bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidences of a component Allee effect for an invasive pathogen:Hymenoscyphus fraxineus, the ash dieback agent
Authors: Laubray Simon , Buée Marc , Marçais Benoît 
Published: October 2022

AbstractInvasive pathogens are a major threat to forest health especially in managed forest with low diversity. The die-back of EuropeanFraxinus spp. caused by the fungusHymenoscyphus fraxineusis the latest example of pathogen invasion causing widespread damage. Host resistance and environment, in particular stand factors were shown to strongly impact disease severity on European ash. The fact thatH. fraxineusreproduce mostly through heterothallic sexual reproduction suggest that an Allee effect could limit the mating success at low host densities, thus limiting inoculum production and disease development. Populations ofH. fraxineuswere monitored during the fruiting period in a network of stands across a host density gradient in forest and non-forest environment. Ash dieback, basal area of ash, density of infected ash leaf debris (rachis) and apothecia in the litter and ascospores load in the air were determined in the different environments during two years. We showed significant differences between forest and non-forest environment with ash dieback, infection rate and inoculum production higher in forest settings. Host density significantly affected disease development, with crown dieback, density of infected rachis in the litter and inoculum production increasing with host density. We also demonstrated that fruiting rate, i.e. the number of apothecia per infected rachis dry weight, is strongly dependent on infected rachis density. Inoculum production is therefore limited at low host densities. Such a component Allee effect could be important inH. fraxineusepidemiology and invasion dynamic.
EPIGENETIC LANDSCAPE OF HEAT STRESS INTERGENERATIONAL INHERITANCE IN A TELEOST FISH
Authors: Brionne Aurélien , Goupil Anne-Sophie , Kica Stéphanie , Lareyre Jean-Jacques , Labbé Catherine , Laurent Audrey 
Published: October 2022

ABSTRACTEpigenetic information is transmitted from cell to cell, and even generation to generation. The question of epigenetic inheritance in fish has become of crucial interest in the recent years, when the mammalian model of methylome erasure in germ cells and embryos was found not to be conserved. Fish, which are particularly exposed to environmental variations might thus be prone to transmit epigenetic alterations to their offspring, driving rapid environmental acclimation. Here, by sequencing spermatozoa and muscle methylomes, we characterized the methylation landscape of paternal gametes in rainbow trout and demonstrated its sensitivity to a 4°C increased rearing temperature during spermatogenesis. We found that spermatozoa methylome primes housekeeping and developmental genes for activation and might be instrumental to early development. Most of these methylation-free promoters were not affected by temperature, attesting the robustness of the epigenetic programming of early development. However, the increase of temperature triggered the differential methylation of 5,359 regions, among which 560 gene promoters control spermiogenesis and lipid metabolism. We therefore report, for the first time in fish, that sperm epigenetic landscape carries marks of parental environmental conditions. In the context of a 4°C temperature increase during spermatogenesis, we describe how rainbow trout sperm DNA methylation might be a molecular basis of intergenerational inheritance and question its role in controlling next generation’s performances and acclimation to climate change.
Chronic IFNα treatment induces leukopoiesis, increased plasma succinate and immune cell metabolic rewiring
Authors: Yennemadi Anjali S. , Jameson Gráinne , Glass Mary , De Pasquale Carolina , Keane Joseph , Bianchi Massimiliano , Leisching Gina 
Published: October 2022

AbstractAlthough clinically effective, the actions of IFNα, either produced endogenously or by therapeutic delivery, remain poorly understood. Emblematic of this research gap is the disparate array of notable side effects that occur in susceptible individuals, such as neuropsychiatric consequences, autoimmune phenomena, and infectious complications. We hypothesised that these complications are driven at least in part by dysregulated cellular metabolism. Male Wistar rats were treated with either 170,000 IU/kg human recombinant IFNα-2a or BSA/saline (0.9% NaCl) three times per week for three weeks. Bone marrow (BM) immune cells were isolated from the excised femurs for glycolytic rate and mitochondrial function assessment using Agilent Seahorse Technology. Frequencies of immune cell populations were assessed by flow cytometry to determine whether leukopoietic changes had occurred in both blood and BM. Plasma levels of lactate and succinate were also determined. BMDMs were metabolically assessed as above, as well as their metabolic response to an antigenic stimulus (iH37Rv). We observed that BM immune cells from IFN-treated rats exhibit a hypermetabolic state (increased basal OCR/GlycoPER) with decreased mitochondrial metabolic respiration and increased non-mitochondrial OCR. Flow cytometry results indicated an increase in immature granulocytes (RP1-SSChi CD45lo) and classical monocytes (CD43lo RP1hi) in the blood, together with increased succinate levels in the plasma. BMDMs from IFN-treated rats retained the hypermetabolic phenotype after differentiation and failed to induce a step-up in glycolysis and mitochondrial respiration after bacterial stimulation. This work provides the first evidence of the effects of IFNα treatment in inducing hypermetabolic immune features that are associated with markers of inflammation, leukopoiesis, and defective responses to bacterial stimulation.
Proteome integral solubility alteration assay combined with multi-criteria decision-making analysis for developing adverse outcome pathways
Authors: Lizano-Fallas Veronica , del Amor Ana Carrasco , Cristobal Susana 
Published: October 2022

ABSTRACTUnderstanding the biological impact of chemicals is hindered by the high number and diversity of compounds in the market. To simplify the chemical risk assessment, the adverse outcome pathway (AOP) method has arisen as a framework to predict the impact of chemical exposure on human and environmental health. The development of this predictive tool requires knowledge of the molecular interaction between chemicals and protein targets. Those molecular initiating events connect alterations of cellular function with physiological impairment. This strategy aims to focus on the complex biological interaction to predict the impact on health. The high-throughput identification of all chemical targets can be obtained by a proteomics-based thermal shift assay, however, selecting the priority target candidate is a biased process strongly dependent on expert knowledge and literature. Here, we unravel new molecular initiating event from a tested chemical combining the target deconvolution by the proteome integral solubility alteration (PISA) assay, and the target selection by an analytical hierarchy process (AHP) approach. In the proof-of-concept study, we identified by PISA assay 8 protein targets for 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) from the soluble proteome from hepatic cells containing 2824 proteins. The definition of the AHP approach facilitates the selection of heat shock protein beta-1 (Hspb1) as the most suitable protein for developing AOPs. Our results demonstrated that the process of target identification is independent from a chemical characterization, and that the process of data curation and target selection is less sensitive to lack of toxicological information. We anticipate that this innovative integration of methods could decipher the chemical-protein interactions from new chemicals including the new alternative chemicals designed for chemical replacement and that would discover new molecular initiating events to support more sustainable methodologies to gain time and resources in chemicals assessment.SYNOPSISOur combined methodologies can determine the most suitable target to develop adverse outcome pathways from the proteome-wide protein target identification.
Diverse patterns of secondary structure across genes and transposable elements are associated with siRNA production and epigenetic fate
Authors: Martin Galen , Solares Edwin , Muyle Aline , Bousios Alexandros , Gaut Brandon S. 
Published: October 2022

ABSTRACTRNA molecules carry information in their primary sequence and also their secondary structure. Secondary structure can confer important functional information, but it is also a potential signal for an RNAi-like host epigenetic response mediated by small interfering RNAs (siRNAs). In this study, we predicted local secondary structures in features of the maize genome, focusing on small regions that had folding energies similar to pre-miRNA loci. We found secondary structures to be common in retrotransposons, inHelitrons, and in genes. These structured regions mapped higher diversities of siRNAs than regions without structure, explaining up to 24% of variation of the siRNA distribution across some TE types. Among genes, those with secondary structure were 1.5-fold more highly expressed, on average, than genes without secondary structure. However, these genes were also more variably expressed across the 26 NAM lines, and this variability correlated with the number of mapping siRNAs. We conclude that local stem-loop structures are a nearly ubiquitous feature of expressed regions of the maize genome, that they correlate with higher siRNA mapping, and that they can represent a trade-off between functional need and the potentially negative consequences of siRNA production.
DISRUPTION OF SYMPATHETIC OUTFLOW TO INTRA-ABDOMINAL ORGANS EMULATES THE METABOLIC EFFECTS OF SLEEVE GASTRECTOMY IN OBESE MICE
Authors: Schwartz Gary J. , Batista Rogerio O. , Lopatinsky Natalie R. , Kraljević Marko , Jiang Caroline S. , Dirnberger Amanda S. , Emiliano Ana B. 
Published: October 2022

ABSTRACTAlthough sleeve gastrectomy (SG) is the most commonly performed bariatric surgery in the US, its mechanistic underpinnings have not been fully determined. Thus, we set out to investigate whether SG’s effects on the peripheral sympathetic system could mediate the metabolic effects of SG. The celiac-superior mesenteric ganglia (CSMG) lie juxtaposed to the stomach and supply the sympathetic innervation of the stomach, as well as to numerous intra-abdominal organs relevant to metabolism. Here we investigated the effects of SG on the CSMG. SG led to the degeneration of neurons in the CSMG, as evidenced by chromatolysis, which was not found in control mice. Furthermore, CSMG ablation (CGX) completely recapitulated the glycemic and weight loss effects of SG, promoting weight loss at the expense of fat mass in both males and females. Glycemic improvement was robust in males but much more modest in female mice. Norepinephrine tissue content measurement by high performance liquid chromatography revealed that liver, duodenum, and ileum were organs where both SG and CGX displayed evidence of significant sympathetic denervation. Both SG and CGX were associated with increased levels of glucagon-like peptide 1 (GLP-1) and high free fatty acid content in the stools. In conclusion, CSMG neuronal degeneration caused by SG appears to be a mediator of the metabolic effects of this type of bariatric surgery.
Persistent Homology-based Functional Connectivity Explains Cognitive Ability: Life-span Study
Authors: Ryu Hyunnam , Habeck Christian G. , Stern Yaakov , Lee Seonjoo 
Published: October 2022

AbstractBrain-segregation attributes in resting-state functional networks have been widely investigated to understand cognition and cognitive aging using various approaches (e.g., average connectivity within/between networks and brain system segregation). While these approaches have assumed that resting-state functional networks operate in a modular structure, a complementary perspective assumes that a core-periphery or rich club structure accounts for brain functions where the hubs are tightly interconnected to each other to allow for integrated processing. We introduce a novel method, persistent homology (PH)-based functional connectivity, to quantify the pattern of information during the integrated processing. We also investigate whether PH-based functional connectivity explains cognitive performance and compare the amount of variability in explaining cognitive performance for three sets of independent variables: (1) PH-based functional connectivity, (2) graph theory-based measures, and (3) brain system segregation. Resting-state functional connectivity data were extracted from 279 healthy participants, and cognitive ability scores were generated in four domains (fluid reasoning, episodic memory, vocabulary, and processing speed). The results first highlight the pattern of brain-information flow over whole brain regions (i.e., integrated processing) accounts for more variance of cognitive abilities than either brain system segregation or the graph theory-based network topology measure. The results also show that fluid reasoning and vocabulary performance significantly decrease as the strength of the additional information flow on functional connectivity with the shortest path increases.
Surface-based Characterization of Gastric Anatomy and Motility using Magnetic Resonance Imaging and Neural Ordinary Differential Equation
Authors: Wang Xiaokai , Cao Jiayue , Han Kuan , Choi Minkyu , She Yushi , Scheven Ulrich , Avci Recep , Du Peng , Cheng Leo K. , Di Natale Madeleine R , Furness John B , Liu Zhongming 
Published: October 2022

AbstractGastrointestinal magnetic resonance imaging (MRI) provides rich spatiotemporal data about the volume and movement of the food inside the stomach, but does not directly report on the muscular activity of the stomach itself. Here we describe a novel approach to characterize the motility of the stomach wall that drives the volumetric changes of the gastric content. In this approach, a surface template was used as a deformable model of the stomach wall. A neural ordinary differential equation (ODE) was optimized to model a diffeomorphic flow that ascribed the deformation of the stomach wall to a continuous biomedical process. Driven by this diffeomorphic flow, the surface template of the stomach progressively changes its shape over time or between conditions, while preserving its topology and manifoldness. We tested this approach with MRI data collected from 10 Sprague Dawley rats under a lightly anesthetized condition. Our proposed approach allowed us to characterize gastric anatomy and motility with a surface coordinate system common to every individual. Anatomical and motility features could be characterized for each individual, and then compared and summarized across individuals for group-level analysis. As a result, high-resolution functional maps were generated to reveal the spatial, temporal, and spectral characteristics of muscle activity as well as the coordination of motor events across different gastric regions. The relationship between muscle thickness and gastric motility was also evaluated throughout the entire stomach wall. Such a structure-function relationship was used to delineate two distinctive functional regions of the stomach. These results demonstrate the efficacy of using GI-MRI to measure and model gastric anatomy and function. This approach described herein is expected to enable non-invasive and accurate mapping of gastric motility throughout the entire stomach for both preclinical and clinical studies.
Multi-location trials identify stable high yielding spring bread and durum wheat cultivars in Mexico
Authors: Valenzuela-Antelo Jorge L , Benitez-Riquelme Ignacio , Vargas-Hernandez Mateo , Huerta-Espino Julio , Bentley Alison R , Villaseñor-Mir Hector E , Pinera-Chavez Francisco J 
Published: October 2022

ABSTRACTDetermining the stability and consistency of grain yield performance requires accurate evaluation of genotypes in different environments. In Mexico, annual national spring wheat irrigated trials are conducted to assess elite bread and durum wheat performance in different testing environments (TEs) in the main wheat-growing areas. These trials provide data supporting release of new cultivars and aim to also address Mexican wheat value chain grain needs. In this study we analyzed 30 bread and durum wheat trial results from the 2012/13 and 2013/14 growing cycles conducted across TEs in northwest, north and central Mexico. Environmental variability (location, sowing timing, and irrigation schemes) across the national spring wheat irrigated trials enabled genotype by environment interaction to be effectively evaluated. We identified genotypes with high and stable grain yield across TEs of the wheat-growing areas of Mexico. The bread cultivars Bacorehuis F2015 and Borlaug100 F2014, and the durum cultivars Barobampo C2015, CONASIST C2015 and Anatoly C2011 were high yielding and gave stable performance in most of the TEs. This analysis demonstrates the utility of multi-year, multi-environment testing and analysis to identify improved wheat cultivars to meet wheat production demand in Mexico.
Highly Excretable Gold Supraclusters for TranslatableIn VivoRaman Imaging of Tumors
Authors: Yu Jung Ho , Jeong Myeong Seon , Cruz Emma Olivia , Alam Israt S. , Tumbale Spencer K. , Zlitni Aimen , Lee Song Yeul , Park Yong Il , Ferrara Katherine , Kwon Seung-Hae , Gambhir Sanjiv S. , Rao Jianghong 
Published: October 2022

ABSTRACTRaman spectroscopy provides excellent specificity forin vivopreclinical imaging through a readout of fingerprint-like spectra. To achieve sufficient sensitivity forin vivoRaman imaging, metallic gold nanoparticles larger than 10 nm were employed to amplify Raman signals via surface-enhanced Raman scattering (SERS). However, the inability to excrete such large gold nanoparticles has restricted the translation of Raman imaging. Here we present Raman-active metallic gold supraclusters that are biodegradable and excretable as nanoclusters. Although the small size of the gold nanocluster building blocks compromises the electromagnetic field enhancement effect, the supraclusters exhibit bright and prominent Raman scattering comparable to that of large gold nanoparticle-based SERS nanotags due to high loading of NIR-resonant Raman dyes and much suppressed fluorescence background by metallic supraclusters. The bright Raman scattering of the supraclusters was pH-responsive, and we successfully performedin vivoRaman imaging of acidic tumors in mice. Furthermore, in contrast to large gold nanoparticles that remain in the liver and spleen, the supraclusters dissociated into small nanoclusters, and 73% of the administered dose to mice was excreted over 4 months. The highly excretable Raman supraclusters demonstrated here offer great potential for clinical applications ofin vivoRaman imaging by replacing non-excretable large gold nanoparticles.
The genome ofLactuca saligna, a wild relative of lettuce, provides insight into non-host resistance to the downy mildewBremia lactucae
Authors: Xiong Wei , Berke Lidija , Michelmore Richard , van Workum Dirk-Jan M. , Becker Frank F.M. , Schijlen Elio , Bakker Linda V. , Peters Sander , van Treuren Rob , Jeuken Marieke , Bouwmeester Klaas , Schranz M. Eric 
Published: October 2022

SummaryLactuca salignaL. is a wild relative of cultivated lettuce (Lactuca sativaL.), with which it is partially interfertile. Hybrid progeny suffer from hybrid incompatibilities (HI), resulting in reduced fertility and distorted transmission ratios.Lactuca salignadisplays broad spectrum resistance against lettuce downy mildew caused byBremia lactucaeRegel and is considered a non-host species. This phenomenon of resistance inL. salignais called non-host resistance (NHR). One possible mechanism behind this NHR is through the plant–pathogen interaction triggered by pathogen-recognition receptors, including nucleotide-binding leucin-rich repeats (NLRs) and receptor-like kinases (RLKs). We report a chromosome-level genome assembly ofL. saligna(accession CGN05327), leading to the identification of two large paracentric inversions (>50 Mb) betweenL. salignaandL. sativa. Genome-wide searches delineated the major resistance clusters as regions enriched inNLRs andRLKs. Three of the enriched regions co-locate with previously identified NHR intervals. RNA-seq analysis ofBremiainfected lettuce identified several differentially expressedRLKs in NHR regions. Three tandem wall-associated kinase-encoding genes (WAKs) in the NHR8 interval display particularly high expression changes at an early stage of infection. We proposeRLKs as strong candidate(s) for determinants for the NHR phenotype ofL. saligna.
Biostatistics and its impact on hazard characterization using in vitro developmental neurotoxicity assays
Authors: Keßel Hagen Eike , Masjosthusmann Stefan , Bartmann Kristina , Blum Jonathan , Dönmez Arif , Förster Nils , Klose Jördis , Mosig Axel , Pahl Melanie , Leist Marcel , Scholze Martin , Fritsche Ellen 
Published: October 2022

AbstractIn the field of hazard assessment, Benchmark concentrations (BMC) and their associated uncertainty are of particular interest for regulatory decision making. The BMC estimation consists of various statistical decisions to be made, which depend largely on factors such as experimental design and assay endpoint features. In current data practice, the experimenter is often responsible for the data analysis and therefore relies on statistical software without being aware about the software default settings and how they can impact the outputs of data analysis. To provide more insight into how statistical decision making can influence the outcomes of data analysis and interpretation, we have used case studies on a large dataset produced by a developmental neurotoxicity (DNT) in vitro battery (DNT IVB). Here we focused on the BMC and its confidence interval (CI) estimation, as well as on the final hazard classification. We identified five crucial statistical decisions experimenter have to face during data analysis: choice of replicate averaging, response data normalization, regression modelling, BMC and CI estimation, as well as choice of benchmark response levels. In addition, the strength of our data evaluation platform is the integration of endpoint-specific hazard classifications, including flagging systems for uncertain cases, which none of the so far existing statistical data analysis platforms provide. The insights gained in this study demonstrate how important fit-for-purpose, internationally harmonized and accepted data evaluation and analysis procedures are for an objective hazard classification.
Genetic architecture of behavioural resilience to ocean acidification
Authors: Lehmann Robert , Schunter Celia , Welch Megan J. , Arold Stefan T. , Nilsson Göran E. , Tegner Jesper N. , Munday Philip L. , Ravasi Timothy 
Published: October 2022

AbstractGenetic variation is essential for adaptation to rapid environmental changes. Identifying genetic variation associated with climate-change related phenotypes is therefore the necessary first step towards predictive models of genomic vulnerability.Here we used a whole-genome scan to identify candidate genetic variants associated with differences in behavioural resilience to ocean acidification in a coral reef fish. We identified three genomic regions that differ between individuals that are behaviourally tolerant compared with behaviourally sensitive to elevated CO2. These include a dopamine receptor (drd4rs), cadherin related family member 5-like (cdhr5l), Synapse-associated protein 1 (syap1), and GRB2 Associated Regulator of MAPK1 Subtype 2 (garem2), which have previously been found to modify behaviour related to boldness, novelty seeking, and learning in other species, and differ between behaviourally tolerant and sensitive individuals.Consequently, the identified genes are promising candidates in the search of the genetic underpinnings and adaptive potential of behavioural resilience to ocean acidification in fishes.