bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cis-inhibition suppresses basal Notch signalling during sensory organ precursor selection
Authors: Troost Tobias , Binshtok Udi , Sprinzak David , Klein Thomas 
Published: July 2022

AbstractThe emergence of the sensory organ precursor (SOP) from the proneural equivalence group in Drosophila melanogaster is a paradigm for studying single cell fate specification through the process of lateral inhibition. Classical lateral inhibition models describing this selection process are based on a transcriptional feedback mechanism where inhibitory signals between neighbouring cells, mediated by Notch pathway, are coupled to an intracellular circuit regulating the expression of the Notch ligand Delta (Dl). It was previously shown that in addition to its ability to trans-activate Notch in neighbouring cells, Dl can also cis-inhibit Notch in the same cell. However, it remains unclear what role does cis-inhibition play during SOP selection, and how it contributes to the selection of only one SOP. Here we address these questions using the unexpected observation that the mammalian ligand Delta-like 1 (Dll1) can trans-activate but not cis-inhibit Notch in Drosophila. We develop a mathematical model for SOP selection, termed the two-channel SOP (TCS) model, where Dl activity, but not its expression, is regulated by two channels associated with the two E3 ubiquitin ligases Neuralized (Neur) and Mindbomb1 (Mib1). While the Neur-dependent channel is regulated by Notch signalling, the Mib1-dependent channel is not, leading to tissue-wide basal inhibitory activity. We show theoretically and experimentally that cis-inhibition is required for suppressing Mib1-dependent basal Notch activity. Thus, our results highlight the trade-off between basal Notch activity and cis-inhibition as a mechanism for singling out an SOP from the proneural equivalence group.
Bulb growth potential is independent of leaf longevity for the spring ephemeralErythronium americanumKer-Gawl
Authors: Bertrand Hugo , Lapointe Line 
Published: July 2022

AbstractGrowth in most spring ephemerals is decreased under warmer temperatures. Although photosynthetic activities are improved at warmer temperatures, leaves senesce earlier, which prevents the bulb from reaching a larger size. A longer leaf life duration during a warm spring, therefore, may improve bulb mass. We tested this hypothesis by modulating leaf life span ofErythronium americanumthrough the application of Promalin® (PRO; cytokinins and gibberellins) that prolonged, or silver thiosulphate (STS) that reduced leaf duration. Gas exchange and chlorophyll fluorescence were measured along with leaf and bulb carbohydrate concentrations. Plants were also pulse labelled with13CO2to monitor sugar transport to the bulb. Lower photosynthetic rates and shorter leaf life span of STS plants reduced the quantity of C that they assimilated during the season, resulting in a smaller bulb compared to Control plants. PRO plants maintained their photosynthetic rates for a longer period than Control plants, yet final bulb biomass did not differ between them. We conclude that seasonal growth forE. americanumis not limited by leaf life duration under warm growing conditions, but rather by limited sink growth capacity. Under global warming, spring geophytes might be at risk of being reduced in size and eventually, reproducing less frequently.HighlightWarmer springs negatively affect trout lily growth and delaying leaf senescence in this spring ephemeral does not translate into a larger bulb if temperatures remain high during springtime.
NeuronBridge: an intuitive web application for neuronal morphology search across large data sets
Authors: Clements Jody , Goina Cristian , Hubbard Philip M. , Kawase Takashi , Olbris Donald J. , Otsuna Hideo , Svirskas Robert , Rokicki Konrad 
Published: July 2022

AbstractNeuroscience research in Drosophila is benefiting from large-scale connectomics efforts using electron microscopy (EM) to reveal all the neurons in a brain and their connections. In order to exploit this knowledge base, researchers target individual neurons and study their function. Therefore, vast libraries of fly driver lines expressing fluorescent reporter genes in sets of neurons have been created and imaged using confocal light microscopy (LM). However, creating a fly line for driving gene expression within a single neuron found in the EM connectome remains a challenge, as it typically requires identifying a pair of fly lines where only the neuron of interest is expressed in both. This task and other emerging scientific workflows require finding similar neurons across large data sets imaged using different modalities. Here, we present NeuronBridge, a web application for easily and rapidly finding putative morphological matches between large datasets of neurons imaged using different modalities. We describe the functionality and construction of the NeuronBridge service, including its user-friendly GUI, data model, serverless cloud architecture, and massively parallel image search engine. NeuronBridge is openly accessible at http://neuronbridge.janelia.org/.
Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
Authors: Soni Komal , Sivadas Anusree , Horváth Attila , Dobrev Nikolay , Hayashi Rippei , Kiss Leo , Simon Bernd , Wild Klemens , Sinning Irmgard , Fischer Tamás 
Published: July 2022

AbstractThe S. pombe orthologue of the human PAXT complex, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex which targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA transcripts as part of the cleavage and polyadenylation factor (CPF/CPSF). In this study we identified and characterised the interaction between Pla1 and the MTREC complex core component Red1 and analysed the functional relevance of this interaction in vivo. Our crystal structure of the Pla1-Red1 complex showed that a 58-residue fragment in Red1 binds to the RNA recognition motif domain of Pla1 and tethers it to the MTREC complex. Structure-based Pla1-Red1 interaction mutations showed that Pla1, as part of MTREC complex, hyper-adenylates CUTs for their efficient degradation. Interestingly, the Red1-Pla1 interaction was also required for the efficient assembly of the fission yeast facultative heterochromatic islands. Together, our data suggest a complex interplay between the RNA surveillance and 3’-end processing machineries.
Building Bridges: Mycelium Mediated Plant-Plant Electrophysiological Communication
Authors: Thomas Matthew Adam , Cooper Robin Lewis 
Published: July 2022

AbstractWhether through root secretions or by emitting volatile organic compounds, plant communication has been well-documented. While electrical activity has been documented in plants and mycorrhizal bodies on the individual and ramet, electrical propagation as a means of communication between plants has been hypothesized but understudied. This study aimed to test the hypothesis that plants can communicate with one another electrically via conductively isolated mycelial pathways. We created a bio-electric circuit linking two plants using a mycelial network with a blend of endomycorrhizal fungi grown on potato dextrose agar forming the isolated conductive pathway between plants. Using this plant-fungal biocircuit we assessed electrical propagation between Pisum sativum and Cucumis sativus We found that electrical signals were reliably conducted across the mycelial bridges from one plant to another upon the induction of a wound response. Our findings provide evidence that mechanical input can be communicated between plant species and opens the door to testing how this information can affect plant and fungal physiology.Simple SummaryMost plants form underground relationships with fungi. These relationships are mutually beneficial. The plants and fungi share, trade, and distribute resources between themselves, their neighbors, and their offspring. Plants employ diverse methods to detect and respond to their environment and the production of electric signals is one of these methods. It would be favorable to a plant’s survival and the survival of their neighbors, if this plant could transmit and share the information these electrical signals contain. Possible avenues of transmission exist in the roots, and the fungi these roots are in contact with. If a fungal mass is in contact with the roots of multiple plants, it could propagate electrical signals throughout the plant network. We found that electric signals were reliably transmitted from one plant to another via fungal pathways upon the induction of a wound response. Our findings provide evidence that mechanical input can be communicated between plant species and opens the door to testing how this information can affect plant physiology.
Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance
Authors: Cabrera Kevin , Hoard Duncan S. , Martinez Daniel I. , Wunderlich Zeba 
Published: July 2022

AbstractMost multicellular organisms, including fruit flies, possess an innate immune response, but lack an adaptive immune response. Even without adaptive immunity, “immune priming” allows organisms to survive a second infection more effectively after an initial, non-lethal infection. We used Drosophila melanogaster to study the transcriptional program that underlies priming. Using an insect-derived strain of Gram-positive Enterococcus faecalis, we found a low dose infection enhances survival of a subsequent high dose infection. The enhanced survival in primed animals does not correlate with a decreased bacterial load, implying that the organisms tolerate, rather than resist the infection. We measured the transcriptome associated with immune priming in the fly immune organs: the fat body and hemocytes. We found many genes that were only upregulated in re-infected flies. In contrast, there are very few genes that either remained transcriptionally active throughout the experiment or more efficiently re-activated upon reinfection. Measurements of priming in immune deficient mutants revealed IMD signaling is largely dispensable for responding to a single infection, but needed to fully prime; while Toll signaling is required to respond to a single infection, but dispensable for priming. Overall, we found a primed immune response to E. faecalis relies on immune tolerance rather than bacterial resistance and drives a unique transcriptional response.
DNA-binding mechanism and evolution of Replication Protein A
Authors: Madru Clément , Martinez-Carranza Markel , Laurent Sébastien , Alberti Alessandra C. , Chevreuil Maelenn , Raynal Bertrand , Haouz Ahmed , Le Meur Rémy A. , Delarue Marc , Flament Didier , Krupovic Mart , Legrand Pierre , Sauguet Ludovic 
Published: July 2022

ABSTRACTReplication Protein A (RPA) is a heterotrimeric single stranded DNA-binding protein with essential roles in DNA replication, recombination and repair, in both eukaryotic and archaeal cells. By using an integrative approach that combines three crystal structures, four cryo-EM structures in complex with single-stranded DNA (ssDNA) of different lengths, we extensively characterized RPA from Pyrococcus abyssi in different states. These structures show two essential features conserved in eukaryotes: a trimeric core and a module that promotes cooperative binding to ssDNA, as well as a newly identified archaeal-specific domain. These structures reveal for the first time how ssDNA is handed over from one RPA complex to the other, and uncover an unanticipated mechanism of self-association on ssDNA tracts. This work constitutes a significant step forward in the molecular understanding of the structure and DNA-binding mechanism of RPA, with far-reaching implications for the evolution of this primordial replication factor in Archaea and Eukarya.
Testis-specific H2BFWT disrupts nucleosome integrity through reductions of DNA-histone interactions
Authors: Ding Dongbo , Pang Matthew Y.H. , Deng Mingxi , Nguyen Thi Thuy , Sun Xulun , Xu Zhichun , Zhang Yingyi , Zhai Yuanliang , Yan Yan , Ishibashi Toyotaka 
Published: July 2022

AbstractDuring spermatogenesis, multiple testis-specific histone variants are involved in the dynamic chromatin transitions. H2BFWT is a primate testis-specific H2B variant with hitherto unclear functions, and SNPs of H2BFWT are closely associated with male non-obstructive infertility. Here, we found that H2BFWT is preferentially localized in the sub-telomeric regions and the promoters of genes highly expressed in testis from differentiated spermatogonia to early spermatocytes. Cryo-EM structural analysis shows that H2BFWT nucleosomes are defined by weakened interactions between H2A-H2BFWT dimer and H4, and between histone octamer and DNA. Furthermore, one of its SNPs, H2BFWTH100R further destabilizes nucleosomes and increases the nucleosome unwrapping rate by interfering with the interaction with H4K91. Our results suggest that H2BFWT may be necessary for the regulation of spermatogenesis-related gene expression by decreasing transcriptional barriers, and that H2BFWTH100R overdrives its nucleosome-destabilizing effects which causes infertility.
mTORC1 hyperactivation causes sensory integration deficits due to habenula impairment
Authors: Doszyn Olga , Kedra Magdalena , Zmorzynska Justyna 
Published: July 2022

AbstractMechanistic target of rapamycin complex 1 (mTORC1) is an integration hub for extracellular and intracellular signals necessary for proper brain development. Hyperactivation of mTORC1 is found in many developmental diseases, including autism spectrum disorder (ASD). Atypical reactivity to sensory stimuli is often found in patients with ASD. The most frequent hereditary cause of ASD is Tuberous Sclerosis Complex (TSC), in which inactivating mutations in the TSC1 or TSC2 genes result in hyperactivation of the mTORC1 pathway. We have discovered that the zebrafish model of TSC, tsc2vu242/vu242 mutants lack light preference, a behavior requiring integration of multiple sensory inputs. Here, we show that the lack of light preference in tsc2vu242/vu242 zebrafish is caused by aberrant sensory integration of light stimuli in the left dorsal habenula. Single-cell calcium imaging analysis revealed that tsc2vu242/vu242 fish showed impaired function of the left dorsal habenula, in which neurons exhibited higher activity and lacked habituation to the light stimuli resulting in atypical response to light. Lack of light-preference behavior and abnormal neuronal activity in the left dorsal habenula were rescued by rapamycin, indicating that hyperactive mTorC1 causes aberrant habenula function and impaired sensory integration resulting in lack of light preference. Our results link sensory integration deficits seen in TSC patients suffering from ASD with hyperactive mTORC1 and suggest that mTORC1 hyperactivity contributes to atypical reactivity to sensory stimuli in ASD.
Pore-forming protein βγ-CAT drives extracellular nutrient scavenging under cell starvation
Authors: Liu Ling-Zhen , Liu Long , Shi Zhi-Hong , Bian Xian-Ling , Wang Qi-Quan , Xiang Yang , Zhang Yun 
Published: July 2022

AbstractNutrient acquisition is essential for cells. βγ-CAT is a pore-forming protein (PFP) and trefoil factor complex assembled under tight regulation identified in toad Bombina maxima. Here, we reported that B. maxima cells secreted βγ-CAT under glucose and glutamine deficiency to scavenge extracellular proteins for their nutrient supply and survival. AMP-activated kinase signaling positively regulated the expression and secretion of βγ-CAT. The PFP complex promoted albumin and ovalbumin uptake through endolysosomal pathways. Elevated intracellular amino acids, enhanced ATP production, and eventually prolonged cell survival were observed in the presence of βγ-CAT and extracellular albumin or ovalbumin. Liposome assays indicated that high concentration of ATP (around 1–5 mM) negatively regulated the opening of βγ-CAT channels. Collectively, these results uncovered that βγ-CAT is an essential element in cell nutrient scavenging under cell starvation by driving vesicular uptake of extracellular proteins, providing a new paradigm for PFPs in cell nutrient acquisition and metabolic flexibility.
stAPAminer: Mining Spatial Patterns of Alternative Polyadenylation for Spatially Resolved Transcriptomic Studies
Authors: Ji Guoli , Tang Qi , Zhu Sheng , Zhu Junyi , Ye Pengchao , Xia Shuting , Wu Xiaohui 
Published: July 2022

AbstractAlternative polyadenylation (APA) contributes to transcriptome complexity and gene expression regulation, which has been implicated in various cellular processes and diseases. Single-cell RNA-seq (scRNA-seq) has led to the profile of APA at the single-cell level, however, the spatial information of cells is not preserved in scRNA-seq. Alternatively, spatial transcriptomics (ST) technologies provide opportunities to decipher the spatial context of the transcriptomic landscape within single cells and/or across tissue sections. Pioneering studies on ST have unveiled potential spatially variable genes and/or splice isoforms, however, the pattern of APA usages in spatial contexts remains unappreciated. Here, we developed a toolkit called stAPAminer for mining spatial patterns of APA from spatial barcoded ST data. APA sites were identified and quantified from the ST data. Particularly, an imputation model based on K-nearest neighbors algorithm was designed for recovering APA signals. Then APA genes with spatial patterns of APA usage variation were identified. By analyzing the well-established ST data of mouse olfactory bulb (MOB), we present a detailed view of spatial APA usage across morphological layers of MOB with stAPAminer. We complied a comprehensive list of genes with spatial APA dynamics and obtained several major spatial expression patterns representing spatial APA dynamics in different morphological layers. Extending this analysis to two additional replicates of the MOB ST data, we found that spatial APA patterns of many genes are reproducible among replicates. stAPAminer employs the power of ST for exploring transcriptional atlas of spatial APA patterns with spatial resolution, which is available at https://github.com/BMILAB/stAPAminer.
Agency and Expectations in Pain Treatment: An Investigation of the Active Inference Model
Authors: Strube Andreas , Horing Björn , Rose Michael , Büchel Christian 
Published: July 2022

AbstractThe fact that we cannot tickle ourselves is traditionally explained by the attenuation of somatosensation by predictions from a forward model of self-generated movements. Alternatively, it has been suggested within the framework of active inference that Bayes-optimal reduction of sensory precision can explain this phenomenon. Combining a pain paradigm with stimulus-related expectations allows to compare both models through predictions from the Bayesian account of expectation-based hypoalgesia, where pain is influenced by the precisions of somatosensation and expectation. In two experiments, heat pain was sham-treated either externally or by the subject, while a cue created higher or lower treatment expectations. Both experiments revealed greater pain relief under self-treatment and high treatment expectations. Electroencephalography revealed a modulation of theta-to-beta frequencies linked to agency and top-down modulations of pain perception. Computational modeling showed that this is better explained by an attenuation of somatosensation than a downregulation of somatosensation precision, favoring the forward model.
Establishment of Transgenic Fluorescent Mice for Screening Synaptogenic Adhesion Molecules
Authors: Yang Lei , Zhang Jingtao , Zhang Yanning , Wang Li , Wang Xiaotong , Wang Shanshan , Li Ke , Wei Mengping , Zhang Chen 
Published: July 2022

AbstractSynapse is the fundamental structure for neurons to transmit information between cells. The proper synapse formation is crucial for developing neural circuits and cognitive functions of the brain. The aberrant synapse formation has been proved to cause many neurological disorders, including autism spectrum disorders and intellectual disability. Synaptic cell adhesion molecules (CAMs) are thought to play a major role in achieving mechanistic cell-cell recognition and initiating synapse formation via trans-synaptic interactions. Although several synaptic CAMs, such as neurexins, neuroligins, SynCAMs, and LRRTMs, have been identified as synaptogenic molecules, these molecules so far as we know cannot fully explain the mechanism of synapse formation. There should be other synaptogenic adhesion molecules that remain undiscovered. Artificial synapse formation (ASF) assays, the commonly used method for screening synaptogenesis molecules, is time-consuming and labor-intensive due to the long-lasting immunostaining step. To skip this step, we generated synaptotagmin 1-tdTomato (Syt1-TDT) transgenic mice by inserting the tdTomato-fused synaptotagmin 1 coding sequence into the genome of C57BL/6J mice. In the brain of Syt1-TDT transgenic mice, the Syt1-TDT signals were widely observed in different areas. In the cultured hippocampal neurons, the Syt1-TDT signals merged with several synaptic markers, suggesting the well synaptic localization of Syt1-TDT. Compared to the wild-type (WT) mouse neurons, cultured hippocampal neurons from Syt1-TDT transgenic mice presented normal synaptic neurotransmission. In ASF assays, neurons from Syt1-TDT transgenic mice could form synaptic connections with HEK293T cells expressing neuroligin2, LRRTM2, and Slitrk2 without immunostaining. Therefore, our work suggested that the Syt1-TDT transgenic mice with the ability to label synapses by tdTomato will be a convenient tool for screening synaptogenic molecules.