bluuebunny/crossref_metadata_2025 huggingface dataset:
A Molecular Basis of Human Brain Connectivity
Authors: Ng Bernard , Tasaki Shinya , Greathouse Kelsey M , Walker Courtney K , Zhang Ada , Covitz Sydney , Cieslak Matt , Adamson Ashley B , Andrade Julia P , Poovey Emily H , Curtis Kendall A , Muhammad Hamad M , Seidlitz Jakob , Satterthwaite Ted , Bennett David A , Seyfried Nicholas T , Vogel Jacob , Gaiteri Chris , Herskowitz Jeremy H
Published: July 2023

Neuroimaging is commonly used to infer human brain connectivity, but those measurements are far-removed from the molecular underpinnings at synapses. To uncover the molecular basis of human brain connectivity, we analyzed a unique cohort of 98 individuals who provided neuroimaging and genetic data contemporaneous with dendritic spine morphometric, proteomic, and gene expression data from the superior frontal and inferior temporal gyri. Through cellular contextualization of the molecular data with dendritic spine morphology, we identified hundreds of proteins related to synapses, energy metabolism, and RNA processing that explain between-individual differences in functional connectivity and structural covariation. By integrating data at the genetic, molecular, subcellular, and tissue levels, we bridged the divergent fields of molecular biology and neuroimaging to identify a molecular basis of brain connectivity.

One-Sentence Summary

Dendritic spine morphometry and synaptic proteins unite the divergent fields of molecular biology and neuroimaging.
The role of agentive and physical forces in the neural representation of motion events
Authors: Karakose-Akbiyik Seda , Sussman Oliver , Wurm Moritz F. , Caramazza Alfonso
Published: July 2023

How does the brain represent information about motion events in relation to agentive and physical forces? In this study, we investigated the neural activity patterns associated with observing animated actions of agents (e.g., an agent hitting a chair) in comparison to similar movements of inanimate objects that were either shaped solely by the physics of the scene (e.g., gravity causing an object to fall down a hill and hit a chair) or initiated by agents (e.g., a visible agent causing an object to hit a chair). Using fMRI-based multivariate pattern analysis, this design allowed testing where in the brain the neural activity patterns associated with motion events change as a function of, or are invariant to, agentive versus physical forces behind them. Cross-decoding revealed a shared neural representation of animate and inanimate motion events that is invariant to agentive or physical forces in regions spanning frontoparietal and posterior temporal cortices. In contrast, the right lateral occipitotemporal cortex showed higher sensitivity to agentive events, while the left dorsal premotor cortex was more sensitive to information about inanimate object events that were solely shaped by the physics of the scene.
Cebranopadol, a novel long-acting opioid agonist with low abuse liability, to treat opioid use disorder: Preclinical evidence of efficacy
Authors: Lunerti Veronica , Shen Qianwei , Li Hongwu , Benvenuti Federica , Soverchia Laura , Narendran Rajesh , Weiss Friedbert , Cannella Nazzareno , Ciccocioppo Roberto
Published: July 2023

The gold standard pharmacological treatment for opioid use disorder (OUD) consists of maintenance therapy with long-acting opioid agonists such as buprenorphine and methadone. Despite these compounds having demonstrated substantial efficacy, a significant number of patients do not show optimal therapeutic responses. Moreover, the abuse liability of these medications remains a major concern. Cebranopadol, is a new, long-acting pan-opioid agonist that also activates the nociception/orphanin FQ NOP receptor. Here we used rats to explore the therapeutic potential of this agent in OUD. First, in operant intravenous self-administration experiments we compared the potential abuse liability of cebranopadol with the prototypical opioid heroin. Under a fixed ratio 1 (FR1) contingency, rats maintained responding for heroin (1, 7, 20, 60 μg/inf) to a larger extent than cebranopadol (0.03, 0.1, 0.3, 1.0, 6.0 μg/inf). When the contingency was switched to a progressive ratio (PR) reinforcement schedule, heroin maintained responding at high levels at all except the lowest dose. Conversely, in the cebranopadol groups responding decreased drastically and the break point (BP) did not differ from saline controls. Next, we demonstrated that oral administration of cebranopadol (0, 25, 50 μg/kg) significantly attenuated drug self-administration independent of heroin dose (1, 7, 20, 60 μg/inf). Cebranopadol also reduced the break point for heroin (20 μg/inf). Furthermore, in a heroin self-administration training extinction/reinstatement paradigm, pretreatment with cebranopadol significantly attenuated yohimbine stress-induced reinstatement of drug seeking. Together, these data indicate that cebranopadol has limited abuse liability compared to heroin and is highly efficacious in attenuating opioid self-administration and stress-induced reinstatement, suggesting clinical potential of this compound for OUD treatment.
Label-free differentiation of functional zones in mature mouse placenta using micro-Raman imaging
Authors: Inanc Arda , Bektas Nayce Ilayda , Kecoglu Ibrahim , Parlatan Ugur , Durkut Begum , Ucak Melike , Unlu Mehmet Burcin , Celik-Ozenci Ciler
Published: July 2023

In histopathology, it is highly crucial to have chemical and structural information about tissues. Additionally, the segmentation of zones within a tissue plays an important role in investigating the functions of these regions for better diagnosis and treatment. The placenta plays an important role in embryonic and fetal development and in the diagnosis of some diseases associated with its dysfunction. This study provides a label-free approach to obtain the images of mature mouse placenta together with the chemical differences between the tissue compartments using Raman spectroscopy. To generate the Raman images, spectra of placental tissue were collected using a custom-built optical setup. The pre-processed spectra were analyzed using statistical and machine learning methods to acquire the Raman maps. We found that the placental regions called decidua and the labyrinth zone are biochemically distinct from the junctional zone. Comparison and evaluation of the Raman maps with histological images of the placental tissue were performed by a histologist and they are found to be in agreement. The results of this study show that Raman spectroscopy offers the possibility of label-free monitoring of the placental tissue from mature mice while revealing important structural information about the zones at the same time.
InvasiveArgemone mexicana’s suppressive effects onPhaseolus vulgarisandZea maysgermination and growth
Authors: Ojija Fredrick
Published: July 2023

InvasiveArgemone mexicanaplant species is invading many ecosystems in East Africa. However, there have not been many studies to assess how it affects plants. In petri dishes and pot experiments, we investigated the suppressive effects ofA. mexicanaonPhaseolus vulgarisand Zea mays germination and seedling growth. To investigate its suppressive effects on the test plant, different concentrations ofA. mexicanaleaf (AmL) crude extract were applied to the seeds and seedlings ofP. vulgarisandZ. mays. At higher concentrations (70% and 100%), the findings showed that AmL crude extract concentrations reduced the germination and growth ofP. vulgarisandZ. maysseeds. Compared to seeds that germinated at lower concentrations and in the control (0%) group, fewer seeds at higher concentrations grew. Accordingly, higher concentrations, relative to lower ones and controls, retarded seed germination. Additionally, the fresh biomass, root lengths, stem diameters, and heights ofP. vulgarisseedlings were reduced under 75% and 100% AmL concentrations, which had a negative impact on their growth vigor. Although this study shows thatP. vulgarisandZ. maysgermination and growth were inhibited byA. mexicanacrude extract, field research experiments are needed to investigate the suppressive effects of this invasive weed on other plant species. Due to its detrimental impact on plant growth, the study recommends further management ofA. mexicanato protect biodiversity. It is expected that these results will be helpful in developing policies and programs for managing invasive plants while taking into account the effects on people’s livelihoods.
Accuracy of retrospective birth location data – An analysis based on siblings
Authors: von Hinke Stephanie , Vitt Nicolai
Published: July 2023

Many surveys ask participants to retrospectively record their location of birth. This paper examines the accuracy of such data in the UK Biobank using a sample of siblings. Comparison of reported birth locations for siblings with different age gaps allows us to estimate the probabilities of household moves and of misreported birth locations. We find an annual probability of 1.2% for household moves of one kilometre or more, suggesting that geographical mobility during childhood was low. Our results furthermore show a sizeable probability of misreporting, with 28% of birth coordinates, 16% of local districts and 6% of counties of birth being incorrectly reported. We show that such error can lead to substantial attenuation bias when investigating the impacts of location-based exposures, especially when there is little spatial correlation and limited time variation in the exposure variable. Sibling fixed effect models are shown to be particularly vulnerable to the attenuation bias.
Detection of viral infection in cell lines using ViralCellDetector
Authors: Shankar Rama , Paithankar Shreya , Gupta Suchir , Chen Bin
Published: July 2023

Cell lines are commonly used in research to study biology, including gene expression regulation, cancer progression, and drug responses. However, cross-contaminations with bacteria, mycoplasma, and viruses are common issues in cell line experiments. Detection of bacteria and mycoplasma infections in cell lines is relatively easy but identifying viral infections in cell lines is difficult. Currently, there are no established methods or tools available for detecting viral infections in cell lines. To address this challenge, we developed a tool called ViralCellDetector that detects viruses through mapping RNA-seq data to a library of virus genome. Using this tool, we observed that around 10% of experiments with the MCF7 cell line were likely infected with viruses. Furthermore, to facilitate the detection of samples with unknown sources of viral infection, we identified the differentially expressed genes involved in viral infection from two different cell lines and used these genes in a machine learning approach to classify infected samples based on the host response gene expression biomarkers. Our model reclassifies the infected and non-infected samples with an AUC of 0.91 and an accuracy of 0.93. Overall, our mapping- and marker-based approaches can detect viral infections in any cell line simply based on readily accessible RNA-seq data, allowing researchers to avoid the use of unintentionally infected cell lines in their studies.
Transcriptome and translatome comparison of tissues fromArabidopsis thaliana
Authors: Vélez-Bermúdez Isabel Cristina , Lin Wen-Dar , Chou Shu-Jen , Chen Ai-Ping , Schmidt Wolfgang
Published: July 2023

Translation is one of the multiple complementary steps that orchestrates gene activity. In contrast to the straightforwardness of transcriptional surveys, genome-wide profiles of the translational landscape of plant cells remain technically challenging and are less well explored. Protein-coding genes are expressed at a variable degree of efficiency, resulting in pronounced discordance among the regulatory levels that govern gene activity. Ribo-Seq provides an extremely useful tool for estimating translation efficiency, but limited data sets are available for plants. Here, we provide comparative inventories of expressed and translated RNA populations, generated by mRNA sequencing (RNA-Seq) and ribosome footprinting (Ribo-Seq) of shoots and roots ofArabidopsis thalianaseedlings. Our data set provides information on the translational fitness of protein-coding mRNAs and lncRNAs that may aid in obtaining a comprehensive picture of the regulatory levels governing genes activity across the genome.
Characterization of Tumor-Associated Endothelial Cells and the Development of a Prognostic Model in Pancreatic Ductal Adenocarcinoma
Authors: Wu Jun , Liu Yang , Fu Qi , Cao Zhi , Li Xun , Ma Xiaodong
Published: July 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a complex tumor microenvironment. Angiogenesis is of paramount importance in the proliferation and metastasis of PDAC. However, currently, there are no well-defined biomarkers available to guide the prognosis and treatment of PDAC.

Results

In this study, we investigated the interactions between tumor-associated endothelial cells (TAECs) and tumor cells in PDAC, and identified a specific subset of TAECs characterized by high expression of COL4A1. COL4A1+ endothelial cells interact with tumor cells through the COLLAGEN signaling pathway to promote tumor cell proliferation, migration, and invasion. We also observed activation of HOXD9 in COL4A1+ endothelial cells. Based on these findings, we developed a prognostic model called TaEMS, which accurately predicts patient prognosis. TaEMS identified high-risk patients enriched in cell cycle-related pathways and low-risk patients enriched in focal adhesions, smooth muscle regulation, and immune pathways. Moreover, high-risk patients displayed a reduced level of immune cell infiltration, indicating the presence of a “cold tumor” phenotype.

Conclusions

Overall, our study uncovered an intricate crosstalk between TAECs and tumor cells in PDAC, emphasizing the role of HOXD9 and highlighting the potential of TaEMS as a prognostic biomarker for precise therapies.
Spatial Metabolome Lipidome and Glycome from a Single brain Section
Authors: Clarke Harrison A. , Ma Xin , Shedlock Cameron J. , Medina Terrymar , Hawkinson Tara R. , Wu Lei , Ribas Roberto A. , Keohane Shannon , Ravi Sakthivel , Bizon Jennifer , Burke Sara , Abisambra Jose Francisco , Merritt Matthew , Prentice Boone , Vander Kooi Craig W. , Gentry Matthew S. , Chen Li , Sun Ramon C.
Published: July 2023

Metabolites, lipids, and glycans are fundamental biomolecules involved in complex biological systems. They are metabolically channeled through a myriad of pathways and molecular processes that define the physiology and pathology of an organism. Here, we present a blueprint for the simultaneous analysis of spatial metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. Complimenting an original experimental protocol, our workflow includes a computational framework called Spatial Augmented Multiomics Interface (Sami) that offers multiomics integration, high dimensionality clustering, spatial anatomical mapping with matched multiomics features, and metabolic pathway enrichment to providing unprecedented insights into the spatial distribution and interaction of these biomolecules in mammalian tissue biology.
Characterization of the RofA regulon in the pandemic M1globaland emergent M1UKlineages ofStreptococcus pyogenes
Authors: Zhi Xiangyun , Vieira Ana , Huse Kristin , Martel Paulo J. , Lobkowicz Ludmila , Li Ho Kwong , Croucher Nick , Andrew Ivan , Game Laurence , Sriskandan Shiranee
Published: July 2023

Background & Aims

The standalone regulator RofA is a positive regulator of the pilus locus inStreptococcus pyogenes. Found in only certainemmgenotypes, RofA has been reported to regulate other virulence factors, although its role in the globally dominantemm1S. pyogenesis unclear. Given the recent emergence of a newemm1 (M1UK) toxigenic lineage that is distinguished by three non-synonymous SNPs inrofA, we characterized therofAregulon in sixemm1 strains, that are representative of the two contemporary majoremm1 lineages (M1globaland M1UK) using RNAseq analysis, and then determined the specific role of the M1UK-specificrofASNPs.

Results

Deletion ofrofAin three M1globalstrains led to altered expression of 14 genes, including six non-pilus locus genes. In M1UKstrains, deletion ofrofAled to altered expression of 16 genes, including 9 genes that were unique to M1UK. Only the pilus locus genes were common to the RofA regulons of both lineages, while transcriptomic changes varied between strains even within the same lineage. Although introduction of the 3 SNPs intorofAdid not impact gene expression in an M1globalstrain, reversal of 3 SNPs in an M1UKstrain led to an unexpected number of transcriptomic changes that in part recapitulated transcriptomic changes seen when deleting RofA in the same strain. Computational analysis predicted interactions with a key histidine residue in the PRD domain of RofA would differ between M1UKand M1global.

RofA is a positive regulator of the pilus locus in allemm1 strains but effects on other genes are strain- and lineage-specific, with no clear, common DNA binding motif. The SNPs inrofAthat characterize M1UKmay impact regulation of RofA; whether they alter phosphorylation of the RofA PRD domain requires further investigation.

Author summary

RofA belongs to the group of “mga-like” bacterial regulatory proteins that comprise a DNA binding domain as well as a phosphorylation domain (PRD) that is responsive to changes in sugar availability. In certainemmgenotypes ofStreptococcus pyogenes,rofAsits upstream of the pilus locus, to act as a positive regulator. The recent emergence of a SpeA exotoxin-producing sublineage ofemm1S. pyogenes, (M1UK) has focused attention on the role of RofA; M1UKand its associated sublineages are characterized by 3 non-synonymous SNPs inrofA,that include adjacent SNPs in the PRD domain. Here, we determine the impact ofrofAdeletion and the 3rofASNPs in both the widely disseminated M1globalclone and the newly emergent M1UKclone. While production of SpeA undoubtedly contributes to infection pathogenesis, the evolution of M1UKpoints to a role for metabolic regulatory rewiring in success of this lineage.
Investigation of latent representation of toxicopathological images extracted by CNN model for understanding compound propertiesin vivo
Authors: Maedera Shotaro , Mizuno Tadahaya , Kusuhara Hiroyuki
Published: July 2023

Toxicopathological images acquired during safety assessment elucidate an individual’s biological responses to a given compound, and their numerization can yield valuable insights contributing to the assessment of compound properties. Currently, toxicopathological images are mainly encoded as pathological findings, evaluated by pathologists, which introduces challenges when used as input for modeling, specifically in terms of representation capability and comparability. In this study, we assessed the usefulness of latent representations extracted from toxicopathological images using Convolutional Neural Network (CNN) in estimating compound propertiesin vivo. Special emphasis was placed on examining the impact of learning pathological findings, the depth of frozen layers during learning, and the selection of the layer for latent representation. Our findings demonstrate that a machine learning model fed with the latent representation as input surpassed the performance of a model directly employing pathological findings as input, particularly in the classification of a compound’s Mechanism of Action and in predicting late-phase findings from early-phase images in repeated-dose tests. While learning pathological findings did improve accuracy, the magnitude of improvement was relatively modest. Similarly, the effect of freezing layers during learning was also limited. Notably, the selection of the layer for latent representation had a substantial impact on the accurate estimation of compound propertiesin vivo.
Whole-brain dynamics and hormonal fluctuations across the menstrual cycle: The role of progesterone and age in healthy women
Authors: Avila-Varela Daniela S. , Hidalgo-Lopez Esmeralda , Dagnino Paulina Clara , Acero-Pousa Irene , Agua Elvira del , Deco Gustavo , Pletzer Belinda , Escrichs Anira
Published: July 2023

Recent neuroimaging research suggests that female sex hormone fluctuations modulate brain activity. Nevertheless, how brain network dynamics change across the female menstrual cycle remains largely unknown. Here, we investigated the dynamical complexity u nderlying three menstrual cycle phases (i.e., early follicular, pre-ovulatory, and mid-luteal) in 60 healthy naturally-cycling women scanned using resting-state fMRI. Our results revealed that the preovulatory phase exhibited the highest variability over time (node-metastability) across the whole-brain functional network compared to the early follicular and mid-luteal phases, while the early follicular showed the lowest. Additionally, we found that large-scale resting-state networks reconfigure along the menstrual cycle phases. Finally, we used multilevel mixed-effects models to examine the impact of hormonal fluctuations and age on whole-brain and resting-state networks. We found significant age-related changes across the whole brain, control, and dorsolateral attention networks. Additionally, we observed progesterone-related changes, specifically within limbic and somatomotor networks. Overall, these findings evidence that both age and progesterone modulate brain network dynamics along the menstrual cycle.
Differentiable Search of Evolutionary Trees
Authors: Hettiarachchi Ramith , Swartz Avi , Ovchinnikov Sergey
Published: July 2023

Inferring the most probable evolutionary tree given leaf nodes is an important problem in computational biology that reveals the evolutionary relationships between species. Due to the exponential growth of possible tree topologies, finding the best tree in polynomial time becomes computationally infeasible. In this work, we propose a novel differentiable approach as an alternative to traditional heuristic-based combinatorial tree search methods in phylogeny. The optimization objective of interest in this work is to find the most parsimonious tree (i.e., to minimize the total number of evolutionary changes in the tree). We empirically evaluate our method using randomly generated trees of up to 128 leaves, with each node represented by a 256-length protein sequence. Our method exhibits promising convergence (< 1% error for trees up to 32 leaves, < 8% error up to 128 leaves, given only leaf node information), illustrating its potential in much broader phylogenetic inference problems and possible integration with end-to-end differentiable models. The code to reproduce the experiments in this paper can be found athttps://github.ramith.io/diff-evol-tree-search.
Hospital length of stay and discharge type prediction using deep learning
Authors: Ramachandra Vikas , Sanghi Prateek
Published: July 2023

The length of hospital stay (LOS) and the type of discharge are important indicators of how well care is provided at a hospital. The purpose of this study is to leverage in-patient data collected at the hospital to help determine the factors that influence the length of hospital stay and type of discharge. Our research focuses on estimating if the person survived or not after they were admitted to the hospital, as well as the type of discharge. The study uses a retrospective design and examines information from hospital discharged patients’ medical records. Demographic information, diagnosis, treatment, and discharge status were included in the data. We have used the PEDALFAST dataset which stands for PEDiatric Validation of Variables in Trauma. A survey of patients to find out how they feel about the quality of care they received while they were in the hospital was also a part of the study dataset. The findings of this study will shed light on the ways in which various factors influence the LOS in the hospital and the type of discharge, assisting in the formulation of strategies to enhance the quality and effectiveness of health care delivery.
Publication bias in otorhinolaryngology meta-analyses in 2021
Authors: Mohammadian Fatemeh , Bastaninejad Shahin , Irani Shirin
Published: July 2023

Introduction

One concern in meta-analyses is the presence of publication bias (PB) which leads to the dissemination of inflated results. In this study, we assessed how much the meta-analyses in the field of otorhinolaryngology in 2021 evaluated the presence of PB.

Methods

Six of the most influential journals in the field were selected. A search was conducted, and data were extracted from the included studies. In cases where PB was not assessed by the authors, we evaluated the risk of its presence by designing funnel plots and performing statistical tests.

Results

75 systematic reviews were included. 51% of them used at least one method for assessing the risk of PB, with the visual inspection of a funnel plot being the most frequent method used. 29% of the studies reported a high risk of PB presence. We replicated the results of 11 meta-analyses that did not assess the risk of PB and found that 63.6% were at high risk.

Discussion

Our results indicate that systematic reviews published in some of the most influential journals in the field do not implement enough measures in their search strategies to reduce the risk of PB, nor do they assess the risk of its presence.
Meta-analysis on Plasmodium falciparum sulfadoxine-pyrimethamine resistance-conferring mutations in India identifies hot spots for genetic surveillance
Authors: Sinha Abhinav , Kar Sonalika , Chauhan Charu , Yadav CP , Kori Lokesh
Published: July 2023

Background

India is on track to eliminate malaria by 2030 but emerging resistance to the first-line antimalarials is a recognized threat. As Artesunate+Sulfadoxine-Pyrimethamine (AS+SP) is the drug-of-choice for uncomplicated P. falciparum malaria in most of India, it becomes evident to systematically monitor the validated mutations in Pfdhfr and Pfdhps genes across India. No systematic and robust countrywide surveillance has been reported for these parameters in India.

Methods

We included studies that reported data on SP-resistance markers in P. falciparum across India from 2008. Five major databases were exhaustively searched. Individual and pooled prevalence estimates of mutations were obtained through random- and fixed-effect models. The study is registered with PROSPERO (CRD42021236012).

Results

A total of 37 publications with data from 80 districts, 21 states and 3 UTs were included. The two PfDHFR mutations, C59R and S108N were the most prevalent mutations and appear to be stabilized/fixed. Although rarest overall, the prevalence of I164L was observed to be as high as 32%. The PfDHFR double mutants were the most prevalent overall. The prevalence of triple and quadruple mutations was 6% and 5%, respectively which is an area of immediate concern. For PfDHPS, the most prevalent mutation was A437G. For PfDHFR/PfDHPS quintuple and sextuple mutations, it was observed that despite a low overall prevalence of these mutations, some areas are critical for surveillance.

Conclusion

The analysis brings forward the SP-resistance hot spots and emphasizes critical gaps, and challenges, and suggests focal and local malaria genetic surveillance (including drug resistance markers) till malaria is eliminated.

Key points

This manuscript concludes that currently used first-line drugs for P. falciparum malaria, particularly sulfadoxine-pyrimethamine, have a high likelihood of failing in near future. Although currently effective, the evidence is backed by molecular meta-analyses data on drug resistance markers in India. The policy makers and program managers may use this robust data to decide whether it is time to change these currently used anti-malarials in India before it is too late. It also identifies certain hot spots for continuous genetic monitoring of the molecular markers for timely actions.
Extraordinary preservation of gene collinearity over three hundred million years revealed in homosporous lycophytes
Authors: Li Cheng , Wickell David , Kuo Li-Yaung , Chen Xueqing , Nie Bao , Liao Xuezhu , Peng Dan , Ji Jiaojiao , Jenkins Jerry , Williams Mellissa , Shu Shengqiang , Plott Chris , Barry Kerrie , Rajasekar Shanmugam , Grimwood Jane , Han Xiaoxu , Sun Shichao , Hou Zhuangwei , He Weijun , Dai Guanhua , Sun Cheng , Schmutz Jeremy , Leebens-Mack James H. , Li Fay-Wei , Wang Li
Published: July 2023

Homosporous lycophytes (Lycopodiaceae) are a deeply diverged lineage in the plant tree of life, having split from heterosporous lycophytes (SelaginellaandIsoetes) ∼400 million years ago (MYA). Compared to the heterosporous lineage, Lycopodiaceae has markedly larger genome sizes and remains the last major plant clade for which no genomic data has been available. Here, we present chromosomal genome assemblies for two homosporous lycophyte species, the allotetraploidHuperzia asiaticaand the diploidDiphasiastrum complanatum. Remarkably, despite that the two species diverged ∼350 MYA, around 30% of the genes are still in syntenic blocks. Furthermore, both genomes had undergone independent whole genome duplications and the resulting intra-genomic syntenies have likewise been preserved relatively well. Such slow genome evolution over deep time is in stark contrast to heterosporous lycophytes and is correlated with a decelerated rate of nucleotide substitution. Together, the genomes ofH. asiaticaandD. complanatumnot only fill a crucial gap in the plant genomic landscape, but also uncover a possibly unique genomic contrast between homosporous and heterosporous species.
Antimicrobial activity of diverse chemotypes ofLippia graveolensagainstAeromonas hydrophilaisolated from tilapia
Authors: García-Pérez Josué , Pérez-Sabino Juan , Mendoza-Elvira Susana , da Silva Antonio Jorge Ribeiro , Ulloa-Rojas Juan
Published: July 2023

Objetive

This study aimed to evaluate the antimicrobial efficacy of essential oil (EO) from diverse chemotypes ofLippia graveolensagainst oxytetracycline-resistantAeromonas hydrophila, which primarily affects the tilapia aquaculture (Oreochromissp) in Guatemala.

Methodology

L. graveolenswere collected in three departments in Guatemala, the EO was obtained by hydrodistillation and characterized by gas chromatography and mass spectrometry (GC/MS). Subsequently, an antimicrobial assay was conducted by screening the disk and dilution susceptibility tests, and evaluation of synergistic interactions among the chemotypes, each test being carried out in triplicate.

Results

The analysis revealed the presence of twenty-seven compounds in the EO obtained from the chemotypes, the main class being monoterpene. The major constituents identified were cis-Dihydro-β-terpineol (8.84%) in chemotype I, carvacrol (51.82%) in chemotype II, and thymol (79.62%) in chemotype III. All EO chemotypes ofL. graveolensdemonstrated the ability to inhibit theA. hydrophilagrowth. Thymol chemotype exhibited the strongest inhibitory effect against bacterial growth, with a minimum inhibitory concentration (MIC) of 92.4 µg/mL and a minimum bactericidal concentration (MBC) of 184.8 µg/mL. Furthermore, the results suggest that there is no synergistic or additive effect when combining different chemotypes ofL. graveolens.

Conclusions

This the first report ofL. graveolenschemotypes exhibiting antimicrobial activity against oxytetracycline-resistantA. hydrophila. The findings suggest the chemotype thymol could be a potential treatment for infections in the tilapia aquaculture in Guatemala.
A structural and functional analysis of opal stop codon translational readthrough during Chikungunya Virus replication
Authors: Li Raymond , Sun Kaiwen , Tuplin Andrew , Harris Mark
Published: July 2023

Chikungunya virus (CHIKV) is an alphavirus, transmitted byAedesspecies mosquitoes. The CHIKV positive-sense RNA genome contains two open reading frames, coding for the non-structural (nsP) and structural proteins of the virus. The non-structural polyprotein precursor is proteolytically cleaved to generate nsP1-4. Intriguingly most isolates of CHIKV (and other alphaviruses) possess an opal stop codon close to the 3’ end of the nsP3 coding sequence and translational readthrough is necessary to produce full-length nsP3 and the nsP4 RNA polymerase. Here we investigate the role of this stop codon by replacing the arginine codon with all three stop codons in the context of both a subgenomic replicon and infectious CHIKV. Both opal and amber stop codons were tolerated in mammalian cells, but the ochre was not. In mosquito cells all three stop codons were tolerated. Using SHAPE analysis we interrogated the structure of a putative stem loop 3’ of the stop codon and used mutagenesis to probe the importance of a short base-paired region at the base of this structure. Our data reveal that this stem is not required for stop codon translational readthrough, and we conclude that other factors must facilitate this process to permit productive CHIKV replication.
Integrated genetic code expansion and structural bioinformatics reveal disrupted supramolecular assembly in a genetic disorder
Authors: Marino Valerio , Phromkrasae Wanchana , Bertacchi Michele , Cassini Paul , Chakrabandhu Krittalak , Dell’Orco Daniele , Studer Michèle
Published: July 2023

Deciphering the structural effects of variants is essential for understanding the pathophysiological mechanisms of genetic diseases. Using a neurodevelopmental disorder called Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) as a genetic disease model, we applied a combined Genetic Code Expansion (GCE) and structural bioinformatics strategy to assess the pathogenic impact of several human NR2F1 variants. Nonsense mutations in the ligand binding domain (LBD) resulted in truncated proteins, while missense variants significantly affected the folding of NR2F1 monomers as well as its supramolecular complexes. The GCE-enabled covalent and site-specific capture of transient supramolecular interactions in living cells revealed the variable quaternary conformations of NR2F1 variants and pinpointed the disrupted interplay with dimeric partners and the newly identified cofactor, CRABP2, while the computational analyses of the NR2F1 structure delineated the molecular basis of the impact of the variants on the isolated and complexed structures. The revealed consequence of the pathogenic mutations on the conformation, supramolecular interplay, and alterations in the cell cycle, viability, and subcellular localization of the different variants reflect the heterogeneous disease spectrum and establish the foundation for further understanding the complexity of BBSOAS.
Development of a Whole-Cell Biosensor for β-Lactamase Inhibitor Discovery
Authors: Jeffs Mitchell A. , Gray Rachel A.V. , Sheth Prameet M. , Lohans Christopher T.
Published: July 2023

The clinical utility of the β-lactam antibiotics has been endangered by the production of β-lactamases by β-lactam-resistant pathogenic bacteria such asEscherichia coli, Pseudomonas aeruginosaandAcinetobacter baumannii. Collectively, these enzymes can degrade every clinically available β-lactam, jeopardizing antimicrobial therapy. Although extensive efforts have been made to develop β-lactamase inhibitors, inhibitor-resistant β-lactamases emerge rapidly. In addition, there are currently no clinically available inhibitors against the metallo-β-lactamases, a group of β-lactamases of great global concern. To further inhibitor discovery efforts, new assays are required to assess inhibitor efficacy, particularly in a cellular context. We report the development of a whole-cellE. colibiosensor which can quantify β-lactamase inhibition in a cellular context. Upon administration of an effective inhibitor, a β-lactam is rescued from β- lactamase-catalyzed degradation, resulting in the emission of a luminescent signal by the biosensor. This platform was validated using a panel of clinically relevant β-lactamases and was applied to quantitatively study the potency of a selection of currently used and reported β-lactamase inhibitors. This rapid method can account for factors like membrane permeability and can be employed to identify new β-lactamase inhibitors.
A novel inducible von Willebrand Factor Cre Recombinase mouse strain to study microvascular endothelial cell-specific biological processesin vivo
Authors: Yadav Dinesh , Conner Jeremy A. , Wang Yimin , Saunders Thomas L. , Ubogu Eroboghene E.
Published: July 2023

Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs. In order to study microvascular endothelial cell-specific biological processes, we developed a Tamoxifen-inducible von Willebrand Factor (vWF) Cre recombinase mouse in the SJL background. The transgene consists of the human vWF promoter with the microvascular endothelial cell-selective 734 base pair sequence to drive Cre recombinase fused to a mutant estrogen ligand-binding domain [ERT2] that requires Tamoxifen for activity (CreERT2) followed by a polyadenylation (polyA) signal. We initially observed Tamoxifen-inducible restricted bone marrow megakaryocyte and sciatic nerve microvascular endothelial cell Cre recombinase expression in offspring of a mixed strain hemizygous C57BL/6- SJL founder mouse bred with mT/mG mice, with >90% bone marrow megakaryocyte expression efficiency. Founder mouse offspring were backcrossed to the SJL background by speed congenics, and intercrossed for >10 generations to develop hemizygous Tamoxifen-inducible vWF Cre recombinase (vWF-iCre/+) SJL mice with stable transgene insertion in chromosome 1. Microvascular endothelial cell-specific Cre recombinase expression occurred in the sciatic nerves, brains, spleens, kidneys and gastrocnemius muscles of adult vWF-iCre/+ SJL mice bred with Ai14 mice, with retained low level bone marrow and splenic megakaryocyte expression. This novel mouse strain would support hypothesis-driven mechanistic studies to decipher the role(s) of specific genes transcribed by microvascular endothelial cells during development, as well as in physiologic and pathophysiologic states in an organ- and time-dependent manner.
#SuperLibrarian – the evolving role of librarians in technology spaces
Authors: Pierre – Robertson Petronetta
Published: July 2023

Purpose

The purpose of this paper is to discuss changes in the roles of librarians against the backdrop of emerging technologies.

Design/methodology/approach

Through reflection on practice drawn from the author’s 30 years in librarianship, this paper explores the evolving role of librarians in the constantly developing technological environment and demonstrates how librarians can combine information resources, technology and research assistance in these constantly changing spaces. It also explores how technology enhances the role of the librarian, with specific reference to ChatGPT.

Findings

The author stressed the need for library courses for credit to allow for feedback, assessment and critical thinking. The need for continuing professional development for librarians was highlighted. Additionally, areas such as Scholarly Publishing, Metrics and Analytics, Academic Integrity and Intellectual Property were identified as areas of focus for the 21st century Librarian.

Research limitations/implications

This study is limited to changes in roles as a result of emerging technologies which impact librarians. It is set in the Caribbean.

Practical implications

This paper is relevant for librarians, regardless of their geographical location, who are also required to be fluid, keep on the cutting edge, adapt and adopt to deliver service in the face of constantly advancing technology.

Originality/value

This paper is a reflection on an original experience from a Caribbean territory. it also explores recent developments in technology, more specifically ChatGPT, and its impact on the roles of librarians. It provides contributions to the ongoing discourse on the evolving role of the librarian from a different perspective.
Defining and establishing a restaurant wine culture
Authors: Taylor D. Christopher , Russen Michelle , Dawson Mary , Reynolds Dennis
Published: July 2023

Purpose

Applying signaling theory to Schein’s organizational culture framework, this study aims to explain how restaurants communicate that their establishments value wine through multiple cultural attributes.

Design/methodology/approach

A phenomenological research design was adopted to conduct three focus groups with 14 restaurateurs about wine culture. Conversational analysis with Straussian coding was used.

Findings

A comprehensive definition of wine culture was provided, and five factors emerged that signal the presence of a wine culture. A wine presence includes a wine list, marketing efforts, community involvement and restaurant aesthetics. Employee traits are defined by individual attributes, communications skills and overall knowledge (training). Restaurant identity reflects the cultural alignment and customer relationship expectations set forth by ownership. Organizational structure reflects a restaurant’s hierarchy within which an individual or department is afforded the freedom to invest in wine. Future alignment reflects generational differences and trends in wine preferences and consumption.

Research limitations/implications

Researchers are provided a wine-culture definition and framework for wine research. Restaurants can use the study’s findings to formulate strategies for establishing a wine culture.

Originality/value

This study provided a framework for restaurateurs who wish to be known for wine to implement. Researchers and restaurateurs may facilitate communication between guests, staff and an organization regarding wine as a means of creating a competitive advantage.
The impact of heterogeneity of service trade policy restrictions on manufacturing exports of China: focus on free trade agreements
Authors: Gao Ming , Zhuo Fanchao
Published: July 2023

Purpose

Based on the research of free trade agreements on alleviating service trade policy heterogeneity and its impact on manufacturing exports, this article aims to not only provide a basis for China's strategy of promoting regional economic integration, but also provide a policy reference for the manufacturing industry to expand the export market space.

Design/methodology/approach

This study uses the two principles of “answering” and “scoring” to quantify the indicators of service trade policy heterogeneity to test the relationship between heterogeneity of service trade policy, free trade agreement and manufacturing export.

Findings

According to empirical study, the export of Chinese manufacturing firms is severely hampered by the variety of service trade regulations, and the bigger the enterprise, the more hampered it is. In comparison to communications, transport and commerce, the financial industry's policy heterogeneity has a greater negative impact on certain industries. The major methods used to reduce the impact of service trade policy heterogeneity on manufacturing exports are product price increases and product quantity reductions. Also, by reducing the heterogeneity of service trade regulations and fostering industrial exports, the free trade agreement that China has signed can be quite successful. The open commitment in the area of national treatment, however, can reduce policy heterogeneity and advance manufacturing.

Originality/value

In the area of market access, the effect of export is superior to the open promise. Thus, in order to effectively support the stabilization of international trade, China should actively encourage the negotiation and signing of higher-quality and mutually beneficial free trade agreements.
Drivers of tax avoidance by MNEs in the developing countries under the digital economy: a modified-TISM approach
Authors: Pandey Kavita , Yadav Surendra S. , Sharma Seema
Published: July 2023

Purpose

The present research identifies a total of nine factors influencing tax avoidance under the international taxation regime of the developing countries and establishes a hierarchical relationship through modeling of the identified factors using modified-total interpretive structural modeling (M-TISM).

Design/methodology/approach

Due to “scale without mass” properties of the digital economy, businesses reduce their physical presence in the countries of economic activities. Aided with digital features, multinational enterprises (MNEs) avoid, abolish, or adopt flexible tax burden in the developing nations through by-passing the permanent establishment condition for company taxes or the income characterization prerequisite for royalty taxation. The present research endeavors to identify the drivers of tax avoidance in the developing countries, especially exacerbated due to digital technologies (economy). In addition, the authors also examine the hierarchical relation between the extracted drivers of tax avoidance.

Findings

This research presents a considerable driving force of elements like historical foundation of tax-treaties, dominance of the developed countries, influence of trade bodies in policy matters and finally information and communications technologies (ICTs).

Originality/value

Identified elements drive the actors like professional enablers, tax havens, international organizations, and intangible assets in the form of intellectual properties (IPs) which act upon tax arbitrage situations both under the domestic and treaty regulations, finally culminating into profit shifting, tax manipulations or avoidance.
Promoting sustainable and human-centric industry 5.0: a thematic analysis of emerging research topics and opportunities
Authors: Rajumesh Sivarajah
Published: July 2023

Purpose

The study aims to explore the overall growth trend, top publishing countries, co-authorship and author keywords in the field of Industry 5.0.

Design/methodology/approach

This study presents the outcomes of a bibliometric analysis conducted using VOSviewer software. The analysis retrieved data from the Scopus database, including citations, co-authors, keywords, bibliometric coupling and co-occurrence.

Findings

The findings reveal a significant increase in publications and citations related to Industry 5.0 in recent years. China, the USA and India emerge as the leading countries driving research in this field. The co-authorship analysis indicates limited collaboration among authors, with only 48 out of 354 authors being linked through co-authorship. Through co-occurrence analysis, the investigation identifies the most frequently occurring keywords in the research, with “Industry 5.0” and “Industry 4.0” being the most frequently co-occurring keywords. The bibliographic coupling analysis identifies six clusters of research themes.

Research limitations/implications

The study solely relies on data gathered from the Scopus database for analysis on a specific date. Therefore, data from other databases collected at different times may yield different observations and findings.

Practical implications

This study enhances the knowledge of professionals and academia in Industry 5.0, enabling the professionals to efficiently and sustainably manage the sector.

Originality/value

The bibliometric analysis presented in this study provides valuable insights into the contributions made by authors, keywords and co-authors to the field of Industry 5.0. Additionally, the thematic analysis summarized in this study is a novel contribution to the field.