bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivoCRISPR screens identify novel virulence genes among proteins of unassigned subcellular localization inToxoplasma
Authors: Tachibana Yuta , Sasai Miwa , Yamamoto Masahiro 
Published: January 2024

ABSTRACTThe research field to identify and characterize virulence genes inToxoplasma gondiihas been dramatically advanced by a series ofin vivoCRISPR screens. Although subcellular localizations of thousands of proteins were predicted by the spatial proteomic method called hyperLOPIT, those of more than 1000 proteins remained unassigned and their essentiality in virulence was also unknown. In this study, we generated two small-scale gRNA libraries targeting approximately 600 hyperLOPIT-unassigned proteins and performedin vivoCRISPR screens. As a result, we identified severalin vivofitness-conferring genes that were previously unreported. We further characterized two candidates, TgGTPase and TgRimM, which are localized in the cytoplasm and the apicoplast, respectively. Both genes are essential for parasite virulence and widely conserved in the phylum Apicomplexa. Collectively, our current study provides a resource for estimating thein vivoessentiality ofToxoplasmaproteins with previously unknown localizations.IMPORTANCEToxoplasma gondiiis a protozoan parasite that causes severe infection in immunocompromised patients or newborns.Toxoplasmapossesses more than 8000 genes; however, the genes that determine parasite virulence were not fully identified. The apicomplexan parasites, includingToxoplasma, developed unique organelles that do not exist in other model organisms; thus, determining the subcellular location of parasite proteins is important for understanding their functions. Here, we usedin vivoCRISPR genetic screens that enabled us to investigate hundreds of genes inToxoplasmaduring mouse infection. We screened approximately 600 parasite proteins with previously unknown subcellular localizations. We identified many novel genes that confer parasite fitness in mice. Among the top hits, we characterized two essential virulence genes, TgGTPase and TgRimM, which are widely conserved in the phylum Apicomplexa. Our findings will contribute to understanding how apicomplexans adapt to the host environment and cause disease.
Degradome analysis to identify direct protein substrates of small-molecule degraders
Authors: Jochem Marco , Schrempf Anna , Wagner Lina-Marie , Cisneros Jose , Ng Amanda , Winter Georg E. , Krijgsveld Jeroen 
Published: January 2024

AbstractTargeted protein degradation (TPD) has emerged as a powerful strategy to selectively eliminate cellular proteins using small-molecule degraders, offering therapeutic promise for targeting proteins that are otherwise undruggable. However, a remaining challenge is to unambiguously identify primary TPD targets that are distinct from secondary downstream effects in the proteome. Here we introduce an approach that combines stable isotope labeling and click-chemistry for selective quantification of protein degradation by mass spectrometry, excluding confounding effects of altered transcription and translation induced by target depletion. We show that the approach efficiently operates at the time scale of TPD (hours) and we demonstrate its utility by analyzing the Cyclin K degraders dCeMM2 and dCeMM4, which induce widespread transcriptional downregulation, and the GSPT1 degrader CC-885, an inhibitor of protein translation. Additionally, we apply it to characterize compound 1, a previously uncharacterized degrader, and identify the zinc-finger protein FIZ1 as a degraded target.
Limited variation in microbial communities across populations ofMacrostelesleafhoppers (Hemiptera: Cicadellidae)
Authors: Mulio Sandra Åhlén , Zwolińska Agnieszka , Klejdysz Tomasz , Prus-Frankowska Monika , Michalik Anna , Kolasa Michał , Łukasik Piotr 
Published: January 2024

SummaryMicrobial symbionts play important roles in insect biology, but their diversity, distribution, and dynamics over time across host populations are poorly understood. We surveyed the spatio-temporal distribution of bacterial symbionts in the broadly distributed and economically significant leafhopper genusMacrosteles, with emphasis onMacrosteles laevis, using host and symbiont marker gene amplicon sequencing. The cytochrome oxidase I (COI) gene data revealed no strong genetic differentiation acrossM. laevispopulations, significant levels of heteroplasmy, and multiple cases of parasitoid infections. 16S rRNA data confirmed the universal presence of the ancient nutritional endosymbiontsSulciaandNasuiaand a high prevalence ofArsenophonus. Interestingly, in contrast to most previously surveyed species, inM. laeviswe found only occasional cases of infection with facultative endosymbionts and other bacteria. There was no significant variation in symbiont prevalence across populations, or among sampling years for the same population. Facultative endosymbionts includingRickettsia,Wolbachia,Cardinium, andLariskella, were more common in other Macrosteles species. Combined, our data demonstrate that not all species show clear spatial and temporal variation in genetic structure and microbial prevalence. However, simultaneous characterization of host and symbiont marker gene amplicons in large insect collections can help understand the dynamics of host-microbe interactions.
Depot-Specific mRNA Expression Programs in Human Adipocytes Suggest Physiological Specialization via Distinct Developmental Programs
Authors: Clemons Heather J. , Hogan Daniel J. , Brown Patrick O. 
Published: January 2024

ABSTRACTAdipose tissue is distributed in diverse locations throughout the human body. Not much is known about the extent to which anatomically distinct adipose depots are functionally distinct, specialized organs, nor whether depot-specific characteristics result from intrinsic developmental programs, as opposed to reversible physiological responses to differences in tissue microenvironment. We used DNA microarrays to compare mRNA expression patterns of isolated human adipocytes and cultured adipose stem cells, before and afterex vivoadipocyte differentiation, from seven anatomically diverse adipose tissue depots. Adipocytes from different depots displayed distinct gene-expression programs, which were most closely shared with anatomically related depots. These depot-specific differences in gene expression were recapitulated when adipocyte progenitor cells from each site were differentiatedex vivo,suggesting that progenitor cells from specific anatomic sites are deterministically programmed to differentiate into depot-specific adipocytes. mRNAs whose expression differed between anatomically diverse groups of depots (e.g., subcutaneous vs. internal) suggest important functional specializations. Many developmental transcription factors showed striking depot-specific patterns of expression, suggesting that adipocytes in each anatomic depot are programmed during early development in concert with anatomically related tissues and organs. Our results support the hypothesis that adipocytes from different depots are functionally distinct and that their depot-specific specialization reflects distinct developmental programs.
Non-contact detection of pyrethroids widely used in vector control byAnophelesmosquitoes
Authors: Kambou Sassan Simplice , Valente Adeline , Agnew Philip , de Sales Hien Domonbabele François , Yerbanga Rakiswendé Serge , Moiroux Nicolas , Dabire Kounbobr Roch , Pennetier Cédric , Cohuet Anna , Carrasco David 
Published: January 2024

AbstractPyrethroids are the most widely used insecticides to control vector borne diseases including malaria. Physiological resistance mechanisms to these insecticides have been well described, whereas those for behavioral resistance remain overlooked. Field data suggest the presence of spatial sensory detection byAnophelesmosquitoes of the pyrethroid molecules used in insecticide-based control tools, such as long-lasting insecticide nets or insecticide residual spraying, opening the way to the emergence of a wide range of behavioral adaptations among malaria vectors. However, the spatial sensory detection of these molecules is controversial and needs to be demonstrated. The goal of this study was to behaviorally characterize the non-contact detection of three of the most common pyrethroids used for malaria vector control: permethrin, deltamethrin an ⍺-cypermethrin.To reach this goal, we recorded the behavior (takeoff response) ofAnopheles gambiaepyrethroid-sensitive and resistant laboratory strains, as well as field collected mosquitoes from the Gambiae complex, when exposed to the headspace of bottles containing different doses of the insecticides at 25 and 35°C, in order to represent a range of laboratory and field temperatures.We found the proportion of laboratory susceptible and resistant female mosquitoes that took off was, in all treatments, dose and the temperature dependent. Sensitive mosquitoes were significantly more prone to take off only in the presence of ⍺-cypermethrin, whereas sensitive and resistant mosquitoes showed similar responses to permethrin and deltamethrin. Field-collected mosquitoes of the Gambiae complex were also responsive to permethrin, independently of the species identity (An. gambiae,An. coluzziandAn. arabiensis) or their genotypes for thekdrmutation, known to confer resistance to pyrethroids.The observed ability ofAnophelesspp. mosquitoes to detect insecticides without contact could favor the evolution of behavioral modifications that may allow them to avoid or reduce the adverse effect of insecticides and thus, the development of behavioral resistance.
Decreasing ganglioside synthesis delays motor and cognitive symptom onset inSpg11knockout mice
Authors: Fortier Manon , Cauhapé Margaux , Buono Suzie , Becker Julien , Menuet Alexia , Branchu Julien , Ricca Ivana , Mero Serena , Dorgham Karim , Hachimi Khalid-Hamid El , Dobrenis Kostantin , Colsch Benoit , Samaroo Dominic , Devaux Morgan , Durr Alexandra , Stevanin Giovanni , Santorelli Filippo M. , Colombo Sophie , Cowling Belinda , Darios Frédéric 
Published: January 2024

AbstractBiallelic variants in theSPG11gene account for the most common form of autosomal recessive hereditary spastic paraplegia characterized by motor and cognitive impairment, with currently no therapeutic option. We previously observed in aSpg11knockout mouse that neurodegeneration is associated with accumulation of gangliosides in lysosomes. To test whether a substrate reduction therapy could be a therapeutic option, we downregulated the key enzyme involved in ganglioside biosynthesis using an AAV-PHP.eB viral vector expressing a miRNA targetingSt3gal5. Downregulation ofSt3gal5inSpg11knockout mice prevented the accumulation of gangliosides, delayed the onset of motor and cognitive symptoms, and prevented the upregulation of serum levels of neurofilament light chain, a biomarker widely used in neurodegenerative diseases. Importantly, similar results were observed upon treatment ofSpg11knockout mice with venglustat, a pharmacological inhibitor of glucosylceramide synthase expected to decrease ganglioside synthesis. Downregulation ofSt3gal5or venglustat treatment ofSpg11knockout mice strongly decreased the formation of axonal spheroids, previously associated with impaired trafficking. Venglustat had similar effect on cultured human SPG11 neurons. In conclusion, this work identifies the first disease-modifying therapeutic strategy in SPG11, and provides data supporting its relevance for therapeutic testing in SPG11 patients.
Encoding of vibrotactile stimuli by mechanoreceptors in rodent glabrous skin
Authors: Medlock Laura , Al-Basha Dhekra , Halawa Adel , Dedek Christopher , Ratté Stéphanie , Prescott Steven A. 
Published: January 2024

AbstractSomatosensory coding in rodents has been mostly studied in the whisker system and hairy skin, whereas the function of low-threshold mechanoreceptors (LTMRs) in rodent glabrous skin has received scant attention, unlike in primates where glabrous skin has been the focus. The relative activation of different LTMR subtypes carries information about vibrotactile stimuli, as does the rate and temporal patterning of LTMR spikes. Rate coding depends on the probability of a spike occurring on each stimulus cycle (reliability) whereas temporal coding depends on the timing of spikes relative to the stimulus cycle (precision). Usingin vivoextracellular recordings in rats and mice, we measured the reliability and precision of LTMR responses to different tactile stimuli including sustained pressure and vibration. Similar to other species, rodent LTMRs were separated into rapid-adapting (RA) or slow-adapting (SA) based on their response to sustained pressure. However, unlike the dichotomous frequency preference characteristic of RAI and RAII afferents in other species, rodent RAs fell along a continuum. Fitting generalized linear models (GLMs) to experimental data reproduced the reliability and precision of rodent RAs. The resulting model parameters highlight key mechanistic differences across the RA spectrum; specifically, the integration window of different RAs transitions from wide to narrow as tuning preferences across the population move from low to high frequencies. Our results show that rodent RAs can support both rate and temporal coding, but their heterogeneity suggests that co-activation patterns play a greater role in population coding than for dichotomously tuned primates RAs.Significance StatementOur sense of touch starts with activation of nerve fibres in the skin. Although response properties of various fibre types are well-established in other species (e.g. primates), quantitative characterization in rats and mice is limited. To fill this gap, we performed a comprehensive electrophysiological investigation into the coding properties of tactile fibres in rodent non-hairy skin and then simulated these fibres to explain differences in their responses. We show that rodent tactile fibres resemble those from other species, but that their heterogeneity at the population level may differ, with potentially important implications for encoding of touch. Simulations reveal intrinsic mechanisms that support this heterogeneity and provide a useful tool to explore somatosensation in rodents.
Ultrafast all-electrical universal nanoqubits
Authors: Perkins David T. S. , Ferreira Aires 
Published: January 2024

We propose how to create, control, and read out real-space localized spin qubits in proximitized finite graphene nanoribbon (GNR) systems using purely electrical methods. Our proposed are formed of in-gap singlet-triplet states that emerge through the interplay of Coulomb and relativistic spin-dependent interactions in GNRs placed on a magnetic substrate. Application of an electric field perpendicular to the GNR heterostructure leads to a sudden change in the proximity couplings, i.e., a quantum quench, which enables us to deterministically rotate the nanoqubit to any arbitrary point on the Bloch sphere. We predict these spin qubits to undergo Rabi oscillations with optimal visibility and frequencies in excess of 10 GHz. Our findings open up an avenue for the realization of graphene-based quantum computing with ultrafast all-electrical methods.

Published by the American Physical Society
2024
Acceptance of the metaverse: a laboratory experiment on augmented and virtual reality shopping
Authors: Xi Nannan , Chen Juan , Gama Filipe , Korkeila Henry , Hamari Juho 
Published: January 2024

PurposeIn recent years, there has been significant interest in adopting XR (extended reality) technologies such as VR (virtual reality) and AR (augmented reality), particularly in retail. However, extending activities through reality-mediation is still mostly believed to offer an inferior experience due to their shortcomings in usability, wearability, graphical fidelity, etc. This study aims to address the research gap by experimentally examining the acceptance of metaverse shopping.Design/methodology/approachThis study conducts a 2 (VR: with vs. without) × 2 (AR: with vs. without) between-subjects laboratory experiment involving 157 participants in simulated daily shopping environments. This study builds a physical brick-and-mortar store at the campus and stocked it with approximately 600 products with accompanying product information and pricing. The XR devices and a 3D laser scanner were used in constructing the three XR shopping conditions.FindingsResults indicate that XR can offer an experience comparable to, or even surpassing, traditional shopping in terms of its instrumental and hedonic aspects, regardless of a slightly reduced perception of usability. AR negatively affected perceived ease of use, while VR significantly increased perceived enjoyment. It is surprising that the lower perceived ease of use appeared to be disconnected from the attitude toward metaverse shopping.Originality/valueThis study provides important experimental evidence on the acceptance of XR shopping, and the finding that low perceived ease of use may not always be detrimental adds to the theory of technology adoption as a whole. Additionally, it provides an important reference point for future randomized controlled studies exploring the effects of technology on adoption.
Market shared liability: an alternative to proportionally impose guilt in civil lawsuits against corporations causing land degradation
Authors: Anand Ghansham , Putri Dita Elvia Kusuma , Adam Tristania Faisa 
Published: January 2024

Purpose
This paper aims to analyze the legal framework of land degradation in Asia and provide market shared liability as a new theory to solve a problem regarding the difficulty for judges to determine the percentage of compensation for corporations responsible for land degradation. This paper aims also presents a theory to solve the problem of the vacuum of legal responsibility theory, which can make corporations proportionally responsible in terms of causing land degradation.

Design/methodology/approach
This was done through legal research methods, mainly with systematical interpretation. The approach used in this paper is conceptual, statute and comparative approach.

Findings
By analyzing the related legal norms, it can be understood that in Asian countries, such as Indonesia, Thailand and Malaysia, there are regulations regarding land degradation. However, the regulations in these countries are not specific and tend to focus on nature conservation, which has an impact on handling land degradation. Therefore, it needs special regulation to deal with land degradation. One of the things that need to be regulated about land degradation is a market shared liability.

Research limitations/implications
This research is limited to regulation in the Asia region. By analyzing the regulation, this paper will provide an analysis about the land degradation regulation mechanism in Asia and give an analysis about market shared liability as one of the solution to handling land degradation. Having the same ground rules will create synergies between countries in Asia to handle land degradation.

Originality/value
This paper is the first systematic legal research comparing regulations from three nations in Asia on land degradation and the first paper to provide market shared liability as a solution to handling land degradation.
The use of technology in facing the COVID-19 negative consequences and the associated opportunity for digital entrepreneurship in KSA
Authors: Alanzi Sami , Ratten Vanessa 
Published: January 2024

PurposeThis article introduces the key findings from investigating technology's role in mitigating the business slowdown enforced by the COVID-19 pandemic and the associated increased reliance on technological means among Saudi firms and citizens to facilitate business operations and other daily life routines, and the impact of this increase in technology adoption on the Saudi digital ecosystem and creating an inviting environment to digital entrepreneurship.Design/methodology/approachA qualitative interview methodology is undertaken to understand Saudi managers’ perceptions about the COVID-19 pandemic and digital entrepreneurship.FindingsA significant finding is that now than ever before, the Saudi market is ready to accommodate more digital entrepreneurial ventures and digitalisation support services. Due to the pandemic's negative implications on the Saudi economy and the business slowdown associated with social distancing measures, a substantial increase in digital orientation and a need for technological solutions were noticed among Saudi firms. This means more attention needs to be placed on how Saudi firms can capitalise on the knowledge economy and digital revolution.Originality/valueSaudi citizens have become more reliant on technology to manage daily activities and shop for their needs, creating opportunities for digital entrepreneurship to serve and fulfil firms' and people's increased demand for technology solutions.
Filling the SME credit gap: a systematic review of blockchain-based SME finance literature
Authors: Kumar Deepak , Phani B.V. , Chilamkurti Naveen , Saurabh Suman , Ratten Vanessa 
Published: January 2024

PurposeThe review examines the existing literature on blockchain-based small and medium enterprise (SME) finance and highlights its trend, themes, opportunities and challenges. Based on these factors, the authors create a framework for the existing literature on blockchain-based SME financing and lay down future research paths.Design/methodology/approachThe review follows a systematic approach. It includes 53 articles encompassing multiple dimensions of blockchain-based SME finance, including peer-to-peer lending platforms, supply chain finance (SCF), decentralized lending protocols and tokenization of assets. The review critically evaluates these approaches' theoretical underpinnings, empirical evidence and practical implementations.FindingsThe review demonstrates that blockchain-based SME finance holds significant promise in addressing the credit gap by leveraging blockchain technology's decentralized and transparent nature. Benefits identified include reduced information asymmetry, improved access to financing, enhanced credit assessment processes and increased financial inclusion. However, the literature acknowledges several challenges and limitations, such as regulatory uncertainties, scalability issues, operational complexities and potential security risks.Originality/valueThe article contributes to the growing knowledge of blockchain-based SME finance by synthesizing and evaluating the existing literature. It also provides a framework for the existing literature in the area and future research paths. The study offers insights for researchers, policymakers and practitioners seeking to understand the potential of blockchain technology in filling the SME credit gap and fostering economic development through improved access to finance for SMEs.
Perceptions of older people about the use of cell phones in Argentina: a contribution from the gerontotechnological perspective
Authors: Revollo Sarmiento Elsa Araceli , Krzemien Deisy , López Moreno Maria Celeste , Vivas Leticia 
Published: January 2024

Purpose
The purpose of this paper is to describe the perceptions that older people in Argentina have about the use of cell phones and to analyze their influence on user behavior. At the same time, it was intended to analyze whether sociodemographic factors influence these perceptions.

Design/methodology/approach
The authors conducted a study with a non-experimental, cross-sectional and cross-correlational design; a non-probabilistic sample of 138 intentionally selected older people was chosen.

Findings
The frequency and years of cell phone use, as well as the applications used, are influenced by the perceptions that older people have about cell phone use. In addition, it was found that age, gender and socio-educational level determine the perceptions that older people have about cell phone use.

Originality/value
This research has implications for interventions aimed at improving older people’s functional health. Understanding the perceptions of older people in relation to technology will enable the enhancement of its utility to foster an autonomous lifestyle and social integration in old age.