bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACTLyme 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 SUMMARYTransmitted 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

AbstractThe 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

AbstractAdult 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.
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

AbstractSourdoughs 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.ImportanceThe 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

AbstractTransgenerational 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

AbstractCognitive 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.
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

AbstractPeptidoglycan 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.
Hypothalamic connectivities and self-evaluated aggression in young adults
Authors: Yao Yuxing Jared , Chen Yu , Li Chiang-Shan R. 
Published: September 2024

AbstractIntroductionThe 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.MethodsWe 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.ResultsThe 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.ConclusionsThese 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

AbstractMutT 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.ImportanceMutT 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
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

PurposeThis 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/approachThe 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.FindingsThe 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/valueThis 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.