bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced antifungal activity of NK-92 cells againstCandida albicansmediated by a mannan-specific chimeric antigen receptor
Authors: de Campos Gabriela Yamazaki , Guimarães Júlia Garcia , Machado Michele Procópio , Oliveira Brito Patrícia Kellen Martins , Shin Ben , Di Maio Antonio , dos Santos Douglas , Palma Patricia Vianna Bonini , dos Reis Thaila Fernanda , Goldman Gustavo Henrique , Palma Angelina S. , Matthews Steve J. , Feizi Ten , Liu Yan , da Silva Thiago Aparecido 
Published: November 2024

AbstractChimeric antigen receptors (CARs) offer promising prospects for innovative cell-based therapies against invasive fungal infections such as invasive candidiasis. Here, we have developed four CARs targetingCandida albicanswith distinct single-chain variable fragments (scFvs): scFv3-CAR, scFv5-CAR, scFv12-CAR, and scFvκ3-1-CAR. In T cells, scFv5-CAR induced IL-2 expression in response toC. albicanshyphae, while scFv3-CAR and scFv12-CAR did not mediate cell activation againstC. albicans. Notably, scFvκ3-1-CAR mediated the strongest cell activation againstC. albicansyeast, hyphae, and other clinically relevantCandidaspecies. scFvκ3-1-CAR-NK-92 cells exhibited elevated IFN-γ and CD107a expression, reducingC. albicansviability. NOD scid gamma (NSG) mice treated with scFvκ3-1-CAR-NK-92 cells had reducedC. albicansburden in the kidney 24 hours postinfection. We showed that scFvκ3-1-CAR targetsC. albicansmannan but no other glycans in glycan microarray screening analyses. These findings reveal the scFvκ3-1-CAR potential as a therapeutic strategy for treatingCandidaspp. by modifying peripheral blood mononuclear cells.ImportanceRecent studies on novel immunotherapies, including chimeric antigen receptor (CAR)-T cells, have shown promising results in preclinical models against invasive fungal infections (IFIs). However, the application of CAR technology in natural killer (NK) cells for treating IFIs remains unexplored. NK cells play a key role in early fungal clearance due to their antifungal activity mediated by granzymes, perforins, and the secretion of proinflammatory cytokines. This study is the first to demonstrate the feasibility and efficacy of CAR-modified NK cells targetingCandidaspp. We provided proof-of-concept data showing that CAR-expressing NK cells exhibit enhanced activation and antifungal effects against clinically relevantCandidaspecies by targeting mannan in the fungal cell wall. These findings are significant as they open new avenues for developing CAR-NK-based therapies to treat invasive candidiasis – a severe infection with limited treatment options and high mortality rates, particularly in immunocompromised patients.
GABA and glycine synaptic release on axotomized motoneuron cell bodies promotes motor axon regeneration
Authors: Wood Ryan L. , Calvo Paula M. , McCallum William M. , English Arthur W. , Alvarez Francisco J. 
Published: November 2024

AbstractMotor axon regeneration after traumatic nerve injuries is a slow process that adversely influences patient outcomes because muscle reinnervation delays result in irreversible muscle atrophy and suboptimal axon regeneration. This advocates for investigating methods to accelerate motor axon growth. Electrical nerve stimulation and exercise both enhance motor axon regeneration in rodents and patients, but these interventions cannot always be easily implemented. A roadblock to uncover novel therapeutic approaches based on the effects of activity is the lack of understanding of the synaptic drives responsible for activity-mediated facilitation of axon regeneration. We hypothesized that the relevant excitatory inputs facilitating axon regrowth originate in GABA/glycine synapses which become depolarizing after downregulation of the potassium chloride cotransporter 2 in motoneurons following axotomy. To test this, we injected tetanus toxin (TeTx) in the tibialis anterior (TA) muscle of mice to block the release of GABA/glycine specifically on TA motoneurons. Thereafter, we axotomized all sciatic motoneurons by nerve crush and analyzed the time-courses of muscle reinnervation in TeTx- treated (TA) and untreated (lateral gastrocnemius, LG) motoneurons. Muscle reinnervation was slower in TA motoneurons with blocked GABA/glycine synapses, as measured by recovery of M- responses and anatomical reinnervation of neuromuscular junctions. Post-hoc immunohistochemistry confirmed the removal of the vesicular associated membrane proteins 1 and 2 by TeTx activity, specifically from inhibitory synapses. These proteins are necessary for exocytotic release of neurotransmitters. Therefore, we conclude that GABA/glycine neurotransmission on regenerating motoneurons facilitates axon growth and muscle reinnervation and discuss possible interventions to modulate these inputs on regenerating motoneurons.
Identification of TAP2 protein variants resistant to inhibition by the HSV1 ICP47 protein
Authors: Nagy Gregory , Presley Rebecca , Dhar Shruti , Jeon Hyeongseon , Moreira Lynn , Tull Olivia , Gupta Arkobrato , Chung Dongjun , Tsichlis Philip N. , Parvin Jeffrey D. 
Published: November 2024

ABSTRACTHerpes Simplex Virus 1 evades the host immune system by expressing a protein, ICP47, that binds to and inhibits the heterodimeric Transporter Associated with Antigen Processing (TAP). We screened a library of 1786 variants in TAP2, one of the components of the TAP heterodimer, and identified 39 variants that were resistant to inhibition by ICP47. Of these 39 variants, five were individually tested, and three (T257I, S274H, and T244R) were confirmed to be significantly resistant to inhibition by ICP47. This resistance to inhibition did not extend to the Epstein Barr Virus BNLF2a protein, another viral factor known to inhibit antigen presentation by targeting TAP. These three residues localize close to the binding site of ICP47, on the 3D structure of TAP, but only Ser274 is spatially close to the antigenic peptide binding site of TAP. These results functionally resolve the TAP2 residues required for peptide binding from those required for ICP47 binding and identify TAP2 residues whose targeting with small molecule inhibitors could effectively prevent Herpes virus downregulation of antigen processing.AUTHOR SUMMARYT cells detect virus infected cells via viral peptides in complex with the major histocompatibility complex type I (MHC-I) on the cell surface. Herpes Simplex Virus 1 expression of the ICP47 protein allows the virus to evade detection and clearance of infected cells by host T cells. ICP47 binds to the TAP1/TAP2 protein complex and prevents the loading of antigenic peptides onto the MHC-I protein complex and thereby blocks the antigen processing. In this study, we screened for and identified variants of TAP2 with single amino acid substitutions that are no longer inhibited by ICP47. TAP2 proteins with the identified amino acid substitutions functioned normally in antigen processing even in the presence of ICP47. Results from this study create the potential strategy for drugs that target the identified portions of the TAP2 protein and block ICP47 inhibition of antigen processing while retaining normal TAP1/TAP2 function and thus suggest a new antiviral therapeutic approach for herpes virus infections.
Targeted activation of microglial PPARδ reprograms immunometabolism and enhances insulin sensitivity in diet-induced obesity
Authors: Jiao Han , Cázarez-Márquez Fernando , Guo Shanshan , Kalsbeek Andries , Krammer Gertjan , Yi Chun-Xia 
Published: November 2024

AbstractMicroglia play a crucial role in maintaining neuronal health through phagocytosis, a function that becomes compromised during diet-induced obesity and is associated with altered lipid metabolism. Previous research demonstrated that disrupting lipid metabolism in microglia, such as through lipoprotein lipase deficiency, impairs their phagocytic function and exacerbates obesity, glucose dysregulation, and hypothalamic neuron dysfunction. This study investigated whether enhancing lipid metabolism via peroxisome proliferator-activated receptor delta (PPARδ) activation could counteract obesity-related metabolic disturbances. Thermal proteome profiling identified GW0742 as the most potent PPARδ ligand among those tested. GW0742 enhanced microglial phagocytosis, reduced inflammation, and shifted energy metabolism towards glycolysis over oxidative phosphorylation. Targeted delivery of GW0742 using nanoparticles (NPs-GW0742) to microglia in the mediobasal hypothalamus of obese rats significantly improved insulin sensitivity without affecting body weight or food intake. Enhanced microglial activation was evidenced by increased soma size and coverage. These findings underscore the importance of microglial lipid metabolism in systemic glucose regulation and highlight the potential of PPARδ-targeted therapies to mitigate hypothalamic inflammation and improve metabolic health in obesity.
CD40 ligation-induced ERK activation promotes autophagy which leads to enhanced radiosensitivity in cervical carcinoma cells
Authors: Liu Baocai , Zhang Yadong , Wang Quan , Wang Qian , Wang Zhixin , Feng Li 
Published: November 2024

AbstractCD40, a member of the tumor necrosis factor (TNF) receptor superfamily, plays an important role not only in the immune system, but also in tumor progression. CD40 ligation reportedly promotes autophagy in immune cells. However, the effects of CD40 ligation on autophagy and its mechanism in solid tumor cells are still unclear. In this study, we find that CD40 ligation promotes autophagosome formation, and consequently promotes autophagic flux in cervical cancer cells. Mechanically, this effect relies on that ERK contributes to CD40 ligation-induced ATG13 upregulation by p53. Furthermore, we demonstrates that CD40 ligation-induced autophagy increases the radiosensitivity of cervical cancer cells. Taken together, our results provide new evidence for involvement of the CD40 pathway in autophagy and radiotherapy in cervical cancer cells.
Inter- and Intrahemispheric Sources of Vestibular Signals to V1
Authors: Bouvier Guy , Sanzeni Alessandro , Hamada Elizabeth , Brunel Nicolas , Scanziani Massimo 
Published: November 2024

AbstractHead movements are sensed by the vestibular organs. Unlike classical senses, signals from vestibular organs are not conveyed to a dedicated cortical area but are broadcast throughout the cortex. Surprisingly, the routes taken by vestibular signals to reach the cortex are still largely uncharted. Here we show that the primary visual cortex (V1) receives real-time head movement signals — direction, velocity, and acceleration — from the ipsilateral pulvinar and contralateral visual cortex. The ipsilateral pulvinar provides the main head movement signal, with a bias toward contraversive movements (e.g. clockwise movements in left V1). Conversely, the contralateral visual cortex provides head movement signals during ipsiversive movements. Crucially, head movement variables encoded in V1 are already encoded in the pulvinar, suggesting that those variables are computed subcortically. Thus, the convergence of inter- and intrahemispheric signals endows V1 with a rich representation of the animal’s head movements.
Microglia-Dependent and Independent Modulation of Brain Lipid Metabolism in Alzheimer’s Disease Revealed by Pharmacological and Genetic Microglial Depletion
Authors: Xu Ziying , Shabestari Sepideh Kiani , Barannikov Savannah , Bieniek Kevin F. , Blurton-Jones Mathew , Palavicini Juan Pablo , Han Xianlin 
Published: November 2024

AbstractAbnormal lipid metabolism in Alzheimer’s disease (AD) was first documented by Alois Alzheimer in his early observations of patients with a then unrecognized brain disease, which he noted was characterized by a significant presence of “adipose inclusions” or “lipoid granules”. Despite this early recognition, until recently the significance of abnormal lipid metabolism in AD has been largely overlooked by the scientific community for decades, highlighting a critical gap in our understanding of this complex disease. In the past decade, numerous loci and genes with genome-wide significant evidence of affecting AD risk have been reported. Notably, a significant portion of these AD risk genes are either preferentially or exclusively expressed by microglia in the brain and/or code for enzymes that directly or indirectly regulate lipid metabolism. This suggests a major, yet uncharacterized, role of microglia in modulating brain lipid metabolism under AD pathological conditions. In our study, we dissected microglia-dependent and independent regulation of lipid metabolism in an AD-like mouse model of amyloidosis, 5xFAD, taking advantage of pharmacological and genetic interventions to eliminate microglia. Using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL), we identified overt changes in a number of AD-associated lipids (ADALs) in postmortem patient brains and mouse models of amyloidosis. This included bis(monoacylglycerol)phosphate (BMP), a lipid class enriched in endosomal/lysosomal compartments, and the two most abundant classes of lysophospholipids: lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), which are commonly associated with inflammation. Our findings revealed that microglial depletion prevented the accumulation of arachidonic acid-containing BMP species, which are associated with lysosomal activation induced by amyloidosis via a mechanism that involves progranulin, coded by AD risk geneGRN, as shown by targeted transcriptomics, immunoblotting, and immunofluorescence. Surprisingly, AD-associated LPC and LPE accumulation was not driven by microglia. Instead, LPC accumulation correlated with astrocytic activation, while LPE accumulation seems to be associated with oxidative stress. In summary, we uncovered novel microglia-dependent and independent mechanisms that drive lipid dysregulation in AD. These findings may be mechanistically linked with the early glial lipoid deposits described by Dr. Alzheimer.Abstract FigureGraphical Abstract.
Neural evidence for decision-making underlying attractive serial dependence
Authors: Shan Jiangang , Hajonides Jasper E. , Myers Nicholas E. 
Published: November 2024

SummaryRecall of stimuli is biased by stimulus history, variously manifested as an attractive bias toward or repulsive bias from previous stimuli (i.e., serial dependence). It is unclear when attractive vs repulsive biases arise and if they share neural mechanisms. A recent model of attractive serial dependence proposes a two-stage process in which adaptation causes a repulsive bias during encoding that is later counteracted by an attractive bias at the decision-making stage in a Bayesian-inference-like manner. Neural evidence exists for a repulsive bias at encoding, but evidence for the attractive bias during the response period has been more elusive. We recently [1] showed that while different stimuli in trial history exerted different (attractive or repulsive) serial biases on behavioral reports, during encoding the neural representation of the current item was always repulsively biased. Here we assessed whether this discrepancy between neural and behavioral effects is resolved during subsequent decision-making. Multivariate decoding of magnetoencephalography data during working memory recall showed a neural distinction between attractive and repulsive biases: an attractive neural bias emerged only late in recall. But stimuli that created a repulsive bias on behavior led to a repulsive neural bias early in the recall phase, suggesting that it had already been incorporated earlier. Our results suggest that attractive (but not repulsive) serial dependence arises during decision-making, and that priors that influence post-perceptual decision-making are updated by the previous trial’s target, but not by other stimuli.
Value-based education in NEP 2020: fostering ethical and moral growth through Dharma
Authors: Isser Suyasha Singh , Raj Nihal , Tomar Mayank , Marwaha Sanjana Sharma , Shastri Swati 
Published: November 2024

PurposeThe research examines how the principle of Dharma can be included in the Indian National Education Policy (NEP) 2020. The study seeks to know how Dharma as an educational framework can be infused with contemporary education to promote moral and ethical development as well as intellectual growth among students in India.Design/methodology/approachThis research uses qualitative analysis of NEP 2020 documents and literature related to Indian Knowledge Systems (IKS) and the concept of Dharma. It analyses the philosophical bases behind NEP including traditional texts like Vedas, Upanishads, among others. Moreover, this study also evaluates how current Dharma teachings are implemented into curriculum by assessing its present status of incorporation as a part of Indian Knowledge System.FindingsThis research has found that national educational reforms have considered many traditional Indian beliefs and values, but they have not done enough when it comes to incorporating Indian Knowledge System and the concept of Dharma into practice through the curriculum. The paper advocates for a system that is grounded on morals, thus blending the current learning standards with cultural heritage. These findings call for continuous endeavouring in order to embed ethical and moral dimensions of Dharma across all levels within India’s education systems.Practical implicationsThe integration of Dharma and IKS in education can enhance the development of well-rounded individuals who are not only intellectually competent but also ethically and morally grounded. This strong foundation of Dharma will also act as a personal and professional guide. Educators and policymakers can use these insights to design curricula that promote holistic growth, aligning with both global educational standards and cultural values.Originality/valueThis paper examines the philosophical and ethical foundation of NEP 2020 instead of only considering its pedagogical and skill-enhancement characteristics, thereby giving a fresh viewpoint. It contributes to the discussion on educational reforms in India by highlighting how present educational needs should be linked with traditional values. The research shows that the concept of dharma can help learners develop holistically so that they can meet present-day problems without losing touch with timeless morals.
A bibliometric analysis on the role of corporate governance in micro, small and medium enterprises
Authors: Gora Kapil , Yadav Mahender 
Published: November 2024

Purpose
The purpose of this study is to analyse the existing research on the significance of corporate governance in micro, small and medium-sized enterprises (MSMEs) to identify significant contributors, emerging trends and prospective future research areas.

Design/methodology/approach
The authors perform a bibliometric analysis using a data set of 343 papers extracted from the Scopus database. R-studio software was used for performance analysis, while VOSviewer software was used for scientific mapping.

Findings
The study’s findings demonstrate that the research has attracted the attention of academics, which has led to a major rise in research over the previous two decades. “Corporate Ownership and Control” is the top contributing journal with the publication of 16 articles. The USA and UK are the top most productive countries. Simon Fraser University of Canada is the most contributing institution. Moreover, this study has identified four major themes: corporate governance assistance to small and medium enterprises, the role of corporate governance in society and management, family ownership and its importance in entrepreneurship, corporate governance issues, family firms and firm performance. Furthermore, the paper also defines the future research scope in each theme.

Originality/value
This study serves as a guide by mapping and analysing the intellectual structure of the corporate governance of MSMEs’ publications. Through this research, the authors better understand the academicians, managers, entrepreneurs and regulators about the condition of entrepreneurship and how they help businesses improve their performance. To the best of the authors’ knowledge, this is the first study to thoroughly analyse the literature on the role of corporate governance in MSMEs using bibliometrics.
GREEN WATECH: low-cost technology for wastewater treatment
Authors: Agarwal Manish , Anirudhan Anil , Dutta Sanjib 
Published: November 2024

Learning outcomes
After completion of the case study, the students will be able to discuss how social entrepreneurs identify problems and convert them into opportunities, analyze the challenges faced by social entrepreneurs in setting up and growing a new venture and formulate an expansion strategy for a startup.

Case overview/synopsis
Over 2.6 billion people worldwide needed access to sanitation services, and most of them stayed in rural areas. Lack of access to sanitation had several negative consequences. In the Middle East North Africa (MENA) region, sanitation was one of the major challenges, with 66 million people still lacking basic sanitation facilities. Additionally, a very small proportion of the wastewater was properly treated. This lack of access to sanitation was a major barrier to economic development and poverty reduction. Out of the 17 most water-stressed countries in the world, 11 were in the MENA region. About 15 million people in rural Morocco did not have a proper and sustainable sanitation system. However, there was an enormous opportunity to use wastewater as a resource. The global market for wastewater treatment services was valued at US$53bn in 2021, and it was expected to grow to more than US$71bn by 2026. Two Moroccan scientists – Dr Salma Bougarrani and Dr Lahbib Latrach, who were born and brought up in Morocco and had seen the wastewater problem very closely, decided to help the people at the bottom of pyramid (BoP) after completing their PhD in environment and water treatment technologies and multisoil-layering technology. They founded GREEN WATECH, a social enterprise, in 2018, which provided a low-cost, efficient and practical solution for wastewater management in the rural areas of Morocco. GREEN WATECH won many awards and cash prizes for its product and business plan. The company had already reached five regions of Morocco and positively impacted the lives of thousands of Moroccans. The founders were planning to expand to areas in the rest of Morocco and other African and Middle East countries. GREEN WATECH had the potential to significantly impact the lives of people in rural areas and help improve wastewater management systems in developing countries through its patented technology. However, the founders faced several challenges in making their dream a reality. They needed a bigger team to expand to different locations and countries but were finding it difficult to get the right people. They also needed funds to expand their geographical reach but found it tough to get investors as they were still unable to break even. It remained to be seen how the founders of GREEN WATECH would achieve their expansion goals and help people at the BoP in other developing countries.

Complexity academic level
This case study is suited to the Master of Business Administration/Master of Science and executive program.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.