bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zooarchaeological investigation of the Hoabinhian exploitation of reptiles and amphibians in Thailand and Cambodia with a focus on the Yellow-headed Tortoise (Indotestudo elongata(Blyth, 1854))
Authors: Bochaton Corentin , Chantasri Sirikanya , Maneechote Melada , Claude Julien , Griggo Christophe , Naksri Wilailuck , Forestier Hubert , Sophady Heng , Auertrakulvit Prasit , Bowonsachoti Jutinach , Zeitoun Valéry 
Published: April 2023

ABSTRACTWhile non-marine turtles are almost ubiquitous in the archaeological record of Southeast Asia, their zooarchaeological examination has been inadequately pursued within this tropical region. This gap in research hinders a complete comprehension of past human subsistence strategies and economies, as only a limited number of comprehensive studies encompassing all the taxa found in archaeological sites have been conducted thus far. This constraint becomes particularly significant in relation to prehistoric hunter-gatherer populations, who might have extensively utilized inland chelonian taxa. In order to initiate a new approach to the study of past human-turtle interactions in Southeast Asia, we propose an in-depth zooarchaeological analysis of turtle bone remains recovered from four Hoabinhian Hunter-gatherer archaeological assemblages located in Thailand and Cambodia, dating from the Late Pleistocene to the first half of the Holocene. Our study focuses on the bone remains attributed to the Yellow-headed Tortoise (Indotestudo elongata) as it is the most represented taxon in archaeological assemblages in the region of study. For this species, we developed osteometric equations enabling the estimation of the carapace size of the archaeological individuals. This allowed us to study the size structure of the archaeological populations at different sites and to reveal the human exploitation strategies of these animals. We observed a significant taphonomic homogeneity among the studied assemblages, along with similarities in the diversity of hunted reptile and amphibian taxa as well as the size of the exploited tortoises. These findings suggest consistent subsistence behaviors across distinct sites, despite their varying environmental conditions, and raise the possibility of cultural similarities across different periods and regions. Additionally, we provide a baseline for future zooarchaeological studies and a methodological framework for the detailed analysis of archaeological turtle bones in continental Southeast Asia.
Vessel normalization and maturation promotes nanoparticle delivery to solid tumors while minimizing metastases
Authors: Izci Mukaddes , Maksoudian Christy , Gonçalves Filipa , Chu Tianjiao , Luci Carla Rios , Bolea-Fernandez Eduardo , Vanhaecke Frank , Manshian Bella B. , Soenen Stefaan J. 
Published: April 2023

AbstractNanoparticle delivery to solid tumors is known to be an inefficient process and various studies have tried to increase efficacy, but mechanistic and comparative studies remain scarce. Here, we use pharmacological agents to study the effect of vessel normalization or vessel disintegration on nanoparticle delivery to solid tumors. Using a multiparametric approach, we find that vessel disintegration fails to improve nanoparticle delivery and instead seems to have a limiting effect. Vessel normalization, however, improves delivery efficacy for nanoparticles ranging from 20 to 60 nm diameter. The normalization of the tumor blood vessels results in reduced hypoxia, reduced necrosis and an increase inPlvap+CD276+endothelial cells, which have been linked with nanoparticle delivery. Interestingly, where vessel disintegration stimulated cancer cell intravasation and associated metastases, vessel normalization impeded these processes. Together, these data reveal that, vessel normalization may be a safer and more suited approach for improving nanoparticle delivery to solid tumors, but its efficacy is limited by nanoparticle diameter and tumor parameters.Graphical abstract
The dynamic interaction between predator and prey drives mesopredator movement and foraging ecology
Authors: Florko Katie R.N. , Ross Tyler R. , Ferguson Steven H. , Northrup Joseph M. , Obbard Martyn E. , Thiemann Gregory W. , Yurkowski David J. , Auger-Méthé Marie 
Published: April 2023

AbstractPrey availability is a fundamental driver of animal distribution, movement, and foraging ecology. The perceived risk of predation also influences these aspects of animal ecology. Our paper explores how animals balance these tradeoffs, which are seldom analyzed together. Such understanding becomes increasingly important as species that face anthropogenic-caused ecosystem change. In the Arctic, there has been substantial research on consequences of sea ice loss, however our understanding of top-down and bottom-up processes is limited. Ringed seals (Pusa hispida) and polar bears (Ursus maritimus), form a strong predator-prey relationship but limited information is available explaining how fear of polar bears affects ringed seal ecology. Using a large tracking dataset from 26 ringed seals with >70,000 dives and >10,000 locations, we explored the influence of top-down (polar bear space use based on >18,000 locations) and bottom-up (modeled fish distribution) processes on the movement, habitat selection, and foraging behavior of this mesopredator. Our results suggest that polar bears spatially restrict seal movements and reduce the amount of time they spend in area-restricted search and at depth, which likely decreases the seals’ foraging success. However, we found tradeoffs between predation risk and foraging, where ringed seals were more likely to be present and dive for a long duration in high-risk areas when prey diversity was high. Prey habitat use models that excluded predators overestimated core space use. These findings illustrate the dynamic tradeoffs that mesopredators are forced to make when balancing the risk of predation and need to forage.Significance StatementOur paper explores how animals balance finding food and avoiding predators. This balancing act is often poorly understood, particularly in Arctic ecosystems, but is necessary for understanding and conserving species. Our results show that interactions between polar bear presence and prey diversity explain the foraging behavior, habitat selection, and activity budgets of ringed seals. Seals constrained their movements to areas with low predation risk, but entered high-risk areas if prey diversity was high. Additionally, our inference on the relationship between ringed seals and their prey would be overlooked if the potential risk of polar bear predation was not included. Our study advances our understanding of the complex dynamics in predator-prey ecology, which is essential to incorporate when identifying critical habitat.
Stromule geometry allows optimal spatial regulation of organelle interactions in the quasi-2D cytoplasm
Authors: Erickson Jessica Lee , Prautsch Jennifer , Reynvoet Frisine , Niemeyer Frederik , Hause Gerd , Johnston Iain G. , Schattat Martin 
Published: April 2023

AbstractIn plant cells, plastids form elongated extensions called stromules, the regulation and purposes of which remain unclear. Here we quantitatively explore how different stromule structures serve to enhance the ability of a plastid to interact with other organelles: increasing the effective space for interaction and biomolecular exchange between organelles. Strikingly, electron microscopy and confocal imaging showed that the cytoplasm inArabidopsis thalianaandNicotiana benthamianaepidermal cells is extremely thin (around 100 nm in regions without organelles), meaning that inter-organelle interactions effectively take place in 2D. We combine these imaging modalities with mathematical modelling and newin plantaexperiments to demonstrate how different the elongation of stromules (single or multiple, linear or branching) could be employed to optimise different aspects of inter-organelle interaction capacity in this 2D space. Stromule formation and branching is shown to provide a proportionally higher benefit to interaction capacity in 2D than in 3D. Additionally we find this benefit depends on optimal plastid spacing. We hypothesize that cells can promote the formation of different stromule architectures in the quasi-2D cytoplasm to optimise their interaction interface to meet specific requirements. These results provide new insight into the mechanisms underlying the transition from low to high stromule numbers during biotic stress, the consequences for interaction with smaller organelles, how plastid access and plastid to nucleus signalling is balanced, as well as the impact of plastid density on organelle interaction.
Being a tree crop increases the odds of experiencing yield declines irrespective of pollinator dependence
Authors: Aizen Marcelo A. , Gleiser Gabriela , Kitzberger Thomas , Milla Rubén 
Published: April 2023

ABSTRACTCrop yields,i.e., harvestable production per unit of cropland area, are in decline for a number of crops and regions, but the drivers of this process are poorly known. Global decreases in pollinator abundance and diversity have been proposed as a major driver of yield declines in crops that depend on animals, mostly bees, to produce fruits and seeds. Alternatively, widespread tree mortality has been directly and indirectly related to global climate change, which could also explain yield decreases in tree crops. As tree crops are expected to be more dependent on pollinators than other crop types, disentangling the relative influence of growth form and pollinator dependence is relevant to identify the ultimate factors driving yield declines. Yield decline, defined here as a negative average annual yearly change in yield from 1961 to 2020, was measured in 4270 time series, involving 136 crops and 163 countries and territories. About one-fourth of all time series showed declines in crop yield, a characteristic associated with both high pollinator dependence and a tree growth form. Because pollinator dependence and plant growth form were partially correlated, we disentangled the effect of each of these two predictors using a series of generalized linear mixed models that evaluated direct and indirect associations. Our analyses revealed a stronger association of yield decline with growth form than with pollinator dependence, a relationship that persisted after partialling out the effect of pollinator dependence. In particular, yield declines were more common among tree than herbaceous and shrub crops in all major regions but in Africa, a continent showing a high incidence of yield declines irrespective of growth form. These results suggest that pollinator decline is not the main reason behind crop productivity loss, but that other factors such as climate change could be already affecting crop yield.
Multiscale Model for Ion Transport in Cellular Media and Applications in Smooth Muscle Cells
Authors: Xiao Chun , Sun Yishui , Huang Huaxiong , Song Zilong , Yue Xingye , David Tim , Xu Shixin 
Published: April 2023

AbstractIon transport in biological tissues is crucial in the study of many biological and pathological problems. Some multi-cellular structures, like the smooth muscles on vessel walls, can be treated as periodic bi-domain structures consisting of the intracellular space (ICS) and extracellular space (ECS) with semipermeable membranes in between. In this work, we first use a multi-scale asymptotic method to derive a macroscopic homogenized bidomain model from the microscopic electro-neutral (EN) model with different diffusion coefficients and nonlinear interface conditions. Then, the obtained homogenized model is applied to study ion transportation and micro-circulation in multi-celluar tissues under the impact of agonists, an internal calcium source, and extracellular potassium. Our model serves as a useful bridge between existing ordinary differential equation models and partial differential models that take into consideration spatial variation. On the one hand, numerical results show that ECS variables are almost invariant in the first two scenarios and confirm the validity of existing single-domain models, which treat variables in the ECS as constants. On the other hand, only the bidomain model is applicable to consider the effect of local extracellular potassium. Finally, the membrane potential of syncytia formed by connected cells is found to play an important role in the propagation of oscillation from the stimulus region to the non-stimulus region.Author summarySmooth muscle cells (SMCs) play a vital role in neurovascular coupling, which is the mechanism by which changes in neural activity are linked to alterations in blood flow. Dysfunctional SMCs can have significant implications for human health. The activation of SMCs is primarily regulated by the intracellular concentration of calcium ions (Ca2+). A multi-scale model for ion transport in multicellular tissue with varying connectivity has been proposed to investigate SMC activation under different stimuli. The simulation results confirm the critical role of gap junctions in wave propagation and vasoconstriction in the vessel wall. The blockage of gap junctions prevents the spread of the wave. Furthermore, the propagation of membrane potential is the primary cause of wave propagation.
Exosomal microRNA signature from plasma-derived extracellular vesicles in gastric cancer
Authors: Rincón-Riveros Andrés , Villegas Victoria E. , Quintero Motta Nicolle Stefania , López-Kleine Liliana , Rodríguezand Josefa Antonia 
Published: April 2023

AbstractBackgroundGastric cancer is a heterogeneous pathology that represents the fifth most frequent malignancy in the world, with more than 750,000 deaths by 2020. With significant repercussions in public health, this pathology lacks biomarkers for early diagnosis, with endoscopy biopsy being the golden test for its detection. In the exploration of new strategies to control gastric cancer in recent years, liquid biopsy appears as a potential source of biomarkers using non-invasive procedures.MethodsHere we present the characterization of miRNAs contained in plasma-derived exosomes from patients with gastric cancer. Extracellular vesicles (EVs) were isolated using size-exclusion chromatography (SEC) and their characterization was performed by electron microscopy, protein expression, and nanoparticle analysis techniques. Total RNA from isolated exosomes was obtained for small RNA-seq analysis.ResultsTranscriptomic miRNA data were used to identify differentially expressed miRNAs between patients with benign and malignant gastric diseases, which resulted in a molecular signature of nine miRNAs, that were used in a regression model to classify individuals as either having benign or malignant disease. Further, we compared benign-malignant patients at different stages of gastric cancer, and we detected 15 differentially expressed miRNAs. Among these 15 miRNAs, miR-92a-3p, miR451a, and miR126-3p were identified as winners due to their clinical and regulatory relevance.ResultsOur results offer relevant information of a Colombian case study allowing us to propose three transcriptomic gastric cancer biomarkers in liquid biopsy.Graphical AbstractSummaryEVs are structures surrounded by a lipid bilayer that facilitate intercellular communication by transporting biomolecules commonly referred to as part of liquid biopsy. In this study, we examine the miRNAs contents of plasma isolated EVs from patients with both benign gastric diseases and gastric cancer to identify potential biomarkers for gastric cancer.
An RNA Damage Response Network Mediates the Lethality of 5-FU in Clinically Relevant Tumor Types
Authors: Chen Jung-Kuei , Merrick Karl A. , Kong Yi Wen , Izrael-Tomasevic Anita , Eng George , Handly Erika D. , Patterson Jesse C. , Cannell Ian G. , Suarez-Lopez Lucia , Hosios Aaron M. , Dinh Anh , Kirkpatrick Donald S. , Yu Kebing , Rose Christopher M. , Hernandez Jonathan M. , Hwangbo Haeun , Palmer Adam C. , Vander Heiden Matthew G. , Yilmaz Ömer H. , Yaffe Michael B. 
Published: April 2023

Abstract5-fluorouracil (5-FU) is a successful and broadly used anti-cancer therapeutic. A major mechanism of action of 5-FU is thought to be through thymidylate synthase (TYMS) inhibition resulting in dTTP depletion and activation of the DNA damage response. This suggests that 5-FU should synergize with other DNA damaging agents. However, we found that combinations of 5-FU and oxaliplatin or irinotecan failed to display any evidence of synergy in clinical trials, and resulted in sub-additive killing in a panel of colorectal cancer (CRC) cell lines. In seeking to understand this antagonism, we unexpectedly found that an RNA damage response during ribosome biogenesis dominates the drug’s efficacy in tumor types for which 5-FU shows clinical benefit. 5-FU has an inherent bias for RNA incorporation, and blocking this greatly reduced drug-induced lethality, indicating that accumulation of damaged RNA is more deleterious than the lack of new RNA synthesis. Using 5-FU metabolites that specifically incorporate into either RNA or DNA revealed that CRC cell lines and patient-derived colorectal cancer organoids are inherently more sensitive to RNA damage. This difference held true in cell lines from other tissues in which 5-FU has shown clinical utility, whereas cell lines from tumor tissues that lack clinical 5-FU responsiveness typically showed greater sensitivity to the drug’s DNA damage effects. Analysis of changes in the phosphoproteome and ubiquitinome shows RNA damage triggers the selective ubiquitination of multiple ribosomal proteins leading to autophagy-dependent rRNA catabolism and proteasome-dependent degradation of ubiquitinated ribosome proteins. Further, RNA damage response to 5-FU is selectively enhanced by compounds that promote ribosome biogenesis, such as KDM2A inhibitors. These results demonstrate the presence of a strong RNA damage response linked to apoptotic cell death, with clear utility of combinatorially targeting this response in cancer therapy.
Pooled effector library screening in protoplasts rapidly identifies novelAvrgenes
Authors: Arndell Taj , Chen Jian , Sperschneider Jana , Upadhyaya Narayana M , Blundell Cheryl , Niesner Nathalie , Wang Aihua , Swain Steve , Luo Ming , Ayliffe Michael A , Figueroa Melania , Vanhercke Thomas , Dodds Peter N 
Published: April 2023

AbstractCrop breeding for durable disease resistance is challenging due to the rapid evolution of pathogen virulence. While progress in resistance (R) gene cloning and stacking has accelerated in recent years1-3, the identification of corresponding avirulence (Avr) genes in many pathogens is hampered by the lack of high-throughput screening options. To address this technology gap, we developed a platform for pooled library screening in plant protoplasts for rapid identification of interactingR/Avrpairs. We validated this platform by isolating known and novelAvrgenes from wheat stem rust (Puccinia graminisf. sp.tritici) by screening a designed library of putative effectors against individualRgenes. RapidAvrgene identification provides molecular tools to understand and track pathogen virulence evolution by genotype surveillance and optimiseRgene deployment and stacking strategies. This screening platform is broadly applicable to many crop pathogens, whilst also adaptable for screening genes involved in other protoplast-selectable traits.
Conformational dynamics of the μ-opioid receptor determine ligand intrinsic efficacy
Authors: Zhao Jiawei , Elgeti Matthias , O’Brien Evan S. , Sár Cecília P. , Daibani Amal EI , Heng Jie , Sun Xiaoou , Che Tao , Hubbell Wayne L. , Kobilka Brian K. , Chen Chunlai 
Published: April 2023

AbstractThe μ-opioid receptor (μOR) is an important target for pain management and the molecular understanding of drug action will facilitate the development of better therapeutics. Here we show, using double electron-electron resonance (DEER) and single-molecule fluorescence resonance energy transfer (smFRET), how ligand-specific conformational changes of the μOR translate into a broad range of intrinsic efficacies at the transducer level. We identify several cytoplasmic receptor conformations interconverting on different timescales, including a pre-activated receptor conformation which is capable of G protein binding, and a fully activated conformation which dramatically lowers GDP affinity within the ternary complex. Interaction of β-arrestin-1 with the μOR core binding site appears less specific and occurs with much lower affinity than binding of G protein Gi.One-Sentence SummaryLigand-dependent conformational dynamics of the μ-opioid receptor determine downstream signaling efficacy.
Hungarian Grey cattle grazing outperforms mowing during wet meadow restoration following plantation forest clear-cut
Authors: Szitár Katalin , Kabai Melinda , Zimmermann Zita , Szabó Gábor , Reis Bruna Paolinelli , Somay László 
Published: April 2023

AbstractLand-use change and ecological invasion are two main drivers of biodiversity loss, and the restoration of semi-natural wet grasslands is needed to tackle invasive species and re-establish grassland biodiversity on former forest plantations. This study tested the effectiveness of two widely used management techniques (grazing by traditional Hungarian Grey cattle and mowing once a year in August) as a restoration method of wet meadows in a former forest plantation invaded by goldenrod species in Central Hungary. We compared the vegetation composition of grazed, mowed, and reference areas with semi-natural wet meadow vegetation based on plant biomass, species richness and cover of species groups of species origin, life span, growth form, and social behaviour types of Borhidi determining the grazing value and the nature conservation value of the grasslands. We found that grazing by Hungarian Grey cattle resulted in a vegetation that was more similar to the reference wet meadows than mowing once a year in late summer. Grazing was superior to mowing in terms of goldenrod control, total species richness and cover, as well as the abundance of natives, perennials, herbs, and legumes. However, in the grazed area, we detected more disturbance-tolerant and annual species than in the mowed area. Despite the improved vegetation condition in the grazed area, we identified substantial disparities between the grazed and reference areas after three years of grazing. Based on our results, we advise using continuous extensive grazing to restore and maintain semi-natural wet meadows.
The Soybean Expression Atlas v2: a comprehensive database of over 5000 RNA-seq samples
Authors: Almeida-Silva Fabricio , Pedrosa-Silva Francisnei , Venancio Thiago M. 
Published: April 2023

ABSTRACTSoybean is a crucial crop worldwide, used as a source of food, feed, and industrial products due to its high protein and oil content. Previously, the rapid accumulation of soybean RNA-seq data in public databases and the computational challenges of processing raw RNA-seq data motivated us to develop the Soybean Expression Atlas, a gene expression database of over a thousand RNA-seq samples. Over the past few years, our database has allowed researchers to explore the expression profiles of important gene families, discover genes associated with agronomic traits, and understand the transcriptional dynamic of cellular processes. Here, we present the Soybean Expression Atlas v2, an updated version of our database with a 4-fold increase in the number of samples, featuring transcript- and gene-level transcript abundance matrices for 5481 publicly available RNA-seq samples. New features in our database include the availability of transcript-level abundance estimates and equivalence classes to explore differential transcript usage, abundance estimates in bias-corrected counts to increase the accuracy of differential gene expression analyses, a new web interface with improved data visualization and user experience, and a reproducible and scalable pipeline available as an R package. The Soybean Expression Atlas v2 is available athttps://soyatlas.venanciogroup.uenf.br/, and it will accelerate soybean research, empowering researchers with high-quality and easily accessible gene expression data.