bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural killer cell-mimic nanoparticles can actively target and kill acute myeloid leukemia cells
Authors: Alizadeh Zeinabad Hojjat , Yeoh Wen Jie , Lomora Mihai , Banz Yara , Riether Carsten , Krebs Philippe , Szegezdi Eva 
Published: September 2022

AbstractNatural killer (NK) cells are effector lymphocytes of the innate immune system which play a crucial role in recognizing and killing emerging tumor cells. However, as the tumor evolves, it develops mechanisms to inactivate NK cells or hide from them. Here, we engineered a modular nanoplatform that acts as NK cells (NK cell-mimics), carrying the tumor-recognition and death ligand-mediated tumor-killing properties of an NK cell, yet without being subject to tumor-mediated inactivation. In particular, NK cell mimic nanoparticles (NK.NPs) incorporate two key features of activated NK cells: cytotoxic activity via the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), and an adjustable tumor cell recognition feature based on functionalization with the NK cell Fc-binding receptor (CD16, FCGR3A) peptide, enabling the NK.NPs to bind antibodies targeting tumor antigens. NK.NPs showed potent in vitro cytotoxicity against a broad panel of cancer cell lines. Upon functionalizing the NK.NPs with daratumumab, a clinically used antibody specific for the CD38 protein expressed by AML cells, NK.NPs effectively targeted and eliminated patient-derived acute myeloid leukemia (AML) blasts and leukemia-initiating cells as well as CD38-positive AML cells in vivo, in a disseminated AML xenograft system. Specifically, NK.NPs lead to a significant reduction of AML burden in the bone marrow, spleen, and peripheral blood compared to non-targeted TRAIL-functionalized liposomes. Taken together, these findings demonstrate that NK.NPs are effective in mimicking NK cells’ antitumorigenic function and thereby underline their use as therapeutic tools.
Branch point evolution controls species-specific alternative splicing and regulates long term potentiation
Authors: Franz Andreas , Weber A. Ioana , Preußner Marco , Dimos Nicole , Stumpf Alexander , Ji Yanlong , Moreno-Velasquez Laura , Voigt Anne , Schulz Frederic , Neumann Alexander , Kuropka Benno , Kühn Ralf , Urlaub Henning , Schmitz Dietmar , Wahl Markus C. , Heyd Florian 
Published: September 2022

AbstractRegulation and functionality of species-specific alternative splicing has remained enigmatic to the present date. Calcium/calmodulin-dependent protein kinase IIβ (CaMKIIβ) is expressed in several splice variants and plays a key role in learning and memory. Here, we identify and characterize several primate-specific CAMK2B splice isoforms, which show altered kinetic properties and changes in substrate specificity. Furthermore, we demonstrate that primate-specific Camk2β alternative splicing is achieved through branch point weakening during evolution. We show that reducing branch point and splice site strengths during evolution globally renders constitutive exons alternative, thus providing a paradigm for cis-directed species-specific alternative splicing regulation. Using CRISPR/Cas9 we introduced a weaker human branch point into the mouse genome, resulting in human-like CAMK2B splicing in the brain of mutant mice. We observe a strong impairment of long-term potentiation in CA3-CA1 synapses of mutant mice, thus connecting branch point-controlled, species-specific alternative splicing with a fundamental function in learning and memory.
Amyloidogenic Propensity of Self-Assembling Peptides and their Adjuvant Potential for use as DNA Vaccines
Authors: Shrimali Paresh C. , Chen Sheng , Dreher Rachel , Howard Matthew K. , Buck Jeremy , Kim Darren , Rudra Jai S. , Jackrel Meredith E. 
Published: September 2022

ABSTRACTDe novo designed peptides that self-assemble into cross-β rich fibrillar biomaterials have been pursued as an innovative platform for the development of adjuvant- and inflammation-free vaccines. However, they share structural properties similar to amyloid species implicated in neurodegenerative diseases, which has been a long-standing concern for their translation. Here, we comprehensively characterize the amyloidogenic character of the amphipathic self-assembling cross-β peptide KFE8, compared to pathological amyloid and amyloid-like proteins α-synuclein (α-syn) and TDP-43. Further, we developed plasmid-based DNA vaccines with the KFE8 backbone serving as a fibrillizing scaffold for delivery of a GFP model antigen. We find that expression of tandem repeats of KFE8 is non-toxic and can be efficiently cleared by autophagy. We also demonstrate that synthetic KFE8 nanofibers do not cross-seed amyloid formation of α-syn in mammalian cells compared to α-syn preformed fibrils. In mice, vaccination with plasmids encoding the KFE32-GFP fusion protein elicited robust immune responses, inducing production of significantly higher levels of anti-GFP antibodies compared to soluble GFP or α-syn tagged GFP. Antigen-specific CD8+T cells were also detected in the spleens of vaccinated mice and cytokine profiles from antigen recall assays indicate a balanced Th1/Th2 response. These findings illustrate that cross-β-rich peptide nanofibers have distinct properties from those of pathological amyloidogenic proteins, and are an attractive platform for the development of DNA vaccines with self-adjuvanting properties and improved safety profiles.
Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light induced damage in Drosophila
Authors: Hebbar Sarita , Traikov Sofia , Hälsig Catrin , Knust Elisabeth 
Published: September 2022

AbstractTissue health is regulated by a myriad of exogenous or endogenous factors. Here we investigated the role of the conserved Kynurenine pathway (KP) in maintaining retinal homeostasis in the context of light stress in Drosophila melanogaster. cinnabar, cardinal and, scarlet, are fly genes that encode different steps in the KP. Along with white, these genes are known regulators of brown pigment (ommochrome) biosynthesis. Using white as a sensitized genetic background, we showed that mutations in cinnabar, cardinal, and scarlet differentially modulate light-induced retinal damage. Mass Spectrometric measurements of KP metabolites in flies with different genetic combinations support the notion that increased levels of 3-hydroxykynurenine (3OH-K) and Xanthurenic acid (XA) enhance retinal damage, whereas Kynurenic Acid (KYNA) and Kynurenine (K) are neuro-protective. This conclusion was corroborated by showing that feeding 3OH-K results in enhanced retinal damage, whereas feeding KYNA protects the retina in sensitized genetic backgrounds. Interestingly, the harmful effects of free 3OH-K are diminished by its sub-cellular compartmentalization within the cell. Sequestering of 3OH-K enables the quenching of its toxicity through conversion to brown pigment or conjugation to proteins. This work enabled us to decouple the role of these KP genes in ommochrome formation from their role in retinal homeostasis. Additionally, it puts forward new hypotheses on the importance of the balance of KP metabolites and their compartmentalization in disease alleviation.
Ceramide-1-phosphate transfer protein enhances lipid transport by disrupting hydrophobic lipid–membrane contacts
Authors: Rogers Julia R. , Geissler Phillip L. 
Published: September 2022

AbstractCellular distributions of the sphingolipid ceramide-1-phosphate (C1P) impact essential biological processes. C1P levels are spatiotemporally regulated by ceramide-1-phosphate transfer protein (CPTP), which efficiently shuttles C1P between organelle membranes. Yet, how CPTP rapidly extracts and inserts C1P into a membrane remains unknown. Here, we devise a multiscale simulation approach to elucidate biophysical details of CPTP-mediated C1P transport. We find that CPTP binds a membrane poised to extract and insert C1P and that membrane binding promotes conformational changes in CPTP that facilitate C1P uptake and release. By significantly disrupting a lipid’s local hydrophobic environment in the membrane, CPTP lowers the activation free energy barrier for passive C1P desorption and enhances C1P extraction from the membrane. Upon uptake of C1P, further conformational changes may aid membrane unbinding in a manner reminiscent of the electrostatic switching mechanism used by other lipid transfer proteins. Insertion of C1P into an acceptor membrane, eased by a decrease in membrane order by CPTP, restarts the transfer cycle. Most notably, we provide molecular evidence for CPTP’s ability to catalyze C1P extraction by breaking hydrophobic C1P–membrane contacts with compensatory hydrophobic lipid–protein contacts. Our work, thus, provides biophysical insights into how CPTP efficiently traffics C1P between membranes to maintain sphingolipid homeostasis and, additionally, presents a simulation method aptly suited for uncovering the catalytic mechanisms of other lipid transfer proteins.Author summaryCritical cellular processes require spatiotemporal regulation of sphingolipid levels among organelle membranes. Programmed cell death and inflammation, for example, are impacted by the distribution of ceramide-1-phosphate (C1P). C1P levels are specifically altered by ceramide-1-phosphate transfer protein (CPTP), which mediates C1P intermembrane transport. Using a multiscale simulation approach tailored to studying lipid transport, we elucidate key steps in the molecular mechanism used by CPTP to rapidly transport C1P between membranes: Through conformational changes that are coupled to membrane binding, CPTP significantly disrupts C1P’s local hydrophobic environment in a membrane and catalyzes its extraction. Since this catalytic mechanism is biophysically related to that of passive lipid transport, it may be ubiquitously used by lipid transport proteins to rapidly traffic lipids between membranes and ensure membrane homeostasis. Our multiscale simulation approach offers a framework to test this hypothesis and, thus, further our molecular knowledge of how lipid transfer proteins function to regulate cellular lipid distributions.
MAM: Flexible Monte-Carlo Agent based Model for Modelling COVID-19 Spread
Authors: De-Leon Hilla , Aran Dvir 
Published: September 2022

AbstractIn the two and half years since SARS-CoV-2 was first detected in China, hundreds of millions of people have been infected and millions have died. Along with the immediate need for treatment solutions, the COVID-19 pandemic has reinforced the need for mathematical models that can predict the spread of the pandemic in an ever-changing environment. The susceptible-infectious-removed (SIR) model has been widely used to model COVID-19 transmission, however, with limited success. Here, we present a novel, dynamic Monte-Carlo Agent-based Model (MAM), which is based on the basic principles of statistical physics. Using data from Israel on three major outbreaks, we compare predictions made by SIR and MAM, and show that MAM outperforms SIR in all aspects. Furthermore, MAM is a flexible model and allows to accurately examine the effects of vaccinations in different subgroups, and the effects of the introduction of new variants.
Study on the interactions between cisplatin and cadherin
Authors: Wang Xitong , Sun Jixiang , Shao Kai , Zhi Hongxin , Lin Yamei , Fu Yujie , Liu Zhiguo 
Published: September 2022

AbstractCisplatin is an important platinum drug in the chemotherapy of many malignant tumors in clinical application. It is well accepted that its main target is DNA molecule. However, recent studies have shown that platinum drugs may also act on some important functional proteins in the human body and have complicate effects on their efficacy. E-cadherin is newly discovered glycoproteins which have been regarded as the important signs of the occurrence and development of some tumors. In this study, the interactions between cisplatin and E-cadherin were explored by fluorescence spectroscopy and atomic force microscopy (AFM). The fluorescence spectroscopy results indicated that cisplatin can efficiently quench the fluorescence of E-cadherin, and the calculated binding constant Kb was 3.20×106 (25°C), 1.36 ×106(31°C) and 8.22×105 L mol-1 (37°C). The thermodynamic parameters ΔH <0, ΔS <0, ΔG <0, reveal that the fluorescence quenching effect of cisplatin on E-cadherin is static quenching, which is dominated by hydrogen bond and van der Waals interaction. The AFM results revealed that there was a staggered interaction between the intermolecular domains of E-cadherin to form a long spherical chain structure. The addition of cisplatin could significantly affect the staggered effect of the E-cadherin molecules. All these results confirmed that there are strong interactions between cisplatin and cadherin.
Impact of technology, health and consumer-related factors on continued usage intention of wearable fitness tracking (WFT) devices
Authors: Puri Sandeep , Pandey Shweta , Chawla Deepak 
Published: September 2022

PurposeThis paper aims to explore factors impacting wearable fitness tracking (WFT) device continued usage intention from perspectives of technology attributes (autonomy benefits), health attributes (self-health management benefits, diet-control benefits and health self-efficacy), and consumer attributes (age, gender, technological innovativeness, symbolic benefits, social benefits and hedonic benefits).Design/methodology/approachThe study integrates constructs from the technology acceptance theories and the health promotion model to develop the research model and hypothesis. The empirical analysis was conducted using data from 217 respondents from India. Logistic regression was used to identify factors that discriminate between groups with low and high continued usage intentions.FindingsResults indicate higher continued usage intention for WFT devices is driven by perceived benefits-health, autonomy, social and hedonic, and individual characteristics-technological innovativeness and perceived health self-efficacy. Further, perceived symbolic benefits, diet control benefits, age, and gender does not discriminate between the groups with low and high continued usage intentions.Research limitations/implicationsThe results may be limited to the context of the sample and the factors considered. The study suggests future research areas.Practical implicationsThe paper offers insights for marketers, governments, insurance firms, and related healthcare services on promoting higher usage of WFT devices to yield dual benefits of preventive healthcare and higher profitability.Originality/valueThe study extends existing research by examining factors across consumer, health, and technological domains in a single framework and adds to the limited research in the context of usage of WFT devices in developing countries.
Evaluating team dynamics in interdisciplinary science teams
Authors: Bolduc Sara , Knox John , Ristroph E. Barrett 
Published: September 2022

PurposeThis article considers how the evaluation of research teams can better account for the challenges of transdisciplinarity, including their larger team size and more diverse and permeable membership, as well as the tensions between institutional pressures on individuals to publish and team goals.Design/methodology/approachAn evaluation team was retained from 2015 to 2020 to conduct a comprehensive external evaluation of a five-year EPSCoR-funded program undertaken by a transdisciplinary research team. The formative portion of the evaluation involved monitoring the program’s developmental progress, while the summative portion tracked observable program outputs and outcomes as evidence of progress toward short- and long-term goals. The evaluation team systematically reviewed internal assessments and gathered additional data for an external assessment via periodic participation in team meetings, participant interviews and an online formative team survey (starting in Year 2).FindingsSurvey participants had a better understanding of the project’s “Goals and Vision” compared to other aspects. “Work Roles,” and particularly the timeliness of decision-making, were perceived to be a “Big Problem,” specifically in regard to heavy travel by key managers/leadership. For “Communication Channels,” Year 2 tensions included differing views on the extent to which management should be collaborative versus “hierarchical.” These concerns about communication demonstrate that differences in language, culture or status impact the efficiency and working relationship of the team. “Authorship Credit/Intellectual Property” was raised most consistently each year as an area of concern.Originality/valueThe study involves the use of a unique survey approach.
The Russian Federation's renewable energy development determinants: evidence from empirical research
Authors: Kilinc-Ata Nurcan , Dolmatov Ilya 
Published: September 2022

PurposeThe Russian Federation is one of the world’s largest exporters of fossil-based energy sources such as oil, natural gas and coal. Approximately 90% of the energy production in the Russian Federation consists of oil, natural gas and coal. Renewable energy (RE) in the Russian Federation mainly comprises hydroelectric energy. The purpose of this paper is to identify the factors that influenced the growth of RE resources in the Russian Federation between 1990 and 2020.Design/methodology/approachThe unit root tests augmented Dickey and Fuller and Phillips and Perron, as well as Johansen cointegration and Granger causality approaches, were used. This study was conducted using vector error correction models for the years 1990–2020.FindingsThe cointegration method's findings demonstrate that while a rise in non-RE sources has a negative impact on RE development, an increase in income, energy consumption, trade openness and CO2emissions has a favorable impact on RE expansion. The vector error correction model Granger causality test also shows a unidirectional relationship between RE and non-RE sources, gross domestic product, energy consumption and CO2emissions. Trade openness, on the other hand, has no causal association with RE.Practical implicationsThe Russian Federation must consider the practical implications of RE sources. However, there is a greater need for the Russian Federation to frame sound energy policies for RE development.Originality/valueThis paper aims to fill a gap in the literature on Russian RE development. Furthermore, the results of the methodological analysis can be used to guide policymakers in the field of RE development. This paper is also more policy-relevant and is quite useful in the context of sustainable energy development.
Blending traditionalism with legalism: a typology of understanding corporate governance systems in Ghanaian Family-owned businesses (FOBs) from a Bourdieusian perspective
Authors: Agyenim-Boateng Cletus , Iddrisu Sulemana , Otieku James 
Published: September 2022

PurposeThis paper aims to examine the nature of corporate governance systems in Ghanaian Family-owned Businesses (FOBs). Specifically, the study investigates the nature of boardroom decisions structures, sources of governance regulations and family roles in corporate governance.Design/methodology/approachDrawing on Bourdieusian perspectives of the field, capital, habitus and doxa, a case study design is used to gather detailed insights about the phenomena. Purposively, the study conducts 20 interviews with participants from 15 FOBs in Ghana. The interview data are complemented with secondary sources, such as FOB handbooks, website information, legal documents and scriptures. Subsequently, data gathered were thematically analysed.FindingsThe study finds that human actors blended traditionally tacit and legally expressed boardroom decisions structures in FOBs governance. Again, traditional values, social acceptance of religious sociology and regulatory frameworks of the field dictate corporate governance practices in FOBs. In multiple family ownerships, orthodoxy of doxa is challenged; hence, power struggles and family roles in governance depend on capital possessed by social actors.Practical implicationsTo continue as a going concern, FOBs must be mindful of traditional, religious sociology of family and regulatory frameworks within the field in which they operate. This is because, without this, the going concern of FOBs becomes suspicious and highly unlikely, especially where there are multiple family ownership and generations.Originality/valueThe previous literature predominantly focussed on formal boardroom structures in addressing FOBs' corporate governance issues. Notwithstanding, family governance risk of domineering and distrust associated with traditional and relational governance mechanisms remain under-represented and inconclusive, especially in Sub-Saharan Africa.
Islamic social financing and efficient zakat distribution: impact of fintech adoption among the asnaf in Malaysia
Authors: Ahmad Khaliq , Yahaya Muhamad Hasif 
Published: September 2022

Purpose
The purpose of this study is to investigate the impact factors towards the use of mobile banking among the asnaf for efficient zakat payments by using the unified theory of acceptance and use of technology (UTAUT2) model with additional constructs such as religiosity, attitude and trust (initial trust model) in the Malaysian context.

Design/methodology/approach
The structural equation modelling is used to analyse the data collected from 470 asnaf in Selangor, Malaysia, using the survey methodology.

Findings
This study highlights factors that could influence the asnaf to adopt financial technology (fintech) in order for them to enjoy the benefit of efficient zakat distribution by the zakat institutions.

Research limitations/implications
This study only investigates and contributes added value from the Malaysian context. While it may be similar to other countries that share similar demographic profiles, it might differ for countries that do not have any demographic similarities with Malaysia.

Practical implications
The result of this study highlights the significant factor that practitioners (zakat institutions) in Malaysia could improve fintech adoption and at the same time enhance the efficiency of zakat distribution for the asnaf.

Social implications
This research is basically addressing Islamic social financing. Thus, this study has social implications to address the society's poverty eradication scheme pertaining to the efficiency of zakat institutions in Malaysia for the speedier zakat payments to the asnaf. However, other emerging issues also arise particularly in using the zakat funds by the zakat institutions. By right whatever expenditure that the institutions use from the zakat funds need to have the consent from the asnaf because of their religious and legal rights. Hence, this new gap found from the findings of this study could be further explored by other researchers in future studies especially focusing on the drive towards more efficient administration by the zakat institutions of Malaysia in particular and other zakat institutions spread over Muslim countries elsewhere.

Originality/value
This study found that the UTAUT2 model is rarely used and adopted in investigating technology acceptance and adoption especially when it is related to religious matters such as zakat. Indeed, the findings of this study could be acknowledged as something of original value and significance, therefore contributes to the body of knowledge in this field.