bluuebunny/crossref_metadata_2025 huggingface dataset:
Exogenous stimulation ofTanacetum vulgareroots with pipecolic acid leads to tissue-specific responses in terpenoid composition
Authors: Rahimova Humay , Heinen Robin , Weber Baris , Weisser Wolfgang W. , Schnitzler Jörg-Peter
Published: April 2024

Tanacetum vulgareL., known as tansy, is a perennial plant with a highly variable terpenoid composition, with mono- and sesquiterpenoids being the most abundant. The high diversity of terpenoids is known to play an important role in mediating ecological interactions. However, the distribution of terpenoids in different tissues and the inducibility of terpenoids in these tissues by biotic stress are poorly understood.

In this study, we investigated the changes in terpenoid profiles and concentrations in different plant organs following treatment of roots with pipecolic acid (Pip). Pipecolic acid is a non-proteinogenic amino acid that triggers defense responses in plants. It is often used to induce systemic resistance (SAR) in plants under controlled conditions.

Examination of the tissues showed that the leaves and midribs contained mainly monoterpenoids, while the coarse and fine roots of the plants contained mainly sesquiterpenoids. The rhizomes occupied an intermediate position by presenting the terpenoid profiles of both the midribs and roots but also the unique compounds of its own. Treatment with pipecolic acid led to an increase in the concentration of mono- and sesquiterpenoids in all tissues except rhizomes. However, a significantly higher amount of sesquiterpenoids was formed in root tissues in response to Pip compared to shoots.

The metabolic atlas for terpenoids presented here shows that there is an exceptionally strong differentiation of terpenoid patterns and terpenoid contents in the different tissues of tansy. This, together with the differential inducibility by biotic stress, suggests that the chemical diversity of terpenoids may play an important role in the ecological interactions of tansy and in the defense against biotic stressors that feed on the below- and above-ground organs of the plant.
The gut-brain vagal axis scales hippocampal memory processes and plasticity
Authors: Onimus Oriane , Arrivet Faustine , de Oliveira Souza Isis Nem , Bertrand Benoit , Castel Julien , Luquet Serge , Mothet Jean-Pierre , Heck Nicolas , Gangarossa Giuseppe
Published: April 2024

The vagus nerve serves as an interoceptive relay between the body and the brain. Despite its well-established role in feeding behaviors, energy metabolism, and cognitive functions, the intricate functional processes linking the vagus nerve to the hippocampus and its contribution to learning and memory dynamics remain still elusive.

Here, we investigated whether and how the gut-brain vagal axis contributes to hippocampal learning and memory processes at behavioral, functional, cellular, and molecular levels. Our results indicate that the integrity of the vagal axis is essential for long-term recognition memories, while sparing other forms of memory. In addition, by combing multi-scale approaches, our findings show that the gut-brain vagal tone exerts a permissive role in scaling intracellular signaling events, gene expressions, hippocampal dendritic spines density as well as functional long-term plasticities (LTD and LTP). These results highlight the critical role of the gut-brain vagal axis in maintaining the spontaneous and homeostatic functions of hippocampal ensembles and in regulating their learning and memory functions.

In conclusion, our study provides comprehensive insights into the multifaceted involvement of the gut-brain vagal axis in shaping time-dependent hippocampal learning and memory dynamics. Understanding the mechanisms underlying this interoceptive body-brain neuronal communication may pave the way for novel therapeutic approaches in conditions associated with cognitive decline, including neurodegenerative disorders.

Highlights

The gut-brain vagal axis contributes to long-term recognition memories

The gut-brain vagal axis is dispensable for short-term memories

The vagal axis regulates molecular and signaling dynamics in the hippocampus

The gut-brain vagal tone shapes the structural density of hippocampal dendritic spines

The gut-brain vagal tone ensures physiological forms of synaptic plasticity
SMAD4 and KRAS status shape malignant-stromal crosstalk in pancreatic cancer
Authors: Lloyd Eloise G. , Jihad Muntadher , Manansala Judhell S. , Li Wenlong , Cheng Priscilla S. W. , Teles Sara Pinto , Mucciolo Gianluca , Henríquez Joaquín Araos , Ashworth Sally , Luo Weike , Harish Sneha , Johnson Paul M. , Veghini Lisa , Zaccaria Marta , Brais Rebecca , Vallespinos Mireia , Corbo Vincenzo , Biffi Giulia
Published: April 2024

Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing to the dismal prognosis associated with this cancer. Evidence suggests that the stromal composition of PDAC is shaped by mutations within malignant cells; however, most pre-clinical models of PDAC are driven byKrasG12Dand mutantTrp53and have not assessed the contribution of other known oncogenic drivers, includingKRASG12Vand alterations inCDKN2AandSMAD4. To increase understanding of malignant cell-stroma crosstalk in PDAC, we analyzedTrp53-mutant mouse models driven byKrasG12DorKrasG12Vin whichSmad4was wild-type or deleted.KrasG12D;Smad4-deleted PDAC developed a fibro-inflammatory rich stroma with increased JAK/STAT malignant cell signaling and an enhanced therapeutic response to JAK/STAT inhibition. In stark contrast, the stroma ofSmad4-deletedKrasG12VPDAC was differently altered, and the malignant compartment lacked JAK/STAT signaling dependency. Thus, malignant cell genotype impacts malignant-stromal phenotype in PDAC, directly affecting therapeutic efficacy.

STATEMENT OF SIGNIFICANCE

Understanding malignant cell-stroma crosstalk in PDAC has focused on models containingKrasG12Dand mutantTrp53. Here, we show that PDAC driven byKrasG12DorKrasG12Vin whichSmad4is deleted display differences in malignant-stromal signaling and treatment sensitivity, highlighting the importance of understanding genotype-phenotype relationships for precision PDAC therapy.
Stem cell models of TAFAZZIN deficiency reveal novel tissue-specific pathologies in Barth Syndrome
Authors: Sniezek Carney Olivia , Harris Kodi William , Wohlfarter Yvonne , Lee Kyuna , Butschek Grant , Anzmann Arianna , Claypool Steven M , Hamacher-Brady Anne , Keller Markus , Vernon Hilary J.
Published: April 2024

Barth syndrome (BTHS) is a rare mitochondrial disease caused by pathogenic variants in the gene TAFAZZIN, which leads to abnormal cardiolipin (CL) metabolism on the inner mitochondrial membrane. AlthoughTAFAZZINis ubiquitously expressed, BTHS involves a complex combination of tissue specific phenotypes including cardiomyopathy, neutropenia, skeletal myopathy, and growth delays, with a relatively minimal neurological burden. To understand both the developmental and functional effects of TAZ-deficiency in different tissues, we generated isogenic TAZ knockout (TAZ- KO) and WT cardiomyocytes (CMs) and neural progenitor cells (NPCs) from CRISPR-edited induced pluripotent stem cells (iPSCs). In TAZ-KO CMs we discovered evidence of dysregulated mitophagy including dysmorphic mitochondria and mitochondrial cristae, differential expression of key autophagy-associated genes, and an inability of TAZ-deficient CMs to properly initiate stress-induced mitophagy. In TAZ-deficient NPCs we identified novel phenotypes including a reduction in CIV abundance and CIV activity in the CIII2&CIV2 intermediate complex. Interestingly, while CL acyl chain manipulation was unable to alter mitophagy defects in TAZ-KO CMs, we found that linoleic acid or oleic acid supplementation was able to partially restore CIV abundance in TAZ-deficient NPCs. Taken together, our results have implications for understanding the tissue-specific pathology of BTHS and potential for tissue-specific therapeutic targeting. Moreover, our results highlight an emerging role for mitophagy in the cardiac pathophysiology of BTHS and reveal a potential neuron-specific bioenergetic phenotype.
Rhizobial effector NopM ubiquitinates Nod factor receptor NFR5 and promotes rhizobial infection inLotus japonicus
Authors: Wang Yanan , Bao Hanbin , Lei Yutao , Yuan Lifa , Li Haoxing , Zhu Hui , Xin Dawei , Staehelin Christian , Cao Yangrong
Published: April 2024

Bacterial pathogens and nitrogen-fixing rhizobia employ type III protein secretion system (T3SS) effectors as potent tools to manipulate plant signaling pathways, thereby facilitating infection and host colonization. However, the molecular mechanisms by which rhizobial effectors affect legume infection remain largely elusive. In this study, we investigated the symbiotic role of T3SS effectors in the interaction betweenSinorhizobium frediiNGR234 andLotus japonicus. Mutants deficient in the T3SS genesTts1orNopAshowed enhanced rhizobial infection ofL. japonicusroots. Further mutant analysis showed that the NopT effector negatively affects infection, while the NopM effector in the absence of NopT promotes infection. Notably, NopM interacts with the Nod factor receptors LjNFR1 and LjNFR5. NopM ubiquitinates LjNFR5 on ten lysine residues as identified using mass spectrometry. Expression ofNopMinL. japonicusresulted in an approximately twofold increase in LjNFR5 protein levels and enhanced rhizobial infection. Our findings indicate that NopM directly interferes with the symbiotic signaling pathway through interaction and ubiquitination of Nod factor receptors, which likely benefits rhizobial infection ofL. japonicus. Our research contributes to the intricate interplay between the Nod factor signaling pathway and rhizobial T3SS effectors delivered into host cells.

Significance Statement

This study unravels intricate mechanisms underlying the symbiotic interaction betweenSinorhizobium frediiNGR234 andLotus japonicus. By focusing on the role of the rhizobial effector NopM, this research sheds light on how bacteria manipulate host symbiotic signaling to promote infection and colonization. NopM interacts with NFRs and ubiquitinates LjNFR5, suggesting a novel strategy employed by rhizobia to enhance symbiotic signaling.
Impact of Species-Specific Plant Growth-Promoting Rhizobacteria (PGPR) on Maize (Zea mays) Phenotypic and Biochemical Diversity
Authors: Singh Swapnil , Roychowdhury Rajib , Mukherjee Arkadeep , Kaur Harleen , Kaur Ravneet , Jagota Neetu , Sandhu Surinder , Kumar Vinod , Gupta Mahiti , Ahn Young-Ho , Meshram Vineet , Sharma Ashish
Published: April 2024

Maize (Zea mays) is a vital cereal crop used as a staple diet in many countries. In contemporary farming practises, inoculation with plant-growth-promoting rhizobacteria (PGPR) can be promoted as a sustainable alternative to chemical fertilizers and pesticides in cereal crops including maize. For experimental verification of the above-mentioned hypothesis, four PGPR inoculantsPseudomonas fluorescens,P. putida, Azospirillum lipoferumandBacillus subtiliswere applied to three maize genotypes (AXE*, PMH1 and PMH10) and their effects were studied by measurement of various morphological and biochemical paramters. Substantial increase in the amount of chlorophyll a (45%), chlorophyll b (100%), total chlorophyll (95%), nitrate reductase (22%), superoxide dismutase (52%), protein content (16%), methionine content (31.8%), grain protein content (69%) were recorded over the control (non-treated or mock) plants. Morphological parameters also exhibited an increase in leaf number (53%), fresh weight (41%) and dry weight (62%) in test plants. Comparable outcome was observed for whole cob weight showing an increase of 42%, cob weight (60%), hundred-grain weight (25.9%), maize grain yield m-2(18%) and yield ha-1(18%) over the control. This study highlights the efficacy of the aforementioned four PGPR species as the most effective for maize crops.Bacillus subtilisandAzospirillum lipoferummay be considered species-specific PGPRs due to their superior performance compared to other strains. The considerable growth-promoting advantages observed in maize plants treated with bacterial inoculation indicated that PGPRs have the potential to be employed as sustainable solutions in maize production.
Non-invasive fasciculation assessment of gastrocnemius failed to show diagnostic or prognostic utility in ALS
Authors: Muir Robbie , O’Shea Brendan , Iniesta Raquel , Masood Urooba , Cabassi Cristina , Planinc Domen , Hodson-Tole Emma , Drakakis Emmanuel , Boutelle Martyn , Shaw Christopher E , Bashford James
Published: April 2024

Objectives

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, affecting both upper and lower motor neurons. High-density surface electromyography is a non-invasive measure of muscle fasciculations, a phenomenon prevalent early in the disease. Previous studies highlighted the clinical importance of these measures from the biceps brachii muscle. Our study aimed to investigate the diagnostic and prognostic value of the medial gastrocnemius muscle.

Methods

We performed a retrospective study of 49 ALS and 25 control participants. Means comparisons, logistic regression, receiver operating characteristic analysis, Kaplan-Meier analysis, and a multilevel Cox model were used to determine the predictive utility of fasciculation potential (FP) parameters including FP frequency, median amplitude, and amplitude dispersion.

Results

FP parameters demonstrated a poor ability to differentiate between ALS and controls, with ROC analysis producing areas under the curve between 0.58 and 0.63. Furthermore, there was no association between FP parameters and ALS prognosis in the Cox model.

Conclusions

FP parameters from the medial gastrocnemius muscle are not useful for the diagnosis or prognosis of ALS patients.

Significance

Our results highlight the poor clinical utility of fasciculation quantification in the medial gastrocnemius muscle. Future studies should focus on recordings from more clinically relevant muscles earlier in the disease.

Highlights

Fasciculation parameters from the medial gastrocnemius muscle have poor ability to differentiate ALS patients from controls.

Fasciculation parameters from the medial gastrocnemius muscle cannot reliably predict the prognosis of ALS patients.

Future studies should measure more clinically relevant muscles at an earlier stage in the disease course over a protracted period.
Comparative genomics of the extremophileCryomyces antarcticusand other psychrophilic Dothideomycetes
Authors: Gomez Sandra V. , Sic Wily , Haridas Sajeet , LaButti Kurt , Eichenberger Joanne , Kaur Navneet , Lipzen Anna , Barry Kerrie , Goodwin Stephen B. , Gribskov Michael , Grigoriev Igor V.
Published: April 2024

Cryomyces antarcticusis an endolithic fungus that inhabits rock outcrops in Antarctica. It survives extremes of cold, humidity and solar radiation in one of the least habitable environments on Earth. This fungus is unusual because it produces heavily melanized, meristematic growth and is thought to be haploid and asexual. Due to its growth in the most extreme environment, it has been suggested as an organism that could survive on Mars. However, the mechanisms it uses to achieve its extremophilic nature are not known. Over a billion years of fungal evolution has enabled representatives of this kingdom to populate almost all parts of planet Earth and to adapt to some of its most uninhabitable environments including extremes of temperature, salinity, pH, water, light, or other sources of radiation. Comparative genomics can provide clues to the processes underlying biological diversity, evolution, and adaptation. This effort has been greatly facilitated by the 1000 Fungal Genomes project and the JGI MycoCosm portal where sequenced genomes have been assembled into phylogenetic and ecological groups representing different projects, lifestyles, ecologies, and evolutionary histories. Comparative genomics within and between these groups provides insights into fungal adaptations, for example to extreme environmental conditions. Here, we analyze twoCryomycesgenomes in the context of additional psychrophilic fungi, as well as non-psychrophilic fungi with diverse lifestyles selected from the MycoCosm database. This analysis identifies families of genes that are expanded and contracted inCryomycesand other psychrophiles and may explain their extremophilic lifestyle. Higher GC contents of genes and of bases in the third positions of codons may help to stabilize DNA under extreme conditions. Numerous smaller contigs inC. antarcticussuggest the presence of an alternative haplotype that could indicate that the sequenced isolate is diploid or dikaryotic. These analyses provide a first step to unraveling the secrets of the extreme lifestyle ofC. antarcticus.
Emergent survival and extinction of species within gut bacterial communities
Authors: van den Berg Naomi Iris , Tramontano Melanie , Guan Rui , Andrejev Sergej , Blasche Sonja , Kim Yongkyu , Klünemann Martina , Brochado Ana Rita , Kalmar Lajos , Telzerow Anja , Bork Peer , Sevin Daniel C. , Typas Athanasios , Patil Kiran R.
Published: April 2024

Synthetic communities can help uncover metabolic forces shaping microbial ecosystems. Yet, in case of the gut microbiota, culturing in undefined media has prevented detection of metabolic dependencies. Here we show, using chemically defined media, how species survival is jointly determined by supplied resources and community metabolism. We used 63 representative gut bacterial strains and varied inoculum compositions to assemble stable communities in 14 defined media. Over 95% of the species showed markedly improved or diminished performance relative to monoculture in at least one condition, including 153 cases (21%) of emergent survival, i.e., species incapable of surviving on their own but thriving in a community, and 252 (35%) community-driven extinctions. Through single species additions and exclusions, metabolomic analysis, and ecological modelling, we demonstrate how inter-species dependencies – especially in poor media – are mediated by biotic nutrient supply. Our results highlight communal metabolic dividend as a key biotic force promoting emergent survival and diversity.
Plant-animal below-ground interaction modifies plant phenotype and its above-ground interaction: a review and new case study
Authors: Vaca-Benito Celia , Ferrón Camilo , Velázquez de Castro Antonio J. , Muñoz-Pajares A. Jesús , Abdelaziz Mohamed , García-Muñoz Ana
Published: April 2024

Ecological interactions play a role in promoting and maintaining biodiversity. These interactions form complex networks of interconnected species. Therefore, changes resulting from an interaction in one of the partners can have indirect consequences on subsequent interactions with other species. Since the mutualism-antagonism continuum is a gradient, a shift in the strength and sign of an interaction is possible, highlighting the dynamic nature of interaction networks. In flowering plants, a wide variety of below- and above-ground interactions are established with a single host plant. Changes in the host, derived from such interactions, can modulate the outcome of the remaining connections in both strength and sign, and the overall configuration of the network. Thus, a species can mediate community-wide consequences through its interaction with the host by altering the plant phenotype. We present a case study where a root infection has unexpected consequences on the pollination host, driving phenotypic changes. This study provides new data on the dynamism of species interactions and the importance of obtaining a global view of interaction networks. Disentangling the direct and indirect effects of interactions and their impact on the rest of the interactions in wild communities is essential for a good understanding of the evolutionary and ecological mechanisms that promote and maintain biodiversity.
Crystallographic Fragment Screen of Coxsackievirus A16 2A Protease identifies new opportunities for the development of broad-spectrum anti-enterovirals
Authors: Lithgo Ryan M. , Tomlinson Charles W.E. , Fairhead Michael , Winokan Max , Thompson Warren , Wild Conor , Aschenbrenner Jasmin Cara , Balcomb Blake H. , Marples Peter G. , Chandran Anu V , Golding Mathew , Koekemoer Lizbe , Williams Eleanor P. , Wang SiYl , Ni Xiaomin , MacLean Elizabeth , Giroud Charline , Godoy Andre Schutzer , Xavier Mary-Ann , Walsh Martin , Fearon Daren , von Delft Frank
Published: April 2024

Enterovirusesare the causative agents of paediatric hand-foot-and-mouth disease, and a target for pandemic preparedness due to the risk of higher order complications in a large-scale outbreak. The 2A protease of these viruses is responsible for the self-cleavage of the poly protein, allowing for correct folding and assembly of capsid proteins in the final stages of viral replication. These 2A proteases are highly conserved betweenEnterovirusspecies, such asEnterovirus A71 and Coxsackievirus A16. Inhibition of the 2A protease deranges capsid folding and assembly, preventing formation of mature virions in host cells and making the protease a valuable target for antiviral activity. Herein, we describe a crystallographic fragment screening campaign that identified 75 fragments which bind to the 2A protease including 38 unique compounds shown to bind within the active site. These fragments reveal a path for the development of non-peptidomimetic inhibitors of the 2A protease with broad-spectrum anti-enteroviral activity.
An extended omnigenic model explains genome-phenome relationships for complex traits in global sorghum diversity
Authors: Hu Zhenbin , Wang Xu , Marla Sandeep R. , Poland Jesse , Morris Geoffrey P.
Published: April 2024

A central finding of complex trait genetics is the geometric distribution of effect sizes, but the biological basis of this phenomena is not understood. The omnigenic model (OM) could explain this architecture, with oligogenic variation arising from direct regulatory genes (core genes) and polygenic variation from indirect regulators (peripheraltransregulators). Plant yield is a canonical complex trait and here we tested the OM using genome-phenome analysis of biomass yield in global sorghum diversity. We used field-based phenomics to characterize dynamic growth and yield formation traits, then decomposed oligogenic and polygenic components of variation using genome-wide association studies (GWAS), genome-wide prediction (GWP), and tissue-specific transcriptome analyses. We identified major dynamic QTL, including several persistent (Dw1,Dw3) or transient (ELF3) QTL at known genes, consistent with the oligogenic-core of the OM. Next, we evaluated a key prediction on the peripheral-polygenic component – a positive correlation between GWP marker loadings and gene expression in relevant tissues. GWP loadings are indeed correlated with gene expression in relevant tissues. However, correlations are often higher with non-relevant tissues from earlier growth stages or tissues, which is not predicted by within-tissuetransregulation for the peripheral-polygenic component (the “omnigenic in space” model). Therefore, these findings suggest that genes expressed in early growth stages, with indirect effects on later traits, are contributing to polygenic variation (“omnigenic in time”). Together, our findings suggest that an extended OM, with regulatory effects both in space and in time, could explain the ubiquitous geometric genetic architecture of complex traits.
P66 is a bacterial mimic of CD47 that binds the anti-phagocytic receptor SIRPα and facilitates macrophage evasion byBorrelia burgdorferi
Authors: Tal Michal Caspi , Hansen Paige S. , Ogasawara Haley A. , Feng Qingying , Volk Regan F. , Lee Brandon , Casebeer Sara E. , Blacker Grace S. , Shoham Maia , Galloway Sarah D. , Sapiro Anne L. , Hayes Beth , Dulgeroff Laughing Bear Torrez , Raveh Tal , Pothineni Venkata Raveendra , Potula Hari-Hara SK , Rajadas Jayakumar , Bastounis Effie E. , Chou Seemay , Robinson William H. , Coburn Jenifer , Weissman Irving L. , Zaro Balyn W.
Published: April 2024

Summary Paragraph

Innate immunity, the first line of defense against pathogens, relies on efficient elimination of invading agents by phagocytes. In the co-evolution of host and pathogen, pathogens developed mechanisms to dampen and evade phagocytic clearance. Here, we report that bacterial pathogens can evade clearance by macrophages through mimicry at the mammalian anti-phagocytic “don’t eat me” signaling axis between CD47 (ligand) and SIRPα (receptor). We identified a protein, P66, on the surface ofBorrelia burgdorferithat, like CD47, is necessary and sufficient to bind the macrophage receptor SIRPα. Expression of the gene encoding the protein is required for bacteria to bind SIRPα or a high-affinity CD47 reagent. Genetic deletion ofp66increases phagocytosis by macrophages. Blockade of P66 during infection promotes clearance of the bacteria. This study demonstrates that mimicry of the mammalian anti-phagocytic protein CD47 byB. burgdorferiinhibits macrophage-mediated bacterial clearance. Such a mechanism has broad implications for understanding of host-pathogen interactions and expands the function of the established innate immune checkpoint receptor SIRPα. Moreover, this report reveals P66 as a novel therapeutic target in the treatment of Lyme Disease.
Interactome dynamics during heat stress signal transmission and reception
Authors: Park Sung-Gun , Keller Andrew , Kaiser Nathan K. , Bruce James E.
Published: April 2024

Among evolved molecular mechanisms, cellular stress response to altered environmental conditions to promote survival is among the most fundamental. The presence of stress-induced unfolded or misfolded proteins and molecular registration of these events constitute early steps in cellular stress response. However, what stress-induced changes in protein conformations and protein-protein interactions within cells initiate stress response and how these features are recognized by cellular systems are questions that have remained difficult to answer, requiring new approaches. Quantitativein vivochemical cross-linking coupled with mass spectrometry (qXL-MS) is an emerging technology that provides new insight on protein conformations, protein-protein interactions and how the interactome changes during perturbation within cells, organelles, and even tissues. In this work, qXL-MS and quantitative proteome analyses were applied to identify significant time-dependent interactome changes that occur prior to large-scale proteome abundance remodeling within cells subjected to heat stress. Interactome changes were identified within minutes of applied heat stress, including stress-induced changes in chaperone systems as expected due to altered functional demand. However, global analysis of all interactome changes revealed the largest significant enrichment in the gene ontology molecular function term of RNA binding. This group included more than 100 proteins among multiple components of protein synthesis machinery, including mRNA binding, spliceosomes, and ribosomes. These interactome data provide new conformational insight on the complex relationship that exists between transcription, translation and cellular stress response mechanisms. Moreover, stress-dependent interactome changes suggest that in addition to conformational stabilization of RNA-binding proteins, adaptation of RNA as interacting ligands offers an additional fitness benefit resultant from generally lower RNA thermal stability. As such, RNA ligands also serve as fundamental temperature sensors that signal stress through decreased conformational regulation of their protein partners as was observed in these interactome dynamics.
Multiomic analysis reveals developmental dynamics of the human heart in health and disease
Authors: Cranley James , Kanemaru Kazumasa , Bayraktar Semih , Knight-Schrijver Vincent , Pett Jan Patrick , Polanski Krzysztof , Dabrowska Monika , Mulas Ilaria , Richardson Laura , Semprich Claudia I. , Kapuge Rakeshlal , Perera Shani , He Xiaoling , Ho Siew Yen , Yayon Nadav , Tuck Liz , Roberts Kenny , Palmer Jack A. , Davaapil Hongorzul , Gambardella Laure , Patel Minal , Tyser Richard , Sinha Sanjay , Teichmann Sarah A.
Published: April 2024

Developmental dynamics encompass both the specification of cell types and their spatial organisation into multicellular niches. Here we harness the power of single-cell and spatial multiomics to unravel embryonic and foetal cardiac tissue niches, which lead to the development of a new tool, TissueTypist. We reveal that cardiac-resident macrophages likely originate from the yolk sac, forming heterogeneous subsets. CX3CR1+macrophages with a microglia-like profile localise in the sinoatrial node, which may contribute to axon guidance for the innervating autonomic neurons. Foetal pacemaker cells exhibit distinct characteristics compared to their adult counterparts, including the expression of genes that are known to promote parasympathetic innervation. We highlight the enhancer-mediated gene regulatory networks governing atrial and ventricular cardiomyocyte specification. The maturation of atrial cardiomyocytes into distinct left and right phenotypes, driven by transcription factors linked to atrial septal defect genes, underscores the significance of this process for healthy heart development. In the ventricle, cellular and transcriptional gradients along both pseudotime and the transmural axis provide a new molecular understanding of myocardial compaction. Finally, generating data from Trisomy 21 hearts and comparing this with the euploid atlas, we reveal a reduced abundance of specific cell types including compact cardiomyocytes. Overall, this extensive dataset and our precomputed models will form a valuable resource for the field.
The mechanoreceptor PIEZO1 is a novel oncogene in glioma by promoting astrocyte reactivity
Authors: Blanco-Carlon Pablo , Navarro Aguadero Miguel Ángel , Aguilar-Garrido Pedro , Otero-Sobrino Álvaro , Hernández-Sánchez María , Arroyo-Barea Andrés , Graña-Castro Osvaldo , Gargini Ricardo , García-Martín Rosa María , Hernández-Laín Aurelio , Pérez-Martínez Manuel , Gómez Alonso Jesús , Ortega Sagrario , Martínez-López Joaquín , Gallardo Miguel , Velasco-Estévez María
Published: April 2024

Glioblastoma is the most common and aggressive brain tumour in adults. Despite advances in its molecular characterization, there is a gap-of-knowledge in the identification ofbona fidedrivers and potential therapeutic targets that could change the clinical picture. Mechanoreception, the sensing of mechanical cues by cells, has proven to be an important factor in cell biology, particularly in cancer. Piezo1 is a mechanoreceptor found in all cells and seems to play a role in different cancer types, such as gastric, breast or lung cancer. However, there is still lack of understanding about its role in the onset and progression of glioblastoma. Here, we show that Piezo1 acts as an oncogene in glioma by potentially promoting chronic astrocyte reactivity. We developed a novel transgenic murine model of Piezo1 overexpression in astrocytes. These animals had a significant reduction in overall survival and developed glioma with a penetrance of 30%. We also developed a PIEZO1-overexpressing U251 cell line and found that it had a more aggressive and reactive-like phenotype. Finally, we correlated the levels of PIEZO1 with the clinical outcome of a cohort of glioblastoma patients and observed that PIEZO1 is a biomarker of worse prognosis. However, PIEZO1 only correlated with worse prognosis in male patients, suggesting a sexual dimorphism. In conclusion, we identified Piezo1 as abona fidedriver of glioma, revealing its implication in astrocyte reactivity and identifying it as a biomarker for glioma in the clinic.
Aerobic Adaptation and Metabolic Dynamics ofPropionibacterium freudenreichiiDSM 20271: Insights from Comparative Transcriptomics and Surfaceome Analysis
Authors: Loivamaa Iida , Sillanpää Annika , Deptula Paulina , Chamlagain Bhawani , Edelmann Minnamari , Auvinen Petri , Nyman Tuula A. , Savijoki Kirsi , Piironen Vieno , Varmanen Pekka
Published: April 2024

Propionibacterium freudenreichii(PFR) DSM 20271 is a bacterium known for its ability to thrive in diverse environments and to produce vitamin B12. Despite its anaerobic preference, recent studies have elucidated its ability to prosper in the presence of oxygen, prompting a deeper exploration of its physiology under aerobic conditions. Here, we investigated the response of DSM 20271 to aerobic growth by employing comparative transcriptomic and surfaceome analyses alongside metabolite profiling. Cultivation under controlled partial pressure of oxygen (pO2) conditions revealed significant increases in biomass formation and altered metabolite production, notably of B12 vitamin, pseudovitamin-B12, propionate and acetate, under aerobic conditions. Transcriptomic analysis identified differential expression of genes involved in lactate metabolism, TCA cycle, and electron transport chain, suggesting metabolic adjustments to aerobic environments. Moreover, surfaceome analysis unveiled growth environment-dependent changes in surface protein abundance, with implications for sensing and adaptation to atmospheric conditions. Supplementation experiments with key compounds highlighted the potential for enhancing aerobic growth, emphasizing the importance of iron and α-ketoglutarate availability. Furthermore, in liquid culture, FeSO4supplementation led to increased heme production and reduced vitamin B12 production, highlighting the impact of oxygen and iron availability on the metabolic pathways. These findings deepen our understanding ofPFR’s physiological responses to oxygen availability and offer insights for optimizing its growth in industrial applications.

Importance

The study of the response ofPropionibacterium freudenreichiito aerobic growth is crucial for understanding how this bacterium adapts to different environments and produces essential compounds like vitamin B12. By investigating its physiological changes under aerobic conditions, we can gain insights into its metabolic adjustments and potential for enhanced growth. These findings not only deepen our understanding ofP. freudenreichiiresponses to oxygen availability but also offer valuable information for optimizing its growth in industrial applications. This research sheds light on the adaptive mechanisms of this bacterium, providing a foundation for further exploration and potential applications in various fields.
Toward nanophotonic optical isolation via inverse design of energy transfer in nonreciprocal media
Authors: Cisowski Claire M. , Waller Madeline C. , Bennett Robert
Published: April 2024

In this paper we generalize the adjoint method of inverse design to nonreciprocal media. As a test case, we use three-dimensional topology optimization via the level-set method to optimize one-way energy transfer for pointlike source and observation points. To achieve this we introduce a suite of tools, chiefly what we term the “Faraday-adjoint” method which allows for efficient shape optimization in the presence of magneto-optical media. We carry out an optimization based on a very general equation that we derive for energy transfer in a nonreciprocal medium, and link finite-different time-domain numerics to analytics via a modified Born series generalized to a tensor permittivity. This paper represents a stepping stone towards practical nanophotonic optical isolation, often regarded as the “holy grail” of integrated photonics.

Published by the American Physical Society
2024
Benzo[a][1,4]benzothiazino[3,2-c]phenothiazine
Authors: Bader Mamoun M. , Pham Phuong-Truc T. , Abu Khodair Salma S. , Saleh Maysoon I.
Published: April 2024

The title compound, C22H12N2S2, crystallizes in space group P21/c with four molecules in the asymmetric unit. The heterocyclic molecule is quasi-planar with a dihedral angle between the phenyl rings on the periphery of the molecule of 1.73 (19)°. Short H...S (2.92 Å) and C—H...π [2.836 (3) Å] contacts are observed in the crystal with shorted π–π stacking distances of 3.438 (3) Å along the b axis. Surprisingly, and unlike a closely related material, this molecule readily forms large crystals by sublimation and by slow evaporation from dichloromethane. The maximum absorbance in the UV-Vis spectrum is at 533 nm. Emission was measured upon excitation at 533 nm with a fluorescence λmax of 658 nm and cutoff of 900 nm.
Toward a sustainable research agenda on food eco-labelling in the business and management research domain
Authors: Geldres-Weiss Valeska V. , Nicolas Carolina , Massa Nathaniel P.
Published: April 2024

Purpose

This study aims to critically review the research on food eco-labels to identify research gaps and recommend future research directions in business and management.

Design/methodology/approach

A hybrid integrated review combines bibliometric analysis with an in-depth framework-based study of theory–context–characteristics–methodology (TCCM) and reviews quality research published over 21 years between 2002 and 2022.

Findings

We identify key research themes and the knowledge structure of food eco-label research. Future researchers should explore food eco-label dynamics and phenomena in areas related to consumer behaviour, information, consumer knowledge, environmental concerns, trust, packaging and willingness-to-pay as antecedent factors.

Research limitations/implications

This review contributes to the business and management literature by quantifying existing research and consolidating its evolution. The articles were sourced from the established Web of Science (WoS) database. Other databases should be included in future reviews. We also focus on research published in business and management. Further studies could include research beyond such specialised domains.

Practical implications

Consumers need more information on the objectives and meaning of food eco-labels. The dissemination of knowledge on eco-labels, as well as effective communication and information on eco-labels, are relevant to future research issues.

Social implications

The knowledge derived from this research holds significant potential in shaping policies and devising tools aimed at reducing the carbon footprint linked to food production and consumption. Considering the substantial impact of these activities on our planet’s carbon footprint, addressing food security and sustainability emerges as a crucial concern for humanity. Recognising the importance of eco-label communication and information becomes particularly pertinent for future generations, who stand to bear the most substantial impact of climate change and sustainable development. These generations are also more inclined toward embracing and implementing sustainable practices.

Originality/value

There are no comprehensive, integrated reviews exploring the methods, variables and constructs used in studies on food eco-labels based on all articles published in WoS journals in the business and management domains. This is the first comprehensive literature review using a hybrid approach (bibliometric review with TCCM framework) in the field of food eco-label research.
Madrasah management strategies through Madrasah Reform program: an evidence from Indonesia
Authors: Haddade Hasyim , Nur Askar , Achruh Andi , Rasyid Muhammad Nur Akbar , Ibrahim Andi
Published: April 2024

Purpose

Improving the quality of madrasah in the digital era is a must. This can be committed by strengthening aspects of madrasah governance through implementing management strategies that refer more to the integration of technology and Islamic education. This research focuses on madrasah management strategies through the Madrasah Reform program.

Design/methodology/approach

This research uses a case study research design that focuses attention on strategic aspects of developing madrasah through the Madrasah Reform program. The informants in this study were 18 people consisting of three madrasah heads from Madrasah Ibtidaiyah (MI), Madrasah Tsanawiyah (MTs) and Madrasah Aliyah (MA), five teachers and 10 students. Data collection in this study used in-depth and semi-structured interviews with madrasah heads and teachers regarding the implementation of the Madrasah Reform program and also regarding madrasah management strategies at three levels of education.

Findings

This study shows that the strategy of managing madrasahs through the Madrasah Reform program in three madrasahs in Indonesia has had a positive impact on improving the quality of madrasahs, although there are still aspects that require development.

Research limitations/implications

This research implies that the quality of madrasah in the digital era is determined by management strategies based on the use of educational technology.

Practical implications

This program has implications for the development of the quality of human resources in educational institutions, especially in relation to digital literacy among students and teaching staff. The use of digital technology, which is one of the main projections of the Madrasah Reform program, is continuously able to change the face of education in a more modern direction, both in terms of governance and the learning process, so that the output of this program, especially what occurs at Madrasah Madani, is significant development in the aspects of digital literacy and technology. Which is the main criterion in facing a digital-based educational context.

Social implications

For a policy aspect, the success of the Madrasah Reform program at Madrasah Madani can be used as a blueprint or model for implementing this program in Islamic educational institutions, specifically Madrasas in South Sulawesi and in general at Madrasas throughout Indonesia.

Originality/value

This proves that Madrasah Reform program is a program that can be implemented in madrasahs to improve the quality of madrasah management in the digital era while continuing to carry out simultaneous improvements and evaluations of the program.
Reconceptualizing time and space: employee voices from the nonvoluntary work from home context
Authors: Vohra Veena , Anand Anjni
Published: April 2024

Purpose

This paper aims to explore how employees reconceptualized their time and space to order and structure their lives in an unprecedented scenario of nonvoluntary work from home.

Design/methodology/approach

Set in the context of lockdowns due to the pandemic scenario, the study uses a constructivist approach to collect data through in-depth online interviews to understand how employees coped with the challenges emanating in a nonvoluntary work from home situation. The respondents were purposively selected to reflect a diverse pool in terms of gender, familial responsibilities and age/tenure.

Findings

The findings present temporal and spatial themes that provide several insights into how employees made sense of time and space as resources to navigate their challenging work-home roles.

Research limitations/implications

In the present study, the authors found that when boundaries get violated, it does not necessarily manifest in the form of dissatisfaction with one or the other domain. The respondents in the current study show-cased adjustment mechanism to cope with the boundary permeability that happened. They adopted ways in which they could safe-guard their multiple identities in the situation they found themselves in, do justice to the salient roles in their lives, emerge as more empathetic humans and look forward to a brighter and more hopeful future. This opens-up a possibility of studying the theory behind human behavior in crisis-like situations and the degree of acceptance that people show when they find themselves in undesirable-unalterable situations.

Practical implications

A mental reorientation is required on the part of both employees and employers to navigate smoothly in this new “normal” and find more sustainable solutions to the problem if the remote working or hybrid mode of working becomes mainstay. Clear demarcations between work and nonwork time are a key element to ensure proper work schedules for remote workers. Offline meetings and get-togethers can be organized on a periodic basis to facilitate employee interaction and engagement. Participation of employees in key decisions becomes more important in such situations as it makes employees feel more connected with their work space.

Originality/value

To the best of the authors’ knowledge, the study is original as it is set in a completely unprecedented situation of lockdowns (during the pandemic) that affected the lives of everyone in some way or the other. The findings of the study are unique and insightful, as they help understand the sense-making mechanism adopted by people to successfully navigate through the crisis.
Study of factors affecting customer patronage: engagement model of health insurance
Authors: Bhattacharyya Atanu , Rana Avinash , Imran Khan Mohd
Published: April 2024

Purpose

Improving health outcomes requires a robust health-care service model that delivers cost-efficient services and increase customer patronage. The purpose of this study is to examine how service quality and convenience influence perceived value, satisfaction and customer patronage of health insurance policyholders. Based on contemporary research, this study further investigates the moderating role of trust, inertia, insurer type and word-of-mouth (WOM) on relationship between satisfaction and customer patronage.

Design/methodology/approach

This study conceptualized the dimensions of SERVQUAL and SERVCON as drivers of perceived value leading to satisfaction and finally customer patronage in presence of four moderators. To test the hypotheses, data from 500 consumers who had a running health insurance policy was collected and analyzed using partial least square path modeling.

Findings

The results of this study showed service quality and convenience dimensions significantly affected perceived value. Perceived value strongly influenced satisfaction and customer patronage intentions. Satisfaction had a significant positive effect on patronage. WOM and trust moderated the satisfaction–patronage relationship for recommendation intention but not repurchase intention. The moderators had an indirect bearing on customer patronage.

Social implications

Such an engagement ecosystem can be considered to be a revolution, as it will change the way businesses are conducted and how stakeholders interact with one another.

Originality/value

This study adapts and integrates the SERVQUAL and SERVCON models to health insurance domain. Second, this study conceptualizes a modified view of post-benefit convenience relevant for health insurance as policy renewal intention rather than returns/exchanges. This addresses a gap in the SERVCON scale's applicability to insurance services. This study also makes a novel attempt of examining implication of WOM and trust in health insurance domain.