bluuebunny/crossref_metadata_2025_split huggingface dataset:
Permissive central tolerance plus defective peripheral checkpoints licence pathogenic memory B cells in CASPR2-antibody encephalitis
Authors: Sun Bo , Fernandes Dominique , Kienzler Anne-Kathrin , Paneva Sofija , Harrison Ruby , Ramanathan Sudarshini , Harrison Anna L , Makuch Mateusz , Fichtner Miriam L , Donat Robert F. , Akdeniz Deniz , Bayuangga Halwan , Im Min Gyu , Williams Robyn , Vasconcelos Ana , Thomsen Selina , Fower Andrew , Sun Ruyue , Fox Hannah , Mgbachi Victor , Davies Alexander , Tseng Mandy , Handel Adam , Kelly Mark , Zhao Meng , Bancroft James , Bashford-Rogers Rachael , Pluvinage John V , Dandekar Ravi , Alvarenga Bonny D. , Dustin Lynn , Rinaldi Simon , Owens Ray , Anthony Daniel , Bennett David L , Waters Patrick , Davis Simon J. , Wilson Michael R , O’Connor Kevin C , Soltys John , Carvalho Ana Luisa , Irani Sarosh R 
Published: January 2025

AbstractAutoimmunity affects 10% of the population. Within this umbrella, autoantibody-mediated diseases targeting one autoantigen provide a unique opportunity to comprehensively understand the developmental pathway of disease-causing B cells and autoantibodies. While such autoreactivities are believed to be generated during germinal centre reactions, the roles of earlier immune checkpoints in autoantigen-specific B cell tolerance are poorly understood. We address this concept in patients with CASPR2-autoantibody encephalitis and healthy controls. In both groups, comparable and high (∼0.5%) frequencies of unmutated CASPR2-reactive naïve B cells were identified. By contrast, CASPR2-reactive memory B cells were exclusive to patients, and their B cell receptors demonstrated affinity-enhancing somatic mutations with heterogenous binding kinetics. These effector molecules possessed epitope-dependent pathogenic effectsin vitroneuronal cultures andin vivo.The unmutated common ancestors of these memory B cells showed a distinctive balance between strong CASPR2 reactivity and very limited binding across the remaining human proteome. Our results are the first to propose mechanisms underlying autoantigen-specific tolerance in humans. We identify permissive central tolerance, defective peripheral tolerance and heterogenous autoantibody binding properties as sequential pathogenic steps which licence CASPR2-directed pathology. By leveraging the basic immunobiology, we rationally direct tolerance-restoring approaches in CASPR2-antibody diseases. This paradigm is applicable across autoimmune conditions.
Extensive length and homology dependent chimerism in pool-packaged AAV libraries
Authors: Lalanne Jean-Benoît , Mich John K. , Huynh Chau , Hunker Avery C. , McDiarmid Troy A. , Levi Boaz P. , Ting Jonathan T. , Shendure Jay 
Published: January 2025

AbstractAdeno-associated viruses (AAVs) have emerged as the foremost gene therapy delivery vehicles due to their versatility, durability, and safety profile. Here we demonstrate extensive chimerism, manifesting as pervasive barcode swapping, among complex AAV libraries that are packaged as a pool. The observed chimerism is length- and homology-dependent but capsid-independent, in some cases affecting the majority of packaged AAV genomes. These results have implications for the design and deployment of functional AAV libraries in both research and clinical settings.
Targeted Sortase A Inhibition by Novel Peptidomimetic Antivirulents against Staphylococcal Infections
Authors: Hintzen Jordi C. J. , Rahimi Shadi , Tietze Daniel , Zhang Jian , Mijakovic Ivan , Tietze Alesia A. 
Published: January 2025

AbstractAntibiotic resistance is a critical public health issue, causing resistant bacterial strains to be increasingly difficult to control. Antivirulence therapies, which target bacterial virulence factors rather than kill bacteria, present a promising approach. Sortase enzymes, particularly SrtA, are crucial for Gram-positive bacterial virulence by anchoring surface proteins essential for bacterial adhesion and biofilm formation to the bacterial outer cell wall. This study evaluates the selectivity of the peptidomimetic inhibitor BzLPRDSar towards various Gram-positive bacteria. The BzLPRDSar significantly inhibited biofilm formation in multidrug-resistantS. aureusandS. epidermidis. Conversely, it showed variable and generally lower selectivity to Gram-positive species such asE. faecalis, B. cereusandS. agalactiae. The selectivity towards Staphylococcus species is attributed to conserved structural elements in the SrtA enzyme, particularly the β7/β8 loop region with a key tryptophan, likely facilitating strong binding interactions with the inhibitor.ImportanceThis study addresses the pressing issue of antibiotic resistance by exploring antivirulence therapy as an innovative alternative to conventional antibiotics, focusing on inhibiting bacterial virulence rather than bacterial growth. By evaluating the selectivity of the peptidomimetic inhibitor BzLPRDSar against various Gram-positive bacteria, the study highlights its potent selectivity in inhibiting biofilm formation in multidrug-resistantS. aureusandS. epidermidis. The findings underscore the potential of targeting conserved structural elements in bacterial Sortase enzymes, particularly in Staphylococcal species, to develop more selective and effective antivirulence therapies.
Characterization of the ligand binding pocket of the virulence regulator Rns, a Member of the AraC/XylS family of transcription factors
Authors: Tolbert Jessica D , Talbot Kacey M , Kull F. Jon , Munson George P , Midgett Charles R 
Published: January 2025

AbstractDiarrheal disease caused by Gram-negative enteric pathogens such as enterotoxigenicEscherichia coli(ETEC),Vibrio cholerae,Shigella spp., and,Salmonella spp.are a leading cause of morbidity and mortality of children; especially, in low resource nations. While progress has been made in reducing this burden, there remains a need to develop efficacious therapies.Recently, we determined the structure of Rns, a member of the AraC/XylS family that regulates the expression of pili and other virulence factors in ETEC. The structure revealed decanoic acid bound between the N- and C-terminal domains. To test the hypothesis that bound decanoic acid directly inhibits Rns, we used its structure to identify residues that are necessary for ligand binding. Removal of the positive side chains of R75 and H20 rendered Rns insensitive to fatty acid inhibition. Additionally, mutations designed to occlude decanoic acid binding also produced a variant that was fatty acid insensitive. We also observed that this variant is structurally more flexible than wildtype Rns with decanoic acid; suggesting that bound fatty acid contributes to structural rigidity.These studies precisely demonstrate Rns binding pocket residues critical for binding fatty acids and inhibition of DNA binding. This supports our hypothesis that fatty acids must bind in the binding pocket to inhibit AraC regulators. Further work by us and others suggests inhibition of AraC virulence regulators by fatty acids is a common paradigm among many bacterial pathogens. Therefore, understanding the molecular basis of this inhibition lays the groundwork for the development of small molecule therapeutics targeting enteric disease.
KAT6A acetylation drives metabolic adaptation to mediate cellular growth and mitochondrial metabolism through AMPK interaction
Authors: Keller Mariko Aoyagi , Ivessa Andreas , Liu Tong , Li Hong , Romanienko Peter J , Nakamura Michinari 
Published: January 2025

ABSTRACTDiets influence metabolism and disease susceptibility, with lysine acetyltransferases (KATs) serving as key regulators through acetyl-CoA. We have previously demonstrated that a ketogenic diet alleviates cardiac pathology, though the underlying mechanisms remain largely unknown. Here we show that KAT6A acetylation is crucial for mitochondrial function and cell growth. Proteomic analysis revealed that KAT6A is acetylated at lysine (K)816 in the hearts of mice fed a ketogenic diet under hypertension, which enhances its interaction with AMPK regulatory subunits. RNA-sequencing analysis demonstrated that the KAT6A acetylation-mimetic mutant stimulates AMPK signaling in cardiomyocytes. Moreover, the acetylation-mimetic mutant mitigated phenylephrine-induced mitochondrial dysfunction and cardiomyocyte hypertrophy via AMPK activation. However, KAT6A-K816R acetylation-resistant knock-in mice unexpectedly exhibited smaller hearts with enhanced AMPK activity, conferring protection against neurohumoral stress-induced cardiac hypertrophy and remodeling. These findings indicate that KAT6A regulates metabolism and cellular growth by interacting with and modulating AMPK activity through K816-acetylation in a cell type-specific manner.
Overcoming Fluorescence Loss in mEOS-based AAA+ Unfoldase Reporters Through Covalent Linkage
Authors: Walter Isabella R. , Smith Baylee A. , Castanzo Dominic , Wohlever Matthew L. 
Published: January 2025

AbstractRecent work has demonstrated that the soluble photoconvertable fluorescent protein mEOS can be a reporter for AAA+ (ATPases Associated with diverse cellular Activities) unfoldase activity. Given that many AAA+ proteins process membrane proteins, we sought to adapt mEOS for use with membrane protein substrates. However, direct genetic fusion of mEOS to a membrane protein completely abolished fluorescence, severely limiting the utility of mEOS for studying AAA+ proteins. To circumvent this challenge, we separately purified mEOS and a AAA+ degron, covalently linked them via Sortase, and photoconverted the linked construct. This innovative approach preserves fluorescence and enables functional analysis, offering a broadly applicable platform for the study of membrane associated AAA+ proteins.
Reusing wasted bioresources for crop protection: Calcinated oyster shell powder enhances rhizospheric microbial-mediated suppression of root-knot nematodes
Authors: Jiang Qipeng , Wang Yong , Yu Jiamin , Wang Jinfeng , Jiang Lianqiang , Guo Shiping , Qian Yu , Yu Xiangwen , Liu Dongyang , Xi Daojiang , Deng Quan , Ding Wei , Li Shili 
Published: January 2025

ABSTRACTThe root-knot nematode (RKN)Meloidogyne incognitais one of the most destructive plant-parasitic nematodes (PPNs) affecting crop production worldwide. Our earlier study revealed that calcinated oyster shell powder (OSP) effectively suppressed tobacco RKN disease. However, the suppression mechanism of OSP against RKNs remain unknown. Our study revealed that calcinated OSP reduced the tobacco root–knot index by more than 38% by inhibiting the migration of second-stage juveniles ofMeloidogyne incognita(J2) in the soil. Furthermore, OSP reduced the J2 density in the tobacco rhizosphere by 43.69% and significantly increased the soil pH by 0.68; moreover, OSP increased the contents of soil exchangeable calcium (ExchCa) and exchangeable magnesium (ExchMg) by more than 50%. Moreover, soil properties, including ExchMg, ExchCa and pH, enhanced the microbial-mediated suppression of J2. Specifically, Proteobacteria and Gemmatimonadota dominated the microbial community suppressing RKN, and fungal richness contributed to the suppression of RKNs; in addition, Chloroflexi and Acidobacteria dominated the microbial community promoting RKN prosperity. Our study revealed that the reuse of wasted oyster shell powder as an innovative antagonist is a promising avenue for ecofriendly RKN management strategies.IMPORTANCEThere is increased demand for ecofriendly RKN management strategies, and this study is the first to propose that the reuse of wasted oyster shell powder as an innovative antagonist against RKNs is effective, and calcinated oyster shell powder can reduce tobacco root-knot index andMeloidogyne incognita(J2) density by inhibiting the migration of J2s and enhancing the microbially mediated suppression of J2s in the tobacco rhizosphere. Moreover, several soil microbial and physicochemical indicators, including the contents of soil exchangeable calcium, exchangeable magnesium, pH and the relative abundance of Proteobacteria, Gemmatimonadota, Chloroflexi and Acidobacteria in plant rhizosphere were suggested to guide the development of ecofriendly PPN management strategies.
Temporal and protein-specific S-palmitoylation supports synaptic and neural network plasticity
Authors: Pyty Agata , Ijaz Rabia , Buszka Anna , Miłek Jacek , Figiel Iza , Wardaszka Patrycja , Roszkowska Matylda , Mierzwa Natalia , Wojtas Adam , Kerstein Eli , Serwa Remigiusz , Kalita Katarzyna , Dzakpasu Rhonda , Dziembowska Magdalena , Włodarczyk Jakub , Wójtowicz Tomasz 
Published: January 2025

AbstractS-palmitoylation, a dynamic post-translational modification, has long been suggested to play a pivotal role in synaptic plasticity, learning, and memory. However, its precise impact on synaptic proteins and function remains unclear. In this study, we show that acute protein depalmitoylation in the hippocampus differentially affects short- and long-term synaptic plasticity, depending on synapse type. Strikingly, depalmitoylation also reprograms neuronal spiking timing following associative network activation. Our research identifies pre- and postsynaptic proteins dynamically regulated by S-palmitoylation during synaptic plasticity and suggests this modification occurs in isolated excitatory synapses. We also demonstrate that S-palmitoylation targets specific proteins within minutes and is not proteome-wide. These findings mark a significant advance in understanding how lipid modifications drive neural adaptability, memory, and learning.
Distinct modes of dopamine modulation on striatopallidal synaptic transmission
Authors: Lee Youngeun , Reva Maria , Kim Ki Jung , Kim Yemin , Cho Eunjeong , Kim Hyun-Jin , Jeong Minseok , Myung Kyungjae , Li Yulong , Lee Seung Eun , Kim Eunjoon , Lee C. Justin , Lüscher Christian , Kim Jae-Ick 
Published: January 2025

AbstractDopamine (DA) affects voluntary movement by modulating basal ganglia function. In the classical model, DA depletion leads to overactivity of the indirect pathway and excessively inhibits the thalamus, resulting in hypokinesia. The contribution of DA on striatopallidal synapses, an initial hub in the indirect pathway connecting the striatum to the external globus pallidus (GPe), remains poorly understood because of the sparse DA innervation. Here, we combine optogenetic projection targeting, whole cell patch clamp recordings in acute brain slices from mice, and computational modeling to overcome this limitation. We show that DA activates D2R receptors (D2Rs) and D4 receptors (D4Rs) differentially in distinct GPe subregions. In a pinwheel-like fashion, dorsolateral and ventromedial GPe expresses high levels of D2Rs, which exert presynaptic inhibition, while in dorsomedial and ventrolateral GPe D4Rs cause postsynaptic inhibition. DA depletion by 6-OHDA (6-hydroxydopamine) reverses the region- specific effect of DA, shifting it in the opposite direction and contributing to hypokinesia. These findings reveal the mechanism by which the different modality information conveyed spatially through the indirect pathway is differentially modulated by DA at striatopallidal synapses.
Complex-valued three-dimensional atomic spectroscopy with Gaussian-assisted inline holography
Authors: Huang Xing , Wang Yuzhuo , Zhao Jian , Wu Saijun 
Published: January 2025

When a laser-cooled atomic sample is optically excited, the envelope of coherent forward scattering can often be decomposed into a few complex Gaussian profiles. The convenience of Gaussian propagation helps address key challenges in digital holography. In this paper, we develop a Gaussian-decomposition-assisted approach to inline holography for single-shot, simultaneous measurements of absorption and phase-shift profiles of small atomic samples sparsely distributed in three dimensions. The samples' axial positions are resolved with micrometer resolution and their spectroscopy are extracted from complex-valued images recorded at various probe frequencies. The phase-angle readout is not only robust against transition saturation but also insensitive to atom-number and optical-pumping-induced interaction-strength fluctuations. Benefiting from such features, we achieve hundred-kHz-level single-shot resolution to the transition frequency of a Rb87 D2 line, with merely hundreds of atoms. We further demonstrate single-shot three-dimensional field sensing by measuring local light shifts to the atomic array with micrometer spatial resolution.

Published by the American Physical Society
2025
Effect of employee emotional competence on customer emotional attachment: the roles of service recovery satisfaction and service failure severity
Authors: Saleem Salman , Umar Rana Muhammad , Oduro Stephen 
Published: January 2025

PurposeThis study aims to enhance our understanding of employee emotional competence (EEC) in the context of service failure and recovery. Accordingly, the present study investigates the relationship between perceived EEC and customer emotional attachment (CEA) through the mediating role of service recovery satisfaction (RES). Furthermore, the study examines the moderating impact of service failure severity (SFS) on the relationship between perceived EEC and RES.Design/methodology/approachA self-administered online survey was carried out to collect data. Using a convenience sampling technique, 195 US consumers were recruited from Prolific Academic. To test the hypotheses, this study employed partial least squares structural equation modeling (PLS-SEM).FindingsAccording to the analysis, perceived EEC impacts CEA directly and indirectly via RES. Additionally, the study finds that consumers reported feeling more emotionally connected to the restaurant when they were satisfied with service recovery. Finally, the study identified that the connection between perceived EEC and RES increases with service failure severity.Practical implicationsThis study emphasizes enhancing EEC through organization-wide training to increase customer satisfaction and emotional attachment to the service organization. Furthermore, it underscores the need for comprehensive employee training to categorize service failure severity and formulate appropriate recovery strategies.Originality/valueThe authors believe this is the first RES study to examine perceived EEC’s effect on CEA. By combining the affect infusion and cognitive appraisal theories to examine recovery satisfaction, this study contributes to the existing body of research on service recovery by shedding light on the relationship between perceived EEC and CEA. Furthermore, the study offers preliminary findings indicating an increase in the impact of perceived EEC on RES during high failure severity (SFS).
The effect of third-party certifications on corporate social responsibility communication authenticity and credibility
Authors: Marschlich Sarah , Hurtado Ellis 
Published: January 2025

PurposeAccusations of greenwashing and corporate scandals have increased individuals’ skepticism of companies and their CSR claims. As a result, corporations seek to improve individuals’ perceptions of the credibility and authenticity of their CSR communication. Using signaling theory, this study tested to what extent external certifications from a non-profit organization act as a signal to affect individuals’ skepticism toward CSR, which, in turn, could influence individuals’ perceptions of CSR communication authenticity and credibility.Design/methodology/approachWe conducted a one-factorial (CSR communication with or without CSR certification) between-subjects online experiment, surveying 184 individuals. Mediation analyses were performed to test our hypotheses. Participants were randomly assigned to a made-up corporate website text in which corporate efforts were either certified with the B Corporation Certification, one of the most established non-profit organization’s certifications of CSR or in which no certification was indicated.FindingsThe results demonstrate that external CSR certifications decrease individuals’ CSR skepticism and increase the perceived authenticity and credibility of CSR communication. CSR skepticism partially mediated the effect between the certification condition and CSR communication authenticity and credibility.Originality/valueThe study advances CSR communication research by providing empirical evidence of the positive effect of CSR certifications on the perceived authenticity and credibility of CSR communication. Businesses can signal the veracity of their CSR claims by obtaining a CSR certification, which decreases individuals’ skepticism toward CSR.
Challenges to the implementation of design for adaptability among design professionals in Ghana
Authors: Kotei-Martin Jenefailus Nikoi , Agyekum Kofi , Salgin Burcu , Pittri Hayford , Botchway Edward Ayebeng , Gasue Rhoda , Aklashie Samuel 
Published: January 2025

PurposeThe increase in waste and carbon emissions from the construction industry continues to fester although sustainable design approaches such as designing for adaptability (DfA) have been approved as a viable option to minimize construction waste and greenhouse gases while providing cost savings on building projects. This paper examines the views of design professionals on the challenges to implementing DfA in the Ghanaian construction industry (GCI).Design/methodology/approachA critical comparative review of the related literature was conducted on the international challenges to implementing adaptability. After the review, 16 challenges were identified and used as the basis of the questionnaire survey in the Ghanaian context. By using a quantitative approach, a close-ended structured questionnaire was used to seek the views of 236 design professionals operating in the GCI regarding these factors. Data retrieved were analysed using descriptive and inferential statistics.FindingsThe findings revealed the key challenges to implementing DfA among design professionals in Ghana to include “limited funding for adaptable buildings”, “lack of collaboration between design professionals, contractors and clients towards the realization of adaptable buildings”, “limited demand for adaptable buildings” and “lack of education and training programs on design for adaptability practices”.Originality/valueThe novelty or originality of this study lies in its focus on the GCI, an area where the concept of DfA has rarely been examined in practice despite its recognized potential benefits in reducing waste and emissions. The study offers a detailed and comprehensive understanding of the multifaceted challenges faced by design professionals in Ghana. This level of detail is crucial for devising targeted strategies to promote DfA in the region.