bluuebunny/crossref_metadata_2025 huggingface dataset:
Rising temperature drives tipping points in mutualistic networks
Authors: Bhandary Subhendu , Deb Smita , Sharathi Dutta Partha
Published: February 2023

The effect of climate warming on species' physiological parameters, including growth rate, mortality rate and handling time, is well established from empirical data. However, with an alarming rise in global temperature more than ever, predicting the interactive influence of these changes on mutualistic communities remains uncertain. Using 139 real plant–pollinator networks sampled across the globe and a modelling approach, we study the impact of species’ individual thermal responses on mutualistic communities. We show that at low mutualistic strength plant–pollinator networks are at potential risk of rapid transitions at higher temperatures. Evidently, generalist species play a critical role in guiding tipping points in mutualistic networks. Further, we derive stability criteria for the networks in a range of temperatures using a two-dimensional reduced model. We identify network structures that can ascertain the delay of a community collapse. Until the end of this century, on account of increasing climate warming many real mutualistic networks are likely to be under the threat of sudden collapse, and we frame strategies to mitigate this. Together, our results indicate that knowing individual species' thermal responses and network structure can improve predictions for communities facing rapid transitions.
Energy-shaping control of a muscular octopus arm moving in three dimensions
Authors: Chang Heng-Sheng , Halder Udit , Shih Chia-Hsien , Naughton Noel , Gazzola Mattia , Mehta Prashant G.
Published: February 2023

Flexible octopus arms exhibit an exceptional ability to coordinate large numbers of degrees of freedom and perform complex manipulation tasks. As a consequence, these systems continue to attract the attention of biologists and roboticists alike. In this article, we develop a three-dimensional model of a soft octopus arm, equipped with biomechanically realistic muscle actuation. Internal forces and couples exerted by all major muscle groups are considered. An energy-shaping control method is described to coordinate muscle activity so as to grasp and reach in three-dimensional space. Key contributions of this article are as follows: (i) modelling of major muscle groups to elicit three-dimensional movements; (ii) a mathematical formulation for muscle activations based on a stored energy function; and (iii) a computationally efficient procedure to design task-specific equilibrium configurations, obtained by solving an optimization problem in the Special Euclidean groupSE(3). Muscle controls are then iteratively computed based on the co-state variable arising from the solution of the optimization problem. The approach is numerically demonstrated in the physically accurate software environmentElastica. Results of numerical experiments mimicking observed octopus behaviours are reported.
Local infectious disease experience influences vaccine refusal rates: a natural experiment
Authors: Angelopoulos Konstantinos , Stewart Gillian , Mancy Rebecca
Published: February 2023

Vaccination has been critical to the decline in infectious disease prevalence in recent centuries. Nonetheless, vaccine refusal has increased in recent years, with complacency associated with reductions in disease prevalence highlighted as an important contributor. We exploit a natural experiment in Glasgow at the beginning of the twentieth century to investigate whether prior local experience of an infectious disease matters for vaccination decisions. Our study is based on smallpox surveillance data and administrative records of parental refusal to vaccinate their infants. We analyse variation between administrative units of Glasgow in cases and deaths from smallpox during two epidemics over the period 1900–1904, and vaccine refusal following its legalization in Scotland in 1907 after a long period of compulsory vaccination. We find that lower local disease incidence and mortality during the epidemics were associated with higher rates of subsequent vaccine refusal. This finding indicates that complacency influenced vaccination decisions in periods of higher infectious disease risk, responding to local prior experience of the relevant disease, and has not emerged solely in the context of the generally low levels of infectious disease risk of recent decades. These results suggest that vaccine delivery strategies may benefit from information on local variation in incidence.
Distinct developmental mechanisms influence sexual dimorphisms in the milkweed bugOncopeltus fasciatus
Authors: Just Josefine , Laslo Mara , Lee Ye Jin , Yarnell Michael , Zhang Zhuofan , Angelini David R.
Published: February 2023

Sexual dimorphism is common in animals. The most complete model of sex determination comes fromDrosophila melanogaster, where the relative dosage of autosomes and X chromosomes leads indirectly to sex-specific transcripts ofdoublesex(dsx). Female Dsx interacts with a mediator complex protein encoded byintersex(ix) to activate female development. In males, the transcription factor encoded byfruitless(fru) promotes male-specific behaviour. The genetics of sex determination have been examined in a small number of other insects, yet several questions remain about the plesiomorphic state. Isdsxrequired for female and male development? Isfruconserved in male behaviour or morphology? Are other components such asixfunctionally conserved? To address these questions, we report expression and functional tests ofdsx,ixandfruin the hemipteranOncopeltus fasciatus, characterizing three sexual dimorphisms.dsxpreventsixphenotypes in all sexes and dimorphic traits in the milkweed bug.ixandfruare expressed across the body, in females and males.fruandixalso affect the genitalia of both sexes, but have effects limited to different dimorphic structures in different sexes. These results reveal roles forixandfrudistinct from other insects, and demonstrate distinct development mechanisms in different sexually dimorphic structures.
By a whisker: the sensory role of vibrissae in hovering flight in nectarivorous bats
Authors: Amichai Eran , Boerma David B. , Page Rachel A. , Swartz Sharon M. , ter Hofstede Hannah M.
Published: February 2023

Whiskers are important tactile structures widely used across mammals for a variety of sensory functions, but it is not known how bats—representing about a fifth of all extant mammal species—use them. Nectar-eating bats typically have long vibrissae (long, stiff hairs) arranged in a forward-facing brush-like formation that is not present in most non-nectarivorous bats. They also commonly use a unique flight strategy to access their food—hovering flight. Here we investigated whether these species use their vibrissae to optimize their feeding by assisting fine flight control. We used behavioural experiments to test if bats' flight trajectory into the flower changed after vibrissa removal, and phylogenetic comparative methods to test whether vibrissa length is related to nectarivory. We found that bat flight trajectory was altered after vibrissae removal and that nectarivorous bats possess longer vibrissae than non-nectivorous species, providing evidence of an additional source of information in bats’ diverse sensory toolkit.
A 17-year time-series of fungal environmental DNA from a coastal marine ecosystem reveals long-term seasonal-scale and inter-annual diversity patterns
Authors: Chrismas Nathan , Allen Ro , Allen Michael J. , Bird Kimberley , Cunliffe Michael
Published: February 2023

Changing patterns in diversity are a feature of many habitats, with seasonality a major driver of ecosystem structure and function. In coastal marine plankton-based ecosystems, seasonality has been established through long-term time-series of bacterioplankton and protists. Alongside these groups, fungi also inhabit coastal marine ecosystems. If and how marine fungi show long-term intra- and inter-annual diversity patterns is unknown, preventing a comprehensive understanding of marine fungal ecology. Here, we use a 17-year environmental DNA time-series from the English Channel to determine long-term marine fungal diversity patterns. We show that fungal community structure progresses at seasonal and monthly scales and is only weakly related to environmental parameters. Communities restructured every 52-weeks suggesting long-term stability in diversity patterns. Some major marine fungal genera have clear inter-annual recurrence patterns, re-appearing in the annual cycle at the same period. Low relative abundance taxa that are likely non-marine show seasonal input to the coastal marine ecosystem suggesting land–sea exchange regularly takes place. Our results demonstrate long-term intra- and inter-annual marine fungal diversity patterns. We anticipate this study could form the basis for better understanding the ecology of marine fungi and how they fit in the structure and function of the wider coastal marine ecosystem.
Discrepancies between the drivers of alpha and beta plant diversity in arable field margins
Authors: Boinot Sébastien , Alignier Audrey
Published: February 2023

Field margins are major habitats for biodiversity conservation and ecosystem functioning in agricultural landscapes, but biotic homogenization of plant communities threatens their ecological and agronomic functions. Our objective is to determine the drivers of plant diversity in field margins for conservation and restoration purposes. To do so, we assessed the effects of field margin structure and long-term management over 20 years (1995–2015) on the taxonomic and functional α- and β-diversity, and the functional composition of herbaceous plant communities. In 2015, we surveyed 302 field margins in bocage landscapes of Brittany, northwestern France. Results were very similar between taxonomic and functional diversity but revealed important discrepancies between the drivers of α- and β-diversity. Deep ditches, mowing and grazing increased α-diversity but did not affect β-diversity. Denser hedgerows had lower α-diversity than other field margins but strongly contributed to β-diversity by harbouring more unique sets of species or life strategies. Long-term herbicide spraying in field margins and cropping intensity in adjacent habitats did not affect α-diversity, but had more complex effects on β-diversity and selected for common weeds. All in all, preservation of dense hedgerows, abandonment of herbicide spraying, and protection against agrochemical drifts are key measures to prevent the establishment of common weeds and biotic homogenization of herbaceous plant communities in field margins. Above all, our study shows how important it is to go beyond α-diversity to make robust conservation and restoration decisions.
Identification of essential genes in Coxiella burnetii
Authors: Metters Georgie , Hemsley Claudia , Norville Isobel , Titball Richard
Published: February 2023

Coxiella burnetii

is an intracellular pathogen responsible for causing Q fever in humans, a disease with varied presentations ranging from a mild flu-like sickness to a debilitating illness that can result in endocarditis. The intracellular lifestyle of

C. burnetii

is unique, residing in an acidic phagolysosome-like compartment within host cells. An understanding of the core molecular biology of

C. burnetii

will greatly increase our understanding of

C. burnetii

growth, survival and pathogenesis. We used transposon-directed insertion site sequencing (TraDIS) to reveal

C. burnetii

Nine Mile Phase II genes fundamental for growth and in vitro survival. Screening a transposon library containing >10 000 unique transposon mutants revealed 512 predicted essential genes. Essential routes of synthesis were identified for the mevalonate pathway, as well as peptidoglycan and biotin synthesis. Some essential genes identified (e.g. predicted type IV secretion system effector genes) are typically considered to be associated with

C. burnetii

virulence, a caveat concerning the axenic media used in the study. Investigation into the conservation of the essential genes identified revealed that 78 % are conserved across all

C. burnetii

strains sequenced to date, which probably play critical functions. This is the first report of a whole genome transposon screen in

C. burnetii

that has been undertaken for the identification of essential genes.
Corporately Owned Plants need Space: An Analysis on Plant Biodiversity in Toronto’s Privately-owned Publicly Accessible Spaces
Authors: Ho Matthew R
Published: February 2023

Urban plant biodiversity is a growing ecological concern for city planners and ecologists. While parks are serviced by the public sector, and yards are pruned by the private citizen, a growing proportion of urban green space is managed by corporations. Despite biodiversity targets set by city councils and public committees, actual plant surveys have not been performed. Employing coordinate data of Privately-Owned Publicly-accessible Spaces (POPS) from the City of Toronto, we sampled plant species richness in nine corporately-managed green spaces. Using linear mixed-effect models, we compared richness with various green space characteristics and found that site area is an important predictor. Our results concur with prior studies showing that habitat area may cause significant impacts to urbanized plant biodiversity.
TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis
Authors: Yu Pengcheng , Qu Ning , Zhu Rui , Hu Jiaqian , Han Peizhen , Tan Licheng , Gan Hualei , He Cong , Fang Chuantao , Lei Yubin , Li Jian , He Chenxi , Lan Fei , Shi Xiao , Wei Wenjun , Wang Yu , Ji Qinghai , Yu Fa-Xing , Wang Yu-Long
Published: February 2023

TERT reactivation occurs frequently in human malignancies. While BRAF activating mutation widely existed in cancers at various stages, TERT reactivation mainly occurs in advanced tumors. However,in vivoevidence for TERT role in cancer progression and the underlying mechanism is currently lacking. In this study, we induced TERT and/or BRAF V600E expression in mouse thyroid epithelium. TERT overexpression alone had no evident effect on tumor initiation. BRAFVEexpression itself induced mediocre papillary thyroid cancer (PTC). Notably, the co-expression of BRAFVEand TERT resulted in aggressive poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome revealed that tumors from co-mutant mice were highly heterogeneous and dedifferentiation process significantly correlated with ribosomal pathways. Mechanistically, TERT boosted ribosomal RNA expression and protein synthesis. CX-5461, a rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation. Thus, TERT promotes thyroid cancer progression by inducing dedifferentiation, and ribosome biogenesis inhibition represents a potential treatment strategy for TERT-reactivated cancers.

Highlights

➢

TERT accelerated thyroid cancer dedifferentiation and metastasisin vivo

➢

TERT regulated rRNA metabolism and MTORC1/ S6K/RPS6 activities

➢

CX-5461 inhibited the progression of TERT-reactivated melanoma and thyroid cancer

➢

Inhibition of rRNA induced redifferentiation of advanced thyroid cancer with TERT activation
Ryanodine receptor 2 inhibition reduces dispersion of cardiac repolarization, improves contractile function and prevents sudden arrhythmic death in failing hearts
Authors: Joshi Pooja , Estes Shanea , DeMazumder Deeptankar , Knollmann Bjorn C. , Dey Swati
Published: February 2023

Introduction

Sudden cardiac death (SCD) from ventricular tachycardia/fibrillation (VT/VF) are a leading cause of death, but current therapies are limited. Despite extensive research on drugs targeting sarcolemmal ion channels, none have proven sufficiently effective for preventing SCD. Sarcoplasmic ryanodine receptor 2 (RyR2) Ca2+release channels, the downstream effectors of sarcolemmal ion channels, are underexplored in this context. Recent evidence implicates reactive oxygen species (ROS)- mediated oxidation and hyperactivity of RyR2s in the pathophysiology of SCD.

Objective

To test the hypothesis that RyR2 inhibition of failing arrhythmogenic hearts reduces sarcoplasmic Ca2+leak and repolarization lability, mitigates VT/VF/SCD and improves contractile function.

Methods

We used a guinea pig model that replicates key clinical aspects of human nonischemic HF, such as a prolonged QT interval, a high prevalence of spontaneous arrhythmic SCD, and profound Ca2+leak via a hyperactive RyR2. HF animals were randomized to receive dantrolene (DS) or placebo in early or chronic HF. We assessed the incidence of VT/VF and SCD (primary outcome), ECG heart rate and QT variability, echocardiographic left ventricular (LV) structure and function, immunohistochemical LV fibrosis, and sarcoplasmic RyR2 oxidation.

Results

DS treatment prevented VT/VF and SCD by decreasing dispersion of repolarization and ventricular arrhythmias. Compared to placebo, DS lowered resting heart rate, preserved chronotropic competency during transient β-adrenergic challenge, and improved heart rate variability and cardiac function.

Conclusion

Inhibition of RyR2 hyperactivity with dantrolene mitigates the vicious cycle of sarcoplasmic Ca2+leak-induced increases in diastolic Ca2+and ROS-mediated RyR2 oxidation, thereby increasing repolarization lability and protecting against VT/VF/SCD. Moreover, the consequent increase in sarcoplasmic Ca2+load improves contractile function. These potentially life-saving effects of RyR2 inhibition warrant further investigation, such as clinical studies of repurposing dantrolene as a potential new therapy for heart failure and/or SCD.
Study Protocol for the Pilot Evaluation for SMartphone-adaptable Artificial Intelligence for PRediction and DeTection of Left Ventricular Systolic Dysfunction (The SMART-LV Pilot Study Protocol)
Authors: Dhingra Lovedeep Singh , Aminorroaya Arya , Sangha Veer , Khunte Akshay , Oikonomou Evangelos K , Mortazavi Bobak J , McNamara Robert , Herrin Jeph , Wilson Francis P , Krumholz Harlan M , Khera Rohan
Published: February 2023

Introduction

Despite a prevalence of 3-5% among adults, asymptomatic left ventricular systolic dysfunction (LVSD) remains underdiagnosed. There is a critical need for an accurate and widely accessible screening strategy for LVSD, given its association with preventable morbidity and premature mortality. A novel deep learning approach has demonstrated the ability to detect LVSD directly from ECG images, with retrospective validation across multiple institutions. There is a lack of prospective validation. In this pilot study, we evaluate the feasibility of screening and recruiting individuals for prospective echocardiography based on an image-based artificial intelligence (AI)-ECG algorithm applied to the ECG repository at a large academic medical center.

Research Methods and Analysis

This is the protocol for a prospective cohort study in outpatient primary care clinics of the Yale New Haven Hospital (YNHH). Adult patients who have undergone a 12-lead ECG without subsequent echocardiogram as a part of routine clinical care within 90 days of the ECG will be identified in the electronic health record (EHR). The AI-ECG model for LVSD will be deployed to YNHH ECG repository to define the probability of LVSD, identifying 5 patients each with high and low probability of LVSD. After discussion with primary care physicians, and subsequent contact by the study team, screened participants will be invited for and undergo an echocardiogram. The study participants and the cardiologists conducting the echocardiograms will be blinded to the results of the AI-ECG screen. The analysis will focus on feasibility metrics: the proportion (i) of all patients undergoing ECGs who have high probability of LVSD without subsequent echocardiogram, (ii) of patients who agree to participate in the study, and (iii) that undergo an echocardiogram. A descriptive exploration of the comparison of the AI-ECG and echocardiogram results will also be reported.

Ethics and Dissemination

All patient EHR data required for assessing eligibility and conducting the AI-ECG screening will be accessed through secure servers approved for protected health information. Potential participants will only be contacted after they have discussed the study information with their primary care physician. All participants will be required to provide written informed consent before participation and data will be deidentified prior to analysis. This study protocol has been approved by the Yale Institutional Review Board (Protocol Number: 2000034006) and has been registered atClinicalTrials.gov(Identifier:NCT05630170). The results of the future validation study will be published in peer-reviewed journals and summaries will be provided to the study participants.
The Impact of Pathogenic and Artificial Mutations on Claudin-5 Selectivity from Molecular Dynamics Simulations
Authors: Berselli Alessandro , Alberini Giulio , Benfenati Fabio , Maragliano Luca
Published: February 2023

Tight junctions (TJs) are multi-protein complexes at the interface between adjacent endothelial or epithelial cells. In the blood-brain barrier (BBB), they are responsible for sealing the paracellular spaces and their backbone is formed by Claudin-5 (Cldn5) proteins. Despite the important role in preserving brain homeostasis, little is known on how Cldn5 oligomers assemble. Different structural models have been suggested, where Cldn5 protomers from opposite cells associate to generate paracellular pores that do not allow the passage of ions or small molecules. Recently, the first Cldn5 pathogenic mutation, G60R, was identified and shown to induce anion selectivity in the BBB TJs. This offers an excellent opportunity to further assess the structural models. In this work, we performed umbrella sampling molecular dynamics simulations to study the permeation of single Na+, Cl−and H2O through two distinct G60R Cldn5 paracellular models. Only one of them, called Pore I, reproduces the functional modification observed in the experiments, displaying a free energy (FE) minimum for Cl−and a barrier for Na+at the central constriction, consistent with the formation of an anionic channel. To further test the validity of the model, we performed the same calculations for the Q57D and the Q63D mutants, which affect two side-chains in the constriction site. In particular, Q57 is conserved among various Cldns, with few exceptions such as the two cation permeable homologs Cldn15 and Cldn10b. In both cases, we obtain that the FE profiles are modified with respect to the wild-type system, facilitating the passage of cations. Our calculations are the firstin-silicodescription of the effect of a Cldn5 pathogenic mutation, and provide a further assessment of the Pore I model for Cldn5-based TJ architectures, yielding new atom-detailed insight on the selective permeability of the paracellular spaces in BBB.
Biochemical and Genetic Evidence Supports Fyv6 as a Second-Step Splicing Factor inSaccharomyces cerevisiae
Authors: Lipinski Karli A. , Senn Katherine A. , Zeps Natalie J. , Hoskins Aaron A.
Published: February 2023

Precursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of 5 small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density. It was also proposed that Fyv6 might be the functionalS. cerevisiaehomolog of FAM192A; however, no biochemical or genetic data has been reported to support this hypothesis. Herein, we show that Fyv6 is a splicing factor and acts during exon ligation. Deletion ofFYV6results in genetic interactions with the essential splicing factors Prp8, Prp16, and Prp22; decreases splicingin vivoof reporter genes harboring intron substitutions that limit the rate of exon ligation; and changes 3’ splice site (SS) selection. Together, these data suggest that Fyv6 is a component of the spliceosome and the potential functional and structural homolog of human FAM192A.
Antibiotic hyper-resistance in a class I aminoacyl-tRNA synthetase with altered active site signature motif
Authors: Brkic A. , Leibundgut M. , Jablonska J. , Zanki V. , Car Z. , Petrovic-Perokovic V. , Maršavelski A. , Ban N. , Gruic-Sovulj I.
Published: February 2023

Antibiotics target key biological processes that include protein synthesis. Bacteria respond by developing resistance, which increases rapidly due to antibiotics overuse. Mupirocin, a clinically used natural antibiotic, inhibits isoleucyl-tRNA synthetase (IleRS), an enzyme that links isoleucine to its tRNAIlefor protein synthesis. Two IleRSs, mupirocin-sensitive IleRS1 and resistant IleRS2, coexist in bacteria. The latter may also be found in resistantStaphylococcus aureusclinical isolates. Here, we describe the structural basis of mupirocin resistance and unravel a mechanism of hyper-resistance evolved by some IleRS2 proteins. We surprisingly find that an up to 103-fold increase in resistance originates from alteration of the HIGH motif, a signature motif of the class I aminoacyl-tRNA synthetases to which IleRSs belong. The structural analysis demonstrates how an altered HIGH motif could be adopted in IleRS2 but not IleRS1, providing insight into an elegant mechanism for coevolution of the key catalytic motif and associated antibiotic resistance.
Identification of two β-cell subtypes by 7 independent criteria
Authors: Dror Erez , Fagnocchi Luca , Wegert Vanessa , Apostle Stefanos , Grimaldi Brooke , Gruber Tim , Panzeri Ilaria , Heyne Steffen , Höffler Kira Daniela , Kreiner Victor , Ching Reagan , Lu Tess Tsai-Hsiu , Semwal Ayush , Johnson Ben , Senapati Parijat , Lempradl Adelheid M. , Schones Dustin , Imhof Axel , Shen Hui , Pospisilik John Andrew
Published: February 2023

Despite the recent explosion in surveys of cell-type heterogeneity, the mechanisms that specify and stabilize highly related cell subtypes remain poorly understood. Here, focusing initially on exploring quantitative histone mark heterogeneity, we identify two major sub-types of pancreatic β-cells (βHIand βLO). βHIand βLOcells differ in their size, morphology, cytosolic and nuclear ultrastructure, transcriptional output, epigenomes, cell surface marker, and function. Importantly, βHIand βLOcells can be FACS separated live into CD24+(βHI) and CD24-(βLO) fractions. From an epigenetic viewpoint, βHI-cells exhibit ∼4-fold higher levels of H3K27me3, more compacted chromatin, and distinct chromatin organization that associates with a specific pattern of transcriptional output. Functionally, βHIcells have increased mitochondrial mass, activity, and insulin secretion bothin vivoandex vivo. Critically,EedandJmjd3loss-of-function studies demonstrate that H3K27me3 dosage is a significant regulator of βHI/ βLOcell ratioin vivo,yielding some of the first-ever specific models of β-cell sub-type distortion. βHIand βLOsub-types are conserved in humans with βHI-cells enriched in human Type-2 diabetes. These data identify two novel and fundamentally distinct β-cell subtypes and identify epigenetic dosage as a novel regulator of β-cell subtype specification and heterogeneity.

Highlights

Quantitative H3K27me3 heterogeneity reveals 2 common β-cell subtypes

βHIand βLOcells are stably distinct by 7 independent sets of parameters

H3K27me3 dosage controls βHI/ βLOratio in vivo

βHIand βLOcells are conserved in humans and enriched in Type-2 diabetes
The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes
Authors: Raguseo Federica , Huyghebaert Anouk , Li Jessica , Balendra Rubika , Howe Marija Petrić , Wang Yiran , Vadukul Devkee M. , Tanase Diana A. , Maher Thomas E. , Malouf Layla , Rubio-Sánchez Roger , Aprile Francesco A. , Elani Yuval , Patani Rickie , Michele Lorenzo Di , Antonio Marco Di
Published: February 2023

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is the expansion of the intronic hexanucleotide repeat (GGGGCC)ninC9orf72. Here, we investigated the formation of nucleic-acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of the diseases. We observed significant aggregation of the hexanucleotide sequence (GGGGCC)n, which we associated to the formation of multimolecular G-quadruplexes (mG4s), using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions led to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validated the biological relevance of our findings by demonstrating the ability of a G4-selective fluorescent probe to penetrateC9orf72mutant human motor neurons derived from ALS patients, which revealed clear fluorescent signal in putative condensates. Our findings strongly suggest that RNA G- rich repetitive sequences can form protein-free condensates sustained by multimolecular G- quadruplexes, highlighting their potential relevance as therapeutic targets forC9orf72mutation related ALS and FTD.
Pseudouridine prevalence in Kaposi’s sarcoma-associated herpesvirus transcriptome reveals an essential mechanism for viral replication
Authors: Mottram Timothy J. , Harper Katherine L. , Vasconcelos Elton J. R. , Anene Chinedu A. , Whitehouse Adrian
Published: February 2023

Pseudouridylation is a prevalent RNA modification shown to occur in tRNAs, rRNAs, snoRNAs and most recently mRNAs and lncRNAs. Emerging evidence suggests that this dynamic RNA modification is implicated in altering gene expression by regulating RNA stability, modulating translation elongation and modifying amino acid substitution rates. However, the role of pseudouridylation in infection is poorly understood. Here we demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) manipulates the pseudouridylation pathway to enhance replication. We show the pseudouridine synthases (PUS), PUS1 and PUS7 are essential for efficient KSHV lytic replication, supported by the redistribution of both PUS1 and PUS7 to viral replication and transcription complexes. We present a comprehensive analysis of KSHV RNA pseudouridylation, revealing hundreds of modified RNAs at single-nucleotide resolution. Notably, we further demonstrate that pseudouridylation of the KSHV-encoded polyadenylated nuclear RNA (PAN) plays a significant role in the stability of PAN RNA and in the association of the KSHV ORF57 protein. Our findings reveal a novel and essential role of pseudouridine modification in the KSHV replication cycle.
Vibrio choleraephage ICP3 requires O1 antigen for infection
Authors: Beckman Drew A. , Waters Christopher M.
Published: February 2023

In its natural aquatic environment, the bacterial pathogenVibrio cholerae, the causative agent of the enteric disease cholera, is in constant competition with bacterial viruses known as phages. Following ICP3 infection,V. choleraecultures that exhibited phage killing always recovered overnight, and clones isolated from these regrowth populations exhibited complete resistance to subsequent infections. Whole genome sequencing of these resistant mutants revealed seven distinct mutations in genes encoding for enzymes involved in O1 antigen biosynthesis, demonstrating that the O1 antigen is a previously uncharacterized putative receptor of ICP3. To further elucidate the specificity of the resistance conferred by these mutations, they were challenged with theV. cholerae-specific phages ICP1 and ICP2. All seven O1 antigen mutants demonstrated pan-resistance to ICP1 but not ICP2, which utilizes the OmpU outer membrane protein as a receptor. We show that resistant mutations to ICP1 and ICP3 evolve at a significantly higher frequency than ICP2, but these mutations have a significant fitness tradeoff toV. choleraeand are unable to evolve in the presence of an antimicrobial that mimics host cell defensins.
Live Imaging of Mitochondria in the Intact Fly Wing
Authors: Mattedi Francesca , Maddison Daniel C. , Smith Gaynor Ann , Vagnoni Alessio
Published: February 2023

Detailed mechanisms governing the transport of mitochondria in neurons have recently emerged, although it is still poorly understood how the regulation of transport is coordinated in space and time within the physiological context of an organism. Here, we provide a protocol to study the intracellular dynamics of mitochondria in the wing neurons of adultDrosophilain situ. The mounting and imaging procedures that we describe are suitable for use on most microscopes, and they can be easily implemented in any laboratory. Our noninvasive mounting procedures, combined with the translucency of the wing cuticle in adult animals, makes the wing nervous system accessible to advanced microscopy studies in a physiological environment. Combining the powerful genetics ofDrosophilawith time-lapse live imaging, users of this protocol will be able to analyze mitochondrial dynamics over time in a subset of sensory neurons in the wing. These cells extend long axons with a stereotypical plus-end-out microtubule orientation that represents a unique model to understand the logic of neuronal cargo transport, including the mitochondria. Finally, the neurons in this tissue respond to mechanical and chemical stimulation of the sensory organs of the wing, opening up the possibility of coupling the study of mitochondrial dynamics with the modulation of neuronal activity in agingDrosophila. We anticipate that the unique characteristics of this in vivo system will contribute to the discovery of novel mechanisms that regulate mitochondrial dynamics within an organismal context with relevant implications for the pathogenesis of age-dependent neurological disorders.
Using Videography to Study the Biomechanics and Behavior of Freely Moving Mosquitoes
Authors: Dickerson Andrew K. , Muijres Florian T. , Pieters Remco
Published: February 2023

Female mosquitoes of most species require a blood meal for egg development. When biting a human host to collect this blood meal, they can spread dangerous diseases such as malaria, yellow fever, or dengue. Researchers use videography to study many aspects of mosquito behavior, including in-flight host-seeking, takeoff, and landing behaviors, as well as probing and blood feeding, and more. Here, we introduce protocols on how to use videography to capture and analyze mosquito movements at high spatial and temporal resolution, in two and three dimensions.
Influence of curvature distribution smoothing on the reduction of aerofoil self-noise
Authors: Shen Xiang , Avital Eldad , Ikram Zaheer , Yang Liming , Korakianitis Theodosios , Dala Laurent
Published: February 2023

Purpose

This paper aims to investigate the influence of smooth curvature distributions on the self-noise of a low Reynolds number aerofoil and to unveil the flow mechanisms in the phenomenon.

Design/methodology/approach

In this paper, large Eddy simulation (LES) approach was performed to investigate the unsteady aerodynamic performance of both the original aerofoil E387 and the redesigned aerofoil A7 in a time-dependent study of boundary layer characteristics at Reynolds number 100,000 and angle of attack (AoA) 4-degree. The aerofoil A7 is redesigned from E387 by removing the irregularities in the surface curvature distributions and keeping a nearly identical geometry. Flow vorticity magnitude of both aerofoils, along with the spectra of the vertical fluctuating velocity component and noise level, are analysed to demonstrate the bubble flapping process near the trailing edge (TE) and the vortex shedding phenomenon.

Findings

This paper provides quantitative insights about how the flapping process of the laminar separation bubble (LSB) within the boundary layer near the TE affects the aerofoil self-noise. It is found that the aerofoil A7 with smooth curvature distributions presents a 10% smaller LSB compared to the aerofoil E387 at Reynolds number 100,000 and AoA 4-degree. The LES results also suggest that curvature distribution smoothing leads to a 6.5% reduction in overall broadband noise level.

Originality/value

This paper fulfils an identified need to reveal the unknown flow structure and the boundary layer characteristics that resulted in the self-noise reduction phenomenon yielded by curvature distribution smoothing.
Going green: an application of personal value theory to understand consumers visiting intention toward green hotels in Pakistan
Authors: Raza Ali , Farrukh Muhammad
Published: February 2023

Purpose

Personal values, ascribed responsibility and green self-identity (GSI) have been analyzed separately for a long time, but a more in-depth investigation is required on the relationships between these variables and their combined effects on consumers' visiting intention toward green hotels. Thus, this study aims to draw on Schwartz's (1992) personal values framework and ascribed responsibility. It expands the Schwartz personal values framework by incorporating GSI as a moderator to understanding consumers' visiting intention toward green hotels.

Design/methodology/approach

Partial least squares-structural equation modeling was used to analyze 387 responses collected through a self-administered structured questionnaire from hotel consumers in Pakistan.

Findings

The findings revealed that ascribed responsibility and self-transcendence values were significant factors in predicting consumers' intention toward green hotels. Moreover, GSI significantly moderated between self-conservation values, self-transcendence values and attitude. However, the association between self-conservation values and attitude was found insignificant.

Practical implications

This study can assist hotel management in planning and implementing efficient hotel marketing strategies. Hospitality marketers should heed attention to self-transcendence values, ascribed responsibility and stress on using these aspects to sustain green hotels' adoption.

Originality/value

The study contributes to the literature on the antecedents of consumers' visiting intention toward green hotels by expanding the Schwartz personal values framework by adding ascribed responsibility. Further, the authors incorporated GSI as a moderator to understand consumers' visiting intentions toward green hotels in Pakistan.
Emerging perspectives and challenges for virtual collaborative learning in an institution of higher education: a case of Lesotho
Authors: Matee Gloria Lihotetso , Motlohi Nthabiseng , Nkiwane Palesa
Published: February 2023

Purpose

This study aims to investigate emerging perspectives and challenges which teaching staff and students in the Faculties of Business and Accounting, Health and Education as well as Computing encountered in using Virtual Collaborative Learning during their classes in one accredited institution of higher education in Maseru district Lesotho. Previously conducted studies reveal that although similar studies to the current one have been conducted in different countries across the globe, conducting them in another different country such as Lesotho and in a different context might provide new information.

Design/methodology/approach

The study draws on Lev Vygotsky’s social constructivism as the theoretical framework because it is relevant and appropriate. The study was buttressed by constructivism paradigm, qualitative design as well as a qualitative case study. A purposive sampling technique was used in this study. A sample of 35 students and 11 teaching staff from the 3 respective faculties were used as participants of the study. This qualitative case study was based on online questionnaires issued to the participants using emails for data collection. Data were generated based on the themes which emerged.

Findings

The findings of the study suggest that majority of students found Virtual Collaborative Learning helpful and a user-friendly tool. However, lack of resources, clear instructions from the teaching staff and cooperation, internet connectivity issues, as well as data expenses have been identified as stumbling blocks that discourage students’ satisfactory engagement in Virtual Collaborative Learning. The findings further revealed various strategies including encouraging students to cooperate, grading students’ participation on online platforms and consultations could be used to overcome the challenges encountered in using Virtual Collaborative Learning. For generalisability and understanding of the breadth of the students and teaching staff experiences and challenges of Virtual Collaborative Learning, the authors recommend further study to be conducted on a larger representative sample, using the established themes of the current study.

Research limitations/implications

Using face-to-face interviews and classroom observations for data collection would have been more suitable for a qualitative methodology. However, due to COVID-19 regulations that restrict contact and limit lessons on online platforms, an online questionnaire was used for data collection.

Originality/value

This research reveals emerging perspectives and challenges which are encountered by teaching staff and students while using Virtual Collaborative Learning in one institution of higher education in Maseru Lesotho.
Employing string similarity metrics of partners to estimate audit team continuity: determinant and its effects on audit outcomes and pricing
Authors: Frendy  , Takeda Fumiko
Published: February 2023

Purpose

Partners are responsible for allocating audit tasks and facilitating knowledge sharing among team members. This study considers changes in the composition of partners to proxy for the continuity of the audit team. This study examines the effect of audit team continuity on audit outcomes (audit quality and report lags), pricing and its determinant (lead partner experience), which have not been thoroughly examined in previous studies.

Design/methodology/approach

This study employs string similarity metrics to measure audit team continuity. The study employs multivariate panel data regression empirical models to estimate a sample of 26,007 firm-years of listed Japanese companies from 2008 to 2019.

Findings

The study reveals that audit team continuity is negatively associated with audit fees, regardless of the auditor’s size. This finding contributes to the existing literature by showing that audit team continuity represents one of the determinant factors of audit fee. For clients of large audit firms, companies with higher (lower) audit team continuity issue audit reports in less (more) time. The experience of lead partners is a strong predictor of audit team continuity, irrespective of audit firm size. Audit quality is not associated with audit team continuity for either large or small audit firms.

Originality/value

This study proposes and examines audit team continuity measures that employ string similarity metrics to quantify changes in the composition of partners in consecutive audit engagements. Audit team continuity expands upon the tenure of individual audit partners, which is commonly used in prior literature as a measure of client–partner relationships.
Interrelationship between strategic factors, technology and organizational learning: a systematic literature review
Authors: Sharan Kushagra , Dhayanithy Deepak , Sethi Deepa
Published: February 2023

Purpose

This paper aims to examine the relationship between organizational learning (OL) and technology through the lens of strategic factors and to ascertain future research directions.

Design/methodology/approach

The systematic literature review method was applied in three stages to the 76 articles obtained from Scopus, Web of Science, Google Scholar and EBSCO databases.

Findings

This research revealed the evolution of the role of OL in innovation, performance, knowledge management and technological adoption and showcases a detailed conceptual model relating technology outcomes (technological innovation and capabilities) to OL outcomes (technology absorptive capacity, technological proactivity, as well as information technology [IT] and organization process alignment).

Research limitations/implications

This review includes articles mainly in English and excludes conference proceedings.

Practical implications

This research attempts to guide managers and policymakers to foster an organizational culture conducive to technological adoption and OL. It helps organizations develop strategies for new product development, including strategic alliances and strategic leadership.

Originality/value

This review formalizes the linkages between technological absorptive capacity, technological proactivity and IT with technological innovation and capabilities. It identifies research gaps and elucidates future research directions.
Evolution of cannabis regulations and their overlooked link with money laundering: Australia as a critical case study
Authors: Tiwari Milind , Ferrill Jamie
Published: February 2023

Purpose

The purpose of this paper is to interrogate if the legal status of a cannabis affects money laundering activity. The legal status of cannabis continues to evolve globally; at the same time, its market remains enormous. Much of this market represents dirty money from criminal acts, which often requires laundering. In the context of changing cannabis regulations, legislation, and policies, the authors propose the possible implications such changes may have on the extent of money laundering.

Design/methodology/approach

This paper proposes the implications of the evolution of cannabis regulations on money laundering activities, using the theoretical underpinning of rational choice. Using Australia as a replicable critical case study, the paper, using the Walker gravity model and using United Nations Office on Drugs and Crime-reported prices of cannabis from 2003 to 2017 and Australian Criminal Intelligence Commission reports empirically validates the effects of cannabis regulations on the proceeds available for laundering.

Findings

This study finds support for the argument that prohibitive measures toward cannabis use contribute to increases in the need to launder generated proceeds.

Research limitations/implications

The findings can be replicated in other countries and may contribute to novel propositions within the debate on the legalization of cannabis use, which has, thus, far primarily focused on the areas of health, crime, taxation and education.

Originality/value

To the best of the authors’ knowledge, no study has yet attempted to provide an economic analysis of the effects of cannabis policy changes on money laundering.