bluuebunny/crossref_metadata_2025 huggingface dataset:
Apical constriction induces tissue rupture in a proliferative epithelium
Authors: Osswald Mariana , Barros-Carvalho André , Carmo Ana M , Loyer Nicolas , Gracio Patricia C , Sunkel Claudio , Homem Catarina C , Januschke Jens , Morais-de-Sá Eurico
Published: March 2022

Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Deregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncovered howDrosophilaaPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries culturedex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we could modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation rapidly induces apical constriction in non-mitotic cells, producing pulling forces that ultimately detach dividing and neighbouring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, since it was prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side was sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the firstin vivoevidence that excessive tissue stress can break the epithelial barrier during proliferation.
Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy
Authors: Barnkob Mike Bogetofte , Vitting-Seerup Kristoffer , Olsen Lars Rønn
Published: March 2022

The development of novel chimeric antigen receptor (CAR) cell therapies is rapidly growing, with 299 new agents being reported and 109 new clinical trials initiated so far this year. One critical lesson from approved CD19-specific CAR therapies is that target isoform switching has been shown to cause tumor relapse, but little is known about the isoforms of CAR targets in solid cancers. Here we assess the protein isoform landscape and identify both the challenges and opportunities protein isoform switching present as CAR therapy is applied to solid cancers.
Engineering bacterial blight-resistant plants through CRISPR/Cas9-targeted editing of theMeSWEET10apromoter in cassava
Authors: Wang Yajie , Geng Mengting , Pan Ranran , Zhang Tong , Lu Xiaohua , Zhen Xinghou , Che Yannian , Li Ruimei , Liu Jiao , Chen Yinhua , Guo Jianchun , Yao Yuan
Published: March 2022

Cassava starch is a widely used raw materials for industrial production. However, cassava bacterial blight (CBB) caused byXanthomonas axonopodispv.manihotis(Xam) results in severe yield losses and is the most destructive bacterial disease in all worldwide cassava planting regions. This study showed that editing of the promoter in the disease-susceptibility geneMeSWEET10aof SC8 cassava confers resistance to CBB. All mutated cassava lines had normal morphological and yield-related traits as the wild type. The results lay a research foundation for breeding cassava resistant to bacterial blight.

Highlights

MeSWEET10agene in SC8 cultivar is hijacked by TALE20 fromXam11strain.

Editing of theMeSWEET10apromoter in SC8 cultivar confers resistance to CBB.

All the mutated cassava lines had similar yield-related traits compared to wild-type.
Critical role of PCYT2 in muscle health and aging
Authors: Cikes Domagoj , Elsayad Kareem , Sezgin Erdinc , Koitai Erika , Ferenc Torma , Orthofer Michael , Yarwood Rebecca , Heinz Leonhard X. , Sedlyarov Vitaly , Miranda Nasser Darwish , Taylor Adrian , Grapentine Sophie , al-Murshedi Fathiya , Abott Anne , Weidinger Adelheid , Kutchukian Candice , Sanchez Colline , Cronin Shane J.F. , Novatchkova Maria , Kavirayani Anoop , Schuetz Thomas , Haubner Bernhard , Haas Lisa , Hagelkruys Astrid , Jackowski Suzanne , Kozlov Andrey , Jacquemond Vincent , Knauf Claude , Superti-Furga Giulio , Rullman Eric , Gustafsson Thomas , McDermot John , Lowe Martin , Radak Zsolt , Chamberlain Jeffrey S. , Bakovic Marica , Banka Siddharth , Penninger Josef M.
Published: March 2022

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing, affecting hundreds of millions of people. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases represents an important goal in improving human health. Here, we show that phosphatidylethanolamine cytidyltransferase (PCYT2/ECT), the critical enzyme of the Kennedy branch of phosphatidylethanolamine (PE) synthesis pathway, has an essential role in muscle health. Human genetic deficiency inPCYT2causes a severe disease with failure to thrive and progressive muscle weakness.Pcyt2mutant zebrafish recapitulate the patient phenotypes, indicating that the role of PCYT2/PE in muscle is evolutionary conserved. Muscle specificPcyt2knockout mice exhibited failure to thrive, impaired muscle development, progressive muscle weakness, muscle loss, accelerated ageing, and reduced lifespan. Mechanistically, Pcyt2 deficiency affects mitochondrial bioenergetics and physicochemical properties of the myofiber membrane lipid bilayer, in particular under exercise strain. We also show that PCYT2 activity declines in the aging muscles of humans and mice. AAV-based delivery of PCYT2 rescued muscle weakness inPcyt2knock-out mice and, importantly, improved muscle strength in old mice, offering a novel therapeutic avenue for rare disease patients and muscle aging. Thus, PCYT2 plays a fundamental, specific, and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2 synthesized PE lipids to severe muscle dystrophy, exercise intolerance and aging.
Neovascularization and the recruitment of CD31+ cells from the bone marrow are unique under regenerative but not wound repair conditions
Authors: Bedelbaeva Kamila , Zhang Young , Azlanukov Azamat , Gourevitch Dmitri , Strehin Iossif , Messersmith Phillip , Heber-Katz Ellen
Published: March 2022

The long-noted observation that endostatin is a potent inhibitor of tumor vasculature but has little or no effect on wound repair or pregnancy remains an “as of yet unexplained but remarkable phenomenon”(1). However, there is another path to wound healing, epimorphic regeneration, and here we present data in mice demonstrating that endostatin is, in fact, a potent inhibitor of epimorphic regeneration. In this study, we show that a rege nerative response seen in the spontaneously regenerating MRL mouse involves CD31+ endothelial precursors that migrate from the bone marrow into the wound site and form new vessels, unlike that seen in the non-regenerating C57BL/6 mouse injury site. Furthermore, this appears to relate to the induction of HIF-1a, an inducer of regeneration (2). Inducing epimorphic regeneration in otherwise non-regenerating mice via an enhanced HIF-1a response by employing the PHD inhibitor 1,4-DPCA/hydrogel, a HIF-1a stabilizer, results in the same increased bone marrow-derived CD31+ endothelial precursor response and increased vasculogenesis. This regenerative response is completely blocked by endostatin, supporting the notion that vascularization induced during regeneration shares similarities to the tumor vasculature.
Taxonomic and functional shifts in the perinatal gut microbiome of rhesus macaques
Authors: Rhoades Nicholas S. , Cinco Isaac R. , Hendrickson Sara M. , Slifka Mark K. , Messaoudi Ilhem
Published: March 2022

Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables such as diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the perinatal and post-partum periods in 25 rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched during pregnancy while Treponema, Lachnospiraceae, and Methanosphaera were more abundant post-partum. Functionally, pregnancy was associated with increased abundance in the pathway to produce the beneficial short chain fatty acid (SCFA), butyrate, while pathways associated with starch degradation and folate transformation were more abundant postpartum. These data demonstrate dramatic changes in the maternal gut even in the absence of dietary changes and suggest that rhesus macaques could provide a valuable model to determine how changes in the microbiome correlate to other physiological changes in pregnancy.
Simulating semantic dementia in a brain-constrained model of action and object words learning
Authors: Efremov Aleksei , Kuptsova Anastasia , Wennekers Thomas , Shtyrov Yury , Gutkin Boris , Garagnani Max
Published: March 2022

The nature of semantic knowledge – conceptual information stored in the brain – is highly debated in the field of cognitive science. Experimental and clinical data specify various cortical regions involved in the processing of meaning. Those include semantic hubs that take part in semantic processing in general as well as sensorimotor areas that process specific conceptual categories according to their modality. Biologically inspired neurocomputational models can help adjudicate between different theories about the exact roles of those regions in the functioning of the semantic system.

Here, we used an existing neuroanatomically constrained model of frontotemporal brain areas implicated in language acquisition and grounding. We adapted it to replicate and explain the effects of semantic dementia on word processing abilities. Semantic dementia is a disease characterized by semantic knowledge deterioration that correlates with neural damage in the anterior temporal lobe. The behavior of our model is in accordance with clinical data – namely, word recognition performance decreases as SD lesions progress, whereas word repetition abilities remain preserved, or are less affected. Furthermore, our model makes novel predictions about category-specific effects of SD – namely, our simulation results indicate that word processing should be more impaired for object-than for action-related words, and that white matter degradation should lead to more severe consequences than the same proportion of grey matter degradation.

The present results provide a mechanistic, cortical-level explanatory account of a range of language impairments as observed in clinical populations during the onset and progress of semantic dementia.
Adaptive brain changes to virtual lesions interfering with visual processing
Authors: Raffin Estelle , Salamanca-Giron Roberto F. , Huxlin Krystel R. , Reynaud Olivier , Mattera Loan , Martuzzi Roberto , Hummel Friedhelm C.
Published: March 2022

Understanding the causal relationship between a focal lesion and network (re)organization is crucial to accurately predict the resulting large-scale symptoms of a lesion. In this study, we applied short trains of 10 Hz TMS to healthy participants over the early visual areas (EVA) or the medio-temporal area (hMT+/MT) during a motion discrimination task and at rest, while concurrent fMRI was acquired. TMS applied in the early stage of motion processing induced a specific deficit in judging motion direction in both sites, while global motion perception was preserved. This was associated with a common suppression of local brain activity and network activity. In contrast, we report distinct topological network properties depending on the disrupted site. Networks associated with EVA perturbation displayed a more robust and efficient functional reorganization, suggesting that EVA might be more resilient to focal perturbations. While contributing to a better understanding of the impact and potential mechanisms of TMS perturbation, these results provide a model for focal lesions in the visual motion processing system.

Highlights

TMS-induced perturbation of the early visual areas (EVA) or the mediotemporal area (hMT+/V5) area selectively impairs motion direction discrimination.

The TMS perturbation is associated with a local down-scaling of BOLD activity in both areas, potentially specific to task-related neuronal populations during motion discrimination.

The two visual areas display distinct topological networks’ adaptations in response to TMS, reflecting different levels of networks resilience to a focal lesion.

TMS-fMRI coupling can be used to assess ‘disconnectomics’ and to precisely map how a local perturbation propagates to large-scale behavioural deficits.

Graphical abstract
SlS5H silencing reveals specific pathogen-triggered salicylic acid metabolism in tomato
Authors: Payá C , Minguillón S , Hernández M , Miguel SM , Campos L , Rodrigo I , Bellés JM , López-Gresa MP , Lisón P
Published: March 2022

The phytohormone salicylic acid (SA or 2-hydroxybenzoic acid) plays an important role in plant biotic and abiotic responses. Gentisic acid (GA or 2,5-Dihydroxybenzoic acid, 2,5-DHBA) is the product of the SA 5-hydroxylation which is catalysed by the S5H enzyme, also known as DMR6. GA has been described to accumulate at high levels in compatible plant-pathogen interactions such as tomato plants infected by Citrus Exocortis Viroid (CEVd), and to a much lesser extend upon Pseudomonas syringae DC3000 pv. tomato (Pst) infection. Here we describe the specific effect that tomato SlS5H impairment produces on both plant-pathogen interactions. The induction of SlS5H in tomato plants by different pathogens was corroborated by qRT-PCR and correlated with previously described 2,5-DHBA accumulations. Transient SlS5H over-expression assays in Nicotiana benthamiana confirmed that SA is a substrate for SlS5H in vivo. RNAi_SlS5H tomato transgenic plants were generated and characterized upon CEVd and Pst infections. Transgenic tomato plants displayed an activation of defences and therefore a loss of susceptibility against both pathogens, and alternative SA homeostasis seems to occur for each specific interaction. Metabolomic assays revealed that whilst the glycosylated form of SA was the most discriminant metabolite found in CEVd infected RNAi_SlS5H transgenic plants, trans-feruloyldopamine, feruloylquinic acid, feruloylgalactarate and 2-hydroxyglutarate were the most accumulated compounds in the Pst-infected transgenic tomato leaves. Transgenic lines also displayed hyper susceptibility to Botrytis cinerea, as well as a smaller size and early senescence. Collectively, our results reveal a novel mechanism by which tomato plants specifically set SA homeostasis upon different pathogen attacks.

One sentence summary

The impairment of SA hydroxylation in tomato plants uncovers specific SA homeostasis upon CEVd or Pseudomonas syringae infections.
Beyond pulsed inhibition: Alpha oscillations modulate attenuation and amplification of neural activity in the awake resting-state
Authors: Lombardi Fabrizio , Herrmann Hans J. , Parrino Liborio , Plenz Dietmar , Scarpetta Silvia , Vaudano Anna Elisabetta , de Arcangelis Lucilla , Shriki Oren
Published: March 2022

The alpha rhythm is a distinctive feature of the awake resting-state of the human brain. Recent evidence suggests that alpha plays an active role in information processing, modulating behavioral and cognitive performance. However, the functional role of alpha oscillations in the resting-state neuronal dynamics remains poorly understood. To address this question, we investigate collective neural activity during resting wake and NREM sleep, a physiologic state with marginal presence of alpha rhythm. We show that, during resting wake, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over timescales of a few alpha cycles to amplify neural activity. Furthermore, we show that long-term, intermittent fluctuations in alpha amplitude—known as the “waxing and waning” phenomenon—are associated with an attenuation-amplification mechanism acting over the timescales of several seconds and described by a power law decay of the activity rate in the “waning” phase. Importantly, we do not observe such dynamics during NREM sleep. The results suggest that the alpha rhythm acts as a “pacemaker” for the alternation of inhibition and excitation bouts across multiple timescales, the “waxing and waning” being a long-term control mechanism of cortical excitability. The amplification regime observed beyond the timescales of the individual alpha cycle suggests in turn that alpha oscillations might modulate the intensity of neural activity not only through pulses of inhibition, as proposed in the pulsed inhibition hypothesis, but also by timely enhancing excitation (or dis-inhibition).
What are oxytocin assays measuring? Epitope mapping, metabolites, and comparisons of wildtype & knockout mouse urine
Authors: Gnanadesikan Gitanjali E. , Hammock Elizabeth A.D. , Tecot Stacey R. , Lewis Rebecca J. , Hart Russ , Carter C. Sue , MacLean Evan L.
Published: March 2022

Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference—with knockout samples measuring below the assay’s limit of detection—while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good parallelism and spike recovery across multiple species (mice, dogs, sifakas, humans). Our results suggest that immunoassays of urine samples may be particularly susceptible to interference, even when using common extraction protocols, but that this interference can be successfully managed using a novel mixed-mode cation exchange extraction.
De-heterogeneity of the eukaryotic viral reference database (EVRD) improves the accuracy and efficiency of viromic analysis
Authors: Chen Junjie , Yan Xiaomin , Sun Yue , Ren Zilin , Yan Guangzhi , Wang Guoshuai , Liu Yuhang , Zhao Zihan , Liu Yang , Tu Changchun , He Biao
Published: March 2022

Widespread in public databases, the notorious contamination in virus reference databases often leads to confusing even wrong conclusions in applications like viral disease diagnosis and viromic analysis, highlighting the need of a high-quality database. Here, we report the comprehensive scrutiny and the purification of the largest viral sequence collections of GenBank and UniProt by detection and characterization of heterogeneous sequences (HGSs). A total of 766 nucleotide- and 276 amino acid-HGSs were determined with length up to 6,605 bp, which were widely distributed in 39 families, with many involving highly public health-related viruses, such as hepatitis C virus, Crimea-Congo hemorrhagic fever virus and filovirus. Majority of these HGSs are sequences of a wide range of hosts including humans, with the rest resulting from vectors, misclassification and laboratory components. However, these HGSs cannot be simply considered as exotic contaminants, since part of which are resultants of natural occurrence or artificial engineering of the viruses. Nevertheless, they significantly disturb the genomic analysis, and hence were deleted from the database. A further augmentation was implemented with addition of the risk and vaccine sequences, which finally results in a high-quality eukaryotic virus reference database (EVRD). EVRD showed higher accuracy and less time-consuming without coverage compromise by reducing false positives than other integrated databases in viromic analysis. EVRD is freely accessible with favorable application in viral disease diagnosis, taxonomic clustering, viromic analysis and novel virus detection.
A cell non-autonomous FOXO/DAF-16-mediated germline quality assurance program that responds to somatic DNA damage
Authors: Sarkar Gautam Chandra , Rautela Umanshi , Goyala Anita , Datta Sudeshna , Anand Nikhita , Singh Anupama , Singh Prachi , Chamoli Manish , Mukhopadhyay Arnab
Published: March 2022

Germline integrity is critical for progeny fitness. Organisms deploy the DNA damage response (DDR) signalling to protect germline from genotoxic stress, facilitating cell-cycle arrest of germ cells and DNA repair or their apoptosis. Cell-autonomous regulation of germline quality is well-studied; however, how quality is enforced cell non-autonomously on sensing somatic DNA damage is less known. Using Caenorhabditis elegans, we show that DDR disruption, only in the uterus, when insulin-IGF-1 signalling (IIS) is low, arrests germline development and induces sterility in a FOXO/DAF-16 transcription factor (TF)-dependent manner. Without FOXO/DAF-16, germ cells of the IIS mutant escape arrest to produce poor quality oocytes, showing that the TF imposes strict quality control during low IIS. In response to low IIS in neurons, FOXO/DAF-16 works cell autonomously as well as non-autonomously to facilitate the arrest. Activated FOXO/DAF-16 promotes transcription of checkpoint and DDR genes, protecting germline integrity. However, on reducing DDR during low IIS, the TF decreases ERK/MPK-1 signaling below a threshold, and transcriptionally downregulates genes involved in spermatogenesis-to-oogenesis switch as well as cdk-1/Cyclin B to promote germline arrest. Altogether, our study reveals how cell non-autonomous function of FOXO/DAF-16 promotes germline quality and progeny fitness in response to somatic DNA damage.

Significance Statement

Reproductive decisions are supervised processes that take into account various inputs like cellular energy availability and status of damage repair in order to ensure healthy progeny. In this study, we show that the absence of optimal DNA damage repair in the somatic uterine tissues prevents oocyte development by the cell-autonomous as well non-autonomous function of activated FOXO transcription factor DAF-16. Thus, this study elucidates a new surveillance role of FOXO/DAF-16 in somatic tissues that ensures progeny fitness.
CDK4 deletion in mice prevents fat accumulation and increases endurance capacity through activation of estrogen-related receptor (ERR)-driven oxidative metabolism in skeletal muscle
Authors: Barquissau Valentin , Zanou Nadège , Geller Sarah , Castillo-Armengol Judit , Marzetta Flavia , Huber Katharina , Ziegler Dorian , Lopez-Mejia Isabel , Fernandez Joan Blanco , Roger Catherine , Guex Nicolas , Preitner Frédéric , Vanacker Jean-Marc , Fajas Lluis
Published: March 2022

Cyclin-dependent kinase 4 (CDK4) canonical role is to control cell cycle progression from G1 to S phases. However, recent studies reported that CDK4 regulates energy metabolism in non-proliferating cells such as hepatocytes or adipocytes. The objective of our work is to study CDK4 function in skeletal muscle using a model of mice lacking CDK4 (cdk4-/-). By coupling treadmill running to indirect calorimetry, we show thatcdk4-/-mice display improved endurance and higher capacity to use fat as fuel during exercise. Isolated muscles lacking CDK4 are more resistant to fatigue in response to repeated contractions and have increased oxidative capacity and mitochondrial content compared tocdk4+/+muscles. Transcriptomic analysis reveals upregulation of genes controlled by the nuclear receptors estrogen-related receptors (ERRs) incdk4-/-skeletal muscle, associated with elevated levels of the ERR co-activator PGC1a. Supporting in vivo results, C2C12 myotubes treated with a CDK4 inhibitor have increased mitochondrial oxygen consumption, PGC1α expression and ERR transcriptional activity measured by a luciferase reporter. In normal housing conditions,cdk4-/-mice show an increased basal metabolic rate and are resistant to weight gain and fat accumulation. In conclusion, our study uncovers a role for CDK4 in the control of skeletal muscle metabolism. Moreover, CDK4 inhibition may be an alternative strategy against obesity-associated metabolic disorders.
Collagen-VI expression is negatively mechanosensitive in pancreatic cancer cells and supports the metastatic niche
Authors: Papalazarou Vasileios , Drew James , Juin Amelie , Spence Heather J. , Nixon Colin , Salmeron-Sanchez Manuel , Machesky Laura M.
Published: March 2022

Pancreatic cancer is a deadly disease with high rates of metastasis, though how tumor cells establish metastatic lesions is not fully understood. A key feature of primary pancreatic tumors is extensive fibrosis due to deposition of extracellular matrix. While pancreatic cancer cells are programmed by stimuli derived from a stiff ECM, metastasis requires loss of attachment as well as adaptation to a softer microenvironment upon reaching distant sites. Growing evidence suggests that stiff ECM influences pancreatic cancer cell behaviour. Here we argue that this influence is reversible and that pancreatic cancer cells can be reprogrammed upon sensing of soft substrates. Through use of engineered polyacrylamide hydrogels with tuneable mechanical properties, we show that Collagen-VI is specifically upregulated on soft substrates, due to a lack of integrin engagement and low YAP1 activity. Collagen-VI supports migration in vitro and metastasis formation in vivo. Metastatic nodules formed by pancreatic cancer cells lacking Col6a1 expression, were characterised by stromal cell-derived collagen-VI deposition, suggesting that collagen-VI, either cancer or stroma derived, is an essential component of the metastatic niche.

Summary Statement

Collagen-VI is expressed by pancreatic tumors and metastases in a mechanosensitive way to promote niche colonisation.
A tissue boundary orchestrates the segregation of inner ear sensory organs
Authors: Chen Ziqi , Żak Magdalena , Xu Shuting , de Andrés Javier , Daudet Nicolas
Published: March 2022

The inner ear contains distinct sensory organs, produced sequentially by segregation from a large sensory-competent domain in the developing otic vesicle. To understand the mechanistic basis of this process, we investigated the changes in prosensory cell patterning, proliferation and character during the segregation of some of the vestibular organs in the mouse and chicken otic vesicle. We discovered a specialized boundary domain, located at the interface of segregating organs. It is composed of prosensory cells that gradually enlarge, elongate and are ultimately diverted from a prosensory fate. Strikingly, the boundary cells align their apical borders and constrict basally at the interface of cells expressing or not the Lmx1a transcription factor, an orthologue of drosophila Apterous. The boundary domain is absent inLmx1a-deficient mice, which exhibit defects in sensory organ segregation, and is disrupted by the inhibition of ROCK-dependent actomyosin contractility. Altogether, our results suggest that actomyosin-dependent tissue boundaries ensure the proper separation of inner ear sensory organs and uncover striking homologies between this process and the compartmentalization of the drosophila wing disc by lineage-restricted boundaries.
GTEM cell design for controlled exposure to electromagnetic fields in biological system
Authors: Tao J. , Li Z.-G. , Vuong T.-H. , Kunduzova O.
Published: March 2022

This study describes a structure design of the Gigaherz Transverse Electromagnetic (GTEM) cell for electromagnetic tests in biological systems. Using electromagnetic simulation software we show that the optimization of final structure assures the criteria imposed on a low level of reflection towards the radio frequency generator, and a fairly uniform field in the test zone. A sensitivity study was also conducted when the cell was loaded with a few samples under test. We report that the level of reflection remains adequate as long as the test volume remains limited in relation to the size of the cell. The first estimation results on the SAR values are consistent with the distribution of the fields in the cell. A cell was fabricated with the design data, and tested for the reflection level. The measurements confirm the results of simulations.
A mechanistic spatiotemporal model for drug resistant infections
Authors: Lee Tamsin E. , De Salazar Pablo M.
Published: March 2022

Effective public health strategies for preventing infectious diseases require a deep understanding of transmission dynamics. However, epidemiological data alone is often insufficient for guiding public health action, as transmission patterns emerge from complex human-environment interactions. Additionally, collecting empirical data is frequently limited by cost and logistical challenges, especially in low-resource settings. Consequently, health policy increasingly relies on inference models that account for spatial and temporal dimensions, confounding factors, and uncertainty.

In this work, we introduce a novel hierarchical mechanistic Bayesian model based on ecological diffusion to improve epidemiological inference for spreading pathogens. This model is specifically designed to reveal underlying spatiotemporal dynamics from empirical data, explicitly accounting for sampling bias and uncertainty. To demonstrate its effectiveness, we apply the model to simulated data of a drug-resistant pathogen and formally compare its performance to state-of-the-art epidemiological regression models.

Our findings show that the model accurately identifies transmission patterns and is particularly effective at pinpointing transmission hotspots and predicting spread pathways—critical capabilities for controlling drug-resistant pathogens. While reliable monitoring remains challenging in low-resource environments, this model addresses demographic sampling bias and spatiotemporal complexities, though concentrated sampling in presumed high-risk areas can sometimes distort transmission insights.

The proposed framework can inform targeted public health interventions in the early stages of resistance emergence, offering valuable guidance for resource-constrained settings.
Unruly octopuses are the rule: Octopus vulgaris use multiple and individually variable strategies in an episodic-like memory task
Authors: Lisa Poncet , Coraline Desnous , Cécile Bellanger , Christelle Jozet-Alves
Published: March 2022

The evolution of complex cognition can be explained by different hypotheses, mutually non-exclusive: the social intelligence hypothesis, the ecological intelligence hypothesis and the predator-prey interaction hypothesis. Episodic-like memory can be used as a proxy to study complex cognition. This ability has mainly been studied through experimental tasks where subjects have to remember what they ate, where and when or in which context. Seemingly quite common in mammals and corvids, episodic-like memory abilities have been observed in only one invertebrate species: the common cuttlefish, a cephalopod mollusc. To explore if this ability is common to all cephalopods or if it has emerged to face specific constraints, we conducted an episodic-like memory task with seven Octopus vulgaris. Only one individual learnt the replenishing rates during the training and subsequently showed episodic-like memory abilities, whereas the other individuals favoured simpler foraging strategies, such as avoidance of familiarity and alternation, use of win-stay strategy and risk-sensitivity. A high variability in the use of these strategies was observed between and within individuals throughout the training. Since octopuses seem to live under lighter environmental pressure than cuttlefish, they may not need to rely on episodic-like memory abilities to optimize foraging as cuttlefish do. These results highlight the differences in the use of complex cognitive abilities between cuttlefish and octopuses, which might be linked with different environmental, predatory and social constraints.

Summary statement

When trained in an episodic-like memory task, common octopuses favour individually variable foraging strategies rather than keeping track of time to solve the task as cuttlefish do.
TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance
Authors: Yang Acong , Ros Xavier Bofill-De , Stanton Ryan , Shao Tie-Juan , Villanueva Patricia , Gu Shuo
Published: March 2022

TENTs generate miRNA isoforms by 3’ tailing. However, little is known about how tailing regulates miRNA function. Here, we generated isogenic HEK293T cell lines in which TENT2, TUT4 and TUT7 were knocked out individually or in combination. Together with rescue experiments, we characterized TENT-specific effects by deep sequencing, Northern blot andin vitroassays. We found that 3’ tailing is not random but highly specific. In addition to its known adenylation, TENT2 contributes to guanylation and uridylation on mature miRNAs. TUT4 uridylates most miRNAs whereas TUT7 is dispensable. Removing adenylation has a marginal impact on miRNA levels. By contrast, abolishing uridylation leads to dysregulation of a set of miRNAs. Besides let-7, miR-181b and miR-222 are negatively regulated by TUT4/7 via distinct mechanisms while the miR-888 cluster is upregulated specifically by TUT7. Our results uncover the selective actions of TENTs in generating 3’ isomiRs and pave the way to investigate their functions.
Monomodular Pseudomonas aeruginosa phage JG004 lysozyme (Pae87) contains a bacterial surface-active antimicrobial peptide-like region and a possible substrate-binding subdomain
Authors: Vázquez Roberto , Seoane-Blanco Mateo , Rivero-Buceta Virginia , Ruiz Susana , van Raaij Mark J. , García Pedro
Published: March 2022

Phage lysins are a source of novel antimicrobials to tackle the bacterial antibiotic-resistance crisis. The engineering of phage lysins is being explored as a game-changing technological strategy to introduce a more precise approach in the way in which antimicrobial therapy is applied. Such engineering efforts will benefit from a better understanding of lysin structure and function. In this work, the antimicrobial activity of the endolysin from Pseudomonas aeruginosa phage JG004, termed Pae87, has been characterized. This lysin had previously been identified as an antimicrobial agent candidate that is able to interact with the Gram-negative surface and disrupt it. Further evidence is provided here based on a structural and biochemical study. A high-resolution crystal structure of Pae87 complexed with a peptidoglycan fragment showed a separate substrate-binding region within the catalytic domain, 18 Å away from the catalytic site and located on the opposite side of the lysin molecule. This substrate-binding region was conserved among phylogenetically related lysins lacking an additional cell-wall-binding domain, but not among those containing such a module. Two glutamic acids were identified to be relevant for the peptidoglycan-degradation activity, although the antimicrobial activity of Pae87 was seemingly unrelated. In contrast, an antimicrobial peptide-like region within the Pae87 C-terminus, named P87, was found to be able to actively disturb the outer membrane and display antibacterial activity by itself. Therefore, an antimicrobial mechanism for Pae87 is proposed in which the P87 peptide plays the role of binding to the outer membrane and disrupting the cell-wall function, either with or without the participation of the catalytic activity of Pae87.
Application of the technology acceptance model to food delivery apps
Authors: Lee Won Seok , Song Myungkeun , Moon Joonho , Tang Ruohan
Published: March 2022

Purpose

This study explores food delivery app users and technology acceptance model as a theoretical underpinning. This study thus investigated the determinants of usefulness, ease of use and intention to use for food delivery app service.

Design/methodology/approach

The variables of delivery time, diverse menu, quarantine, review quality and ease of use are employed as determinants of usefulness. The antecedents of ease of use are easy registration and easy payment. This study also examined the association between ease of use, usefulness and intention to use. This study collected data using Amazon Mechanical Turk, and the number of valid observations for statistical analysis was 484. A structural equation model was used to test the hypotheses.

Findings

Regarding the results, usefulness was positively affected by delivery time, quarantine, review quality and ease of use. Additionally, ease of use was positively impacted by easy registration and easy payment. Finally, this study showed that ease of use positively affects both usefulness and intention to use, and usefulness is positively associated with intention to use.

Originality/value

This study contributes to the literature by ensuring the explanatory power of technology acceptance model for food delivery app.
The effect of business ethics and governance score on tax avoidance: a European perspective
Authors: Abdelmoula Lassaad , Chouaibi Salim , Chouaibi Jamel
Published: March 2022

Purpose

The purpose of this study is to examine the effect of business ethics and governance score on tax avoidance.

Design/methodology/approach

The sample used consists of 432 European companies belonging to the STOXX600 index during the period ranging from 2010 to 2019. The authors use the linear regression with a panel data.

Findings

The results show a negative and significant relationship between business ethics and tax avoidance. In addition, the governance is negatively and significantly correlated with tax avoidance. Similarly, this paper finds a negative and significant joint impact of business ethics and governance score on tax avoidance.

Practical implications

The findings of this paper could help firms consider their future growth opportunities in a context where the approach of business ethics occupies a central position in the business valuation.

Originality/value

This study is motivated by the low number of works in the context of the tax avoidance. It makes an important contribution to the academic literature through adding to the limited body of research on business ethics and governance score in a company setting. The firms strongly focusing on ethics and governance score are more likely to reduce their tax avoidance activities. Thus, these corporations aim to preserve their reputation and image. In this regard, it is worth saying that a positive reputation can increase the shareholder value. Accordingly, companies find a powerful strategy in their commitment and their ethical and responsible behavior, allowing them to maintain their good image and reputation.
Reimagining leadership through lessons from the life of Aurelia Erskine Brazeal
Authors: George Atim Eneida
Published: March 2022

Purpose

The purpose of this study is to fill a gap in the literature by examining the import and impact of the generative leadership philosophy and praxis of Ambassador Aurelia Erskine Brazeal, an African American Female Foreign Service Officer.

Design/methodology/approach

This single subject case study, augmented by portraiture, employs an interdisciplinary methodological design also using polyvocal narrative, oral history and arts-based research.

Findings

The research revealed that a prosocial disposition, compassion, strategic vision, clarity of purpose, commitment to fair play, focus on balance, hearing everyone out and the practice of leadership as a potentiating art are the hallmarks of a generative leadership praxis.

Research limitations/implications

The research posits that to be effective in the 21st century, leaders would do well to incorporate generative leadership qualities and characteristics into their praxis.

Practical implications

This study found that listening, co-creating connections and safe spaces, promoting dialog, critical reflection and collective action are as important to diplomatic tradecraft as they are to generative leadership practice.

Social implications

The challenge of epistemic exclusion suggests that a well-conceived case study examining the life, leadership philosophy and praxis of Aurelia Erskine Brazeal – an individual of merit and distinction – can serve as an exemplar in efforts to reimagine public leadership in the 21st century.

Originality/value

The value of this research is found in its phenomenological approach which shares insights drawn from personal biography as well as key perspectives on public history.
Challenge-based, interdisciplinary learning for sustainability in doctoral education
Authors: Piccardo Chiara , Goto Yutaka , Koca Deniz , Aalto Pasi , Hughes Mark
Published: March 2022

Purpose

Doctoral candidates possess specialized knowledge that could support sustainability transitions. Doctoral education, however, often focusses on discipline-specific topics and working methods, making it difficult to “see the bigger picture”. This summer school on wood construction gathered doctoral candidates from different fields to explore how solutions to complex sustainability issues could be found by working together across disciplines and by engaging multiple stakeholders. The purpose of this study is to report the pedagogical approaches taken and to understand whether these fostered the candidates’ ability to develop systemic solutions and professional competency.

Design/methodology/approach

Twenty doctoral candidates from various backgrounds participated in a two-week summer school organized by a consortium of four universities. Interdisciplinary groups worked on real-life challenges using a systemic approach to co-create tangible solutions. To support the creation of socio-technical innovations, stakeholders and experts from different fields were involved. The participants completed two questionnaires during the summer school to help elucidate their learning experiences.

Findings

The doctoral candidates showed strong willingness to cooperate across disciplines, though they found it important to connect this learning experience to their research. The candidates reported that the experience enhanced their ability to work in a multidisciplinary capacity. The experience identified a solid basis for interdisciplinary learning principles that could be replicated.

Originality/value

The summer school focussed on an innovative learning experience based on a systems thinking approach and the development of interdisciplinary capacity in the research-business ecosystem.
Impact of internal remittance on households' use of bank services: evidence from Vietnam
Authors: Nguyen Thu Thi Hoai , Le Hung Manh , Hoi Le Quoc , Pham Hang Thu
Published: March 2022

Purpose

This study estimates impact of remittances from internal migration on households' use of bank services in Vietnam.

Design/methodology/approach

This study uses data from the Vietnam Household Living Standards Survey and the two-stage least squares method (2SLS).

Findings

The results show that receiving internal remittance increases households' probability of having bank accounts and using card services. However, these impacts are different between rural and urban areas.

Research limitations/implications

The results of this study reveal the useful role of internal remittance in increasing the probability of households using bank services, thereby enhancing financial inclusion in Vietnam.

Originality/value

Different from the previous studies, the purpose of this paper is to analyse the impact of internal remittance on the use of bank services in Vietnam at the household level. This paper targets internal migration because it is the main type of migration in Vietnam. Besides, to the best of the authors’ knowledge, this research is the first one that compares the role of internal remittance on households' use of bank services in rural and urban areas in Vietnam.
Halal tourism as a strategic option for South Korean tourism
Authors: Marlinda Ajeng Puspa , Al-Fadhat Faris , Cipto Bambang , Jubba Hasse
Published: March 2022

Purpose

This study aims to investigate the opinion of a group of informants in Seoul – South Korea’s foremost destination – on the possibility of developing a halal tourism policy that is closer to the wishes of Muslim customers, which is also in line with Islamic principles.

Design/methodology/approach

This research investigated the perceptions of 17 key informants. The data was conducted through interview about the possibility of developing an industry that is more in line with the lifestyle of Muslim tourists and more in line with halal criteria.

Findings

This study shows that the idea is quite attractive, especially among Seoul tourism industry players and even the South Korean Government itself. Although the potential for halal tourism is recognized, its development is currently divided into three groups, namely, groups that support the development of the policy, groups that reject and groups who do not care about it.

Originality/value

The research in this paper shows further developments from the studies that have been conducted in Djerba, Tunisia, that halal tourism carried out in Seoul, South Korea, has become a priority for the government through agencies/institutions/communities related to the halal industry.