bluuebunny/crossref_metadata_2025 huggingface dataset:
THE OLFACTORY RECEPTOR Olfr78 REGULATES DIFFERENTIATION OF ENTEROCHROMAFFIN CELLS IN THE MOUSE COLON
Authors: Dinsart Gilles , Leprovots Morgane , Lefort Anne , Libert Frédérick , Quesnel Yannick , Veithen Alex , Vassart Gilbert , Huysseune Sandra , Parmentier Marc , Garcia Marie-Isabelle
Published: April 2023

The gastrointestinal epithelium constitutes a chemosensory system for microbiota-derived metabolites such as Short Chain Fatty Acids (SCFA). In this study, we investigated spatial distribution of Olfr78, one of the SCFA receptors, in the mouse intestine and studied the transcriptome of colon enteroendocrine cells expressing Olfr78. The receptor is principally detected in the enterochromaffin and L subtypes in the proximal and distal colon, respectively. Using the Olfr78-GFP and VilCre/Olfr78flox transgenic mouse lines, we reveal that loss of epithelial Olfr78 results in impaired enterochromaffin cell differentiation, blocking cells in an undefined secretory lineage state. This is accompanied by dysbiosis, characterized by an increasedFirmicutes/Bacteroidetes ratio, as well as a less efficient antioxidant system in colon crypts. Using organoid cultures, we further show that maintenance of enterochromaffin cells involves activation of the Olfr78 receptor via the SCFA ligand acetate. Altogether, this work provides evidence that Olfr78 contributes to colon homeostasis by regulating enterochromaffin cell differentiation.
A Multi-omic Analysis of the Human Lung Reveals Distinct Cell Specific Aging and Senescence Molecular Programs
Authors: De Man Ruben , McDonough John E , Adams Taylor S , Manning Edward P , Myers Greg , Vos Robin , Ceulemans Laurens , Dupont Lieven , Vanaudenaerde Bart M , Wuyts Wim A , Rosas Ivan O , Hagood James S. , Ambalavanan Namasivayam , Niklason Laura , Hansen Kirk C , Yan Xiting , Kaminski Naftali
Published: April 2023

Age is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) data. Our analysis revealed age-associated gene networks that reflected hallmarks of aging, including mitochondrial dysfunction, inflammation, and cellular senescence. Cell type deconvolution revealed age-associated changes in the cellular composition of the lung: decreased alveolar epithelial cells and increased fibroblasts and endothelial cells. In the alveolar microenvironment, aging is characterized by decreased AT2B cells and reduced surfactant production, a finding that was validated by scRNAseq and IHC. We showed that a previously reported senescence signature, SenMayo, captures cells expressing canonical senescence markers. SenMayo signature also identified cell-type specific senescence-associated co-expression modules that have distinct molecular functions, including ECM regulation, cell signaling, and damage response pathways. Analysis of somatic mutations showed that burden was highest in lymphocytes and endothelial cells and was associated with high expression of senescence signature. Finally, aging and senescence gene expression modules were associated with differentially methylated regions, with inflammatory markers such asIL1B, IL6R, andTNFbeing significantly regulated with age. Our findings provide new insights into the mechanisms underlying lung aging and may have implications for the development of interventions to prevent or treat age-related lung diseases.
D-Serine agonism of GluN1-GluN3 NMDA receptors regulates the activity of enteric neurons and coordinates gut motility
Authors: Osorio Nancy , Martineau Magalie , Fortea Marina , Rouget Céline , Penalba Virginie , Lee Cindy J. , Boesmans Werend , Rolli-Derkinderen Malvyne , Patel Amit V. , Mondielli Grégoire , Conrod Sandrine , Labat-Gest Vivien , Papin Amandine , Sasabe Jumpei , Sweedler Jonathan V. , Berghe Pieter Vanden , Delmas Patrick , Mothet Jean-Pierre
Published: April 2023

The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive. Here, by using an array of immunohistochemistry, molecular profiling and functional assays, we uncover a new role for D-serine (D-Ser) and non-conventional GluN1-GluN3 N-methyl D-aspartate receptors (NMDARs) in regulating ENS functions. We demonstrate that D-Ser is produced by serine racemase (SR) expressed in enteric neurons. By using bothin situpatch clamp recording and calcium imaging, we show that D-Ser alone acts as an excitatory neurotransmitter in the ENS independently of the conventional GluN1-GluN2 NMDARs. Instead, D-Ser directly gates the non-conventional GluN1-GluN3 NMDARs in enteric neurons from both mouse and guinea-pig. Pharmacological inhibition or potentiation of GluN1-GluN3 NMDARs had opposite effects on mouse colonic motor activities, while genetically driven loss of SR impairs gut transit and fluid content of pellet output. Our results demonstrate the existence of native GluN1-GluN3 NMDARs in enteric neurons and open new perspectives on the exploration of excitatory D-Ser receptors in gut function and diseases.
Leveraging a new data resource to define the response ofC. neoformansto environmental signals
Authors: Kang Yu Sung , Jung Jeffery , Brown Holly , Mateusiak Chase , Doering Tamara L. , Brent Michael R.
Published: April 2023

Cryptococcus neoformansis an opportunistic fungal pathogen with a polysaccharide capsule that becomes greatly enlarged in the mammalian host and duringin vitrogrowth under host-like conditions. To understand how individual environmental signals affect capsule size and gene expression, we grew cells in all combinations of five signals implicated in capsule size and systematically measured cell and capsule sizes. We also sampled these cultures over time and performed RNA-Seq in quadruplicate, yielding 881 RNA-Seq samples. Analysis of the resulting data sets showed that capsule induction in tissue culture medium, typically used to represent host-like conditions, requires the presence of either CO2or exogenous cyclic AMP (cAMP). Surprisingly, adding either of these pushes overall gene expression in the opposite direction from tissue culture media alone, even though both are required for capsule development. Another unexpected finding was that rich medium blocks capsule growth completely. Statistical analysis further revealed many genes whose expression is associated with capsule thickness; deletion of one of these significantly reduced capsule size. Beyond illuminating capsule induction, our massive, uniformly collected dataset will be a significant resource for the research community.

IMPORTANCE

Cryptococcus neoformansis an opportunistic yeast that kills ∼150,000 people each year. This major impact on human health makes it imperative to understand the basic biology ofC. neoformansand the factors that mediate its virulence. One key virulence factor is a polysaccharide capsule that expands greatly during infection. To help define capsule synthesis and fungal biology, we provided cells with many different combinations of host-like signals and sampled the cultures over time for transcriptional analysis. The resulting time resolved data set is by far the largest gene expression resource ever produced forC. neoformans(881 RNA-seq samples), further enriched by accompanying capsule images and measurements. It revealed surprising findings, including that rich medium suppresses capsule size regardless of other signals. This landmark data resource will be enormously valuable to the research community as it continues to define the relationships between environmental signals and cryptococcal gene expression, biology, and virulence.
Auditory hemispheric asymmetry as a specialization for actions and objects
Authors: Robert Paul , Zatorre Robert , Gupta Akanksha , Sein Julien , Anton Jean-Luc , Belin Pascal , Thoret Etienne , Morillon Benjamin
Published: April 2023

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on two complementary and perceptually relevant acoustic invariants — actions and objects — that are processed asymmetrically and sufficient to model and categorize any sound. We observed that environmental sounds are an independent combination of purely temporal and spectral acoustic modulations. Behaviorally, discrimination of actions relied on temporal modulations, while discrimination of objects relied on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are respectively decoded in the left and right hemispheres, in bilateral superior temporal and left inferior frontal regions. This asymmetry reffects a generic differential processing — through differential neural sensitivity to temporal and spectral modulations present in all environmental sounds — that supports the efficient categorization of actions and objects. These results provide an ecologically valid framework of the functional role of auditory brain asymmetry.
Investigation of the usefulness of liver-specific deconvolution method toward legacy data utilization
Authors: Azuma Iori , Mizuno Tadahaya , Morita Katsuhisa , Suzuki Yutaka , Kusuhara Hiroyuki
Published: April 2023

Background

Immune responses in the liver are related to the development and progression of liver failure, and precise prediction of their behavior is important. Deconvolution is a methodology for estimating the immune cell proportions from the transcriptome, and it is mainly applied to blood-derived samples and tumor tissues. However, the influence of tissue-specific modeling on the estimation results has rarely been investigated. In this study, we constructed a system to evaluate the performance of the deconvolution method on liver transcriptome data.

Results

We prepared seven mouse liver injury models using small-molecule compounds with known hepatotoxicity and established a dataset with corresponding liver bulk RNA-Seq and immune cell proportions, covering various immune responses. RNA-Seq expression for nine leukocyte subsets and four liver-associated cell types were obtained from the Gene Expression Omnibus (GEO) to provide a reference covering liver component cells. Here, we found that the combination of reference cell sets affects the estimation results of reference-based deconvolution methods. We established a liver tissue-specific deconvolution by optimizing the reference cell set for each cell to be estimated. We applied this model to independent datasets and showed that liver-specific modeling focusing on reference cell sets is highly extrapolatable.

Conclusions

We provide an approach of liver-specific modeling when applying reference-based deconvolution to bulk RNA-Seq data and show its importance. It is expected to enable sophisticated estimation from rich tissue data accumulated in public databases and to obtain information on aggregated immune cell trafficking.
Assessing drug safety by identifying the axis of arrhythmia in cardiomyocyte electrophysiology
Authors: Heitmann Stewart , Vandenberg Jamie I , Hill Adam P
Published: April 2023

Many classes of drugs can induce fatal cardiac arrhythmias by disrupting the electrophysiology of cardiomyocytes. Safety guidelines thus require all new drugs to be assessed for pro-arrhythmic risk prior to conducting human trials. The standard safety protocols primarily focus on drug blockade of the delayed-rectifier potassium current (IKr). Yet the risk is better assessed using four key ion currents (IKr, ICaL, INaL, IKs). We simulated 100,000 phenotypically diverse cardiomyocytes to identify the underlying relationship between the blockade of those currents and the emergence of ectopic beats in the action potential. We call that relationship the axis of arrhythmia. It serves as a yardstick for quantifying the arrhythmogenic risk of any drug from its profile of multi-channel block alone. We tested it on 109 drugs and found that it predicted the clinical risk labels with an accuracy of 88.1% to 90.8%. Pharmacologists can use our method to assess the safety of novel drugs without resorting to animal testing or unwieldy computer simulations.

Significance Statement

Many classes of drugs interfere with the electrical signaling of the heart, leading to arrhythmias and cardiac arrest. Newly developed drugs must therefore undergo mandatory safety testing in animals prior to human trials. Computational models of cardiac electrophysiology offer an ethical alternative, but the current methods are difficult to apply beyond specialist computing laboratories. This study uses such models to identify the underlying relationship between drugs and cardiac arrhythmias. Those findings are then translated into a compact metric that can be applied using simple pen and paper calculations. The new metric allows pharmacology laboratories to assess the safety of novel drugs without using animals or unwieldy computer simulations.
Does ipsilateral remapping following hand loss impact motor control of the intact hand?
Authors: Tucciarelli Raffaele , Ejaz Naveed , Wesselink Daan B. , Kolli Vijay , Hodgetts Carl J. , Diedrichsen Jörn , Makin Tamar
Published: April 2023

What happens once a cortical territory becomes functionally redundant? We addressed brain and behavioural adaptations for the intact hand in individuals with a missing hand. Previous studies reported increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping) in acquired amputees, but not in individuals with a congenitally missing hand (one-handers). It is unclear whether remapping in amputees involves recruiting more neural resources to support the intact hand, and whether such activity is increased in tasks that demand greater motor control. We investigated sensorimotor learning and neural representation of the intact hand in one-handers and amputees using a multi-finger configuration task, as well as univariate and multivariate fMRI. We found that ipsilateral activity increased with motor demand - but only in the amputees group. However, these changes did not reflect behavioural differences. The representation of the finger configurations, as revealed by multivariate analysis, was stronger in amputees and closer to the typical representation found in controls’ contralateral hand territory, compared to one-handers. This collaborative contra-ipsilateral activity may reflect the intact hand’s efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Together with a supplementary structural white matter analysis, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life.

Significant Statement

We studied whether brain resources in the missing-hand territory support demanding intact hand motor control in people who were born with one hand or lost a hand later in life. We found that amputees had increased activity in the brain area used for the missing hand, but no improvement in the performance of their intact hand. This collaborative contra-ipsilateral activity may reflect the intact hand’s efference copy. One-handers showed slight deficits while learning to perform complex motor movements, but no brain activity differences in the missing hand territory, compared to controls. Our results suggest that brain plasticity is limited and may depend on early life experiences.
Compensation or preservation? Different roles of functional lateralization in speech perception in older non-musicians and musicians
Authors: Jin Xinhu , Zhang Lei , Wu Guowei , Wang Xiuyi , Du Yi
Published: April 2023

Musical training can offset age-related decline of speech perception in noisy environments. However, whether functional compensation or functional preservation the older musicians adopt to counteract the adverse effects of aging is unclear yet, so do older non-musicians. Here, we employed the fundamental brain organization feature named functional lateralization, and calculated network-based lateralization indices (LIs) of resting-state functional connectivity (FC) in 23 older musicians (OM), 23 older non-musicians (ONM), and 24 young non-musicians (YNM). OM outperformed ONM and almost equalized YNM in speech-in-noise/speech tasks. In parallel, ONM exhibited reduced lateralization than YNM in LI of intrahemispheric FC (LI_intra) in cingulo-opercular network (CON) and interhemispheric heterotopic FC (LI_he) in language network (LAN). Moreover, OM showed higher neural alignment to YNM (i.e., similar lateralization pattern) than ONM in LI_intra in CON, LAN, frontoparietal network (FPN) and default mode network (DMN) and LI_he in DMN. These findings suggest that musical training contributes to the preservation of youth-like lateralization in older adults. Furthermore, stronger left-lateralized and lower alignment-to-young of LI_intra in somatomotor network (SMN) and dorsal attention network (DAN) and LI_he in DMN correlated with better speech performance in ONM. In contrast, stronger right-lateralized LI_intra in FPN and DAN and higher alignment-to-young of LI_he in LAN correlated with better performance in OM. Thus, functional preservation and compensation of lateralization may play different roles in speech perception in noise for the elderly with and without musical expertise, respectively. Our findings provide insight into successful aging theories from the unique perspective of functional lateralization and speech perception.

Significance statement

As a positive lifestyle which contributes to neural resource enrichment, musical training experience may mitigate age-related decline in speech perception in noise through both functional compensation and preservation. What is unknown is whether older musicians rely more on one of these mechanisms, and how is it different from older non-musicians. From a unique perspective of functional lateralization, we found that high-performing older musicians showed stronger preservation of youth-like lateralization with a more right-lateralized pattern whereas high-performing older non-musicians were associated with stronger scaffolding of compensatory networks with a more left-lateralized pattern. Our findings suggest that older musicians and non-musicians exhibit different coping strategies in terms of functional lateralization against aging, which would largely enrich aging theories and inspire training intervention.
Antivirals against monkeypox infections
Authors: Chiem Kevin , Nogales Aitor , Lorenzo Maria , Vasquez Desarey Morales , Xiang Yan , Gupta Yogesh K. , Blasco Rafael , de la Torre Juan Carlos , Martínez-Sobrido Luis
Published: April 2023

Monkeypox virus (MPXV) infection in humans are historically restricted to endemic regions in Africa. However, in 2022, an alarming number of MPXV cases have been reported globally with evidence of person-to-person transmission. Because of this, the World Health Organization (WHO) declared the MPXV outbreak a public health emergency of international concern. MPXV vaccines are limited and only two antivirals, tecovirimat and brincidofovir, approved by the United States (US) Food and Drug Administration (FDA) for the treatment of smallpox, are currently available for the treatment of MPXV infection. Here, we evaluated 19 compounds previously shown to inhibit different RNA viruses for their ability to inhibit Orthopoxvirus infections. We first used recombinant vaccinia virus (rVACV) expressing fluorescence (Scarlet or GFP) and luciferase (Nluc) reporter genes to identify compounds with anti-Orthopoxvirus activity. Seven compounds from the ReFRAME library (antimycin A, mycophenolic acid, AVN- 944, pyrazofurin, mycophenolate mofetil, azaribine, and brequinar) and six compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) showed antiviral activity against rVACV. Notably, the anti-VACV activity of some of the compounds in the ReFRAME library (antimycin A, mycophenolic acid, AVN- 944, mycophenolate mofetil, and brequinar) and all the compounds from the NPC library (buparvaquone, valinomycin, narasin, monensin, rotenone, and mubritinib) were confirmed with MPXV, demonstrating the broad-spectrum antiviral activity against Orthopoxviruses and their potential to be used for the antiviral treatment of MPXV, or other Orthopoxvirus, infections.

IMPORTANCE

Despite the eradication of smallpox, some Orthopoxviruses remain important human pathogens, as exemplified by the recent 2022 monkeypox virus (MPXV) outbreak. Although smallpox vaccines are effective against MPXV, there is presently limited access to those vaccines. In addition, current antiviral treatment against MPXV infections is limited to the use of the FDA-approved drugs tecovirimat and brincidofovir. Thus, there is an urgent need to identify novel antivirals for the treatment of MPXV, and other potentially zoonotic Orthopoxvirus infections. Here, we show that thirteen compounds, derived from two different libraries, previously found to inhibit several RNA viruses, exhibit also antiviral activity against VACV. Notably, eleven compounds also displayed antiviral activity against MPXV, demonstrating their potential to be incorporated into the therapeutic armamentarium to combat Orthopoxvirus infections.
Fetal manipulation of maternal metabolism is a critical function ofIgf2imprinting
Authors: Lopez-Tello Jorge , Yong Hannah E. J. , Sandovici Ionel , Christoforou Efthimia , Salazar-Petres Esteban , Boyland Rebecca , Napso Tina , Constancia Miguel , Sferruzzi-Perri Amanda N.
Published: April 2023

Maternal-offspring interactions in mammals are mainly characterised by cooperation, but also conflict. Over evolutionary time, the fetus has evolved to manipulate the mother’s physiology to increase nutrient transfer through the placenta, but these mechanisms are poorly characterized. The imprintedIgf2(insulin-like growth factor 2) gene is highly expressed in mouse placental cells with endocrine functions. Here, we show that in the mouse, deletion ofIgf2in these cells leads to impaired placental endocrine signalling to the mother, but remarkably does not result in changes in placental morphology, growth or size. Mechanistically, we find thatIgf2via defective production of hormones, including prolactins, is essential for the establishment of the insulin-resistance state during pregnancy, and the appropriate partitioning of nutrients to the developing fetus. Consequently, fetuses are growth restricted and hypoglycemic, due to impaired placental glucose transfer from the mother to the fetus. Furthermore,Igf2loss from placental endocrine cells has long-lasting effects on offspring adiposity and glucose homeostasis in adult life. Our study provides long-sought compelling experimental evidence for an intrinsic fetal manipulation system, which operates in the placenta to modify maternal metabolism and resource allocation to the fetus, with consequences for offspring metabolic health in later life.
Imaging-based screening identifies modulators of theeIF3translation initiation factor complex inCandida albicans
Authors: Metzner Katura , O’Meara Matthew J , Halligan Benjamin , Wotring Jesse W. , Sexton Jonathan Z , O’Meara Teresa R
Published: April 2023

Fungal pathogens likeCandida albicanscan cause devastating human disease. Treatment of candidemia is complicated by the high rate of resistance to common antifungal therapies. Additionally, there is host toxicity associated with many antifungal compounds due to the conservation between essential mammalian and fungal proteins. An attractive new approach for antimicrobial development is to target virulence factors: non-essential processes that are required for the organism to cause disease in human hosts. This approach expands the potential target space while reducing the selective pressure towards resistance, as these targets are not essential for viability. InC. albicans,a key virulence factor is the ability to transition to hyphal morphology. We developed a high-throughput image analysis pipeline to distinguish between yeast and filamentous growth inC. albicansat the single cell level. Based on this phenotypic assay, we screened the FDA drug repurposing library of 2,017 compounds for their ability to inhibit filamentation and identified 33 compounds that block the hyphal transition inC. albicanswith IC50values ranging from 0.2 to 150 µM. Multiple compounds showed a phenyl vinyl sulfone chemotype, prompting further analysis. Of these phenyl vinyl sulfones, NSC 697923 displayed the most efficacy, and by selecting for resistant mutants, we identifiedeIF3as the target of NSC 697923 inC. albicans.
Resin acids play key roles in shaping microbial communities during degradation of spruce bark
Authors: Ristinmaa Amanda Sörensen , Rangel Albert Tafur , Idström Alexander , Valenzuela Sebastian , Kerkhoven Eduard J. , Pope Phillip B. , Hasani Merima , Larsbrink Johan
Published: April 2023

The bark is the outermost defense of trees against microbial attack, largely thanks to toxicity and prevalence of extractive compounds. Nevertheless, bark decomposes in nature, though by which species and mechanisms remains unknown. Here, we have followed the development of microbial enrichments growing on spruce bark over six months, by monitoring both chemical changes in the material and performing community and metagenomic analyses. Carbohydrate metabolism was unexpectedly limited, and instead a key activity was metabolism of extractives. Resin acid degradation was principally linked to community diversification with specific bacteria revealed to dominate the process. Metagenome-guided isolation facilitated the recovery of the dominant enrichment strain in pure culture, which represents a new species (Pseudomonas abieticivoranssp. nov.), that can grow on resin acids as a sole carbon source. Our results illuminate key stages in degradation of an abundant renewable resource, and how defensive extractive compounds have major roles in shaping microbiomes.
Uncovering the heterogeneity of pancreatic endothelial cells using integrative and comparative single cell gene expression analysis
Authors: Khan Safwat T. , Ahuja Neha , Taib Sonia , Vohra Shabana , Cleaver Ondine , Nunes Sara S
Published: April 2023

The pancreatic islet vasculature displays tissue-specific physiological and functional adaptations that support rapid glucose sensing and insulin response by β-cells. To uncover the transcriptomic basis of this specialization, we performed a meta-analysis of multi-organ single cell RNA sequencing atlases employing a unique strategy to avoid transcriptomic contamination. We identified biologically relevant genes involved in sphingosine-1-phosphate-mediated insulin-secretion (PLPP1, RDX, CDC42EP1), islet basement membrane formation (SPARC, COL15A1), endothelial cell (EC) permeability (PLVAP, EHD4), membrane transporters (CD320, SLCO2A1)and developmental transcription factors (NKX2-3, AHR). These were validatedin silicoin independent datasets. We further established the first integrated transcriptomic atlas of human pancreatic ECs and described two unique capillary subpopulations: exocrine and endocrine pancreas ECs. We validated the spatial localization of key markers using RNAscope™ and immunofluorescence staining on mouse pancreatic tissue cross-sections. Our findings provide novel insights into pancreatic EC heterogeneity and islet EC function with potential implications in therapeutic strategies.
Melatonin alleviates LPS-induced abnormal pregnancy through MTNR1B regulation of m6A
Authors: Zhao Shisu , Dong Yanjun , Li Yuanyuan , Wang Zixu , Chen Yaoxing , Dong Yulan
Published: April 2023

Pregnancy is a very complex and delicate process, inflammation in early pregnancy may result in pregnancy loss or defective implantation. Melatonin, mainly produced from the pineal body, which exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent modification of eukaryotic mRNA. The aim of this study was to investigate the association between melatonin and m6A during pregnancy and elaborate the underlying protective mechanism of melatonin during pregnancy. In vitro, melatonin was found to alleviated LPS-induced reductions in the number of implantation sites. Besides, melatonin was found to alleviate the activation of inflammation, autophagy and apoptosis pathways. In vitro studies demonstrated that melatonin regulated several downstream pathways in an m6A-dependent manner via melatonin receptor MTNR1B. Our findings revealed the important roles of m6A in the establishment of pregnancy and discovered a new mechanism of how melatonin protects pregnancy.
Conserved enhancer logic controls the notochord expression of vertebrateBrachyury
Authors: Kemmler Cassie L. , Smolikova Jana , Moran Hannah R. , Mannion Brandon J. , Knapp Dunja , Lim Fabian , Czarkwiani Anna , Aguayo Viviana Hermosilla , Rapp Vincent , Fitch Olivia E. , Bötschi Seraina , Selleri Licia , Farley Emma , Braasch Ingo , Yun Maximina , Visel Axel , Osterwalder Marco , Mosimann Christian , Kozmik Zbynek , Burger Alexa
Published: April 2023

The cell type-specific expression of key transcription factors is central to development. Brachyury/T/TBXT is a major transcription factor for gastrulation, tailbud patterning, and notochord formation; however, how its expression is controlled in the mammalian notochord has remained elusive. Here, we identify the complement of notochord-specific enhancers in the mammalianBrachyury/T/TBXTgene. Using transgenic assays in zebrafish, axolotl, and mouse, we discover threeBrachyury-controlling notochord enhancersT3, C, andIin human, mouse, and marsupial genomes. Acting as Brachyury-responsive, auto-regulatory shadow enhancers, deletion of all three enhancers in mouse abolishes Brachyury/T expression selectively in the notochord, causing specific trunk and neural tube defects without gastrulation or tailbud defects. Sequence and functional conservation ofBrachyury-driving notochord enhancers with thebrachyury/tbxtbloci from diverse lineages of fishes dates their origin to the last common ancestor of jawed vertebrates. Our data define the enhancers forBrachyury/T/TBXTBnotochord expression as ancient mechanism in axis development.
2-(3-Methyl-2-oxoquinoxalin-1-yl)-N-(4-methylphenyl)acetamide
Authors: Missioui Mohcine , Alsubari Abdulsalam , Mague Joel T. , Essassi El Mokhtar , Ramli Youssef
Published: April 2023

The quinoxaline moiety in the title molecule, C18H17N3O2, is not quite planar and the p-tolyl group is rotationally disordered over two nearly equally populated sets of sites. In the crystal, N—H...O and C—H...O hydrogen bonds form chains extending along the b-axis direction. Due to the disorder of the p-tolyl rings, short C...C distances are observed between adjacent chains.
Escaping transparent, asymmetrical and agentive accountability? Entrepreneurial accounts and researchers' countertransference
Authors: Besson Madeleine , Jacquinot Philippe , Jardat Rémi , Moriceau Jean-Luc
Published: April 2023

Purpose

This article of exploratory research provides a critical perspective on accountability, focusing on three characteristics: transparency, asymmetry and individual agency. An experimental method is developed, calling for an ethics of accountability.

Design/methodology/approach

Four entrepreneurs have given accounts of themselves and their projects in life cycle interviews. This article applies Devereux's approach (1967), which allows for opacity (the “unconscious”) to oneself and to others with symmetry between analysts and analysed, and a lack of demarcation between the observer and the observed.

Findings

A tragic entrepreneurial accountability trap of continuous self-justification was discovered, which pertains both to the entrepreneurs and the researchers. Nonetheless, the researchers as inspired by Devereux's method were able to realize a form of accounterability.

Social implications

This article shows that the demands for transparent, asymmetrical and agentive accountability call for ethical reflection. The request for accounts, as resulting in the accounts given and the research conducted into accountability, are all sources of constraints. Differing the accountability situation may lessen the constraints.

Originality/value

This study introduces Devereux's method as an investigative tool in accountability research, opening up new perspectives on communication and analysis. This article shows the researcher as situated both inside and outside of the accountability mechanisms. This article explores a singular form of accountability; that of entrepreneurs who seemingly only account for the future, thereby disconnecting them from others.
The well-being of female administrative staff in managerial positions in Polish Higher Education Institutions
Authors: Górak-Sosnowska Katarzyna , Piwowar-Sulej Katarzyna
Published: April 2023

Purpose

The aim of the paper is to theoretically and empirically explore the issue of well-being (WB) of female administrative employees who work on managerial positions at higher education institutions (HEIs).

Design/methodology/approach

This study is based on both literature studies and explorative empirical research conducted in Poland with the use of snowball sampling. It adopted a questionnaire authored by Parker and Hyett and covered 121 respondents.

Findings

Literature studies show that invisibility of work, low level of empowerment, increased stress, workload and expectations, reduced resources, high level of anxiety, fatigue and low level of vitality negatively impact the WB of HEIs’ administrative staff. The presented research provides insight into the internal structure of the administrative staff’s WB. Both the main construct (i.e. employees’ WB) and its subconstructs are on moderate level. Respondents’ age and tasks performed are correlated only with the subconstruct of WB in the form of intrusion of work into private life.

Research limitations/implications

Although the research is not based on large sample, it provides both practical and theoretical implications.

Originality/value

Most of studies discuss the issue of WB of scholars. The paper fills the research gap in terms of examining female administrative employees who work on managerial positions at HEIs.
Digital transformation and strategic agility during the COVID-19 crisis: the role of the intangible capital conversion
Authors: Bounfour Ahmed , Housel Thomas , Silkey Trent , Nonnis Alberto
Published: April 2023

Purpose

The purpose of the current study is to illustrate the importance of strategic agility (SA), the capacity to respond agilely to a rapidly changing environment, for digitally transforming firms during the COVID-19 crisis. A secondary purpose of the study is to conceptually frame SA as a function of the creative to realized intangible capital (IC) ratio.

Design/methodology/approach

To inferentially corroborate the hypothesis, this study exploits the results of a recent firm-level survey, conducted under the H2020 project GlobalInto (2021). Via OLS and ordered logistic regressions, the relationship among SA, economic performance and IC was tested.

Findings

The exploratory findings implied that the more strategically agile companies were those that responded more effectively to the pandemic crisis, but only if they were ahead in terms of digital transformation. Moreover, the results implied that firms that were able to efficiently convert their creative IC into realized IC were the most strategically agile.

Originality/value

This study developed a new conceptual framework for digitally transforming firms that included the role of SA and the IC conversion ratio in the context of extreme threats to the survival of firms. Some preliminary practical recommendations were offered to management about how to measure the IC conversion ratio as well as how to stimulate and reward greater creativity among employees, filling a notable gap in the SA literature that provides less than precise guidance about how this concept can be measured.
Predicting the effect of different magnetic fields on the solute segregation during direct chill casting of large-size magnesium alloy slab
Authors: Duan Wenchao , Yang Yiqiang , Liu Wenhong , Zhang Zhiqiang , Cui Jianzhong
Published: April 2023

Purpose

The purpose of this paper is to reveal the solute segregation behavior in the molten and solidified regions during direct chill (DC) casting of a large-size magnesium alloy slab under no magnetic field (NMF), harmonic magnetic field (HMF), pulsed magnetic field (PMF) and two types of out-of-phase pulsed magnetic field (OPMF).

Design/methodology/approach

A 3-D multiphysical coupling mathematical model is used to evaluate the corresponding physical fields. The coupling issue is addressed using the method of separating step and result inheritance.

Findings

The results suggest that the solute deficiency tends to occur in the central part, while the solute-enriched area appears near the fillet in the molten and solidified regions. Applying magnetic field could greatly homogenize the solute field in the two-phase region. The variance of relative segregation level in the solidified cross-section under NMF is 38.1%, while it is 21.9%, 18.6%, 16.4% and 12.4% under OPMF2 (the current phase in the upper coil is ahead of the lower coil), HMF, PMF and OPMF1 (the current phase in the upper coil lags behind the lower coil), respectively, indicating that OPMF1 is more effective to reduce the macrosegregation level.

Originality/value

There are few reports on the solute segregation degree in rectangle slab under magnetic field, especially for magnesium alloy slab. This paper can act a reference to make clear the solute transport behavior and help reduce the macrosegregation level during DC casting.
Interactive CSR campaign and symbolic brand benefits: a moderated mediation model of brand trust and self-congruity in the restaurant industry
Authors: Sung Kyong Sik , Lee Seoki
Published: April 2023

Purpose

Drawing on symbolic interaction theory (SIT), this study aims to identify what makes corporate social responsibility (CSR) communication more favorable to customers in the chain restaurants context. Specifically, this study examines the direct relationships between the interactivity of CSR communication, brand trust and brand sincerity. In addition, the mediating role of brand trust (i.e. separate dimensions of brand reliability and intentions) and the moderated mediating role of self-congruity are explored.

Design/methodology/approach

A total of 418 US consumers with past experiences of participating in CSR campaigns organized by chain restaurants on social media were recruited using the online survey method of nonprobability sampling through Amazon Mechanical Turk in December 2021.

Findings

The results of this study revealed that the interactivity of CSR communication on social media affects brand sincerity; brand reliability and brand intentions mediate the positive effect of interactivity of CSR communication on brand sincerity; and customer’s self-congruity moderated the positive mediation effect via brand reliability.

Practical implications

Chain restaurant marketers need to understand the important role of interactivity as a key element of CSR communication on social media to help develop brand trust and brand sincerity in chain restaurants.

Originality/value

This study expands on SIT to support the symbolic benefits of interactive CSR communication on social media.
The patterns of anger regulation among school principals and their sources
Authors: Oplatka Izhar , Nupar Idit
Published: April 2023

Purpose

The purpose of this study was to explore school principals' sources of felt anger and to trace their forms of anger regulation in the workplace.

Design/methodology/approach

Based on semi-structured interviews with 30 elementary and secondary school principals in Israel, a typology of anger regulation is presented and analyzed.

Findings

The typology includes three types of perceived anger regulation: anger and surface acting, a moderate expression of anger and an authentic expression of anger. While teachers and students may provoke the principal's anger, most commonly external constituencies (e.g. Ministry of Education, Local Education Authorities) trigger their intense anger. Concluding the paper are suggestions for further research on anger in educational leadership and practical recommendations.

Originality/value

study fills the gap in knowledge about emotion regulation in educational leadership, in general, and increases our insights into the values and norms that delineate the degree to which anger expression is appropriate in the school, in particular.
Hybrid partial differential elliptical Rubik’s cube algorithm on image security analysis
Authors: Desam Vamsi , CH Pradeep Reddy
Published: April 2023

Purpose

Several chaotic system-based encryption techniques have been presented in recent years to protect digital images using cryptography. The challenges of key distribution and administration make symmetric encryption difficult. The purpose of this paper is to address these concerns, the novel hybrid partial differential elliptical Rubik’s cube algorithm is developed in this study as an asymmetric image encryption approach. This novel algorithm generates a random weighted matrix, and uses the masking method on image pixels with Rubik’s cube principle. Security analysis has been conducted, it enhances and increases the reliability of the proposed algorithm against a variety of attacks including statistical and differential attacks.

Design/methodology/approach

In this light, a differential elliptical model is designed with two phases for image encryption and decryption. A modified image is achieved by rotating and mixing intensities of rows and columns with a masking matrix derived from the key generation technique using a unique approach based on the elliptic curve and Rubik’s cube principle.

Findings

To evaluate the security level, the proposed algorithm is tested with statistical and differential attacks on a different set of test images with peak signal-to-noise ratio, unified average changed intensity and number of pixel change rate performance metrics. These results proved that the proposed image encryption method is completely reliable and enhances image security during transmission.

Originality/value

The elliptic curve–based encryption is hard to break by hackers and adding a Rubik’s cube principle makes it even more complex and nearly impossible to decode. The proposed method provides reduced key size.
Perinatal outcomes of socially disadvantaged women in Australia: A population‐based retrospective cohort study
Authors: Faulks Fiona , Shafiei Touran , McLachlan Helen , Forster Della , Mogren Ingrid , Copnell Beverley , Edvardsson Kristina
Published: April 2023

Objective

To examine the perinatal outcomes of women who experience social disadvantage using population‐based perinatal data collected between 1999 and 2016.

Design

Population‐based, retrospective cohort study.

Setting

Victoria, Australia.

Population or Sample

A total of 1 188 872 singleton births were included.

Methods

Cohort study using routinely collected perinatal data. Multiple logistic regression was performed to determine associations between social disadvantage and adverse maternal and neonatal outcomes with confidence limits set at 99%. Time‐trend analysis for perinatal outcomes was performed in relation to area‐level disadvantage measures.

Main Outcome Measures

Incidence of maternal admission to intensive care unit (ICU), postpartum haemorrhage (PPH) and caesarean section, perinatal mortality, preterm birth, low birthweight (LBW), and admission to special care nursery/neonatal intensive care unit (SCN/NICU).

Results

Social disadvantage was associated with higher odds of adverse perinatal outcomes. Disadvantaged women were more likely to be admitted to ICU, have a PPH or experience perinatal mortality (stillbirth or neonatal death) and their neonates were more likely to be admitted to SCN/NICU, be born preterm and be LBW. A persistent social gradient existed across time for the most disadvantaged women for all outcomes except caesarean section.

Conclusions

Social disadvantage has a marked negative impact on perinatal outcomes. This aligns with national and international evidence regarding the impact of disadvantage. Strategies that improve access to, and reduce fragmentation in, maternity care in addition to initiatives that address the social determinants of health may contribute to improving perinatal outcomes for socially disadvantaged women.
Enhancing traceability of wheat quality through the supply chain
Authors: Nadimi Mohammad , Hawley Eric , Liu Jing , Hildebrand Kurt , Sopiwnyk Elaine , Paliwal Jitendra
Published: April 2023

With the growing global population, the need for food is expected to grow tremendously in the next few decades. One of the key tools to address such growing food demand is minimizing grain losses and optimizing food processing operations. Hence, several research studies are underway to reduce grain losses/degradation at the farm (upon harvest) and later during the milling and baking processes. However, less attention has been paid to changes in grain quality between harvest and milling. This paper aims to address this knowledge gap and discusses possible strategies for preserving grain quality (for Canadian wheat in particular) during unit operations at primary, process, or terminal elevators. To this end, the importance of wheat flour quality metrics is briefly described, followed by a discussion on the effect of grain properties on such quality parameters. This work also explores how drying, storage, blending, and cleaning, as some of the common post‐harvest unit operations, could affect grain's end‐product quality. Finally, an overview of the available techniques for grain quality monitoring is provided, followed by a discussion on existing gaps and potential solutions for quality traceability throughout the wheat supply chain.
COVID in Australia: HR managers' challenges and opportunities
Authors: Connell Julie , Burgess John , Larkin Roslyn
Published: April 2023

Transitions to working from home due to the COVID pandemic led to a proliferation of literature and industry reports on changed work practices. However, this study set out to advance understanding of how human resource professionals managed the crises – adding to the limited literature on this perspective. Data was collected during late 2020/early 2021 through interviews with human resource professionals. Data was analysed using coding techniques enabling findings to be organised into relevant concepts and categories. Contributions to practice include the range of challenges and opportunities associated with working from home, which are outlined here as technical and behavioural recommendations. These include the need for improved IT support and IT literacy across the workforce; issues linked to employee isolation, managing privacy, workload, and the management of remote employees. This paper draws on institutional theory, stressing the importance of context in shaping HRM strategies in times of crises.