bluuebunny/crossref_metadata_2025 huggingface dataset:
Incorporating recirculation effects into metrics of feeding performance for current-feeding zooplankton
Authors: Samsami Kiarash , Sanchez Arias Ludivine , Redd Haven , Stoll Rob , Pepper Rachel E. , Fu Henry Chien
Published: March 2024

The feeding performance of zooplankton influences their evolution and can explain their behaviour. A commonly used metric for feeding performance is the volume of fluid that flows through a filtering surface and is scanned for food. Here, we show that such a metric may give incorrect results for organisms that produce recirculatory flows, so that fluid flowing through the filter may have been already filtered of food. In a numerical model, we construct a feeding metric that correctly accounts for recirculation in a sessile model organism inspired by our experimental observations of
Vorticella
and its flow field. Our metric tracks the history of current-borne particles to determine if they have already been filtered by the filtering surface. Examining the pathlines of food particles reveals that the capture of fresh particles preferentially involves the tips of cilia, which we corroborate in observations of feeding
Vorticella
. We compare the amount of fresh nutrient particles carried to the organism with other metrics of feeding, and show that metrics that do not take into account the history of particles cannot correctly compute the volume of freshly scanned fluid.
Prosocial punishment bots breed social punishment in human players
Authors: Shen Chen , He Zhixue , Shi Lei , Wang Zhen , Tanimoto Jun
Published: March 2024

Prosocial punishment, an important factor to stabilize cooperation in social dilemma games, often faces challenges like second-order free-riders—who cooperate but avoid punishing to save costs—and antisocial punishers, who defect and retaliate against cooperators. Addressing these challenges, our study introduces prosocial punishment bots that consistently cooperate and punish free-riders. Our findings reveal that these bots significantly promote the emergence of prosocial punishment among normal players due to their ‘sticky effect’—an unwavering commitment to cooperation and punishment that magnetically attracts their opponents to emulate this strategy. Additionally, we observe that the prevalence of prosocial punishment is greatly enhanced when normal players exhibit a tendency to follow a ‘copying the majority’ strategy, or when bots are strategically placed in high-degree nodes within scale-free networks. Conversely, bots designed for defection or antisocial punishment diminish overall cooperation levels. This stark contrast underscores the critical role of strategic bot design in enhancing cooperative behaviours in human/AI interactions. Our findings open new avenues in evolutionary game theory, demonstrating the potential of human–machine collaboration in solving the conundrum of punishment.
Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise
Authors: Lee Earric , Nissinen Tuuli A. , Yla-Outinen Laura , Jalkanen Aaro , Karppinen Jari E. , Vieira-Potter Victoria , Lipponen Arto , Karvinen Sira
Published: March 2024

Objective: Estrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon. Methods: We studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n=64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography. Results: OVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p≤0.005). OVX reduced maximal running capacity by 17% (p=0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p=0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p≤0.024). Conclusions: Our results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.
Insects visitFusarium xyrophilumpseudoflowers on the hostXyris surinamensis(Xyridaceae) and carry fungal DNA on their bodies
Authors: Torres-Cruz Terry J. , Cofer Tristan M. , Kaminsky Laura M. , Ré Lauren A. , Johnson Jack R. , Vaughn Alexis , Tumlinson James H. , Laraba Imane , Proctor Robert H. , Kim Hye-Seon , Bell Terrence H. , Aime M. Catherine , Skvarla Michael J. , Geiser David M.
Published: March 2024

The fungusFusarium xyrophilumproduces flower-like structures (i.e., pseudoflowers) that were recently discovered on yellow-eyed grasses (Xyrisspp.) in Guyana. It is unknown whether these pseudoflowers, which are composed entirely of fungal tissue, are true mimics that attract insects as a means of fungal dispersal. We evaluated the potential ofF. xyrophilumto affect insect visitation patterns to flowers and pseudoflowers by 1) documenting insect visitation toX. surinamensisin Guyana, 2) measuring the presence ofF. xyrophilumDNA on insects, and 3) evaluating fluorescence and volatile production on flowers and pseudoflowers. We report for the first time Vespidae, Formicidae, Salticidae, Acrididae, and Tetrigidae visitingXyris. Diverse insects, including Conocephalini spp. (meadow katydids; Tettigoniidae),Camponotusspp. (carpenter ants; Formicidae), and a Geometridae sp. (geometer moths) were found to visit flowers and pseudoflowers.Fusarium xyrophilumDNA was detected on 3/12 (25%) of captured insect bodies using conventional and quantitative PCR. Volatiles produced in the field by pseudoflowers and flowers were similar, except for the presence of a sesquiterpene, putatively identified here as α-gurjunene, which was detected both inF. xyrophilumpure cultures and field-collected pseudoflower samples, but not from flowers. The production of this sesquiterpene byF. xyrophilumand the fluorescence ofX. surinamensispeduncles represent potential signals involved in insect attraction for this system. These observations, along with the overlap in insect visitors of flowers and pseudoflowers and the detection ofF. xyrophilumDNA on insect bodies, are consistent with insect visitors being vectors ofXyrispollen andF. xyrophilumpropagules between host plants.
A new type of AmpC β-lactamases defined by PIB-1, a metal-dependent carbapenem-hydrolyzing β-lactamase, fromPseudomonas aeruginosa: structural and functional analysis
Authors: Medrano Francisco Javier , Hernando-Amado Sara , Martínez José Luis , Romero Antonio
Published: March 2024

Antibiotic resistance is one of most important health concerns nowadays. β-lactamases are the most important resistance determinants. Based on their structural and functional characteristics β-lactamases are grouped in four categories. AmpC β-lactamases are cephalosporinases presenting a set of highly conserved residues. Here we crystallized PIB-1, aPseudomonas aeruginosachromosomally-encoded β-lactamase. Its crystal structure shows it is an AmpC β-lactamase, although the number of conserved residues is low. Functional analysis showed that PIB-1 is able to degrade carbapenems but not the typical substrate of AmpC β-lactamases, cephalosporins. Besides, the catalytic activity of PIB-1 increases in the presence of metal ions. Metals do not bind to the active center and increase the degradation of the antibiotic. They induce the formation of trimers. This suggests that the oligomer is more active than the monomer. While PIB-1 is structurally an AmpC β-lactamase, the low sequence conservation, substrate profile and its metal-dependence, prompts us to position this enzyme as the founder of a new group inside the AmpC β-lactamases. Consequently, the diversity of AmpC β-lactamases might be wider than expected.
HyperGen: Compact and Efficient Genome Sketching using Hyperdimensional Vectors
Authors: Xu Weihong , Hsu Po-Kai , Moshiri Niema , Yu Shimeng , Rosing Tajana
Published: March 2024

Motivation

Genomic distance estimation is a critical workload since exact computation for whole-genome similarity metrics such as Average Nucleotide Identity (ANI) incurs prohibitive runtime overhead. Genome sketching is a fast and memory-efficient solution to estimate ANI similarity by distilling representativek-mers from the original sequences. In this work, we present HyperGen that improves accuracy, runtime performance, and memory efficiency for large-scale ANI estimation. Unlike existing genome sketching algorithms that convert large genome files into discretek-mer hashes, HyperGen leverages the emerging hyperdimensional computing (HDC) to encode genomes into quasi-orthogonal vectors (Hypervector, HV) in high-dimensional space. HV is compact and can preserve more information, allowing for accurate ANI estimation while reducing required sketch sizes. In particular, the HV sketch representation in HyperGen allows efficient ANI estimation using vector multiplication, which naturally benefits from highly optimized general matrix multiply (GEMM) routines. As a result, HyperGen enables the efficient sketching and ANI estimation for massive genome collections.

Results

We evaluate HyperGen’s sketching and database search performance using several genome datasets at various scales. HyperGen is able to achieve comparable or superior ANI estimation error and linearity compared to other sketch-based counterparts. The measurement results show that HyperGen is one of the fastest tools for both genome sketching and database search. Meanwhile, HyperGen produces memory-efficient sketch files while ensuring high ANI estimation accuracy.

Availability

A Rust implementation of HyperGen is freely available under the MIT license as an open-source software project athttps://github.com/wh-xu/Hyper-Gen. The scripts to reproduce the experimental results can be accessed athttps://github.com/wh-xu/experiment-hyper-gen.

Contact

wexu@ucsd.edu
Development of a new genotype–phenotype linked antibody screening system
Authors: Watanabe Takashi , Hata Hikaru , Mochizuki Yoshiki , Yokoyama Fumie , Hasegawa Tomoko , Kumar Naveen , Kurosaki Tomohiro , Ohara Osamu , Fukuyama Hidehiro
Published: March 2024

Antibodies are powerful tools for the therapy and diagnosis of various diseases. In addition to conventional hybridoma-based screening, recombinant antibody-based screening has become a common choice; however, its application is hampered by two factors: 1) screening starts after Ig gene cloning and recombinant antibody production only, and 2) the antibody is composed of paired chains, heavy and light, commonly expressed by two independent expression vectors. Here, we introduce a method for the rapid screening of recombinant monoclonal antibodies by establishing a Golden Gate-based dual-expression vector andin-vivoexpression of membrane-bound antibodies. Using this system, we demonstrate the rapid isolation of influenza cross-reactive antibodies with high affinity from immunized mice within 7 days. This system is particularly useful for isolating therapeutic or diagnostic antibodies, e.g., during foreseen pandemics.

Impact Statement

A Golden Gate-based dual-expression vector enables rapid screening, which facilitates efficient isolation of high-affinity cross-reactive antibodies for therapeutic or diagnostic use and provides a crucial advance for pandemic preparedness.
Overexpression of barley heat stress transcription factor HvHsfA6a provide thermotolerance by thermopriming
Authors: Chaudhary Reeku , Baliyan Suchi , Sirohi Parul , Singh Sweta , Mishra Sumit Kumar , Rajkumar Mohan Singh , Saini Shashank Sagar , Germain Hugo , Sircar Debabrata , Chauhan Harsh
Published: March 2024

Adverse impacts of climate change, including high temperature on cereal crop production, have been evidenced globally. In plants, heat shock factors (HSFs) are crucial components of heat stress associated rescue mechanisms and are also required for normal biological processes. Here, we functionally characterized a highly heat stress responsiveHvHSFA6ain barley by developing constitutively overexpressing transgenic lines. These transgenic lines showed heat tolerant phenotype via improved photosynthesis, antioxidants and upregulation of HSPs and metabolites involved in stress amelioration and keeping thermomemory as compared to wild type plants. Global transcriptomics and ChIP sequencing revealed that HvHSFA6a orchestrates the expression of several genes through direct binding with other HSFs containing consensus HSE in their promoter regions. A GC-MS based metabolomics analysis also revealed the alterations in key metabolic processes such as carbohydrate metabolism, citric acid cycle, amino acids and secondary metabolism. Higher accumulation of key metabolites such as sucrose, galactinol, shikimate and ascorbate has been observed under both control and heat stress in transgenic lines as compared to wild type plants. Taken together, the results suggest that overexpression ofHvHsfA6aprime the plants for heat stress conditions by alteration in gene expression and metabolic status.

Highlight

Priming is a mechanism by which plants respond to various abiotic and biotic stresses. Through multi omics approach we found that barley HsfA6a provide thermotolernce in transgenic plants through priming effect on transcriptome and metabolome.
Molecular insights into the atypical activation mechanism of GPR156 in maintaining auditory function
Authors: Ma Xiangyu , Chen Li-Nan , Liao Menghui , Zhang Liyan , Xi Kun , Guo Jiamin , Shen Cangsong , Shen Dan-Dan , Cai Pengjun , Shen Qingya , Qi Jieyu , Zhang Huibing , Zang Shao-Kun , Dong Ying-Jun , Miao Luwei , Qin Jiao , Ji Su-Yu , Li Yue , Liu Jianfeng , Mao Chunyou , Zhang Yan , Chai Renjie
Published: March 2024

The class C orphan GPCR GPR156, which lacks the typical extracellular region, plays a pivotal role in auditory function through Gi2/3. Here, we demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and we further present two cryo-EM structures of human GPR156. The GPR156 dimer in both the apo state and Gi3protein-coupled state adopt a TM5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. The C-terminus plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. These observations explain how GPCR activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function.
Synth4bench: a framework for generating synthetic genomics data for the evaluation of tumor-only somatic variant calling algorithms
Authors: Fragkouli Styliani-Christina , Pechlivanis Nikos , Anastasiadou Anastasia , Karakatsoulis Georgios , Orfanou Aspasia , Kollia Panagoula , Agathangelidis Andreas , Psomopoulos Fotis
Published: March 2024

Motivation

Somatic variant calling algorithms are widely used to detect genomic alterations associated with cancer. Evaluating their performance, even though being crucial, can be challenging due to the lack of high-quality ground truth datasets. To address this issue, we developed a synthetic data generation framework for benchmarking these algorithms, focusing on the TP53 gene, utilizing the NEATv3.3 simulator. We thoroughly evaluated the performance of Mutect2, Freebayes, VarDict, VarScan2 and LoFreq and compared their results with our synthetic ground truth, while observing their behavior. Synth4bench attempts to shed light on the underlying principles of each variant caller by presenting them with data from a given range across the genomics data feature space and inspecting their response.

Results

Using synthetic dataset as ground truth provides an excellent approach for evaluating the performance of tumor-only somatic variant calling algorithms. Our findings are supported by an independent statistical analysis that was performed on the same data and output from all callers. Overall, synth4bench leverages the effort of benchmarking algorithms by offering the opportunity to utilize a generated ground truth dataset. This kind of framework is essential in the field of cancer genomics, where precision is an ultimate necessity, especially for variants of low frequency. In this context, our approach makes comparison of various algorithms transparent, straightforward and also enhances their comparability.

Availability

synth4bench is available athttps://github.com/BiodataAnalysisGroup/synth4benchand all data available athttps://zenodo.org/records/10683211.
In silico genomic surveillance by CoVerage predicts and characterizes SARS-CoV-2 Variants of Interest
Authors: Norwood Katrina , Deng Zhi-Luo , Reimering Susanne , Robertson Gary , Foroughmand-Araabi Mohammad-Hadi , Goliaei Sama , Hoelzer Martin , McHardy Alice Carolyn
Published: March 2024

Rapidly evolving viral pathogens such as SARS-CoV-2 continuously accumulate amino acid changes, some of which affect transmissibility, virulence or improve the virus' ability to escape host immunity. Since the beginning of the pandemic and establishment of SARS-CoV-2 as a human pathogen, multiple lineages with concerning phenotypic alterations, so called Variants of Concern (VOCs), have emerged and risen to predominance. To optimize public health management and to ensure the continued efficacy of vaccines, the early detection of such variants of interest is essential. Therefore, large-scale viral genomic surveillance programs have been initiated worldwide, with data being deposited in public repositories in a timely manner. However, technologies for their continuous interpretation are currently lacking. Here, we describe the CoVerage system (www.sarscoverage.org) for viral genomic surveillance, which continuously predicts and characterizes novel and emerging potential Variants of Interest (pVOIs) from country-wise lineage frequency dynamics together with their antigenic and evolutionary alterations utilizing the GISAID viral genome resource. In a comprehensive assessment of VOIs, VOCs and VUMs identified, we demonstrate how CoVerage can be used to swiftly identify and characterize such variants, with a lead time of almost three months relative to them reaching their maximal abundances. CoVerage can facilitate the timely identification and assessment of future SARS-CoV-2 variants relevant for public health.
Highly multiplexed design of an allosteric transcription factor to sense novel ligands
Authors: Nishikawa Kyle K. , Chen Jackie , Acheson Justin F. , Harbaugh Svetlana V. , Huss Phil , Frenkel Max , Novy Nathan , Sieren Hailey R. , Lodewyk Ella C. , Lee Daniel H. , Chávez Jorge L. , Fox Brian G. , Raman Srivatsan
Published: March 2024

Allosteric transcription factors (aTF), widely used as biosensors, have proven challenging to design for detecting novel molecules because mutation of ligand-binding residues often disrupts allostery. We developed Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screened a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures – four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone – as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identified novel biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design showed shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we developed cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid, scalable design of new biosensors, overcoming constraints of natural biosensors.
A tale of two fusion proteins: understanding the metastability of human respiratory syncytial virus and metapneumovirus and implications for rational design of uncleaved prefusion-closed trimers
Authors: Lee Yi-Zong , Han Jerome , Zhang Yi-Nan , Ward Garrett , Gomes Keegan Braz , Auclair Sarah , Stanfield Robyn L. , He Linling , Wilson Ian A. , Zhu Jiang
Published: March 2024

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we designed uncleaved prefusion-closed (UFC) trimers for the fusion (F) proteins of both viruses by examining mutations critical to F metastability. For RSV, we assessed four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identified key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we developed a stable UFC trimer with a truncated F2-F1linkage and an interprotomer disulfide bond. Tens of UFC constructs were characterized by negative-stain electron microscopy (nsEM), x-ray crystallography (11 RSV-F and one hMPV-F structures), and antigenic profiling. Using an optimized RSV-F UFC trimer as bait, we identified three potent RSV neutralizing antibodies (NAbs) from a phage-displayed human antibody library, with a public NAb lineage targeting sites Ø and V and two cross-pneumovirus NAbs recognizing site III. In mouse immunization, rationally designed RSV-F and hMPV-F UFC trimers induced robust antibody responses with high neutralizing titers. Our study provides a foundation for future prefusion F-based RSV and hMPV vaccine development.

ONE-SENTENCE SUMMARY

The metastability analysis of fusion proteins has informed rational design of uncleaved prefusion-closed trimers for RSV and hMPV vaccine development.
Immune Signatures of SARS-CoV-2 Infection Resolution in Human Lung Tissues
Authors: Kenney Devin , O’Connell Aoife K. , Tseng Anna E. , Turcinovic Jacquelyn , Sheehan Maegan L. , Nitido Adam D. , Montanaro Paige , Gertje Hans P. , Ericsson Maria , Connor John H. , Vrbanac Vladimir , Crossland Nicholas A. , Harly Christelle , Balazs Alejandro B. , Douam Florian
Published: March 2024

While human autopsy samples have provided insights into pulmonary immune mechanisms associated with severe viral respiratory diseases, the mechanisms that contribute to a clinically favorable resolution of viral respiratory infections remain unclear due to the lack of proper experimental systems. Using mice co-engrafted with a genetically matched human immune system and fetal lung xenograft (fLX), we mapped the immunological events defining successful resolution of SARS-CoV-2 infection in human lung tissues. Viral infection is rapidly cleared from fLX following a peak of viral replication, histopathological manifestations of lung disease and loss of AT2 program, as reported in human COVID-19 patients. Infection resolution is associated with the activation of a limited number of hematopoietic subsets, including inflammatory monocytes and non-canonical double-negative T-cells with cytotoxic functions, which are highly enriched in viral RNA and dissipate upon infection resolution. Activation of specific human fibroblast and endothelial subsets also elicit robust antiviral and monocyte chemotaxis signatures, respectively. Notably, systemic depletion of human CD4+ cells, but not CD3+ cells, abrogates infection resolution in fLX and induces persistent infection, supporting evidence that peripheral CD4+ monocytes are important contributors to SARS-CoV-2 infection resolution in lung tissues. Collectively, our findings unravel a comprehensive picture of the immunological events defining effective resolution of SARS-CoV-2 infection in human lung tissues, revealing markedly divergent immunological trajectories between resolving and fatal COVID-19 cases.
Cryo-EM inspired NMR analysis reveals a pH-induced conformational switching mechanism for imparting dynamics to Betanodavirus protrusions
Authors: Štěrbová Petra , Wang Chun-Hsiung , Carillo Kathleen J.D. , Lou Yuan-Chao , Kato Takayuki , Namba Keiichi , Tzou Der-Lii M. , Chang Wei-Hau
Published: March 2024

Nervous necrosis virus (NNV), a non-enveloped betanodavirus, causes neuropathies and retinopathies in farmed fish, damaging aquaculture worldwide. NNV has 60 conspicuous surface protrusions comprising the protrusion domain (P-domain) of its capsid protein. Although NNV protrusions play critical roles in infectivity, the underlying dynamics remain unclear. Our cryogenic electron microscopy (cryo-EM)-derived structures of Dragon grouper (Epinephelus lanceolatus) NNV reveal that the protrusions undergo low-pH-induced compaction and movement. We show that the P-domain is monomeric in solution at a pH germane to infection (7.0). Moreover, nuclear magnetic resonance (NMR) structures reveal a peptide (amino acids 311-330) that adopts a flexible loop to form an open pocket. NMR spectral analysis at pH 5.0 aided by molecular dynamics (MD) simulations show that this loop switches to a β-strand under acidic conditions, eliciting pocket closure and P-domain trimerization, highlighting a unique pH-sensing feature. Our docking analysis revealed the N-terminal moiety of sialic acid inserted into and interacting with conserved residues in the pocket. Additionally, a low-pH-induced conformational change in the linker region via peptide bond isomerization conferred malleability on the protrusions. Our work uncovers the protrusion dynamics of a betanodavirus governing its infectivity through a pH-dependent conformational switching mechanism, providing insights into complex virus-host interactions.
A comparison between full-length 16S rRNA Oxford Nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues
Authors: Yeo Kenny , Connell James , Bouras George , Smith Eric , Murphy William , Hodge John-Charles , Krishnan Suren , Wormald Peter-John , Valentine Rowan , Psaltis Alkis James , Vreugde Sarah , Fenix Kevin Aaron
Published: March 2024

Introduction

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S ribosomal RNA (rRNA) short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina). To date, this is the largest study using HNC tissues samples to perform FL-ONT of the 16S rRNA using ONT.

Methods

Sequencing of the full-length and the V3-V4 16S rRNA region was conducted on tumour samples from 26 HNC patients, using ONT and Illumina technologies respectively. Paired sample analysis was applied to compare differences in diversities and abundance of microbial communities. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS.

Results

We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina technologies. However, beta-diversity was significantly different between techniques (PERMANOVA - R2= 0.083, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in microbial abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (81.3% v.s. 62.5%).

Conclusions

FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing. Depending on application purposes, both methods are suitable for identification of microbial communities, with FL-ONT being more superior at species level.
Exo70 promotes herpesvirus secretory vesicle tethering and virion release in an exocyst complex-dependent manner
Authors: Ma Wenqing , Xu Yanan , Xie Jialin , He Luteng , Wang Lin , Yu Jie , Sun Fachao , He Daniel Chang , Wang Hongmei , He Hongbin
Published: March 2024

The exocyst complex, a multisubunit protein complex, mediates secretory vesicles fusion with the plasma membrane (PM) to deliver materials to the cell surface or to release cargoes to the extracellular space, but whether it is related to viral secretory vesicles tethering and virion release is unknown. Here, we identified that the exocyst complex subunit Exo70 promotes the trafficking of herpesvirus secretory vesicles and the release of mature virions in an exocyst complex-dependent manner. Mechanistically, mutation of Exo70 Lys632 and Lys635 diminishes viral secretory vesicles anchoring to PM. Moreover, the small GTPase Rab11a is necessary for the transport of viral secretory vesicles, and the Snapin-Exo70-SNAP23 axis is involved in fusion of viral secretory vesicles to the PM and release of virions. Most significantly, we discovered that Endosidin2 (ES2), an inhibitor of exocytosis via the exocyst complex, provides protection against herpesvirus infection in cells and mice. Overall, these findings unveil a previously uncharacterized role and mechanism of the exocyst complex in viral replication, highlighting its potential as an effective strategy against herpesvirus infection.

Author summary

Herpesviruses, such as herpes simplex virus 1 (HSV-1) and bovine herpes virus type 1 (BoHV-1), are highly prevalent pathogens that establish lifelong infections and cause various diseases in humans and animals. While the mechanisms underlying the transport of herpesvirus secretory vesicles from the Golgi to the PM and the subsequent viral release are still poorly understood. In our study, we have discovered that Exo70 promotes the trafficking of HSV-1 and BoHV-1 secretory vesicles and facilitates the release of mature virions in an exocyst complex-dependent manner. Mechanistically, both knockdown of Exo70 and a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-binding-deficient mutant of Exo70 caused virions to be trapped in the cytoplasm and unable to tether to PM, indicating that the binding of Exo70 to PI(4,5)P2 is critical for the docking virus secretory vesicles with PM. Additionally, the Snapin-Exo70-SNAP23 axis plays a pivotal role in the fusion between viral secretory vesicles and the PM, ultimately facilitating the release of virions. We found that Rab11a is necessary for viral secretory vesicle trafficking mediated by Exo70. Most importantly, we discovered that ES2, a transport inhibitor that combines with Exo70 to terminate the final stage of exocytosis via the exocyst complex, can protect cells and mice from α-herpesvirus infection.
RegionalPlasmodium falciparumsubpopulations and malaria transmission connectivity in Africa detected with an enlarged panel of genome-wide microsatellite loci
Authors: Demba Martha Anita , Kamau Edwin , Raman Jaishree , Mane Karim , Emenga-Etego Lucas , Apinjo Tobias , Isheghoma Deus , Golassa Lemu , Maiga Oumou , Ghansah Anita , Bouyou-Akotet Marielle , Yavo William , Randrianarivelojosia Milijoana , Diop Fadel Muhammadou , Oriero Eniyou , Jeffries David , D’Alessandro Umberto , Djimde Abdoulaye , Amambua-Ngwa Alfred
Published: March 2024

Unravelling the genetic diversity ofPlasmodium falciparummalaria parasite provides critical information on how populations are affected by interventions and the environment, especially the evolution of molecular markers associated with parasite fitness and adaptation to drugs and vaccines. This study expands previous studies based on small sets of microsatellite loci, which often showed limited substructure in African populations ofP. falciparum. Combining several short tandem repeat detection algorithms, we genotyped and analysed 2329 polymorphic microsatellite loci from next-generation sequences of 992 low-complexity P. falciparumisolates from 15 sub-Saharan African countries. Based on pairwise relatedness, we identified seven subpopulations and gene flow between the Central and Eastern African populations. The most divergent subpopulation was from Ethiopia, while unexpected unique subpopulations from Gabon and Malawi were resolved. Isolates from the Democratic Republic of Congo shared ancestry with multiple regional populations, suggesting a possible founder population of P. falciparum from the Congo basin, where there was stronger geneflow eastwards to Tanzania, and Kenya. and Malawi. The most differentiated microsatellite loci were those around theP. falciparumdihydropteroate synthase (Pfdhps) gene associated with sulphadoxine resistance. Haplotypes around thePfdhpsgene separated the West, Central, and East Africa parasite populations into distinct clusters, suggesting independent local evolution ofPfdhps-associated sulphadoxine resistance alleles in each African region. Overall, this study presents genome-wide microsatellites as markers for resolving P. falciparum population diversity, structure, and evolution in populations like Africa, where there is high gene flow.
Digital taxation, artificial intelligence and Tax Administration 3.0: improving tax compliance behavior – a systematic literature review using textometry (2016–2023)
Authors: Belahouaoui Rida , Attak El Houssain
Published: March 2024

Purpose

This paper aims to analyze the impact of tax digitalization, focusing on artificial intelligence (AI), machine learning and blockchain technologies, on enhancing tax compliance behavior in various contexts. It seeks to understand how these emerging digital tools influence taxpayer behaviors and compliance levels and to assess their effectiveness in reducing tax evasion and avoidance practices.

Design/methodology/approach

Using a systematic review technique with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method, this study evaluates 62 papers collected from the Scopus database. The papers were analyzed through textometry of titles, abstracts and keywords to identify prevailing trends and insights.

Findings

The review reveals that digitalization, particularly through AI and blockchain, significantly enhances tax compliance and operational efficiency. However, challenges persist, especially in emerging economies, regarding the adoption and integration of these technologies in tax systems. The findings indicate a global trend toward digital Tax Administration 3.0, emphasizing the importance of regulatory frameworks, capacity building and simplification for small and medium enterprises (SMEs).

Practical implications

The findings provide guidance for policymakers and tax administrations, underscoring the necessity of strategic planning, regulatory backing and global cooperation to effectively use digital technologies in tax compliance. Emphasizing the need for tailored support for SMEs, the study also calls for expanded research in less represented areas and specific sectors, such as SMEs and developing economies, to deepen global insights into digital tax compliance.

Originality/value

This study has attempted to fill the gap in the literature on the comprehensive impact of fiscal digitalization, particularly AI-based, on tax compliance across different global contexts, adding to the discourse on digital taxation.
The impacts of multiple privacy regulations and national security infrastructure on health information exchange: a study of hospitals across Europe
Authors: Shrivastava Utkarsh , Han Bernard , Zhou Ying , Razi Muhammad
Published: March 2024

Purpose

Sharing patient health information (PHI) among hospitals has been much slower than the adoption of health record systems. This paper aims to investigate if privacy regulation (PR) or security measures (SMs) influence hospitals’ use of health information exchange (HIE) to share PHI with other providers (e.g. physicians, labs, hospitals). The study specifically focuses on how multiple PRs can impede and a strong national security infrastructure (NSI) can support HIE.

Design/methodology/approach

The study uses secondary data from a multi-national and multi-hospital survey administered by the European Union. The multi-level structure of the cross-sectional panel data is used to test the influence of both hospital-level (e.g. PR) and national-level variables (e.g. NSI) on HIE. A total of nine types of HIE, three types of PRs, nine SMs and other relevant control variables are considered. This study uses a two-level random intercept generalized linear model to test the hypothesis proposed in the study.

Findings

The study finds that national-level PRs (NLPR) have the strongest positive influence on HIE in comparison to regional (RLPR) and hospital-level (HLPR) PRs. Moreover, the study finds evidence that the presence of RLPR and HLPR, on average, decreases the positive impact of NLPR by 264%. The SMs also have a significant and positive impact on HIE. Adoption of an additional SM can increase the odds of engaging in a certain type of HIE between 21% and 61%. On the other hand, a strong NSI can also amplify the positive impact of SM on certain types of HIE.

Originality/value

This study extends prior research on the role of PRs in enabling HIE by considering the complexities brought up by adopting multiple PRs. NLPRs have the strongest impact on HIE in comparison to RLPRs or HLPRs. Moreover, public infrastructure initiatives such as those related to secure communications can also complement SMs adopted by the providers by encouraging HIE.
Attention Autism™ training for occupational therapists: a pilot study
Authors: Ruttledge Aideen
Published: March 2024

Purpose

At present, there is no reference to Attention Autism (AA) as a framework and therapeutic tool with autistic children in occupational therapy (OT) literature. By way of introducing AA as a potential intervention to the OT community, this study aims to investigate the extent to which participation in a two-day AA training could contribute to increasing confidence and inspire changes in practice for Irish occupational therapists (OTs) supporting autistic children.

Design/methodology/approach

A pilot study design with mixed qualitative and quantitative methods was used to evaluate the impact of a two-day AA training on six OTs. The OTs support autistic children throughout Ireland across public, private and voluntary sectors. They completed brief, non-standardised questionnaires 2 weeks before the training (Time 1) and again 12 weeks post (Time 2) training session. At Time 2, additional exploratory questions were answered by OTs regarding their use of AA in practice.

Findings

This explorative study’s quantitative findings presented percentage change increases within three areas of confidence for all OTs. These include establishing attention, motivating and developing functional skill goals with autistic children. One of the participants did not score any change in confidence in a fourth area, building rapport, however, the five other participants scored percentage change increases. Qualitative data provided by participants showed that they were implementing AA in practice since attending the training. Five of the participants reported positive experiences of using AA and one participant reported the programme was not suitable for her caseload because of their level of understanding and need.

Research limitations/implications

This was a small, exploratory, practice-based study. As this is the first study exploring this area of practice for OTs, to the best of the authors’ knowledge, there were no standardised methods of assessment available, therefore a self-designed survey was used by the author which had a limited number of open-ended questions and four Likert scale questions. This study was also limited in that there was one main researcher who also delivered the two-day AA training. The sample data set was small which resulted in the limitation of the choice of methods used to analyse the quantitative data. Percentage changes were used as the only available and reliable method for a small data set.

Originality/value

Findings of this study, despite their preliminary nature, indicate that AA training may be a useful professional development consideration for OTs who provide a service for autistic children. Further AA research in OT is required including larger and more rigorous studies. An alternative training option of The Curiosity Programme may be considered for OTs supporting children who may not yet be ready to participate in AA.
Managing a Gen-Z workforce – what family firms need to know: a perspectives article
Authors: Stevanovski Mare , Zhan Likun (David) , Mustafa Michael
Published: March 2024

Purpose

This paper highlights the opportunities and challenges for family firms in managing Generation Z (Gen-Z) employees. This perspective article explores several considerations for family firms in managing their Gen-Z employees and the potential implications for their socioemotional wealth (SEW).

Design/methodology/approach

The authors provide a brief review of what is known about the values/work habits of Gen-Z employees and attracting, retaining and managing nonfamily employees in family firms.

Findings

The unique values, motivations and working styles of Gen-Z employees suggest the need for family business leaders to adopt a different approach to managing these employees. A focus on Gen-Z’s psychological contract, technological savviness and entrepreneurial orientation is provided with respect to how they can be managed.

Originality/value

The authors suggest the importance of approaching NFEs as a heterogenous group and offer avenues for future research with prospective research questions to better understand nonfamily Generation Z employees’ place in the family firm.
Happy knowledge creators sustain nations: scale development and validation of happiness at work
Authors: Khatri Puja , Kumari Preeti , Thomas Asha
Published: March 2024

Purpose

The significant role of universities in generating and diffusing new knowledge in the interest of society has positioned faculty as knowledge creators. The present study contributes to the domain of positive psychology by heeding the happiness call in academia. The research intends to develop and validate a scale for measuring happiness at work (HAW) for knowledge creators.

Design/methodology/approach

The study is systematically designed across a series of four independent studies: (1) Dimensionality and item analysis, (2) scale purification, (3) scale refinement and nomological validation and (4) generalizability. Additionally, common method bias (CMB) was checked utilizing the marker variable technique.

Findings

HAW has been established as a second-order reflective-reflective construct with six factors, namely work satisfaction, self-directedness, self-love, positive thinking, positive social relationships and work-family balance. The nomological validity and generalizability of the scale have also been established.

Research limitations/implications

The study is an attempt to address an important topic of HAW among knowledge creators. By conceptualizing HAW as a combination of intraindividual and organizational factors, this study offers a comprehensive measure of HAW that was previously absent in the literature. The results of the study will assist management in making strategic decisions to ensure the HAW of knowledge creators.

Originality/value

Knowledge creators’ happiness is a major concern in academia and has received little attention till date. The primary contribution of this study is the conceptualization and development of a validated scale for measuring knowledge creators’ HAW. A valid and reliable scale for measuring HAW would enable researchers to gain fresh perspectives on the essence, attributes and quantification of this particularly noteworthy construct.
The Causal Effect of Financial Crisis and Its Long‐Run Impact on Fertility
Authors: Keng Shao‐Hsun
Published: March 2024

This paper examines the effect of the 2008 financial crisis on Taiwan's fertility by exploiting a natural experiment in which public‐sector workers are unaffected due to job security. The financial crisis reduces the number of children by increasing the first‐birth interval, which leads to a lower probability of first birth. Women aged 33–38 experienced the largest decline in the probability of first birth, increasing the risks of permanent childlessness. Low‐income households and those with less‐educated spouses have a greater increase in the first‐birth interval. The number of children and the probability of first birth remain significantly lower 9 years after 2008.
Chronic TNF exposure induces glucocorticoid‐like immunosuppression in the alveolar macrophages of aged mice that enhances their susceptibility to pneumonia
Authors: Kruckow Katherine L. , Murray Elizabeth , Shayhidin Elnur , Rosenberg Alexander F. , Bowdish Dawn M. E. , Orihuela Carlos J.
Published: March 2024

Chronic low‐grade inflammation, particularly elevated tumor necrosis factor (TNF) levels, occurs due to advanced age and is associated with greater susceptibility to infection. One reason for this is age‐dependent macrophage dysfunction (ADMD). Herein, we use the adoptive transfer of alveolar macrophages (AM) from aged mice into the airway of young mice to show that inherent age‐related defects in AM were sufficient to increase the susceptibility to Streptococcus pneumoniae, a Gram‐positive bacterium and the leading cause of community‐acquired pneumonia. MAPK phosphorylation arrays using AM lysates from young and aged wild‐type (WT) and TNF knockout (KO) mice revealed multilevel TNF‐mediated suppression of kinase activity in aged mice. RNAseq analyses of AM validated the suppression of MAPK signaling as a consequence of TNF during aging. Two regulatory phosphatases that suppress MAPK signaling, Dusp1 and Ptprs, were confirmed to be upregulated with age and as a result of TNF exposure both ex vivo and in vitro. Dusp1 is known to be responsible for glucocorticoid‐mediated immune suppression, and dexamethasone treatment increased Dusp1 and Ptprs expression in cells and recapitulated the ADMD phenotype. In young mice, treatment with dexamethasone increased the levels of Dusp1 and Ptprs and their susceptibility to infection. TNF‐neutralizing antibody reduced Dusp1 and Ptprs levels in AM from aged mice and reduced pneumonia severity following bacterial challenge. We conclude that chronic exposure to TNF increases the expression of the glucocorticoid‐associated MAPK signaling suppressors, Dusp1 and Ptprs, which inhibits AM activation and increases susceptibility to bacterial pneumonia in older adults.