bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reciprocal recurrent selection based on genetic complementation: An efficient way to build heterosis in diploids due to directional dominance
Authors: Covarrubias-Pazaran Giovanny , Werner Christian , Gemenet Dorcus 
Published: July 2022

AbstractDepending on the trait architecture and reproduction system, selection strategies in plant breeding focus on the accumulation of additive, dominance effects, or both. Innovation in the accumulation of dominance-effect-based heterosis has been limited since the proposal of GCA-based approaches and very few strategies to exploit it better have been proposed. We propose the use of a new surrogate of genetic complementation between genetic pools to increase accumulation of dominance effects and heterosis. We simulated breeding programs to show how reciprocal recurrent selection by genetic complementation would build the dominance-based heterosis but cheaper than GCA-based approaches and used real phenotypic data from hybrid maize to demonstrate the underlying concepts. We found reciprocal recurrent selection by genetic complementation to be an attractive and viable strategy to exploit dominance, build de novo heterotic pools and boost the current GCA-based approaches. If demonstrated in practice, we hypothesized that this approach would lower the cost of breeding drastically and contribute to food security.Key messageHeterotic patterns can be developed quickly through genetic complementation surrogates to produce high-performance hybrids at a low cost in diploid species displaying dominance and boost GCA-based approaches in hybrid breeding.
Land-use preferences of the European green toad (Bufotes viridis) in the city of Vienna (Austria): the importance of open land in urban environments
Authors: Landler Lukas , Burgstaller Stephan , Schweiger Silke 
Published: July 2022

AbstractUrban areas are increasing worldwide, which poses treats to animal wildlife. However, in certain cases cities can provide refuges for endangered animals. The European green toad (Bufotes viridis) is one of such examples, which is known from cities throughout their distribution. In contrast, considerable areas of their former (primary) habitats have been degraded. The primary habitats of this species include steppes and wild river floodplains, both characterized by dynamic changes and the presence of open areas. We used available green toad observation data (2007-2020) to model the effects of land-use types on occurrence probability in the city of Vienna. Forest and densely populated areas were highly significantly negatively associated with green toad presence, while transformation/construction site areas showed a strong positive effect. Such occurrence pattern might be characteristic for early succession species, which depend on stochastic environmental disturbances (e.g., droughts and floods) in their primary habitats. We argue that urban landscape planning should appreciate the potential ecological value of open land in cities which is either in a transition phase or a permanent wasteland. Ecological managing of such landscape could vastly increase urban biodiversity.
Uncertainty alters the balance between incremental learning and episodic memory
Authors: Nicholas Jonathan , Daw Nathaniel D. , Shohamy Daphna 
Published: July 2022

AbstractA key question in decision making is how humans arbitrate between competing learning and memory systems to maximize reward. We address this question by probing the balance between the effects, on choice, of incremental trial-and-error learning versus episodic memories of individual events. Although a rich literature has studied incremental learning in isolation, the role of episodic memory in decision making has only recently drawn focus, and little research disentangles their separate contributions. We hypothesized that the brain arbitrates rationally between these two systems, relying on each in circumstances to which it is most suited, as indicated by uncertainty. We tested this hypothesis by directly contrasting contributions of episodic and incremental influence to decisions, while manipulating the relative uncertainty of incremental learning using a well-established manipulation of reward volatility. Across two large, independent samples of young adults, participants traded these influences off rationally, depending more on episodic information when incremental summaries were more uncertain. These results support the proposal that the brain optimizes the balance between different forms of learning and memory according to their relative uncertainties and elucidate the circumstances under which episodic memory informs decisions.
Large library docking for novel SARS-CoV-2 main protease non-covalent and covalent inhibitors
Authors: Fink Elissa A. , Bardine Conner , Gahbauer Stefan , Singh Isha , White Kris , Gu Shuo , Wan Xiaobo , Ary Beatrice , Glenn Isabella , O’Connell Joseph , O’Donnell Henry , Fajtová Pavla , Lyu Jiankun , Vigneron Seth , Young Nicholas J. , Kondratov Ivan S. , O’Donoghue Anthony J. , Moroz Yurii , Taunton Jack , Renslo Adam R. , Irwin John J. , García-Sastre Adolfo , Shoichet Brian K. , Craik Charles S. 
Published: July 2022

AbstractAntiviral therapeutics to treat SARS-CoV-2 are much desired for the on-going pandemic. A well-precedented viral enzyme is the main protease (MPro), which is now targeted by an approved drug and by several investigational drugs. With the inevitable liabilities of these new drugs, and facing viral resistance, there remains a call for new chemical scaffolds against MPro. We virtually docked 1.2 billion non-covalent and a new library of 6.5 million electrophilic molecules against the enzyme structure. From these, 29 non-covalent and 11 covalent inhibitors were identified in 37 series, the most potent having an IC50 of 29 μM and 20 μM, respectively. Several series were optimized, resulting in inhibitors active in the low micromolar range. Subsequent crystallography confirmed the docking predicted binding modes and may template further optimization. Together, these compounds reveal new chemotypes to aid in further discovery of MPro inhibitors for SARS-CoV-2 and other future coronaviruses.
Human-specific progenitor sub-domain contributes to extended neurogenesis and increased motor neuron production
Authors: Jang Sumin , Gunmit Elias , Wichterle Hynek 
Published: July 2022

SUMMARYNeurogenesis lasts ~10 times longer in developing humans compared to mice, resulting in >1000-fold more neurons in the human central nervous system. Expansion of human neocortex has been in part attributed to the population of outer radial glia and amplifying progenitors that increase the output of neurogenic lineages. However, outer radial glia appear to be absent in many regions of the developing human nervous system, prompting us to search for alternative populations of progenitors that contribute to the expansion of human neurogenesis in one such region - the developing spinal cord. To this end, we performed high-temporal resolution single-cell expression analysis of human and mouse motor neuron progenitors generated from pluripotent stem cells in vitro. Alignment of human and mouse data using canonical correlation analysis identified “human-specific” progenitor clusters characterized by early co-expression of NKX2-2 and OLIG2 that lacked an orthologous murine counterpart. A matching progenitor population has been previously described in the human embryonic spinal cord1, but its function remained unknown. Our lineage tracing analysis demonstrates that these cells function as ventral motor neuron progenitors (vpMNs), but in contrast to classical pMNs, vpMNs exhibit increased Notch activity and generate motor neurons in a delayed and protracted manner. Concomitantly, vpMNs undergo more rounds of cell division before undergoing neurogenesis, leading to ~2-fold increase in total motor neuron output, and contributing preferentially to later-born, limb-innervating motor neuron subtypes. Thus, instead of relying on transit-amplifying progenitors, human spinal cord evolved a novel progenitor subdomain that extends timescales and expands output of human motor neurogenesis.
Beyond sequence similarity: cross-phyla protein annotation by structural prediction and alignment
Authors: Ruperti Fabian , Papadopoulos Nikolaos , Musser Jacob , Mirdita Milot , Steinegger Martin , Arendt Detlev 
Published: July 2022

AbstractBackgroundAnnotating protein function is a major goal in molecular biology, yet experimentally determined knowledge is often limited to a few model organisms. In non-model species, the sequence-based prediction of gene orthology can be used to infer function, however this approach loses predictive power with longer evolutionary distances. Here we propose a pipeline for the functional annotation of proteins using structural similarity, exploiting the fact that protein structures are directly linked to function and can be more conserved than protein sequences.ResultsWe propose a pipeline of openly available tools for the functional annotation of proteins via structural similarity (MorF:MorphologFinder) and use it to annotate the complete proteome of a sponge. Sponges are highly relevant for inferring the early history of animals, yet their proteomes remain sparsely annotated. MorF accurately predicts the functions of proteins with known homology in>90% cases, and annotates an additional 50% of the proteome beyond standard sequence-based methods. Using this, we uncover new functions for sponge cell types, including extensive FGF, TGF and Ephrin signalling in sponge epithelia, and redox metabolism and control in myopeptidocytes. Notably, we also annotate genes specific to the enigmatic sponge mesocytes, proposing they function to digest cell walls.ConclusionsOur work demonstrates that structural similarity is a powerful approach that complements and extends sequence similarity searches to identify homologous proteins over long evolutionary distances. We anticipate this to be a powerful approach that boosts discovery in numerous -omics datasets, especially for non-model organisms.
High-order thalamic and motor cortex inputs integrate sublinearly into tuft dendrites of pyramidal neurons in mouse somatosensory cortex
Authors: Han Young-Eun , Choi Joon Ho , Kim Kyungsoo , Kang Seongtak , Park Hyungju , Choi Ji-Woong , Rah Jong-Cheol 
Published: July 2022

AbstractTuft dendrites of pyramidal neurons housed in layer 1 of the neocortex form extensive excitatory synaptic connections with long-range cortical and high-order thalamic axons, along with diverse inhibitory inputs. Recently, we reported that synapses from the vibrissal primary motor cortex (vM1) and posterior medial thalamic nucleus (POm) are spatially clustered together in the same set of distal dendrites, suggesting a close functional interaction. In this study, we evaluated how these two types of synapses interact with each other using in vivo two-photon Ca2+ imaging and electrophysiology. We observed that dendritic Ca2+ responses could be efficiently evoked by electrical stimulation of POm or vM1 in the overlapping set of dendritic branches, rejecting the idea of branch-wise origin-selective synaptic wiring. Surprisingly, the Ca2+ responses upon coincident POm and vM1 stimulation summed sublinearly. We attribute this sublinearity to mutual inhibition via inhibitory neurons because synaptic currents generated by POm and vM1 also integrated sublinearly, but pharmacologically isolated direct synaptic currents summed linearly. Inhibitory neurons receiving POm inputs in the superficial cortical layer negatively regulated vM1-evoked responses. Finally, POm and vM1 innervated overlapping but distinct populations of somatostatin-expressing inhibitory neurons. Thus, POm and vM1 inputs negatively modulate each other in the mouse somatosensory cortex.
Effects of Variation in Urine Sample Storage Conditions on 16S Urogenital Microbiome Analyses
Authors: Kumar Tanya , Bryant MacKenzie , Cantrell Kalen , Song Se Jin , McDonald Daniel , Tubb Helena M. , Farmer Sawyer , Lukacz Emily S. , Brubaker Linda , Knight Rob 
Published: July 2022

AbstractReplicability is a well-established challenge in microbiome research with a variety of contributing factors at all stages, from sample collection to code execution. Here, we focus on voided urine sample storage conditions for urogenital microbiome analysis. Using urine samples collected from 10 healthy adult women, we investigated the microbiome preservation efficacy of AssayAssure® Genelock (as opposed to no preservative) under different temperature conditions. We varied temperature over 48 hours in order to examine the impact of conditions samples may experience with home voided urine collection and shipping to a central biorepository. The following common lab and shipping conditions were investigated: -20C, ambient temperature, 4C, a freeze-thaw cycle, and a heat cycle. At 48 hours, all samples were stored at -80C until processing. After generating 16S rRNA gene amplicon sequencing data using the highly sensitive KatharoSeq protocol, we observed individual variation in both alpha and beta diversity metrics below interhuman differences, corroborating reports of individual microbiome variability in other specimen types. While there was no significant difference in beta diversity when comparing AssayAssure® Genelock vs. no preservative, we did observe a higher concordance with AssayAssure samples shipped at colder temperatures (−20C and 4C) when compared to the samples shipped at -20C without preservative. Our results indicate that AssayAssure does not introduce a significant amount of microbial bias when used on a range of temperatures but is most effective at colder temperatures.ImportanceThe urogenital microbiome is an understudied yet important human microbiome niche. Research has been stimulated by the relatively recent discovery that urine is not sterile: urinary tract microbes have been linked to health problems including urinary infections, incontinence, and cancer. The quality of life and economic impact of UTIs and urgency incontinence alone are enormous, with $3.5 billion and $82.6 billion respectively spent in the U.S. annually. Given the low biomass of urine, novelty of the field, and well-established replicability bias in microbiome studies, it is critical to study storage conditions on urine samples to minimize microbial biases. Efficient and reliable preservation methods permit home self-sample collection and shipping, increasing the accessibility of larger-scale studies. Here, we examined both buffer and temperature variation effects on 16S rRNA gene amplicon sequencing results from urogenital samples, providing data on the consequences of common storage methods on urogenital microbiome results.
Tryptophan specialized metabolism and ER body-resident myrosinases modulate root microbiota assembly
Authors: Basak Arpan Kumar , Piasecka Anna , Hucklenbroich Jana , Türksoy Gözde Merve , Guan Rui , Zhang Pengfan , Getzke Felix , Garrido-Oter Ruben , Hacquard Stephane , Strzałka Kazimierz , Bednarek Paweł , Yamada Kenji , Nakano Ryohei Thomas 
Published: July 2022

AbstractIndole glucosinolates (IGs) are tryptophan (Trp)-derived sulfur-containing specialized metabolites that play a crucial role in plant-microbe interactions in plants of the order Brassicales, including Arabidopsis thaliana. Despite the growing body of evidence implicating IG biosynthetic pathways in root-microbiota interactions, how myrosinases, the enzymes that convert inert IGs into bioactive intermediate/terminal products, contribute to this process remains unknown. Here, we describe the roles of the PYK10 and BGLU21 myrosinases in root-microbiota assembly partly via metabolites secreted from roots into the rhizosphere. PYK10 and BGLU21 localize to the endoplasmic reticulum (ER) body, an ER-derived organelle observed in plants of the family Brassicaceae. We investigated the root microbiota structure of mutants defective in the Trp metabolic (cyp79b2b3 and myb34/51/122) and ER body (nai1 and pyk10bglu21) pathways and found that these factors together contribute to the assembly of root microbiota. Microbial community composition in soils as well as in bacterial synthetic communities (SynComs) treated with root exudates axenically collected from pyk10bglu21 and cyp79b2b3 differed significantly from those treated with exudates derived from wild-type plants, pointing to a direct role of root-exuded compounds. We also show that growth of the pyk10bglu21 and cyp79b2b3 mutants was severely inhibited by fungal endophytes isolated from healthy A. thaliana plants. Overall, our findings demonstrate that root ER body-resident myrosinases influencing the secretion of Trp-derived specialized metabolites represent a lineage-specific innovation that evolved in Brassicaceae to regulate root microbiota structure.SignificanceER bodies were first identified in roots of Brassicaceae plants more than 50 years ago, but their physiological functions have remained uncharacterized. A series of previous studies have suggested their possible role in root-microbe interactions. Here, we provide clear experimental evidence showing a role for ER bodies in root-microbiota interactions, which overlaps with that of root-exuded Trp-derived metabolites. Our findings delineate a plant lineage-specific innovation involving intracellular compartments and metabolic enzymes that evolved to regulate plant-microbe interactions at the root-soil interface.
Towards a mesoscale physical modeling framework for stereotactic-EEG recordings
Authors: Mercadal Borja , Lopez-Sola Edmundo , Galan-Gadea Adrià , Al Harrach Mariam , Sanchez-Todo Roser , Salvador Ricardo , Bartolomei Fabrice , Wendling Fabrice , Ruffini Giulio 
Published: July 2022

AbstractObjectiveStereotactic-EEG (SEEG) and scalp EEG recordings can be modeled using mesoscale neural mass population models (NMM). However, the relationship between those mathematical models and the physics of the measurements is unclear. In addition, it is challenging to represent SEEG data by combining NMMs and volume conductor models due to the intermediate spatial scale represented by these measurements.ApproachWe provide a framework combining the multicompartmental modeling formalism and a detailed geometrical model to simulate the transmembrane currents that appear in layer 3, 5 and 6 pyramidal cells due to a synaptic input. With this approach, it is possible to realistically simulate the current source density (CSD) depth profile inside a cortical patch due to inputs localized into a single cortical layer and the induced voltage measured by two SEEG contacts using a volume conductor model. Based on this approach, we built a framework to connect the activity of a NMM with a volume conductor model and we simulated an example of SEEG signal as a proof of concept.Main resultsCSD depends strongly on the distribution of the synaptic inputs onto the different cortical layers and the equivalent current dipole strengths display substantial differences (of up to a factor of four in magnitude in our example). Thus, the inputs coming from different neural populations do not contribute equally to the electrophysiological recordings. A direct consequence of this is that the raw output of neural mass models is not a good proxy for electrical recordings. We also show that the simplest CSD model that can accurately reproduce SEEG measurements can be constructed from discrete monopolar sources (one per cortical layer).SignificanceOur results highlight the importance of including a physical model in NMMs to represent measurements. We provide a framework connecting microscale neuron models with the neural mass formalism and with physical models of the measurement process that can improve the accuracy of predicted electrophysiological recordings.
Membrane lipid reshaping underlies oxidative stress sensing by the mitochondrial proteins UCP1 and ANT1
Authors: Jovanović Olga , Chekashkina Ksenia , Škulj Sanja , Žuna Kristina , Vazdar Mario , Bashkirov Pavel V. , Pohl Elena E. 
Published: July 2022

AbstractOxidative stress and ROS are important players in the pathogenesis of several diseases. Besides the direct modification of proteins, ROS modify lipids with negative spontaneous curvature, such as phosphatidylethanolamine (PE), producing PE adducts and lysolipids. The formation of PE-adducts potentiates the protonophoric activity of the uncoupling protein 1 (UCP1), but the molecular mechanism remains obscure. Here, we connected the ROS-mediated lipid shape alteration with the membrane mechanical properties and function of UCP1 and adenine nucleotide translocase 1 (ANT1). We found that lysophosphatidylcholines (OPC and MPC) and PE adducts decrease a bending modulus in lipid bilayers and increase the protonophoric activity of both proteins. Furthermore, MD simulations revealed that modified PEs and lysolipids alter the membrane lateral pressure profile in the same direction and range, indicating that modified PEs act as lipids with positive spontaneous curvature. Both results indicate that oxidative stress decreases stored curvature elastic stress (SCES) in the lipid bilayer membrane. In conclusion, we demonstrate that UCP1 and ANT1 sense SCES and propose a new regulatory mechanism for the function of these proteins.
Dichotomous Intrinsic Properties of Adult Accumbens Medium Spiny Neurons Vanish in the Fragile X Mouse Model of Autism
Authors: Giua Gabriele , Lassalle Olivier , Makrini-Maleville Leila , Valjent Emmanuel , Chavis Pascale , Manzoni Olivier J.J. 
Published: July 2022

AbstractFragile X syndrome (FXS), the most common cause of autism and inherited intellectual disability, is caused by the mutation of a single gene, fmr1, which encodes the Fragile X mental retardation protein (FMRP). FXS patients suffer from cognitive, emotional, and social deficits indicative of dysfunction in the nucleus accumbens (NAc), a structure central to the control of social behavior. The major cell type of the NAc, medium spiny neurons (MSNs), are differentiated in two subtypes based on their expression of either dopamine D1 or D2 receptors, their connectivity, and associated behavioral functions. Understanding how the absence of FMRP differentially affects the cellular properties of MSNs is a necessary step to categorize FXS cellular endophenotypes. To address this question, we comprehensively compared the intrinsic passive and active properties of MSN subtypes identified in a novel Fmr1-/y :: Drd1a-tdTomato mouse model allowing in-situ identification of MSN subtypes in FXS mice. Although fmr1 transcripts and their gene product, FMRP, were found in both MSNs subtypes, the results suggest cell-autonomous functions for Fmr1. The opposite membrane properties and action potential kinetics that normally discriminate D1- from D2- MSNs in WT mouse is either reversed or abolished in Fmr1-/y :: Drd1a-tdTomato mice. Multivariate analysis shed light on the compound effects of Fmr1 ablation by revealing how the phenotypic traits that distinguish each cell type in WT are modified in FXS. Together these data show that in Fragile X mice the normal dichotomy that characterizes NAc D1- and D2-MSNs is thrown out of balance, leading to a uniform phenotype that could underlie selected aspects of the pathology.