilio Francesco , Brisse Sylvain
Published: November 2021

Klebsiella pneumoniaespecies complex (KpSC) is a leading cause of multidrug-resistant human infections. To better understand the potential contribution of food as a vehicle of KpSC, we conducted a multicentric study to define an optimal culture method for its recovery from food matrices, and to characterize food isolates phenotypically and genotypically. Chicken meat (n=160) and salad (n=145) samples were collected in five European countries and screened for KpSC presence using culture-based and ZKIR qPCR methods. Enrichment using buffered peptone water followed by streaking on Simmons citrate agar with inositol (44°C/48h) was defined as the most suitable selective culture method for KpSC recovery. High prevalence of KpSC was found in chicken meat (60% and 52% by ZKIR qPCR and culture approach, respectively) and salad (30% and 21%, respectively) samples. Genomic analyses revealed high genetic diversity with the dominance of phylogroups Kp1 (91%) and Kp3 (6%). 82% of isolates presented a natural antimicrobial susceptibility phenotype and genotype, with only four CTX-M-15-producing isolates detected. Notably, identical genotypes were found across samples: same food type and same country (15 cases); different food types and same country (1); same food type and two countries (1), suggesting high rates of transmission of KpSC within the food sector. Our study provides a novel isolation strategy for KpSC from food matrices and reinforces the view of food as a potential source of KpSC colonization in humans.

Importance

Bacteria of theKlebsiella pneumoniaespecies complex (KpSC) are ubiquitous andK. pneumoniae(Kp) is a leading cause of antibiotic-resistant infections in humans and animals. Despite the urgent public health threat represented by Kp, there is a lack of knowledge on the contribution of food sources to colonization and subsequent infection in humans. This is partly due to the absence of standardized methods for characterizing KpSC presence in food matrices. Our multicentric study provides and implements a novel isolation strategy for KpSC from food matrices and shows that KpSC members are highly prevalent in salads and chicken meat, reinforcing the view of food as a potential source of KpSC colonization in humans. Despite the large genetic diversity and the low-levels of resistance detected, the occurrence of identical genotypes across samples suggests high rates of transmission of KpSC within the food sector, which need to be further explored to define possible control strategies.
Identification of differentially expressed genes and signaling pathways in gestational diabetes mellitus by integrated bioinformatics analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: November 2021

Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy. Numerous biomarkers have been identified that are linked with the occurrence and development of GDM. The aim of this investigation was to identify differentially expressed genes (DEGs) in GDM using a bioinformatics approach to elucidate their molecular pathogenesis. GDM associated expression profiling by high throughput sequencing dataset (GSE154377) was obtained from Gene Expression Omnibus (GEO) database including 28 normal pregnancy samples and 33 GDM samples. DEGs were identified using DESeq2. The gene ontology (GO) and REACTOME pathway enrichments of DEGs were performed by g:Profiler. Protein-protein interaction (PPI) networks were assembled with Cytoscape software and separated into modules using the PEWCC1 algorithm. MiRNA-hub gene regulatory network and TF-hub gene regulatory network were performed with the miRNet database and NetworkAnalyst database. Receiver Operating Characteristic (ROC) analyses was conducted to validate the hub genes. A total of 953 DEGs were identified, of which 478 DEGs were up regulated and 475 DEGs were down regulated. Furthermore, GO and REACTOME pathway enrichment analysis demonstrated that these DEGs were mainly enriched in multicellular organismal process, cell activation, formation of the cornified envelope and hemostasis. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB were identified as key genes in the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network. TRIM54, ELAVL2, PTN, KIT, BMPR1B, APP, SRC, ITGA4, RPA1 and ACTB in GDM were validated using ROC analysis. This investigation provides further insights into the molecular pathogenesis of GDM, which might facilitate the diagnosis and treatment of GDM.
Correspondence analysis for dimension reduction, batch integration, and visualization of single-cell RNA-seq data
Authors: Hsu Lauren L. , Culhane Aedín C.
Published: November 2021

Effective dimension reduction is essential for single cell RNA-seq (scRNAseq) analysis. Principal component analysis (PCA) is widely used, but requires continuous, normally-distributed data; therefore, it is often coupled with log-transformation in scRNAseq applications, which can distort the data and obscure meaningful variation. We describe correspondence analysis (CA), a count-based alternative to PCA. CA is based on decomposition of a chi-squared residual matrix, avoiding distortive logtransformation. To address overdispersion and high sparsity in scRNAseq data, we propose five adaptations of CA, which are fast, scalable, and outperform standard CA and glmPCA, to compute cell embeddings with more performant or comparable clustering accuracy in 8 out of 9 datasets. In particular, we find that CA with Freeman-Tukey residuals (CA-FT) performs especially well across diverse datasets. Other advantages of the CA framework include visualization of associations between genes and cell populations in a “CA biplot,” and extension to multi-table analysis; we introducecorralmfor integrative multi-table dimension reduction of scRNAseq data. We implement CA for scRNAseq data incorral, an R/Bioconductor package which interfaces directly with single cell classes in Bioconductor. Switching from PCA to CA is achieved through a simple pipeline substitution and improves dimension reduction of scRNAseq datasets.
High-throughput tuning of ovarian cancer spheroids for on-chip invasion assays
Authors: Chen Changchong , He Yong , Lopez Elliot , Carreiras Franck , Yamada Ayako , Schanne-Klein Marie-Claire , Lambert Ambroise , Chen Yong , Aimé Carole
Published: November 2021

We developed an invasion assay by using microfabricated culture devices. First, ovarian tumor spheroids were generated with a culture patch device consisting of an agarose membrane formed with a honeycomb microframe – thepatch– and gelatin nanofiber backbone. By changing the dimensions of the honeycomb compartments we were able to control the number of cells and size of the spheroids. When the spheroids were placed on a patch coated with a thin membrane of fibrillary type I collagen, spheroid disruption was observed due to substrate induced cell migration. This process is straightforward and should be applicable to other cancer types, as well as assays under microfluidic conditions, thereby holding the potential for use in tumor modeling and anti-cancer drug development.
A scale-invariant perturbative approach to study information communication in dynamic brain networks
Authors: Mohan Varun Madan , Banerjee Arpan
Published: November 2021

How communication among neuronal ensembles shapes functional brain dynamics at the large scale is a question of fundamental importance to Neuroscience. To date, researchers have primarily relied on two alternative ways to address this issue 1) in-silico neurodynamical modelling of functional brain dynamics by choosing biophysically inspired non-linear systems, interacting via a connection topology driven by empirical data; and 2) identifying topological measures to quantify network structure and studying them in tandem with functional metrics of interest, e.g. co-variation of time series in brain regions from fast (EEG/ MEG) and slow (fMRI) timescales. While the modelling approaches are limited in scope to only scales of the nervous system for which dynamical models are well defined, the latter approach does not take into account how the network architecture and intrinsic regional node dynamics contribute together to inter-regional communication in the brain. Thus, developing a generalized scale-invariant measure of interaction between network topology and constituent regional dynamics can potentially resolve how transmission of perturbations in brain networks alter function e.g. by neuropathologies, or the intervention strategies designed to mitigate them. In this work, we introduce a recently developed theoretical perturbative framework in network science into a neuroscientific framework, to conceptualize the interaction of regional dynamics and network architecture in a quantifiable manner. This framework further provides insights into the information communication contributions of putative regions and sub-networks in the brain, irrespective of the observational scale of the phenomenon (firing rates to BOLD fMRI time series). The proposed approach can directly quantify network-dynamical interactions without reliance on a specific class of models or response characteristics: linear/nonlinear. By simply gauging the asymmetries in responses to perturbations, we obtain insights into the significance of regions in communication and their influence over the rest of the network. Moreover, coupling perturbations with functional lesions can also answer which regions contribute the most to information spread: a quantity termed Flow. The simplicity of the proposed technique allows translation to an experimental setting where the response asymmetries and flow can inversely act as a window into the dynamics of regions. For proof-of-concept, we apply the perturbative approach on in-silico data generated for human resting state network dynamics, using different established dynamical models that mimic empirical observations. We also apply the perturbation approach at the level of large scale Resting State Networks (RSNs) to gauge the range of network-dynamical interactions in mediating information flow across brain regions.
Synchrony and idiosyncrasy in the gut microbiome of wild baboons
Authors: Björk Johannes R. , Dasari Mauna R. , Roche Kim , Grieneisen Laura , Gould Trevor J. , Grenier Jean-Christophe , Yotova Vania , Gottel Neil , Jansen David , Gesquiere Laurence R. , Gordon Jacob B. , Learn Niki H. , Wango Tim L. , Mututua Raphael S. , Warutere J. Kinyua , Siodi Long’ida , Mukherjee Sayan , Barreiro Luis B. , Alberts Susan C. , Gilbert Jack A. , Tung Jenny , Blekhman Ran , Archie Elizabeth A.
Published: November 2021

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments, and medications, but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here we leverage extensive gut microbial time series from wild baboons—hosts who experience little interindividual dietary and environmental heterogeneity—to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiome dynamics were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, likely because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host’s personalized dynamics. Indeed, host-specific factors, especially host identity, explained 10 times the deviance in longitudinal microbial dynamics, compared to factors shared across hosts. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artifact of modern human environments, and that synchronizing forces in the gut microbiome (e.g., shared environments, diets, and microbial dispersal) are often not strong enough to overwhelm drivers of microbiome personalization, including host genetics, priority effects, horizontal gene transfer, and functional redundancy.
Social preference in rats not impacted by posterior parietal activity despite overall changes in familiarity-based social behavior
Authors: Wise Taylor B. , Burwell Rebecca D. , Templer Victoria L.
Published: November 2021

Recent literature points to a potential link between the evolution of complex social behavior and the posterior parietal cortex (PPC) in primates including humans (Parkinson & Wheatley, 2013). Thus far, this theory has been overlooked in other highly social animals that may have also evolved due to social selective pressures. In rodents, there is limited knowledge on the involvement of the PPC on sociality, and most studies of such behavior are limited to understanding social preference. We investigated the role of the PPC through two experiments using the 3-Chamber Sociability and Social Novelty test in rats (Crawley, 2004). In Experiment 1, we used a standard 3-Chamber paradigm, which included two novel demonstrators. In Experiment 2, this paradigm was altered to increase the difference in familiarity between demonstrators such that one demonstrator was highly familiar to the subject and the other was entirely novel. Rats with pre-testing permanent neurotoxic lesions were compared to sham surgery control rats, and the same rats were used for both experiments. Experiments 1 and 2 showed that both groups of rats preferred general social interaction, suggesting no deficit in sociability following PPC damage, regardless of demonstrator identity. Further, experimental and control rats showed similar levels of novelty preference following PPC damage, with novelty preferences increasing in Experiment 2. We argue that heightened novelty preference in Experiment 2 may reflect the increased difference in familiarity between demonstrators. Within the confines of the 3-Chamber task, our results suggest that PPC function was not required for general sociability or social novelty recognition. Because the PPC is implicated in abstract cognition, we argue that existing social tests in rodents may not adequately measure the complex cognitive capacities thought to be supported by the PPC. Future studies should investigate the role of the PPC in social cognition by employing behavioral tasks that require higher cognitive demand rather than testing inherent preference for social partners. Outside of our investigation of the PPC, these results show that social novelty preference can be manipulated through changes in familiarity of demonstrators, and that rats can discriminate others’ social identities.
Genome of the bi-annual Rio Pearlfish (Nematolebias whitei), a killifish model species for Eco-Evo-Devo
Authors: Thompson Andrew W. , Wojtas Harrison , Davoll Myles , Braasch Ingo
Published: November 2021

The Rio Pearlfish Nematolebias whitei is a bi-annual killifish species inhabiting seasonal pools of the Rio de Janeiro region that dry twice per year. Embryos enter dormant diapause stages in the soil, waiting for the inundation of the habitat which triggers hatching and commencement of a new life cycle. This species represents a convergent, independent origin of annualism from other emerging killifish model species. While some transcriptomic datasets are available for Rio Pearlfish, thus far a sequenced genome has been unavailable. Here we present a high quality, 1.2Gb chromosome-level genome assembly, genome annotations and a comparative genomic investigation of the Rio Pearlfish as representative of a vertebrate clade that evolved environmentally-cued hatching. We show conservation of 3-D genome structure across teleost fish evolution, developmental stages, tissues and cell types. Our analysis of mobile DNA shows that Rio Pearlfish, like other annual killifishes, possesses an expanded transposable element profile with implications for rapid aging and adaptation to harsh conditions. We use the Rio Pearlfish genome to identify its hatching enzyme gene repertoire and the location of the hatching gland, a key first step in understanding the developmental genetic control of hatching. The Rio Pearlfish genome expands the comparative genomic toolkit available to study convergent origins of seasonal life histories, diapause, and rapid aging phenotypes. We present the first set of genomic resources for this emerging model organism, critical for future functional genetic and multi-omic explorations of “Eco-Evo-Devo” phenotypes in resilience and adaptation to extreme environments.

Significance:

Seasonal or annual killifishes are emerging models for aging, life history adaptions to extreme environments, and ecological evolutionary developmental biology (Eco-Evo-Devo). Most studies have thus far focused on the African turquoise killifish Nothobranchius furzeri and the South American Austrofundulus limneaus. We sequenced and analyzed the genome of the Rio Pearlfish Nematolebias whitei from the Rio de Janeiro region, a seasonal species representing a convergent origin of seasonality from other sequenced killifish species, strengthening the comparative potential of Aplocheiloid killifishes as a model clade for the comparative and functional genomics of animal resilience to environmental change.
Measurements and simulations of microtubule growth imply strong longitudinal interactions and reveal a role for GDP on the elongating end
Authors: Cleary Joseph M. , Kim Tae , Cook Annan S. I. , Hancock William O. , Rice Luke M.
Published: November 2021

Microtubule polymerization dynamics result from the biochemical interactions of αβ-tubulin with the polymer end, but a quantitative understanding has been challenging to establish. We used interference reflection microscopy to make improved measurements of microtubule growth rates and growth fluctuations in the presence and absence of GTP hydrolysis. In the absence of GTP hydrolysis, microtubules grew steadily with very low fluctuations. These data were best described by a computational model implementing slow assembly kinetics, such that the rate of microtubule elongation is primarily limited by the rate of αβ-tubulin associations. With GTPase present, microtubules displayed substantially larger growth fluctuations than expected based on the no GTPase measurements. Our modeling showed that these larger fluctuations occurred because exposure of GDP-tubulin on the microtubule end transiently ‘poisoned’ growth, yielding a wider range of growth rate compared to GTP only conditions. Our experiments and modeling point to slow association kinetics (strong longitudinal interactions), such that drugs and regulatory proteins that alter microtubule dynamics could do so by modulating either the association or dissociation rate of tubulin from the microtubule tip. By causing slower growth, exposure of GDP tubulin at the growing microtubule end may be an important early event determining catastrophe.
A new early-branching armoured dinosaur from the Lower Jurassic of southwestern China
Authors: Yao Xi , Barrett Paul M , Yang Lei , Xu Xing , Bi Shundong
Published: November 2021

The early evolutionary history of the armoured dinosaurs (Thyreophora) is obscured by its patchily distributed fossil record and by conflicting views on the relationships of its Early Jurassic representatives. Here, we describe an early-diverging thyreophoran from the Lower Jurassic Fengjiahe Formation of Yunnan Province, China, on the basis of an associated partial skeleton that includes skull, axial, limb and armour elements. It can be diagnosed as a new taxon based on numerous cranial and postcranial autapomorphies and is further distinguished from all other thyreophorans by a unique combination of character states. Although the robust postcranium is similar to that of more deeply nested ankylosaurs and stegosaurs, phylogenetic analysis recovers it as either the sister taxon of Emausaurus or of the clade Scelidosaurus+Eurypoda. This new taxon, XXXX XXXX, represents the first valid thyreophoran dinosaur to be described from the Early Jurassic of Asia and confirms the rapid geographic spread and diversification of the clade after its first appearance in the Hettangian. Its heavy build and distinctive armour also hint at previously unrealised morphological diversity early in the clade’s history.
Identifying cell-to-cell variability in internalisation using flow cytometry
Authors: Browning Alexander P , Ansari Niloufar , Drovandi Christopher , Johnston Angus P R , Simpson Matthew J , Jenner Adrianne L
Published: November 2021

Biological heterogeneity is a primary contributor to the variation observed in experiments that probe dynamical processes, such as internalisation. Given that internalisation is a critical process by which many therapeutics and viruses reach their intracellular site of action, quantifying cell-to-cell variability in internalisation is of high biological interest. Yet, it is common for studies of internalisation to neglect cell-to-cell variability. We develop a simple mathematical model of internalisation that captures the dynamical behaviour, cell-to-cell variation, and extrinsic noise introduced by flow cytometry. We calibrate our model through a novel distribution-matching approximate Bayesian computation algorithm to flow cytometry data of internalisation of anti-transferrin receptor antibody in a human B-cell lymphoblastoid cell line. Our model reproduces experimental observations, identifies cell-to-cell variability in the internalisation and recycling rates, and, importantly, provides information relating to inferential uncertainty. Given that our approach is agnostic to sample size and signal-to-noise ratio, our modelling framework is broadly applicable to identify biological variability in single-cell data from internalisation assays and similar experiments that probe cellular dynamical processes.
A Hybrid Communication Pattern in Human Brain Structural Network Revealed by Evolutionary Computation
Authors: Liang Quanmin , Ma Junji , Chen Xitian , Dai Zhengjia , Lin Ying
Published: November 2021

The human brain functional connectivity network (FCN) is constrained and shaped by the communication processes in the structural connectivity network (SCN). The underlying communication mechanism thus becomes a critical issue for understanding the formation and organization of the FCN. A number of communication models supported by different routing strategies have been proposed, with shortest path (SP), random diffusion (DIF), and spatial navigation (NAV) as the most typical, respectively requiring network global knowledge, local knowledge, and both for path seeking. Yet these models all assumed every brain region to use one routing strategy uniformly, ignoring convergent evidence that supports the regional heterogeneity in both terms of biological substrates and functional roles. In this regard, the current study developed a hybrid communication model that allowed each brain region to choose a routing strategy from SP, DIF, and NAV independently. A genetic algorithm was designed to uncover the underlying region-wise hybrid routing strategy (namely HYB). The HYB was found to outperform the three typical routing strategies in predicting FCN and facilitating robust communication. Analyses on HYB further revealed that brain regions in lower-order functional modules inclined to route signals using global knowledge, while those in higher-order functional modules preferred DIF that requires only local knowledge. Compared to regions that used global knowledge for routing, regions using DIF had denser structural connections, participated in more functional modules, but played a less dominant role within modules. Together, our findings further evidenced that hybrid routing underpins efficient SCN communication and locally heterogeneous structure-function coupling.
Tetraspanin Cd9b plays a role in fertility in zebrafish
Authors: Greaves S , Marsay KS , Monk PN , Roehl H , Partridge LJ
Published: November 2021

In mice, CD9 expression on the egg is required for efficient sperm-egg fusion and no effects on ovulation or male fertility are observed in CD9 null animals. Here we show thatcd9bKO zebrafish also appear to have fertility defects. In contrast to mice, fewer eggs were laid bycd9bKO zebrafish pairs and, of the eggs laid, a lower percentage were fertilised.In vitrofertilization (IVF) was used to demonstrate that factors such as courting behaviour, adult size and mate choice were not causing the unexpected decrease in clutch size. The decrease in egg numbers could be rescued by exchanging eithercd9bKO partner, male or female, for a wildtype (WT) partner. However, the fertilisation defect could only be rescued by crossing acd9bKO female with a WT male. Our results indicate that Cd9b has several roles in fish fertility, affecting both clutch size and egg fertilisation.

Highlights

cd9bmutant pairs lay fewer eggs and of the eggs laid, fewer are fertilised.

Mutation incd9bdoes not affect primordial germ cell number or migration.

Reduction in number of eggs and fertility is not due to courting behaviour, fish size or mate choice.

cd9bmutation in either gender affects the number of eggs laid.

Mutation ofcd9bin the males affects fertilisation efficiency but mutation ofcd9bin the females does not.
Survival of Campylobacter jejuni in Amoebae enhances subsequent invasion of mammalian cells
Authors: Nasher Fauzy , Wren Brendan W.
Published: November 2021

The ubiquitous unicellular eukaryote, Acanthamoeba, is known to play a role in the survival and dissemination of Campylobacter jejuni. C. jejuni is the leading cause of bacterial foodborne gastroenteritis world-wide and is a major public health problem. The ability of C. jejuni to interact and potentially invade epithelial cells is thought to be key for disease development in humans. We examined C. jejuni grown under standard laboratory conditions,11168HCBA with that harvested from within Acanthamoeba castellanii (11168HAC/CBA) or Acanthamoeba polyphaga (11168HAP/CBA), and compared their ability to invade different cell lines. C. jejuni harvested from within amoebae had a ∼3.7-fold increase in invasiveness into T84 human epithelial cells and a striking ∼11-fold increase for re-entry into A. castellanii cells. We also investigated the invasiveness and survivability of six diverse representative C. jejuni strains within Acanthamoeba spp., our results confirm that invasion and survivability is likely host cell dependent. Our survival assay data led us to conclude that Acanthamoeba spp. are a transient host for C. jejuni and that survival within amoebae pre-adapts C. jejuni and enhances subsequent cell invasion. This study provides new insight into C. jejuni interactions with amoebae and its increased invasiveness potential in mammalian hosts.
Gene conversion explains elevated diversity in the immunity modulating APL1 gene of the malaria vector Anopheles funestus
Authors: Hearn Jack , Riveron Jacob M. , Irving Helen , Weedall Gareth D. , Wondji Charles S.
Published: November 2021

The leucine rich repeat gene APL1 is a key component of immunity to Plasmodium and other microbial pathogens in Anopheles mosquitoes. In the malaria vector Anopheles funestus the APL1 gene has four paralogues which occur along the same chromosome arm. We show that APL1 has exceptional levels of non-synonymous polymorphism across the range of An. funestus with an average πn of 0.027 versus a genome-wide average of 0.002, and πn (and πs) is consistently high in populations across Africa. The pattern of APL1 diversity was consistent between independent pooled-template and target-enrichment datasets, however no link between APL1 diversity and insecticide-resistance was observed with the phenotyped target-enrichment dataset. Two further innate immunity genes of the gambicin anti-microbial peptide family had πn/πs ratios greater than one, possibly driven by either positive or balancing selection. Cecropin antimicrobial peptides were expressed much more highly than other anti-microbial peptide genes, an observation discordant with current models of anti-microbial peptide activity. The observed APL1 diversity likely results from gene conversion between paralogs, as evidenced by shared polymorphisms, overlapping read mappings, and recombination events among paralogues. Gene conversion at APL1 versus alternative explanations is concordant with similarly elevated diversity in APL1 and TEP1 loci in An. gambiae. In contrast, the more closely related An. stephensi which also encodes a single-copy of APL1 does not show this elevated diversity. We hypothesise that a more open chromatin formation at the APL1 locus due to higher gene expression than its paralogues enhances gene conversion, and therefore increased polymorphism, at APL1.
Listeria monocytogenes requires cellular respiration for NAD+ regeneration and pathogenesis
Authors: Rivera-Lugo Rafael , Deng David , Anaya-Sanchez Andrea , Tejedor-Sanz Sara , Reyes Ruiz Valeria M , Smith Hans B , Titov Denis V , Sauer John-Demian , Skaar Eric P , Ajo-Franklin Caroline M , Portnoy Daniel A , Light Samuel H
Published: November 2021

Cellular respiration is essential for multiple bacterial pathogens and a validated antibiotic target. In addition to driving oxidative phosphorylation, bacterial respiration has a variety of ancillary functions that obscure its contribution to pathogenesis. We find here that the intracellular pathogen Listeria monocytogenes encodes two respiratory pathways which are partially functionally redundant and indispensable for pathogenesis. Loss of respiration decreased NAD+ regeneration, but this could be specifically reversed by heterologous expression of a water-forming NADH oxidase (NOX). NOX expression fully rescued intracellular growth defects and increased L. monocytogenes loads >1,000-fold in a mouse infection model. Consistent with NAD+ regeneration maintaining L. monocytogenes viability and enabling immune evasion, a respiration-deficient strain exhibited elevated bacteriolysis within the host cytosol and NOX rescued this phenotype. These studies show that NAD+ regeneration, rather than oxidative phosphorylation, represents the primary role of L. monocytogenes respiration and highlight the nuanced relationship between bacterial metabolism, physiology, and pathogenesis.
Single chain models illustrate the 3D RNA folding shape during translation
Authors: Guo Tianze , Modi Olivia L. , Hirano Jillian , Guzman Horacio V. , Tsuboi Tatsuhisa
Published: November 2021

The three-dimensional conformation of RNA is important in the function and fate of the molecule. The common conformation of mRNA is formed based on the closed-loop structure and internal base pairings with the activity of the ribosome movements. However, recent reports suggest that the closed-loop structure might not be formed in many mRNAs. This implies that mRNA can be considered as a single polymer in the cell. We developed TRIP; Three-dimensional RNA Illustration Program, to model the three-dimensional RNA folding shape based on single-chain models. We identified the angle restriction of each bead component from previously reported single-molecule FISH experimental data. This simulation method was able to recapitulate the mRNA conformation change of the translation activity and three-dimensional positional interaction between organelle and its localized mRNAs. Within the analyzed cases base-pairing interactions only have minor effects on the three-dimensional mRNA conformation, and instead single-chain polymer characteristics have a more significant impact on the conformation. This method will be used to predict the aggregation mechanism of mRNA and long noncoding RNA in specific cellular conditions such as nucleolus and phase-separated granules.
Directed evolution of colE1 plasmid replication compatibility: a fast tractable tunable model for investigating biological orthogonality
Authors: Chaillou Santiago , Stamou Eleftheria-Pinelopi , Torres Leticia , Riesco Ana B. , Hazelton Warren , Pinheiro Vitor B.
Published: November 2021

Plasmids of the ColE1 family are among the most frequently used plasmids in molecular biology. They were adopted early in the field for many biotechnology applications, and as model systems to study plasmid biology. The mechanism of replication of ColE1 plasmids is well understood, involving the interaction between a plasmid-encoded sense-antisense gene pair (RNAI and RNAII). Because of its mechanism of replication, bacterial cells cannot maintain two different plasmids with the same origin, with one being rapidly lost from the population – a process known as plasmid incompatibility. While mutations in the regulatory genes RNAI and RNAII have been reported to make colE1 plasmids more compatible, there has been no attempt to engineer compatible colE1 origins, which can be used for multi-plasmid applications and that can bypass design constrains created by the current limited plasmid origin repertoire available. Here, we show that by targeting sequence diversity to the loop regions of RNAI (and RNAII), it is possible to select new viable colE1 origins that are compatible with the wild-type one. We demonstrate origin compatibility is not simply determined by sequence divergence in the loops, and that pairwise compatibility is not an accurate guide for higher order interactions. We identify potential principles to engineer plasmid copy number independently from other regulatory strategies and we propose plasmid compatibility as a tractable model to study biological orthogonality. New characterised plasmid origins increase flexibility and accessible complexity of design for challenging synthetic biology applications where biological circuits can be dispersed between multiple independent genetic elements.
The reproduction of Gram-negative protoplasts and the influence of environmental conditions on this process
Authors: Kanaparthi Dheeraj , Lampe Marko , Krohn Jan-Hagen , Zhu Baoli , Klingl Andreas , Lueders Tillmann
Published: November 2021

Bacterial protoplasts are known to reproduce independently of canonical molecular biological processes. Their reproduction is shown to be mediated entirely by the physicochemical properties of cell constituents. However, the physiochemical properties of the cell constituents are influenced by the environmental conditions like salinity, salt composition, and mechanical stresses experienced by a cell in natural environments. The influence of such environmental conditions on protoplast reproduction is seldom investigated. Here, we studied protoplast reproduction in their native environmental conditions. Contrary to the previous perceptions of protoplasts reproducing in an erratic manner, cells in our study reproduced in a defined sequence of steps. The process of their reproduction can be explained by an interplay between intracellular metabolism, the physicochemical properties of cell constituents, and the nature of cations in the growth media. We observed a minimal leakage of intracellular constituents during protoplast reproduction, suggesting an efficient reproduction. However, the efficiency of reproduction is determined by the environmental conditions. Under favorable environmental conditions, protoplasts reproduce with nearly similar efficiency to cells that possess a cell wall. In short, here we demonstrate the simplest method of cellular reproduction and the influence of environmental conditions on this process.
Impact of COVID-19 pandemic on financial reporting and disclosure practices: empirical evidence from Bangladesh
Authors: Sultana Reajmin , Ghosh Ratan , Sen Kanon Kumar
Published: November 2021

Purpose

To investigate the consequence of COVID-19 pandemic on the financial reporting and disclosure (FRD) practices, the study has been conducted. Moreover, this paper highlights the significance of FRD practices in any emergency period and its relevance with legitimacy theory in Bangladesh Perspective.

Design/methodology/approach

The COVID-19 pandemic has adverse impact on business. Hence, all the business activities have been categorized into five major aspects which are financial factors, business operations, business contracts, business value and stakeholders. These five major activities have been considered as independent variable. By analyzing various policy recommendations and guidelines of global and local accounting bodies, a structured questionnaire was developed in association with related IAS and IFRSs. Then, it was distributed among the accounting professionals of Bangladesh who are currently engaged in financial statement preparation and auditing services. Finally, data was analyzed through structural equation modeling (SEM) to test the hypothetical relationship between dependent variable and independent variable.

Findings

This study finds that financial factors, business contracts and stakeholders have significant relationship with the financial reporting and disclosure practices during the COVID-19 pandemic period. However, business operation and business value have no significant relationship with financial reporting and disclosure practices.

Research limitations/implications

This study tries to analyze why and how firms should disclose essential information (both financial and non-financial) to the financial statement users during the COVID-19 pandemic. This study can be used as benchmark to issue a separate policy or standard for reporting any kind of adverse event in the financial reporting and disclosure practices.

Originality/value

To our best knowledge, we believe that this is first kind of study undertaken to investigate the consequence of COVID-19 pandemic on the FRD practices in the context of Bangladesh. This study is kind of exploratory in nature. Hence, future studies can explore industry-based financial reporting and disclosure practice in any pandemic period.
Lifestyle segmentation of older Koreans: a longitudinal comparison of segments and life satisfaction
Authors: Jung Kwon , Jung Jihye
Published: November 2021

Purpose

Aging is a global phenomenon for many countries, and South Korea has become the fastest aging country in the world. The purpose of this study is to identify and validate a representative typology of older Koreans based on their lifestyle and value orientations. This study also makes a longitudinal comparison of these segments in two waves using similar survey data collected in 2009 and 2017 and examines any meaningful changes that occurred during the periods.

Design/methodology/approach

Using survey data collected from 750 older adults living in four major cities in Korea, this study conducted factor and cluster analysis to identify lifestyle segmentation of elderly Koreans. Both descriptive and mean comparison analyses are followed to characterize the segments with relevant demographic and behavioral variables. In addition, this study makes a longitudinal comparison of these segments in two waves (2009 and 2017) and examines any meaningful changes that occurred during the periods.

Findings

Six distinctive lifestyle segments of elderly Koreans are identified. The longitudinal comparison reveals some changes that occurred during the period. The level of importance of values and things to own has been declined during the period on most of the aspects, which can be interpreted that older Koreans become more realistic and practical. The level of life satisfaction between the two periods turned out to be similar. However, satisfaction in material comfort and health has been improved during the period, which means that the perception of their financial and physical aspects has been improved over the years.

Originality/value

First, based on Tempest et al.’s three grey discontinuity framework (2002), the segmentation model provides comprehensive coverage of psychological transitions experienced by older people due to economic, physical and mental discontinuities with age. Second, this might be the first longitudinal study to examine the changes in segmentation over time in terms of the lifestyle of older adults. Practically, the findings of this study provide useful insights for policymakers in developing aging-related policies as well as for marketers who are interested or currently doing business in Korea or Asian consumer markets.
Numerical calculation of transient electric field considering space charge in oil-paper insulation of converter transformers
Authors: Xiu Liancheng , Du Zhiye , Tian Yu , He Jingxuan , Cai Hongwei , Yi Fan
Published: November 2021

Purpose

The purpose of this paper is to develop a numerical simulation method based on the transient upstream finite element method (FEM) and Schottky emission theory to reveal the distribution characteristics of space charge in oil-paper insulation.

Design/methodology/approach

The main insulation medium of the converter transformer in high voltage direct current transmission is oil-paper insulation. However, the influence of space charge is difficult to be fully considered in the insulation design and simulation of converter transformers. To reveal the influence characteristics of the space charge, this paper proposes a numerical simulation method based on Schottky emission theory and the transient upstream FEM. This method considers the influence of factors, such as carrier mobility, carrier recombination coefficient, trap capture coefficient and diffusion coefficient on the basis of multi-physics field coupling calculation of the electric field and fluid field.

Findings

A numerical simulation method considering multiple charge states is proposed for the space charge problem in oil-paper insulation. Meanwhile, a space charge measurement platform based on the electrostatic capacitance probe method for oil-paper insulation structure is built, and the effectiveness and accuracy of the numerical simulation method is verified.

Originality/value

A variety of models are calculated and analyzed by the numerical simulation method in this paper, and the distribution characteristics of the space charge and total electric field in oil-paper insulation medium with single-layer, polarity reversal of plate voltage and double-layer are obtained. The research results of this paper have the guiding significance for the engineering application of oil-paper insulation and the optimal design of converter transformer insulation.
Brouges footwear: launching a Ghanian shoe brand
Authors: Vidal Jorge Fernandez
Published: November 2021

Study level/applicability:

This case is intended for use in undergraduate, MBA and Executive Education courses in Strategy, Business in Africa, Entrepreneurship and Investing in Emerging Markets.

Subject area:

Strategy, Business in Africa, Entrepreneurship and Investing in Emerging Markets.

Case synopsis

Eric Kyere founded Brouges in 2015, an African brand, with the objective of designing, manufacturing and selling great shoes. His original plan was to produce Brouges’ shoes in Africa, but had several problems with suppliers (e.g. poor quality, poor raw materials, etc.). Therefore, Brouges had to partner with a European manufacturer to produce its first batch of shoes. Shortly thereafter, Eric partnered with Michael Asare Bediako, a young Ghanaian investor and entrepreneur, who had advanced plans to build a shoemaking factory in Ghana. The factory was likely to open in early 2021, following major delays caused by the COVID-19 pandemic. This would be a major milestone for Brouges and a key step in Eric’s entrepreneurial journey. However, how can Eric and Brouges manage the challenge of growing and building a manufacturing and retail organization? How could they succeed where others had failed?

Leaning objectives

This case has five pedagogical objectives: strategic choices: evaluate the strategic choices that companies need to make (based on their predefined goals and aspirations) and show that they are effectively an integrated cascade of choices that need to be consistent and coherent; strategic planning: apply and analyze the key steps and key decision to be made as part of a high-level strategic plan; value proposition: apply and analyze the concept and key components of a company’s value proposition, leveraging Tovstiga’s framework; doing business in Africa: evaluate the specific generic challenges of doing business in Africa, particularly in the manufacturing sector; generalizability of frameworks: this case shows that the same frameworks that are used to analyze large firms and mature markets can be applied to smaller firms in less developed markets.

Complexity academic level

This case is intended for use in undergraduate, MBA and Executive Education courses in Strategy, Business in Africa, Entrepreneurship and Investing in Emerging Markets.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS: 3 Entrepreneurship.