bluuebunny/crossref_metadata_2025_split huggingface dataset:
A homing rescue gene drive with multiplexed gRNAs reaches high frequency in cage populations but generates functional resistance
Authors: Chen Jingheng , Hou Shibo , Feng Ruobing , Xu Xuejiao , Liang Nan , Champer Jackson 
Published: November 2023

AbstractCRISPR homing gene drive is a potent technology with considerable potential for managing populations of medically and agriculturally significant insects. It induces a bias in the inheritance of the drive allele in progeny, rapidly spreading desired genes throughout the population. Homing drives operate by Cas9 cleavage followed by homology-directed repair, copying the drive allele to the wild-type chromosome. However, resistance alleles formed by end-joining repair pose a significant obstacle to the spread of the drive. To address this challenge, we created a homing drive targeting the essential but haplosufficienthairygene. Our strategy involves spreading the drive construct through the homing process, eliminating nonfunctional resistance, which are recessive lethal, while rescuing drive-carrying individuals with a recoded version ofhairy. This strategy eliminates resistance more slowly than a previous strategy targeting haplolethal genes, but it may be easier to construct in non-model organisms. Our drive inheritance rate was moderate, and multigenerational cage studies showed quick drive spread to 96-97% of the population. However, the drive failed to reach the whole population due to the formation of functional resistance alleles, despite use of four gRNAs, a strategy that previously was successful at preventing functional resistance. Sequencing showed that these alleles had a large deletion and must have utilized an alternate start codon. The resistance allele had a modest fitness advantage over the drive in a cage study, which could prevent long-term persistence of the drive, especially if cargo genes had an additional fitness cost. Thus, revised design strategies targeting more essential regions of a target gene may often be necessary to avoid such functional resistance, even when using multiplexed gRNAs.
Structural and functional characterisation of the interaction between the influenza A virus RNA polymerase and the CTD of host RNA Polymerase II
Authors: Keown Jeremy , Baazaoui Alaa , Šebesta Marek , Štefl Richard , Carrique Loic , Fodor Ervin , Grimes Jonathan 
Published: November 2023

ABSTRACTInfluenza A viruses (IAV), causing seasonal epidemics and occasional pandemics, rely on interactions with host proteins for their RNA genome transcription and replication. The viral RNA polymerase utilizes host RNA polymerase II (Pol II) and interacts with the serine 5 phosphorylated (pS5) C-terminal domain (CTD) of Pol II to initiate transcription. Our study, using single-particle electron cryomicroscopy (cryo-EM), reveals the structure of the 1918 pandemic IAV polymerase bound to a synthetic pS5 CTD heptad repeat peptide. The structure shows that the CTD peptide binds at the C-terminal domain of the PA viral polymerase subunit (PA-C) and reveals a previously unobserved position of the 627 domain of the PB2 subunit near the CTD. We identify crucial residues of the CTD peptide mediating interactions with positively charged cavities on PA-C, explaining the preference of the viral polymerase for pS5 CTD. Functional analysis of mutants targeting the CTD-binding site within PA-C reveals reduced transcriptional function with normal replication, while other mutants display defects in both transcription and replication, highlighting the multifunctional role of PA-C in viral RNA synthesis. Our study provides insights into the structural and functional aspects of the influenza virus polymerase-host Pol II interaction and identifies a target for antiviral development.
pH selects for distinct N2O-reducing microbiomes in tropical soil microcosms
Authors: Sun Yanchen , Yin Yongchao , He Guang , Cha Gyuhyon , Ayala-del-Río Héctor L. , González Grizelle , Konstantinidis Konstantinos T. , Löffler Frank E. 
Published: November 2023

AbstractNitrous oxide (N2O), a greenhouse gas with ozone destruction potential, is mitigated by the microbial reduction to dinitrogen catalyzed by N2O reductase (NosZ). Bacteria with NosZ activity have been studied at circumneutral pH but the microbiology of low pH N2O reduction has remained elusive. Acidic (pH<5) tropical forest soils were collected in the Luquillo Experimental Forest in Puerto Rico, and microcosms maintained with low (0.02mM) and high (2mM) N2O assessed N2O reduction at pH 4.5 and 7.3. All microcosms consumed N2O, but long lag times of up to 7 months were observed in microcosms with 2 mM N2O. Comparative metagenome analysis revealed thatRhodocyclaceaedominated in circumneutral microcosms under both N2O feeding regimes. In acidic microcosms,Peptococcaceaedominated in high-N2O, andHyphomicrobiaceaein low-N2O microcosms. Seventeen metagenome-assembled genomes (MAGs) recovered from these microcosms harborednosoperons, with all eight MAGs derived from acidic microcosms carrying the clade II typenosZ, lacking nitrite reductase genes (nirS,nirK). Five of these MAGs represented novel taxa indicating an unexplored N2O-reducing diversity exists in acidic tropical soils. A survey of pH 3.5-5.7 soil metagenome datasets revealed thatnosZgenes commonly occur, suggesting broad distribution of N2O reduction potential in acidic soils.
Connectomic reconstruction predicts the functional organization of visual inputs to the navigation center of theDrosophilabrain
Authors: Garner Dustin , Kind Emil , Nern Aljoscha , Houghton Lucy , Zhao Arthur , Sancer Gizem , Rubin Gerald M. , Wernet Mathias F. , Kim Sung Soo 
Published: November 2023

AbstractMany animals, including humans, navigate their surroundings by visual input, yet we understand little about how visual information is transformed and integrated by the navigation system. InDrosophila melanogaster, compass neurons in the donut-shaped ellipsoid body of the central complex generate a sense of direction by integrating visual input from ring neurons, a part of the anterior visual pathway (AVP). Here, we densely reconstruct all neurons in the AVP using FlyWire, an AI-assisted tool for analyzing electron-microscopy data. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons, which connect the medulla in the optic lobe to the small unit of anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons, which connect the anterior optic tubercle to the bulb neuropil; and ring neurons, which connect the bulb to the ellipsoid body. Based on neuronal morphologies, connectivity between different neural classes, and the locations of synapses, we identified non-overlapping channels originating from four types of MeTu neurons, which we further divided into ten subtypes based on the presynaptic connections in medulla and postsynaptic connections in AOTUsu. To gain an objective measure of the natural variation within the pathway, we quantified the differences between anterior visual pathways from both hemispheres and between two electron-microscopy datasets. Furthermore, we infer potential visual features and the visual area from which any given ring neuron receives input by combining the connectivity of the entire AVP, the MeTu neurons’ dendritic fields, and presynaptic connectivity in the optic lobes. These results provide a strong foundation for understanding how distinct visual features are extracted and transformed across multiple processing stages to provide critical information for computing the fly’s sense of direction.
A fluorogenic complementation tool kit for interrogating lipid droplet-organelle interaction
Authors: Li Xiao , Gamuyao Rico , Wu Ming-Lun , Cho Woo Jung , Kurtz Nathan B. , King Sharon V. , Petersen R.A. , Stabley Daniel R. , Lindow Caleb , Climer Leslie , Shirinifard Abbas , Ferrara Francesca , Throm Robert E. , Robinson Camenzind G. , Carisey Alex , Tebo Alison G. , Chang Chi-Lun 
Published: November 2023

AbstractContact sites between lipid droplets and other organelles are essential for cellular lipid and energy homeostasis. Detection of these contact sites at nanometer scale over time in living cells is challenging. Here, we developed a tool kit for detecting contact sites based onFluorogen-ActivatedBimolecular complementation atCONtact sites, FABCON, using a reversible, low affinity split fluorescent protein, splitFAST. FABCON labels contact sites with minimal perturbation to organelle interaction. Via FABCON, we quantitatively demonstrated that endoplasmic reticulum (ER)- and mitochondria (mito)-lipid droplet contact sites are dynamic foci in distinct metabolic conditions, such as during lipid droplet biogenesis and consumption. An automated analysis pipeline further classified individual contact sites into distinct subgroups based on size, likely reflecting differential regulation and function. Moreover, FABCON is generalizable to visualize a repertoire of organelle contact sites including ER-mito. Altogether, FABCON reveals insights into the dynamic regulation of lipid droplet-organelle contact sites and generates new hypotheses for further mechanistical interrogation during metabolic switch.
Proteomic profiling of aging brains identifies key proteins by which cognitively healthy centenarians defy their age by decades
Authors: Ganz Andrea B. , Zhang Meng , Koopmans Frank , Li Ka Wan , Miedema Suzanne S.M. , Rozemuller Annemieke J.M. , Hulsman Marc ,   Netherlands Brain Bank, Scheltens Philip , Hoozemans Jeroen J.M. , Reinders Marcel J.T. , Smit August B. , Holstege Henne 
Published: November 2023

AbstractSome individuals reach extreme ages without any signs of cognitive decline. Here, we show that based on key proteins, cognitively healthy centenarians have a biologically younger brain. We compared the brain proteomic signatures of 58 self-reported cognitively healthy centenarians with 61 non-demented individuals and 91 AD patients. The abundance of 472 proteins strongly associated with AD Braak stages of which 64 were differentially regulated in centenarians. With increasing Braak stages, the abundance of toxic peptides of MAPT increased in AD patients, while these remained low in centenarians. Furthermore, the abundance of 174 proteins strongly changed with age, of which 108 were differentially regulated in centenarians. In fact, in brains from centenarians the abundances of essential proteins were representative of brains from individuals who were a median 18- and up to 28-years ‘younger’. The proteins involved represent diverse cellular processes, and suggest that maintained protein homeostasis is central in maintaining brain-health.
An integrated approach of TAM and TPB with financial literacy and perceived risk for influence on online trading intention
Authors: Raut Rajdeep Kumar , Kumar Santosh 
Published: November 2023

Purpose
This paper aims to propose a decision-making framework by investigating the impact of perceived risk and computer self-efficacy on the intention to use online stock trading. Furthermore, it demonstrates the mediation effect of attitude and perceived risk as well as the moderating effect of financial literacy.

Design/methodology/approach
An integration of two popular models, technology acceptance model (TAM) and theory of planned behaviour (TPB), is used to provide a sound theoretical base and enhance the understanding of investors’ behaviour towards online trading platforms. The proposed hypothesised model was examined using structural equation modelling.

Findings
The results obtained from this study indicate that all variables, except subjective norms, had a significant impact on investors’ intention to trade online. Perceived risk was found to be a partial mediator between computer self-efficacy and the intention of investors. Finally, financial literacy was also found as a significant moderator for online trading intention of investors.

Practical implications
This study shows the significance of using the TAM and TPB together to provide a comprehensive understanding of the factors that influence an investor’s behaviour in adopting and using technology for online trading. The hybrid approach of TAM and TPB could be considered for a more nuanced and complete understanding of technology adoption and usage in risky affairs like investment decisions. Again, the significant moderating role of financial literacy provides a lance to look into the scope for improvements in investment decision-makings.

Originality/value
The paper develops an assessment framework for analysing the variables based on the hybrid approach for online trading intention in the context of a developing country.
Rising home bakers in India: leveraging online platforms for sales and marketing
Authors: Trivedi Twinkle Milan 
Published: November 2023

Learning outcomes
Upon completion of the case study, the students will be able to understand brand differentiation and marketing challenges faced by small businesses in emerging markets; recognize the significance of marketing strategies for a growing business in emerging markets; assimilate paid, owned and earned media to improvise the effectiveness of firm’s communication and digital marketing strategy; analyze the relevance of social media marketing in developing a brand; and create a content marketing strategy.

Case overview/synopsis
The case dilemma involved a possible course of action that Fusion Creations faced at the beginning of 2022 about marketing strategies across paid, earned and owned media. “Fusion Creations” was the creation of two sisters who were avid cake bakers since young age. They identified the demand for homemade cakes and the growing number of home bakers in India. It was during the Covid-19 pandemic that they faced challenges in terms of lockdown and scarcity of supply for baking essentials. Moreover, although the pandemic had brought most sections of the society worldwide to a standstill, home bakers were thriving. After the pandemic, these home bakers turned their passion into full-time profession. It was time for the sisters to view this stage as a challenge because of competition from aspiring entrepreneurs and rising home bakers, and convert it into an opportunity. Can Fusion Creation leverage the online social media platforms for their product sales and marketing? With presence established on various social media platforms, were they doing it right, or was there a better way? A few questions lay in front of Chaitali and Kena, owners and bakers of Fusion Creations.

Complexity academic level
This case is written for use in digital and social media marketing classes for graduation-level courses. The focus of the case aligns well with discussions of digital and social media marketing strategy. The case also has application in discussions regarding implementation of digital marketing strategy. Instructors that choose to emphasize social media strategies could assign this case to explore online marketing and digital communication.

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS8: Marketing.
The influence of the labour market and COVID-19 on human resource practices in SMEs in China: a longitudinal study
Authors: Li Shaoheng , Rees Christopher J. , Zhang Hui 
Published: November 2023

PurposeThe purpose of this study is to investigate the evolving perceptions and human resource (HR) responses of owners and HR managers of Chinese small and medium-sized enterprises (SMEs) towards local labour markets in the context of the impact of the coronavirus disease 2019 (COVID-19) pandemic.Design/methodology/approachThis study adopts a two-stage longitudinal qualitative approach involving 52 interviews with owners and HR managers of Chinese SMEs in the pre- and post-pandemic time periods.FindingsThe findings reveal a shift from the perceptions of a general labour shortage to perceptions of specialised talent shortages and increasing geographical disparities in local labour markets. They further reveal that SMEs are increasingly likely to adopt efficiency-oriented, flexibility-enhancing HR practices in the face of high uncertainty.Practical implicationsThe findings provide insights into the nature of the constraints of SMEs' sustainable development that need to be addressed by policymakers, SME owners and HR managers when they devise and implement policies relating to structure optimisation, labour market integration and mobility enhancement.Originality/valueIn contrast to extant literature that has examined the labour market at the national level, this study explores the views of SMEs (the demand side) by taking a localised perspective on how SMEs have responded to change through their HR practices.
Computer simulation of two phase power-law nanofluid of blood flow through a curved overlapping stenosed artery with induced magnetic field: entropy generation optimization
Authors: Kumawat Chandan , Sharma Bhupendra Kumar , Muhammad Taseer , Ali Liaqat 
Published: November 2023

Purpose
The purpose of this study is to determine the impact of two-phase power law nanofluid on a curved arterial blood flow under the presence of ovelapped stenosis. Over the past couple of decades, the percentage of deaths associated with blood vessel diseases has risen sharply to nearly one third of all fatalities. For vascular disease to be stopped in its tracks, it is essential to understand the vascular geometry and blood flow within the artery. In recent scenarios, because of higher thermal properties and the ability to move across stenosis and tumor cells, nanoparticles are becoming a more common and effective approach in treating cardiovascular diseases and cancer cells.

Design/methodology/approach
The present mathematical study investigates the blood flow behavior in the overlapped stenosed curved artery with cylinder shape catheter. The induced magnetic field and entropy generation for blood flow in the presence of a heat source, magnetic field and nanoparticle (Fe3O4) have been analyzed numerically. Blood is considered in artery as two-phases: core and plasma region. Power-law fluid has been considered for core region fluid, whereas Newtonian fluid is considered in the plasma region. Strongly implicit Stone’s method has been considered to solve the system of nonlinear partial differential equations (PDE’s) with 10–6 tolerance error.

Findings
The influence of various parameters has been discussed graphically. This study concludes that arterial curvature increases the probability of atherosclerosis deposition, while using an external heating source flow temperature and entropy production. In addition, if the thermal treatment procedure is carried out inside a magnetic field, it will aid in controlling blood flow velocity.

Originality/value
The findings of this computational analysis hold great significance for clinical researchers and biologists, as they offer the ability to anticipate the occurrence of endothelial cell injury and plaque accumulation in curved arteries with specific wall shear stress patterns. Consequently, these insights may contribute to the potential alleviation of the severity of these illnesses. Furthermore, the application of nanoparticles and external heat sources in the discipline of blood circulation has potential in the medically healing of illness conditions such as stenosis, cancer cells and muscular discomfort through the usage of beneficial effects.
Households’ entry into non-farm entrepreneurship and the market exit of enterprises in rural Ethiopia
Authors: Abegaz Melaku , Ngoboka Pascal 
Published: November 2023

Purpose This paper examines household and community characteristics that influence the entry of rural households into non-farm entrepreneurship and investigates the various factors that influence the market exit of non-farm enterprises (NFEs).Design/methodology/approach The authors use data from three rounds (2011/12, 2013/14 and 2015/16) of the World Bank’s Living Standards Measurement Study – Integrated Surveys on Agriculture (LSMS-ISA). The authors employ panel logit and multilevel logit models to examine the probability of opening one or more enterprises and the enterprise exit rates.Findings Results indicate that the likelihood of starting a NFE is positively associated with primary education attainment, access to credit, experiencing idiosyncratic shocks and availability of formal financial institutions. Age, higher education attainment and rising farm input prices constrain entry into non-farm entrepreneurship. The enterprise exit rate is negatively associated with small-town residence, wealth, access to tar/gravel roads and cellphone communication.Practical implications Policymakers and administrators should strive to address the challenges that communities face in transportation, communication and financial services. Policies aimed at stabilizing prices and increasing access to mobile communication, primary education and road infrastructure could help expand the rural non-farm sector.Originality/value Previous studies primarily examined the determinants of participation in NFEs at a given time using cross-sectional data. The current study uses panel data to study the dynamics of NFE ownership by investigating households’ decisions to enter into or exit from the sector.Peer reviewThe peer review history for this article is available at https://publons.com/publon/10.1108/IJSE-09-2022-0611
Institutional quality, shadow economy and entrepreneurship: international evidence
Authors: Tran Pham Toan Khanh 
Published: November 2023

PurposeThe impacts of institutional quality on entrepreneurship are well established. However, the effects of an external factor, such as the shadow economy, that moderates this relationship have largely been neglected in existing literature. As such, this paper investigates how the shadow economy moderates the effects of institutional quality on entrepreneurship in a global sample of 79 economies from 2006 to 2018, when the latest required data are available.Design/methodology/approachThis paper utilizes the fixed-effect and generalized method of moments (GMM) estimation techniques. Various scenarios have been considered for the robustness of the analysis, including different estimation techniques, different estimates of the shadow economy and various subsamples of countries with different income levels.FindingsEmpirical findings indicate that improved institutional quality boosts entrepreneurship activities, while the extended shadow economy is associated with reduced entrepreneurship activities. Interestingly, the positive impacts of institutional quality on entrepreneurship will be lessened with a larger shadow economy. These findings have remained largely unchanged across samples of countries and different proxies and estimation techniques.Practical implicationsFindings from this paper offer policymakers the relationships between institutional quality, shadow economy and entrepreneurship and the moderating effects of shadow economy on the institutional quality–entrepreneurship nexus. The implication is that institutional quality should be strengthened while the shadow economy should be controlled to promote entrepreneurship initiatives.Originality/valueTo the best of the author's knowledge, this is the first empirical study to explore the moderating effects of the shadow economy on the institutional quality–entrepreneurship nexus.