bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluvoxamine maleate ameliorates Alzheimer disease pathology by mitigating amyloid-beta load and neuroinflammation in 5XFAD mice
Authors: Kaur Sukhleen , Sharma Kuhu , Sharma Ankita , Sandha Kamalpreet Kaur , Ali Syed Mudassir , Ahmed Riyaz , Ramajayan P. , Singh Parvinder Pal , Ahmed Zabeer , Kumar Ajay 
Published: December 2023

AbstractBackgroundAlzheimer pathology (AD) is accompanied by the deposition of amyloid beta (Aβ) and chronic neuroinflammation, where NLRP3 inflammasome is particularly involved. In this study, we found that the OCD drug fluvoxamine maleate (FXN) can potently ameliorate AD pathology in 5XFAD mice by autophagy-mediated clearance of Aβ and inhibition of NLRP3 inflammasome.MethodsWe used mice primary astrocytes to establish the mechanism of action of FXN against NLRP3 inflammasome by using various techniques like ELISA, Western blotting, confocal microscopy, Immunofluorescence, etc. The validation of the anti-AD activity of FXN was done in transgenic 5XFAD mice after two months of treatment followed by behavior analysis and studying inflammatory and autophagy proteins along with immunohistochemistry analysis for Aβ load in the hippocampi.ResultsOur data showed that FXN induces autophagy to inhibit NF-κB and NLRP3 inflammasome at a low concentration of 78 nM apart from directly inhibiting NLRP3 inflammasome in primary astrocytes. FXN activated the PRKAA2 pathway through CAMKK2 signaling, which led to the induction of autophagy in primary astrocytes. FXN inhibited the ATP-mediated NLRP3 inflammasome through autophagic degradation of NF-κB and thus caused the downregulation of pro-IL-1β and NLRP3. The anti-NLRP3 inflammasome effect of FXN was reversed when autophagy was inhibited either by genetic knockdown of the PRKAA2 pathway or by bafilomycin A1.Furthermore, FXN treatment led to improved AD pathology in 5XFAD mice, which displayed a significant improvement in multiple behavior parameters like working memory and neuromuscular coordination and they behaved more like wild-type animals. We found that FXN improved behavior in 5XFAD mice by clearing the Aβ deposits from the hippocampi along with a significant reduction in multiple inflammatory proteins, including NF-κB, GFAP, IBA1, IL-1β, TNF-α, and IL-6 associated with NF-κB and NLRP3 inflammasome in the brain. Moreover, these changes were accompanied by increased expression of autophagic proteins.ConclusionOur data suggest that to ameliorate AD pathology, FXN simultaneously targets two key pathological features of AD that is Aβ deposits and neuroinflammation. Being an approved drug, FXN can be pushed as a potential drug candidate for human studies against AD.
Diverging roles of TRPV1 and TRPM2 in warm-temperature detection
Authors: Abd El Hay Muad Y. , Kamm Gretel B. , Tlaie Alejandro , Siemens Jan 
Published: December 2023

The accurate perception of innocuous temperatures, particularly those experienced as pleasantly warm, is essential for achieving thermal comfort and maintaining thermoregulatory balance. Warm-sensitive neurons (WSN) innervating the skin play a central role in non-painful warmth detection. The TRP ion channels TRPV1 and TRPM2 have been suggested as sensors of warm temperature in WSNs. However, the precise contribution of these channels to the process of warmth detection is not fully understood.A significant challenge in analysing WSNs lies in their scarcity: fewer than 10 % of sensory neurons in the rodent dorsal root ganglion (DRG) respond to innocuous warm temperatures. In this study, we examined >20,000 cultured mouse DRG neurons using calcium imaging and discovered distinct contributions of TRPV1 and TRPM2 to warm-temperature sensitivity. TRPV1, and to a lesser extent TRPM2, affect the abundance of WSNs, with TRPV1 mediating the rapid, dynamic response to warmth and TRPM2 subtly affecting the population response of WSNs. By carefully tracking animal movement in a whole-body thermal preference paradigm, we observe that these cellular differences correlate with nuanced thermal behaviours. Utilizing a drift-diffusion model to quantitatively analyse the decision-making process of animals exposed to different environmental temperatures, we found that: TRPV1 deletion primarily impairs the precision of evidence accumulation, whereas TRPM2 deletion significantly increases the total duration of exposure to warmer environments that are avoided by wildtype mice.Our findings provide valuable insights into the distinct molecular responses to warmth stimuli, and underpin the subtle aspects of thermal decision-making when encountering minor temperature variations.
Structure and mechanism of Zorya anti-phage defense system
Authors: Hu Haidai , Hughes Thomas C.D. , Popp Philipp F. , Roa-Eguiara Aritz , Martin Freddie J.O. , Rutbeek Nicole R. , Hendriks Ivo Alexander , Payne Leighton J. , Yan Yumeng , Sousa Victor Klein de , Wang Yong , Nielsen Michael Lund , Berry Richard M. , Erhardt Marc , Jackson Simon A. , Taylor Nicholas M.I. 
Published: December 2023

SummaryZorya is a recently identified and widely distributed bacterial immune system, which protects against phage invasion. It consists of a predicted membrane-embedded complex (ZorAB) and soluble components that differ among Zorya subtypes, notably ZorC and ZorD, in type I Zorya systems. Here, we reveal the molecular basis of the Zorya defense system using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies. We demonstrate that ZorAB shares the stoichiometry of other 5:2 inner membrane ion-driven rotary motors. Additionally, ZorA5B2features a dimeric ZorB peptidoglycan binding domain and a pentameric α-helical coiled-coil tail made of ZorA that projects approximately 700 Å into the cytoplasm. We further characterize the structure and function of the soluble Zorya components, ZorC and ZorD, and find that they harbour DNA binding and nuclease activity, respectively. Comprehensive functional and mutational analyses demonstrates that all Zorya components work in concert to protect bacterial cells against invading phages. We present evidence that ZorAB operates as an ion-driven motor that becomes activated and anchors to the cell wall upon sensing of cell envelope perturbations during phage invasion. Subsequently, ZorAB transfers the phage invasion signal through the ZorA cytoplasmic tail to the soluble effectors, which function to prevent phage propagation. In summary, our study elucidates the foundational mechanisms of Zorya function and reveals a novel triggering signal for the rapid activation of an anti-phage defense system.
Modulation of neural gene networks by estradiol in old rhesus macaque females
Authors: Cervera-Juanes Rita , Zimmerman Kip D. , Wilhelm Larry , Zhu Dongqin , Bodie Jessica , Kohama Steven G. , Urbanski Henryk F. 
Published: December 2023

AbstractThe postmenopausal decrease in circulating estradiol (E2) levels has been shown to contribute to several adverse physiological and psychiatric effects. To elucidate the molecular effects of E2 on the brain, we examined differential gene expression and DNA methylation (DNAm) patterns in the nonhuman primate brain following ovariectomy (Ov) and subsequent E2 treatment. We identified several dysregulated molecular networks, including MAPK signaling and dopaminergic synapse response, that are associated with ovariectomy and shared across two different brain areas, the occipital cortex (OC) and prefrontal cortex (PFC). The finding that hypomethylation (p=1.6×10-51) and upregulation (p=3.8×10-3) ofUBE2Macross both brain regions, provide strong evidence for molecular differences in the brain induced by E2 depletion. Additionally, differential expression (p=1.9×10-4; interactionp=3.5×10-2) ofLTBRin the PFC, provides further support for the role E2 plays in the brain, by demonstrating that the regulation of some genes that are altered by ovariectomy may also be modulated by Ov followed by hormone replacement therapy (HRT). These results present real opportunities to understand the specific biological mechanisms that are altered with depleted E2. Given E2’s potential role in cognitive decline and neuroinflammation, our findings could lead to the discovery of novel therapeutics to slow cognitive decline. Together, this work represents a major step towards understanding molecular changes in the brain that are caused by ovariectomy and how E2 treatment may revert or protect against the negative neuro-related consequences caused by a depletion in estrogen as women approach menopause.
Cell surface sculpting using logic-gated protein actuators
Authors: Kofoed Christian , Tay Nicholas E. S. , Ye Xuanjia , Erkalo Girum , Muir Tom W. 
Published: December 2023

AbstractCell differentiation and tissue specialization lead to unique cellular surface landscapes and exacerbated or loss of expression patterns can result in further heterogenicity distinctive of pathological phenotypes1–3. Immunotherapies and emerging protein therapeutics seek to exploit such differences by engaging cell populations selectively based on their surface markers. Since a single surface antigen rarely defines a specific cell type4,5, the development of programmable molecular systems that integrate multiple cell surface features to convert on-target inputs to user-defined outputs is highly desirable. Here, we describe an autonomous decision-making protein device driven by proximity-gated proteintrans-splicing that allows local generation of an active protein from two otherwise inactive fragments. We show that this protein actuator platform can perform various Boolean logic operations on cell surfaces, allowing highly selective recruitment of enzymatic and cytotoxic activities to specific cells within mixed populations. Due to its intrinsic modularity and tunability, this technology is expected to be compatible with different types of inputs, targeting modalities and functional outputs, and as such will have broad application in the synthetic biology and biotechnology areas.
Estimating the frequency of virulence against anStbgene inZymoseptoria triticipopulations by bulk phenotyping on checkerboard microcanopies of wheat NILs
Authors: Suffert Frédéric , Le Prieur Stéphanie , Gélisse Sandrine , Dzialo Emmie , Saintenac Cyrille , Marcel Thierry C. 
Published: December 2023

AbstractMonitoring virulent strains within fungal pathogen populations is crucial to improve host resistance deployment strategies. Such monitoring increasingly involves field pathogenomics studies of molecular polymorphisms in genomes based on high-throughput screening technologies. However, it is not always straightforward to predict virulence phenotypes from these polymorphisms andin plantaphenotyping remains necessary. We developed a method for ‘bulk phenotyping on checkerboard microcanopies of wheat near-isogenic lines’ (BPC) for estimating the frequency of virulence against anStbgene in populations ofZymoseptoria tritici, the causal agent ofSeptoria triticiblotch in wheat, without the need for strain-by-strain phenotyping. Our method involves the uniform inoculation of a microcanopy of two wheat lines – one with the resistance gene and the other without it – with a multi-strain cocktail representative of the population to be characterized, followed by the differential quantification of infection points (lesions). UsingStb16q, a resistance gene that has recently broken down in Europe, we found a robust correlation between the ratio of the mean number of lesions on each wheat line and the frequency of virulent strains in the inoculum. Using pairs of virulent and avirulent strains, and synthetic populations consisting of 10 virulent strains and 10 avirulent strains mixed in different proportions, we validated the principle of the method and established standard curves at virulence frequencies close to those observed in natural conditions. We discuss the potential of this method for virulence monitoring in combination with recently developed molecular methods.
Control of three-carbon amino acid homeostasis by promiscuous importers and exporters inBacillus subtilis: Role of the sleeping beauty family of amino acid exporters
Authors: Warneke Robert , Herzberg Christina , Daniel Richard , Hormes Björn , Stülke Jörg 
Published: December 2023

ABSTRACTThe Gram-positive model bacteriumBacillus subtiliscan acquire amino acids by import,de novobiosynthesis, or by degradation of proteins and peptides. The accumulation of several amino acids inhibits growth ofB. subtilis, probably due to misincorporation into cellular macromolecules such as proteins or peptidoglycan or due to interference with other amino acid biosynthetic pathways. Here, we studied the adaptation ofB. subtilisto toxic concentrations of the three-carbon amino acids L-alanine, β-alanine, and 2,3-diaminopropionic acid as well as glycine. Resistance to the non-proteinogenic amino acid β-alanine, which is a precursor for the vitamin B5 and thus for coenzyme A biosynthesis is achieved by mutations that either activate a cryptic amino acid exporter, AexA (previously YdeD), or inactivate the amino acid importers AimA, AimB (previously YbxG), and BcaP. TheaexAgene is very poorly expressed under most conditions studied. However, mutations afecting the transcription factor AerA (previously YdeC), can result in strong constitutiveaexAexpression. AexA is the founding member of a conserved family of amino acid exporters inB. subtilis, which are all very poorly expressed. Therefore, we suggest to call this family “sleeping beauty family of amino acid exporters”. 2,3-Diaminopropionic acid can also be exported by AexA, and this amino acid also seems to be a natural substrate of AerA/ AexA, as it can cause a slight but significant induction ofaexAexpression, and AexA also provides some natural resistance towards 2,3-diaminopropionic acid. Moreover, our work shows how low specificity amino acid transporters contribute to amino acid homeostasis inB. subtilis.IMPORTANCEEven thoughB. subtilisis of of the most-studied bacteria, amino acid homeostasis in this organism is not fully understood. We have identified import and export systems for the C2 and C3 amino acids. Our work demonstrates that the responsible amino acid permeases contribute in a rather promiscuitive way to amino acid uptake. In addition, we have discovered AexA, the first member of a family of very poorly expressed amino acid exporters, that we call “sleeping beauty amino acid exporters”. The expression of these transporters is typically triggered by mutations in corresponding regulator genes that are acquired upon exposure to toxic amino acids. These exporters are ubiquitous in all domains of life. It is tempting to speculate that many of them are not expressed until the cells experience a selective pressure by toxic compounds and that the protect the cells from rare but potentially dangerous accounters with such compounds.
Performance analysis of FEC based SR motor drive using fuzzy tuned PI controller
Authors: Damarla Indira , M. Venmathi , V. Krishnakumar , P. Anbarasan 
Published: December 2023

Purpose
In this paper, a new front end converter (FEC) topology has been proposed for the switched reluctance (SR) motor drive. This study aims to present the performance analysis of FEC-based SR motor drive using various types of control schemes like conventional proportional integral (PI) controller, fuzzy logic controller (FLC) and fuzzy-tuned proportional integral controller (Fuzzy-PI).

Design/methodology/approach
The proposed FEC-based SR motor drive with various control strategies is derived for the torque ripple minimization and speed control.

Findings
The steady state and the dynamic response of the FEC-based SR motor drive are analyzed using three different controllers under change in speed and loading conditions. The Fuzzy-PI-based control scheme improves the dynamic response of the system when compared with the FLC and the conventional PI controller.

Originality/value
The hardware prototype has been implemented for the FEC-based SR motor drive by using the Xilinx SPARTAN 6 FPGA processor. The experimental verification has been conducted and the results have been measured under steady state and dynamic conditions.
Social media and nonprofit fundraising: the influence of Facebook likes
Authors: Haruvy Ernan E. , Popkowski Leszczyc Peter T.L. 
Published: December 2023

PurposeThis paper aims to demonstrate that Facebook likes affect outcomes in nonprofit settings. Specifically, Facebook likes influence affinity to nonprofits, which, in turn, affects fundraising outcomes.Design/methodology/approachThe authors report three studies that establish that relationship. To examine social contagion, Study 1 – an auction field study – relies on selling artwork created by underprivileged youth. To isolate signaling, Study 2 manipulates the number of total Facebook likes on a page. To isolate commitment escalation, Study 3 manipulates whether a participant clicks a Facebook like.FindingsThe results show that Facebook likes increase willingness to contribute in nonprofit settings and that the process goes through affinity, as well as through Facebook impressions and bidding intensity. The total number of Facebook likes has a direct signaling effect and an indirect social contagion effect.Research limitations/implicationsThe effectiveness of the proposed mechanisms is limited to nonprofit settings and only applies to short-term effects.Practical implicationsFacebook likes serve as both a quality signal and a commitment mechanism. The magnitude of commitment escalation is larger, and the relationship is moderated by familiarity with the organization. Managers should target Facebook likes at those less familiar with the organization and should prioritize getting a potential donor to leave a like as a step leading to donation, in essence mapping a donor journey from prospective to active, where Facebook likes play an essential role in the journey. In a charity auction setting, the donor journey involves an additional step of bidder intensity.Social implicationsThe approach the authors study is shown effective in nonprofit settings but does not appear to extend to corporate social responsibility more broadly.Originality/valueTo the best of the authors’ knowledge, this study is the first investigation to map Facebook likes to a seller’s journey through signals and commitment, as well as the only investigation to map Facebook likes to charity auctions and show the effectiveness of this in the field.
Mastering timely deliveries using dynamic capabilities: perspectives from logistics service providers and shippers
Authors: Özcan Seda , Oflaç Bengü Sevil , Tokcaer Sinem , Özpeynirci Özgür 
Published: December 2023

PurposeThe criticality of late deliveries in transportation lies in the threat of considerable multi-level supply chain costs. This study aims to reveal the dynamic capabilities playing a facilitating role in preventing delay, thus providing timely delivery, as well as developing an understanding of how and when those capabilities are activated within the supply chain network.Design/methodology/approachAn exploratory study was conducted involving 16 semi-structured expert interviews with the representatives of logistics service providers and shippers. Following an interpretive phenomenology framework, the prevention phenomenon was explained.FindingsFindings revealed two preventive capability categories in delay prevention: (1) proactive capabilities, referring to the enabling actions planned before departure, and (2) reactive capabilities, referring to actions planned after departure. Findings pinpoint that, in addition to the proactive capabilities, reactive capabilities enabled by innovative problem-solving actions are crucial for adapting to a dynamically changing environment in prevention. Moreover, this study shows that prevention capabilities are characterized by tangible and intangible resources and integration of resources with external links which constitute a delay prevention network within a wider service ecosystem.Originality/valueThis study stands out with its specific focus on delay prevention capabilities and enabling actions from the perspectives of logistics service providers and shippers. The premises of the resource-based view are combined with dynamic capabilities theory, leading to a proposed time-based taxonomy of proactive and reactive capabilities in supply chains, aimed at creating value and strengthening resilience.
Exploring personality traits in the knowledge-sharing behavior: the role of agreeableness and conscientiousness among Malaysian tertiary academics
Authors: Paiman Norazha , Fauzi Muhammad Ashraf , Norizan Natrika , Abdul Rashid Aida , Tan Christine Nya-Ling , Wider Walton , Ravesangar Kamalesh , Selvam Gowri 
Published: December 2023

PurposeThe research aims to provide a nuanced understanding of the complex social, psychological and organizational factors that serve as the foundation driving academics' knowledge-sharing behavior (KSB) within an academic enclave.Design/methodology/approachA cross-sectional research design using the partial least squares structural equation modeling (PLS-SEM) approach was employed to examine the determinants of personality traits among tertiary academics in Malaysia in relation to their KSB. To this end, a self-administered survey was distributed to a sample group of 526 respondents.FindingsIt is evident that conscientiousness and agreeableness are the personality traits that play a significant role in promoting KSB among academics in higher learning institutions (HLIs). These personality traits are positively linked with academics' willingness to transfer and receive knowledge. In contrast, the personality trait of openness to experience does not significantly influence KSB.Research limitations/implicationsThis study has employed a four-item measurement for evaluating the three distinct personality traits. Despite employing a brief measurement tool, the study has demonstrated significant reliability and validity, particularly in terms of convergent and discriminant validity.Practical implicationsThe present study has revealed that conscientiousness in academics is intimately linked with their KSB, which is of paramount importance in the output-based education system. Notably, agreeableness among academics also conveys a positive effect on knowledge sharing (KS) in HLIs, as it cultivates trust and helpfulness among individuals and facilitates the exchange of valuable tacit knowledge.Originality/valueThis research explores the relationship between personality traits and KSB among Malaysian academics in HLIs. The study adopts the theories of planned behavior (TPB) and social capital theory (SCT) as theoretical ground, providing a nuanced understanding of the underlying motivations and mechanisms driving academics' knowledge-sharing behavior within the unique socio-cultural context of Southeast Asia.