bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colony-like Protocell Superstructures
Authors: Spustova Karolina , Katke Chinmay , Pedrueza Villalmanzo Esteban , Ryskulov Ruslan , Kaplan C. Nadir , Gözen Irep 
Published: September 2021

AbstractWe report the formation, growth, and dynamics of model protocell superstructures on solid surfaces, resembling single cell colonies. These structures, consisting of several layers of lipidic compartments enveloped in a dome-shaped outer lipid bilayer, emerged as a result of spontaneous shape transformation of lipid agglomerates deposited on thin film aluminum surfaces. Collective protocell structures were observed to be mechanically more stable compared to isolated spherical compartments. We show that the model colonies encapsulate DNA and accommodate non-enzymatic, strand displacement DNA reactions. The membrane envelope is able to disassemble and expose individual daughter protocells, which can migrate and attach via nano-tethers to distant surface locations, while maintaining their encapsulated contents. Some colonies feature ‘exo-compartments’, which spontaneously extend out of the enveloping bilayer, internalize DNA, and merge again with the superstructure. A continuum elastohydrodynamic theory that we developed reveals that the subcompartment formation must be governed by attractive van der Waals (vdW) interactions between the membrane and surface. The balance between membrane bending and vdW interactions yields a critical length scale of 273 nm, above which the membrane invaginations can form subcompartments. The findings support our hypotheses that in extension of the ‘lipid world hypothesis’, protocells may have existed in the form of colonies, potentially benefiting from the increased mechanical stability provided by a superstructure.
A Taphrina strain infecting the model plant Arabidopsis thaliana
Authors: Christita Margaretta , Auzane Agate , Wang Kai , Sipilä Timo , Auvinen Petri , Paulin Lars , Salojärvi Jarkko , Overmyer Kirk 
Published: September 2021

AbstractYeasts are important plant-associated organisms that can modulate host immunity to either promote or prevent disease. Mechanisms of plant-yeast interactions, specifically of yeast perception by the plant innate immune system, remain unknown. Progress has been hindered by the scarcity of yeast species associated with the model plant Arabidopsis thaliana (Arabidopsis). We have previously isolated Taphrina strain M11 from wild Arabidopsis in the field. Taphrina are poorly studied dimorphic yeast-like fungi that are plant pathogens, often producing plant hormones and causing tumour-like and leaf deformation symptoms on their hosts. Here we characterize the interaction of M11 with Arabidopsis. Infection of Arabidopsis with the birch pathogen T. betulina, used as a non-host control, shows early HR, enhanced ROS accumulation, and limitation of growth, demonstrating that Arabidopsis had immunity against non-adapted yeasts. M11 triggered limited cell death, an attenuated ROS response, and grew in planta, as well as subtle but clear leaf deformation symptoms, demonstrating it is pathogenic. Hormone responsive promoter-reporter analysis demonstrated activation of cytokinin signalling during infection. Mutant infection assays indicate jasmonate and ethylene were required for immunity against M11. Analysis of the Taphrina M11 genome was used to mine evidence for yeast specific PAMPs which may underlie host immune responses against yeast-like fungi.
Reactivating Hippocampal-Mediated Memories During Reconsolidation to Disrupt Fear
Authors: Grella Stephanie L. , Fortin Amanda H. , Ruesch Evan , Bladon John H. , Reynolds Leanna F. , Gross Abby , Shpokayte Monika , Cincotta Christine , Zaki Yosif , Ramirez Steve 
Published: September 2021

AbstractMemories are stored in the brain as cellular ensembles activated during learning and reactivated during retrieval. Using the Tet-tag system in mice, we label dorsal dentate gyrus neurons activated by positive, neutral or negative experiences with channelrhodopsin-2. Following fear-conditioning, these cells are artificially reactivated during fear memory recall. Optical stimulation of a competing positive memory is sufficient to update the memory during reconsolidation, thereby reducing conditioned fear acutely and enduringly. Moreover, mice demonstrate operant responding for reactivation of a positive memory, confirming its rewarding properties. These results show that interference from a rewarding experience can counteract negative affective states. While memory-updating, induced by memory reactivation, involves a relatively small set of neurons, we also find that activating a large population of randomly labeled dorsal dentate gyrus neurons is effective in promoting reconsolidation. Importantly, memory-updating is specific to the fear memory. These findings implicate the dorsal dentate gyrus as a potential therapeutic node for modulating memories to suppress fear.
Experimental and computational analysis of calcium dynamics in 22q11.2 deletion model astrocytes
Authors: Maly Ivan V. , Hofmann Wilma A. , Pletnikov Mikhail V. 
Published: September 2021

ABSTRACTIntracellular calcium dynamics in spontaneously active cells such as neurons or astrocytes is an information-rich readout of the physiological state of the cell. Methods for deriving mechanistic information from biological time courses, as well as for algorithmically extracting cellular activity time courses from imaging data, have significantly advanced in recent years but been mostly applied to neuronal data. At the same time, the role for astrocytes, a type of glial brain cells, in cognition and psychiatric diseases remains poorly understood. Using calcium imaging, computer vision, and Bayesian kinetic inference, we analyze calcium dynamics in primary astrocytes derived from control orDf1/+ mice, a model of 22q11.2 deletion syndrome (DiGeorge syndrome). Inference of highest-likelihood molecular kinetic characteristics from the intracellular calcium time courses pinpoints a significant change in the activity of the sarcoendoplasmic reticulum calcium ATPase (SERCA). Applying a SERCA inhibitor to the control cells reproduces the differences detected in the deletion-bearing cells. Our work identifies for the first time the molecular changes driving the calcium kinetics in 22q11.2 deletion model astrocytes. We conclude that Bayesian kinetic inference is a useful tool for mechanistic dissection of a complex cellular phenotype, calcium dynamics, in glial cells. This method has the potential to facilitate formulation of specific hypotheses concerning the underlying molecular mechanisms, prioritization of experiments testing such hypotheses, and, in the future, individualized functional molecular diagnostics.
Gene flow between two thick-billed grasswren subspecies with low dispersal creates a genomic pattern of isolation-by-distance
Authors: Slender Amy L. , Louter Marina , Myers Steven A. , Bradford Tessa , Gardner Michael G. , Kleindorfer Sonia 
Published: September 2021

AbstractContextIn the era of the Anthropocene, habitat loss and environmental change threaten the persistence of many species. Genotyping-By-Sequencing (GBS) is a useful molecular tool for understanding how patterns of gene flow are associated with contemporary habitat distributions that may be affected by environmental change. Two parapatric subspecies of the threatened thick-billed grasswren (TBGW; Amytornis modestus) more frequently occur in different plant communities. As such, a preference for plant community type could reduce subspecific introgression and increase genetic diversity at the parapatric boundary.AimsWe aimed to measure gene flow within and among two TBGW subspecies and tested whether divergent genomic markers were associated with plant community type.MethodsWe sequenced 118 individuals from either of the two TBGW subspecies or in the region of parapatry and identified 7583 SNPs through ddRADseq.Key resultsWe found evidence of asymmetric gene flow and a genomic pattern of isolation-by-distance. There were sixteen genomic outliers correlated with plant community type (regardless of location).ConclusionsThese findings show that plant community type does not prevent introgression in one subspecies (A. m. raglessi), but low dispersal and habitat heterogeneity could contribute to the maintenance of distinct subspecific morphotypes. Local adaptation in different plant community types could also provide a mechanism for future divergence.ImplicationsWe suggest subspecific introgression could increase genetic variation and the adaptive potential of the species, facilitating species persistence under conditions of climate change.Introgression between grasswren subspeciesCharacterising gene flow facilitates conservation management. This study used genomic markers to measure gene flow between thick-billed grasswren subspecies and found results that support taxonomic identification of the two subspecies and suggests grasswrens have low dispersal and may benefit from increased genetic diversity. Recognition of models of divergence with gene flow will be necessary for future conservation management.
Context-dependence in the symbiosis between Dictyostelium discoideum and Paraburkholderia
Authors: Scott Trey J. , Queller David C. , Strassmann Joan E. 
Published: September 2021

AbstractSymbiotic interactions change with environmental context. Measuring these context-dependent effects in hosts and symbionts is critical to determining the nature of symbiotic interactions. We investigated context-dependence in the symbiosis between social amoeba hosts and their inedible Paraburkholderia bacterial symbionts, where the context is the abundance of host food bacteria. Paraburkholderia have been shown to harm hosts dispersed to food-rich environments, but aid hosts dispersed to food-poor environments by allowing hosts to carry food bacteria. Through measuring symbiont density and host spore production, we show that this food context matters in three other ways. First, it matters for symbionts, who suffer a greater cost from competition with food bacteria in the food-rich context. Second, it matters for host-symbiont conflict, changing how symbiont density negatively impacts host spore production. Third, data-based simulations show that symbiosis often provides a long-term fitness advantage for hosts after rounds of growth and dispersal in variable food-contexts, especially when conditions are harsh with little food. These results show how food context can have many consequences for the Dictyostelium-Paraburkholderia symbiosis and that both sides can frequently benefit.Impact StatementMany organisms form symbiotic relationships with other species. These symbioses often exhibit context-dependence, where the sign or magnitude of one partner’s effect on the other will change in different environments. Context-dependent effects make it difficult to assign interactions to categories like mutualisms or antagonisms because they involve both benefits and costs depending on the environment. However, in some cases, accounting for context-dependence can clarify an interaction so that it more easily fits a mutualism or antagonism. We investigated context-dependence using the symbiosis between Dictyostelium discoideum and two symbiotic Paraburkholderia species. In this symbiosis, Paraburkholderia bacteria allow hosts to carry food bacteria to food-poor contexts, where hosts rarely survive without food, but reduce host fitness in the more hospitable food-rich contexts. The effect of food context on Paraburkholderia symbionts is unknown. We show that Paraburkholderia symbionts are also affected by this context, through facing reduced competition after being dispersed by hosts to food-poor contexts. We also identify a new way that symbionts affect hosts, where symbiont density reduces host fitness, but less so in food-poor contexts. Finally, we use simulations to show that infected hosts benefit in the long-term across variable food contexts, especially in the harshest environments with little food. These results show that context-dependence in symbiosis can have many consequences for hosts and symbionts, though in general for D. discoideum and Paraburkholderia, both are likely to benefit.
Towards Compilation of Balanced Protein Stability Datasets: Flattening the ΔΔG Curve through Systematic Under-sampling
Authors: Kebabci Narod , Timucin Ahmet Can , Timucin Emel 
Published: September 2021

AbstractProtein stability datasets contain neutral mutations that are highly concentrated in a much narrower ΔΔG range than destabilizing and stabilizing mutations. Notwith-standing their high density, often studies analyzing stability datasets and/or predictors ignore the neutral mutations and use a binary classification scheme labeling only destabilizing and stabilizing mutations. Recognizing that highly concentrated neutral mutations would affect the quality of stability datasets, we have explored three protein stability datasets; S2648, PON-tstab and the symmetric Ssymthat differ in size and quality. A characteristic leptokurtic shape in the ΔΔG distributions of all three datasets including the curated and symmetric ones were reported due to concentrated neutral mutations. To further investigate the impact of neutral mutations on ΔΔG predictions, we have comprehensively assessed the performance of eleven predictors on the PON-tstab dataset. Correlation and error analyses showed that all of the predictors performed the best on the neutral mutations while their performance became gradually worse as the ΔΔG of the mutations departed further from the neutral zone regardless of the direction, implying a bias towards dense mutations. To this end, after unraveling the role of concentrated neutral mutations in biases of stability datasets, we described a systematic under-sampling approach to balance the ΔΔG distributions. Before under-sampling, mutations were clustered based on their biochemical and/or structural features and then three mutations were systematically selected from every 2 kcal/mol of each cluster. Upon implementation of this approach by distinct clustering schemes, we generated five subsets varying in size and ΔΔG distributions. All subsets notably showed amelioration of not only the shape of ΔΔG distributions but also other pre-existing imbalances in the frequency distributions. We also reported differences in the performance of the predictors between the parent and under-sampled subsets due to the enrichment of previously under-represented mutations in the subsets. Altogether, this study not only elaborated the pivotal role of concentrated mutations in the dataset biases but also contemplated and realized a rational strategy to tackle this and other forms of biases. Under-sampling code is available on GitHub (https://github.com/narodkebabci/gRoR).
Combining genotypes and T cell receptor distributions to infer genetic loci determining V(D)J recombination probabilities
Authors: Russell Magdalena L , Souquette Aisha , Levine David M , Allen E Kaitlynn , Kuan Guillermina , Simon Noah , Balmaseda Angel , Gordon Aubree , Thomas Paul G , Matsen Frederick A , Bradley Philip 
Published: September 2021

AbstractEvery T cell receptor (TCR) repertoire is shaped by a complex probabilistic tangle of genetically determined biases and immune exposures. T cells combine a random V(D)J recombination process with a selection process to generate highly diverse and functional TCRs. The extent to which an individual’s genetic background is associated with their resulting TCR repertoire diversity has yet to be fully explored. Using a previously published repertoire sequencing dataset paired with high-resolution genome-wide genotyping from a large human cohort, we infer specific genetic loci associated with V(D)J recombination probabilities using genome-wide association inference. We show that V(D)J gene usage profiles are associated with variation in theTCRBlocus and, specifically for the functional TCR repertoire, variation in the major histocompatibility complex locus. Further, we identify specific variations in the genes encoding the Artemis protein and the TdT protein to be associated with biasing junctional nucleotide deletion and N-insertion, respectively. These results refine our understanding of genetically-determined TCR repertoire biases by confirming and extending previous studies on the genetic determinants of V(D)J gene usage and providing the first examples oftransgenetic variants which are associated with modifying junctional diversity. Together, these insights lay the groundwork for further explorations into how immune responses vary between individuals.
Physical and functional interactome atlas of human receptor tyrosine kinases
Authors: Salokas Kari , Öhman Tiina , Liu Xiaonan , Chowdhury Iftekhar , Gawriyski Lisa , Keskitalo Salla , Varjosalo Markku 
Published: September 2021

SummaryMuch cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite their central roles, the functions of many RTKs are still poorly understood. To resolve the lack of systematic knowledge, we used three complementary methods to map the molecular context and substrate profiles of RTKs. We used affinity purification coupled to mass spectrometry (AP-MS) to characterize stable binding partners and RTK-protein complexes, proximity-dependent biotin identification (BioID) to identify transient and proximal interactions, and an in vitro kinase assay to identify RTK substrates. To identify how kinase interactions depend on kinase activity, we also used kinase-deficient mutants. Our data represent a comprehensive, systemic mapping of RTK interactions and substrates. This resource adds information regarding well-studied RTKs, offers insights into the functions of less well-studied RTKs, and highlights RTK-RTK interactions and shared signaling pathways.
Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes
Authors: Calia Andrea Bonaccini , Masvidal-Codina Eduard , Smith Trevor M. , Schäfer Nathan , Rathore Daman , Rodríguez-Lucas Elisa , Illa Xavi , De la Cruz Jose M. , Del Corro Elena , Prats-Alfonso Elisabet , Viana Damià , Bousquet Jessica , Hébert Clement , Martínez-Aguilar Javier , Sperling Justin R. , Drummond Matthew , Halder Arnab , Dodd Abbie , Barr Katharine , Savage Sinead , Fornell Jordina , Sort Jordi , Guger Christoph , Villa Rosa , Kostarelos Kostas , Wykes Rob , Guimerà-Brunet Anton , Garrido Jose A. 
Published: September 2021

ABSTRACTMapping the entire frequency bandwidth of neuronal oscillations in the brain is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously infraslow activity (<0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. Here we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record infraslow and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency epileptic activity through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.
Evolutionary history of an Alpine archaeognath (Machilis pallida) – insights from different variant types
Authors: Haider Marlene , Schilling Martin P. , Moest Markus H. , Steiner Florian M. , Schlick-Steiner Birgit C. , Arthofer Wolfgang 
Published: September 2021

AbstractReconstruction of species histories is a central aspect of evolutionary biology. Patterns of genetic variation within and among populations can be leveraged to elucidate evolutionary processes and demographic histories. However, interpreting genetic signatures and unraveling the contributing processes can be challenging, in particular for non-model organisms with complex reproductive modes and genome organization. One way forward is the combined consideration of patterns revealed by different molecular markers (nuclear vs. mitochondrial) and types of variants (common vs. rare) that differ in their age, mode and rate of evolution. Here, we applied this approach to Machilis pallida (Archaeognatha), an Alpine jumping bristletail considered parthenogenetic and triploid. We generated de-novo transcriptome and mitochondrial assemblies to obtain high-density data to investigate patterns of mitochondrial and common and rare nuclear variation in 17 M. pallida individuals sampled across the Alps from all known populations. We find that the different variant types capture distinct aspects of the evolutionary history and discuss the observed patterns in the context of parthenogenesis, polyploidy and survival during glaciation. This study highlights the potential of different variant types to unravel complex evolutionary scenarios and the suitability of M. pallida and the genus Machilis as a study system for the evolution of sexual strategies and polyploidization during environmental change. We also emphasize the need for further research which will be stimulated and facilitated by these newly generated resources and insights.
Haplotype-level metabarcoding of freshwater macroinvertebrate species: a prospective tool for population genetic analysis
Authors: Serrana Joeselle M. , Watanabe Kozo 
Published: September 2021

ABSTRACTThe development and evaluation of DNA metabarcoding protocols for haplotype-level resolution require attention, specifically for population genetic analysis, i.e., parallel estimation of genetic diversity and dispersal patterns among multiple species present in a bulk sample. Further exploration and assessment of the laboratory and bioinformatics strategies are warranted to unlock the potential of metabarcoding-inferred population genetic analysis. Here, we assessed the inference of freshwater macroinvertebrate haplotypes from DNA metabarcoding data using mock samples with known Sanger-sequenced haplotypes. We also examined the influence of different DNA template concentrations and PCR cycles on detecting true haplotypes and the reduction of spurious haplotypes obtained from DNA metabarcoding. We tested our haplotyping strategy on a mock sample containing 20 specimens from four species with known haplotypes based on the 658-bp Folmer region of the mitochondrial cytochrome c oxidase gene. The read processing and denoising step resulted in 14 zero-radius operational taxonomic units (ZOTUs) of 421-bp length, with 12 ZOTUs having 100% match with 12 of the Sanger haplotype sequences. Quality passing reads relatively increased with increasing PCR cycles, and the relative abundance of each ZOTUs was consistent for each cycle number. This suggests that increasing the cycle number from 24 to 64 did not affect the relative abundance of quality passing filter reads of each ZOTUs. Our study demonstrated the ability of DNA metabarcoding to infer intraspecific variability while highlighting the challenges that need to be addressed before its possible applications to population genetic studies.