bluuebunny/crossref_metadata_2025 huggingface dataset:
SARS-CoV-2 evolves increased infection elicited cell death and fusion in an immunosuppressed individual
Authors: Lustig Gila , Ganga Yashica , Rodel Hylton , Tegally Houriiyah , Jackson Laurelle , Cele Sandile , Khan Khadija , Jule Zesuliwe , Reedoy Kajal , Karim Farina , Bernstein Mallory , Moosa Mahomed-Yunus S. , Archary Derseree , de Oliveira Tulio , Lessells Richard , Abdool Karim Salim S. , Sigal Alex
Published: November 2022

The milder clinical manifestations of Omicron infection relative to pre-Omicron SARS-CoV-2 raises the possibility that extensive evolution results in reduced pathogenicity. To test this hypothesis, we quantified induction of cell fusion and cell death in SARS-CoV-2 evolved from ancestral virus during long-term infection. Both cell fusion and death were reduced in Omicron BA.1 infection relative to ancestral virus. Evolved virus was isolated at different times during a 6-month infection in an immunosuppressed individual with advanced HIV disease. The virus isolated 16 days post-reported symptom onset induced fusogenicity and cell death at levels similar to BA.1. However, fusogenicity was increased in virus isolated at 6 months post-symptoms to levels intermediate between BA.1 and ancestral SARS-CoV-2. Similarly, infected cell death showed a graded increase from earlier to later isolates. These results may indicate that, at least by the cellular measures used here, evolution in long-term infection does not necessarily attenuate the virus.
Reconstructing the formation of Hmong-Mien genetic fine-structure
Authors: Xia Zi-Yang , Chen Xingcai , Wang Chuan-Chao , Deng Qiongying
Published: November 2022

The linguistic, historical, and subsistent uniqueness of Hmong-Mien (HM) speakers offers a wonderful opportunity to investigate how these factors impact the genetic structure. Nevertheless, the genetic differentiation among HM-speaking populations and the formation process behind are far from well characterized in previous studies. Here, we generated genome-wide data from 67 Yao ethnicity samples and analyzed them together with published data, particularly by leveraging haplotype-based methods. We identify that the fine-scale genetic substructure of HM-speaking populations corresponds better to linguistic classification than to geography, while the parallel of serial founder events and language differentiations can be found in West Hmongic speakers. Multiple lines of evidence indicate that ~500-year-old GaoHuaHua individuals are most closely related to West Hmongic-speaking Bunu. The excessive level of the genetic bottleneck of HM speakers, especially Bunu, is in agreement with their long-term practice of slash-and-burn agriculture. The inferred admixture dates in most of the HM-speaking populations overlap the reign of the Ming dynasty (1368 – 1644 CE). Besides the common genetic origin of HM speakers, their external ancestry majorly comes from neighboring Han Chinese and Kra-Dai speakers in South China. Conclusively, our analysis reveals the recent isolation and admixture events that contribute to the fine-scale genetic formation of present-day HM-speaking populations underrepresented in previous studies.
AGO2a but not AGO2b mediates antiviral defense against the infection of wildtype Cucumber mosaic virus in tomato
Authors: Zhao Li-Ling , Chen Ying-Fang , Xiao Xing-Ming , Gao Hai-Ying , Cao Jia-Min , Zhang Zhong-Kai , Guo Zhongxin
Published: November 2022

Evolutionarily conserved antiviral RNA interference (RNAi) mediates a primary antiviral innate immunity preventing the infection of broad spectrum viruses in plants. However, the detailed mechanism in plants is still largely unknown, especially in important agricultural crops including tomato. On the other aspect, varieties of pathogenic viruses evolve to possess Viral Suppressor of RNA silencing (VSR) to suppress antiviral RNAi in host. Due to the prevalence of VSR, it is still skeptical that antiviral RNAi truly functions to prevent the invasion of natural wildtype viruses in plants and animals. In the research, it is for the first time we applied CRISPR-Cas9 to generateago2a, ago2borago2abmutants for two differentiatedSolanum lycopersicumAGO2, one key effector in antiviral RNAi. We found that AGO2a but not AGO2b was significantly induced to inhibit the propagation of not only VSR-deficient Cucumber mosaic virus (CMV) but also wildtype CMV-Fny in tomato, however, both AGO2a and AGO2b did not regulate disease induction after the infection of either virus. Our findings firstly reveal a prominent role of AGO2a in antiviral RNAi innate immunity in tomato and demonstrate that antiviral RNAi evolves to defend the infection of natural wildtype CMV-Fny in tomato, however AGO2a-mediated antiviral RNAi does not play major roles in promoting tolerance of tomato plants to CMV infection for maintaining health.
Pretrained language models and weight redistribution achieve precisekcatprediction
Authors: Yu Han , Luo Xiaozhou
Published: November 2022

The enzyme turnover number (kcat) is a meaningful and valuable kinetic parameter, reflecting the catalytic efficiency of an enzyme to a specific substrate, which determines the global proteome allocation, metabolic fluxes and cell growth. Here, we present a precisekcatprediction model (PreKcat) leveraging pretrained language models and a weight redistribution strategy. PreKcat significantly outperforms the previouskcatprediction method in terms of various evaluation metrics. We also confirmed the ability of PreKcat to discriminate enzymes of different metabolic contexts and different types. Additionally, the proposed weight redistribution strategies effectively reduce the prediction error of highkcatvalues and capture minor effects of amino acid substitutions on two crucial enzymes of the naringenin synthetic pathway, leading to obvious distinctions. Overall, the presentedkcatprediction model provides a valuable tool for deciphering the mechanisms of enzyme kinetics and enables novel insights into enzymology and biomedical applications.
Peptide-MHC Structure Prediction With Mixed Residue and Atom Graph Neural Network
Authors: Delaunay Antoine P. , Fu Yunguan , Bégué Alberto , McHardy Robert , Djermani Bachir A. , Rooney Michael , Tovchigrechko Andrey , Copoiu Liviu , Skwark Marcin J. , Carranza Nicolas Lopez , Lang Maren , Beguir Karim , Şahin Uğur
Published: November 2022

Neoantigen-targeting vaccines have achieved breakthrough success in cancer immunotherapy by eliciting immune responses against neoantigens, which are proteins uniquely produced by cancer cells. During the immune response, the interactions between peptides and major histocompatibility complexes (MHC) play an important role as peptides must be bound and presented by MHC to be recognised by the immune system. However, only limited experimentally determined peptide-MHC (pMHC) structures are available, andin-silicostructure modelling is therefore used for studying their interactions. Current approaches mainly use Monte Carlo sampling and energy minimisation, and are often computationally expensive. On the other hand, the advent of large high-quality proteomic data sets has led to an unprecedented opportunity for deep learning-based methods with pMHC structure prediction becoming feasible with these trained protein folding models. In this work, we present a graph neural network-based model for pMHC structure prediction, which takes an amino acid-level pMHC graph and an atomic-level peptide graph as inputs and predicts the peptide backbone conformation. With a novel weighted reconstruction loss, the trained model achieved a similar accuracy to AlphaFold 2, requiring only 1.7M learnable parameters compared to 93M, representing a more than 98% reduction in the number of required parameters.
CRISPRi inDeinococcus radiodurans
Authors: Misra Chitra S. , Pandey Neha , Appukuttan Deepti , Rath Devashish
Published: November 2022

The extremely radiation resistant bacterium,Deinococcus radiodurans, is a microbe of importance, both, for studying stress tolerance mechanisms and as a chassis for industrial biotechnology. However, the molecular tools available for use in this organism continue to be limiting. In view of this, the CRISPR-Cas tools provide a large repertoire of applications for gene manipulation. We show the utility of the type I-E Cascade system for knocking down gene expression in this organism. A single-vector system was designed for expression of the Cascade components as well as the crRNA. The type I-E Cascade system was better tolerated than the type II-A Cas9 system inD. radiodurans. An assayable acid phosphatase gene,phoNintegrated into the genome of this organism could be knocked down to 10% of its activity using the Cascade system. Cascade-based knockdown ofssb, a gene important for radiation resistance resulted in poor recovery post irradiation. Targeting the Radiation and Desiccation Resistance Motif (RDRM), upstream of thessb, prevented de-repression of its expression upon radiation exposure. In addition to this, multi-locus targeting was demonstrated on the deinococcal genome, by knocking down bothphoNandssbexpression simultaneously. The programmable CRISPRi tool developed in this study will facilitate study of essential genes, hypothetical genes, cis-elements involved in radiation response as well as enable metabolic engineering in this organism. Further the tool is amenable for implementing high-throughput approaches for such studies.
Enzymatic assembly of small synthetic genes with repetitive elements
Authors: Nguyen Michael T. A. , Gobry Martin Vincent , Vallina Néstor Sampedro , Pothoulakis Georgios , Andersen Ebbe Sloth
Published: November 2022

Gene synthesis efficiency has greatly improved in recent years but is limited when it comes to repetitive sequences and results in synthesis failure or delays by DNA synthesis vendors. This is representing a major obstacle for the development of synthetic biology, since repetitive elements are increasingly being used in design of genetic circuits and design of biomolecular nanostructures. Here, we describe a method for the assembly of small synthetic genes with repetitive elements: First, a gene of interest is splitin silicointo small synthons of up to 80 base pairs flanked by Golden Gate-compatible overhangs. Then, synthons are made by oligo extension and finally assembled into a synthetic gene by Golden Gate Assembly. We demonstrate the method by constructing eight challenging genes with repetitive elements e.g., multiple repeats of RNA aptamers and RNA origami scaffolds with multiple identical aptamers. The genes range in size from 133 to 456 base pairs and are assembled with fidelities of up to 87.5 %. The method was developed to facilitate our own specific research but may be of general use for constructing challenging and repetitive genes and thus a valuable addition to the molecular cloning toolbox.
MERISTEM-DEFECTIVE / DEFECTIVELY ORGANIZED TRIBUTARIES2 regulates the balance between stemness and differentiation in the root meristem through RNA splicing control
Authors: Thompson Helen L. , Shen Weiran , Matus Rodrigo , Kakkar Medhavi , Jones Carl , Dolan David , Grellscheid Sushma , Yang Xiyan , Zhang Na , Mozaffari-Jovin Sina , Chen Chunli , Zhang Xianlong , Topping Jennifer F. , Lindsey Keith
Published: November 2022

Plants respond to environmental stresses through controlled stem cell maintenance and meristem activity. One level of transcriptional control is RNA alternative splicing. However the mechanistic link between stress, meristem function and RNA splicing is poorly understood. TheMERISTEM-DEFECTIVE(MDF)/DEFECTIVELY ORGANIZED TRIBUTARIES(DOT2) gene of Arabidopsis encodes a SR-related family protein, required for meristem function and leaf vascularization, and is the likely orthologue of the human SART1 and yeast snu66 splicing factors. MDF is required for the correct splicing and expression of key transcripts associated with root meristem function. We identifiedRSZ33andACC1, both known to regulate cell patterning, as splicing targets required for MDF function in the meristem.MDFexpression is modulated by osmotic and cold stress, associated with differential splicing and specific isoform accumulation and shuttling between nucleus and cytosol, and acts in part via a splicing targetSR34. We propose a model in which MDF controls splicing in the root meristem to promote stemness and repress stress response and cell differentiation pathways.

Summary statement

The protein MERISTEM-DEFECTIVE regulates Arabidopsis meristem function through its role as a splicing factor, mediated through splicing targets RSZ33, ACC1 and SR34.
Promoting translational readthrough to augment fibrillin-1 (FBN1) deposition in Marfan syndrome fibroblasts: A proof-of-concept study
Authors: Balic Zerina , Hubmacher Dirk
Published: November 2022

Marfan syndrome (MFS) is a connective tissue disorder characterized by long bone overgrowth, enlargement of the aorta, ocular anomalies and other symptoms. Current treatment focuses on managing aortic aneurysms to avoid dissection or rupture. However, no cures are available. MFS is caused by one of >1,800 dominant pathogenic variants inFBN1, which encodes the extracellular matrix (ECM) protein fibrillin-1. A significant number ofFBN1variants result in premature termination codons (PTCs). Recently, small molecules were identified that can promote translational readthrough of PTCs and were evaluated in preclinical and clinical trials for several genetic disorders. Here, we show that the translational readthrough drugs ataluren and gentamicin ameliorated FBN1 deposition in some MFS patient-derived skin fibroblast lines harboring PTC variants inFBN1. In contrast, inhibitors of NMD were cytotoxic to the skin fibroblast lines that we analyzed. We conclude that promoting translational readthrough of PTC variants inFBN1could result in a therapeutic benefit for MFS patients with specific PTCs inFBN1and that its efficacy will likely depend on the PTC sequence context, the amino acids that are incorporated in FBN1 after PTC suppression and the overall increase of FBN1 deposition in the ECM.
Apicomplexans predict thermal stress mortality in the Mediterranean coralParamuricea clavata
Authors: Bonacolta Anthony M , Miravall Jordi , Gómez-Gras Daniel , Ledoux Jean-Baptiste , López-Sendino Paula , Garrabou Joaquim , Massana Ramon , del Campo Javier
Published: November 2022

The octocoralParamuricea clavatais an ecosystem architect of the Mediterranean temperate reefs that is currently threatened by episodic mass mortality events related to global warming. Local average thermal regimes nor recent thermal history have been shown to play a significant role in population thermotolerance in this species. The microbiome, however, may play an active role in the thermal stress susceptibility of corals, potentially holding the answer as to why corals show differential sensitivity to heat-stress. To investigate this, the prokaryotic and eukaryotic microbiome ofP. clavatacollected from around the Mediterranean was characterized before experimental heat-stress to determine if its microbial composition influences the thermal response of the holobiont. We found that the prokaryotic community was not informative in predicting the thermal susceptibility ofP. clavata. On the other hand, members ofP. clavata’smicroeukaryotic community were significantly correlated with thermal stress sensitivity. Syndiniales from theDino-Group I Clade 1were significantly enriched in thermally resistant corals, while the apicomplexan corallicolids were significantly enriched in thermally susceptible corals. Corallicolids are associated with 70% of coral genera around the world, yet the ecological role of this general anthozoan symbiont has yet to be determined. We hypothesize thatP. clavatamortality following heat-stress may be caused by a shift from apparent commensalism to parasitism in the corallicolid-coral host relationship driven by the added stress. Our results show the potential importance of corallicolids and the rest of the microeukaryotic community of corals to understanding thermal stress response in corals and provides a useful tool to guide conservation efforts and future research into coral-associated microeukaryotes.
Active smelling in the American cockroach
Authors: Hoffmann Antoine , Couzin-Fuchs Einat
Published: November 2022

2

Motion plays an essential role in sensory acquisition. From changing the position in which information can be acquired to fine scale probing and active sensing, animals actively control the way they interact with the environment. In olfaction, movement impacts the time and location of odour sampling as well as the flow of odour molecules around the olfactory organs. Employing a high-resolution analysis, we investigate how the insect antennae interact with the olfactory environment in a species with a well studied olfactory system – the American cockroach. Cockroaches were tested in a wind-tunnel setup during the presentation of odours with different attractivity levels: colony extract, butanol and linalool. Our analysis revealed significant changes in antennal kinematics when odours are presented, including a shift towards the stream position, an increase in vertical movement and high-frequency local oscillations. Nevertheless, the antennal shifting occurred predominantly in a single antenna while the overall range covered by both antennae was maintained throughout. These findings hold true for both static and moving stimuli and are more pronounced for attractive odours. Furthermore, we find that upon odour encounter, there is an increased occurrence of high-frequency antennal sweeps and vertical strokes, which are shown to impact the olfactory environment’s statistics directly. Our study lays out a tractable system for exploring the tight coupling between sensing and movement, in which antennal sweeps, in parallel to mammalian sniffing, are actively involved in facilitating odour capture and transport, generating odour intermittency in environments with low air movement where cockroaches dwell.
Accuracy and completeness of long read metagenomic assemblies
Authors: Buttler Jeremy , Drown Devin
Published: November 2022

Microbes, we can learn how microbes influence the surrounding environment, contribute to human health, and understand which pathogen interactions result in differences in disease severity. Metagenomics can be used as a tool to explore the interactions between microbes. Metagenomic assemblies built using long read nanopore data depend on the read level accuracy. The read level accuracy of nanopore sequencing has made dramatic improvements over the past several years. However, we do not know if the increased read level accuracy allows for faster assemblers to make as accurate metagenomic assemblies as slower assemblers. Here, we present the results of a benchmarking study comparing three commonly used long read assemblers, Flye, Raven, and Redbean. We used a prepared DNA standard of seven bacteria as our input community. We prepared a sequencing library on the VolTRAX V2 sequence using a MinION mk1b. We basecalled using the latest version of Guppy with the super-accuracy model. We found that increasing read depth benefited each of the assemblers, and nearly complete community member chromosomes were assembled with as little as 10x read depth. Polishing assemblies using Medaka had a predictable improvement in quality. Some assemblers struggled with particular members of the bacterial community, but we found Flye to be the most robust across taxa. We found Flye was the most effective assembler for recovering plasmids. Based on Flye’s consistency for chromosomes and increased effectiveness at assembling plasmids, we would recommend using Flye in future metagenomic studies.
Molecular and cellular similarities in the brain of SARS-CoV-2 and Alzheimer’s disease individuals
Authors: Griggs Elizabeth , Trageser Kyle , Naughton Sean , Yang Eun-Jeong , Mathew Brian , Van Hyfte Grace , Hellmers Linh , Jette Nathalie , Estill Molly , Shen Li , Fischer Tracy , Pasinetti Giulio Maria
Published: November 2022

Infection with the etiological agent of COVID-19, SARS-CoV-2, appears capable of impacting cognition, which some patients with Post-acute Sequelae of SARS-CoV-2 (PASC). To evaluate neuro-pathophysiological consequences of SARS-CoV-2 infection, we examine transcriptional and cellular signatures in the Broadman area 9 (BA9) of the frontal cortex and the hippocampal formation (HF) in SARS-CoV-2, Alzheimer’s disease (AD) and SARS-CoV-2 infected AD individuals, compared to age- and gender-matched neurological cases. Here we show similar alterations of neuroinflammation and blood-brain barrier integrity in SARS-CoV-2, AD, and SARS-CoV-2 infected AD individuals. Distribution of microglial changes reflected by the increase of Iba-1 reveal nodular morphological alterations in SARS-CoV-2 infected AD individuals. Similarly, HIF-1α is significantly upregulated in the context of SARS-CoV-2 infection in the same brain regions regardless of AD status. The finding may help to inform decision-making regarding therapeutic treatments in patients with neuro-PASC, especially those at increased risk of developing AD.

Teaser

SARS-CoV-2 and Alzheimer’s disease share similar neuroinflammatory processes, which may help explain neuro-PASC.
Alternative paths to immune activation: the role of costimulatory risk genes for polygenic inflammatory disease in T helper cells
Authors: Voda Alexandru-Ioan , Correa Kristina , Hamp Jonathan , Moscrop Chloe , Dustin Michael , Jostins-Dean Luke
Published: November 2022

T cell activation pathways have been repeatedly implicated by genetic studies as being enriched for risk genes for immune and inflammatory diseases. Many of these risk genes code for costimulatory receptors or ligands. Costimulatory receptors are cell surface proteins on T cells, which are engaged by costimulatory ligands on antigen-presenting cells. Both costimulation and antigen binding are required to trigger T cell activation. In order to study the different pathways activated by these costimulatory risk molecules, and the role they may play in inflammatory disease genetics, we carried out gene expression (RNA-seq) and chromatin accessibility (ATAC-seq) profiling of naive and memory CD4+ T cells (N=5 donors) activated via four different costimulatory receptors: CD28 (the standard molecule used forin vitroactivation studies), along with alternative costimulatory molecules ICOS, CD6, and CD27.

Most, but not all, activation genes and regions are shared by different costimulation conditions. Alternative costimulation induced lower proliferation and cytokine production, but higher lysosome production, altered metabolic processing, and indications of “signal seeking” behaviour (homing and expression of costimulatory and cytokine receptors). We validated a number of these functions at the surface protein level using orthogonal experimental techniques. We found the strongest enrichment of heritability for inflammatory bowel disease in shared regions upregulated by all costimulatory molecules. However, some risk variants and genes were only induced by alternative costimulation, and the impact of these variants on expression were less often successfully mapped in studies of T cells activated by traditional CD28 costimulation. This suggests that future genetics studies of gene expression in activated T cells may benefit from including alternative costimulation conditions.
Bursts in biosynthetic gene cluster transcription are accompanied by surges of natural compound production in the myxobacteriumSorangiumsp
Authors: Boldt Judith , Lukoševičiūtė Laima , Fu Chengzhang , Steglich Matthias , Bunk Boyke , Junker Vera , Gollasch Aileen , Trunkwalter Birte , Mohr Kathrin I. , Beckstette Michael , Wink Joachim , Overmann Jörg , Müller Rolf , Nübel Ulrich
Published: November 2022

We have investigated the time course of genome-wide transcription in the myxobacteriumSorangiumsp. So ce836 in relation to its production of natural compounds. Time-resolved RNA sequencing revealed that core biosynthesis genes from 48 biosynthetic gene clusters (BGCs; 92% of all BGCs encoded in the genome) were actively transcribed at specific time points in a batch culture. The majority (80%) of polyketide synthase and non-ribosomal peptide synthetase genes displayed distinct peaks of transcription during exponential bacterial growth. Strikingly, these bursts in BGC transcriptional activity were associated with surges in the production of known natural compounds, indicating that their biosynthesis was critially regulated at the transcriptional level. In contrast, BGC read counts from single time points had limited predictive value about biosynthetic activity, since transcription levels varied >100-fold among BGCs with detected natural products. Taken together, our time-course data provide unique insights into the dynamics of natural compound biosynthesis and its regulation in a wild-type myxobacterium, challenging the commonly cited notion of preferential BGC expression under nutrient-limited conditions. The close association observed between BGC transcription and compound production warrants additional efforts to develop genetic engineering tools for myxobacterial producer strains, to boost compound yields by manipulating transcriptional activity.
Theta oscillations and minor hallucinations in Parkinson’s disease reveal decrease in frontal lobe functions and later cognitive decline
Authors: Bernasconi Fosco , Pagonabarraga Javier , Bejr-Kasem Helena , Martinez-Horta Saul , Kulisevsky Jaime , Blanke Olaf
Published: November 2022

Cognitive decline and hallucinations are common and debilitating non-motor symptoms, occurring during later phases of Parkinson’s disease (PD). Minor hallucinations (MH), appear at early phases and have been suggested to predict cognitive impairment in PD, however, this has not been well-established by clinical research. Here, we investigated whether non-demented PD patients with MH show altered brain oscillations and whether such MH-related electrophysiological changes are associated with cognitive impairments that increase over time. Combining model-driven EEG analysis with neuropsychiatric and neuropsychological examinations in 75 PD patients, we reveal enhanced frontal theta oscillations in PD patients suffering from MH and link these oscillatory changes with lower cognitive frontal-subcortical functions. Neuropsychological follow-up examinations five years later confirmed MH-specific theta oscillations and revealed a stronger decline in frontal-subcortical functions in MH-patients with stronger frontal theta alterations, defining an MH and theta oscillation-based early marker of a cognitive decline in PD.
Mouse HP1γ regulates TRF1 expression and telomere stability
Authors: Stylianakis Emmanouil , Festenstein Richard , Vannier Jean-Baptiste
Published: November 2022

Aims

TElomeric Repeat-containing RNA are long non-coding RNAs generated from the telomeres. TERRAs are essential for the establishment of heterochromatin marks at telomeres, which serve for the binding of Heterochromatin Protein 1 (HP1), a protein family of epigenetic modifiers involved with chromatin compaction and gene silencing. While HP1γ is enriched on gene bodies of actively transcribed human and mouse genes, it is unclear if its transcriptional role is important for HP1γ function in telomere cohesion and telomere maintenance. We aimed to study the effect of mouse HP1γ on the transcription of telomere factors and molecules that can affect telomere maintenance.

Main methods

We investigated the telomere function of HP1γ by using deficient mouse embryonic fibroblasts (MEFs) deriving from 13.5 embryonic day embryos compared to their litter mate controls. We used gene expression analysis of HP1γ deficient MEFs and validated the molecular and mechanistic consequences of HP1γ loss by telomere FISH, immunofluorescence, RT-qPCR and DNA-RNA Immunoprecipitation (DRIP).

Key findings

Loss of HP1γ in primary MEFs leads to a downregulation of various telomere and telomere-accessory transcripts, including shelterin protein TRF1. Its downregulation is associated with increased telomere replication stress and DNA damage (γH2AX), effects more profound in females. We suggest that the source for the impaired telomere maintenance is a consequence of increased telomeric DNA-RNA hybrids and TERRAs arising at and from mouse chromosomes 18 and X.

Significance

Our results suggest an important transcriptional control by mouse HP1γ of various telomere factors including TRF1 protein and TERRAs that has profound consequences on telomere stability, with a potential sexually dimorphic nature.
Multiple genes evolved for fungal septal pore plugging identified via large-scale localization and functional screenings
Authors: Mamun Md. Abdulla Al , Cao Wei , Nakamura Shugo , Maruyama Jun-ichi
Published: November 2022

Multicellular organisms exhibit cytoplasmic exchange using porous structures for cooperation among cells. Fungal multicellular lineages have evolved septal pores for this function. Interconnected hyphal cells possess the risk of wound-related cytoplasmic loss unless the septal pores are plugged. However, the gene evolution of regulatory mechanisms underlying fungal septal pore plugging remains poorly understood. To identify novel septal components, 776 uncharacterized proteins were identified using genomic comparisons between septal pore-bearing and -lacking ascomycete species. We then determined their subcellular localizations, and in total 62 proteins localized to the septum or septal pore. We analyzed the effects of deleting the encoding genes on septal pore plugging upon hyphal wounding. Of the 62 proteins, 23 were involved in regulating septal pore plugging. Here, using orthologous group and phylogenetic analyses, this study suggests that septal pore regulation has evolved either by co-option of preexisting genes or by Pezizomycotina-specific gene acquisition.
Joint X-ray/neutron structure of Lentinus similis AA9_A at room temperature
Authors: Tandrup Tobias , Lo Leggio Leila , Meilleur Flora
Published: November 2022

Lytic polysaccharide monooxygenases (LPMOs) are copper metalloenzymes which cleave polysaccharides oxidatively and are important in pathogen biology, carbon cycling and biotechnology. The Lentinus similis family AA9 isoform A (LsAA9_A) has been extensively studied as a model system because its activity towards smaller soluble saccharide substrates has allowed detailed structural characterization of its interaction with a variety of substrates by X-ray crystallography at high resolution. Here, the joint X-ray/neutron room-temperature crystallographic structure of carbohydrate-free LsAA9_A in the copper(II) resting state refined against X-ray and neutron data at 2.1 and 2.8 Å resolution, respectively, is presented. The results provide an experimental determination of the protonation states of the copper(II)-coordinating residues and second-shell residues in LsAA9_A, paving the way for future neutron crystallographic studies of LPMO–carbohydrate complexes.
Legal issues of the broadcast and simultaneous Internet transmission of open university courses
Authors: Haruo Kodama
Published: November 2022

Purpose

The purpose of this paper is to investigate the legal issues of simultaneous Internet transmission of broadcasting programs of the Open University of Japan (OUJ) and to take legal measures to promote the mutual utilization of open university courses in Japan, the UK, China and Korea.

Design/methodology/approach

The author examines the legal relationship regarding Internet simultaneous distribution of broadcast courses at the OUJ. The author then considers the legal relationship between the UK, China and South Korea regarding the simultaneous transmission of broadcast courses over the internet. Based on that consideration, this paper clarifies legal measures to promote its utilization.

Findings

Internet transmission of broadcasting courses will be webcasting. Arguably, it can be assumed to be streaming and on-demand, albeit controversial. Webcasting will be publicly transmitted, but there is only an on-demand provision for Internet transmission. As webcasting is streaming and on-demand, it involves reproduction of broadcasting courses. Therefore, webcasting needs to provide streaming provision for public transmission rights and associate them with reproduction right.

Originality/value

The originality of this paper lies in clarifying the legal response of the object, subject and rights of webcasting from the perspective of the OUJ, in order to dispel legal problems that may arise in the future against this unexplored phenomenon. Additionally, this paper is valuable in that it presents legal consistency from the point of view of the comparative laws of Japan, the UK, China and South Korea, based on an examination of the legal response in Japan.
Understanding the spillover effects of manufacturer-initiated reward on observers’ compliance: a social learning perspective
Authors: Liu Cuijuan , Xiao Zhenxin , Gao Yu , Dong Maggie Chuoyan , Gao Shanxing
Published: November 2022

Purpose

Although manufacturer-initiated rewards are widely used to secure distributors’ compliance, the spillover effect on unrewarded distributors (i.e. observers) in the same distribution channel is under-researched. Using insights from social learning theory, this paper aims to investigate how manufacturer-initiated rewards affect observers’ expectation of reward and shape observers’ compliance toward the manufacturer. Furthermore, this paper explores how such effects are contingent upon distributor relationship features.

Design/methodology/approach

To test the hypotheses, hierarchical multiple regression and bootstrapping analyses were performed using survey data from 280 Chinese distributors.

Findings

The magnitude of a manufacturer-initiated reward to a distributor stimulates expectation of reward among observers, which enhances compliance; observers’ expectation of reward mediates the impact of reward magnitude on compliance. Moreover, network centrality (of the rewarded peer) negatively moderates the positive impact of reward magnitude on observers’ expectation of reward, whereas observers’ dependence (on the manufacturer) positively moderates this dynamic.

Practical implications

Manufacturers should pay attention to the spillover effects of rewards. Overall, they should use rewards of appropriate magnitude to show willingness to recognize outstanding distributors. This will inspire unrewarded distributors, which will then be more compliant. Furthermore, manufacturers should know that specific types of distributor relationship features may significantly vary the spillover effects.

Originality/value

This study illuminates the spillover effects of manufacturer-initiated reward by opening the “black box” of the link between reward magnitude and observers’ compliance and by specifying the effects’ boundary conditions.
The effect of YouTube comment interaction on video engagement: focusing on interactivity centralization and creators' interactivity
Authors: Byun Unji , Jang Moonkyoung , Baek Hyunmi
Published: November 2022

Purpose

This study aims to reveal the effect of comment interactions on video engagement of users in video-sharing platforms.

Design/methodology/approach

The authors collected 87,232 comments on 647 videos of Korean beauty creators on YouTube and conducted a social network analysis and a hierarchical regression analysis.

Findings

The results present that the more evenly interactive participants write and receive replies in the comments section, the more users' video engagement increases. The more creators reply to user comments and the more reactions they present, the more video engagement increases. Additionally, the influence of the creator's interaction on user engagement increased as the number of commenting participants decreased.

Practical implications

This study has implications for platform operators regarding comment section design and proposes interaction strategies for content creators to induce users' video engagement.

Originality/value

Compared to previous studies, this study empirically verifies the influence of interactions on video-sharing platforms in detail by confirming the influence of user interaction structures and creator's participation in the interaction on video engagement.
Teaching undergraduates to develop concise and compelling scholarly communication through storytelling
Authors: Ford–Baxter Tiffanie , Faulkner Kendall
Published: November 2022

Purpose

This article reviews current librarian instructional approaches for poster and oral presentation assignments and showcases a new approach using the Pixar Pitch outline.

Design/methodology/approach

The authors adapted the Pixar Pitch framework to aid students in synthesizing complex information and improving their communication strategies.

Findings

Librarians are frequently involved in teaching strategic searching and topic development in instruction sessions for students preparing to communicate research through posters and presentations. Students need to understand how to communicate effectively and prepare information for various audiences, skills closely linked to several threshold concepts in the ACRL Framework for Information Literacy. However, this area remains less taught by librarians. This article presents one approach for librarians to become involved in this instruction.

Originality/value

There is currently minimal research on using the Pixar Pitch within higher education; most use appears in publications in the communications field.
Factors at multiple scales drive parasite community structure
Authors: Brian Joshua I. , Aldridge David C.
Published: November 2022

Understanding how ecological communities are assembled remains a key goal of ecosystem ecology. Because communities are hierarchical, factors acting at multiple scales can contribute to patterns of community structure. Parasites provide a natural system to explore this idea, as they exist as discrete communities within host individuals, which are themselves part of a community and metacommunity.

We aimed to understand the relative contribution of multi‐scale drivers in parasite community assembly and assess how patterns at one level may mask those occurring at another. Specifically, we wanted to disentangle patterns caused by passive sampling from those determined by ecological drivers, and how these vary with scale.

We applied a Markov Random Fields model and assessed measures of β‐diversity and nestedness for 420 replicate parasite infracommunities (parasite assemblages in host individuals) across two freshwater mussel host species, three sites and two time periods, comparing our results to simulations from four different ecologically relevant null models.

We showed that β‐diversity between sites (explaining 25% of variation in parasite distribution) and host species (41%) is greater than expected, and β‐diversity between individual hosts is smaller than expected, even after accounting for parasite prevalence and characteristics of host individuals. Furthermore, parasite communities were significantly less nested than expected once parasite prevalence and host characteristics were both accounted for, but more nested than expected otherwise, suggesting a degree of modularity at the within‐host level that is masked if underlying host and parasite characteristics are not taken into account. The Markov Random Fields model provided evidence for possible competitive within‐host parasite interactions, providing a mechanism for the observed infracommunity modularity.

An integrative approach that examines factors at multiple scales is necessary to understand the composition of ecological communities. Furthermore, patterns at one level can alter the interpretation of ecologically important drivers at another if variation at higher scales is not accounted for.
Prognostic value of inflammatory and nutritional indexes among advanced NSCLC patients receiving PD‐1 inhibitor therapy
Authors: Fang Qiyu , Yu Jia , Li Wei , Luo Jie , Deng Qinfang , Chen Bin , He Yayi , Zhang Jie , Zhou Caicun
Published: November 2022

Though immunotherapy has to some extent improved the prognosis of patients with advanced non‐small cell lung cancer (NSCLC), only a few patients benefit. Furthermore, immunotherapy efficacy is affected by inflammatory and nutritional status of patients. To investigate whether dynamics of inflammatory and nutritional indexes were associated with prognosis, 223 patients were analysed retrospectively. The inflammatory indexes of interest were neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and systemic immune‐inflammation index (SII) while prognostic nutritional index (PNI) and the haemoglobin, albumin, lymphocyte and platelet (HALP) score were considered as nutritional indexes. Patients were divided into high and low groups or into ‘increase’ and ‘decrease’ groups based on pre‐treatment cut‐off values and index dynamics after 6‐week follow‐up respectively. High pre‐treatment PLR (OR = 2.612) and increase in NLR during follow‐up (OR = 2.516) were significantly associated with lower objective response rates. Using multivariable analysis, high pre‐treatment PLR (HR, 2.319) and increase in SII (HR, 1.731) predicted shorter progression‐free survival, while high pre‐treatment NLR (HR, 1.635), increase in NLR (HR, 1.663) and PLR (HR, 1.691) and decrease in PNI (HR, 0.611) predicted worse overall survival. The nomogram's C‐index in inside validation was 0.718 (95% CI: 0.670–0.766). Our results indicated both nutritional and inflammatory indexes are associated with survival outcomes. Inflammatory indexes were additionally linked to treatment response. Index dynamics are better predictors than baseline values in predicting survival in advanced NSCLC patients receiving PD‐1 inhibitor combined with chemotherapy as first‐line.
Empirical Evidence on the Incidence and Persistence of Energy Poverty in Australia
Authors: Vera‐Toscano Esperanza , Brown Heather
Published: November 2022

Energy poverty is a temporary condition, yet a non‐negligible share of the Australian population suffers persistent energy disadvantage. Using the Household, Income and Labour Dynamics in Australia (HILDA) survey, we observe that single individuals, single‐parent households and those with a disabled household member are at high risk of persistent energy poverty. This is also true for non‐working individuals and immigrants from non‐English‐speaking countries. Nevertheless, highly educated individuals, those living in metropolitan areas and homeowners are less likely to persistently experience energy poverty. Government investment in energy efficiency is crucial to reduce electricity bills and have healthier homes.
Board Diversity and Firm Performance: The Role of Contextual Variables
Authors: Pandey Nitesh , Baker H. Kent , Kumar Satish , Gupta Prashant , Ali Searat
Published: November 2022

We examine the dynamic relationship between board diversity and firm performance in an Indian context using a systems generalized method of moments and control function approach. Our baseline analysis shows that board diversity positively influences accounting performance but negatively affects market performance. Additional analysis reveals that contextual variables, including board independence, firm size, firm age, promoter shareholdings, industry sector, women's participation in STEM education and the workforce and gross domestic product moderate this relationship significantly. We also find improved market performance after enacting the Companies Act 2013. Overall, these results highlight the critical role of performance measurement and contextual variables in the diversity–performance nexus.
Wireless emergency alerts: Public understanding, trust, and preferences following the 2021 US nationwide test
Authors: Bean Hamilton , Grevstad Nels
Published: November 2022

On August 11, 2021, the US Federal Emergency Management Agency and Federal Communications Commission (FCC) conducted the second national test of the wireless emergency alerts (WEA) system. The first test was conducted in 2018. This study offers an analysis of a nationwide survey (N = 1056) administered in the days immediately following the 2021 national test. The analysis indicates that a substantial number of respondents do not well understand the uses of the WEA system, especially the “National Alert” message class. However, more respondents believe that the “National Alert” message class label would signal more trustworthy information than the “Presidential Alert” message class label, a finding that bolsters the FCC's 2021 decision to abandon the “Presidential Alert” message class label. Despite a lack of accurate understanding of message classes and opt‐out options, a substantial number of respondents trust the WEA system to work properly. A clear majority of respondents would appreciate device‐based public education materials about the WEA system. The implications of the survey findings for WEA system management and public education are discussed.
NADHdehydrogenases drive inward electron transfer inShewanella oneidensisMR‐1
Authors: Tefft Nicholas M. , Ford Kathryne , TerAvest Michaela A.
Published: November 2022

Shewanella oneidensisMR‐1 is a promising chassis organism for microbial electrosynthesis because it has a well‐defined biochemical pathway (the Mtr pathway) that can connect extracellular electrodes to respiratory electron carriers inside the cell. We previously found that the Mtr pathway can be used to transfer electrons from a cathode to intracellular electron carriers and drive reduction reactions. In this work, we hypothesized that native NADH dehydrogenases form an essential link between the Mtr pathway and NADH in the cytoplasm. To test this hypothesis, we compared the ability of various mutant strains to accept electrons from a cathode and transfer them to an NADH‐dependent reaction in the cytoplasm, reduction of acetoin to 2,3‐butanediol. We found that deletion of genes encoding NADH dehydrogenases from the genome blocked electron transfer from a cathode to NADH in the cytoplasm, preventing the conversion of acetoin to 2,3‐butanediol. However, electron transfer to fumarate was not blocked by the gene deletions, indicating that NADH dehydrogenase deletion specifically impacted NADH generation and did not cause a general defect in extracellular electron transfer. Proton motive force (PMF) is linked to the function of the NADH dehydrogenases. We added a protonophore to collapse PMF and observed that it blocked inward electron transfer to acetoin but not fumarate. Together these results indicate a link between the Mtr pathway and intracellular NADH. Future work to optimize microbial electrosynthesis inS. oneidensisMR‐1 should focus on optimizing flux through NADH dehydrogenases.