bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olive mill wastewater as a source of by-products promoting plant defense against microbial pathogens
Authors: Salvati Ascenzo , Sciubba Fabio , Diomaiuti Alessandra , Leone Gian Paolo , Pizzichini Daniele , Bellincampi Daniela , Pontiggia Daniela 
Published: June 2024

AbstractOlive oil is a core component of the Mediterranean diet known for its nutritional properties and health benefits. Olive industry is moving to novel extraction systems for higher oil yield and quality and for waste reduction, which is a relevant problem in the process due to its toxicity and high disposal costs. Multi-Phase Decanter (DMF) is a modern two-phase system performed without adding water during the process. Using DMF, a wet by-product indicated as pâté and consisting of the fruit pulp and vegetation water (VW) is recovered. The pâté has a high content of potentially bioactive molecules that may be exploited to promote plant resistance against microbial pathogens. In this work, to identify by/products of biological interest, the VW recovered from the pâté by centrifugation was subjected to fractionation by tangential-flow membrane filtration (TFMF), combining microfiltration (MF) and ultrafiltration (UF). High-resolution NMR spectroscopy indicated the presence of bioactive molecules such as flavonoids, hydroxytyrosol and oleuropein with known antimicrobial activity. High-Performance Anion Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD) was performed to detect the presence of pectic oligosaccharides in the fractions, showing the enrichment, in the UF-concentrate fraction, of oligogalacturonides (OGs), well known for the ability to elicit defense responses and protect plants against pathogen infections.Arabidopsis thalianaplants treated with TFMF fractions displayed induction of defense responses and exhibited resistance against microbial pathogens without adverse effects on growth and fitness. This study shows that pâté by-products can potentially be exploited in agriculture as sustainable plant phyto-protectant.Graphical abstract(image created with BioRender)
Positive feedback between demographic and selective fluctuations can greatly amplify the random fluctuation of population size
Authors: Kim Yuseob 
Published: June 2024

ABSTRACTPopulation sizes fluctuate over time probably due to random variability in the external environment. However, the severity of such fluctuations should depend on the characteristics of a species shaped in its evolutionary history. Previous studies have suggested that species are likely to evolve to minimize demographic fluctuations because an allele causing a smaller variance in offspring number is advantageous. However, this study finds that evolution in the opposite direction, favoring a mutation causing larger fitness fluctuation, occurs in a simple eco-evolutionary model under a randomly changing environment. This requires that (1) the mutant allele is under fluctuating selection within a subset, the field, of the population but neutral in another subset, the refuge, and (2) the field-to-refuge ratio of the carrying capacity is positively correlated to the fitness of the mutant allele. A general condition for the fixation of such a mutation was derived to depend on the relative strengths of demographic and fitness fluctuations and the mutational effect on the carrying capacity. Multi-locus simulations revealed that positive feedback between demography and selection accelerates the sequential fixations of fluctuation-amplifying mutations, leading to a drastic size fluctuation. This study therefore offers an unconventional explanation for large demographic fluctuations.
Leveraging the transient statistics of quantal content to infer neuronal synaptic transmission
Authors: Vahdat Zahra , Gambrell Oliver , Fisch Jonas , Friauf Eckhard , Singh Abhyudai 
Published: June 2024

AbstractQuantal parameters of synapses are fundamental for the temporal dynamics of neurotransmitter release, forming the basis of interneuronal communication. We propose a class of models that capture the stochastic dynamics of quantal content (QC) - the number of SV fusion events per action potential (AP). Considering the probabilistic and time-varying nature of SV docking, undocking, and AP-triggered fusion, we derive anexactstatistical distribution for the QC over time. Analyzing this distribution at steady-state and its associated autocorrelation function, we show that QC fluctuation statistics can be leveraged for inferring key presynaptic parameters, such as the probability of SV fusion (release probability), and SV replenishment at empty docking sites (refilling probability). Our model predictions are tested with electrophysiological data obtained from 50-Hz stimulation of auditory MNTB-LSO synapses in brainstem slices of juvenile mice. Our results show that while synaptic depression can be explained by low and constant refilling/release probabilities, this scenario is inconsistent with the statistics of the electrophysiological data that show a low QC Fano factor and almost uncorrelated successive QCs. Our systematic analysis yields a model that couples a high release probability to a time-varying refilling probability to explain both the synaptic depression and its associated statistical fluctuations. In summary, we provide a general approach that exploits stochastic signatures in QCs to infer neurotransmission-regulating processes that are indistinguishable from just analyzing averaged synaptic responses.
Structural Basis of Differential Gene Expression at eQTLs Loci from High-Resolution Ensemble Models of 3D Single-Cell Chromatin Conformations
Authors: Du Lin , Farooq Hammad , Delafrouz Pourya , Liang Jie 
Published: June 2024

ABSTRACTMotivationTechniques such as high-throughput chromosome conformation capture (Hi-C) have provided a wealth of information on the organization of the nucleus and the genome important for understanding gene expression regulation. Additionally, Genome-Wide Association Studies (GWASs) have uncovered thousands of loci related to complex traits. Expression quantitative trait loci (eQTL) studies have further linked the genetic variants to alteration in expression levels of associated target genes across individuals. However, the functional roles of many eQTLs located in non-coding regions are unclear. Current joint analyses of Hi-C and eQTLs data lack advanced computational tools, limiting what can be learned from these data.ResultIn this work, we developed a computational method for simultaneous analysis of Hi-C and eQTL data. Our method can identify a small set of non-random interactions from all Hi-C interactions. Using these non-random interactions, we reconstruct large ensemble (×105) of high-resolution single-cell 3D chromatin conformations with thorough sampling, which accurately replicate Hi-C measurements. Our results revealed the presence of many-body interactions in chromatin conformation at single-cell level in eQTL locus, offering detailed view into how three-dimensional structures of chromatin form the physical foundation for gene regulation, including how genetic variants of eQTLs affect the expression level of their associated eGenes.Furthermore, our method can deconvolve chromatin heterogeneity and investigate the spatial associations of eQTLs and eGenes at subpopulation level to reveal their regulatory impacts on gene expression. Together, ensemble modeling of thoroughly sampled single cell chromatin conformations from Hi-C, along with eQTL data, helps to decipher how chromatin 3D structures provide the physical basis for gene regulation, expression control, and aid in understanding of the overall structure-function relationships of genome organization.Availability and implementation: It is available athttps://github.com/uic-liang-lab/3DChromFolding-eQTL-Loci
Unraveling biological processes and EGFR pathway regulation by the protein tyrosine phosphatase PTPRH in non-small cell lung cancer
Authors: Ortiz Mylena M. O. , Patel Deeya M. , Swiatnicki Matthew , Andrechek Eran 
Published: June 2024

AbstractThe delicate balance of protein phosphorylation is often disrupted in cancers, with hyperactivity of kinases and inactivation of phosphatases driving cell proliferation and survival pathways. PTPRH, a protein tyrosine phosphatase, is deregulated or mutated in certain cancers, including non-small cell lung cancer (NSCLC). However, the biological processes that PTPRH is involved in and how they may contribute to tumorigenesis are unknown. Previous studies have linked PTPRH to the regulation of the EGFR pathway but the full extension of this regulation and the underlying mechanisms remain to be elucidated. We found that PTPRH knockout tends to increase the phosphorylation levels of EGFR at the tyrosine residue 1173 (1197), whereas overexpression of PTPRH wild-type significantly decreases phosphorylation in one of the NSCLC cell lines. Surprisingly, disruption of the extracellular or intracellular domains of the phosphatase leads to EGFR dephosphorylation in a similar manner. Co-immunoprecipitation and proximity-dependent biotinylation (BioID) experiments demonstrated that PTPRH do not directly interact with EGFR, but rather with CDK5RAP3 and EIF2AK2, two proteins reported to regulate the downstream pathway NF-κB. In addition, BioID revealed 55 novel PTPRH interactors in NSCLC cells, which are enrichedin translation and RNA-associated pathways. Guided by RNA sequencing analysis, we observed that overexpression of the phosphatase downregulates multiple oncogenic signature pathways and modulates the gene expression of 34 protein tyrosine phosphatases and 45 tyrosine kinases, EGFR included. Together, these results shed light on the importance of PTPRH in regulating biological and cellular processes and how its inactivation may support cancer progression.
Mealtime alters daily rhythm in nuclear O-GlcNAcome to regulate hepatic gene expression
Authors: Liu Xianhui , Cai Yao D , Mendiola Aron Judd P. , Xu Xuehan , Luo Yige , Zheng Haiyan , Zhao Caifeng , Chen Ching-Hsuan , Xiang Yang K. , Chiu Joanna 
Published: June 2024

AbstractThe liver circadian clock and hepatic transcriptome are highly responsive to metabolic signals generated from feeding-fasting rhythm. Previous studies have identified a number of nutrient-sensitive signaling pathways that could interpret metabolic input to regulate rhythmic hepatic biology. Here, we investigated the role of O-GlcNAcylation, a nutrient-sensitive post-translational modification (PTM) in mediating metabolic regulation of rhythmic biology in the liver. We observed daily oscillation of global nuclear protein O-GlcNAcylation in the liver of mice subjected to natural nighttime-restricted feeding (NRF). O-GlcNAcomic analysis revealed that 11.54% of 719 O-GlcNAcylated proteins are rhythmically O-GlcNAcylated over a 24-hour day-night cycle. Proteins involved in gene expression were enriched among rhythmically O-GlcNAcylated nuclear proteins, suggesting rhythmic O-GlcNAcylation may directly shape the daily rhythmicity of the hepatic transcriptome. Furthermore, we showed that rhythmic O-GlcNAcylation can also indirectly modulate the hepatic transcriptome by interacting with phosphorylation. Specifically, several proteins harboring O-GlcNAcylation-phosphorylation interplay motif exhibit rhythmic O-GlcNAcylation and phosphorylation. We propose that O-GlcNAcylation may occur at a phospho-degron of a key circadian transcriptional activator, circadian locomotor output cycles kaput (CLOCK), thus regulating its stability and transcriptional output. Finally, we report that unnatural day time-restricted feeding (DRF) dampens O-GlcNAcylation rhythm, suggesting the disruption in liver transcriptomic rhythm previously observed in DRF condition could be mediated by dysregulation of daily protein O-GlcNAcylation rhythm. In summary, our results provide new mechanistic insights into metabolic regulation of daily hepatic transcriptomic rhythm via interplay between O-GlcNAcylation and phosphorylation and shed light on the deleterious effects of improper mealtimes.
Clinical exome sequencing data from patients with inborn errors of immunity: cohort level meta-analysis and the benefit of systematic reanalysis
Authors: Vorsteveld Emil E. , Van der Made Caspar I. , Smeekens Sanne P. , Schuurs-Hoeijmakers Janneke H. , Astuti Galuh , Diepstra Heleen , Gilissen Christian , Hoenselaar Evelien , Janssen Alice , van Roozendaal Kees , Sikkema-van Engelen Jettie , Steyaert Wouter , Weiss Marjan M. , Yntema Helger G. , Mantere Tuomo , AlZahrani Mofareh S. , van Aerde Koen , Derfalvi Beata , Faqeih Eissa Ali , Henriet Stefanie S.V. , van Hoof Elise , Idressi Eman , Issekutz Thomas B. , Jongmans Marjolijn C.J. , Keski-Filppula Riikka , Krapels Ingrid , te Loo Maroeska , Mulders-Manders Catharina M. , ten Oever Jaap , Potjewijd Judith , Sarhan Nora Tarig , Slot Marjan C. , Terhal Paulien A. , Thijs Herman , Vandersteen Anthony , Vanhoutte Els K. , van de Veerdonk Frank , van Well Gijs , Netea Mihai G. , Simons Annet , Hoischen Alexander 
Published: June 2024

AbstractWhile next generation sequencing has expanded the scientific understanding of Inborn Errors of Immunity (IEI), the clinical use of exome sequencing is still emerging. We performed a cohort level meta-analysis by revisiting clinical exome data from 1,300 IEI patients using an updatedin-silicogene panel for IEI. Variants were classified and curated through expert review. The molecular diagnostic yield after standard exome analysis was 11.8%. A systematic reanalysis resulted in the identification of variants of interest in 5.2% of undiagnosed patients, of which 75.4% were (candidate) disease-causing, increasing the molecular diagnostic yield to 15.2%. We find a high degree of actionability in IEI patients with a genetic diagnosis (76.4%). Despite the modest absolute diagnostic gain, these data support the benefit of iterative exome reanalysis in patients with IEI conveying the notion that our current understanding of genes and variants involved in IEI is by far not saturated.
Reconfiguration of the visual code and retinal cell type complement in closely related diurnal and nocturnal mice
Authors: Allen Annette E , Hahn Joshua , Richardson Rose , Pantiru Andreea , Mouland Josh , Baño-Otalora Beatriz , Monavarfeshani Aboozar , Yan Wenjun , Williams Christopher , Wynne Jonathan , Rodgers Jessica , Milosavljevic Nina , Orlowska-Feuer Patrycja , Storchi Riccardo , Sanes Joshua R. , Shekhar Karthik , Lucas Robert J 
Published: June 2024

AbstractHow does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours.Rhabdomys pumilioare diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnalMus musculus. High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals thatRhabdomysattains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.
A Discard-and-Restart MD algorithm for the sampling of realistic protein transition states and enhance structure-based drug discovery
Authors: Ianeselli Alan , Howard Jonathon , Gerstein Mark B. 
Published: June 2024

ABSTRACTWe introduce a Discard-and-Restart molecular dynamics (MD) algorithm tailored for the sampling of realistic protein transition states. It aids computational structure-based drug discovery by reducing the simulation times to compute transition pathways by up to 2000x. The algorithm iteratively performs short MD simulations and measures their proximity to a target state via a collective variable (CV) loss, which can be defined in a flexible fashion, locally or globally. Using the loss, if the trajectory proceeds toward the target, the MD simulation continues. Otherwise, it is discarded and a new MD simulation is restarted, with new initial velocities randomly drawn from a Boltzmann distribution. The discard-and-restart algorithm demonstrates efficacy and atomistic accuracy in capturing the folding pathways in several contexts: (1) fast-folding small protein domains; (2) the folding intermediate of the prion protein PrP; and (3) the spontaneous partial unfolding of α-Tubulin, a crucial event for microtubule severing. During each iteration of the algorithm, we are able to perform AI-based analysis of the transitory conformations to find binding pockets, which could potentially represent druggable sites. Overall, our algorithm enables systematic and computationally efficient exploration of conformational landscapes, enhancing the design of ligands targeting dynamic protein states.
The role of alternative splicing in marine-freshwater divergence in threespine stickleback
Authors: Rodríguez-Ramírez Carlos E. , Peichel Catherine L. 
Published: June 2024

AbstractAlternative splicing (AS) regulates which parts of a gene are kept in the messenger RNA and has long been appreciated as a mechanism to increase the diversity of the proteome within eukaryotic species. There is a growing body of evidence that AS might also play an important role in adaptive evolution. However, the overall contribution of AS to phenotypic evolution and adaptation is still unknown. In this study we asked whether AS played a role in adaptation to divergent marine and freshwater habitats in threespine stickleback (Gasterosteus aculeatus). Using two published gill RNAseq datasets, we identified differentially expressed and differentially spliced genes (DEGs and DSGs) between population pairs of marine-freshwater stickleback in the Northeast Pacific and tested whether they are preferentially found in regions of the genome involved in freshwater-marine divergence. We found over one hundred DSGs, and they were found more often than expected by chance in peaks of genetic divergence and quantitative trait loci (QTL) that underlie phenotypic divergence between ecotypes. The enrichment of DSGs in these regions is similar to the enrichment of DEGs. Furthermore, we find that among the different types of AS, mutually exclusive exon splicing is the most strongly correlated with genetic divergence between ecotypes. Taken together, our results suggests that AS might have played a role in the adaptive divergence of marine and freshwater sticklebacks and that some types of AS might contribute more than others to adaptation.
Polarization gratings aided common-path Hilbert holotomography for high-throughput lipid droplets content assay
Authors: Zdańkowski Piotr , Winnik Julianna , Rogalski Mikołaj , Marzejon Marcin J. , Wdowiak Emilia , Dudka Wioleta , Józwik Michał , Trusiak Maciej 
Published: June 2024

AbstractIn this contribution we present a novel polarization gratings aided common-path Hilbert holotomography (CP-HHT) for high-throughput 3D refractive index imaging. Addressing limitations in current holotomography methods, we leverage the extended space-bandwidth product (SBP) through robust phase demodulation using Hilbert spiral transform. Thanks to the application of polarization diffraction gratings our system enables fully tailored holographic settings such as fringe density and shear, thus allowing flexible hologram demodulation, while maintaining simplicity and robustness. The performance is tested on a 3D-printed (using two-photon polymerization) brain phantom and fixed HeLa cells supplemented with cholesterol and oleic acids. Reconstruction analysis using the brain phantom indicates that the Hilbert method provides comparable results and resolution to the Fourier transform method in a significantly expanded measurement throughput. Our CP-HHT approach demonstrates the unique (not possible by fluorescence) high-throughput (especially when compared to cryogenic electron microscopy) capability to differentiate between cholesterol esters vs. triacylglycerol (TAG) rich lipid droplets (LDs), thus has potential for label-free biological research at sub-cellular level. The quantitative analysis of LDs’ refractive index emphasizes the method’s sensitivity in distinguishing between LDs with different neutral lipid content, offering new insights into LD heterogeneity, thus reinforcing the versatility and applicability of our CP-HHT system in broader bioimaging applications.
ExploitingPseudomonas syringaeType 3 secretion to study effector contribution to disease in spinach
Authors: Mendel Melanie , Zuijdgeest Xander C. L. , Berg Femke van den , Meer Leroy van der , Elberse Joyce , Skiadas Petros , Seidl Michael F , Ackerveken Guido Van den , Jonge Ronnie de 
Published: June 2024

AbstractIntensive cultivation practices of spinach create favourable conditions for the emergence and rapid evolution of pathogens, causing substantial economic damage. Research on host-pathogen interactions and host immunity in various leafy greens benefits from advanced biotechnological tools. The absence of specialised tools for spinach, however, constrains our understanding of spinach immunity. Here, we explored the potential of Type III Secretion System (T3SS)-mediated delivery to study the activity of pathogen effectors in spinach. We identified thePseudomonas syringaepv. tomatoDC3000 (DC3000) polymutant D36E, which lacks 36 known T3SS effectors (T3Es), as a promising T3SS-dependent effector delivery system in spinach. Unlike DC3000, which causes visual disease symptoms on spinach, D36E did not induce visible disease symptoms. Using D36E effector delivery, we screened 28 known DC3000 T3Es individually on spinach for effects on disease symptom development, bacterial proliferation reflecting bacterial virulence, and ROS bursts as a proxy for early immune responses. All three assays identified T3Es AvrE1 and HopM1 as crucial determinants of DC3000-like infection on spinach. Additionally, we observed that the T3E HopAD1 strongly suppressed ROS production in spinach. We present the first experimental evidence of plant pathogen effector activities in spinach. By establishing the D36E-effector delivery system in spinach, we pave the way for high-throughput effector studies on spinach. This system provides a critical link between genomics-based effector predictions in spinach pathogens and experimental validation, which is a crucial step for knowledge-driven resistance breeding in non-model crops like spinach.