bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inexperienced bumble bees are poor at securely landing regardless of flower orientation or presence of labellum
Authors: McWaters S.R. , Popp S. , Rivera M. D. , Mendoza F. , Dornhaus A. 
Published: July 2024

AbstractThe mutualism between bees and flowers creates strong selection on both the structure of the flower and behavior of the bee to maximize pollination and foraging success, respectively. Previous research has primarily assessed the costs of foraging by quantifying the time and accuracy of search, and handling time of the flower. However, there is little attention given to the actual success of landing, and it is often not explicitly stated whether failed landing attempts are taken into consideration. We show here that landing attempts often are unsuccessful, especially in inexperienced bees. Orientation of artificial flowers in our experiment neither influenced the preference nor landing success of a naive bumble bee forager. The presence of a labellum, often considered to serve as a landing platform, also did not influence landing success, indicating that it may mostly play a role in flower recognition or act as a nectar guide. Failed landing attempts may thus play an under-recognized role in the foraging efficiency and behavior of bees, and learning may be key in individual bee landing efficiency, not just flower recognition. Further research should aim to quantify the costs of landing failures and consider the role of experience in individual bee landing success.
Mortality, morbidity, and post-operative complications of typhoid intestinal perforations: global systematic review and meta-analysis
Authors: Hagedoorn Nienke N. , Birkhold Megan , Murthy Shruti , Rathan Meera D. , Marchello Christian S. , Crump John A. 
Published: July 2024

STRUCTURED ABSTRACTObjectiveWe aimed to review global studies reporting on mortality, morbidity, and post-operative complications in patients with typhoid intestinal perforation (TIP).Summary Background DataTIP is a serious and life-threatening complication of typhoid fever that requires emergency surgery and an important driver of typhoid burden.MethodsWe searched multiple databases for articles reporting case-fatality ratio (CFR) or complications in patients with TIP undergoing surgery published from 1980 through 30 January 2024. We described the prevalence of each reported complication. Of patients with TIP, we pooled CFR using random-effects meta-analysis and stratified by United Nations region, sex, and number of perforations per patient.ResultsWe included 46 articles reporting on 4,317 patients with TIP. The most prevalent post-operative complications were wound or surgical site infection in 1,537 (50.7%) of 3,030 patients, wound dehiscence in 308 (16.1%) of 1,909, and chest infection in 136 (15.6%) of 872. Overall, the pooled CFR (95%CI) of patients with TIP was 15.6% (12.5-18.9%), and was 20.5% (17.1-23.9%) in 30 observations from the African region, 5.7% (2.6-9.6%) in 15 observations from the Asian region, and 12.2% (0.90-30.4%) in three observations from the Americas. The Pearson’s correlation coefficient of median year of data collection and CFR was -0.01 (p=0.95) for Africa and -0.69 (p <0.01) for Asia.ConclusionsDisability and death associated with TIP remains substantial. Efforts to reduce the occurrence of TIP through typhoid prevention with vaccine and non-vaccine measures, and increased access to and quality of surgical services for those with TIP are warranted.
Phospholipase Cγ regulates lacrimal gland branching by competing with PI3K in phosphoinositide metabolism
Authors: Wang Qian , Tao Chenqi , Wu Yihua , Anderson Karen E. , Hannan Abdul , Lin Chyuan-sheng , Hawkins Phillip , Stephens Len , Zhang Xin 
Published: July 2024

AbstractAlthough the regulation of branching morphogenesis by spatially distributed cues is well established, the role of intracellular signaling in determining the branching pattern remains poorly understood. In this study, we investigated the regulation and function of phospholipase C gamma (PLCγ) in Fibroblast Growth Factor (FGF) signaling in lacrimal gland development. We showed that deletion ofPLCγ1in the lacrimal gland epithelium leads to ectopic branching and acinar hyperplasia, which was phenocopied by either mutating the PLCγ1 binding site on Fgfr2 or disabling any of its SH2 domains.PLCγ1inactivation did not change the level of Fgfr2 or affect MAPK signaling, but instead led to sustained AKT phosphorylation due to increased PIP3 production. Consistent with this,PLCγ1mutant phenotype can be reproduced by elevation of PI3K signaling inPtenknockout and attenuated by blocking AKT signaling. This study demonstrated that PLCγ modulates PI3K signaling by shifting phosphoinositide metabolism, revealing an important role of signaling dynamics in conjunction with spatial cues in shaping branching morphogenesis.
An Atlas of Protein Phosphorylation Dynamics During Interferon Signaling
Authors: Busnadiego Idoia , Lork Marie , Fernbach Sonja , Schiefer Samira , Tsolakos Nikos , Hale Benjamin G. 
Published: July 2024

AbstractInterferons (IFNs, types I-III) have pleiotropic functions in promoting antiviral and anti-tumor responses, as well as in modulating inflammation. Dissecting the signaling mechanisms elicited by different IFNs is therefore critical to understand their phenotypes. Here, we use mass spectrometry to investigate the early temporal dynamics of cellular protein phosphorylation in response to stimulation with IFNα2, IFNβ, IFNω, IFNγ, and IFNλ1, representing all IFN types. We report an atlas of over 700 common or unique phosphorylation events reprogrammed by these IFNs, revealing both previously known and uncharacterized modifications. Functional screening and mechanistic studies identify that several factors differentially-modified in response to IFNs contribute to host antiviral responses, either directly or by supporting IFN-stimulated gene or protein production. Among these, phosphorylation of PLEKHG3 at serine-1081 creates a phospho-regulated binding motif for the docking of 14-3-3 proteins, and together these factors contribute to coordinating efficient IFN-stimulated gene expression independent of early JAK/STAT signaling. Our findings map the global phosphorylation landscapes regulated by IFN types I, II, and III, and provide a key resource to explore their functional consequences.
Glial voltage-gated K+channels modulate the neural abiotic stress tolerance ofDrosophila melanogaster
Authors: Andersen Mads Kuhlmann , Livingston Dawson B. H. , Robertson R. Meldrum , MacMillan Heath A. 
Published: July 2024

AbstractSevere abiotic stress causes insects to lose nervous function and enter a state of paralytic coma. Central to this loss of function is a spreading depolarization (SD), where a characteristic collapse of ion gradients depolarizes neuronal and glial membranes and rapidly shuts down the CNS. Despite representing a critical limit to CNS function, the stress threshold that elicits SD can be altered by the process of acclimation, though the mechanisms underlying this response remain largely unknown. Here, we made electrophysiological measurements of SD and investigated the role of K+channels in acclimation of the CNS stress response ofDrosophila melanogaster. First, we demonstrate that improved cold tolerance in the CNS elicited by cold acclimation was abolished by pharmacological blockade of K+channels with voltage-gated K+channels representing most of this effect. Next, we used the UAS/Gal4 model system to screen for candidate genes encoding glial voltage-gated K+channels and found that knockdown ofsei- andShaw-encoded channels mimicked the effect of K+blockade in cold-acclimated flies. Furthermore we show that the knockdown of glialsei-encoded channels also impair tolerance to anoxia and heat stress. These findings suggest that voltage-gated K+channels, especially those encoded bysei, are integral to the CNS stress- and acclimation-response and we posit that this is elicited through mechanisms involving glial spatial buffering and barrier function. Establishing such causal links between tissue-specific expression of candidate genes and SD mechanisms will inevitably aid our understanding of insect ecophysiology and SD-related neuropathologies.New and NoteworthyUsing thermal acclimation and pharmacology, we demonstrate that voltage-gated K+channels are involved in setting the threshold for cold-induced spreading depolarization (SD) in theDrosophila melanogasterCNS. Glial knockdown of channels encoded byseiandShawreduced the resistance to cold-induced SD, highlighting their importance in acclimation of the CNS. Glia-specificsei-knockdown also reduced tolerance to anoxia and heat. We posit thatsei-channels are involved the CNS stress- and acclimation-responses through glial spatial buffering mechanisms.
Dynamic regions allosterically connect the USP14 active site with the proteasome interaction surface
Authors: Salomonsson Johannes , Sjöstrand Linda , Eskilson Arvid , Derbyshire Dean , D’Arcy Pádraig , Sunnerhagen Maria , Ahlner Alexandra 
Published: July 2024

AbstractUbiquitin-specificprotease 14 (USP14), is a member of the USP family responsible for the catalytic removal of ubiquitin (Ub) from proteins directed to the proteasome, implicated in the pathogenesis of neurodegeneration and cancer. Crystallography and cryo-EM analysis have identified loop regions crucial for the deubiquitinase activity of USP14, specifically those involved in Ub and proteasome binding. However, the structural changes in USP14 upon ligand binding to these regions are minimal, indicating significant yet uncharacterized dynamic contributions to its function. In this study, through structural and dynamical NMR experiments and functional evaluation, we demonstrate that small mutations designed to impact Ub binding and catalytic activity without disturbing the USP structure display both local and long-range effects. The affected residues connect the active site and the Ub binding region with the proteasome interaction surface through a network of loops, which show varied dynamics on the ps-ms time scale. Collectively, our findings experimentally reveal different aspects of dynamic connections within USP14, suggesting the presence of allosteric networks that link enzyme activity with regulatory function. The novel concept that USP14 allosteric networks are pre-existing, coupled, and activated by regulatory interactions with the USP fold, could be crucial to future targeted drug design.
Berberine Bridge enzyme-like oxidases orchestrate homeostatic control and signaling of oligogalacturonides in defense and wounding
Authors: Salvati Ascenzo , Diomaiuti Alessandra , Locci Federica , Gravino Matteo , Gramegna Giovanna , Ilyas Muhammad , Benedetti Manuel , Costantini Sara , De Caroli Monica , Castel Baptiste , Jones Jonathan D. G. , Cervone Felice , Pontiggia Daniela , De Lorenzo Giulia 
Published: July 2024

ABSTRACTPlant immunity is triggered by endogenous elicitors known as damage-associated molecular patterns (DAMPs). Oligogalacturonides (OGs) are DAMPs released from the cell wall (CW) demethylated homogalacturonan during microbial colonization, mechanical or pest-provoked tissue damage, and physiological CW remodeling. Berberine Bridge Enzyme-like (BBE-l) proteins named OG oxidases (OGOXs) have been proposed to govern OGs homeostasis, which is necessary to avoid deleterious growth-affecting hyper-immunity and possible cell death. Using OGOX1 over-expressing lines andogox1/2double mutants, we show that these enzymes determine the levels of active OGs vs. inactive oxidized products (oxOGs). Theogox1/2-deficient plants have elevated levels of OGs, while plants overexpressing OGOX1 accumulate oxOGs. The balance between OGs and oxOGs affect disease resistance againstPseudomonas syringae pv tomato,Pectobacterium carotovorum,andBotrytis cinereadepending on the microbial capacity to respond to OGs and metabolize oxOGs. Gene expression upon plant infiltration with OGs reveals that OGOXs orchestrate OG signaling in defense as well as upon tissue damage, pointing to these enzymes as apoplastic players in immunity and tissue repair.TeaserOxidases control the homeostasis of oligogalacturonides in the cell wall and play a pivotal role in the plant immunity.
Iron deprivation activates aboveground cell wall biosynthesis inPopulusand the role of PtrbHLH011
Authors: Tadesse Dimiru , Dai Yuqiu , Yang Lin , Yang Yang , Dwivedi Nidhi , Kumaran Desigan , Blaby-Haas Crysten E. , Lipzen Anna , Santiago Kassandra , Barry Kerrie , Liu Chang-Jun , Xie Meng 
Published: July 2024

AbstractLack of mechanistic understanding of the environmental plasticity of secondary cell wall (SCW) biosynthesis hinders the massive bioenergy production on marginal lands. Growing bioenergy crops on marginal lands is appealing to minimize competition for arable land. However, abiotic stresses, particularly iron deficiency stress, are widespread to perturb SCW biosynthesis. In poplar, a major bioenergy crop, we demonstrated that iron deprivation activates stem SCW biosynthesis and identified transcription factor PtrbHLH011 as a possible underlying regulator. PtrbHLH011 is a potent repressor of SCW, whose overexpression resulted in a reduction of stem SCW by over 65%. Our genomic and molecular studies discovered that PtrbHLH011 binds to the AAAGACA sequence and represses essential genes for SCW biosynthesis, flavonoid biosynthesis, and iron homeostasis. Wood formation and iron deprivation downregulates PtrbHLH011 to release the transcriptional repression. Our findings reveal a regulatory mechanism coordinating SCW biosynthesis in response to environmental iron availability and suggest that PtrbHLH011 manipulation may help engineer bioenergy crops with improved performance under marginal conditions.
Maloja: simple and scalable Snakemake workflow orchestration in the cloud
Authors: Giustizia Joseph , Hodgson Wilson , Andress Cameron , Bilkhu Satpal , Macklin James A , Kess Tony 
Published: July 2024

AbstractAs sequencing technologies have matured, bioinformatics tasks have become more complex, computationally demanding, and data intensive. Workflow management software has been developed to aid in simplifying the replicable chaining of complex bioinformatics jobs, and cloud computing has emerged as a potential solution to the computational demands of this work. However, the capacity to effectively deploy these resources is limited by the expertise required to implement these solutions. Here, we develop Maloja, an easily deployed cloud workflow orchestrator. This tool interprets existing scientific workflows written in Snakemake and deploys them in appropriately scaled AWS cloud resources. We test the utility of this new toolset using previously published and custom built Snakemake workflows for ecological genomics tasks, revealing how this tool can facilitate the use of cloud resources without prior cloud architecture expertise.
Rational Design of Frontline Institutional Phage Cocktail for the Treatment of NosocomialEnterobacter cloacaeComplex Infections
Authors: Subedi Dinesh , Gordillo Altamirano Fernando , Deehan Rylee , Perera Avindya , Patwa Ruzeen , Kostoulias Xenia , Korneev Denis , Blakeway Luke , Macesic Nenad , Peleg Anton Y , Barr Jeremy J 
Published: July 2024

AbstractPhage therapy is a promising strategy to treat antimicrobial-resistant infections. Currently, phage therapy applications span personalised treatments that are tailored for a given patient’s infection, through to the use of pre-established cocktails of virulent phages against clinically relevant pathogens. However, both approaches face challenges, with personalised phage therapy being time-consuming and requiring a phage match to a patient’s infection, while phage cocktails may not be effective against a patient’s specific strain. The Alfred Hospital in Melbourne, Australia has reported an ongoing outbreak of infections by theEnterobacter cloacaecomplex (ECC), a group of emerging multidrug-resistant pathogens responsible for considerable morbidity and mortality. Utilising the hospital’s strain collection, built over the last decade, we established an initial three-phage product with 54% ECC coverage that effectively reduced bacterial loads (>99%) in septicaemic mice. We then iteratively improved this product by enhancing phage killing efficiency using phage training and expanded host range through targeted phage isolation against low-coverage ECC strains. This iterative optimisation led to the creation of the productEntelli-02, containing five well characterised virulent phages that target clinical ECC strains through distinct bacterial cell surface receptors. Importantly,Entelli-02exhibits broad host coverage (99%) and efficacy (92%) against The Alfred Hospital’s ECC strain collection (n= 156). We produced this as a therapeutic-grade product, verified and endotoxin unit compliant, ready for use. This approach integrated academic phage research with clinical insights to produce the phage productEntelli-02as an institution-specific phage cocktail with frontline efficacy and on-demand availability.SUMMARYIn briefWe developed a phage product containing five phages with frontline potential to address infections caused by multidrug-resistantEnterobacter cloacaecomplex.
OPUS-TOMO: Deep Learning Framework for Structural Heterogeneity Analysis in Cryo-electron Tomography
Authors: Luo Zhenwei , Wang Qinghua , Ma Jianpeng 
Published: July 2024

AbstractStructural heterogeneity due to the dynamic nature of macromoleculesin situpresents a significant challenge to structural determination by cryo-electron tomography (cryo-ET). In this paper, we present OPUS-TOMO, a deep learning framework for analyzing structural heterogeneity in cryo-ET data. The method adopts a convolutional Encoder-Decoder architecture that adeptly maps real-space subtomograms onto a smooth low-dimensional latent space, which captures the complete landscape of compositional and conformational variations of macromolecules in cryo-ET data. OPUS-TOMO also incorporates algorithms, including a per-particle 3D CTF model and a pose correction network, specifically for handling cryo-ET data. Applications of OPUS-TOMO to multiple real cryo-ET datasets confirm the outstanding capacities of the new method in characterizing structural heterogeneity. The software is available athttps://github.com/alncat/opusTOMO.
Glutathione Oxidation in Cerebrospinal Fluid as a Biomarker of Oxidative Stress in Amyotrophic Lateral Sclerosis
Authors: Pham Trong Khoa , Verber Nick , Turner Martin R , Malaspina Andrea , Collins Mark O. , Mead Richard J. , Shaw Pamela J. 
Published: July 2024

AbstractBackgroundOxidative stress is a key feature of several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). Identification of reliable biomarkers of oxidative stress would be beneficial for drug-target engagement studies.MethodsWe performed unbiased quantitative mass spectrometry (MS)-based analysis to measure changes in protein abundance and oxidation in cerebrospinal fluid (CSF) from a cohort of ALS patients and healthy controls at two time points (approximately four months apart) to capture disease progression. In addition, we developed a sensitive and targeted quantitative MS method to measure glutathione oxidation state in the same sets of CSF samples.ResultsProteomic analysis of CSF revealed statistically significant changes in the abundance of several proteins, including CHIT1, CHI3L1, CHI3L2 and COL18A1 in ALS patients compared to healthy controls at both time points. Several sites of protein oxidation were significantly altered in ALS compared to healthy controls, and total levels of reversible protein oxidation were elevated in ALS patients. Given that glutathione oxidation could be a useful biomarker of oxidative stress, we also measured glutathione and its oxidation state in CSF in the same cohorts of samples. Total GSH (tGSH), GSSG levels and the GSSG/GSH ratio were significantly higher in the ALS than in the healthy control group for both time points. For the first visit, fold changes of tGSH, GSSG, and GSSG/GSH ratio in ALS compared to HC were 1.33 (p = 0.0215), 1.54 (p = 0.0041) and 1.80 (p = 0.0454), respectively. For the second visit, these values were 1.50 (p = 0.0143), 2.00 (p = 0.0018) and 2.14 (p = 0.0120), respectively. Furthermore, we found positive correlations between disease duration until the first visit and total glutathione (tGSH), GSSG and GSSG/GSH ratio. Finally, there was a strong positive correlation between the total intensity of reversibly oxidised proteins and the ratio of GSSG/GSH in ALS patients at both visits.ConclusionWe propose that measuring levels of glutathione oxidation in CSF could act as a stratification biomarker to select ALS patients for antioxidant therapy and an approach to monitor the treatment response to therapeutic agents targeting oxidative stress.
Gene body methylation buffers noise in gene expression in plants
Authors: Zastąpiło Jakub , Emmerson Robyn , Mikheeva Liudmila A , Catoni Marco , Bechtold Ulrike , Zabet Nicolae Radu 
Published: July 2024

AbstractNon-genetic variability in gene expression is an inevitable consequence of stochastic nature of processes driving transcription and translation. Largely thought to be deleterious to cell fitness, it is not uniform across the transcriptome. This implies the existence of (molecular) determinants affecting the degree of gene expression variability, although this remain poorly understood in multicellular systems. In this study, we found a link between gene body methylation and noise in gene expression inArabidopsis thaliana. More specifically, genes with high levels of noise show low levels of gene body methylation, while genes with lower level of noise in gene expression show higher level of gene body methylation. Most importantly, loss of CpG methylation in gene bodies lead to a significant number of genes displaying higher noise in gene expression. This could be compensated by low but significant gain of non-CpG methylation at promoters of certain genes. Overall, our results show that gene body methylation has a functional role and specifically controls the noise in gene expression for a large number of genes.