bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acclimation kinetics of the holoparasitic weedPhelipanche ramosa(Orobanchaceae) during excessive light and heat conditions
Authors: Dayou Olivier , Brun Guillaume , Gennat Charline , Wicke Susann 
Published: December 2023

AbstractHoloparasitic plants, such as broomrape, have abandoned a photosynthesis, relying entirely on the resources of host plants. This departure from an autotrophic lifestyle necessitates significant genetic and metabolic adaptations, offering a unique model system to elucidate responses independent of canonical plastid functions in green plants. In this study, we examined the acclimation kinetics of the holoparasitic weedPhelipanche ramosa(broomrape) under unfavorable temperature and excessive light conditions through a comprehensive time-course analysis of RNA sequence data and physiological monitoring. Our work unveils that suboptimal abiotic conditions induce transcriptional changes in the parasitic plant, involving coordinated expression of nuclear and plastid-encoded genes. Notably, magnesium transporters, critical for heat-induced chlorophyll conversion, were enriched among heat-repressed genes. Additionally, multiple copies of chloroplast-targeted DnaJ proteins, responsible for maintaining CO2assimilation capacity in non-parasitic plants, were identified. Comparative expression analysis with the parasite’s host plants, tomato andArabidopsis, revealed distinct patterns for certain plastid genes inPhelipanche. Furthermore, an elevation in reactive oxygen species (ROS) in the parasite coincided with the upregulation of numerous heat shock protein (HSP) genes, including HSP21, which associates with thylakoid membranes in photosynthetic plants; noteworthily, thylakoids are absent fromPhelipanche’s plastids. Collectively, our findings suggest that plastids of the nonphotosynthetic model plant retains their ancestral role as environmental sensors. This research opens new avenues for functional-genetic research into the nuanced roles of plastids in the lifecycles of parasitic plants.
The deubiquitinase USP9X regulates RIT1 protein abundance and oncogenic phenotypes
Authors: Riley Amanda K. , Grant Michael , Snell Aidan , Vichas Athea , Moorthi Sitapriya , Urisman Anatoly , Castel Pau , Wan Lixin , Berger Alice H. 
Published: December 2023

SUMMARYRIT1is a rare and understudied oncogene in lung cancer. Despite structural similarity to other RAS GTPase proteins such as KRAS, oncogenic RIT1 activity does not appear to be tightly regulated by nucleotide exchange or hydrolysis. Instead, there is a growing understanding that the protein abundance of RIT1 is important for its regulation and function. We previously identified the deubiquitinaseUSP9Xas a RIT1 dependency inRIT1-mutant cells. Here, we demonstrate that both wild-type and mutant forms of RIT1 are substrates of USP9X. Depletion of USP9X leads to decreased RIT1 protein stability and abundance and resensitizes cells to EGFR tyrosine kinase inhibitors. Our work expands upon the current understanding of RIT1 protein regulation and presents USP9X as a key regulator of RIT1-driven oncogenic phenotypes.
Comparative transcriptomics of seed nourishing tissues: uncovering conserved and divergent pathways in seed plants
Authors: Florez-Rueda Ana Marcela , Miguel Célia M. , Figueiredo Duarte D. 
Published: December 2023

SummaryThe evolutionary and ecological success of spermatophytes is intrinsically linked to the seed habit, which provides a protective environment for the initial development of the new generation. This environment includes an ephemeral nourishing tissue that supports embryo growth. In gymnosperms this tissue originates from the asexual proliferation of the maternal megagametophyte, while in angiosperms it is a product of fertilization, and is called the endosperm. The emergence of these nourishing tissues is of profound evolutionary value, and they are also food staples for most of the world’s population. Here, using Orthofinder to infer orthologue genes among novel and previously published datasets, we provide a comparative transcriptomic analysis of seed nourishing tissues from representative species of all main angiosperm clades, including those of early diverging basal angiosperms, and a gymnosperm representative. Our results show that, although the structure and composition of seed nourishing tissues has seen significant divergence along evolution, there are signatures that are conserved throughout the phylogeny. Conversely, we identified processes that are specific to species within the clades studied, and thus illustrate their functional divergence. With this, we aimed to provide a foundation for future studies on the evolutionary history of seed nourishing structures, as well as a resource for gene discovery in new functional studies.Significance StatementWithin seeds a specialized structure is responsible for nourishing the embryo during its development. These nourishing tissues are also important sources of staple foods and feed. Here, we provide novel gene expression datasets of nourishing tissues of early diverging angiosperms, and use this information for a meta-analysis to identify pathways conserved, or divergent, throughout evolution. Thus, we aim to provide a resource for gene discovery for seed biology studies.
A multi-strategy antimicrobial discovery approach reveals new ways to combatChlamydia
Authors: Ölander Magnus , Vázquez Daniel Rea , Meier Karsten , Mooij Lieke , Fredlund Johanna , Puértolas-Balint Fabiola , Calpe Eduard , Díaz María Rayón , van der Wal Karin , Schroeder Bjoern O. , Sixt Barbara Susanne 
Published: December 2023

SummaryWhile the excessive use of broad-spectrum antibiotics is a major driver of the global antibiotic resistance crisis, more selective therapies remain unavailable for the majority of bacterial pathogens. This includesChlamydiaspp., which cause millions of urogenital, ocular, and respiratory infections each year. We here report major conceptual additions to the available toolkit for antichlamydial discovery, including both experimental and computational approaches. Moreover, we report the to date most comprehensive search of the chemical space for novel antichlamydial activities, which identified over sixty compounds that are chemically diverse, structurally different from known antibiotics, non-toxic to human cells, and highly potent in blockingChlamydiagrowth. While some compounds caused a reversible block inChlamydiadevelopment, others could eradicate both established and persistent infections in a bactericidal manner. The most potent antichlamydials displayed compelling selectivity, some also synergies with clinically used antibiotics, as well as interactions profiles enabling predictions of molecular modes of action. Moreover, one compound displayed reduced antichlamydial efficacy in autophagy-deficient cells, suggesting a host- targeted activity. Altogether, we suggest that these novel antichlamydials could serve as tools for advancing our understanding ofChlamydiabiology and as chemical starting points for developing more sustainable therapeutics for one of the most successful groups of intracellular pathogens.
MiRNAs differentially expressed in vegetative and reproductive organs ofMarchantia polymorpha– insights into their expression pattern, gene structures and function
Authors: Aggarwal B , Karlowski MW , Nuc P , Jarmolowski A , Szweykowska-Kulinska Z , Pietrykowska H 
Published: December 2023

AbstractMicroRNAs (miRNAs) regulate gene expression affecting a variety of plant developmental processes. The evolutionary position ofMarchantia polymorphamakes it a significant model to understand miRNA-mediated gene regulatory pathways in plants. Previous studies focused on conserved miRNA-target mRNA modules showed their critical role in Marchantia development. Here, we demonstrate that differential expression of conserved miRNAs and their targets in selected organs of Marchantia additionally underlines their role in regulating fundamental developmental processes. The main aim of this study was to characterize selected liverwort-specific miRNAs, as there is a limited knowledge on their biogenesis, accumulation, targets, and function in Marchantia. We demonstrate their differential accumulation in vegetative and generative organs. We reveal that all liverwort-specific miRNAs examined are encoded by independent transcriptional units. MpmiR11737a, MpmiR11887 and MpmiR11796, annotated as being encoded within protein-encoding genes, have their own independent transcription start sites. The analysis of selected liverwort-specific miRNAs and their pri-miRNAs often reveal correlation in their levels, suggesting transcriptional regulation. However, MpmiR11796 shows a reverse correlation to its pri-miRNA level, suggesting post-transcriptional regulation. Moreover, we identify novel targets for selected liverwort-specific miRNAs and demonstrate an inverse correlation between their expression and miRNA accumulation. In the case of one miRNA precursor, we provide evidence that it encodes two functional miRNAs with two independent targets. Overall, our research sheds light on liverwort-specific miRNA gene structure, provides new data on their biogenesis and expression regulation. Furthermore, identifying their targets, we hypothesize the potential role of these miRNAs in early land plant development and functioning.
High defense system expression broadens protection range at the cost of increased autoimmunity
Authors: Aframian Nitzan , Omer Bendori Shira , Hen Tal , Guler Polina , Eldar Avigdor 
Published: December 2023

AbstractThe evolutionary arms race between bacteria and their phage viruses has given rise to elaborate anti-phage defense mechanisms. Major advances have been made in revealing the molecular details underlying diverse defense systems, but general principles and constraints are largely unkown. Defense systems are often tested against a diverse set of phages, revealing widely varying protection ranges. While these disparities are usually attributed to differences in mechanism, here we show that increasing expression of defense systems can greatly enhance their protection range. This holds true for disparate mechanisms, and is achieved by circumventing phage strategies for overcoming bacterial defense. However, increased defense system expression comes with a heavy cost of autoimmunity. Therefore, the expression level of defense systems controls a tradeoff between protection range on the one hand and autoimmunity on the other. We discuss how this tradeoff may drive the regulation of defense systems expression and the acquisition of multiple systems within the same genome.
Pre-mRNA fate decision safeguards the fidelity of the inflammatory response
Authors: Bestehorn Annika , Fesselet Jeanne , Didusch Sebastian , Zeiler Christina , Doppelmayer Kevin , Borroni Martina , LeHeron Anita , Pfanzagl Vera , Chen WeiQiang , Scinicariello Sara , Baccarini Manuela , Versteeg Gijs A , Hartl Markus , Kovarik Pavel 
Published: December 2023

ABSTRACTThe fidelity of immune responses is dependent on a timely controlled and selective mRNA degradation that is largely driven by RNA-binding proteins (RBPs). It remains unclear whether the selection of an individual mRNA molecule for degradation is governed by stochastic or directed processes. Here, we show that tristetraprolin (TTP, also known as ZFP36), an essential anti-inflammatory RBP, destabilized the target mRNA via a hierarchical molecular assembly. The assembly formation is strictly reliant on TTP interaction with RNA. The TTP homolog ZFP36L1 exhibits similar requirements indicating a broader relevance of this regulatory program. Unexpectedly, the assembly of the cytoplasmic mRNA-destabilization complex is licensed in the nucleus by TTP binding to pre-mRNA while mature cytoplasmic mRNA does not constitute a de novo TTP target. Hence, the fate of an inflammation-induced mRNA is decided concomitantly with its synthesis. This fate decision mechanism prevents the translation of superfluous and potentially harmful inflammation mediators, and ensures an efficient cessation of the immune response irrespective of transcriptional activity.
Motif-VI Loop Acts as a Nucleotide Valve in the West Nile Virus NS3 Helicase
Authors: Roy Priti , Walter Zachary , Berish Lauren , Ramage Holly , McCullagh Martin 
Published: December 2023

AbstractThe flavivirus NS3 helicase (NS3h), a highly conserved protein, plays a pivotal role in virus replication and thus represents a potential drug target for flavivirus pathogenesis. NS3h utilizes nucleotide triphosphate, such as ATP, for hydrolysis energy (ATPase) to translocate on single-stranded nucleic acids, which is an important step in the unwinding of double-stranded nucleic acids. The intermediate states along the ATP binding and hydrolysis cycle, as well as the conformational changes between these states, represent important yet difficult-to-identify targets for potential inhibitors. We use extensive molecular dynamics simulations of apo, ATP, ADP+Pi, and ADP bound to WNV NS3h+ssRNA to model the conformational ensembles along this cycle. Energetic and structural clustering analyses on these trajectories depict a clear trend of differential enthalpic affinity of NS3h with ADP, demonstrating a probable mechanism of hydrolysis turnover regulated by the motif-VI loop (MVIL). These findings were experimentally corroborated using viral replicons encoding three mutations at the D471 position. Replication assays using these mutants demonstrated a substantial reduction in viral replication compared to the wild-type. Molecular simulations of the D471 mutants in the apo state indicate a shift in MVIL populations favoring either a closed or open ‘valve’ conformation, affecting ATP entry or stabilization, respectively. Combining our molecular modeling with experimental evidence highlights a conformation-dependent role for MVIL as a ‘valve’ for the ATP-pocket, presenting a promising target for antiviral development.
The demographic drivers of cultural evolution in bird song: a multilevel study
Authors: Recalde Nilo Merino , Estandía Andrea , Keen Sara C. , Cole Ella F. , Sheldon Ben C. 
Published: December 2023

SummarySocial learning within communities sometimes leads to behavioural patterns that persist over time, which we know as culture. Examples of culture include learned bird and whale songs, cetacean feeding techniques, and avian and mammalian migratory routes. Shaped by neutral and selective forces, animal cultures evolve dynamically and lead to cultural traditions that differ greatly in their diversity and stability. These cultural traits can influence individual and group survival, population structure, and even inform conservation efforts, underscoring the importance of understanding how other population processes interact with social learning to shape culture. Although the impact of social learning mechanisms and biases has been extensively explored, the role of demographic factors—such as population turnover, immigration, and age structure—on cultural evolution has received theoretical attention but rarely been subject to empirical investigation in natural populations. Doing so requires very complete trait sampling and detailed individual life history data, which are hard to acquire in combination. To this end, we built a multi-generational dataset containing over 109,000 songs from >400 individuals from a population of Great Tits (Parus major), which we study using a deep metric learning model to re-identify individuals and quantify song similarity. We show that demographic variation at the small spatial scales at which learning takes place has the potential to strongly impact the pace and outcome of animal cultural evolution. For example, age distributions skewed towards older individuals are associated with slower cultural change and increased diversity, while higher local population turnover leads to elevated rates of cultural change. Our analyses support theoretical expectations for a key role of demographic processes resulting from individual behaviour in determining cultural evolution, and emphasize that these processes interact with species-specific factors such as the timing of song acquisition. Implications extend to large-scale cultural dynamics and the formation of dialects or traditions.
Simulated digestion, uptake and colonic fermentation of Gorse (Ulex europeaus) suggests safe use as a source of protein concentrates and bioactives
Authors: Iyer Ajay , Duncan Gary J. , Hayward Nicholas J. , Bestwick Charles S. , Duncan Sylvia H. , Russell Wendy R. 
Published: December 2023

AbstractBackgroundInvasive plants such as Gorse (Ulex europeaus) may serve as a potentially sustainable source of edible proteins and bioactives through the production of leaf protein concentrates (GLPC). The digestion, uptake and safety of phytochemicals from GLPC and the protein depleted but bioactive rich fraction (PDF) from Gorse was studied using an in vitro simulated digestion model.ResultsBoth the Gorse fractions and their digesta maintained the viability of cultured (Caco-2) intestinal cells above the 80% threshold, suggesting a lack of overt toxicity.In the digestion model, most of the plant metabolites in the digesta were largely confined to the apical fraction of the Caco-2 monolayer (representing the lumen) and were subsequently expected to be delivered to the colon. Food matrix had a significant but marginal effect on the permeability of metabolites across the Caco-2 monolayer. Lastly,in vitrointestinal microbial action appeared to produce beneficial compounds such as enterolactones, and equol.ConclusionThe Gorse fractions lack general overt toxicity to Caco-2 cells. GLPC and PDF provide metabolic substrates for the colonic microbes to produce secondary compounds that are associated with positive health outcomes.
CRISPR/Cas9-mediated genome editing ofFrankliniella occidentalis,the western flower thrips, via embryonic microinjection
Authors: Han Jinlong , Klobasa William , de Oliveira Lucas , Rotenberg Dorith , Whitfield Anna E. , Lorenzen Marcé D. 
Published: December 2023

AbstractThe western flower thrips,Frankliniella occidentalis, poses a significant challenge in global agriculture as a notorious pest and a vector of economically significant orthotospoviruses. However, the limited availability of genetic tools forF. occidentalishampers the advancement of functional genomics and the development of innovative pest control strategies. In this study, we present a robust methodology for generating heritable mutations inF. occidentalisusing the CRISPR/Cas9 genome editing system. Two eye-color genes,white(Fo-w) andcinnabar(Fo-cn), frequently used to assess Cas9 function in insects were identified in theF. occidentalisgenome and targeted for knockout through embryonic microinjection of Cas9 complexed withFo-worFo-cnspecific guide RNAs. HomozygousFo-wandFo-cnknockout lines were established by crossing mutant females and males. TheFo-wknockout line revealed an age-dependent modification of eye-color phenotype. Specifically, while young larvae exhibit ivory-colored eyes, the color transitions to bright red as they age. Unexpectedly, loss ofFo-wfunction also altered body color, withFo-wmutants having a lighter colored body than wild type, suggesting a dual role forFo-win thrips. In contrast, individuals from theFo-cnknockout line consistently displayed bright red eyes throughout all life stages. Molecular analyses validated precise editing of both target genes. This study offers a powerful tool to investigate thrips gene functions and paves the way for the development of genetic technologies for population suppression and/or population replacement as a means of mitigating virus transmission by this vector.
Shoot phenotyping of cytokinin receptors mutants revealed fluorescence parameters as early markers of drought stress
Authors: Šmeringai Ján , Rudolf Jiří , Trtílek Martin , Procházková Schrumpfová Petra , Pernisová Markéta 
Published: December 2023

AbstractPlant phenotyping represents an increasing promise in plant research by providing a complex picture of plant development and fitness. In research focused on various environmental stresses, phenotyping can uncover markers that can sensitively assess the stress impact in very early stages before morphological changes. PlantScreenTMSystem represents a tool dedicated for shoot and root phenotyping in soil enabling high-precision, high-throughput phenotyping of small, mid-size and large plants. The system offers wide range of sensors providing the number of non-invasive analyses of morphological and physiological parameters as well as of pigments, water, or metabolite content.In our work, we combined phenotyping approaches to determine morphological changes and the status of the photosynthetic apparatus in Arabidopsis plants exposed to drought stress. Focused on morphology, the rosette area became smaller after seven days of drought stress when compared to control conditions. Interestingly, cytokinin signalling mutantahk2 ahk3revealed drought resistance compared to other genotypes. The fluorescent parameters showed higher sensitivity even in wild type. Non-photochemical quenching displayed values connected to reduced activity of photosynthetic apparatus after five days of drought stress. Taken together, acquired fluorescence parameters can serve as a marker of drought stress detection before morphological alterations occur.HighlightFluorescence parameters can serve as early markers of drought stress before morphological alterations appear. Shoot phenotyping of cytokinin receptor mutants showed drought resistance in theahk2 ahk3double mutant.
The nucleotide binding domain of NRC-dependent disease resistance proteins is sufficient to activate downstream helper NLR oligomerization and immune signaling
Authors: Contreras Mauricio P. , Pai Hsuan , Thompson Rebecca , Claeys Jules , Adachi Hiroaki , Kamoun Sophien 
Published: December 2023

AbstractNucleotide-binding domain and leucine-rich repeat (NLR) proteins with pathogen sensor activities have evolved to initiate immune signaling by activating helper NLRs. However, the mechanisms underpinning helper NLR activation by sensor NLRs remain poorly understood. Although coiled-coil (CC) type sensor NLRs such as thePotato virus Xdisease resistance protein Rx have been shown to activate the oligomerization of their downstream helpers NRC2 and NRC4, the domains involved in sensor-helper signaling are not known. Here, we show that the nucleotide binding (NB) domain within the NB-ARC of thePotato virus Xdisease resistance protein Rx is necessary and sufficient for oligomerization and immune signaling of downstream helper NLRs. In addition, the NB domains of the disease resistance proteins Gpa2 (cyst nematode resistance), Rpi-amr1, Rpi-amr3 (oomycete resistance) and Sw-5b (virus resistance) are also sufficient to activate their respective downstream NRC helpers. Moreover, the NB domain of Rx and its helper NRC2 form a minimal functional unit that can be transferred from solanaceous plants (lamiids) to the Campanulid species lettuce (Lactuca sativa). Our results challenge the prevailing paradigm that NLR proteins exclusively signal via their N-terminal domains and reveal a signaling activity for the NB domain of NRC-dependent sensor NLRs. We propose a model in which helper NLRs monitor the status of the NB domain of their upstream sensors.