bluuebunny/crossref_metadata_2025 huggingface dataset:
Hippocampal-entorhinal cognitive maps and cortical motor system represent action plans and their outcomes
Authors: Barnaveli Irina , Vigano Simone , Reznik Daniel , Haggard Patrick , Doeller Christian F.
Published: July 2024

Efficiently interacting with the environment requires weighing and selecting among multiple alternative actions based on their associated outcomes. However, the neural mechanisms underlying these processes are still debated. We showed that forming relations between arbitrary action-outcome associations involved building a cognitive map. Using a novel immersive virtual reality paradigm, participants learned 2D abstract motor action-outcome associations and later compared action combinations while their brain activity was monitored with fMRI. We observed a hexadirectional modulation of the activity in entorhinal cortex while participants compared different action plans. Furthermore, hippocampal activity scaled with the 2D similarity between outcomes of these action plans. Conversely, the supplementary motor area (SMA) represented individual actions, showing a stronger response to overlapping action plans. Crucially, the connectivity between hippocampus and SMA was modulated by the similarity between the action plans, suggesting their complementary roles in action evaluation. These findings provide evidence for the role of cognitive maps in action selection, challenging classical models of memory taxonomy and its neural bases.
Early-life Microbiome-Derived HCA Enhances Type 3 Immunity via FXR- dependent m6A RNA methylation
Authors: Yang Zhipeng , Lin Zhiyuan , You Yaojie , Zhang Mei , Gao Ning , Wang Xinru , Peng Jian , Wei Hongkui
Published: July 2024

The gut microbiome plays a crucial role in the development of intestinal immunity during early life, but the underlying mechanisms remain largely unknown. Here, we found oxygen consumption in neonatal rats byS. boulardiiaccelerated the colonization of the microbiome and the development of type 3 immunity, which protected againstS. typhimurium. Microbiome maturation increased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and elevated the levels of Hyocholic acid (HCA). HCA promotes the development of γδT and type 3 innate lymphoid cell (ILC3) by sustaining the stability ofRorcmRNA via the FXR-WTAP- N6-methyl-adenosine (m6A) axis.L. reuteri, a bacterium encoding BSH, was enriched by oxygen consumption in the intestine and promoted intestinal type 3 immunity. However, inhibition of BSH blocks theL. reuteri-induced development of intestinal type 3 immunity. These results reveal the role of microbiome-derived HCA in the regulation of intestinal type 3 immunity during early life.
Comprehensive Phenotyping of Extracellular Vesicles in Blood of Healthy Humans – Insights into Cellular Origin and Biological Variability
Authors: Holcar Marija , Marić Ivica , Tertel Tobias , Goričar Katja , Primožič Urška Čegovnik , Černe Darko , Giebel Bernd , Lenassi Metka
Published: July 2024

Despite immense interest in biomarker applications of extracellular vesicles (EVs) from blood, our understanding of their physiological population in healthy humans remains limited. Using imaging and multiplex bead-based flow cytometry, we comprehensively quantified circulating EVs with respect to their cellular origin in a large cohort of healthy blood donors. We assessed coefficients of variations to characterise their biological variability and explored demographic, clinical, and lifestyle factors contributing to this variability. Cell-specific circulating EV subsets show a wide range of concentrations, which do not directly reflect concentrations of blood cells, indicating diverse patterns of EV subset release and/or uptake, even for EVs originating from the same cell type. Interestingly, tetraspanin+ circulating EVs largely originate from platelets and to a lesser extent from lymphocytes. PCA and association analyses demonstrate high biological inter-individual variability in circulating EVs across healthy humans, which can be only partly explained by the influence of sex, menopausal status, age and smoking on specific circulating EV and/or tetraspanin+ circulating EV subsets. No global influence of the explored subject’s factors on circulating EVs was detected. Our findings provide the first comprehensive, quantitative data towards the cell-origin atlas of blood EVs, with important implications in the clinical use of EVs as biomarkers of disease.
Distinct modes of holobiont specialization among cryptic coral lineages
Authors: Grupstra Carsten G.B. , Meyer-Kaiser Kirstin S. , Bennett Matthew-James , Andres Maikani O. , Juszkiewicz David J. , Fifer James E. , Da-Anoy Jeric P. , Gomez-Campo Kelly , Martinez-Rugerio Isabel , Aichelman Hannah E. , Huzar Alexa K. , Hughes Annabel M. , Rivera Hanny E. , Davies Sarah W.
Published: July 2024

As ocean warming threatens reefs worldwide, identifying corals with adaptations to higher temperatures is critical for conservation. Genetically distinct but morphologically similar (i.e.,cryptic) coral populations can be specialized to extreme habitats and thrive under stressful conditions. These corals often associate with locally beneficial microbiota (Symbiodiniaceae photobionts and bacteria), clouding interpretation of the drivers of thermal tolerance. Here, we leverage a holobiont (massivePorites) with high host-partner fidelity to investigate adaptive variation across classic (“typical” conditions) and extreme reefs characterized by higher temperatures and light attenuation. We uncovered three cryptic lineages that exhibit limited micro-morphological variation; one lineage dominated classic reefs (L1), one had more even distributions (L2), and a third was restricted to extreme reefs (L3). Two lineages were more closely related to populations ∼4300 km away, suggesting that these lineages are widespread. All corals harboredCladocopiumC15 photobionts, but strain-level compositions differed among lineages and reef types. L1 associated with distinct photobionts and bacteria in each reef type, whereas L2 had relatively stable associations. L3 hosted unique photobiont strains, signaling high host-photobiont fidelity. Analysis of light harvesting capacity and thermal tolerance revealed key adaptive variation underpinning survival in distinct habitats. L1 had the highest light absorption efficiency and lowest thermal tolerance, suggesting it is a classic reef specialist. L3 had the lowest light absorption efficiency and the highest thermal tolerance, showing that it is an extreme reef specialist. L2 had intermediate light absorption efficiency and thermal tolerance, signaling habitat generalism, potentially explaining how it survives well in both habitat types. These findings reveal diverging holobiont strategies to cope with extreme conditions. Resolving coral lineages is key to understanding variation in thermal tolerance among coral populations; uncovering thermally-tolerant holobionts can strengthen our understanding of coral evolution and symbiosis, and support global conservation and restoration efforts.
The functional roles of zebrafishHoxA- andHoxD-related clusters in the pectoral fin development
Authors: Ishizaka Mizuki , Maeno Akiteru , Nakazawa Hidemichi , Fujii Renka , Oikawa Sae , Tani Taisei , Kanno Haruna , Koita Rina , Kawamura Akinori
Published: July 2024

The paralogs 9-13Hoxgenes in mouseHoxAandHoxDclusters are critical for limb development. When bothHoxAandHoxDclusters are deleted in mice, significant limb truncation is observed compared to the phenotypes of single and compound mutants ofHox9-13genes in these clusters. In zebrafish, mutations inhox13genes inHoxA- andHoxD-related clusters result in abnormal morphology of pectoral fins, homologous to forelimbs. However, the effect of the simultaneous deletions of entireHoxA- andHoxD-related clusters on pectoral fin development remains unknown. Here, we generated mutants with several combinations ofhoxaa,hoxab, andhoxdacluster deletions and analyzed the pectoral fin development. Inhoxaa-/-;hoxab-/-;hoxda-/-larvae, the endoskeletal disc and the fin-fold are significantly shortened in developing pectoral fins. In addition, we show that this anomaly is due to defects in the pectoral fin growth after the fin bud formation. Furthermore, in the surviving adult mutants, micro-CT scanning reveals defects in the posterior portion of the pectoral fin which is thought to represent latent regions of the limb. Our results further support that the functional role ofHoxAandHoxDclusters is conserved in the paired appendage formation in bony fishes.
Cellular heterogeneity in hypertrophic burn scars in response to carbon dioxide laser therapy
Authors: Chen Yung-Yi , Mahony Christopher , Turner Jason , Smith Charlotte M , Abdulsalam Abdulrazak , Amirize Ezekwe , Prince Amberley , Heagerty Adrian , Roberts Claudia , Croft Adam , Wilson Yvonne , Moiemen Naiem , Lord Janet M
Published: July 2024

Fractional carbon dioxide (AFCO2) laser therapy is used for treating pathological scarring, but the clinical outcomes are variable and the mechanisms of scar reduction poorly understood. We investigated the mechanisms underpinning efficacy of AFCO2laser therapy, performing single-cell RNA sequencing in skin biopsies from patients with hypertrophic scars after AFCO2laser therapy. Patients with younger scars (Good Responder, GR, <6 years from healing) had better scar reduction than patients with older scars (Poor Responder, PR, >6 years from healing) by various measures of scarring. scRNAseq analysis revealed that genes enriched in GR were associated with extracellular matrix and structure organisation (COL14A1,POSTN,SPARC); whereas genes enriched in PR were related to enhanced immune responses (IL-12,MSTN, HLA-DQA). The groups had distinct intercellular communication networks and differentiation trajectories after AFCO2, with regenerative Mesenchymal fibroblasts associated with a good response and inflammatory Secretory Papillary and Inflammatory Fibroblasts with a poor response.
Deciphering the variation in cuticular hydrocarbon profiles of six European honey bee subspecies
Authors: Rodríguez-León Daniel Sebastián , Uzunov Aleksandar , Costa Cecilia , Dylan Elen Sebastián , Charistos Leonidas , Galea Thomas , Gabel Martin , Scheiner Ricarda , Pinto M. Alice , Schmitt Thomas
Published: July 2024

The Western honey bee (Apis mellifera) subspecies exhibit local adaptive traits that evolved in response to the different environments that characterize their native distribution ranges. An important trait is the cuticular hydrocarbon (CHC) profile, which helps preventing desiccation and mediating communication. We compared the CHC profiles of six European subspecies (A. m. mellifera,A. m. carnica,A. m. ligustica,A. m. macedonica,A. m. iberiensis, andA. m. ruttneri) and investigated potential factors shaping their composition. We did not find evidence of adaptation of the CHC profiles of the subspecies to the climatic conditions in their distribution range. Subspecies-specific differences in CHC composition might be explained by phylogenetic constraints or genetic drift. The CHC profiles of foragers were more subspecies-specific than those of nurse bees, while the latter showed more variation in their CHC profiles, likely due to the lower desiccation stress exerted by the controlled environment inside the hive. The strongest profile differences appeared between nurse bees and foragers among all subspecies, suggesting an adaptation to social task and a role in communication. Foragers also showed an increase in the relative amount of alkanes in their profiles compared to nurses, indicating adaptation to climatic conditions.
3D Printed Multifunctional Bioadhesive Patch with Intrinsic Bioelectronic Properties for Decoding Electromechanical and Anisotropic Cardiac Microenvironment
Authors: Dutta Sayan Deb , Patil Tejal V. , Lim Ki-Taek
Published: July 2024

Fabricating anisotropic multifunctional bioadhesive patches with tunable mechanical stiffness, electrical conductivity, antimicrobial activity, and modulating cellular behavior is crucial for the successful management of cardiac tissue injury and boosting immunogenic microenvironments. Direct ink writing (DIW)-based 3D printing holds tremendous potential for developing electroactive cardiac patches (ECPs) with anisotropic microarchitecture. Inspired by the native myocardium, we developed a multifunctional and anisotropic ECP with tunable stiffness by incorporating a highly conductive graphene oxide/nanodiamond (GO@ND) complex into a biocompatible carboxymethyl chitosan/polyvinyl alcohol (CSA) matrix for regulating immunogenic and cardiomyogenic cues. The incorporation of GO@ND enhanced the electrical conductivity (∼22.6 S mm-1) with high interfacial toughness (>250 MJ m-1) and improved the printability (n= 0.5) with concentration-dependent self-assembly into the CSA matrix. We observed that electrical stimulation (EFs; 250 mV/20 min/day) through nanoengineered CSA resulted in broad-spectrum antibacterial activity againstE. coliandS. aureusby 99.29% and 98.74%, respectively, via sustained release of curcumin (Cur). Moreover, the electromechanical study revealed that CSA with higher stiffness (∼6.2 kPa) activated cytoplasmic YAPs during macrophage polarization. Besides, stiffness and EFs regulated human cardiomyocyte differentiation through anisotropic force-driven early activation of Vinculin, triggering the phosphorylation of NFATc3 and activating Lamin A/C in a YAP-dependent manner. Based on these findings, we anticipated that the fabricated nanoengineered patch had tremendous potential for regulating the electro-cardiomyogenic microenvironment with multifunctional abilities.
An ecological-evolutionary perspective on the genomic diversity and habitat preferences of the Acidobacteriota
Authors: McReynolds Ella , Elshahed Mostafa S. , Youssef Noha H.
Published: July 2024

Members of the phylum Acidobacteriota inhabit a wide range of ecosystems including soils. We analyzed the global patterns of distribution and habitat preferences of various Acidobacteriota lineages across major ecosystems (soil, engineered, host-associated, marine, non-marine saline and alkaline, and terrestrial non-soil ecosystem) in 248,559 publicly available metagenomic datasets. Classes Terriglobia, Vicinamibacteria, Blastocatellia, and Thermoanaerobaculia were highly ubiquitous and showed clear preference to soil over non-soil habitats, class Polarisedimenticolia showed comparable ubiquity and preference between soil and non-soil habitats, while classes Aminicenantia and Holophagae showed preferences to non-soil habitats. However, while specific preferences were observed, most Acidobacteriota lineages were habitat generalists rather than specialists, with genomic and/or metagenomic fragments recovered from soil and non-soil habitats at various levels of taxonomic resolution. Comparative analysis of 1930 genomes strongly indicates that phylogenetic affiliation plays a more important role than the habitat from which the genome was recovered in shaping the genomic characteristics and metabolic capacities of theAcidobacteriota. The observed lack of strong habitat specialization and habitat transition driven lineage evolution in the Acidobacteriota suggest ready cross colonization between soil and non-soil habitats. We posit that such capacity is key to the successful establishment of Acidobacteriota as a major component in soil microbiomes post ecosystem disturbance events or during pedogenesis.
SOX21 suppresses GBM growth by repressing AP-1 regulated target genes
Authors: Rrapaj Eltjona , Yuan Juan , Kurtsdotter Idha , Misyurin Vsevolod , Baselli Guido , Persson Oscar , Bergsland Maria , Muhr Jonas
Published: July 2024

Resistance of glioblastoma stem cells (GSCs) to standard treatments is a major cause of glioblastoma (GBM) recurrence. This study examines the potential of the transcription factor SOX21 to inhibit GSC properties and combat GBM progression. Results show that increasing SOX21 levels in primary GSCs induces an anti-tumorigenic gene expression profile, which is substantiated by a significant correlation between high SOX21 expression and improved survival rates of GBM patients. Furthermore, induced SOX21 expression in pre-established GBM reduces tumor growth and significantly extends the survival of orthotopically transplanted mice. SOX21 acts as a tumor suppressor by binding to and epigenetically repressing AP-1-targeted chromatin, thereby downregulating adjacent genes. Consistently, the anti-tumorigenic activities of SOX21 are replicated by small molecules that inhibit AP-1 activity, whereas overexpression of an AP-1 transcription factor reverses these effects. Overall, this research demonstrates the potent role of SOX21 in restricting GBM progression through repression of AP-1-stimulated tumor-promoting gene expression.
PD-1 blockade enhances HIV-1 vaccine-induced CD8⁺ T-cell responses in PWH early ART-treated
Authors: Marin Miguel , Ruiz Alba , Jimenez-Moyano Esther , Ouchi Dan , Blanch-Lombarte Oscar , Peña Ruth , Gorman Dan , Barnard Richard , Hanke Tomas , Clotet Bonaventura , Howell Bonnie , Brander Christian , Mothe Beatriz , Prado Julia G
Published: July 2024

Current HIV-1 therapeutic vaccines do not generate T-cell immune responses in people with HIV-1 (PWH) able to eradicate the virus or to broadly control viral replication. The expression of inhibitory receptors (IRs) may limit vaccine efficacy by reducing specific effector functions in vaccine-induced T-cells. Recently, the clinical use of antibodies targeting IRs or immune checkpoint blockade (ICB) has demonstrated remarkable success in cancer remission. Therefore, there is a potential benefit of using ICB in PWH to improve the effectiveness of vaccine-induced T-cell responses. Here, we evaluated functional changes in vaccine-induced HIV-specific CD8⁺ T-cell responses by in-vitro PD-1 and TIM-3 blockade during immune stimulation in PWH early ART-treated and vaccinated (Etvac). We compared Etvac to PWH early ART-treated (Et) and chronic ART-treated PWH (Chro). Our results demonstrate a significant increase in the functional responses of vaccine-induced HIV-1-specific CD8⁺ T-cells upon PD-1 but not TIM-3 blockade in cellular proliferation, IFNγ production, and activation. Although no effect was found in Et, similar findings were obtained in HIV-1-specific CD8⁺ T-cells in Chro for combined PD-1/TIM-3 blockade. Moreover, we identify in Etvac a direct association between PD-1 expression in CD8+T cells and in vitro response to anti-PD-1 treatment. Our findings support the potential adjuvant effect of PD-1 blockade to improve HIV-1 therapeutic vaccine efficacy in early ART-treated PWH for future human studies.
Evolutionary new centromeres in the snowy owl genome putatively seeded from a transposable element
Authors: Baalsrud H. T. , Garmann-Aarhus B. , Enevoldsen E. L. G. , Krabberød A.K. , Fischer D. , Tooming-Klunderud A. , Skage M. , Árnyasi M. , Sandve S. R. , Jakobsen K.S. , Nielsen R. , Boessenkool S. , Tørresen O. K.
Published: July 2024

Comparative genomic studies in birds have revealed that bird genomes are relatively repeat-poor and stable in terms of karyotype, size, and gene synteny/collinearity compared to other vertebrates. One notable exception is the owls, with cytogenetic studies demonstrating large variations in karyotypes and the evolution of unusual centromeric satellite repeats in some species. However, there has so far not been an investigation into genome architecture and repeat landscape of owls. Here, we present a chromosome-level genome assembly for the snowy owl (Bubo scandiacus). We find that the repeat DNA content in the relatively large snowy owl genome (1.6 Gb) is among the highest reported for any bird genome to date (28.34% compared to an average of ∼10% in other birds). The bulk of the snowy owl genomic repeat landscape consists of centromeric satellite DNA, which appears to have originated from an endogenous retrovirus (ERV1). Using gene collinearity analyses we show that the position of these evolutionary new centromeres (ECNs) are not homologous with chicken centromeres, and are located in regions with collinearity breaks to other bird genomes due to chromosomal rearrangements. Our results support rapid transposable element-driven evolution of lineage-specific centromeres, which could have played a role in reproductive isolation and speciation of the snowy owl.
Brain virtual histology of a lizard species (Podarcis bocagei) using X-ray micro-tomography and deep-learning segmentation
Authors: Zhou Tunhe , Dragunova Yulia , Triki Zegni
Published: July 2024

Lately, there has been an emphasis on the importance of studying inter-individual variation in animal behaviour and cognition and understanding its underlying mechanisms. What was once considered mere noise around population mean can be explained by individual characteristics such as brain morphology and functionality. However, logistical limitations can be faced when studying the brain, especially for research involving wild animals, such as dealing with small sample sizes and time-consuming methods. Here, we combined an efficient and accurate method using X-ray micro-tomography and deep-learning (DL) segmentation to estimate the volume of six main brain areas of wild lizards,Podarcis bocagei: olfactory bulbs, telencephalon, diencephalon, midbrain, cerebellum and brain stem. Through quantitative comparison, we show that a sufficient deep-learning neural network can be trained with as few as five data sets. From this, we applied the trained deep-learning algorithm to obtain volume data of the six brain regions from 29 brains ofPodarcis bocagei. We provide a detailed protocol for our methods, including sample preparation, X-ray tomography, and 3D volumetric segmentation. Our work is open-access and freely available, with the potential to benefit researchers in various fields, such as animal physiology, biomedical studies, and computer sciences.
SYSTEMIC FRATAXIN DEFICIENCY CAUSES TISSUE-DEPENDENT IRON HOMEOSTASIS ALTERATIONS: IMPLICATIONS FOR FRIEDREICH ATAXIA
Authors: Pazos-Gil Maria , Medina-Carbonero Marta , Sanz-Alcázar Arabela , Portillo-Carrasquer Marta , Oliveira Luiza , Hernandez Gonzalo , Sánchez Mayka , Delaspre Fabien , Cabiscol Elisa , Ros Joaquim , Tamarit Jordi
Published: July 2024

Friedreich Ataxia (FA) is a cardio-neurodegenerative disease caused by mutations in the frataxin gene, which result in low frataxin expression. It is well-established that frataxin deficiency affects iron homeostasis, but the tissue-specificity of these alterations is poorly understood. In this study, we have analyzed iron homeostasis alterations in the FXNI151F mouse model, which presents systemic frataxin deficiency and neurological defects resembling FA patients. Iron overload is observed in the brain from 21-week old FXNI151F mice, both males and females, and it does not further accumulate in older animals. It is also observed in livers from 39-week old mutant females, but not in males. Iron signaling is altered in all tissues: in brain and liver Iron Regulatory Protein 1 (IRP1) content is decreased, while in heart increased IRP2 and decreased specific aconitase 2 activity are observed. Remarkably, these cardiac alterations are partially restored in 39- week-old animals, suggesting that the heart is activating an iron-deficiency response to compensate for deficient iron-sulfur biogenesis. Our findings demonstrate that frataxin deficiency affects iron homeostasis in a time dependent and tissue-specific manner, and that the pathological mechanisms in FA comprise both iron accumulation and limited iron availability. Understanding this specificity is crucial for the design of iron-related therapeutic interventions aiming to improve FA symptomatology.
Resolving the source of branch length variation in the Y chromosome phylogeny
Authors: Swiel Yaniv , Kelso Janet , Peyrégne Stéphane
Published: July 2024

Genetic variation in the non-recombining part of the human Y chromosome has provided important insight into the paternal history of human populations. However, a significant and yet unexplained branch length variation of Y chromosome lineages has been observed, notably amongst those that are highly diverged from the human reference Y chromosome. Understanding the origin of this variation, which has previously been attributed to changes in generation time, mutation rate, or efficacy of selection, is important for accurately reconstructing human evolutionary and demographic history.

Here, we analyze Y chromosomes from present-day and ancient modern humans, as well as Neandertals, and show that branch length variation amongst human Y chromosomes cannot solely be explained by differences in demographic or biological processes. Instead, reference bias results in mutations being missed on Y chromosomes that are highly diverged from the reference used for alignment. We show that masking fast-evolving, highly divergent regions of the human Y chromosome mitigates the effect of this bias and enables more accurate determination of branch lengths in the Y chromosome phylogeny. Finally, we show that this approach allows us to estimate the age of ancient samples from Y chromosome sequence data and provide updated TMRCA estimates using the portion of the Y chromosome where the effect of reference bias is minimised.
From a single sequence to evolutionary trajectories: protein language models capture the evolutionary potential of SARS-CoV-2 protein sequences
Authors: Lamb Kieran D , Hughes Joseph , Lytras Spyros , Young Francesca , Koci Orges , Herzig James , Lovell Simon C , Grove Joe , Yuan Ke , Robertson David L
Published: July 2024

Protein language models (PLMs) capture features of protein three-dimensional structure from amino acid sequences alone, without requiring multiple sequence alignments (MSA). The concepts of grammar and semantics from natural language have the potential to capture functional properties of proteins. Here, we investigate how these representations enable assessment of variation due to mutation. Applied to SARS-CoV-2's spike protein using in silico deep mutational scanning (DMS) we demonstrate the PLM, ESM-2, has learned the sequence context within which variation occurs, capturing evolutionary constraint. This recapitulates what conventionally requires MSA data to predict. Unlike other state-of-the-art methods which require protein structures or multiple sequences for training, we show what can be accomplished using an unmodified pretrained PLM. We demonstrate that the grammaticality and semantic scores represent novel metrics. Applied to SARS-CoV-2 variants across the pandemic we show that ESM-2 representations encode the evolutionary history between variants, as well as the distinct nature of variants of concern upon their emergence, associated with shifts in receptor binding and antigenicity. PLM likelihoods can also identify epistatic interactions among sites in the protein. Our results here affirm that PLMs are broadly useful for variant-effect prediction, including unobserved changes, and can be applied to understand novel viral pathogens with the potential to be applied to any protein sequence, pathogen or otherwise.
The Enemy Within: how pathogen-free are your commercial specific pathogen-free mice?
Authors: Mark David , Trolan Mia , Douce Gillian , Roe Andrew J , McHugh Rebecca E
Published: July 2024

Here, we report the incidental isolation and genome sequencing of anE. coliO157:H7 strain isolated from the faeces of commercial, specific-pathogen free mice (BALB/c). The isolate, subsequently named EC_MP01 was found to carry both Shiga toxin 2a and the Locus of Enterocyte Effacement (LEE) pathogenicity island, major virulence factors associated with severe disease in humans. This report draws attention to the limitations of existing screening systems and highlights how strain carriage influence the outputs from such studies.
Cytoplasmic mRNA capping enzyme is regulated by hypoxia inducible factor HIF1α and controls stability of the target lncRNAs during hypoxia
Authors: Islam Safirul , Mukherjee Chandrama
Published: July 2024

Hypoxia-inducible factors (HIFs) regulate the expression of several hypoxia-responsive RNAs (HRR) to sustain cellular homeostasis. Cytoplasmic pool of mRNA capping enzyme (cCE) has been shown to recap its substrate uncapped mRNAs or long noncoding RNAs (lncRNAs) present in the cytoplasm, preventing their degradation, even during arsenite-induced oxidative stress. Here, we examined the effect of hypoxia on cCE and its function in regulating the substrate lncRNAs. Hypoxia induces expression of cCE in HIF1α dependent manner as evidenced by Chromatin immunoprecipitation and HIF1α inhibitor experiments. Furthermore, we found cCE post-transcriptionally controls the stability of its target lncRNAs amidst hypoxia. These results suggest that cCE may act as a posttranscriptional modulator that could alter the cellular response to hypoxia by stabilizing cCE-targeted lncRNAs.
Toxic Small Alarmone Synthetase FaRel2 inhibits translation by pyrophosphorylating tRNAGlyand tRNAThr
Authors: Kurata Tatsuaki , Takegawa Masaki , Ohira Takayuki , Syroegin Egor A. , Atkinson Gemma C. , Johansson Marcus J.O. , Polikanov Yury S. , Garcia-Pino Abel , Suzuki Tsutomu , Hauryliuk Vasili
Published: July 2024

Translation-targeting toxic Small Alarmone Synthetases (toxSAS) are effectors of bacterial Toxin-Antitoxin systems that pyrophosphorylate the 3’-CCA end of tRNA to prevent aminoacylation. toxSAS are implicated in antiphage immunity: phage detection triggers the toxSAS activity to shut down viral production. We show that the toxSAS FaRel2 inspects the tRNA acceptor stem to specifically select tRNAGlyand tRNAThr. The 1st, 2nd, 4thand 5thbase pairs the stem act as the specificity determinants. We show that the toxSASs PhRel2 and CapRelSJ46differ in tRNA specificity from FaRel2, and rationalise this through structural modelling: while the universal 3’-CCA end slots into a highly conserved CCA recognition groove, the acceptor stem recognition region is variable across toxSAS diversity. As phages use tRNA isoacceptors to overcome tRNA-targeting defences, we hypothesise that highly evolvable modular tRNA recognition allows for the escape of viral countermeasures through tRNA substrate specificity switching.
Subconcussive head impacts sustained during American football alter gut microbiome diversity and composition
Authors: Pelland Zack , Zafar Aziz , Ay Ahmet , Belanger Ken
Published: July 2024

Subconcussive head impacts (SHIs) are a public health concern amongst at-risk populations. SHIs are hits to the head that do not typically generate symptoms and are unlikely to meet diagnostic criteria for mild traumatic brain injury (mTBI). Changes in the gut microbiome have been associated with mTBIs and implicated in both acute recovery from and neurodegenerative pathologies associated with repeated mTBI. This study monitored the gut microbiomes and head impact exposure of collegiate American football players across a competition season to determine if SHIs lead to acute and longer-term changes to the gut microbiome. SHI exposure correlates with changes in microbial diversity and composition three days post-exposure, the athletes’ gut microbiomes change significantly across the season, and mixed effects modeling provides evidence for cumulative effects of SHIs. These data provide the first evidence for a link between SHIs and changes in the diversity and composition of the gut microbiome.
Evaluating the effects of archaic protein-altering variants in living human adults
Authors: Molz Barbara , Lana Alberro Mikel , Eising Else , Schijven Dick , Alagöz Gökberk , Francks Clyde , Fisher Simon E.
Published: July 2024

Advances in paleo-genetics allowed the identification of protein-coding changes arising on the lineage leading toHomo sapiens, by comparing genomes of present-day and archaic hominins. Experimental validation of the potential impact of such changes has so far been restricted to functional assays and model organisms. Large-scale biobanking now makes it possible to identify present-day carriers of archaic alleles and to directly assess phenotypic consequences in living adults. We queried exomes of half a million people in the UK Biobank at 37 genomic positions with supposedly fixed human-specific protein-coding changes. This yielded 103 carriers at 17 positions, with variable allele counts across ancestries. Contrasting carriers and non-carriers of an exemplary archaic allele inSSH2, we observed no deviation from the norm in a range of health, psychological, and cognitive traits. We also identified 62 archaic-allele carriers for aTKTL1missense change, previously shown to have large effects on cortical neurogenesis in brain organoids and animal models. Carriers did not show differences in relevant anatomical brain measures, and a substantial proportion had college/university degrees. This work offers an empirical demonstration of how large-scale biobank investigations of living adults can transform our understanding of human evolution. The findings challenge the notion of fixed human-specific genomic changes, highlight that individual interrogation of relevant sites is unlikely to yield major insights into the emergence of complex human traits, and emphasise the importance of including diverse ancestries when investigating origins of our species.
Natural variation in starvation sensitivity maps to a point mutation in phospholipase IPLA2-VIA inDrosophila melanogaster
Authors: Williams Shawn B. , Franklin Brian , Lemieux Faye A. , Rand David M
Published: July 2024

Resistance to starvation is a classic complex trait, where genetic and environmental variables can greatly modify an animal’s ability to survive without nutrients. In this study, we investigate the genetic basis of starvation resistance using complementary quantitative and classical genetic mapping inDrosophila melanogaster. Using the Drosophila Genetics Reference Panel (DGRP) as a starting point, we queried the genetic basis of starvation sensitivity in one of the most sensitive DGRP lines. We localize a major effect locus modifying starvation resistance to the phospholipase iPLA2-VIA. This finding is consistent with the work of others which demonstrate the importance of lipid regulation in starvation stress. Furthermore, we demonstrate that iPLA2-VIA plays a role in the maintenance of sugar reserves post-starvation, which highlights a key dynamic between lipid remodeling, sugar metabolism and resistance to starvation stress.
Mapping the human hematopoietic stem and progenitor cell hierarchy through integrated single-cell proteomics and transcriptomics
Authors: Furtwängler Benjamin , Üresin Nil , Richter Sabrina , Schuster Mikkel Bruhn , Barmpouri Despoina , Holze Henrietta , Wenzel Anne , Grønbæk Kirsten , Theilgaard-Mönch Kim , Theis Fabian J. , Schoof Erwin M. , Porse Bo T
Published: July 2024

Single-cell transcriptomics (scRNA-seq) has enabled the characterization of cell state heterogeneity and recapitulation of differentiation trajectories. However, since proteins are the main functional entities in cells, the exclusive use of mRNA measurements comes at the risk of missing important biological information. Here we leverage recent technological advances in single-cell proteomics by Mass Spectrometry (scp-MS) to generate the first scp-MS dataset of anin vivodifferentiation hierarchy encompassing over 2,500 human CD34+ hematopoietic stem and progenitor cells. Through integration with scRNA-seq, we identify proteins that are important for stem cell quiescence, which were not indicated by their mRNA transcripts, and demonstrate functional expression covariance during differentiation that is only detectable on protein level. Finally, we show that modeling translation dynamics can infer cell progression during differentiation and explain 45% more protein variation from mRNA than linear correlation. Our work serves as a framework for future single-cell multi-omics studies across biological systems.
Autophagy inhibition in intestinal stem cells favors enteroendocrine cell differentiation through Stat92E activity
Authors: Lacarrière-Keïta Camille , Nassari Sonya , Jean Steve
Published: July 2024

Because the intestinal epithelium faces many stresses, dysregulation of essential mechanisms governing gut homeostasis, such as autophagy, has been associated with inflammatory bowel pathologies. InDrosophila melanogaster, the inhibition of autophagy, specifically in adult intestinal stem cells (ISCs), affects their number differently through aging. Appropriate intestinal renewal requires a balance between ISC proliferation and differentiation. Herein, we show that in adult ISCs, the loss of core autophagy genes and regulators of autophagosome-lysosome fusion increased the enteroendocrine cell population and transcriptional activity of Stat92E. Functional experiments with cell fate regulators involved in enteroendocrine or enterocyte differentiation or proliferation suggested that dysfunctional autophagy in adult ISCs enhanced Stat92E activity downstream of Hop/JAK kinase. Finally, lineage-tracing analyses confirmed that autophagy inhibition autonomously promotes enteroendocrine cell differentiation without affecting enterocyte differentiation. Thus, our data demonstrates that, under homeostatic conditions, basal autophagy limits enteroendocrine cell differentiation by controlling Stat92E activity.
Storage stability, nutritional and qualitative attributes of biscuits enriched with terebinth, flaxseed and sesame seeds
Authors: Karakoç Fatma Burcu , Ertaş Nilgün , Aslan Mine
Published: July 2024

Purpose

The utilization of oilseeds in food formulations is prevalent due to their health benefits and nutritional value. These protein-rich oilseeds serve as an affordable and essential source of nutrients and bioactive compounds, fulfilling human protein requirements. As such, this study sought to investigate the impact of partially replacing wheat flour with oilseeds in different proportions on the nutritional and quality characteristics of biscuits.

Design/methodology/approach

Oilseeds, including terebinth, sesame and flaxseed, were partially substituted with wheat flour in amounts of 0, 5, 10, 15, 20 and 25%. The effects of this substitution on the storage stability, nutritional content and physical properties of the resulting biscuits were examined.

Findings

The L* (from 69.75 to 54.06) and b* (from 28.59 to 21.60) color values of biscuits decreased with the supplement of oilseeds. The oilseeds addition increased the protein, fat, energy, and ash values of biscuits. At the highest level of added terebinth, sesame and flaxseed, respectively, the amounts measured were 5984.62 mgGAE/kg, 1553.85 mgGAE/kg and 2169.23 mgGAE/kg, which were higher than the control biscuits (715.39 mgGAE/kg). The incorporation of oilseeds resulted in a substantial decrease in pH and peroxide values, while the moisture content was increased throughout the 6-month storage period. The use of terebinth in biscuits led to better oxidative stability than sesame and flaxseed-containing samples. The biscuit samples with terebinth had a longer induction time. The lowest induction time of biscuits with 25% flaxseed was chosen, approximately 3.5 h.

Research limitations/implications

Oilseed flours, which are rich in lipids, have been shown to enhance the quality of biscuits. However, further studies could aim to reduce the amount of shortening used to improve their quality even further. Reducing the shortening could keep the lipid content at an acceptable amount, especially considering consumers' current expectations for low-fat foods.

Practical implications

Plant-based bioactive are generally known as secondary metabolites and have promising therapeutic attributes, especially antioxidative properties.

Social implications

Thanks to this composition, some of these seeds have proven effective in controlling and preventing metabolic diseases (hypertension, hypercholesterolemia, diabetes, coronary heart disease and several types of cancer) as well as providing interesting properties to foods.

Originality/value

As result, oilseeds can be successfully used as functional and sustainable food ingredients to improve the functional, nutritional and storage stability of biscuits.
Appraisal of policy measures at the beginning of a pandemic: Empirical evidence from the first four months and 12 months of the COVID-19 pandemic
Authors: du Plessis Emile
Published: July 2024

Purpose

The rapid spread of the COVID-19 pandemic upended societies across the world, with billions forced into lockdowns. As countries contemplated instating and rolling back lockdown measures, and considered the impact of pandemic fatigue on policy measures, and furthermore to prepare for the improved management of future pandemics, this study examines the effectiveness of policy measures in limiting the spread of infections and fatalities.

Design/methodology/approach

The methodological approach in the study centres on a fixed effects panel regression analysis and employs the COVID-19 Government Response Stringency Index, which comprises eight containment measures and three health campaigns, with progressive degrees of stringency, in order to investigate the efficacy of government policies.

Findings

Findings suggest that some government policies were effective at reducing implicit mortality rates, infection cases and fatalities during the first four months of the COVID-19 pandemic. Solid stringency measures to reduce mortality rates include public gathering restrictions on more than 100 attendees, and international travel limits for developed countries and islands. Fatalities can further be reduced through the closing of public transport, whereas infection cases also experience benefits from public information campaigns. Comparable results are observed in a robustness test across 12 months.

Originality/value

Some non-pharmaceutical policies are shown to be more effective than others at reducing the spread of infections, fatalities and mortality rates, and support policymakers to manage future pandemics more effectively.
Product-as-a-service from B2C retailers' perspective: a framework of challenges and mitigations
Authors: Koers Lisanne , Steffens Solveigh , Tamerus Saskia , Forslund Helena
Published: July 2024

Purpose

Product-as-a-Service (PaaS) has the potential to enable closed-loop supply chains (CLSC) and decrease environmental impact, but it is only applied on a small scale. The purpose of this paper is to explore and develop a framework of challenges and corresponding mitigations encountered by Business-to-Consumer (B2C) retailers when transitioning to PaaS.

Design/methodology/approach

Data collection drew on a qualitative interview study with two industry experts and four PaaS B2C retailers from different Dutch industries.

Findings

A framework was developed linking 26 challenges in eight clusters—financial, product-related, supply chain-related, consumer-related, human resources, research and development/technology, regulatory and industry-related—to 24 mitigations. The mitigations were elaborated, and theoretical insights for matching challenges with mitigations were provided.

Research limitations/implications

This study expands PaaS literature to the generally under-researched retail context. It contributes to CLSC literature by applying it to a less-studied context, thereby revealing many supply chain-related challenges and mitigations encountered by B2C retailers.

Practical implications

The framework offers practical guidance to retail managers for overcoming or preventing challenges in PaaS, in their endeavours toward adopting environmentally sustainable practices.

Social implications

The study creates awareness about environmental sustainability and the potential to reduce societal impact, in which a PaaS-enabled CLSC is one step.

Originality/value

Studying PaaS and CLSC in a retail context is timely and novel.
Mobile money, food security and coping strategies in a post-conflict and fragile context: evidence from Burundi
Authors: Atta-Aidoo Jonathan , Bizoza Saidi , Matthew Ester Cosmas , Saleh Abdulkarim Onah
Published: July 2024

Purpose

Attaining the Sustainable Development Goal 2 (SDG2) of zero hunger continues to be a challenge in most parts of Sub-Saharan Africa. However, financial inclusion is seen as a potential pathway for reducing food insecurity among poor households. Mobile money is a financial inclusion instrument that is easily accessible to poor households and has the potential to increase the level of financial inclusion. This paper contributes to the literature by examining the determinants of mobile money adoption, its effects on household food security and the choice of coping strategies in Burundi, a post-conflict and fragile country.

Design/methodology/approach

Using survey data that involved 860 households in Burundi, we adopted the Household Hunger Scale (HHS) developed under the Food and Nutrition Technical Assistance Project to measure household food security. We further employ the endogenous switching regression treatment effects model for ordered outcomes and the multivariate probit model to achieve our aims.

Findings

The results of our study reveal that the adoption of mobile money is influenced by factors such as gender, marital status, age, formal education, membership in a social network, area of residence and access to a tarred road network. Additionally, the food security status of a household was determined by marital status, formal education, social network membership, access to tarred roads, off-farm income, access to credit and land tenure security. We confirm that mobile money adoption has a significantly positive effect on the food security status of households with heterogeneity in gender and area of residence. We also find that mobile money adoption reduces the likelihood of households adopting consumption-related coping strategies.

Practical implications

The promotion of mobile money should, therefore, be included in Burundi’s national food security policies.

Originality/value

This study contributes to the literature by providing empirical evidence on the effect of mobile money adoption on household food security and the choice of coping strategies in a post-conflict context.
Asymmetric thresholds of macroeconomic volatility's impact on stock volatility in developing economies: a study in Vietnam
Authors: Nguyen Lien Thi , Nguyen Minh Thi , Nguyen The Manh
Published: July 2024

Purpose

This paper examines the impact of macroeconomic volatility on stock volatility, both under normal conditions and during the COVID-19 pandemic in Vietnam.

Design/methodology/approach

We extend the existing Exponential Generalized Autoregressive Conditional Heteroskedasticity model by adding a new component: the thresholds – the levels of macroeconomic volatility at which the market may respond differently. These thresholds are estimated for both positive and negative volatility.

Findings

The impact of macroeconomic volatility on stock volatility is asymmetric: there are thresholds of macroeconomic volatility at which its pattern changes. These thresholds are higher in the case of positive volatility compared with negative volatility. The thresholds were also higher during the COVID-19 pandemic. Macroeconomic variables influence stock volatility differently depending on market conditions. While GDP is more significant in normal periods, interest rates affect it in both normal and unstable phases.

Research limitations/implications

Our models consider only two variables representing macroeconomic variables: interest rate and GDP. Furthermore, only one lag period of the variables is included in the analysis. In the future, more macrovariables and longer lags could be included when computational techniques advance.

Practical implications

Policymakers should consider the impact of macroeconomic volatility on the stock market when designing policies, especially at thresholds. Similarly, investors should pay more attention to macroeconomic volatility when constructing and managing their portfolios, particularly when such volatility is close to thresholds.

Originality/value

The inclusion of thresholds as parameters to be estimated into the model provides more insights into the impact of macroeconomic variables on stock volatility.