bluuebunny/crossref_metadata_2025_split huggingface dataset:
10β-Hydroxyestra-1,4-diene-3,17-dione Does Not Bind to the Nuclear Estrogen Receptor α
Authors: Prokai-Tatrai Katalin , Prokai Laszlo 
Published: August 2022

ABSTRACTThe lack of nuclear estrogen receptor (ERα and ERβ) bindings of 10β-hydroxyestra-1,4-diene-3,17-dione (HEDD) and structurally related steroidal para-quinols have been shown by an extensive series of multidisciplinary investigational evidence including specific receptor binding studies. In support of the latter, the absence of estrogen-derived para-quinols’ in vivo uterotrophic effects has also been well documented. Via in silico docking, a recent publication by Canário et al. (2022) reported a robust binding of HEDD (Figure 1B) to ERα. The authors claimed a strong binding of HEDD — as strong as that of its natural ligand, 17β-estradiol (E2), the main human estrogen. However, an examination of the virtual binding pocket revealed that at least one residue near the critical ligand-binding site of their reported HEDD–ERα complex was labelled as “unknown” indicating thereby alteration of the receptor’s published structure (Tannenbaum et al, 1998; Bafna et al., 2020) to fit the ligand. Based on these arguments, the contradictory result by Canário et al. (2022) on HEDD’s binding to ERα should be dismissed.
Distinct eosinophil subsets are modulated by agonists of the commensal-metabolite and vitamin B3 receptor GPR109A during allergic-type inflammation
Authors: Azzoni Rossana , Filbey Kara J. , Daw Rufus H. , Krauss Maria Z. , Hepworth Matthew R. , Konkel Joanne E. , Hessel Edith M. , Kannan Yashaswini , Grainger John R. 
Published: August 2022

AbstractEosinophils are key contributors to allergic pathology, however, increasingly eosinophils are described to have important roles in organ health and immunoregulation. Factors that impact these diverse functions of eosinophils are not understood. Here we show in allergic-type lung inflammation, metabolically distinct populations of eosinophils can be identified based on expression of Siglec-F (Siglec-Fhi and Siglec-Fint). Notably, the lung Siglec-Fhi population was responsive to the commensal microbiome, expressing the short-chain fatty acid receptor GPR109A. Animals deficient in GPR109A displayed augmented eosinophilia during allergy. Moreover, transferred GPR109A-deficient eosinophils released more eosinophil peroxidase than controls. Treatment with butyrate or vitamin B3, both GPR109A ligands, reduced Siglec-Fhi eosinophil frequency and activation, which was associated with apoptosis of Siglec-Fhi eosinophils. These findings identify GPR109A as an unappreciated regulator of glycolytic Siglec-Fhi eosinophils, raising the possibility of depleting pathological eosinophil populations in disease states while sparing those with homeostatic functions.
In silicoevidence for the utility of parsimonious root phenotypes for improved vegetative growth and carbon sequestration under drought
Authors: Schäfer Ernst D. , Ajmera Ishan , Farcot Etienne , Owen Markus R. , Band Leah R. , Lynch Jonathan P. 
Published: August 2022

ABSTRACTDrought is a primary constraint to crop yields and climate change is expected to increase the frequency and severity of drought stress in the future. It has been hypothesized that crops can be made more resistant to drought and better able to sequester atmospheric carbon in the soil by selecting appropriate root phenotypes. We introduceOpenSimRoot_v2, an upgraded version of the functional-structural plant/soil modelOpenSimRoot, and use it to test the utility of a maize root phenotype with fewer and steeper axial roots, reduced lateral root branching density, and more aerenchyma formation (i.e. the ‘Steep, Cheap, and Deep’ (SCD) ideotype) and different combinations of underlying SCD root phene states under rainfed and drought conditions in three distinct maize growing pedoclimatic environments in the USA, Nigeria, and Mexico. In all environments where plants are subjected to drought stress the SCD ideotype as well as several intermediate phenotypes lead to greater shoot biomass after 42 days. As an additional advantage, the amount of carbon deposited below 50 cm in the soil is twice as great for the SCD phenotype as for the reference phenotype in 5 out of 6 simulated environments. We conclude that crop growth and deep soil carbon deposition can be improved by breeding maize plants with fewer axial roots, reduced lateral root branching density, and more aerenchyma formation.
Heterodimerization-dependent secretion of BMPs in Drosophila
Authors: Bauer Milena , Aguilar Gustavo , Wharton Kristi A. , Matsuda Shinya , Affolter Markus 
Published: August 2022

AbstractCombinatorial signaling is key to instruct context-dependent cell behaviors. During embryonic development, adult homeostasis and disease, Bone Morphogenetic Proteins (BMPs) act as dimers to instruct specific cellular responses. BMP ligands can form both homo- or heterodimers; however, obtaining direct evidence of the endogenous localization and function of each form has proven challenging. Here, we make use of precise genome editing and direct protein manipulation via protein binders to dissect the existence and functional relevance of BMP homo- and heterodimers in the Drosophila wing imaginal disc. This approach revealed in situ the existence of Dpp (BMP2/4)/Gbb (BMP5/6/7/8) heterodimers. We found that Gbb, despite being produced by all the cells of the wing imaginal disc, is only secreted by the cells in which Dpp is expressed. Dpp and Gbb form a gradient of heterodimers whereas neither Dpp nor Gbb homodimers are evident under endogenous physiological conditions. We find that the formation of heterodimers is critical for obtaining optimal signaling and long-range BMP distribution in the developing wing. These results indicate that Dpp/Gbb heterodimers are the active signal required for epithelial patterning and growth.
The medial entorhinal cortex is necessary for the stimulus control over hippocampal place fields by distal, but not proximal, landmarks
Authors: Allison Elizabeth A.M.A. , Moore Joe W. , Arkell Daisy , Dudchenko Paul A. , Wood Emma R. 
Published: August 2022

AbstractA fundamental property of place cells in the hippocampus is the anchoring of their firing fields to salient landmarks within the environment. However, it is unclear how such information reaches the hippocampus. In the current experiment, we tested the hypothesis that the stimulus control exerted by distal visual landmarks requires input from the medial entorhinal cortex (MEC). Place cells were recorded from mice with ibotenic acid lesions of the MEC (n = 7) and from sham-lesioned mice (n = 6) following 90° rotations of either distal landmarks or proximal cues in a cue controlled environment. We found that lesions of the MEC impaired the anchoring of place fields to distal landmarks, but not proximal cues. We also observed that, relative to sham-lesioned mice, place cells in animals with MEC lesions exhibited significantly reduced spatial information and increased sparsity. These results support the view that distal landmark information reaches the hippocampus via the MEC, but that proximal cue information can do so via an alternative neural pathway.
LambdaPP: Fast and accessible protein-specific phenotype predictions
Authors: Olenyi Tobias , Marquet Céline , Heinzinger Michael , Kröger Benjamin , Nikolova Tiha , Bernhofer Michael , Sändig Philip , Schütze Konstantin , Littmann Maria , Mirdita Milot , Steinegger Martin , Dallago Christian , Rost Burkhard 
Published: August 2022

AbstractThe availability of accurate and fast Artificial Intelligence (AI) solutions predicting aspects of proteins are revolutionizing experimental and computational molecular biology. The webserverLambdaPPaspires to supersede PredictProtein, the first internet server making AI protein predictions available in 1992. Given a protein sequence as input,LambdaPPprovides easily accessible visualizations of protein 3D structure, along with predictions at the protein level (GeneOntology, subcellular location), and the residue level (binding to metal ions, small molecules, and nucleotides; conservation; intrinsic disorder; secondary structure; alpha-helical and beta-barrel transmembrane segments; signal-peptides; variant effect) in seconds. The structure prediction provided byLambdaPP- leveragingColabFold and computed in minutes- is based onMMseqs2multiple sequence alignments. All other feature prediction methods are based on the pLMProtT5. Queried by a protein sequence,LambdaPPcomputes protein and residue predictions almost instantly for various phenotypes, including 3D structure and aspects of protein function.Accessibility StatementLambdaPP is freely available for everyone to use underembed.predictprotein.org, the interactive results for the case study can be found underhttps://embed.predictprotein.org/o/Q9NZC2. The frontend of LambdaPP can be found on GitHub (github.com/sacdallago/embed.predictprotein.org), and can be freely used and distributed under the academic free use license (AFL-2). For high-throughput applications, all methods can be executed locally via the bio-embeddings (bioembeddings.com) python package, or docker image atghcr.io/bioembeddings/bio_embeddings, which also includes the backend of LambdaPP.Impact StatementWe introduce LambdaPP, a webserver integrating fast and accurate sequence-only protein feature predictions based on embeddings from protein Language Models (pLMs) available in seconds along with high-quality protein structure predictions. The intuitive interface invites experts and novices to benefit from the latest machine learning tools. LambdaPP’s unique combination of predicted features may help in formulating hypotheses for experiments and as input to bioinformatics pipelines.
Shifts from non-obligate generalists to obligate specialists in simulations of mutualistic network assembly
Authors: Metz Timo , Blüthgen Nico , Drossel Barbara 
Published: August 2022

AbstractUnderstanding ecosystem recovery after perturbation is crucial for ecosystem conservation. Mutualisms contribute key functions for plants such as pollination and seed dispersal. We modelled the assembly of mutualistic networks based on trait matching between plants and their animal partners that have different degrees of specialization on plant traits. Additionally, we addressed the role of non-obligate animal mutualists, including facultative mutualists or non-resident species that have their main resources outside the target site. Our computer simulations show that non-obligate animals facilitate network assembly during the early stages, furthering colonization by an increase in niche space and reduced competition. While non-obligate and generalist animals provide most of the fitness benefits to plants in the early stages of the assembly, obligate and specialist animals dominate at the end of the assembly. Our results thus demonstrate the combined occurrence of shifts from diet, trait, and habitat generalists to more specialised animals.
Activation of Cerebellar Lobule VI PCTH+–Med Pathway Selectively blocks METH-induced Conditioned Place Preference in mice
Authors: Ge Feifei , Wang Zilin , Wang Guanxiong , Chen Liying , Yang Ping , Wen Jun , Pan Weichao , Yu Wen , Cai Qinglong , Fan Yu , Chang Jiasong , Guan Xiaowei 
Published: August 2022

AbstractThe cerebellum is implicated in drug addiction. However, the cerebellar neuronal circuitry underlying addiction, especially classic pathway of Purkinje cells (PCs) to deep cerebellar nuclei (DCN), are largely unknown. Here, tracing experiments showed robust projections from the cerebellar lobule VI tyrosine hydroxylase (TH)-positive PCs (PCTH+) to CaMKII-positive glutamatergic neurons in medial cerebellar nucleus (MedCaMKII), forming PCTH+–MedCaMKII pathway. Then, mice were subjected to methylamphetamine (METH)-induced conditioned place preference (CPP), showing that METH exposure excited MedCaMKII and inhibited PCTH+. Silencing MedCaMKII by tettox suppressed the formation and expression of METH-induced CPP, but produced serious motor coordination deficits. Chemogenetic activation of lobule VI PCTH+–Med pathway during METH CPP training blocked the formation and expression of METH-induced CPP without affecting motor coordination, locomotor activity and sucrose reinforcements in mice. Our findings revealed a novel cerebellar lobule VI PCTH+–MedCaMKII pathway and pointed out is critical role in encoding METH-preferred behaviors.
A histone deacetylase complex establishes a transgenerationally inherited maternal epigenetic state controlling progeny seed dormancy
Authors: Chen Xiaochao , Macgregor Dana R. , Stefanato Francesca L. , Zhang Naichao , Barros-Galvão Thiago , Penfield Steven 
Published: August 2022

AbstractMother plants play an important role in the control of dormancy and dispersal characters of their progeny. In Arabidopsis seed dormancy is imposed by the embryo-surrounding tissues of the endosperm and seed coat. Here we show that the VERNALIZATION5/VIN3-LIKE 3 (VEL3) gene maintains maternal control over progeny seed dormancy by establishing an epigenetic state early in endosperm development that primes the depth of primary seed dormancy later established during seed maturation. VEL3 relocates MSI1 to the nucleolus and associates with other components of the histone deacetylase complex (HDAC), and is required for gene repression via PRC2 and HDAC at pericentromeric regions established in the central cell. Interestingly, the epigenetic state established by the maternal VEL3 is retained trans-generationally in mature seeds, and controls seed dormancy through the repression of programmed cell death-associated gene ORE1. Our data demonstrates a novel mechanism by which maternal control of progeny seed physiology persists post-shedding, maintaining parental control of seed behaviour.
Deep molecular, cellular and temporal phenotyping of developmental perturbations at whole organism scale
Authors: Saunders Lauren M. , Srivatsan Sanjay R. , Duran Madeleine , Dorrity Michael W. , Ewing Brent , Linbo Tor , Shendure Jay , Raible David W. , Moens Cecilia B. , Kimelman David , Trapnell Cole 
Published: August 2022

AbstractThe maturation of single cell transcriptomic technologies has facilitated the generation of comprehensive cellular atlases from whole embryos. A majority of this data, however, has been collected from wild type embryos without an appreciation for latent variation present in development. Here we present single cell transcriptomic data from 1812 individually resolved developing zebrafish embryos, encompassing 19 time points, 23 genetic perturbations, and totaling 3.2M cells. The high degree of replication in our study (8 or more embryos per condition) allows us to estimate the variance in cell type abundance organism-wide and to detect perturbation-dependent deviance in cell type composition relative to wild type embryos. Our approach is sensitive to rare cell types, resolving developmental trajectories and genetic dependencies in the cranial ganglia neurons, a cell population that comprises less than 1% of the embryo. Additionally, time-series profiling of individual mutants identified a group of brachyury-independent cells with strikingly similar transcriptomes to notochord sheath cells, leading to new hypotheses about the origins of the skull. We anticipate that standardized collection of high-resolution, organism-scale single cell data from large numbers of individual embryos will enable mapping the genetic dependencies of zebrafish cell types, while also addressing long-standing challenges in developmental genetics, including the cellular and transcriptional plasticity underlying phenotypic diversity across individuals.
Choice of climate data influences current and future global invasion risks for twoPhelsumageckos
Authors: Dubos Nicolas , Fieldsend Thomas W. , Roesch Markus A. , Augros Stéphane , Besnard Aurélien , Choeur Arthur , Ineich Ivan , Krysko Kenneth , Leroy Boris , Malone Sparkle L. , Probst Jean-Michel , Raxworthy Christopher , Crottini Angelica 
Published: August 2022

AbstractInvasion risks may be influenced either negatively or positively by climate change, depending on the species. These can be predicted with species distribution models, but projections can be strongly affected by input environmental data (climate data source, Global Circulation Models and Shared Socio-economic Pathways SSP). We modelled the distribution ofPhelsuma grandisandP. laticauda, two Malagasy reptiles that are spreading globally. We accounted for drivers of spread and establishment using socio-economic factors (e.g., distance from ports) and two climate data sources, i.e., Climatologies at High Resolution for the Earth’s and Land Surface Areas (CHELSA) and Worldclim. We further quantified the degree of agreement in invasion risk models that utilised CHELSA and Worldclim data for current and future conditions. Most areas identified as highly exposed to invasion risks were consistently identified (e.g. in Caribbean and Pacific Islands). However, projected risks differed locally. We also found notable differences in quantitative invasion risk (3% difference in suitability scores forP. laticaudaand up to 14% forP. grandis) under current conditions. Despite both species native distributions overlap substantially, climate change will drive opposite responses on invasion risks by 2070 (decrease forP. grandis, increase forP. laticauda). Overall, projections of future invasion risks were the most affected by climate data source, followed by SSP. Our results highlight that assessments of current and future invasion risks are sensitive to the climate data source, especially in Islands. We stress the need to account for multiple climatologies when assessing invasion risks.
Re-inventing pathogen passage for social microbes
Authors: Dimitriu Tatiana , Souissi Wided , Morwool Peter , Darby Alistair , Crickmore Neil , Raymond Ben 
Published: August 2022

AbstractPassage experiments that sequentially infect hosts with parasites have long been used to manipulate virulence. However, in many invertebrate pathogens passage has been applied naively without a full theoretical understanding of how best to select for increased virulence. This has led to very mixed results. Understanding the evolution of virulence is complex because selection on parasites occurs across multiple spatial scales with potentially different conflicts operating on parasites with different life-histories. For example, in social microbes, strong selection on replication rate within hosts can lead to cheating and loss of virulence, because investment in public goods virulence reduces replication rate. In contrast, selection acting at a between host scale maintains virulence by selecting on parasite population size. In this study we tested how different scales of selection and varying mutation supply affect evolution of virulence against resistant hosts in the specialist insect pathogen Bacillus thuringiensis., aiming to optimize methods for strain improvement against a difficult to kill insect target. We show that selection for infectivity using competition between sub-populations in a metapopulation prevents social cheating, acts to retain key virulence plasmids and facilitates increased virulence. Increased virulence was associated with reduced efficiency of sporulation, and loss of function in putative regulatory genes but not with altered expression of known virulence factors. Selection in a metapopulation provides a broadly applicable tool for improving the efficacy of biocontrol agents. Moreover, a structured host population can facilitate artificial selection on infectivity, while selection on life history traits such as faster replication or larger population sizes can reduce virulence can reduce virulence in social microbes.
Improved memory CD8 T cell response to delayed vaccine boost is associated with a distinct molecular signature
Authors: Natalini Ambra , Simonetti Sonia , Favaretto Gabriele , Lucantonio Lorenzo , Peruzzi Giovanna , Muñoz-Ruiz Miguel , Kelly Gavin , Contino Alessandra Maria , Sbrocchi Roberta , Battella Simone , Capone Stefania , Folgori Antonella , Nicosia Alfredo , Santoni Angela , Hayday Adrian C. , Di Rosa Francesca 
Published: August 2022

SummaryAlthough the prime/boost interval can impact vaccine responses, the criteria for deciding its time length are poorly defined. To address this, we examined CD8 T cell responsiveness to boost in a BALB/c mouse model of intramuscular (i.m.) vaccination by priming with HIV-1 gag-encoding Chimpanzee adenovector, and boosting with HIV-1 gag-encoding Modified Vaccinia virus Ankara. We found that boost was more effective at day(d)100 than at d30 post-prime, as evaluated at d45 post-boost by multi-lymphoid organ assessment of gag-specific CD8 T cell frequency, CD62L-expression (as a guide to memory status) andin vivokilling. RNA-sequencing of splenic gag-primed CD8 T cells at d100 revealed a quiescent, but highly responsive signature, that trended toward a central memory (CD62L+) phenotype. Interestingly, gag-specific CD8 T cell frequency selectively diminished in the blood at d100, relative to the spleen, lymph nodes and bone marrow. These results move forward the rational design of prime/boost intervals.
Esearch3D: Propagating gene expression in chromatin networks to illuminate active enhancers
Authors: Heer Maninder , Giudice Luca , Mengoni Claudia , Giugno Rosalba , Rico Daniel 
Published: August 2022

AbstractMost cell type-specific genes are regulated by the interaction of enhancers with their promoters. The identification of enhancers is not trivial as enhancers are diverse in their characteristics and dynamic in their interaction partners. Currently, enhancer-associated features such as histone modifications, co-activators or bi-directional transcription are used in lieu of any definitive and universal enhancer feature. We present Esearch3D, a new approach that leverages network theory approaches to identify active enhancers. Our work is based on the fact that enhancers act as a source of regulatory information to increase the rate of transcription of their target genes and that the flow of this information is mediated by the folding of chromatin in the three-dimensional (3D) nuclear space between the enhancer and the target gene promoter. Esearch3D reverse engineers this flow of information to calculate the likelihood of enhancer activity in intergenic regions by propagating the transcription levels of genes across 3D-genome networks. Regions predicted to have high enhancer activity are shown to be enriched in annotations indicative of enhancer activity. These include: enhancer-associated histone marks, bi-directional CAGE-seq, STARR-seq, P300 and RNA polymerase II ChIP-seq, and expression quantitative trait loci (eQTL). Esearch3D successfully leverages the relationship between chromatin architecture and global transcription and represents a novel approach to predict active enhancers and understand the complex underpinnings of regulatory networks. The method is available at:https://github.com/InfOmics/Esearch3D.