bluuebunny/crossref_metadata_2025 huggingface dataset:
Single cell RNA-sequencing of malaria merozoites reveals that the parasite prepares for life within the red blood cell by activating a gene network
Authors: Piel Laura , Hernandez Celine , Jaszczyszyn Yan , Naquin Delphine , Santos Joana M.
Published: September 2024

The intraerythrocytic developmental cycle (IDC) during which the malaria parasitePlasmodium falciparummultiplies asexually within the human host red blood cell is the symptomatic stage of the life cycle. The IDC initiates when parasite stages called merozoites are released into the bloodstream, following schizont rupture, and invade the host red blood cells. The merozoite is the less studied stage of the IDC, despite its importance for the establishment of infection. We did the first transcriptional profiling of merozoites throughout development inside the schizont and after egress. Merozoites within the schizont, activate a series of tightly regulated gene expression programs, each encoding for proteins implicated in a specific process required for invasion and life within the host. After schizont egress, free merozoites still express some of these programs. Upon invasion, ring cells have a distinct transcriptional profile. The gene expression programs are regulated by specific transcription factors and chromatin accessibility as well as post-transcriptional mechanisms. Our work gains unprecedent insight into gene expression prior to and during host cell invasion and identifies potential new antimalarial targets.

Author Summary

The malaria parasitePlasmodium falciparum, which causes the death of over half a million people each year, has a complex life cycle but symptoms only arise when the parasite invades and develops inside the host red blood cells. The merozoites are responsible for invading the human red blood cells but because they are only briefly extracellular, their gene expression profile had yet to be determined. Here we used single cell RNA-sequencing to establish the gene expression program of merozoites throughout development inside schizonts and once free, prior to host cell invasion. We found that, in order to prepare for invasion and life within the host cell, merozoites activate a series of gene expression programs, each encoding for proteins implicated in a specific process. While some of the genes expressed by merozoites during maturation are still expressed in free merozoites, these transcripts are no longer detected after host cell invasion. This implicates tight regulation of gene expression. We suggest that regulation implicates binding of specific transcription factors, epigenetics as well as post-transcriptional mechanisms.
Heavy-tailed statistics of cortical representational drift are advantageous for stabilised downstream readouts
Authors: Micou Charles , O’Leary Timothy
Published: September 2024

Neural representations of familiar environments and mastered tasks continue to change despite no further refinements to task performance or encoding efficiency. Downstream brain regions that depend on a steady supply of information from a neural population subject to this representational drift face a challenge: they must stabilise their readout using only statistical regularities in neural activity. Recent studies have described how representational drift induces deterioration in the accuracy of fixed decoders. Here, we highlight that while a variety of underlying statistics of drift at the level of individual neurons can produce comparable deterioration of a fixed decoder, these different statistics result in dramatically different deterioration rates in adaptive decoders. We describe an adaptive decoding strategy that can read out from a model drifting population long after fixed decoders degrade completely, and demonstrate that in simulated models this strategy is better-suited to heavy-tailed drift statistics, in which individual neurons make sudden and large changes in tuning. We investigate the extent to which these advantageous statistics manifest in experimental in-vivo measurements of drift by considering two existing and well-studied datasets that observe drift in the posterior parietal cortex and the visual cortex. We find preliminary support for sudden jumps in neural tuning that would allow a downstream observer to more easily distinguish changes in representation from noise. These observations are a step towards refining the larger picture of mechanisms underpinning the robustness of information transfer between brain regions that can function in spite of changes in representation driven both by drift and by the learning of new information.
Plasminogen Activator Inhibitor-1 is internalized by endothelial cells via macropinocytosis to evade degradation
Authors: McAdow Molly , Ahmetaj Gjina , Hauschel Rachel , Eichmann Anne , Sessa William
Published: September 2024

Plasminogen activator inhibitor1 (PAI1) promotes hemostasis and is a biomarker of cardiovascular disease but accumulating evidence supports a role for PAI1 in intracellular biology. Recently, we found that PAI1 directly inhibits endothelial nitric oxide synthase (eNOS) and that exogenous PAI1 is internalized and traffics to eNOS. However, prior work has demonstrated that when PAI1 is internalized via LRP1 and uPAR on the cell surface and is internalized and degraded. Our objective was to identify the mechanism by which PAI1 is internalized and evades degradation. Here, we show that PAI1 is internalized by endothelial cells in an energy-dependent manner and persists in the cell for at least 6 hours. Entry is independent of LRP1, uPAR, or clathrin-mediated endocytosis. It is internalized in large vesicles, is inhibited by amiloride and nocodazole, and is partially dependent on CDC42, consistent with macropinocytosis. We propose that following internalization by macropinocytosis, PAI1 evades degradation, permitting eNOS inhibition.
Identification of Human Pathways Acting on Nuclear Non-Coding RNAs Using the Mirror Forward Genetic Approach
Authors: Che Rui , Panah Monireh , Mirani Bhoomi , Knowles Krista , Ostapovich Anastacia , Majumdar Debarati , Chen Xiaotong , DeSimone Joseph , White William , Noonan Megan , Luo Hong , Alexandrov Andrei
Published: September 2024

Despite critical roles in diseases, human pathways acting on strictly nuclear non-coding RNAs have been refractory to forward genetics. To enable their forward genetic discovery, we developed a single-cell approach that “Mirrors” activities of nuclear pathways with cytoplasmic fluorescence. Application of Mirror to two nuclear pathways targeting MALAT1’s 3′ end, the pathway of its maturation and the other, the degradation pathway blocked by the triple-helical Element for Nuclear Expression (ENE), identified nearly all components of three complexes: Ribonuclease P and the RNA Exosome, including nuclear DIS3, EXOSC10, and C1D, as well as the Nuclear Exosome Targeting (NEXT) complex. Additionally, Mirror identified DEAD-box helicase DDX59 associated with the genetic disorder Oral-Facial-Digital syndrome (OFD), yet lacking known substrates or roles in nuclear RNA degradation. Knockout of DDX59 exhibits stabilization of the full-length MALAT1 with a stability-compromised ENE and increases levels of 3′-extended forms of small nuclear RNAs. It also exhibits extensive retention of minor introns, including in OFD-associated genes, suggesting a mechanism for DDX59 association with OFD. Mirror efficiently identifies pathways acting on strictly nuclear non-coding RNAs, including essential and indirectly-acting components, and, as a result, uncovers unexpected links to human disease.
Adult choline supplementation in a Down syndrome model reduces co-morbidities and improves cognition
Authors: Tallino Savannah , Etebari Rachel , McDonough Ian , Leon Hector , Sepulveda Isabella , Winslow Wendy , Bartholomew Samantha , Perez Sylvia E. , Mufson Elliott J. , Velazquez Ramon
Published: September 2024

Down syndrome (DS) is the most common cause of early-onset Alzheimer’s disease (AD). Dietary choline has been proposed as a modifiable factor to improve cognitive and pathological outcomes of AD, especially as many do not reach adequate daily intake levels. Perinatal choline supplementation (Ch+) in the Ts65Dn mouse model of DS protects offspring against AD-relevant pathology and improves cognition, and dietary Ch+ in adult AD models also ameliorates pathology and improves cognition. However, dietary Ch+ in adult Ts65Dn mice has not yet been explored. To test whether Ch+ in adulthood improves DS co-morbidities, we fed trisomic Ts65Dn mice and disomic littermate controls with either choline normal (ChN; 1.1 g/kg) or Ch+ (5 g/kg) diets from 4.5-14 months of age. We found that Ch+ improved cognitive flexibility in a reverse place preference task and reduced weight gain and peripheral inflammation in female mice, whereas Ch+ improved glucose metabolism in male mice. In conclusion, we found that adulthood Ch+ benefits behavioral and biological factors important for general well-being in DS and related to AD risk.
Evidence of genetic isolation and differentiation among historically fragmented British populations of common juniper,Juniperus communisL.
Authors: Baker J. , Cottrell J. , Ennos R. , Perry A. , A’Hara S. , Green S. , Cavers S.
Published: September 2024

Habitat fragmentation and populations isolation pose a threat to the genetic diversity and adaptability of many species. The common juniper, Juniperus communis L., a keystone species for juniper scrub habitat and one of only three conifers that are native to the UK, has been in decline for more than a century in the UK and across its European range. Remnant UK juniper populations are now highly fragmented and often small, which has raised concerns for their resilience, especially in the face of climate change and the introduction of novel pathogens, such as Phytophthora austrocedri. This work presents a baseline genetic survey of native UK juniper populations and compares patterns of diversity between populations and among three population centres in southern England, the Lake District, and Scotland using both Single Nucleotide Polymorphism (SNP) and Simple Sequence Repeat (SSR) genetic markers. The aim was to evaluate the standing genetic diversity of native juniper stands, the impacts of habitat fragmentation, and to determine whether juniper populations are genetically isolated from one another. We found that juniper populations, while not completely isolated from one another, face substantial barriers to gene flow, especially between the three population centres. These centres also show different patterns of genetic diversity, indicating varying levels of internal gene flow and inbreeding. Our findings can form a baseline from which to monitor the effectiveness of conservation activities, prioritize populations of concern, and guide genetic rescue efforts.
Complement therapeutic Factor H-IgG proteins as pre-exposure prophylaxes against Lyme borreliae infections
Authors: McKaig Connor W. , Malfetano Jill , Tran Y , Yang Xiuli , Pal Utpal , Wycoff Keith , Lin Yi-Pin
Published: September 2024

Lyme disease (LD) is the most common vector-borne disease in the northern hemisphere and is caused by the bacteriaBorrelia burgdorferisensu lato (also known as Lyme borreliae) with no effective prevention available. Lyme borreliae evade complement killing, a critical arm of host immune defense, by producing outer surface proteins that bind to a host complement inhibitor, factor H (FH). These outer surface proteins include CspA and CspZ, which bind to the 6thand 7thshort consensus repeats of FH (SCR(6-7)), and the OspE family of proteins (OspE), which bind to the 19thand 20thSCR (SCR19-20). In this study, we produced two chimeric proteins, FH-Fc, containing the Fc region of immunoglobulin G (Fc) with SCR(6-7) or SCR(19-20). We found that both FH-Fc constructs killedB. burgdorferiin the presence of complement and reduced bacterial colonization and LD-associated joint inflammationin vivo. While SCR(6-7)-Fc displayed Lyme borreliae species-specific bacterial killing, SCR(19-20)-Fc versatilely eradicated all tested bacterial species/strains. This correlated with SCR(6-7)-Fc binding to select variants of CspA and CspZ, but SCR(19-20)-Fc binding to all tested OspE variants. Overall, we demonstrated the concept of using FH-Fc constructs to kill Lyme borreliae and defined underlying mechanisms, highlighting the potential of FH-Fc as a pre-exposure prophylaxis against LD infection.

AUTHOR SUMMARY

Transmitted by ticks, Lyme disease (LD) is the most common vector-borne disease in North America and has experienced an expanded geographical range and increasing number of cases in recent years. No effective prevention is currently available. The causative agent of LD,Borrelia burgdorferisensu lato (Bbsl), is a complex containing a variety of species. To escape from killing by complement, one of the mammalian host defense mechanisms,Bbsl produces outer surface proteins that bind to a complement inhibitor, factor H (FH). These FH-binding proteins (i.e., CspA, CspZ, and OspE) evade complement by recruiting FH to the bacterial surface. Here we produced two FH-Fc fusion proteins, which combine human immunoglobulin Fc with the human FH domains that bind toBbsl FH-binding proteins. We found that FH-Fc constructs killBbslin vitroand prevent colonization and LD manifestations in murine models, correlating with these FH-Fc constructs’ ability to bind to CspA, CspZ, and OspE from respectiveBbsl species. These results suggest the possibility of using FH-Fc as a prevention against LD.
A high-content microscopy drug screening platform for regulators of the extracellular digestion of lipoprotein aggregates by macrophages
Authors: Ma Cheng-I J. , Steinfeld Noah , Wang Weixiang A. , Maxfield Frederick R.
Published: September 2024

The recruitment of macrophages to the intima of arteries is a critical event in atherosclerotic progression. These macrophages accumulate excessive lipid droplets and become “foam cells”, a hallmark of atherosclerosis. Most studies focus on lipid accumulation through macrophage interaction with modified monomeric low-density lipoprotein (LDL). However, in the intima, macrophages predominantly encounter aggregated LDL (agLDL), an interaction that has been studied far less. Macrophages digest agLDL and generate free cholesterol in an extracellular, acidic, hydrolytic compartment. They form a tight seal around agLDL through actin polymerization and deliver lysosomal contents into this space in a process termed digestive exophagy. There is some evidence that inhibiting digestive exophagy to slow cholesterol accumulation in macrophages protects them from becoming foam cells and slows the progression of atherosclerotic lesions. Thus, understanding the mechanisms of digestive exophagy is critical. Here, we describe a high-content microscopy screen on a library of repurposed drugs for compounds that inhibit lysosome exocytosis during digestive exophagy. We identified many hit compounds and further characterized the effects that five of these compounds have on various aspects of digestive exophagy. In addition, three of the five compounds do not inhibit oxidized LDL-induced foam cell formation, indicating the two pathways to foam cell formation can be targeted independently. We demonstrate that this high-content screening platform has great potential as a drug discovery tool with the ability to effectively and efficiently screen for modulators of digestive exophagy.
Myocardial disarray drives metabolic inefficiency in human cardiomyocytes
Authors: Jouve Charlène , Ruiz-Velasco Andrea , Donnarumma Erminia , Le Borgne Rémi , Momken Iman , Pereira Céline , Seguret Magali , Vermersch Eva , Vimont Elodie , Nemazanyy Ivan , Verbavatz Jean-Marc , Bertrand Luc , Wai Timothy , Mericksay Mathias , Hulot Jean-Sébastien
Published: September 2024

Adult cardiomyocytes are embedded within a highly organized myocardial microenvironment that imposes critical geometric cues essential for the alignment and distribution of organelles and the shaping of their unique, rectangular cellular morphology. Despite the association of cardiomyocyte disarray with human heart disease, the functional consequences of this cellular disorganization remain poorly understood. Here, we leveraged micropatterned substrates to promote structural alignment in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), contrasting the effects of mechanical alignment on mitochondrial form and function with hiPSC-CMs cultured under standard unconstrained conditions.

Cardiomyocytes cultured under unconstrained conditions exhibited misaligned sarcomeres and a perinuclear mitochondrial distribution while micropatterned hiPSC-CMs developed linear myofibrils and reconfigured sarcomere and mitochondrial organization, which increased mitochondrial respiration without augmenting mitochondrial mass. Notably, micropatterned hiPSC-CMs exhibited an increased number of mitochondrial-associated membranes, as determined by proximity ligation assays and transmission electron microscopy, suggesting enhanced interactions between the sarcoplasmic reticulum and mitochondria.

Together, these findings demonstrate that mitochondrial-sarcoplasmic architecture and geometry are critical spatial features that ensure bioenergetic efficiency of cardiomyocytes. This work underscores the importance of cellular organization in cardiomyocyte metabolism and function, providing insights into the pathophysiology of cardiac diseases marked by cellular disarray.
Lumen charge governs memristive ion transport in β-barrel nanopores
Authors: Mayer Simon Finn , Mitsioni Marianna , van den Heuvel Lukas , Robin Paul , Ronceray Nathan , Marcaida Maria Jose , Abriata Luciano A. , Krapp Lucien F. , Anton Jana S. , Soussou Sarah , Jeanneret-Grosjean Justin , Fulciniti Alessandro , Moller Alexia , Vacle Sarah , Feletti Lely , Brinkerhoff Henry , Laszlo Andrew H , Gundlach Jens H. , Emmerich Theo , Dal Peraro Matteo , Radenovic Aleksandra
Published: September 2024

β-barrel nanopores are involved in crucial biological processes, from ATP export in mitochondria to bacterial resistance, and represent a promising platform for emerging sequencing technologies. However, the fundamental principles governing ion transport across these nanopores remain poorly understood due to their extreme confinement and heterogeneous lumen charge. In this study, we integrate experimental, numerical, and theoretical approaches to elucidate ion transport mechanisms in these biological nanopores. We identify and characterise two distinct nonlinear phenomena: open-pore rectification and gating. Through extensive mutation analysis of aerolysin nanopores, we demonstrate that open-pore rectification is caused by ionic accumulation driven by the distribution of lumen charges. Additionally, we provide converging evidence suggesting that gating is controlled by electric fields pulling on lumen charges and controlled by local structural deformations. Our findings pave the way for the design of optimised biosensors as well as highly tunable and compact ionic memristors and diodes for biological computing applications. They also establish a rigorous framework for the characterization of biological ion transport processes.
Does strain-level persistence of lactobacilli in long term back-slopped sourdoughs inform on domestication of food-fermenting lactic acid bacteria?
Authors: Pham Vi D. , Xu Zhaohui S. , Simpson David J. , Zhang Justina S. , Gänzle Michael G.
Published: September 2024

Sourdoughs are maintained by back-slopping over long time periods. To determine strain-level persistence of bacteria, we characterized 4 sourdoughs from three bakeries over a period of 3.3, 11, 18 and 19 years. One sourdough included isolates ofLevilactobacillusspp. andFructilactobacillusspp. that differed by fewer than 10 SNPs from the isolates obtained 3.3 years earlier and thus likely represent the same strain. Isolates ofLv. parabrevisdiffered by 200 – 300 SNPs, their genomes were under positive selection, indicating transmission from an external source. In two other sourdoughs, isolates ofFl. sanfranciscensisthat were obtained 11 and 18 years apart differed by 19 and 29 SNPs, respectively, again indicating repeated isolation of the same strain. The isolate ofFl. sanfranciscensisfrom the fourth sourdough differed by 45 SNPs from the isolate obtained 19 years prior. We thus identified strain-level persistence in 3 out of 4 long-term back-slopped sourdoughs, making it possible that strains persisted over periods that are long enough to allow bacterial speciation and domestication.

Importance

The assembly of microbial communities in sourdough is shaped by dispersal and selection. Speciation and domestication of fermentation microbes in back-slopped food fermentations has been documented for food fermenting fungi including sourdough yeasts but not for bacteria, which evolve at a slower rate. Bacterial speciation in food fermentations requires strain-level persistence of fermentation microbes over hundreds or thousands of years. By documenting strain-level persistence in three out of four sourdoughs over a period of up to 18 years, we demonstrate that persistence over hundreds or thousands of years is possible. We thus not only open a new perspective on fermentation control in bakeries but also support the possibility that all humans, despite their cultural diversity, share the same fermentation microbes.
Polycomb-mediated transgenerational epigenetic inheritance of Drosophila eye colour is independent of small RNAs
Authors: Fitz-James Maximilian H. , Sparrow Poppy , Paton Christopher , Sarkies Peter
Published: September 2024

Transgenerational epigenetic inheritance (TEI) describes the process where distinct epigenetic states may be transmitted between generations, resulting in stable gene expression and phenotypic differences between individuals that persist independently of DNA sequence variation. Chromatin modifications have been demonstrated as important in TEI, however, the extent to which they require other signals to establish and maintain epigenetic states is still unclear. Here we investigate whether small non-coding RNAs contribute to different epigenetic states of the Fab2L transgene inDrosophilatriggered by transient chromatin contacts, which requires Polycomb complex activity to deposit the H3K27me3 modification for long-term TEI. Using mutants deficient in known small non-coding RNAs, high throughput sequencing, investigation of chromatin conformation and gene expression analysis we demonstrate that small non-coding RNAs do not contribute directly to initiation or maintenance of silencing. However, we uncover an indirect role for microRNA expression in transgene silencing through effects on Polycomb complex expression. Additionally, we show that a commonly used marker gene,Stubble(Sb), affects Polycomb complex expression, which may be important in interpreting experiments assaying Polycomb function inDrosophiladevelopment. By ruling out a plausible candidate for TEI at the Fab2L transgene our work highlights the variability in different modes of TEI across species.
Longitudinal evidence for the emergence of multiple intelligences in assistance dog puppies
Authors: Salomons Hannah , Ferrans Morgan , Cusato Candler , Moore Kara , Woods Vanessa , Bray Emily , Kennedy Brenda , Block Theadora , Douglas Laura , Roberts Ashton , Gruen Margaret , Hare Brian
Published: September 2024

Cognitive test batteries suggest that adult dogs have different types of cognitive abilities that vary independently. In the current study, we tested puppies repeatedly over a crucial period of development to explore the timing and rate at which these different cognitive skills develop. Service dog puppies (n = 113), raised using two different socialization strategies, were either tested longitudinally (n =91) or at a single time point (n = 22). Subjects tested longitudinally participated in the battery every two weeks during and just beyond their final period of rapid brain growth (from approximately 8-20 weeks of age). Control puppies only participated in the test battery once, which allowed us to evaluate the impact of repeated testing. In support of the multiple intelligences hypothesis (MIH), cognitive skills emerged at different points across the testing period, not simultaneously. Maturational patterns also varied between cognitive skills, with puppies showing adult-like performance on some tasks only weeks after a skill emerged, while never achieving adult performance in others. Differences in rearing strategy did not lead to differences in developmental patterns while, in some cases, repeated testing did. Overall, our findings provide strong support for the MIH by demonstrating differentiated development across the cognitive abilities tested.
Bioinformatic discovery of type 11 secretion system (T11SS) cargo across the Proteobacteria
Authors: Grossman Alex S. , Mucci Nicholas C , Goodrich-Blair Heidi
Published: September 2024

Type 11 secretion systems (T11SS) are broadly distributed among proteobacteria, with more than 3000 T11SS family outer membrane proteins (OMPs) comprising 10 major sequence similarity network (SSN) clusters. Of these, only 7, all from animal-associated cluster 1, have been experimentally verified as secretins of cargo, including adhesins, hemophores, and metal binding proteins. To identify novel cargo of a more diverse set of T11SS, we identified gene families co-occurring in gene neighborhoods with either cluster 1 or marine microbe-associated cluster 3 T11SS OMP genes. We developed bioinformatic controls to ensure perceived co-occurrences are specific to T11SS, and not general to OMPs. We found that both cluster 1 and cluster 3 T11SS OMPs frequently co-occur with single carbon metabolism and nucleotide synthesis pathways, but that only cluster 1 T11SS OMPs had significant co-occurrence with metal and heme pathways, as well as with mobile genetic islands, potentially indicating diversified function of this cluster. Cluster 1 T11SS co-occurrences included 2556 predicted cargo proteins, unified by the presence of a C-terminal β-barrel domain, which fall into 141 predicted UniRef50 clusters and approximately 10 different architectures: 4 similar to known cargo and 6 uncharacterized types. We experimentally demonstrate T11SS-dependent secretion of an uncharacterized cargo type with homology to Plasmin sensitive protein (Pls). Unexpectedly, genes encoding marine cluster 3 T11SS OMPs only rarely co-occurred with the C-terminal β-barrel domain and instead frequently co-occurred with DUF1194-containing genes. Overall, our results show that with sufficiently large-scale and controlled genomic data, T11SS-dependent cargo proteins can be accurately predicted.
Penicillin-binding proteins exhibit catalytic redundancy during asymmetric cell division inClostridioides difficile
Authors: Shrestha Shailab , Dressler Jules M. , McNellis Morgan E. , Shen Aimee
Published: September 2024

Peptidoglycan synthesis is an essential driver of bacterial growth and division. The final steps of this crucial process involve the activity of SEDS family glycosyltransferases that polymerize glycan strands and class B penicillin-binding protein (bPBP) transpeptidases that cross-link them. While most bacteria encode multiple bPBPs that perform specialized roles during specific cellular processes, some bPBPs can play redundant roles that are important for resistance against certain cell wall stresses. Our understanding of these compensatory mechanisms, however, remains incomplete. Endospore-forming bacteria typically encode multiple bPBPs that drive morphological changes required for sporulation. The sporulation-specific bPBP, SpoVD, is important for synthesizing the asymmetric division septum and spore cortex peptidoglycan during sporulation in the pathogenClostridioides difficile. Although SpoVD catalytic activity is essential for cortex synthesis, we show that it is unexpectedly dispensable for SpoVD to mediate asymmetric division. The dispensability of SpoVD’s catalytic activity requires the presence of its SEDS partner, SpoVE, and is facilitated by the catalytic activity of another sporulation-specific bPBP, PBP3. Our data further suggest that PBP3 interacts with components of the asymmetric division machinery, including SpoVD. These findings suggest a possible mechanism by which bPBPs can be functionally redundant in diverse bacteria and facilitate antibiotic resistance.
Impact of carbamate and pyrethroid pesticides on bile acid profiles in an in vitro gut microbiota model
Authors: Zheng Weijia , Bakker Wouter , Jin Maojun , Wang Jing , Rietjens Ivonne
Published: September 2024

The impact on the microbial community following exposure to commonly used pesticides has recently gained increasing interest. In this study, effects of selected carbamates (carbofuran, aldicarb) and pyrethroids (cypermethrin and cyhalothrin) on gut microbiota and related bile acid metabolism were quantified using a 24 h in vitro fermentation model system with mice feces. The results obtained reveal a pesticide induced significant increase the ratio of secondary over primary bile acids, particularly resulting from the enrichment of β-muricholate (βMCA) accompanied by the depletion of ω-muricholate (ωMCA). Besides, the bacterial profile showed significantly increased richness of Eggerthellaceae after 24 h exposure to carbofuran and cyhalothrin, and the genera Enterorhabdus belonging to Eggerthellaceae was found to be highly correlated to the fecal bile acid profile. In conclusion, in an in vitro gut microbial model carbamates and pyrethroids caused alterations of the gut microbial community resulting in the modulation of bile acid transformation. This illustrates that the gut microbiota and its metabolism may be a novel target to consider in future pesticide safety evaluations.
Hypothalamic connectivities and self-evaluated aggression in young adults
Authors: Yao Yuxing Jared , Chen Yu , Li Chiang-Shan R.
Published: September 2024

Introduction

The hypothalamus plays a pivotal role in supporting motivated behavior, including aggression. Previous work suggested differential roles of the medial hypothalamus (MH) and lateral hypothalamus (LH) in aggressive behaviors, but little is known about how their resting-state functional connectivity (rsFC) may relate to aggression in humans.

Methods

We employed the data from the Human Connectome Project (HCP) and examined the rsFC’s of LH and MH in 745 young adults (393 women). We also explored sex differences in the rsFC’s. We processed the imaging data with published routines and evaluated the results of voxel-wise regression on aggression score, as obtained from Achenbach Adult Self Report, with a corrected threshold.

Results

The analysis revealed significant rsFC between the LH and clusters in the middle temporal and occipital gyri across all subjects and in the thalamus for men, both in negative correlation with aggression score. Slope test confirmed sex differences in the correlation between LH-thalamus rsFC and aggression score. No significant rsFC was observed for MH.

Conclusions

These findings suggest a role of LH rsFCs and sex differences in LH-thalamus rsFC in the manifestation of aggression in humans. The findings highlight the need for further research into sex-specific neural pathways in aggression and other related behavioral traits of importance to mental health.
An unusual activity of mycobacterial MutT1 Nudix hydrolase domain as a protein phosphatase regulates nucleoside diphosphate kinase (NDK) function
Authors: Emam Elhassan Ali Fathi , Roy Koyel , Singh Devendra Pratap , Saini Deepak K , Varshney Umesh
Published: September 2024

MutT proteins are Nudix hydrolases characterized by the presence of a Nudix box, GX5EX7REUXEEXGU, where U is a bulky hydrophobic residue and X is any residue. Major MutT proteins hydrolyse 8-oxo-(d)GTP (8-oxo-GTP or 8-oxo-dGTP) to the corresponding 8-oxo-(d)GMP, preventing their incorporation into nucleic acids. Mycobacterial MutT1 comprises an N-terminal domain (NTD) harbouring the Nudix box motif, and a C-terminal domain (CTD) harbouring the RHG histidine phosphatase motif. Interestingly, unlike other MutTs, the MutT1 hydrolyses the mutagenic 8-oxo-(d)GTP to corresponding 8-oxo-(d)GDP. Nucleoside diphosphate kinase (NDK), a conserved protein, carries out reversible conversion of (d)NDPs to (d)NTPs through phospho-NDK (NDK-Pi) intermediate. Recently, we showed that NDK-Piconverts 8-oxo-dGDP to 8-oxo-dGTP and escalates A to C mutations in a MutT deficientEscherichia coli. We now show that bothMycobacterium tuberculosisMutT1, andM. smegmatisMutT1, through their NTD (Nudix hydrolase motifs) function as protein phosphatase to regulate the levels of NDK-Pito NDK and prevent it from catalysing conversion of (d)NDPs to (d)NTPs (including conversion of 8-oxo-dGDP to 8-oxo-dGTP). To corroborate this function, we show thatMsmMutT1 decreases A to C mutations inE. coliunder the conditions ofEcoNDK overexpression.

Importance

MutT proteins, having a Nudix box domain, hydrolyse the mutagenic 8-oxo-dGTP to 8-oxo-dGMP. However, mycobacterial MutT (MutT1) comprises an N-terminal domain (NTD) harboring a Nudix box, and a C-terminal domain (CTD) harboring an RHG histidine phosphatase. Unlike other MutTs, mycobaterial MutT1 hydrolyses 8-oxo-dGTP to 8-oxo-dGDP. Nucleoside diphosphate kinase (NDK), a conserved protein, converts 8-oxo-dGDP to 8-oxo-dGTP through phospho-NDK (NDK-Pi) intermediate, and escalates A to C mutations. Here, we show that the mycobacterial MutT1 is unprecedented in that its NTD (Nudix box), functions as protein phosphatase to regulate NDK-Pilevels and prevents it from converting dNDPs to dNTPs (including 8-oxo-dGDP to 8-oxo-dGTP conversion). In addition, mycobacterial MutT1 decreases A to C mutations inEscherichia coliunder the conditions of NDK overexpression.
Study of possible
DND*
bound states
Authors: Montesinos Victor , Song Jing , Liang Wei-Hong , Oset Eulogio , Nieves Juan , Albaladejo Miguel
Published: September 2024

We start from a recently favored picture in which the Λc(2940) and Λc(2910) correspond mostly to ND* bound states with JP=1/2−,3/2− respectively, and then add a D as a third particle, looking for the possible binding of the DND* three-body system within the framework of the fixed center approximation. We find that the system is bound with respect to the corresponding Λc(2940)D, Λc(2910)D thresholds with a binding of about 60 MeV and a width of about 90 MeV. Alternatively we assume a cluster of ND and a D* meson interacting with the cluster, and we find similar results. The observation of these states of JP=1/2+,3/2+ would provide new and valuable information concerning the DN and D*N interaction, an issue of current debate.

Published by the American Physical Society
2024
Revisiting
C
and
CP
violation in
η→π+π−π0
decay
Authors: Shi Jun , Liang Jian , Gardner Susan
Published: September 2024

The decay η→π+π−π0 is an ideal process in which to study flavor-conserving C and CP violation beyond the Standard Model. We deduce the C- and CP-odd quark operators that contribute to η→π+π−π0 originating from the mass-dimension-six Standard Model effective field theory. The corresponding hadron-level operators that generate a nonvanishing I=0 amplitude at order p6 in the chiral effective theory are presented for the first time, to the best of our knowledge, in addition to the leading-order operators ascribed to the I=2 final state. By fitting the KLOE-2 and the most recent BESIII experimental data, we determine the coefficients of the lowest-order I=0 and I=2 amplitudes and estimate the potential new physics energy scale. We also perform an impact study of the future η→π+π−π0 experiments.

Published by the American Physical Society
2024
Foodtech in motion: innovation and digitalisation of the food service sector in the post-pandemic Spain
Authors: Castillo Cristian , Viu-Roig Marta , Alvarez-Palau Eduard J. , Gottardello Debora
Published: September 2024

Purpose

This research comprehensively analyses the profound impact of Digital Transformation and Process Innovation (DT&PI) on business models (BMs) in the Food Service Sector (FSS), especially in the post-pandemic context. The study is guided by three primary research questions: (1) Identifying key FSS players and their interconnections, (2) Understanding the differentiation strategies these entities employ and (3) Assessing how COVID-19 has altered their BMs.

Design/methodology/approach

The study utilises a rigorous methodology, starting with a thorough analysis of the Business Model Canvas (BMC) for 100 prominent Spanish FSS firms, culminating in a comprehensive sector-wide BMC. Cluster analysis is then applied to group firms based on common attributes and relationships identified in the overall BMC. Additional insights are gathered through semi-structured interviews with representatives from FSS companies.

Findings

The study identifies five distinct clusters of FSS companies, each defined by unique BM strategies. These strategies mainly focus on sales and distribution channels, differentiating between those using multiple channels and those solely relying on digital platforms. Importantly, the study shows that digital transformation in the FSS was already in progress before the pandemic but was greatly expedited by it. COVID-19 stimulated the digitalisation of services, expanding sales channels and diversifying customer engagement.

Originality/value

This research enriches the dynamic capabilities theory by examining how DT&PI influence BM innovation in the FSS, highlighting adaptation to technological trends. It offers a fresh perspective on value creation and stakeholder interaction, contributing to the foundational theory for future FSS BM research.
Competing construals in advertising: the central role of feeling closer to the brand versus closer to other brand users
Authors: Bauer Brittney C.
Published: September 2024

Purpose

While consumer–brand relationships bring to mind commonalities such as shared interests and values, the way consumers construe information can differ depending on the situation and their connections to the brand. This study aims to propose that construal level impacts how consumers process information and looks at how two dimensions of psychological distance affect the persuasiveness of different types of advertising appeals.

Design/methodology/approach

Four experimental studies test the singular effects that social and temporal distance construals have on the persuasiveness of advertising appeals. This research further investigates whether social distance construals can be situationally primed and matched with advertising appeals to improve willingness to pay. Overall, the combined effects are tested when both dimensions are simultaneously activated, but the valence of the construal levels potentially moves in opposite directions.

Findings

Studies 1 and 3 find that matching social distance construals and advertising appeals positively impacts willingness to pay, whereas Study 2 reveals that matching temporal distance construals and advertising appeals also positively effects willingness to pay. Furthermore, Study 4 finds that the social distance dimension has a more dominant impact on willingness to pay, except in near future scenarios when there are combined effects of competing construals.

Research limitations/implications

This research indicates that initial social distance construals are more salient than subsequent temporal distance construals.

Practical implications

This study helps marketers to identify the most effective advertising appeals for consumers with different types of relationships and psychological distance construals.

Originality/value

This study contributes to both theory and practice by extending knowledge of which types of construals are more salient when competing construals are triggered and by helping marketers identify the most effective advertising appeals for consumers under these different conditions.
A comparative analysis of after-stitch strength reduction in sewing threads across woven, nonwoven and composite fabric assemblies
Authors: Chavhan Md Vaseem
Published: September 2024

Purpose

This study aims to investigate the factors influencing the reduction in strength of sewing threads after stitching (after-stitch strength reduction) in different fabric assemblies, including nonwoven fabrics. This research expands upon previous studies, which primarily focused on woven fabrics.

Design/methodology/approach

A full-factorial experimental design was employed, considering three factors: fabric assembly type (woven, nonwoven, composite), yarn type (spun polyester, core-spun polyester) and thread count (30 Tex, 60 Tex). Also, the stitching parameters stitch density (3 spc, 5 spc) and needle count (75 Nm, 100 Nm) were considered. The predictive regression model was also developed with a second-degree order. Tensile testing was conducted on unravelled threads before and after stitching to assess strength reduction.

Findings

Fabric assembly type significantly impacted after-stitch strength reduction, with the composite assembly exhibiting the highest reduction. Yarn type played a crucial role in the composite assembly; core-spun yarn experienced higher strength reduction compared to spun polyester yarn. Thread count consistently affected strength reduction across all fabric assemblies, with finer threads experiencing higher reductions. Stitch density generally had a positive correlation with strength reduction for woven and nonwoven assemblies, but no significant difference was observed in the composite assembly. Needle count did not significantly impact strength reduction for any fabric assembly.

Practical implications

The findings can guide the selection of appropriate sewing threads, yarn types and sewing parameters for different fabric assemblies, including nonwoven fabrics, to optimize seam performance and garment durability.

Originality/value

This study contributes to the understanding of how fabric structure, yarn characteristics and sewing parameters interact to influence sewing thread strength reduction in diverse fabric assemblies, including nonwoven fabrics, which were not previously considered in similar studies. This broader investigation provides valuable insights applicable to a wider range of sewing applications.
Online education – bane or boon? A quantitative plus text mining approach
Authors: Ghosh Arpita , Patra Pradipta
Published: September 2024

Purpose

The COVID-19 pandemic and its aftermath sent the entire educational system across the globe topsy-turvy. Virtual classrooms, online lectures and online evaluations became the order of the day, replacing traditional face to face classroom interactions and examinations conducted physically. While it may be possible to reach out to a larger audience in remote places via online platforms, the new medium lacks personal touch of the past, and is known to cause physical and psychological problems for participants. This study collects primary data from a representative sample of students from emerging economies to study the factors that influence intention to pursue online education.

Design/methodology/approach

ANOVA, Kruskal–Wallis test, exploratory factor analysis (EFA) and multiple linear regression (MLR) have been used to test our hypothesis. We have also used text mining to corroborate statistical test results and ascertain the sentiment of students towards online learning.

Findings

This study not only confirms findings in extant literature that “benefits” is an important factor. It also identifies new factors such as “health”, “evaluation”, “class duration” and “student qualification”, that influence student intention to pursue online education. Sentiment analysis shows that students have positive sentiment coupled with trust towards online education. Text mining shows that “mode of class”, “time or duration of class” and “quality of learning” are important features that students consider.

Originality/value

This is one of the few studies to use quantitative plus text mining method of research to understand intention to pursue online education.
Culture for climate action in Jodhpur: reversing the trajectory from fragility to resilience
Authors: Kanji Repaul , Madapala Jeevan , Sil Sriparna
Published: September 2024

Purpose

This paper documents the outcomes of a year-long intervention designed to address climate challenges in Jodhpur, India. The intervention employed a phased approach that combined traditional knowledge, innovative communication strategies and youth engagement. The question guiding the interventions was: Can traditional knowledge, indigenous practices and place-based wisdom be used for risk-informed sustainable development?

Design/methodology/approach

The project utilised a mixed methods approach to achieve its goals. A documentary titled “Sanchay” was produced, capturing the perspectives of Jodhpur residents on climate risks. An architectural analysis of traditional houses was conducted to identify and understand their inherent climate-smart features. Immersive workshops engaged young minds in exploring climate change through creative expression, equipping them with the knowledge and skills to become agents of change.

Findings

“Sanchay” serves as a novel method for understanding risk through the lens of citizen narratives, offering a valuable complement to traditional top-down risk assessment methods. The architectural report provides evidence for integrating traditional knowledge into sustainable construction practices. The immersive workshops empowered young people to become agents of change within their communities. Finally, the capacity building initiatives strengthened the human resource base for future climate action efforts

Originality/value

This project introduces a novel method for understanding risk through participatory storytelling, centred on the lived experiences of community members. It demonstrates the efficacy of combining traditional knowledge with science and technology for climate action.
Internal marketing orientation and employee innovative behaviour: the mediating role of workforce agility and moderating role of psychological empowerment
Authors: Sackey Baaba Boadziwa , Yang Jingzhao , Quansah Prince Ewudzie , Ekumah Christian Afanyi , Arboh Francisca , Boadu Bright
Published: September 2024

Purpose

The study examined the influence of internal marketing orientation on employees’ innovative behaviour through the mediating role of workforce agility and the moderating role of psychological empowerment.

Design/methodology/approach

We collected 731 valid responses from frontline employees in the hospitality industry in Ghana. The data were analysed using hierarchical regression analysis in SPSS.

Findings

The findings show that internal marketing orientation significantly influenced workforce agility and innovative behaviour. Also, workforce agility significantly influenced employee innovative behaviour. Again, the study found that workforce agility partially mediated the relationship between internal marketing orientation and employee innovative behaviour. Psychological empowerment significantly moderated the relationship between workforce agility and employees innovative behaviour.

Practical implications

In order to promote agile behaviour and enhance innovative thinking when assigning tasks for company products and services, organisations should develop and implement suitable internal marketing orientation programmes and policies regarding opportunities for career growth, promotion and advancement.

Originality/value

This study offers timely empirical insights into how organisations can promote employee innovation, particularly in the hospitality sector, where human capital is imperative for service excellence and competitiveness.