bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of the Local Mechanical Environment on Cell Shape and Chondrogenesis of Mesenchymal Stromal Cells in 3D Biomimetic Composite Materials
Authors: Fenu M. , Muntz I. , Harting D. , Xu J. , D’Este M. , Koenderink G.H. , van Osch G.J.V.M 
Published: September 2023

AbstractEfforts to model and repair connective tissue through engineered tissue constructs have generated great interest in culturing cells in 3d polymer network environments. It has been shown that the polymer environment is influential in determining cellular responses such as differentiation, migration and morphology. Hydrogels are used to mimic the cellular microenvironment, but in most cases hydrogels consisting of one polymeric component are used whereas tissues are composites of different polymers. A clear understanding of how different extracellular components and their mechanical characteristics influence cell behaviour is lacking. Here we developed and characterised composite hydrogels of hyaluronan and fibrin and evaluated their use for cartilage tissue engineering. We demonstrate that these cartilage-mimicking composites have a higher stiffness relative to the individual constituents. Next, we cultured human mesenchymal stromal cells in these 3D hydrogels with chondrogenic media and revealed marked differences in cell morphology, gene expression and cartilage-like matrix deposition depending on the specific extracellular composition. We found that, despite evidence for strong adhesion of the cells to fibrin networks in 2D systems, in 3D systems the primary determinant of cellular morphology is the significantly denser hyaluronan network. Dense hyaluronan hydrogels cause local cell confinement evidenced by rounder cell morphologies, independent of the presence of fibrin. While the composite fibrin-hyaluronan hydrogels led to lower expression of chondrogenic genes than hyaluronan alone, the larger linear modulus and resistance to cell-mediated contraction due to the composite nature of the matrix provides a strong advantage in terms of macroscopic mechanical stability. These findings highlight the potential of multi-component hydrogels for controlling cellular behaviour and bulk mechanical properties of cell-hydrogel constructs independently, therefore opening avenues for better understanding the complex interplay between cells and their extracellular environment and thus improve the biofabrication of connective tissues for disease modelling and tissue regeneration.Graphical Abstract
Enhancing anti-EGFRvIII CAR T cell therapy against glioblastoma with a paracrine SIRPγ-derived CD47 blocker
Authors: Martins Tomás A. , Tatari Nazanin , Kaymak Deniz , Hogan Sabrina , Bartoszek Ewelina M. , Wieboldt Ronja , Ritz Marie-Françoise , Buck Alicia , McDaid Marta , Gerber Alexandra , Beshirova Aisha , Etter Manina M. , Heider Anja , Shekarian Tala , Mohamed Hayget , Schmassmann Philip , Abel Ines , Mariani Luigi , Guzman Raphael , Boulay Jean-Louis , Snijder Berend , Weiss Tobias , Läubli Heinz , Hutter Gregor 
Published: September 2023

AbstractA major challenge for chimeric antigen receptor (CAR) T cell therapy against glioblastoma (GBM) is its immunosuppressive tumor microenvironment (TME), which is densely populated and supported by protumoral glioma-associated microglia and macrophages (GAMs). Targeting of CD47, a “don’t-eat-me” signal overexpressed by tumor cells, disrupts the CD47-SIRPα axis and induces GAM phagocytic function. However, antibody-mediated CD47 blockade monotherapy is associated with toxicity and low bioavailability in solid tumors. To overcome these limitations, we combined local CAR T cell therapy with paracrine GAM modulation for more effective elimination of GBM. To this end, we engineered a new CAR T cell against epidermal growth factor receptor variant III (EGFRvIII) that constitutively secretes a SIRPγ-related protein (SGRP) with high affinity to CD47. Anti-EGFRvIII-SGRP CAR T cells eliminated EGFRvIII+GBM in a dose-dependent mannerin vitroand eradicated orthotopically xenografted EGFRvIII-mosaic GBM by locoregional applicationin vivo.This resulted in significant tumor-free long-term survival, followed by partial tumor control upon tumor re-challenge. The combination of anti-CD47 antibodies with anti-EGFRvIII CAR T cells failed to achieve a similar therapeutic effect, underscoring the importance of sustained paracrine GAM modulation. Multidimensional brain immunofluorescence microscopy and in-depth spectral flow cytometry on GBM-xenografted brains showed that anti-EGFRvIII-SGRP CAR T cells accelerated GBM clearance, increased CD68+cell trafficking to tumor scar sites, and induced myeloid-mediated tumor cell uptake. Additionally, in a peripheral lymphoma mouse xenograft model, anti-CD19-SGRP CAR T cells had superior efficacy compared to conventional anti-CD19 CAR T cells. Validation on human GBM explants revealed that anti-EGFRvIII-SGRP CAR T cells had similar tumor-killing capacity to anti-EGFRvIII CAR monotherapy, but showed a slight improvement in maintenance of tumor-infiltrated CD14+myeloid cells. Thus, local anti-EGFRvIII-SGRP CAR T cell therapy combines the potent antitumor effect of engineered T cells with the modulation of the surrounding innate immune TME, resulting in the additive elimination of bystander EGFRvIII-tumor cells in a manner that overcomes major mechanisms of CAR T cell therapy resistance, including tumor innate immune suppression and antigen escape.
Longitudinal Micro-Computed Tomography Detects Onset and Progression of Pulmonary Fibrosis in ConditionalNedd4-2Deficient Mice
Authors: Leitz Dominik H.W. , Konietzke Philip , Wagner Willi , Mertiny Mara , Benke Claudia , Schneider Thomas , Stiller Wolfram , Kauczor Hans-Ulrich , Mall Marcus A. , Duerr Julia , Wielpütz Mark O. 
Published: September 2023

ABSTRACTObjectivesIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease which is usually diagnosed late in advanced stages. Little is known about the subclinical development of IPF. We previously generated a mouse model with conditionalNedd4-2deficiency (Nedd4-2−/−) that develops IPF-like lung disease. The aim of this study was to characterize the onset and progression of IPF-like lung disease in conditionalNedd4-2−/−mice by longitudinal micro- computed tomography (CT).MethodsIn vivomicro-CT was performed longitudinally in control and conditionalNedd4- 2−/−mice at 1, 2, 3, 4 and 5 months after doxycycline induction. Further, terminalin vivomicro-CT followed by pulmonary function testing andpost mortemmicro-CT was performed in age-matched mice. Micro-CT images were evaluated for pulmonary fibrosis using an adapted fibrosis scoring system.ResultsMicro-CT is sensitive to detect onset and progression of pulmonary fibrosisin vivoand to quantify distinct radiological IPF-like features along disease development in conditionalNedd4-2−/−mice. Nonspecific interstitial alterations were detected from 3 months, whereas key features such as honeycombing-like lesions were detected from 4 months onwards. Pulmonary function inversely correlated within vivo(r=-0.725) andpost mortem(r=-0.535) micro-CT fibrosis scores.ConclusionLongitudinal micro-CT enablesin vivomonitoring of onset and progression and detects radiologic key features of IPF-like lung disease in conditionalNedd4-2−/−mice. Our data support micro-CT as sensitive quantitative endpoint for preclinical evaluation of novel antifibrotic strategies.NEW & NOTEWORTHYIPF diagnosis, particularly in early stages, remains challenging. In this study micro-CT is used in conditionalNedd4-2−/−mice to closely monitor the onset and progression of IPF-like lung disease. This allowed us to track for the first time how nonspecific lung lesions develop into key IPF-like features. This approach offers a non-invasive method to monitor pulmonary fibrosisin vivo, providing a quantitative endpoint for preclinical evaluation of novel antifibrotic strategies.
Weak neuronal glycolysis sustains cognition and organismal fitness
Authors: Jimenez-Blasco Daniel , Agulla Jesús , Lapresa Rebeca , Garcia-Macia Marina , Bobo-Jimenez Veronica , Garcia-Rodriguez Dario , Manjarrez-Raza Israel , Fernandez Emilio , Jeanson Yannick , Khoury Spiro , Portais Jean-Charles , Padro Daniel , Ramos-Cabrer Pedro , Carmeliet Peter , Almeida Angeles , Bolaños Juan P. 
Published: September 2023

AbstractThe energy cost of neuronal activity is mainly sustained by glucose1,2. However, in an apparent paradox, neurons only weakly metabolize glucose through glycolysis3,4,5,6, a circumstance that can be accounted for by the constant degradation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (Pfkfb3)3,7,8, a key glycolysis-promoting enzyme. To evaluate thein vivophysiological significance of this hypo-glycolytic metabolism, here we genetically engineered mice with their neurons transformed into active glycolytic cells through Pfkfb3 expression.In vivomolecular, biochemical, and metabolic flux analyses of these neurons revealed an accumulation of anomalous mitochondria, complex I disassembly, bioenergetic deficiency and mitochondrial redox stress. Notably, glycolysis-mediated NAD+reduction impaired sirtuin-dependent autophagy. Furthermore, these mice displayed cognitive decline and a metabolic syndrome that was mimicked by confining Pfkfb3 expression to hypothalamic neurons. Neuron-specific genetic ablation of mitochondrial redox stress corrected these alterations. Thus, the weak glycolytic nature of neurons is required to sustain higher-order organismal functions.
Apolipoprotein-E transforms intracellular Amyloid-β oligomers to a more toxic state
Authors: Dey Arpan , Verma Aditi , Bhaskar Uchit , Sarkar Bidyut , Kallianpur Mamata , Visvakarma Vicky , Das Anand Kant , Garai Kanchan , Mukherjee Odity , Ishii Kunihiko , Tahara Tahei , Maiti Sudipta 
Published: September 2023

AbstractIt is poorly understood why ApoE variants are major genetic risk factors in Alzheimer’s disease (AD), which is associated with the aggregation of amyloid beta (Aβ). Here we directly image specific changes in small Aβ oligomers in rat brain cells that correlate with the cellular ApoE content. An inhibitor of Aβ-ApoE interaction suppresses this change and concomitantly reduces Aβ toxicity in a dose-dependent manner. Single-molecule techniques show changes both in the conformation and the stoichiometry of the oligomers. hiPSC-derived neural stem cells from Alzheimer’s patients also show similar changes. Interaction with ApoE therefore changes the oligomeric state, membrane affinity, and toxicity of Aβ oligomers, and can be directly read out in live cells. Our findings suggest a rapid and quantitative assay for AD drug discovery.One-sentence summaryApoE causes specific toxicogenic modifications of Aβ oligomers, and these changes can be directly imaged in live cells.
Inhibition of CREB binding and function with a dual-targeting ligand
Authors: Liu Yejun , Joy Stephen T. , Henley Madeleine J. , Yates Joel A. , Merajver Sofia D. , Mapp Anna K. 
Published: September 2023

AbstractCBP/p300 is a master transcriptional coactivator, regulating gene activation by interacting with multiple transcriptional activators. Dysregulation of protein-protein interactions (PPIs) between the CBP/p300 KIX domain and its activators is implicated in a number of cancers including breast, leukemia, and colorectal cancer. However, KIX is typically considered ‘undruggable’ because of its shallow binding surfaces lacking both significant topology and promiscuous binding profiles. We previously reported a dual-targeting peptide (MybLL-tide) that inhibits the KIX-Myb interaction with excellent specificity and potency. Here we demonstrate a branched, second-generation analog, CREBLL-tide, that inhibits the KIX-CREB PPI with higher potency and selectivity. Additionally, the best of these CREBLL-tide analogs shows excellent and selective anti-proliferation activity in breast cancer cells. These results indicate CREBLL-tide is an effective tool for assessing the role of KIX-activator interactions in breast cancer and expanding the dual-targeting strategy for inhibiting KIX and other coactivators that contain multiple binding surfaces.
Interference Requirements of Type III CRISPR-Cas Systems fromThermus thermophilus
Authors: Karneyeva Karyna , Kolesnik Matvey , Livenskyi Alexei , Zgoda Viktor , Zubarev Vasiliy , Trofimova Anna , Artamonova Daria , Ispolatov Yaroslav , Severinov Konstantin 
Published: September 2023

AbstractAmong the diverse prokaryotic adaptive immunity mechanisms, the Type III CRISPR-Cas systems are the most complex. The multisubunit Type III effectors recognize RNA targets complementary to CRISPR RNAs (crRNAs). Target recognition causes synthesis of cyclic oligoadenylates that activate downstream auxiliary effectors, which affect cell physiology in complex and poorly understood ways. Here, we studied the ability of III-A and III-B CRISPR-Cas subtypes fromThermus thermophilusto interfere with plasmid transformation. We find that for both systems, requirements for crRNA-target complementarity sufficient for interference depend on the target transcript abundance, with more abundant targets requiring shorter complementarity segments. This result and thermodynamic calculations indicate that Type III effectors bind their targets in a simple bimolecular reaction with more extensive crRNA-target base pairing compensating for lower target abundance. Since the targeted RNA used in our work is non-essential for either the host or the plasmid, the results also establish that a certain number of target-bound effector complexes must be present in the cell to interfere with plasmid establishment. For the more active III-A system, we determine the minimal length of RNA-duplex sufficient for interference and show that the position of this minimal duplex can vary within the effector. Finally, we show that the III-A immunity is dependent on the HD nuclease domain of the Cas10 subunit. Since this domain is absent from the III-B system the result implies that theT. thermophilusIII-B system must elicit a more efficient cyclic oligoadenylate dependent response to provide the immunity.
Framework of green finance to attain sustainable development goals: an empirical evidence from the TCCM approach
Authors: Annu  , Tripathi Ravindra 
Published: September 2023

PurposeThe study's objectives are to conduct a comprehensive review of existing knowledge, thoroughly understand the present state of green finance, identify emerging research trends, perform content analysis and offer valuable guidance for advancing this field.Design/methodology/approachData has been collected by selecting highly indexed databases, Scopus and Web of Science. These databases are well-known repositories of academic papers, journals and other scholarly publications related to various fields of study. This research uses the PRISMA methodology for conducting a structured literature review and employs a bibliometric approach to summarize the findings of the previous studies. “R” studio and Biblioshiny are used to clean the data and visualize the results. The TCCM framework is utilized to propose potential avenues for future research in the domain of green finance.FindingsThe research uncovers the potential areas in the domain of green finance for future work, encompassing green bonds, the green economy, connectivity, forces, constraints and sustainable development. Furthermore, this process enhances the theoretical underpinnings of scholarly investigations within the discipline by succinctly synthesizing and evaluating preexisting literature. This contribution could facilitate more informed and focused research endeavors in green finance.Practical implicationsThe research findings have practical implications for researchers, practitioners, regulators, legislators, issuers and investors involved in green finance. The results can take initiatives to improve practices related to issuing and pricing green financial products and enhance the understanding of interconnectedness within the field.Originality/valueThis ground-breaking research sheds light on various emerging areas by taking a new approach, including the most widely read articles, authors and journals and the broader conceptual and intellectual framework. That includes finding and expanding original research streams, summarizing the most seminal works, and suggesting new research pathways.
Equity crowdfunding platforms and sustainable impacts: encountering investors and technological initiatives for tackling social and environmental challenges
Authors: Yáñez-Valdés Claudia , Guerrero Maribel 
Published: September 2023

PurposeInnovative initiatives focusing on social and environmental impact often need help to secure traditional financial resources for their launch. Equity crowdfunding platforms (ECF) provide a potential funding source for these initiatives, particularly for technological inventors. This research paper aims to theorize how ECF campaigns attract investors to invest in technological initiatives with social and environmental value proposition impacts.Design/methodology/approachUsing an inductive qualitative approach, the authors have gained insights, from 35 sustainable technological projects sponsored by a Chilean equity-crowdfunding platform, regarding the business model's transformation to achieve sustainable social and environmental impacts.FindingsFindings show that disruptive technologies and sustainable aims are pivotal factors in successfully attracting investors to support sustainable technological initiatives through ECF platforms or campaigns. These factors led investors to actively engage with these projects and contribute to the value-creation process by transforming business models with social and environmental impacts and utilizing sustainable technology to enhance efficiency and optimize available resources.Research limitations/implicationsDue to the nature of this research, researchers must test the proposed conceptual framework using longitudinal quantitative data from multiple ECF platforms, technological solutions and investors worldwide in future research to enhance the comprehension of this phenomenon.Practical implicationsThe findings highlight the significant contribution of ECF platforms and technological portfolios toward creating sustainable impacts. It is a good signal for investors interested in investing in technological initiatives and addressing social and environmental challenges.Social implicationsThe contribution of disruptive technological projects from ECF platforms and ECF investors to tackle social and environmental challenges.Originality/valueThis research theorizes how ECF platforms tackle social challenges by encouraging investors to invest and participate with entrepreneurs in the co-creation process of sustainable technological solutions.
Sarcastic emojis: why don’t you understand?
Authors: Kusaila Daniel , Gerhart Natalie 
Published: September 2023

Purpose
Technology-enabled communication used in workplace settings includes nuanced tools such as emojis, that are interpreted differently by different populations of people. This paper aims to evaluate the use of emojis in work environments, particularly when they are used sarcastically.

Design/methodology/approach
This research uses a survey method administered on MTurk. Overall, 200 participants were included in the analysis. Items were contextualized from prior research and offered on a seven-point Likert scale.

Findings
Females are better able to understand if an emoji is used sarcastically. Additionally, older employees are more capable of interpreting sarcasm than younger employees. Finally, understanding of emojis has a negative relationship with frustration, indicating that when users understand emojis are being used sarcastically, frustration is reduced.

Research limitations/implications
This research is primarily limited by the survey methodology. Despite this, it provides implications for theory of mind and practical understanding of emoji use in professional settings. This research indicates emojis are often misinterpreted in professional settings.

Originality/value
The use of emojis is becoming commonplace. The authors show the use of emojis in a professional setting creates confusion, and in some instances can lead to frustration. This work can help businesses understand how best to manage employees with changing communication tools.
Numerical investigation of laminar heat transfer and fluid flow characteristics of Al2O3nanofluid in a double tube heat exchanger
Authors: Tavousi Ebrahim , Perera Noel , Flynn Dominic , Hasan Reaz 
Published: September 2023

PurposeThe purpose of the study is to numerically investigate the characteristics of laminar heat transfer and fluid flow in a double tube heat exchanger (DTHE) using water-aluminum oxide (Al2O3) nanofluid. The study examines the effects of nanofluid in both counter and parallel flow configurations. Furthermore, an exergy analysis is conducted to assess the impact of nanofluid on exergy destruction.Design/methodology/approachThe single-phase method has been used for Al2O3nanoparticles in water as base fluid in a laminar regime for Reynolds numbers from 400 to 2,000. The effects of nanoparticle volume fractions (0 to 0.1), Nusselt number, Reynolds number, heat transfer coefficient, pressure drop, performance evaluation criteria (PEC) and the impact of counter and parallel flow direction have been studied.FindingsThe findings indicate that the incorporation of nanoparticles into the water enhances the heat transfer rate of DTHE. This enhancement is attributed to the improved thermal properties of the working fluid and its impact on the thermal boundary layer. Nusselt number, heat transfer coefficient, and PEC increase by approximately 19.5%, 58% and 1.2, respectively, in comparison to pure water. Conversely, the pressure drop experiences a 5.3 times increase relative to pure water. Exergy analysis reveals that nanofluids exhibit lower exergy destruction compared to pure water. The single-phase method showed better agreement with the experimental results compared to the two-phase method.Originality/valueDimensionless correlations were derived and validated with experimental and numerical results for the Nusselt number and PEC for both counter and parallel flow configurations based on the Reynolds number and nanoparticles volume fraction with high accuracy to predict the performance of DTHE without performing time-consuming simulations. Also, an exergy analysis was performed to compare the exergy destruction between nanofluid and pure water.