bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous application of enzyme and thermodynamic constraints to metabolic models using an updated Python implementation of GECKO
Authors: Carrasco Muriel Jorge , Long Christopher , Sonnenschein Nikolaus
Published: March 2023

GEnome-scale Metabolic (GEM) models are knowledge bases of the reactions and metabolites of a particular organism. These GEM models allow for the simulation of the metabolism - e.g. calculating growth and production yields - based on the stoichiometry, reaction directionality and uptake rates of the metabolic network. Over the years, several extensions have been added to take into account other actors in metabolism, going beyond pure stoichiometry. One such extension is enzyme-constraint models, which enable the integration of kinetic data and proteomics data into GEM models. Given its relatively recent formulation, there are still challenges in standardization and data reconciliation between the model and the experimental measurements. In this work, we present geckopy 3.0 (Genome-scale model Enzyme Constraints, using Kinetics and Omics in python), an actualization from scratch of the previous python implementation of the same name. This update tackles the aforementioned challenges, in an effort to reach maturity in enzyme-constraint modeling. With the new geckopy, proteins are typed in the SBML document, taking advantage of the SBML Groups extension, in compliance with community standards. Additionally, a suite of relaxation algorithms - in the form of linear and mixed-integer linear programming problems - has been added to facilitate reconciliation of raw proteomics data with the metabolic model. Several functionalities to integrate experimental data were implemented, including an interface layer with pytfa for the usage of thermodynamics and metabolomics constraints. Finally, the relaxation algorithms were benchmarked against public proteomics datasets inEscherichia colifor different conditions, revealing targets for improving the enzyme constrained model and/or the proteomics pipeline.

IMPORTANCE

The metabolism of biological cells is an intricate network of reactions that interconvert chemical compounds, gathering energy and using that energy to grow. The static analysis of these metabolic networks can be turned into a computational model which is able to efficiently output the distribution of fluxes in the network. With the inclusion of enzymes in the network, we can also interpret the role and concentrations of the metabolic proteins. However, the models and the experimental data often clash, resulting in a network that cannot grow. Here, we tackle this situation with a suite of relaxations algorithms in a package called geckopy. Additionally, to ensure that enzyme-constraint models follow the community standards, a format for the proteins is postulated. Geckopy also integrates with other software to allow for adding thermodynamic and metabolomic constraints. We hope that the package and algorithms presented here will serve useful for the constraint-based modeling community.
Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies to self-antigens
Authors: Yao Min , Preall Jonathan , Yeh Johannes , Pappin Darryl , Cifani Paolo , Zhao Yixin , Shen Sophia , Moresco Philip , He Brian , Patel Hardik , Habowski Amber , King Daniel A. , Raphael Kara , Rishi Arvind , Sejpal Divyesh , Weiss Matthew , Tuveson David , Fearon Douglas
Published: March 2023

Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these B cell responses are largely unknown. We sought to discover these antigens by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) sequencing of tumor-infiltrating immune cells from seven primary PDAC samples. We identified activated T and B cell responses and evidence of germinal center reactions. Ig sequencing identified plasma cell (PC) clones expressing isotype-switched and hyper-mutated Igs, suggesting the occurrence of T cell-dependent B cell responses. We assessed the reactivity of 41 recombinant antibodies that represented the products of 235 PCs and 12 B cells toward multiple cell lines and PDAC tissues, and observed frequent staining of intracellular self-antigens. Three of these antigens were identified: the filamentous actin (F-actin), the nucleic protein, RUVBL2, and the mitochondrial protein, HSPD1. Antibody titers to F-actin and HSPD1 were elevated in the plasma of PDAC patients, and also detectable in healthy donors. Thus, PCs in PDAC produce auto-antibodies reacting with intracellular self-antigens, which may result from promotion of pre-existing, autoreactive B cell responses. These observations indicate that the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.
Monarchs sabotage milkweed to acquire toxins, not to disarm plant defence
Authors: Betz Anja , Bischoff Robert , Petschenka Georg
Published: March 2023

Sabotaging milkweed by monarch caterpillars is a textbook example for disarming plant defence. By severing leaf veins, monarchs are thought to prevent toxic latex flow to their feeding site. Here we show that sabotaging by monarch caterpillars is not an avoidance strategy. Instead, caterpillars actively ingest outflowing latex to increase sequestration of toxic latex cardenolides. Comparisons with caterpillars of the related non-sequestering common crow butterfly revealed three lines of evidence supporting our hypothesis. First, monarchs sabotage inconsistently and therefore the behaviour is not mandatory to feed on milkweed, while sabotaging in crows precedes every feeding event. Second, monarchs eagerly drink latex, while crow caterpillars spit out latex during sabotaging. Third, monarchs raised on detached leaves sequestered more cardenolides when latex was supplemented artificially. Hence, we conclude, that monarchs converted the “sabotage to avoid” strategy of their relatives into a “sabotage to consume” strategy for acquiring toxins for defence.
Widespread readthrough events in plants reveal unprecedented plasticity of stop codons
Authors: Zhang Yuqian , Li Hehuan , Shen Yanting , Wang Shunxi , Tian Lei , Yin Haoqiang , Shi Jiawei , Xing Anqi , Zhang Jinghua , Ali Usman , Sami Abdul , Chen Xueyan , Gao Chenxuan , Zhao Yangtao , Lyu Yajing , Wang Xiaoxu , Chen Yanhui , Tian Zhixi , Wu Shu-Biao , Wu Liuji
Published: March 2023

Stop codon readthrough (SCR), the decoding of a stop codon as a sense codon by the ribosome, has important biological implications but remains largely uncharacterized in plants. Here, we identified 1,009 SCR events in two monocots (maize, rice) and two dicots (soybean,Arabidopsis) using a proteogenomic strategy with 80 customized databases. SCR transcripts were mostly significantly shorter and had fewer components than non-SCR transcripts in two monocot plants, although these differences were not as significant in the dicots. Mass spectrometry evidence revealed that all three stop codons involved in SCR events could be recoded as 20 standard amino acids, some of which were also supported by suppressor transfer RNA analysis. In addition, we observed multiple functional signals in the C-terminal extensions of 34 maize SCR proteins, and characterized the structural and subcellular localization changes in the extended protein of BASIC TRANSCRIPTION FACTOR 3. Overall, our study not only demonstrates that SCR events are widespread in plants but also reveals the unprecedented recoding plasticity of stop codons, which provides important new insights into the flexibility of genetic decoding.
Environmental variables and species traits as drivers of wild bee pollination in intensive agroecosystems -a metabarcoding approach
Authors: Querejeta Marina , Marchal Lorène , Pfeiffer Paul , Roncoroni Marilyn , Bretagnolle Vincent , Gaba Sabrina , Boyer Stéphane
Published: March 2023

Wild bees are known to be efficient pollinators of wild plants and cultivated crops and they are essential ecosystem service providers. However, wild bee populations have been suffering from significant declines in the last decades mainly due to the use of agrochemicals. Within this framework, we aimed to characterize wild bees pollination spectrum (i.e. the community of pollinated flowering plants) in intensive agroecosystems, and describe the environmental variables and wild bee species traits influencing the pollination. To do this, we conducted metabarcoding analyses of pollen loads from wild bees collected in sunflower crops in the French region of Nouvelle-Aquitaine. Our study revealed that wild bees visited flowering plants corresponding to 231 different Operational Taxonomic Units, classified in 38 families of which Asteraceae, Brassicaceae and Apiaceae were the most visited and more than 90% of the visited taxa turned out to be wild flowers. We also analysed the potential effect of environmental variables and wild bee species traits in governing their choice of pollinated plants. The community composition of pollinated plants varied depending on the flowering stages of the sunflower and the farming system. Our results also show that pollination niche breadth (alpha diversity) varied depending on the flowering stages of the sunflower but was not different between organic and conventional farming systems.

Regarding wild bee species traits, the community composition of pollinated plants varied in relation to wild bees body sizes and, sociality levels. Our results are consistent with previous studies, suggesting that solitary bees are more specialists when it comes to flower selection than social bees, which are more generalist. The metabarcoding of pollen loads enabled us to draw a global picture of plant-wild bee interactions in an intensive agroecosystem. Our findings support the hypothesis that a higher diversity of weeds may increase wild bee diversity in intensive agroecosystems.
Validity of the cell-extracted proteome as a substrate pool for exploring phosphorylation motifs of kinases
Authors: Niinae Tomoya , Sugiyama Naoyuki , Ishihama Yasushi
Published: March 2023

Three representative protein kinases with different substrate preferences, ERK1 (Pro-directed), CK2 (acidophilic), and PKA (basophilic), were used to investigate phosphorylation sequence motifs in substrate pools consisting of the proteomes from three different cell lines, MCF7 (human mammary carcinoma), HeLa (human cervical carcinoma), and Jurkat (human acute T-cell leukemia). Specifically, recombinant kinases were added to the cell-extracted proteomes to phosphorylate the substratesin vitro. After trypsin digestion, the phosphopeptides were enriched and subjected to nanoLC/MS/MS analysis to identify their phosphorylation sites on a large scale. By analyzing the obtained phosphorylation sites and their surrounding sequences, phosphorylation motifs were extracted for each kinase-substrate proteome pair. We found that each kinase exhibited the same set of phosphorylation motifs, independently of the substrate pool proteome. Furthermore, the identified motifs were also consistent with those found using a completely randomized peptide library. These results indicate that cell-extracted proteomes can provide kinase phosphorylation motifs with sufficient accuracy, even though their sequences are not completely random, supporting the robustness of phosphorylation motif identification based on phosphoproteome analysis of cell extracts as a substrate pool for a kinase of interest.
Investigation of acute encephalitis syndrome with implementation of metagenomic next generation sequencing in Nepal
Authors: Shrestha R , Katuwal N , Tamrakar D , Tato CM , Vanaerschot M , Ahyong V , Gil J , Madhup SK , Gupta BP , Jha R
Published: March 2023

Background

The causative agents of Acute Encephalitis Syndrome remain unknown in 68-75% of the cases. In Nepal, the cases are tested only for Japanese encephalitis, which constitutes only about 15% of the cases. However, there could be several organisms, including vaccine-preventable etiologies that cause acute encephalitis, when identified could direct public health efforts for prevention, including addressing gaps in vaccine coverage.

Objectives

This study employs metagenomic next-generation-sequencing in the exploration of infectious etiologies contributing to acute encephalitis syndrome in Nepal.

Methods

In this study, we investigated 90, Japanese-encephalitis-negative, banked cerebrospinal fluid samples that were collected as part of a national surveillance network in 2016 and 2017. Randomisation was done to include three age groups (<5-years; 5-14-years; >15-years). Only some metadata (age and gender) were available. The investigation was performed in two batches which included total nucleic-acid extraction, followed by individual library preparation (DNA and RNA) and sequencing on Illumina iSeq100. The genomic data were interpreted using Chan-Zuckerberg-ID and confirmed with polymerase-chain-reaction.

Results

Human-alphaherpesvirus-2 and Enterovirus-B were seen in two samples. These hits were confirmed by qPCR and semi-nested PCR respectively. Most of the other samples were marred by low abundance of pathogen, possible freeze-thaw cycles, lack of process controls and associated clinical metadata.

Conclusion

From this study, two documented causative agents were revealed through metagenomic next-generation-sequencing. Insufficiency of clinical metadata, process controls, low pathogen abundance and absence of standard procedures to collect and store samples in nucleic-acid protectants could have impeded the study and incorporated ambiguity while correlating the identified hits to infection. Therefore, there is need of standardized procedures for sample collection, inclusion of process controls and clinical metadata. Despite challenging conditions, this study highlights the usefulness of mNGS to investigate diseases with unknown etiologies and guide development of adequate clinical-management-algorithms and outbreak investigations in Nepal.
Axonal damage and astrocytosis are biological correlates of grey matter network integrity loss: a cohort study in autosomal dominant Alzheimer disease
Authors: Vermunt L. , Sutphen C. , Dicks E. , de Leeuw D.M. , Allegri R. , Berman S.B. , Cash D.M. , Chhatwal J.P. , Cruchaga C. , Day G. , Ewers M. , Farlow M. , Fox N.C. , Ghetti B. , Graff-Radford N. , Hassenstab J. , Jucker M. , Karch C M. , Kuhle J. , Laske C. , Levin J. , Masters C.L , McDade E. , Mori H. , Morris J.C. , Perrin R.J. , Preische O. , Schofield P.R. , Suárez-Calvet M. , Xiong C. , Scheltens P. , Teunissen C.E. , Visser P.J. , Bateman R.J. , Benzinger T.L.S. , Fagan A.M. , Gordon B.A. , Tijms B.M.
Published: March 2023

Brain development and maturation leads to grey matter networks that can be measured using magnetic resonance imaging. Network integrity is an indicator of information processing capacity which declines in neurodegenerative disorders such as Alzheimer disease (AD). The biological mechanisms causing this loss of network integrity remain unknown. Cerebrospinal fluid (CSF) protein biomarkers are available for studying diverse pathological mechanisms in humans and can provide insight into decline. We investigated the relationships between 10 CSF proteins and network integrity in mutation carriers (N=219) and noncarriers (N=136) of the Dominantly Inherited Alzheimer Network Observational study. Abnormalities in Aβ, Tau, synaptic (SNAP-25, neurogranin) and neuronal calcium-sensor protein (VILIP-1) preceded grey matter network disruptions by several years, while inflammation related (YKL-40) and axonal injury (NfL) abnormalities co-occurred and correlated with network integrity. This suggests that axonal loss and inflammation play a role in structural grey matter network changes.

Key points

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Abnormal levels of fluid markers for neuronal damage and inflammatory processes in CSF are associated with grey matter network disruptions.

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The strongest association was with NfL, suggesting that axonal loss may contribute to disrupted network organization as observed in AD.

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Tracking biomarker trajectories over the disease course, changes in CSF biomarkers generally precede changes in brain networks by several years.
Neck pain, dry eye and Sjögren’s syndrome in Latin American students during the first wave of COVID-19: Frequencies and associated factors
Authors: Mejia Christian R. , Gutarra-Laureano Briggitte , Zorrilla-Lizana Ingrid L. , Arias-Chavez Dennis , Fernandez Maria F. , Vera Claudia A. , Vilela-Estrada Martin A. , Serna-Alarcón Victor , Requena Tatiana , Zambrano Lysien Ivania , Turcios Eleonora Espinoza
Published: March 2023

Introduction

Virtual classes brought many changes to the lives of students, not only the fact of being more exposed to screens, but also because of the repercussions.

Aim

To determine the factors associated with suffering from neck pain, dry eye and Sjögren’s syndrome in students in Latin America during the first wave of COVID-19.

Methodology

Analytical cross-sectional study, using the COM and DEQ-5 scales, neck pain and dry eye/Sjögren’s syndrome, respectively, were measured; socio-educational variables were associated with them.

Discussion

Of the 3939 students, those who lived in Panama, Chile and Bolivia were the ones who suffered the most from these pathologies. These pathologies were associated with the greater number of hours of computer use (all values p<0,001) and sex (all values p<0,002), medical students had more frequent dry eye and Sjögren’s syndrome (both p<0,031), Graduate students had more neck pain (p<0.001), but college students had less dry eye (p=0.025) and those at private universities had more neck pain (p=0.024).

Discussion

Important results of these three pathologies were found, this serves so that students can be evaluated in depth in each university, for a specialized diagnosis and try to avoid medium and long-term consequences for the constant use of electronic devices.

Conclusion

Neck pain, dry eye and Sjögren’s syndrome in students were associated with more hours of computer use and female sex, medical students had more frequent dry eye and Sjögren’s syndrome, graduate students had more neck pain, university students had less dry eye and those from private universities had more neck pain.
Patient-specific multi-modal modeling uncovers neurotransmitter receptor involvement in motor and non-motor axes of Parkinson’s disease
Authors: Khan Ahmed Faraz , Adewale Quadri , Lin Sue-Jin , Baumeister Tobias R. , Zeighami Yashar , Carbonell Felix , Palomero-Gallagher Nicola , Iturria-Medina Yasser
Published: March 2023

Multi-systemic neurodegeneration in Parkinson’s disease (PD) is increasingly acknowledged, involving several neurotransmitter systems beyond the classical dopaminergic circuit and resulting in heterogeneous motor and non-motor symptoms. Nevertheless, the mechanistic basis of neuropathological and symptomatic heterogeneity remains unclear. Here, we use patient-specific generative brain modeling to identify neurotransmitter receptor-mediated mechanisms involved in PD progression. Combining receptor maps with longitudinal neuroimaging (PPMI data), we detect a diverse set of receptors influencing gray matter atrophy, microstructural degeneration, and dendrite loss in PD. Importantly, identified receptor mechanisms correlate with symptomatic variability along two distinct axes, representing motor/psychomotor symptoms with large GABAergic contributions, and cholinergically-driven visuospatial dysfunction. Furthermore, we map cortical and subcortical regions where receptors exert significant influence on neurodegeneration. Our work constitutes the first personalized causal model linking the progression of multi-factorial brain reorganization in PD across spatial scales, including molecular systems, accumulation of neuropathology in macroscopic brain regions, and clinical phenotypes.
Associations of weather and air pollution with objective physical activity and sedentary time before and after bariatric surgery: a secondary analysis of a prospective cohort study
Authors: Baillot Aurélie , Bernard Paquito , Jmii Nejm Eddine , Thomas J. Graham , Schumacher Leah M. , Papasavas Pavlos K. , Vithiananthan Sivamainthan , Jones Daniel , Bond Dale S.
Published: March 2023

Background

Most metabolic and bariatric surgery (MBS) patients perform too little moderate-to-vigorous intensity physical activity (MVPA) and too much sedentary time (ST). Identifying factors that influence MVPA and ST in MBS patients is necessary to inform the development of interventions to target these behaviors. Research has focused on individual-level factors and neglected those related to the physical environment (e.g., weather and pollution). These factors may be especially important considering rapid climate change and emerging data that suggest adverse effects of weather and pollution on physical activity are more severe in people with obesity.

Objectives

To examine the associations of weather (maximal, average and Wet Bulb Globe Temperatures), and air pollution indices (air quality index [AQI]) with daily physical activity (PA) of both light (LPA) and MVPA and ST before and after MBS.

Methods

Participants (n=77) wore an accelerometer at pre- and 3, 6, and 12-months post-MBS to assess LPA/MVPA/ST (min/d). These data were combined with participants’ local (Boston, MA or Providence, RI, USA) daily weather and AQI data (extracted from federal weather and environmental websites).

Results

Multilevel generalized additive models showed inverted U-shaped associations between weather indices and MVPA (R2≥ .63, p<.001), with a marked reduction in MVPA for daily maximal temperatures ≥20°C. Sensitivity analysis showed a less marked decrease of MVPA (min/d) during higher temperatures after versus before MBS. Both MVPA before and after MBS (R2=0.64, p<.001) and ST before MBS (R2=0.395; p≤.05) were negatively impacted by higher AQI levels.

Discussion

This study is the first to show that weather and air pollution indices are related to variability in activity behaviors, particularly MVPA, during pre- and post-MBS. Weather/environmental conditions should be considered in MVPA prescription/strategies for MBS patients, especially in the context of climate change.
The structural basis of hyperpromiscuity in a core combinatorial network of Type II toxin-antitoxin and related phage defence systems
Authors: Ernits Karin , Saha Chayan Kumar , Brodiazhenko Tetiana , Chouhan Bhanu , Shenoy Aditi , Duque-Pedraza Julian J , Bojar Veda , Nakamoto Jose A , Kurata Tatsuaki , Egorov Artyom , Shyrokova Lena , Johansson Marcus J. O. , Mets Toomas , Rustamova Aytan , Dzigurski Jelisaveta , Tenson Tanel , Garcia-Pino Abel , Elofsson Arne , Hauryliuk Vasili , Atkinson Gemma Catherine
Published: March 2023

Toxin-antitoxin (TA) systems are a large group of small genetic modules found in prokaryotes and their mobile genetic elements. Type II TAs are encoded as bicistronic (two-gene) operons that encode two proteins: a toxin and neutralising antitoxin. Using our tool NetFlax (standing for Network-FlaGs for toxins and antitoxins) we have performed a large-scale bioinformatic analysis of proteinaceous TAs, revealing interconnected clusters constituting a core network of TA-like gene pairs. To understand the structural basis of toxin neutralisation by antitoxins, we have predicted the structures of 3,419 complexes with AlphaFold2. Together with mutagenesis and functional assays, our structural predictions provide insights into the neutralising mechanism of the hyperpromiscuous Panacea antitoxin domain. In antitoxins composed of standalone Panacea, the domain mediates direct toxin neutralisation, while in multidomain antitoxins the neutralisation is mediated by other domains, such as PAD1, Phd-C and ZFD. We hypothesise that Panacea acts as a sensor that regulates TA activation. We have experimentally validated 16 new NetFlax TA systems. We used functional domain annotations and with metabolic labelling assays to predict their potential mechanisms of toxicity (such as disruption of membrane integrity, inhibition of cell division and abrogation of protein synthesis) as well as biological functions (such as antiphage defence). The interactive version of the NetFlax TA network that includes structural predictions can be accessed at http://netflax.webflags.se/.
Identification and characterization of two CRISPR-Cas systems associated with the mosquito microbiome
Authors: Hegde Shivanand , Rauch Hallie E. , Hughes Grant L. , Shariat Nikki
Published: March 2023

The microbiome profoundly influences many traits in medically relevant vectors such as mosquitoes, and a greater functional understanding of host-microbe interactions may be exploited for novel microbial-based approaches to control mosquito-borne disease. Here, we characterized two CRISPR-Cas systems in a novel bacterium,SerratiaSp. Ag1, that was isolated from the gut of anAnopheles gambiaemosquito. Two distinct CRISPR-Cas systems were identified inSerratiaAg1, CRISPR1 and CRISPR2. Based oncasgene composition, CRISPR1 is classified as a Type I-E CRISPR-Cas system and has a single array, CRISPR1. CRISPR2 is a Type I-F system with two arrays, CRISPR2.1 and CRISPR2.2. RT-PCR analyses show that allcasgenes from both systems are expressed during logarithmic growth in culture media. The direct repeat sequence of CRISPRs 2.1 and 2.2 are identical and found in the arrays of otherSerratiaspp, includingS. marcescensandS. fonticola, whereas CRISPR1 was not. We searched for potential spacer targets and revealed an interesting difference between the two systems: only 9% of CRISPR1 (Type I-E) targets are in phage sequences and 91% are in plasmid sequences. Conversely, ~66% of CRISPR2 (Type I-F), targets are found within phage genomes. Our results highlight the presence of CRISPR loci in gut-associated bacteria of mosquitoes and indicate interplay between symbionts and invasive mobile genetic elements over evolutionary time.

Data Summary

There is no supporting external data generated for this work.
Lysosome damage triggers direct ATG8 conjugation and ATG2 engagement via CASM
Authors: Cross Jake , Durgan Joanne , McEwan David G , Florey Oliver
Published: March 2023

Cells harness multiple pathways to maintain lysosome integrity, a central homeostatic process. Damaged lysosomes can be repaired, or targeted for degradation by lysophagy, a selective autophagy process involving ATG8/LC3. Here, we describe a parallel ATG8/LC3 response to lysosome damage, mechanistically distinct from lysophagy. Using a comprehensive series of biochemical, pharmacological and genetic approaches, we show that lysosome damage induces rapidConjugation ofATG8s toSingleMembranes (CASM). ATG8 proteins are recruited directly onto damaged membranes, independently of ATG13/WIPI2, and conjugated to PS, as well as PE, a molecular hallmark of CASM. Lysosome damage drives V-ATPase V0-V1 association, and direct recruitment of ATG16L1, dependent on K490 (WD40-domain), and sensitive toSalmonellaSopF. Lysosome damage-induced CASM is associated with the formation of dynamic LC3A-positive tubules, and promotes robust LC3A engagement with ATG2, a lipid transfer protein central to lysosome repair. Together, our data identify direct ATG8 conjugation as a rapid response to lysosome damage, with important links to lipid transfer and dynamics.
EGGNet, a generalizable geometric deep learning framework for protein complex pose scoring
Authors: Wang Zichen , Brand Ryan , Adolf-Bryfogle Jared , Grewal Jasleen , Qi Yanjun , Combs Steven A. , Golovach Nataliya , Alford Rebecca , Rangwala Huzefa , Clark Peter M.
Published: March 2023

Computational prediction of molecule-protein interactions has been key for developing new molecules to interact with a target protein for therapeutics development. Past work includes two independent streams of approaches: (1) predicting protein-protein interactions (PPI) between naturally occurring proteins and (2) predicting the binding affinities between proteins and small molecule ligands (aka drug target interaction, or DTI). Studying the two problems in isolation has limited the ability of these computational models to generalize across the PPI and DTI tasks, both of which ultimately involve non-covalent interactions with a protein target. In this work, we developed an Equivariant Graph of Graphs neural Network (EGGNet), a geometric deep learning framework for molecule-protein binding predictions that can handle three types of molecules for interacting with a target protein: (1) small molecules, (2) synthetic peptides and (3) natural proteins. EGGNet leverages a graph of graphs (GoGs) representation constructed from the molecule structures at atomic-resolution and utilizes a multi-resolution equivariant graph neural network (GNN) to learn from such representations. In addition, EGGNet leverages the underlying biophysics and makes use of both atom- and residue-level interactions, which improve EGGNet’s ability to rank candidate poses from blind docking. EGGNet achieves competitive performance on both a public proteinsmall molecule binding affinity prediction task (80.2% top-1 success rate on CASF-2016) and an synthetic protein interface prediction task (88.4% AUPR). We envision that the proposed geometric deep learning framework can generalize to many other protein interaction prediction problems, such as binding site prediction and molecular docking, helping accelerate protein engineering and structure-based drug development.
Identification of a Novel PARP14 Site Motif and Glycohydrolase Specificity Using TLC-MALDI-TOF
Authors: Javed Zeeshan , Nguyen Hannah H. , Harker Kiana , Mohr Christian M. , Vano Pia , Wallace Sean R. , Silvers Clarissa , Sim Colin , Turumella Soumya , Flinn Ally , Carter-O’Connell Ian
Published: March 2023

Transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) to target proteins is mediated by a class of human poly-ADP-ribose polymerases, PARPs, and removal of ADPr is catalyzed by a family of glycohydrolases. Although thousands of potential ADPr modification sites have been identified using high-throughput mass-spectrometry, relatively little is known about sequence specificity encoded near the modification site. Herein, we present a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method that facilitates the discovery and validation of ADPr site motifs. We identify a minimal 5-mer peptide sequence that is sufficient to drive PARP14 specific activity while highlighting the importance of the adjacent residues in PARP14 targeting. We measure the stability of the resultant ester bond and show that non-enzymatic removal is sequence independent and occurs within hours. Finally, we use the ADPr—peptide to highlight differential activities within the glycohydrolase family and their sequence specificities. Our results highlight: 1) the utility of MALDI-TOF in motif discovery and 2) the importance of peptide sequence in governing ADPr transfer and removal.
Beam damage in operando X-ray diffraction studies of Li-ion batteries
Authors: Christensen Christian Kolle , Karlsen Martin Aaskov , Drejer Andreas Østergaard , Andersen Bettina Pilgaard , Jakobsen Christian Lund , Johansen Morten , Sørensen Daniel Risskov , Kantor Innokenty , Jørgensen Mads Ry Vogel , Ravnsbæk Dorthe Bomholdt
Published: March 2023

Operando powder X-ray diffraction (PXRD) is a widely employed method for the investigation of structural evolution and phase transitions in electrodes for rechargeable batteries. Due to the advantages of high brilliance and high X-ray energies, the experiments are often carried out at synchrotron facilities. It is known that the X-ray exposure can cause beam damage in the battery cell, resulting in hindrance of the electrochemical reaction. This study investigates the extent of X-ray beam damage during operando PXRD synchrotron experiments on battery materials with varying X-ray energies, amount of X-ray exposure and battery cell chemistries. Battery cells were exposed to 15, 25 or 35 keV X-rays (with varying dose) during charge or discharge in a battery test cell specially designed for operando experiments. The observed beam damage was probed by µPXRD mapping of the electrodes recovered from the operando battery cell after charge/discharge. The investigation reveals that the beam damage depends strongly on both the X-ray energy and the amount of exposure, and that it also depends strongly on the cell chemistry, i.e. the chemical composition of the electrode.
Syntheses and crystal structures of four 4-(4-methoxyphenyl)piperazin-1-ium salts: trifluoroacetate, 2,3,4,5,6-pentafluorobenzoate, 4-iodobenzoate, and a polymorph with 4-methylbenzoate
Authors: Vinaya  , Basavaraju Yeriyur B. , Yathirajan Hemmige S. , Parkin Sean
Published: March 2023

Syntheses and X-ray crystal structures of four 4-(4-methoxyphenyl)piperazin-1-ium (MeOPP) salts, with 2,2,2-trifluoroacetate, C11H17N2O+·C2F3O2
− (I), 2,3,4,5,6-pentafluorobenzoate, C11H17N2O+·C7F5O2
−·H2O (II), 4-iodobenzoate C11H17N2O+·C7H4IO2
−·H2O (III), and 4-methylbenzoate, C11H17N2O+·C8H7O2
−·H2O (IV) anions are presented. The salts form directly from equimolar quantities of N-(4-methoxyphenyl)piperazine and the corresponding organic acid in methanol and crystallize from 1:1 methanol/ethyl acetate. Salt I is anhydrous whereas II, III, and IV are all monohydrates. In all cases, the MeOPP cation conformation is determined by the torsion about the N—C bond between the piperazinium and 4-methoxybenzene rings. Crystal packing in each structure is largely dictated by N—H...O and (in II, III, and IV) O—H...O hydrogen bonds, although each also features weak C—H...O-type hydrogen bonds. Salt II also has π–π-stacking interactions between cation and anion arene rings, and III exhibits I...I close contacts.
An analog of Titchmarsh's theorem for the Laguerre–Bessel transform
Authors: Rakhimi Larbi , Daher Radouan
Published: March 2023

Purpose

Using a generalized translation operator, this study aims to obtain a generalization of Titchmarsh's theorem for the Laguerre–Bessel transform for functions satisfying the ψ-Laguerre–Bessel–Lipschitz condition in the space L2α (K), where K=0,+∞×0,+∞[.

Design/methodology/approach

The author has employed the results developed by Titchmarsh, of reference number [1].

Findings

In this paper, an analogous of Titchmarsh's theorem is established for Laguerre–Bessel transform.

Originality/value

To the best of the authors’ findings, at the time of submission of this paper, the results reported are new and interesting.
Structural performance of buried reinforced concrete pipelines under deep embankment soil
Authors: Almasabha Ghassan , Shehadeh Ali , Alshboul Odey , Al Hattamleh Omar
Published: March 2023

Purpose

Buried pipelines under various soil embankment heights are cost-effective alternatives to transporting liquid products. This paper aims to assist pipeline architects and professionals in selecting the most cost-effective buried reinforced concrete pipelines under deep embankment soil with minor structural reinforcement while meeting shear stress requirements, safety and reliability constraints.

Design/methodology/approach

It is unfeasible to experimentally assess pipeline efficiency with high soil fill depth. Thus, to fill this gap, this research uses a dependable finite element analysis (FEA) to conduct a parametric study and carry out such an issue. This research considered reinforced concrete pipes with diameters of 25, 50, 75, 100, 125 and 150 cm at depths of 5, 10, 15 and 20 m.

Findings

According to this research, the proposed best pipeline diameter-to-thickness (D/T) proportions for soil embankment heights 5, 10, 15 and 20 m are 8.75, 4.8, 3.5 and 3.1, correspondingly. The cost-effective reinforced concrete (RC) pipeline thickness dramatically rises if the soil embankment reaches 20 m, indicating that the soil embankment depth highly influences it. Most of the analyzed reinforced concrete pipelines had a maximum deflection value of less than 1 cm, telling that the FEA accurately identified the pipeline width, needed flexural steel reinforcement, and concrete crack width while avoiding significant distortion.

Originality/value

The cost-effective thickness for the analyzed structured concrete pipes was calculated by considering the lowest required value of steel reinforcement. An algorithm was developed based on the parametric scientific findings to predict the ideal pipeline D/T ratio. A construction case study was also shown to assist architects and professionals in determining the best reinforced concrete pipeline geometry for a specific soil embankment height.
Stay ahead: CEO education and entry timing within industry merger waves
Authors: Tang Meiling , Zhao Xi , Li Xiangyu , Niu Xiaotong
Published: March 2023

Purpose

This study aims to explore the effect of chief executive officer education on firms’ action timing and acquisition performance in industry merger waves. In addition, this study investigated the moderating influence of CEO duality and firm cash flow on the relationship between education and entry timing.

Design/methodology/approach

Following the methodology for determining merger waves in previous studies, the authors identified 16 industry merger waves of Chinese listed firms from 2008 to 2019. Multiple linear regression was employed to examine the hypotheses.

Findings

The results showed that higher CEO education was associated with early participation in merger waves. CEO duality negatively moderated the education-entry timing relation. The effect of CEO education on entry timing was more pronounced when firms had higher cash flow. Moreover, more educated CEOs materially enhanced acquisition performance in merger waves.

Originality/value

Entry timing in industry merger waves has important implications, as early movers establish competitive advantages and achieve higher acquisition performance. However, the managerial characteristics determining entry timing have not received adequate attention. Meanwhile, studies examining the effect of CEO education on acquisitions are limited. This study explored the effect of CEO education on firms’ entry timing and acquisition performance in merger waves, thereby contributing to the literature on merger waves and managerial characteristics. This study’s findings regarding the moderators of the education-entry timing relation enrich the literature on corporate governance and agency theory.
An exploration of perceptions and use of misinformation on the social Web in Oman
Authors: Shehata Ahmed Maher Khafaga , Al-Suqri Mohammed Nasser , Alsalmi Jamal , Osman Nour Eldin , Alrashdi Said , Khalaf Mustafa Ali
Published: March 2023

Purpose

The purpose of this study is to investigate individuals’ perceptions and behavior when dealing with misinformation on social media platforms. While misinformation is not a new phenomenon, the COVID-19 outbreak has accelerated its spread through social media outlets, leading to widespread exposure to false or misleading information. This exposure can have serious consequences on individuals’ decision-making and behavior, especially when it comes to critical decisions related to education or healthcare. The use of social media as a source of information makes it essential to understand how people perceive and respond to misinformation to develop effective strategies for mitigating its harmful effects.

Design/methodology/approach

This large-scale study explores the Omani individuals’ perceptions and behaviour of misinformation on the social Web in a series of studies that seek to enhance the authorities’ response to misinformation. The study adopted a quantitative approach to collect data. Using WhatsApp as a social networking platform, a survey was disseminated to capture participants’ perceptions and behaviour among different segments of citizens in Oman.

Findings

The findings showed that Omani participants have high verification skills, implying high information literacy skills among them. Additionally, results indicated that misinformation had created doubt and anxiety among the participants. Moreover, it hindered many participants’ ability to take countermeasures and obtain reliable data.

Originality/value

This study was a large-scale study conducted in Oman, making it one of a few studies conducted in the region about perceptions and behaviour towards misinformation. The findings help to understand how different cultures interacted with COVID-19 misinformation. In addition, these findings offer useful insight that can help health information professionals to design preventive resources that help people to obtain accurate information during crises.
Research engagement and research capacity building: a priority for healthcare organisations in the UK
Authors: Peckham Stephen , Zhang Wenjing , Eida Tamsyn , Hashem Ferhana , Kendall Sally
Published: March 2023

Purpose

To research involvement of healthcare staff in the UK and identify practical organisational and policy solutions to improve and boost capacity of the existing workforce to conduct research.

Design/methodology/approach

A mixed-method study presenting three work packages here: secondary analysis of levels of staff research activity, funding, academic outputs and workforce among healthcare organisations in the United Kingdom; 39 Research and Development lead and funder interviews; an online survey of 11 healthcare organisations across the UK, with 1,016 responses from healthcare staff included for analysis; and 51 interviews of healthcare staff in different roles from six UK healthcare organisations.

Findings

Interest in research involvement is strong and widespread but hampered by a lack of systematic organisational support despite national policies and strategies to increase staff engagement in research. While useful, these external strategies have limited universal success due to lack of organisational support. Healthcare organisations should embed research within organisational and human resources policies and increase the visibility of research through strategic organisational goals and governance processes. A systems-based approach is needed.

Research limitations/implications

The research gathered data from a limited number of NHS trusts but these were purposively sampled to provide a range of different acute/community health service organisations in different areas. But data was therefore more detailed and nuanced due to a more in-depth approach.

Practical implications

The findings are relevant for developing policies and practice within healthcare organisations to support research engagement. The findings also set out key policy and strategic recommendations that will support greater research engagement.

Social implications

Increased research activity and engagement in healthcare providers improves healthcare outcomes for patients.

Originality/value

This is a large scale (UK-wide) study involving a broad range of healthcare staff, with good engagement of nurses, midwives and Allied Healthcare Professionals who have not been previously achieved. This allowed valuable analysis of under-researched groups and comparisons by professional groups. The findings highlight the need for tailored action to embed research reporting, skills, professional development and infrastructure into organisational policies, strategies and systems, along with broader system-wide development.
Biculturals in international business negotiations: moving away from the single culture paradigm
Authors: Khakhar Priyan , Rammal Hussain Gulzar , Pereira Vijay
Published: March 2023

Purpose

Biculturals possess higher cultural intelligence than monocultural individuals. This study explores biculturals' key factors and attributes and how their cultural knowledge and identification influence International Business Negotiations (IBNs) and help their firms outperform others.

Design/methodology/approach

Data were collected from semi-structured interviews with 35 bicultural senior managers in Lebanon.

Findings

The findings highlight three essential qualities and behaviors that allow biculturals to act as a bridge between the parties during IBN: adaptability, cultural frame switching (CFS) and creativity.

Originality/value

This study explores the notion of bicultural personnel using their understanding of multiple cultures to be innovative, avoid groupthink and generate new creative ideas that help overcome stalemates during IBNs.
SME internationalisation: past, present and future trends
Authors: Fernandes Cristina , Veiga Pedro Mota , Gerschewski Stephan
Published: March 2023

Purpose

Small- and medium-sized enterprises (SMEs) generally make a crucial contribution to local and national economies. As the market has become increasingly globalised over the past two decades, SMEs often feel the need and/or push to internationalise their business activities. It is in this need that several barriers and challenges are perceived by SMEs, since these companies generally have different characteristics and resources compared to large multinational enterprises (MNEs). Accordingly, given that the literature on internationalisation is rather extensive and relatively fragmented, this study seeks to systematically understand the scientific structure of research on the internationalisation of SMEs, and how it is organised.

Design/methodology/approach

The authors used a bibliometric approach and data co-citation to identify and systematise the scientific publications, intellectual structures and research trends related to SME internationalisation.

Findings

The study research reveals five approaches that theoretically support the internationalisation processes of SMEs: (1) internationalisation and networks; (2) internationalisation and venture capital; (3) internationalisation and intrinsic characteristics; (4) internationalisation and transactional costs; and (5) internationalisation and firm resources and capabilities.

Originality/value

This study has important implications for academics and practitioners who are likely to benefit from a holistic understanding of the different aspects of SME internationalisation.
Unintended change of ownership structure and acquisition of IJVs: the effect of initial structural conditions
Authors: Aib Hamza , Liouville Jacques , Merchant Hemant
Published: March 2023

Purpose

The purpose of this study is to demonstrate the effect of initial international joint ventures (IJV) structural conditions on two main equity-based instability facets: change of IJV ownership structure and acquisition of the IJV by one of the IJV partners. Drawing on the transaction cost theory, the authors examine three key initial structural conditions: IJV formation mode, number of partners and IJV’s ownership structure.

Design/methodology/approach

The authors apply the “Event history analysis” technique to test the hypotheses using a data set of 140 French-foreign JVs.

Findings

The findings show that the mode of an acquisitive IJV and unequal equity positions held by partners increase the likelihood of a change of IJV’s ownership structure and its eventual acquisition by one of the partners. In addition, the findings show that while an increase in the number of IJV partners is directly related to the change of IJV ownership structure, it has a statistically insignificant effect on IJV acquisition.

Originality/value

Drawing on “transaction costs” arguments, this study advances the literature by offering fine-grained results related to the effects of initial structural conditions on aspects of unintended instability in French-foreign JVs.