bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geometric tortuosity at invaginating rod synapses slows glutamate diffusion and shapes synaptic responses: insights from anatomically realistic Monte Carlo simulations
Authors: Thoreson Wallace B. , Bartol Thomas M. , Conoan Nicholas H. , Diamond Jeffrey S. 
Published: October 2024

AbstractAt the first synapse in the vertebrate retina, rod photoreceptor terminals form deep invaginations occupied by multiple second-order rod bipolar and horizontal cell (RBP and HC) dendrites. Synaptic vesicles are released into this invagination at multiple sites beneath an elongated presynaptic ribbon. We investigated the impact of this complex architecture on the diffusion of synaptic glutamate and activity of postsynaptic receptors. We obtained serial electron micrographs of mouse retina and reconstructed four rod terminals along with their postsynaptic RBP and HC dendrites. We incorporated these structures into an anatomically realistic Monte Carlo simulation of neurotransmitter diffusion and receptor activation. We compared passive diffusion of glutamate in these realistic structures to existing, geometrically simplified models of the synapse and found that glutamate exits anatomically realistic synapses ten times more slowly than previously predicted. By comparing simulations with electrophysiological recordings, we modeled synaptic activation of EAAT5 glutamate transporters in rods, AMPA receptors on HC dendrites, and metabotropic glutamate receptors (mGluR6) on RRBP dendrites. Our simulations suggested that ~3,000 EAAT5 transporters populate the rod presynaptic membrane and that, while uptake by surrounding glial Müller cells retrieves much of the glutamate released by rods, binding and uptake by EAAT5 influences RBP response kinetics. The long lifetime of glutamate within the cleft allows mGluR6 on RBP dendrites to temporally integrate the steady stream of vesicles released at this synapse in darkness. Glutamate’s tortuous diffusional path through realistic synaptic geometry confers quantal variability, as release from nearby ribbon sites exerts larger effects on RBP and HC receptors than release from more distant sites. While greater integration may allow slower sustained release rates, added quantal variability complicates the challenging task of detecting brief decreases in release produced by rod light responses at scotopic threshold.
Specific origin selection and excess functional MCM2-7 loading in ORC-deficient cells
Authors: Shibata Yoshiyuki , Peycheva Mihaela , Shibata Etsuko , Malzl Daniel , Pavri Rushad , Dutta Anindya 
Published: October 2024

ABSTRACTThe six subunit Origin Recognition Complex (ORC) loads excess MCM2-7 on chromosomes to promote initiation of DNA replication and is believed to be important for origin specification. Mapping of origins in cancer cell lines engineered to delete three of the subunits,ORC1,ORC2orORC5shows that specific origins are still used and are mostly at the same sites in the genome as in wild type cells. The few thousand origins that were up-regulated in the absence of ORC suggest that GC/TA skewness and simple repeat sequences facilitate, but are not essential for, origin selection in the absence of the six-subunit ORC. Despite the lack of ORC, excess MCM2-7 is still loaded at comparable rates in G1 phase to license dormant origins and is also repeatedly loaded in the same S phase to permit re-replication. Thus, origin specification and excess MCM2-7 loading on origins do not require the six-subunit ORC in human cancer cell lines.
The Causal Role of Beta Band Desynchronization: Individualized High-Definition Transcranial Alternating Current Stimulation Improves Bimanual Motor Control
Authors: Van Hoornweder Sybren , Mora Diego Andres Blanco , Nuyts Marten , Cuypers Koen , Verstraelen Stefanie , Meesen Raf 
Published: October 2024

ABSTRACTObjectiveTo unveil if 3 mA peak-to-peak high-definition β transcranial alternating current stimulation (tACS) applied over C4 –the area overlaying the right sensorimotor cortex– enhances bimanual motor control and affects movement-related β desynchronization (MRβD), thereby providing causal evidence for the polymorphic role of MRβD in motor control.MethodsIn this sham-controlled, crossover study, 36 participants underwent 20 minutes of fixed 20 Hz tACS; tACS individualized to peak β activity during motor planning at baseline; and sham tACS randomized over three consecutive days. Before, during, and after tACS, participants performed a bimanual tracking task (BTT) and 64-channel electroencephalography (EEG) data was measured. Spatiotemporal and temporal clustering statistics with underlying linear mixed effect models were used to test our hypotheses.ResultsIndividualized tACS significantly improved bimanual motor control, both online and offline, and increased online MRβD during motor planning compared to fixed tACS. No offline effects of fixed and individualized tACS on MRβD were found compared to sham, although tACS effects did trend towards the hypothesized MRβD increase. Throughout the course of the study, MRβD and bimanual motor performance improved. Exclusively during motor planning, MRβD was positively associated to bimanual motor performance improvements, emphasizing the functionally polymorphic role of MRβD. tACS was well tolerated and no side-effects occurred.ConclusionIndividualized β-tACS improves bimanual motor control and enhances motor planning MRβD online. These findings provide causal evidence for the importance of MRβD when planning complex motor behavior.
Herpes simplex virus type 1 origin binding protein UL9 tethers and loops origin- and non-origin-DNA intra- and intermolecularly
Authors: Meier Anita F. , Vuckovic Jan , Girvan Paul , Cutts Erin , Brophy Theodora , Ambrose Benjamin , Rueda David S. 
Published: October 2024

AbstractHerpesviruses are ubiquitous human pathogens, which are the causative agent of mild to severe symptoms ranging from cold sore to nasopharyngeal carcinoma. Even though replication of the linear dsDNA genome has been studied for decades, we still lack a complete molecular understanding of its mechanism. It has been proposed, but never shown directly, that the HSV-1 origin binding protein UL9 binds two closely located binding sites within the oriS origin sequence, thereby mediating origin looping, which in turn facilitates replication initiation. Here, we used an array of single-molecule approaches to test this long-standing hypothesis directly. Surprisingly, the data show that UL9 does not loop oriS efficiently. However, we demonstrate that UL9 can form large DNA loops at non-origin sequences very efficiently, as well as tether two oriS DNA molecules intermolecularly. Contrary to the origin bending hypothesis, our findings indicate that UL9 does not loop oriS DNA, but rather may play an alternative role in replication initiation, such as tethering two separate molecules to facilitate recombination.
Biosynthesis of mitis group streptococcal glycolipids and their roles in physiology and antibiotic susceptibility
Authors: Wei Yahan , Chen Guan H. , Yaqub Muneer , Kim Elice , Tillett Lily E , Joyce Luke R. , Dillon Nicholas , Palmer Kelli L. , Guan Ziqiang 
Published: October 2024

AbstractBacterial cell surface components such as lipoteichoic acids (LTAs) play critical roles in host-microbe interactions and alter host responses based on their chemical structures. Mitis group streptococci have commensal and pathogenic interactions with the human host and produce Type IV LTAs that are slightly different in chemical structures between species. To reveal the molecular bases for the intricate interactions between MGS and human hosts, a detailed understanding of the structure and biosynthetic process of MGS LTAs is needed. In this study, we used genomic and lipidomic techniques to elucidate the biosynthetic processes of Type IV LTA and its associated glycolipid anchors, monohexosyl-diacylglycerol and dihexosyl-diacyglycerol, in the infectious endocarditis isolateStreptococcussp. strain 1643. Through establishing a murine sepsis model, we validated the essentiality of these glycolipids in the full virulence ofS. mitis. Additionally, we found that these glycolipids play an important role in protecting the bacteria from antimicrobials. Overall, results obtained through this study both confirm and dispute aspects of the existing model of glycolipids biosynthesis, provide insights into the fundamental roles of bacterial glycolipids, as well as suggest the potential of targeting glycolipids for developing antimicrobial therapeutics.Significance/ImportanceGlycolipids and glycolipid-anchored LTAs are common and essential membrane components in Gram-positive bacteria. Yet, the biosynthesis and functions of LTAs have not been fully understood for many significant Gram-positive pathogens. Through genomic, lipidomic, and animal infection model analyses, as well as antimicrobial susceptibility assays, this study advances our understanding of Type IV LTA biosynthesis and the physiological roles of glycolipids in mitis group streptococci. Overall, our work establishes the essentiality of glycolipids in both bacterial virulence and defense against antimicrobials.
Rod inputs arrive at horizontal cell somas in mouse retina solely via rod-cone coupling
Authors: Thoreson Wallace B. , Sladek Asia L. , Barta Cody L. , Townsend Lou E. 
Published: October 2024

AbstractRod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed to allow spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. Because of spectral overlap between rod and cone visual pigments in mouse, we analyzed photoreceptor inputs into horizontal somata by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somata. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knockout of the exocytotic calcium sensor, synaptotagmin 1. However, rod-driven responses in horizontal somata were unchanged after eliminating synaptic release from rods but abolished by eliminating release from both rods and cones. This suggests that cones transmit rod signals that arrive via rod-cone gap junctions. Consistent with this, eliminating Cx36 gap junctions between rods and cones also abolished rod-driven optogenetic responses in horizontal cell somata. These results show that rod signals reach the somas of B-type horizontal cells exclusively via gap junctions with cones and not by traveling down the axon from the axon terminal.SignificanceRods and cones contact different compartments of retinal horizontal cells: cones contact the soma whereas rods contact a large axon terminal. Cone signals can travel through the axon from soma to terminal, but it is not clear whether rod signals travel the other direction. This latter pathway has been proposed to mediate opponent interactions between rods and cones that could shape vision in dim lights. However, our results show that rod signals cannot travel from axon terminal to soma, but mix with cone signals via gap junctions between the two cell types. This finding limits mechanisms for explaining opponent rod-cone interactions in color and contrast perception.
BROADband brain Network Estimation via Source Separation (BROAD-NESS)
Authors: Bonetti L. , Fernández-Rubio G. , Andersen M. H. , Malvaso C. , Carlomagno F. , Testa C. , Vuust P. , Kringelbach M. L. , Rosso M. 
Published: October 2024

ABSTRACTThis study presents BROADband brain Network Estimation via Source Separation (BROAD- NESS), a novel method tailored for event-related designs, leveraging magnetoencephalography’s (MEG) high temporal and spatial resolution to identify dynamic brain networks without predefined regions. By applying principal component analysis (PCA) to source-reconstructed MEG data from 83 participants in a long-term musical sequence recognition task, BROAD-NESS captured event-related networks more effectively than traditional approaches, revealing two main networks that explained 88% of the variance. The first network, involving the auditory cortices and medial cingulate gyrus, was associated with continuous auditory processing. The second network, encompassing prefrontal and hippocampal regions, inferior temporal cortex, and insula, was linked to memory, confirmed predictions and prediction error processing. With limited computational demands and minimal assumptions, BROAD-NESS offers a powerful tool for studying event-related brain dynamics, enhancing understanding of memory-related networks in recognition of temporal sequences.
Expression of Osteopontin in M2 and M4 intrinsically photosensitive retinal ganglion cells
Authors: Kinder Leonie , Lindner Moritz 
Published: October 2024

AbstractPurposeMelanopsin-expressing intrinsically photosensitive (ip) retinal ganglion cells (RGC) can be divided into six different subtypes (M1 – M6). Yet, only for some of these subtypes specific markers exist that could be employed to study of the function of individual subtypes. Osteopontin (Spp1) marks alpha(α)-RGC, suggesting that, across ipRGC, it would only mark the M4-ipRGC subtype (synonymous to: ON-sustained-αRGC). Recent evidence suggests that osteopontin expression could spread to other ipRGC subtypes. Therefore, this study aims to characterise the expression pattern of osteopontin across ipRGC subtypes.MethodsSingle-cell RNA sequencing data from RGC were analysed to identify expression patterns ofSpp1across ipRGC. Immunohistochemistry (IHC) was performed on retinal cryosections and flatmounts from C57BL/6J mice to characterize the localization of osteopontin across ipRGC. Neurite tracing was employed to study dendritic morphology and identify individual ipRGC subtypes.ResultsscRNAseq analysis revealedSpp1expression in two distinct clusters of ipRGC. IHC confirmed osteopontin co-localization with Smi-32, an established marker for αRGC, including M4-ipRGCs. Spp1 immunoreactivity was moreover identified in one additional group of ipRGC. By dendritic morphology and stratification those cells were clearly identified as M2-ipRGC.ConclusionsOur findings demonstrate that osteopontin is expressed in both M2- and M4-ipRGC, challenging the notion of osteopontin as a marker exclusively for αRGC. IHC double-labelling for osteopontin and melanopsin provides a novel method to identify and differentiate M2 ipRGC from other subtypes. This will support the study ipRGC physiology in a subtype specific manner and may for instance foster research in the field of optic nerve injury.
Autodetachment of Diatomic Carbon Anions from Long-Lived High-Rotation Quartet States
Authors: Schmidt Viviane C. , Čurík Roman , Ončák Milan , Blaum Klaus , George Sebastian , Göck Jürgen , Grieser Manfred , Grussie Florian , von Hahn Robert , Krantz Claude , Kreckel Holger , Novotný Oldřich , Spruck Kaija , Wolf Andreas 
Published: October 2024

We show that strong molecular rotation drastically modifies the autodetachment of C2− ions in the lowest quartet electronic state aΣu+4. In the strong-rotation regime, levels of this state only decay by a process termed “rotationally assisted” autodetachment, whose theoretical description is worked out based on the nonlocal resonance model. For autodetachment linked with the exchange of six rotational quanta, the results reproduce a prominent, hitherto unexplained electron emission signal with a mean decay time near 3 ms, observed on stored C2− ions from a hot ion source.

Published by the American Physical Society
2024
The trajectory of artificial intelligence for competency-based personalised learning: past, present and future
Authors: Dastane Omkar , Turner Jason , Nankervis Alan 
Published: October 2024

PurposeThe study aims to reflect on past research, uncover current trends and propose a future research agenda in the field of artificial intelligence (AI) for competency-based personalised learning.Design/methodology/approachThe study followed the SPAR-4-SLR protocol to retrieve 855 articles related to the field indexed in the Scopus database. Performance analysis, network analysis and science mapping were then performed using VOSviewer and the Biblioshiny app.FindingsThe analysis identified nine clusters of intellectual structure (healthcare, competencies, learning systems, digital transformation, AI literacy, computer-aided education, AI ethics, e-learning and active learning) and twelve themes (including motor, basic, emerging and niche).Originality/valueFollowing an extensive review of the literature, this would appear to be the first study to provide a panoramic view of AI for competency-based personalised learning based on the Scopus database. The core gaps in the current literature have been identified and the corresponding future agenda will be instrumental in shaping future research directions in the field.
How incentive alignment along the supply chain fosters incremental innovation: evidence from defence performance-based contracts
Authors: Alqahtani Faris , Selviaridis Kostas , Stevenson Mark 
Published: October 2024

PurposeTo investigate how providers of product-service bundles design and manage their contracts with upstream suppliers to incentivise incremental innovation for the benefit of their downstream customers, who contract the provider based on performance.Design/methodology/approachAn embedded multiple-case study was conducted to examine elements of a European jet fighter’s manufacturing and after-sales supply chain. The embedded cases concern provider contracts with first-tier suppliers of product and service offerings. Data collection involved 21 semi-structured interviews, documents and other secondary data sources. Data analysis was informed by agency theory to assess the effectiveness of contract design and management in delivering incremental innovation and to identify related contracting strategies.FindingsWe identify four strategies for fostering incremental innovation in contracts between providers and their first-tier suppliers. These include two contract design strategies, i.e. reducing goal incongruence and addressing information asymmetry; and two contract management strategies, i.e. reducing outcome uncertainty and promoting inter-firm integration between providers and sub-suppliers.Practical implicationsThe research offers managerial guidelines regarding how providers can design and manage their tier-one supplier contracts to achieve incremental innovation. These include encouraging early supplier involvement, using focussed KPIs in contracts, and managing product and service-offering suppliers differently.Originality/valueThe research shows the contingent effect during contract design and management of a sub-supplier’s product vs. service offering, which, in turn, impacts incremental innovation. We also find that using focussed key performance indicators in sub-supplier contracts can be effective in improving product and service quality.
Success in small places: NCB forfeiture thrives in Manitoba, a small but mighty Canadian jurisdiction
Authors: Murray Melinda , Simser Jeffrey 
Published: October 2024

Purpose
This paper shows how a small jurisdiction can apply well-designed non-conviction-based (NCB) forfeiture provisions with a dedicated team to have a meaningful impact on financial crime. This paper aims to examine developing jurisprudence, legislation and case law to explore how the NCB laws work. Finally, this paper examines a relatively new area of law for Canada, unexplained wealth orders (UWOs). This paper discussed three recent cases in Western Canada currently before the courts.

Design/methodology/approach
This paper considers legislative and jurisprudential developments relevant to NCB or civil asset forfeiture and in particular considers very recent developments involving UWOs.

Findings
This paper shows how a small jurisdiction can apply well-designed NCB forfeiture provisions with a dedicated team to have a meaningful impact on financial crime.

Research limitations/implications
Some jurisdictions, like the UK, have experienced court losses with their UWO process. Canadian law may have a modest pathway to success in this area, although our jurisprudence is very much in development.

Practical implications
Manitoba is a small jurisdiction with limited resources who are finding ways to have an effective impact on financial crime through the careful application of use of conviction-based forfeiture.

Social implications
Financial crime has an outsized impact on society. This paper shows some of the techniques available to disrupt financial crime.

Originality/value
This paper incorporates developments in 2024 that have not yet been examined.
Uncovering effects of supply chain distance on sustainability adoption: empirical evidence from a multi-stakeholder partnership
Authors: Alves Ana P. Ferreira , Silva Minelle E. , Sauer Philipp C. 
Published: October 2024

Purpose
To investigate the effects of supply chain (SC) distance on sustainability adoption, this study aims to advance the way prior studies on SC sustainability presume that SC structures are well-developed and stable. Since SC members face structural voids in different regions, we recognize that the information flow is impacted as SC partners often have limited knowledge of their direct partners. Thus, by studying a multi-stakeholder partnership, this article sheds light on the institutional foundation of sustainability adoption issues largely neglected to date.

Design/methodology/approach
A qualitative case study was used with members of an MSP (i.e. a roundtable), to understand the beef SC located in Brazil. Overall, 18 h of interview recordings and notes from 18 h of meeting observations were gathered, equaling 36 h of primary data.

Findings
Four dimensions of SC distance (physical, organizational, cultural and institutional) were identified, generating three driving effects on symbolic sustainability adoption and, consequently, a degree of invisibility for beef SC members. The results explain the process of sustainability adoption and highlight that smaller and more upstream suppliers show lower degrees of substantive adoption of SC sustainability practices.

Originality/value
This study investigates how SC distance affects the alignment of SC members in terms of sustainability adoption. By providing reflections on how institutional distance can hinder suppliers from adopting sustainability requirements they received from the SC, this research contributes to shifting from sustainability discourse to real practice and proactive partner engagement.