bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis lateral shoots display two distinct phases of growth angle control
Authors: De Angelis Martina , Kepinski Stefan 
Published: April 2023

AbstractShoot growth angle is a fundamental determinant of plant form. In their later development, lateral branches maintain gravitropic setpoint angles (GSAs) in which growth is set and maintained relative to gravity. The typically non-vertical GSAs are the product of an auxin-dependent antigravitropic offset that counteracts underlying gravitropic response in the branch (Roychoudhryet al., 2013). Here we describe an earlier phase of branch development in which the young lateral shoot grows rootward, independently of gravity, promoting a spreading growth habit. In normal development, this phase of growth is terminated with the onset of the GSA programme, with branches then growing upwards to assume their mature form. The biophysical basis of the early rootward phase of branch growth can be traced back to greater cell proliferation on the upper, adaxial side that upon expansion, drives asymmetric growth. Our data indicate that cytokinin is involved in this process and that the transcription factor TCP1 is an important regulator of lateral shoot adaxial identity and differential ad-abaxial cell proliferation.
Changes in Protein Turn-over rates Regulate Tryptophan and Glucosinolate Biosynthesis, IAA Transport and Photosynthesis inArabidopsisGrowth and Defense Transitions
Authors: Abukhalaf Mohammad , Proksch Carsten , Thieme Domenika , Ziegler Jörg , Hoehenwarter Wolfgang 
Published: April 2023

AbstractAn organism continuously experiences shifts in biological states necessitating extensive rearrangement of physiology and molecular order of the cell. Here we model transitions between optimal growth conditions (homeostasis), fully induced pattern triggered immunity (PTI) and back inArabidopsis thaliana, chronologically measuring changes in protein synthesis and degradation rates, transcript, protein and phytohormone abundance of 99 targets using qPCR and LC-MS parallel reaction monitoring (PRM). Temporally changing synthesis and degradation rates were primary determinants of abundance, next to changes in mRNA levels, of tryptophan, glucosinolate (GS) biosynthesis and photosynthesis associated (PAP) proteins particularly in the earlier establisher phases but also in fully induced PTI. While transcripts returned to growth levels 3 to 16 hours post elicitation, protein levels remained at fully induced PTI levels up to 16 hours into the transitory phase back to optimal growth. A notable exception were polar auxin transporters PIN3 and PIN7 levels which decreased in PTI but quickly returned to initial homeostasis levels after transition, although global auxin levels only decreased by 20%. Tryptophan, GS and JA biosynthesis proteins all increased in abundance in the wild type and themyc234mutant background linking induction of the tryptophan and GS biosynthesis pathways to flg22 treatment and PTI independent of MYC2 and homologs. PAPs abundance was depleted in fully induced PTI however not in themyc234mutant linking this active immune response to these bHLH transcription factors. FERREDOXIN-NADP(+)-OXIDOREDUCTASE (FNR1) synthesis rates decreased while its degradation rate increased in the earlier PTI establisher phase. FNR1 is the penultimate protein in the photosynthetic electron transfer chain and imparts electrons onto NADP+however in its absence electrons are used for oxygen photoreduction and H2O2production, an active defense compound. Thus FNR1 may be a molecular switch that switches photosystem activity between growth and defense under post-transcriptional control. Themyc234mutation generally led to delayed changes in transcript and protein abundance and also abolished IAA depletion. Protein turn-over rates of a set of PAPs were affected in the mutant suggesting a possible positive role of the transcription factors in controlling post-transcriptional regulatory processes in PTI induction.
The small mycobacterial ribosomal protein, bS22, modulates aminoglycoside accessibility to its 16S rRNA helix-44 binding site
Authors: Majumdar Soneya , Deep Ayush , Sharma Manjuli R. , Canestrari Jill , Stone Melissa , Smith Carol , Koripella Ravi K. , Keshavan Pooja , Banavali Nilesh K. , Wade Joseph T. , Gray Todd A. , Derbyshire Keith M. , Agrawal Rajendra K. 
Published: April 2023

AbstractTreatment of tuberculosis continues to be challenging due to the widespread latent form of the disease and the emergence of antibiotic-resistant strains of the pathogen,Mycobacterium tuberculosis. Bacterial ribosomes are a common and effective target for antibiotics. Several second line anti-tuberculosis drugs, e.g. kanamycin, amikacin, and capreomycin, target ribosomal RNA to inhibit protein synthesis. However,M. tuberculosiscan acquire resistance to these drugs, emphasizing the need to identify new drug targets. Previous cryo-EM structures of theM. tuberculosisandM. smegmatisribosomes identified two novel ribosomal proteins, bS22 and bL37, in the vicinity of two crucial drug-binding sites: the mRNA-decoding center on the small (30S), and the peptidyl-transferase center on the large (50S) ribosomal subunits, respectively. The functional significance of these two small proteins is unknown. In this study, we observe that anM. smegmatisstrain lacking thebs22gene shows enhanced susceptibility to kanamycin compared to the wild-type strain. Cryo-EM structures of the ribosomes lacking bS22 in the presence and absence of kanamycin suggest a direct role of bS22 in modulating the 16S rRNA kanamycin-binding site. Our structures suggest that amino-acid residue Lys-16 of bS22 interacts directly with the phosphate backbone of helix 44 of 16S rRNA to influence the micro-configuration of the kanamycin-binding pocket. Our analysis shows that similar interactions occur between eukaryotic homologues of bS22, and their corresponding rRNAs, pointing to a common mechanism of aminoglycoside resistance in higher organisms.
Integrated Phenomics and Genomics reveals genetic loci associated with inflorescence growth inBrassica napus
Authors: Williams Kevin , Hepworth Jo , Nichols Bethany S , Corke Fiona , Woolfenden Hugh , Paajanen Pirita , Steuernagel Burkhard , Østergaard Lars , Morris Richard J , Doonan John H , Wells Rachel 
Published: April 2023

AbstractA fundamental challenge to the production of climate-resilient crops is how to measure dynamic yield-relevant responses to the environment, such as growth rate, at a scale which informs mechanistic understanding and accelerates breeding. The timing, duration and architectural characteristics of inflorescence growth are crucial for optimising crop productivity and have been targets of selection during domestication. We report a robust and versatile procedure for computationally assessing environmentally-responsive flowering dynamics. In the oilseed crop,Brassica napus,there is wide variation in flowering response to winter cold (vernalization). We subjected a diverse set ofB. napusaccessions to different vernalization temperatures and monitored shoot responses using automated image acquisition. We developed methods to computationally infer multiple aspects of flowering from this dynamic data, enabling characterisation of speed, duration and peaks of inflorescence development across different crop types. We input these multiple traits to genome- and transcriptome-wide association studies, and identified potentially causative variation ina prioriphenology genes (includingEARLY FLOWERING3)for known traits and in uncharacterised genes for computed traits. These results could be used in marker assisted breeding to design new ideotypes for improved yield and better adaptation to changing climatic conditions.
The structure of the neurotoxin palytoxin determined by MicroED
Authors: Gillman Cody , Patel Khushboo , Unge Johan , Gonen Tamir 
Published: April 2023

AbstractPalytoxin (PTX) is a potent neurotoxin found in marine animals that can cause serious symptoms such as muscle contractions, haemolysis of red blood cells and potassium leakage. Despite years of research, very little is known about the mechanism of PTX. However, recent advances in the field of cryoEM, specifically the use of microcrystal electron diffraction (MicroED), have allowed us to determine the structure of PTX. It was discovered that PTX folds into a hairpin motif and is able to bind to the extracellular gate of Na,K-ATPase, which is responsible for maintaining the electrochemical gradient across the plasma membrane. These findings, along with molecular docking simulations, have provided important insights into the mechanism of PTX and can potentially aid in the development of molecular agents for treating cases of PTX exposure.
DNA sequence context and the chromatin landscape differentiate sequence-specific transcription factor binding in the human malaria parasite,Plasmodium falciparum
Authors: Bonnell Victoria A. , Zhang Yuning , Brown Alan S. , Horton John , Josling Gabrielle A. , Chiu Tsu-Pei , Rohs Remo , Mahony Shaun , Gordân Raluca , Llinás Manuel 
Published: April 2023

AbstractDevelopment of the human malaria parasite,Plasmodium falciparum,is regulated by a limited number of sequence-specific transcription factors (TFs). However, the mechanisms by which these TFs recognize genome-wide binding sites is still largely unknown. To address TF specificity, we investigated the binding of two TF subsets that either bind CACACA or GTGCAC DNA sequence motifs and further characterized PfAP2-G and PfAP2-EXP which bind unique DNA motifs (GTAC and TGCATGCA). We interrogated the impact of DNA sequence and chromatin context onP. falciparumTF binding by integrating high-throughputin vitroandin vivobinding assays, DNA shape predictions, epigenetic post-translational modifications, and chromatin accessibility. We determined that DNA sequence context minimally impacts binding site selection for CACACA-binding TFs, while chromatin accessibility, epigenetic patterns, co-factor recruitment, and dimerization contribute to differential binding. In contrast, GTGCAC-binding TFs prefer different DNA sequence context in addition to chromatin dynamics. Finally, we find that TFs that preferentially bind divergent DNA motifs may bind overlapping genomic regionsin vivodue to low-affinity binding to other sequence motifs. Our results demonstrate that TF binding site selection relies on a combination of DNA sequence and chromatin features, thereby contributing to the complexity ofP. falciparumgene regulatory mechanisms.Key PointsSequence and chromatin context determine differential DNA-binding specificity ofP. falciparumTFsTFs with paralogous DNA-binding domains inP. falciparumare not functionally redundantTFs with differing sequence-specificity can co-occupy sites through low-affinity DNA interactions
A broad-spectrum α-glucosidase of glycoside hydrolase family 13 fromMarinovumsp., a member of theRoseobacterclade
Authors: Li Jinling , Mui Janice W.-Y. , da Silva Bruna M. , Pires Douglas E.V. , Ascher David B. , Soler Niccolay Madiedo , Goddard-Borger Ethan D. , Williams Spencer J. 
Published: April 2023

AbstractGlycoside hydrolases (GHs) are a diverse group of enzymes that catalyze the hydrolysis of glycosidic bonds. The Carbohydrate-Active enZymes (CAZy) classification organizes GHs into families based on sequence data and function, with fewer than 1% of the predicted proteins characterized biochemically. Consideration of genomic context can provide clues to infer possible enzyme activities for proteins of unknown function. We used the MultiGeneBLAST tool to discover a gene cluster inMarinovumsp., a member of the marineRoseobacterclade, that encodes homologues of enzymes belonging to the sulfoquinovose monooxygenase pathway for sulfosugar catabolism. This cluster lacks a gene encoding a classical family GH31 sulfoquinovosidase candidate, but which instead includes an uncharacterized family GH13 protein (MsGH13) that we hypothesized could be a non-classical sulfoquinovosidase. Surprisingly, recombinantMsGH13 lacks sulfoquinovosidase activity and is a broad spectrum α-glucosidase that is active on a diverse array of α-linked disaccharides, including: maltose, sucrose, nigerose, trehalose, isomaltose, and kojibiose. Using AlphaFold, a 3D model for theMsGH13 enzyme was constructed that predicted its active site shared close similarity with an α-glucosidase fromHalomonassp. H11 of the same GH13 subfamily that shows narrower substrate specificity.
Deep Learning for Flexible and Site-Specific Protein Docking and Design
Authors: McPartlon Matt , Xu Jinbo 
Published: April 2023

AbstractProtein complexes are vital to many biological processes and their understanding can lead to the development of new drugs and therapies. Although the structure of individual protein chains can now be predicted with high accuracy, determining the three-dimensional structure of a complex remains a challenge. Protein docking, the task of computationally determining the structure of a protein complex given the unbound structures of its components (and optionally binding site information), provides a way to predict protein complex structure. Traditional docking methods rely on empirical scoring functions and rigid body simulations to predict the binding poses of two or more proteins. However, they often make unrealistic assumptions about input structures, and are not effective at accommodating conformational flexibility or binding site information. In this work, we present DockGPT (Generative Protein Transformer for Docking), an end-to-end deep learning method for flexible and site-specific protein docking that allows conformational flexibility and can effectively make use of binding site information. Tested on multiple benchmarks with unbound and predicted monomer structures as input, we significantly outperform existing methods in both accuracy and running time. Our performance is especially pronounced for antibody-antigen complexes, where we predict binding poses with high accuracy even in the absence of binding site information. Finally, we highlight our method’s generality by extending it to simultaneously dock and co-design the sequence and structure of antibody complementarity determining regions targeting a specified epitope.
Motility-Induced Phase Separation Mediated by Bacterial Quorum Sensing
Authors: Ridgway Wesley J. M. , Dalwadi Mohit P. , Pearce Philip , Chapman S. Jonathan 
Published: April 2023

AbstractWe study motility-induced phase separation (MIPS) in living active matter, in which cells interact through chemical signalling, or quorum sensing. In contrast to previous theories of MIPS, our multiscale continuum model accounts explicitly for genetic regulation of signal production and motility. Through analysis and simulations, we derive a new criterion for the onset of MIPS that depends on features of the genetic network. Furthermore, we identify and characterise a new type of oscillatory instability that occurs when gene regulation inside cells promotes motility in higher signal concentrations.
Identification and prediction of G-quadruplex RNA-binding proteins with roles in transcription and phase separation
Authors: Luige Johanna , Armaos Alexandros , Tartaglia Gian Gaetano , Vang Ørom Ulf Andersson 
Published: April 2023

AbstractRNA-binding proteins are central for many biological processes and their large-scale identification has demonstrated a broad range of functions. RNA G-quadruplexes are important regulatory elements occurring in both coding and non-coding transcripts, yet our knowledge of their structure-based interactions is limited. Here starting from theoretical prediictions, we show experimentally that a large number of chromatin-binding proteins bind to RNA G-quadruplexes and we classify these based on their RNA G-quadruplex-binding potential. Combining experimental identification of nuclear RNA G-quadruplex-binding proteins with computational analysis, we create a prediction tool that can assign probability score for a protein that it binds RNA G-quadruplexes. We show that predicted G-quadruplex RNA-binding proteins exhibit high degree of protein disorder and hydrophilicity, and suggest involvement in both transcription and phase-separation into membrane-less organelles, particularly the nucleolus. Finally, we present this tool as a web application for estimating RNA G4-binding propensity for proteins of interest athttp://service.tartaglialab.com/new_submission/clever_G4_classifier.
The carboxyl-terminal sequence of PUMA binds to both anti-apoptotic proteins and membranes
Authors: Pemberton James M. , Nguyen Dang , Osterlund Elizabeth J. , Schormann Wiebke , Pogmore Justin P. , Hirmiz Nehad , Leber Brian , Andrews David W. 
Published: April 2023

AbstractAnti-apoptotic proteins such as BCL-XLpromote cell survival by sequestering pro-apoptotic BCL-2 family members, an activity that frequently contributes to tumorigenesis. Thus, the development of small-molecule inhibitors for anti-apoptotic proteins, termed BH3-mimetics, is revolutionizing how we treat cancer. BH3 mimetics kill cells by displacing sequestered pro-apoptotic proteins to initiate tumor-cell death. Recent evidence has demonstrated that in live cells the BH3-only proteins PUMA and BIM resist displacement by BH3-mimetics, while others like tBID do not. Analysis of the molecular mechanism by which PUMA resists BH3-mimetic mediated displacement from full-length anti-apoptotic proteins (BCL-XL, BCL-2, BCL-W and MCL-1) reveals that both the BH3-motif and a novel binding site within the carboxyl-terminal sequence (CTS) of PUMA contribute to binding. Together these sequences bind to anti-apoptotic proteins, which effectively “double-bolt locks” the proteins to resist BH3-mimetic displacement. The pro-apoptotic protein BIM has also been shown to double-bolt lock to anti-apoptotic proteins however, the novel binding sequence in PUMA is unrelated to that in the CTS of BIM and functions independent of PUMA binding to membranes. Moreover, contrary to previous reports, we find that when exogenously expressed, the CTS of PUMA directs the protein primarily to the endoplasmic reticulum (ER) rather than mitochondria and that residues I175 and P180 within the CTS are required for both ER localization and BH3-mimetic resistance. Understanding how PUMA resists BH3-mimetic displacement will be useful in designing more efficacious small-molecule inhibitors of anti-apoptotic BCL-2 proteins.
Reviewing the critical challenges that influence the adoption of the e-learning system in higher educational institutions in the era of the COVID-19 pandemic
Authors: Abdelfattah Fadi , Al Alawi Abrar Mohammed , Dahleez Khalid Abed , El Saleh Ayman 
Published: April 2023

PurposeThis paper aims to review the critical challenges and factors influencing the successful adoption of electronic learning (e-learning) systems in higher educational institutions before and during the current propagation of the coronavirus disease 2019 (COVID-19) pandemic.Design/methodology/approachThis study undertook a literature review concerning the in-depth revision of previous studies published in 2020 and 2021. A total of 100 out of 170 selected research papers were adopted to identify and recognise the factors restricting the application of e-learning systems.FindingsThe findings determine and illuminate the most challenging factors that impact the successful application of online learning, particularly during the wide propagation of the COVID-19 pandemic. The review of the literature provides evidence that technological, organisational and behavioural issues constitute significant drivers that frontier the facilitation of the e-learning process in higher educational institutions.Practical implicationsThe current paper suggests a guide for managers and scholars in educational institutions and acts as a roadmap for practitioners and academics in the educational field and policymakers as this research spotlights the significant factors challenging the e-learning process before and during the pandemic crisis.Originality/valueThe provided in-depth literature review in this research will support the researchers and system designers with a comprehensive review and recent studies conducted before and during the COVID-19 pandemic considering the factors limiting the e-learning process. This paper formulates a valuable contribution to the body of knowledge that will assist the stakeholders in the higher educational institutions' context.Peer reviewThe peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-02-2022-0085.
The funding effect on citation and social attention: the UN Sustainable Development Goals (SDGs) as a case study
Authors: Dorta-González Pablo , Dorta-González María Isabel 
Published: April 2023

PurposeAcademic citation and social attention measure different dimensions in the impact of research results. The authors quantify the contribution of funding to both indicators considering the differences attributable to the research field and access type.Design/methodology/approachCitation and social attention accumulated until the year 2021 of more than 367 thousand research articles published in the year 2018 are studied. The authors consider funding acknowledgments (FAs) in the research articles. The data source is Dimensions, and the units of study are research articles in the United Nation (UN) Sustainable Development Goals (SDGs).FindingsMost cited goals by researchers do not coincide with those that arouse greater social attention. A small proportion of articles accumulates a large part of the citations and most of the social attention. Both citation and social attention grow with funding. Thus, funded research has a greater probability of being cited in academic articles and mentioned in social media. Funded research receives on average two to three times more citations and 2.5 to 4.5 times more social attention than unfunded research. Moreover, the open access (OA) modalities gold and hybrid have the greatest advantages in citation and social attention due to funding.Research limitations/implicationsSpecific topics were studied in a specific period. Studying other topics and/or different time periods might result in different findings.Practical implicationsWhen funding to publish in open or hybrid access journals is not available, it is advisable to self-archiving the pre-print or post-print version in a freely accessible repository.Social implicationsAlthough cautiously, it is also advisable to consider the social impact of the research to complement the scientific impact in the evaluation of the research.Originality/valueThe joint evaluation of the effect of both funding and OA on social attention.