bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental evolution for improved post-infection survival selects for increased disease resistance inDrosophila melanogaster
Authors: Basu Aabeer , Tekade Kimaya , Singh Aparajita , Das Paresh Nath , Prasad Nagaraj Guru 
Published: February 2024

AbstractDisease resistance (defined as the host capacity to limit systemic infection intensity) and disease tolerance (defined as the host capacity to limit infection-induced damage) are two complementary defense strategies that help the hosts maximize their survival and fitness when infected with pathogens and parasites. In addition to the underlying physiological mechanisms, existing theory postulates that these two strategies differ in terms of the conditions under which each strategy evolves in host populations, their evolutionary dynamics, and the ecological and epidemiological consequences of their evolution. Here we explored if one or both of these strategies evolve when host populations are subjected to selection for increased post-infection survival. We experimentally evolvedDrosophila melanogasterpopulations, selecting for the flies that survived an infection with the entomopathogenEnterococcus faecalis, and found that the host populations evolved increased disease resistance in response. This was despite the physiological costs associated with increased resistance. We did not find evidence of any change in disease tolerance in the host populations. We have therefore demonstrated that in an experimental evolution set-up, where insect hosts must survive an infection with a pathogenic bacterium, the hosts evolve improved disease resistance but not disease tolerance.
A flow cytometry protocol for accurate and precise measurement of plant genome size using frozen material
Authors: Soni Abhishek , Constantin Lena , Furtado Agnelo , Henry Robert J 
Published: February 2024

AbstractFlow cytometry is a technique widely applied to infer the ploidy and genome size of plant nuclei. The conventional approach of sample preparation, reliant on fresh plant material to release intact nuclei, requires protocol optimisation for application to many species. The approach often results in poor yields of nuclei, impeding the accurate measurement of genome size and confines the optimal resource allocation and efficiency in genome sequencing which relies on genome size estimation. Here, we present a novel method using frozen plant material that facilitates the release of intact nuclei for genome size estimation. Genome estimates from frozen material are similar to those from fresh material. Accurate and precise estimates can be made by complementing the fluorescence of frozen nuclei with histogram modelling and debris compensation algorithms. This method of nuclei isolation from frozen plant material for flow cytometry-based genome size estimations has special value in estimating the genome size of samples collected and frozen for use in plant genome sequencing. Plant material can be conveniently stored, resampled, and used for DNA or RNA extractions.HighlightFrozen leaf material can be used to isolate nuclei for the accurate estimation of genome size The method proved suitable for difficult samples and did not require specific optimization. The method was especially useful where plant material could not be immediately processed through flow cytometry and allowed the same sample to be used for genomes size estimation and genome sequencing.
Systemically targeting monocytic MDSCs using dendrimers and their cell-level biodistribution kinetics
Authors: Littrell Chad A. , Takacs Gregory P. , Sankara Chenikkayala Siva , Sherman Alexandra , Rubach Kai A. , Garcia Julia S. , Bell Coral , Harrison Jeffrey K. , Zhang Fan 
Published: February 2024

AbstractThe focus of nanoparticlesin vivotrafficking has been mostly on their tissue-level biodistribution and clearance. Recent progress in the nanomedicine field suggests that the targeting of nanoparticles to immune cells can be used to modulate the immune response and enhance therapeutic delivery to the diseased tissue. In the presence of tumor lesions, monocytic-myeloid-derived suppressor cells (M-MDSCs) expand significantly in the bone marrow, egress into peripheral blood, and traffic to the solid tumor, where they help maintain an immuno-suppressive tumor microenvironment. In this study, we investigated the interaction between PAMAM dendrimers and M-MDSCs in two murine models of glioblastoma, by examining the cell-level biodistribution kinetics of the systemically injected dendrimers. We found that M-MDSCs in the tumor and lymphoid organs can efficiently endocytose hydroxyl dendrimers. Interestingly, the trafficking of M-MDSCs from the bone marrow to the tumor contributed to the deposition of hydroxyl dendrimers in the tumor. M-MDSCs showed different capacities of endocytosing dendrimers of different functionalitiesin vivo. This differential uptake was mediated by the unique serum proteins associated with each dendrimer surface functionality. The results of this study set up the framework for developing dendrimer-based immunotherapy to target M-MDSCs for cancer treatment.
Biological Factors Influencing Individual Responses to Propylene Oxide: A Systematic Review of Exogenous Exposure, Endogenous Production and Detoxification
Authors: Gabashvili Irene S. 
Published: February 2024

AbstractObjectiveThis systematic review aims to synthesize current knowledge on Propylene Oxide (PO) in human exhaled breath, examining its presence across various biological matrices and exploring methodologies for its analysis. It seeks to elucidate the sources of PO in the human body and understand individual variability in detoxification processes.MethodsA comprehensive literature search was conducted across 12 databases and specialized repositories, spanning over 10,000 publications without language restrictions until May 16, 2024. Seventeen AI tools were employed to enhance study identification and analysis, focusing on both direct mentions and indirect evidence of PO behavior and detection in the human body. Assessment tools for risk of bias included SYRCLE’s tool for animal studies, the Newcastle-Ottawa Scale for cohort and case-control studies, and the ROBINS-I tool for non-randomized studies. The selection process yielded 89 studies, encompassing a range of research types and species, supplemented by reviews, monographs, and editorials to provide a comprehensive overview.ResultsThe search revealed limited direct evidence on PO concentrations in exhaled breath, with only one reference providing concrete data (0.083 ppb to 0.3 ppb following exposures to 10-25 ppm of propylene). A study of ours, published separately, indicated significantly higher PO concentrations (hundreds of ppb or even ppm) in individuals with environmental sensitivities. Numerous references offered indirect insights into PO’s persistence and detection in blood and urine. The review highlights the enzymes involved in PO metabolism, the evolution of analytical methodologies, and the challenges and potential of AI tools in systematic reviews.ConclusionsThe scarcity of direct evidence on PO in exhaled breath underscores a significant gap in the literature and existing databases. Directly and indirectly relevant sources indicate variability in environmental compound concentrations in exhaled breath, influenced by genetics, health status, metabolism, and the microbiome. The review emphasizes the difficulties in synthesizing data on PO effects due to heterogeneous inputs and complex exposure scenarios. It underscores the need for advanced AI capabilities in literature reviews to capture nuanced, indirect evidence more effectively and calls for targeted research and technological innovation in environmental health sciences. Enhancing AI tools to navigate scientific literature with greater efficacy can leverage PRISMA guidelines and diverse data sources to minimize bias and enhance reliability. This approach will aid in addressing the complex interplay of biological and environmental factors in PO metabolism and toxicity, ultimately improving risk assessments and intervention strategies.
Fusion, fission, and scrambling of the bilaterian genome in Bryozoa
Authors: Lewin Thomas D. , Liao Isabel Jiah-Yih , Chen Mu-En , Bishop John D. D. , Holland Peter W. H. , Luo Yi-Jyun 
Published: February 2024

AbstractGroups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates. Using comparative genomics, we reconstruct the chromosomal evolutionary history of five bryozoans. Multiple ancient chromosome fusions followed by gene mixing led to the near-complete loss of bilaterian linkage groups in the ancestor of extant bryozoans. A second wave of rearrangements, including chromosome fission, then occurred independently in two bryozoan classes, further scrambling bryozoan genomes. We also discover at least five derived chromosomal fusion events shared between bryozoans and brachiopods, supporting the traditional but highly debated Lophophorata hypothesis. Finally, we show that chromosome fusion and fission processes led to the partitioning of genes from bryozoan Hox clusters onto multiple chromosomes. Our findings demonstrate that the canonical bilaterian genome structure has been lost across all studied representatives of an entire phylum; reveal that linkage group fission can occur very frequently in specific lineages; and provide a powerful source of phylogenetic information.
Neutral transcriptome rewiring promotes QDR evolvability at the species level
Authors: Delplace Florent , Khafif Mehdi , Stam Remco , Barbacci Adelin , Raffaele Sylvain 
Published: February 2024

AbstractQuantitative disease resistance (QDR) is an immune response limiting pathogen damage in plants. It involves transcriptomic reprogramming of numerous genes, each having a small contribution to plant immunity. Despite QDR broad-spectrum nature, the evolution of its underlying transcriptome reprogramming remains largely uncharacterized. Here, we analyzed global gene expression in response to the necrotrophic fungusSclerotinia sclerotiorumin 23Arabidopsis thalianaaccessions of diverse origin and contrasted QDR phenotype. Over half of the species pan-transcriptome displayed local responses toS. sclerotiorum, with global reprogramming patterns incongruent with accessions phylogeny. Due to frequent small-amplitude variations, only ∼11% of responsive genes were common across all accessions, defining a core transcriptome enriched in highly-responsive genes. Co-expression and correlation analyses showed that QDR phenotypes result from the integration of numerous genes expression. Promoter sequence comparisons revealed that variation in DNA-binding sites within cis-regulatory regions contributing to gene expression rewiring. Finally, transcriptome-phenotype maps revealed abundant neutral networks connecting diverse QDR transcriptomes with no loss of resistance, hallmarks of robust and evolvable traits. This navigability associated with regulatory variation in core genes highlights their role in QDR evolvability. This work provides insights into the evolution of complex immune responses, informing models for plant disease dynamics.Classification: Biological Sciences, Plant Biology
Bottlebrush polyethylene glycol nanocarriers translocate across human airway epithelium via molecular architecture enhanced endocytosis
Authors: He Zhi-Jian , Huang Baiqiang , Cai Li-Heng 
Published: February 2024

AbstractPulmonary drug delivery is critical to the treatment of respiratory diseases. However, the human airway surface presents multiscale barriers to efficient drug delivery. Here we report a bottlebrush polyethylene glycol (PEG-BB) nanocarrier that can translocate across all barriers within the human airway surface. Guided by the molecular theory, we design a PEG-BB molecule consisting of a linear backbone densely grafted by many (∼1,000) low molecular weight (∼1000 g/mol) PEG chains; this results in a highly anisotropic, wormlike nanocarrier featuring a contour length of ∼250 nm, a cross-section of ∼20 nm, and a hydrodynamic diameter of ∼40 nm. Using the classic air-liquid-interface culture system to recapitulate essential biological features of the human airway surface, we show that PEG-BB rapidly penetrates through endogenous airway mucus and periciliary brush layer (mesh size of 20-40 nm) to be internalized by cells across the whole epithelium. By quantifying the cellular uptake of polymeric carriers of various molecular architectures and manipulating cell proliferation and endocytosis pathways, we show that the translocation of PEG-BB across the epithelium is driven by bottlebrush architecture enhanced endocytosis. Our results demonstrate that large, wormlike bottlebrush PEG polymers, if properly designed, can be used as a novel carrier for pulmonary and mucosal drug delivery.Table of Contents
Ultra-processed food staples dominate mainstream U.S. supermarkets. Americans more than Europeans forced to choose between health and cost
Authors: Amaraggi Bertrand , Wood Wendy , Guinovart Martín Laura , Giménez Sánchez Jaime , Fleta Sánchez Yolanda , de la Garza Puentes Andrea 
Published: February 2024

AbstractBACKGROUNDThe United States (U.S.) is the leading country in ultra-processed food (UPF) consumption, accounting for 60% of caloric intake, compared to a range of 14 to 44% in Europe. Given the increasingly evident health risks of UPF consumption, this is a major health problem. Common UPFs include soft drinks, snacks, processed meats, cookies, and candy. We hypothesized that even basic staple foods in the United States are ultra-processed and aimed to study the UPF prevalence in food staples from popular U.S. supermarkets compared with European countries.METHODOLOGYWe analyzed staple food products (bread, canned goods, cereals, eggs, milk, vegetables, and yogurt) stocked in U.S. supermarket chains (Walmart, Target, and Whole Foods), France (Carrefour), and Spain (Mercadona). Using an algorithm that identifies UPF values based on the NOVA and Food and Agriculture Organization of the United Nations guidelines, we identified the UPF prevalence and average number of UPF markers (cosmetic ingredients/additives).RESULTSThe prevalence of UPFs in budget-friendly supermarkets, Walmart, and Target, is 41-42% higher than Whole Foods, a store focused on quality. Furthermore, UPFs in Walmart and Target have 75% and 57% more UPF markers, respectively, than UPFs in Whole Foods. Around 58% of staples in U.S. leading supermarkets are ultra-processed, which is 41% more than supermarkets in Europe. Furthermore, the U.S. UPFs contain 41% more UPF markers than their EU counterparts.CONCLUSIONMost of the staple food products at mainstream U.S. budget-friendly retailers are ultra-processed, which is not the case at a more premium, quality focused store. Compared to supermarkets in Europe, the U.S. mainstream supermarkets have more UPFs, and those foods also have more UPF markers. Making healthy food choices in the United States is a challenge that is compromised by the high availability and accessibility of UPFs, even among everyday products that constitute the dominant part of the diet of a population. The European model shows the possibility of decreasing the UPF availability in large supermarkets. American consumers need more tools and guidance to identify UPFs along with greater regulation of UPF products to prioritize healthy choices and reduce UPF availability.
One effect and two causes: Growth acceleration and breast cancer risk after hormone replacement therapy
Authors: Hölzel Dieter , Schlesinger-Raab Anne , Halfter Kathrin 
Published: February 2024

AbstractBackgroundAn increased risk for breast cancer (BC) following hormone replacement therapy (HT) with estrogen and progesterone in women has been reported in several studies. However, HTs are associated with two distinct effects, a BC risk (RF) and an acceleration of BC growth (GAF). The interaction of both effects is analyzed.MethodsUsing data from the U.S. population on BC incidence and life expectancy specific cohorts and their disease trajectories are modelled. First, age-specific BCs are randomly generated for the age interval 50-80 years based on public data. Second, this simulated cohort subsequently receives a HT over 4 years that accelerates the growth of prevalent BCs. In a third cohort additional BCs are simulated caused by HT under treatment. The cumulative incidence of BCs is modelled for up to 30 years using different assumptions on BC growth duration, GAF and RF, as well as the duration of HT. The Women’s Health Initiative Study (WHI-S) is also simulated in a fourth cohort assuming a GAF 1.4 and RF 2.0.ResultsStudies modelling the risk of BC after HT imply two main findings: First, the growth of prevalent BCs is accelerated in parallel to the start of HT. This results in an increased BC incidence where the relative risk is equivalent to the GAF. The duration of HT defines the turning point of this increase. The second finding demonstrates that during the 15 years of BC growth an inherent RF for BC through HTs becomes observable only after a comparable delay. The combined effect results in an overlap of age-specific BCs, which develop at the same time, both growing faster under HT.Varying parameters can explain different results in the WHI-S. According to the WHI almost 6 million women decided to discontinue or not to start HT. This offers a valid explanation (assuming a GAF 2) for the 10% decline in incidence around 2002. Estimates which report one million additional BCs associated with HT in Western countries since 1990 can thus, for the most part, be attributed to more rapidly growing prevalent BCs.ConclusionHT accelerates the growth of prevalent BCs and can also cause BCs which become symptomatic after 10 or more years. In combination these effects increase BC incidence. Differentiated information on these inherent risks and benefits should support shared decision-making for HT.
Functional Characterisation of the ATOH1 Molecular Subtype Indicates a Pro-Metastatic Role in Small Cell Lung Cancer
Authors: Catozzi Alessia , Peiris-Pagès Maria , Humphrey Sam , Revill Mitchell , Morgan Derrick , Roebuck Jordan , Chen Yitao , Davies-Williams Bethan , Lallo Alice , Galvin Melanie , Pearce Simon P , Kerr Alastair , Priest Lynsey , Foy Victoria , Carter Mathew , Caeser Rebecca , Chan Joseph , Rudin Charles M. , Blackhall Fiona , Frese Kristopher K , Dive Caroline , Simpson Kathryn L 
Published: February 2024

ABSTRACTMolecular subtypes of Small Cell Lung Cancer (SCLC) have been described based on differential expression of transcription factors (TFs)ASCL1, NEUROD1,POU2F3and immune-related genes. We previously reported an additional subtype based on expression of the neurogenic TFATOH1within our SCLC Circulating tumour cell- Derived eXplant (CDX) model biobank. Here we show that ATOH1 protein was detected in 7/81 preclinical models and 16/102 clinical samples of SCLC. In CDX models, ATOH1 directly regulated neurogenesis and differentiation programs consistent with roles in normal tissues. Inex vivocultures of ATOH1-positive CDX, ATOH1 was required for cell survival.In vivo, ATOH1 depletion slowed tumour growth and suppressed liver metastasis. Our data validate ATOH1 as abona fideoncogenic driver of SCLC with tumour cell survival and pro-metastatic functions. Further investigation to explore ATOH1 driven vulnerabilities for targeted treatment with predictive biomarkers is warranted.
Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity
Authors: Katz Liora S. , Visser Emira J. , Plitzko Kathrin F. , Pennings Marloes A.M. , Cossar Peter J. , Tse Isabelle L. , Kaiser Markus , Brunsveld Luc , Ottmann Christian , Scott Donald K. 
Published: February 2024

AbstractThe Carbohydrate Response Element Binding Protein (ChREBP) is a glucose-responsive transcription factor (TF) with two major splice isoforms (α and β). In chronic hyperglycemia and glucolipotoxicity, ChREBPα-mediated ChREBPβ expression surges, leading to insulin-secreting β-cell dedifferentiation and death. 14-3-3 binding to ChREBPα results in cytoplasmic retention and suppression of transcriptional activity. Thus, small molecule-mediated stabilization of this protein-protein interaction (PPI) may be of therapeutic value. Here, we show that structure-based optimizations of a ‘molecular glue’ compound led to potent ChREBPα/14-3-3 PPI stabilizers with cellular activity. In primary human β-cells, the most active compound retained ChREBPα in the cytoplasm, and efficiently protected β-cells from glucolipotoxicity while maintaining β-cell identity. This study may thus not only provide the basis for the development of a unique class of compounds for the treatment of Type 2 Diabetes but also showcases an alternative ‘molecular glue’ approach for achieving small molecule control of notoriously difficult to target TFs.Graphical Abstract
Consumer preferences for fungus-resistant grape varieties: an explorative segmentation study in Germany
Authors: Kiefer Christoph , Szolnoki Gergely 
Published: February 2024

PurposeThe significance of fungus-resistant grape varieties (FRGVs) has markedly increased across the entire value chain in recent years, becoming increasingly pertinent for the wine industry. The study contributes to the theoretical understanding of consumer behaviour in the wine industry through the identification of different clusters and the analysis of their accessibility to the FRGV on the basis of various criteria.Design/methodology/approachA quantitative survey was conducted involving 644 participants that was screened based on socio-demographic factors to ensure representation of the German population. The collected data were analysed using factor and cluster analyses, alongside various multivariate tests, to statistically elucidate similarities and differences between clusters.FindingsIn total, six clusters were examined, each displaying varying responses to and pre-existing knowledge of resistant grape varieties. In general, as one becomes more involved in the world of wine and develops a sustainable and progressive outlook towards innovations in the wine industry, a positive inclination towards resistant grape varieties can be observed.Practical implicationsPractical implications for each cluster were subsequently derived, potentially facilitating the market entry or penetration of wines produced from FRGV. Experts and Quality-averse consumer desire wines from FRGV to have a unique terroir experience, while young casual drinkers interpret them as part of pop culture. LOHAS can be addressed with sustainability-oriented approaches. Price-sensitive consumer expect good qualities in the entry price segment, and Traditionalists can be reached by preserving traditions in a changing environmental context.Originality/valueThis paper fulfils the identified need to investigate consumer preferences for resistant grape varieties.