bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Xenopus Phenotype Ontology: bridging model organism phenotype data to human health and development
Authors: Fisher Malcolm E. , Segerdell Erik , Matentzoglu Nicolas , Nenni Mardi J. , Fortriede Joshua D. , Chu Stanley , Pells Troy J. , Chaturvedi Praneet , James-Zorn Christina , Sundararaj Nivitha , Lotay Vaneet S. , Ponferrada Virgilio , Wang Dong Zhuo , Kim Eugene , Agalakov Sergei , Arshinoff Bradley I. , Karimi Kamran , Vize Peter D. , Zorn Aaron M. 
Published: November 2021

AbstractBackgroundOntologies of precisely defined, controlled vocabularies are essential to curate the results of biological experiments such that the data are machine searchable, can be computationally analyzed, and are interoperable across the biomedical research continuum. There is also an increasing need for methods to interrelate phenotypic data easily and accurately from experiments in animal models with human development and disease.ResultsHere we present theXenopusPhenotype Ontology (XPO) to annotate phenotypic data from experiments inXenopus, one of the major vertebrate model organisms used to study gene function in development and disease. The XPO implements design patterns from the Unified Phenotype Ontology (uPheno), and the principles outlined by the Open Biological and Biomedical Ontologies (OBO Foundry) to maximize interoperability with other species and facilitate ongoing ontology management. Constructed in Web Ontology Language (OWL) the XPO combines the existing uPheno library of ontology design patterns with additional terms from theXenopusAnatomy Ontology (XAO), the Phenotype and Trait Ontology (PATO) and the Gene Ontology (GO). The integration of these different ontologies into the XPO enables rich phenotypic curation, whilst the uPheno bridging axioms allows phenotypic data fromXenopusexperiments to be related to phenotype data from other model organisms and human disease. Moreover, the simple post-composed uPheno design patterns facilitate ongoing XPO development as the generation of new terms and classes of terms can be substantially automated.ConclusionsThe XPO serves as an example of current best practices to help overcome many of the inherent challenges in harmonizing phenotype data between different species. The XPO currently consists of approximately 22,000 terms and is being used to curate phenotypes by Xenbase, theXenopusModel Organism Knowledgebase, forming a standardized corpus of genotype-phenotype data that can be directly related to other uPheno compliant resources.
Mechanistic insights into the enhancement or inhibition of phase separation by polyubiquitin chains of different lengths or linkages
Authors: Dao Thuy P. , Yang Yiran , Presti Maria F. , Cosgrove Michael S. , Hopkins Jesse B. , Ma Weikang , Loh Stewart N. , Castañeda Carlos A. 
Published: November 2021

SummaryUbiquitin-binding shuttle UBQLN2 mediates crosstalk between proteasomal degradation and autophagy, likely via interactions with K48- and K63-linked polyubiquitin chains, respectively. UBQLN2 is recruited to stress granules in cells and undergoes liquid-liquid phase separation (LLPS)in vitro. However, interactions with ubiquitin or multivalent K48-linked chains eliminate LLPS. Here, we found that, although some polyubiquitin chain types (K11-Ub4 and K48-Ub4) did generally inhibit UBQLN2 LLPS, others (K63-Ub4, M1-Ub4 and a designed tetrameric ubiquitin construct) significantly enhanced LLPS. Using nuclear magnetic resonance (NMR) spectroscopy and complementary biophysical techniques, we demonstrated that these opposing effects stem from differences in chain conformations, but not in affinities between chains and UBQLN2. Chains with extended conformations and increased accessibility to the ubiquitin binding surface significantly promoted UBQLN2 LLPS by enabling a switch between homotypically to partially heterotypically-driven phase separation. Our study provides mechanistic insights into how the structural and conformational properties of polyubiquitin chains contribute to heterotypic phase separation with ubiquitin-binding shuttles and adaptors.HighlightsUbiquitin or short polyubiquitin chains bind to phase separation-driving stickers on UBQLN2 and inhibit its phase separation whereas longer chains provide the multivalency needed to enhance UBQLN2 phase separation.Phase separation of UBQLN2 is promoted over a wide range of Ub:UBQLN2 ratios in the presence of extended M1- and K63-linked Ub4 chains, but not compact K11- and K48-linked Ub4 chains.Chain conformation and accessibility of the Ub interacting surface is a driving factor of UBQLN2/polyUb co-phase separation.UBQLN2 condensates assemble duringin vitroenzymatic assembly of K63-linked polyUb chains as free ubiquitin is reduced.
A de novo matrix for macroscopic living materials from bacteria
Authors: Molinari Sara , Tesoriero Robert F. , Li Dong , Sridhar Swetha , Cai Rong , Soman Jayashree , Ryan Kathleen R. , Ashby Paul D. , Ajo-Franklin Caroline M. 
Published: November 2021

Summary ParagraphEngineered living materials (ELMs) are composites of living cells embedded in a biopolymer matrix that combine the desirable properties of natural biomaterials with non-natural, tailored properties. ELMs with a wide range of sophisticated biological functions have been created by engineering the embedded cells using synthetic biology. Engineering a de novo biomolecular matrix would offer control over material assembly, structure, and composition, thus enabling us to grow macroscopic ELMs with customizable mechanical properties. However, we have lacked the genetic tools and design rules to genetically encode a synthetic matrix that programs collective cell self-organization into macroscopic structures. Here we report growth of macroscopic ELMs from Caulobacter crescentus cells that display and secrete an engineered self-interacting protein. This protein formed an extracellular de novo matrix and assembled cells into hierarchically-ordered, centimeter-scale ELMs. We showed that the mechanical, catalytic, and morphological properties of these ELMs can be tuned through genetic modification of the matrix. Our work identifies novel genetic tools, design and assembly rules for growing macroscopic ELMs with both wide-ranging mechanical properties and customizable functions. We anticipate the modularity of this approach will permit the incorporation of different protein polymers in the de novo matrix, thus allowing to generate ELMs with a variety of desired structures and compositions of the bulk material. We envision specific matrix properties that can be combined synergistically with existing cellular functions to greatly expand the opportunities for ELMs in human health, energy, and the environment.
Recurrent neural circuits overcome partial inactivation by compensation and re-learning
Authors: Bredenberg Colin , Savin Cristina , Kiani Roozbeh 
Published: November 2021

1AbstractTechnical advances in artificial manipulation of neural activity have precipitated a surge in studying the causal contribution of brain circuits to cognition and behavior. However, complexities of neural circuits challenge interpretation of experimental results, necessitating theoretical frameworks for system-atic explorations. Here, we take a step in this direction, using, as a testbed, recurrent neural networks trained to perform a perceptual decision. We show that understanding the computations implemented by network dynamics enables predicting the magnitude of perturbation effects based on changes in the network’s phase plane. Inactivation effects are weaker for distributed network architectures, are more easily discovered with non-discrete behavioral readouts (e.g., reaction times), and vary considerably across multiple tasks implemented by the same circuit. Finally, networks that can “learn” during inactivation recover function quickly, often much faster than the original training time. Our framework explains past empirical observations by clarifying how complex circuits compensate and adapt to perturbations.
Transcriptomic plasticity and symbiont shuffling underpin Pocillopora acclimatization across heat-stress regimes in the Pacific Ocean
Authors: Armstrong Eric J , Lê-Hoang Julie , Carradec Quentin , Aury Jean-Marc , Noel Benjamin , Poulain Julie , Belser Caroline , Da Silva Corinne , Wincker Patrick ,   Tara Pacific Consortium
Published: November 2021

ABSTRACTThe characterization of adaptation and acclimation capacities of coral holobionts is crucial for anticipating the impact of global climate change on coral reefs. Understanding the extent to which the coral host and its photosymbionts contribute to adaptive and/or plastic responses in the coral metaorganism is important. In this study, we highlight new and complex links between coral genomes, transcriptomes, and environmental features in Pocilloporid corals at basin-wide scale. We analyzed metagenomic and metatranscriptomic sequence data from Pocillopora colonies sampled from 11 islands across the Pacific Ocean in order to investigate patterns of gene expression in both the host and photosymbiont across an environmental gradient. Single nucleotide polymorphisms (SNPs) analysis partitioned coral hosts and algal photosymbionts into five genetic lineages each. We observed strong host-symbiont fidelity across environments except at islands where recent and/or historical heat stress may have induced a symbiont shift towards more heat-tolerant lineages in some colonies. Host gene expression profiles were strongly segregated by genetic lineage and environment, and were significantly correlated with several historical sea surface temperature (SST) traits. Symbiont expression profiles were less dependent on environmental context than the host and were primarily driven by algal genotype. Overall, our results suggest a three-tiered strategy underpinning thermal acclimatization in Pocillopora holobionts with 1) host-photosymbiont fidelity, 2) host transcriptomic plasticity, and 3) photosymbiont shuffling playing progressive roles in response to elevated SSTs. Our data provide a reference for the biological state of coral holobionts across the Indo-Pacific and demonstrate the power of disentangling environmental and genetic effects to provide new insights into corals’ capacities for acclimatization and adaptation under environmental change.
Neurotransmission and neuromodulation systems in the learning and memory network ofOctopus vulgaris
Authors: Stern-Mentch Naama , Winter Gabriela , Belenky Michael , Moroz Leonid , Hochner Binyamin 
Published: November 2021

AbstractThe vertical lobe (VL) in the octopus brain plays an essential role in its sophisticated learning and memory. Early anatomical studies suggested that the VL is organized in a “fan-out fan-in” connectivity matrix comprising only three morphologically identified neuron types; input axons from the superior frontal lobe (SFL) innervatingen passantmillions of small amacrine interneurons (AMs) which converge sharply onto large VL output neurons (LNs). Recent physiological studies confirmed the feedforward excitatory connectivity: a glutamatergic synapse at the first SFL-to-AM synaptic layer and a cholinergic AM-to-LNs synapse. SFL-to-AMs synapses show a robust hippocampal-like activity-dependent long-term potentiation (LTP) of transmitter release. 5-HT, octopamine, dopamine and nitric oxide modulate short- and long-term VL synaptic plasticity. Here we present a comprehensive histolabeling study to better characterize the neural elements in the VL. We generally confirmed glutamatergic SFLs and cholinergic AMs. Intense labeling for NOS activity in the AMs neurites fitted with the NO-dependent presynaptic LTP mechanism at the SFL-to-AM synapse. New discoveries here reveal more heterogeneity of the VL neurons than previously thought. GABAergic AMs suggest a subpopulation of inhibitory interneurons in the first input layer. Clear GABA labeling in the cell bodies of LNs supported an inhibitory VL output yet the LNs co-expressed FMRFamide-like neuropeptides suggesting an additional neuromodulatory role of the VL output. Furthermore, a group of LNs was glutamatergic. A new cluster of cells organized in a “deep nucleus” showed rich catecholaminergic labeling and may play a role in intrinsic neuromodulation.In situhybridization and immunolabeling allowed characterization and localization of a rich array of neuropeptides and neuromodulatores, likely involved in reward/punishment signals. This analysis of the fast transmission system, together with the newly found cellular elements helps integrate behavioral, physiological, pharmacological and connectome findings into a more comprehensive understanding of an efficient learning and memory network.
A semantics, energy-based approach to automate biomodel composition
Authors: Shahidi Niloofar , Pan Michael , Tran Kenneth , Crampin Edmund J. , Nickerson David P. 
Published: November 2021

AbstractHierarchical modelling is essential to achieving complex, large-scale models. However, not all modelling schemes support hierarchical composition, and correctly mapping points of connection between models requires comprehensive knowledge of each model’s components and assumptions. To address these challenges in integrating biosimulation models, we propose an approach to automatically and confidently compose biosimulation models. The approach uses bond graphs to combine aspects of physical and thermodynamics-based modelling with biological semantics. We improved on existing approaches by using semantic annotations to automate the recognition of common components. The approach is illustrated by coupling a model of the Ras-MAPK cascade to a model of the upstream activation of EGFR. Through this methodology, we aim to assist researchers and modellers in readily having access to more comprehensive biological systems models.Author summaryDetailed, multi-scale computational models bridging from biomolecular processes to entire organs and bodies have the potential to revolutionise medicine by enabling personalised treatments. One of the key challenges to achieving these models is connecting together the vast number of isolated biosimulation models into a coherent whole. Using recent advances in both modelling techniques and biological standards in the scientific community, we developed an approach to integrate and compose models in a physics-based environment. This provides significant advantages, including the automation of model composition and post-model-composition adjustments. We anticipate that our approach will enable the faster development of realistic and accurate models to understand complex biological systems.
Wnt5A Signaling Blocks Progression of Experimental Visceral Leishmaniasis
Authors: Maity Shreyasi , Chakraborty Arijit , Mahata Sushil , Roy Syamal , Das Anjan Kumar , Sen Malini 
Published: November 2021

AbstractVisceral Leishmaniasis, caused by L. donovani infection is fatal if left untreated. The intrinsic complexity of visceral leishmaniasis complicated further by the increasing emergence of drug resistant L. donovani strains warrants fresh investigations into host defense schemes that counter infections. Accordingly, using a mouse model of experimental visceral leishmaniasis we explored the utility of host Wnt5A in restraining L. donovani infection, using both antimony sensitive and antimony resistant L. donovani strains. We found that Wnt5A heterozygous (Wnt5A +/-) mice are more susceptible to L. donovani infection than their wild type (Wnt5A +/+) counterparts as depicted by the respective Leishman Donovan Units (LDU) enumerated from the liver and spleen harvested from infected mice. Higher LDU in Wnt5A +/-mice correlated with increased level of plasma gammaglobulin, liver granuloma and disorganization of splenic germinal centers. Progression of infection in mice by both antimony sensitive and antimony resistant strains of L. donovani could be prevented by activation of Wnt5A signaling as evident from the lowered LDU and gammaglobulin level, and intactness of splenic germinal centers through intravenous administration of rWnt5A prior to L. donovani infection. Wnt5A mediated blockade of L. donovani infection correlated with the preservation of splenic macrophages and activated T cells, and a TH1 like cytokine thrust. Taken together our results indicate that depletion of Wnt5A promotes susceptibility to visceral leishmaniasis and revamping Wnt5A signaling in the host is able to curb L. donovani infection irrespective of antimony sensitivity or resistance and mitigate the progression of visceral leishmaniasis.
Premature MeCP2 Expression Disturbs the Subtype Specification of Midbrain Dopamine Neurons
Authors: He Xi-Biao , Guo Fang , Li Kexuan , Yan Jiaqing , Lee Sang-Hun 
Published: November 2021

AbstractMidbrain dopamine (DA) neurons are associated with locomotor and psychiatric disorders. DA subtype is specified in ancestral neural precursor cells (NPCs) and maintained throughout neuronal differentiation. Here we show that endogenous expression of MeCP2 coincides with DA subtype specification in mouse mesencephalon, and premature expression of MeCP2 prevents in vitro cultured NPCs from acquiring DA subtype through interfering NURR1 transactivation of DA phenotype genes. By contrast, MeCP2 overexpression does not disturb DA subtype in DA neurons. By analyzing the dynamic change of DNA methylation along DA neuronal differentiation at the promoter of DA phenotype gene tyrosine hydroxylase (Th), we show that Th expression is determined by TET1-mediated de-methylation of NURR1 binding sites within Th promoter. Chromatin immunoprecipitation assays demonstrate that MeCP2 dominates the DNA binding of the corresponding sites thereby blocking TET1 function in DA NPCs, whereas TET1-mediated de-methylation prevents excessive MeCP2 binding in DA neurons. The significance of temporal DNA methylation status is further confirmed by targeted methylation/demethylation experiments showing that targeted de-methylation in DA NPCs protects DA subtype specification from MeCP2 overexpression, whereas targeted methylation disturbs subtype maintenance in MeCP2-overexpressed DA neurons. These findings suggest the appropriate timing of MeCP2 expression as a novel determining factor for guiding NPCs into DA lineage.
An interplay between viruses and bacteria associated with marine sponges from the White Sea revealed by metagenomics
Authors: Rusanova Anastasiia , Fedorchuk Victor , Toshchakov Stepan , Dubiley Svetlana , Sutormin Dmitry 
Published: November 2021

AbstractSponges are remarkable holobionts harboring extremely diverse microbial and viral communities. However, the interactions between the components within holobionts and between a holobiont and environment are largely unknown, especially for polar organisms. To investigate possible interactions within the sponge-associated communities and between them, we probed the microbiomes and viromes of cold-water sympatric sponges Isodictya palmata, Halichondria panicea, and Halichondria sitiens by 16S and shotgun metagenomics. We showed that the bacterial and viral communities associated with these White Sea sponges are species-specific and different from the surrounding water. Extensive mining of bacterial antiphage defense systems in the metagenomes revealed a variety of defense mechanisms. The abundance of defense systems was comparable in the metagenomes of the sponges and the surrounding water, thus distinguishing the White Sea sponges from those inhabiting the tropical seas. We developed a network-based approach for the combined analysis of CRISPR-spacers and protospacers. Using this approach, we showed that the virus-host interactions within the sponge-associated community are typically more abundant than the inter-community interactions. Additionally, we detected the occurrence of viral exchanges between the communities. Our work provides the first insight into the metagenomics of the three cold-water sponge species from the White Sea and paves the way for a comprehensive analysis of the interactions between microbial communities and associated viruses.
A dynamic clamp protocol to artificially modify cell capacitance
Authors: Pfeiffer Paul , Tomás Federico José Barreda , Wu Jiameng , Schleimer Jan-Hendrik , Vida Imre , Schreiber Susanne 
Published: November 2021

AbstractDynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique. We first demonstrate the feasibility to quantitatively modulate capacitance in a mathematical neuron model and then confirm the functionality of capacitance clamp in in vitro experiments in granule cells of rodent dentate gyrus with up to threefold virtual capacitance changes. Clamping of capacitance thus constitutes a novel technique to probe and decipher mechanisms of neuronal signaling in ways that were so far inaccessible to experimental electrophysiology.
Frequency modulated timer regulates mammalian hibernation
Authors: Gibo Shingo , Yamaguchi Yoshifumi , Kurosawa Gen 
Published: November 2021

AbstractMammalian hibernators decrease basal metabolism and body temperature (Tb) to minimize energy expenditure in harsh seasons. During hibernation, Tb drops to low temperature (<10 °C) and remains constant for days, known as deep torpor in small mammalian hibernators. Spontaneous interbout arousals interrupt torpor bouts, when Tb recovers to euthermic state ~37 °C. Torpor-interbout arousal event repeats during several months of hibernation. However, little is known about mechanisms governing Tb fluctuation across torpor-interbout arousal cycles during hibernation. Recent improvement in data-logging techniques enables us to monitor Tb for more than hundred days with high precision, opening up new avenues for quantitative analysis to address the principle governing Tb fluctuation. Here, we analyzed Tb fluctuation across torpor-interbout arousal cycle of Syrian hamster, which can hibernate in response to chronic cold and short photoperiod under a laboratory condition, using generalized harmonic analysis and discovered a model with frequency modulation quantitatively reproducing Tb fluctuation. This analysis also identified an unexpectedly longer period of 120–430 days as the period that modulates another period of several days, generating Tb fluctuation for Syrian hamster. We propose that concerted action of two endogenous periods governs torpor-interbout arousal cycles during hibernation.