bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation and ubiquitination independent endocytosis of BRI1
Authors: Alves Neubus Claus Lucas , Liu Derui , Hohmann Ulrich , Vukašinović Nemanja , Pleskot Roman , Liu Jing , Schiffner Alexei , Jaillais Yvon , Wu Guang , Wolf Sebastian , Van Damme Daniël , Hothorn Michael , Russinova Eugenia 
Published: July 2022

AbstractThe brassinosteroid (BR) hormone and its plasma membrane receptor BR INSENSITIVE1 (BRI1) is one of the best-studied receptor-ligand pairs for understanding the interplay between receptor endocytosis and signaling in plants. BR signaling is mainly determined by the plasma membrane pool of BRI1, whereas BRI1 endocytosis ensures signal attenuation. Since BRs are ubiquitously distributed in the plant, the tools available to study BRI1 function without interference from endogenous BRs are limited. Here, we designed a BR-binding-deficient mutant based on protein sequence-structure analysis and homology modeling of BRI1 and its close homologues. This new tool allowed us to re-examine the BRI1 endocytosis and signal attenuation model. We show that despite decreased phosphorylation and ubiquitination, the BR-binding-deficient BRI1 was internalized similar to the wild type form. These results reinforce the hypothesis that BRI1 is internalized via parallel endocytic routes and machineries. In addition, BR-binding-deficient mutant provides opportunities to study non-canonical ligand-independent BRI1 functions.
Quinolinate Promotes Immune Tolerance through Macrophage Polarization in Glioblastoma
Authors: Kesarwani Pravin , Kant Shiva , Zhao Yi , Chinnaiyan Prakash 
Published: July 2022

ABSTRACTThere has been considerable scientific effort dedicated to understanding the biologic consequence and therapeutic implications of aberrant tryptophan metabolism in brain tumors and neurodegenerative diseases. An overwhelming majority of this work has focused on the upstream metabolism of tryptophan; however, this has not resulted in clinical application. Using global metabolomic profiling of patient-derived brain tumors, we identify the downstream metabolism of tryptophan and accumulation of quinolinate (QA) as a metabolic node in glioblastoma and went on to demonstrate its critical role in promoting immune tolerance. QA acts as a “metabolic checkpoint” in glioblastoma by inducing NMDA receptor activation and Foxo1/PPARγ signaling, resulting in amplification of immune suppressive macrophages. Using a genetically-engineered mouse model designed to inhibit production of QA, we identify kynureninase as a promising therapeutic target to revert the potent immune suppressive microenvironment in glioblastoma. These findings offer the scientific community an opportunity to revisit the biologic consequence of this pathway as it relates to oncogenesis and neurodegenerative disease and a framework for developing new immune modulatory agents to further clinical gains in these otherwise incurable diseases.
A branching model of cell fate decisions in the enteric nervous system
Authors: Laddach Anna , Chng Song Hui , Lasrado Reena , Progatzky Fränze , Shapiro Michael , Artemov Artem , Castaneda Marisol Sampedro , Erickson Alek , Bon-Frauches Ana Carina , Kleinjung Jens , Boeing Stefan , Ultanir Sila , Adameyko Igor , Pachnis Vassilis 
Published: July 2022

AbstractHow neurogenesis and gliogenesis are coordinated during development and why mature glial cells often share properties with neuroectodermal progenitors remains unclear. Here, we have used single cell RNA sequencing to map the regulatory landscape of neuronal and glial differentiation in the mammalian enteric nervous system (ENS). Our analysis indicates that neurogenic trajectories branch directly from a linear gliogenic axis defined by autonomic neural crest cells adopting sequential states as they progressively lose their strong neurogenic bias and acquire properties of adult enteric glia. We identify gene modules associated with transcriptional programs driving enteric neurogenesis and cell state transitions along the gliogenic axis. By comparing the chromatin accessibility profile of autonomic neural crest and adult enteric glia we provide evidence that the latter maintain an epigenetic memory of their neurogenic past. Finally, we demonstrate that adult enteric glia maintain neurogenic potential and are capable of generating enteric neurons in certain contexts by activating transcriptional programs employed by early ENS progenitors. Our studies uncover a novel configuration of enteric neurogenesis and gliogenesis that enables the coordinate development of ENS lineages and provides a mechanistic explanation for the ability of enteric glia to be functionally integrated into the adult intestine and simultaneously maintain attributes of early ENS progenitors.
Mapping Pharmacologically-induced Functional Reorganisation onto the Brain’s Neurotransmitter Landscape
Authors: Luppi Andrea I. , Hansen Justine Y. , Adapa Ram , Carhart-Harris Robin L. , Roseman Leor , Timmermann Christopher , Golkowski Daniel , Ranft Andreas , Ilg Rüdiger , Jordan Denis , Bonhomme Vincent , Vanhaudenhuyse Audrey , Demertzi Athena , Jaquet Oceane , Bahri Mohamed Ali , Alnagger Naji L.N. , Cardone Paolo , Peattie Alexander R. D. , Manktelow Anne E. , de Araujo Draulio B. , Sensi Stefano L. , Owen Adrian M. , Naci Lorina , Menon David K. , Misic Bratislav , Stamatakis Emmanuel A. 
Published: July 2022

AbstractTo understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brain’s rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brain’s functional architecture.
OptoPi: An open source flexible platform for the analysis of small animal behaviour
Authors: Cano-Ferrer Xavier , Roberts Ruairí J.V. , French Alice S. , de Folter Joost , Gong Hui , Nightingale Luke , Strange Amy , Imbert Albane , Prieto-Godino Lucia L. 
Published: July 2022

AbstractBehaviour is the ultimate output of neural circuit computations, and therefore its analysis is a cornerstone of neuroscience research. However, every animal and experimental paradigm requires different illumination conditions to capture and, in some cases, manipulate specific behavioural features. This means that researchers often develop, from scratch, their own solutions and experimental set-ups. Here, we present OptoPi, an open source, affordable (∼ £600), behavioural arena with accompanying multi-animal tracking software. The system features highly customisable and reproducible visible and infrared illumination and allows for temporally precise optogenetic stimulation. OptoPi acquires images using a Raspberry Pi camera, features motorised LED-based illumination, Arduino control, as well as spectrum and irradiance monitoring to fine-tune illumination conditions with real time feedback. Our open-source software (BIO) can be used to simultaneously track multiple animals while accurately keeping individual animal’s identity both in on-line and off-line modes. We demonstrate the functionality of OptoPi by recording and tracking under different illumination conditions the spontaneous behaviour of larval zebrafish as well as adult Drosophila flies and their first instar larvae, an experimental animal that due to its small size and transparency has classically been hard to track. Further, we showcase OptoPi’s optogenetic capabilities through a series of experiments using transgenic Drosophila larvae.
The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein
Authors: Piacentini Sara , Riccio Anna , Santopolo Silvia , Pauciullo Silvia , Frazia Simone La , Rossi Antonio , Rossignol Jean-Francois , Santoro M. Gabriella 
Published: July 2022

AbstractCoronaviridaeis recognized as one of the most rapidly evolving virus family as a consequence of the high genomic nucleotide substitution rates and recombination. The family comprises a large number of enveloped, positive-sense single-stranded RNA viruses, causing an array of diseases of varying severity in animals and humans. To date, seven human coronaviruses (HCoV) have been identified, namely HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1, which are globally circulating in the human population (seasonal HCoV, sHCoV), and the highly pathogenic SARS-CoV, MERS-CoV and SARS-CoV-2. Seasonal HCoV are estimated to contribute to 15-30% of common cold cases in humans; although diseases are generally self-limiting, sHCoV can sometimes cause severe lower respiratory infections, as well as enteric and neurological diseases. No specific treatment is presently available for sHCoV infections. Herein we show that the anti-infective drug nitazoxanide has a potent antiviral activity against three human endemic coronaviruses, the Alpha-coronaviruses HCoV-229E and HCoV-NL63, and the Beta-coronavirus HCoV-OC43 in cell culture with IC50ranging between 0.05 and 0.15 μg/ml and high selectivity indexes. We found that nitazoxanide does not affect HCoV adsorption, entry or uncoating, but acts at postentry level and interferes with the spike glycoprotein maturation, hampering its terminal glycosylation at an endoglycosidase H-sensitive stage. Altogether the results indicate that nitazoxanide, due to its broad-spectrum anti-coronavirus activity, may represent a readily available useful tool in the treatment of seasonal coronavirus infections.
Comparative analyses of the N-glycoproteomes in HCT116 cancer cells and their non-tumorigenic DNMT1/3b double knockout (DKO1) cells and insight into the Mannose-6-phosphate pathway
Authors: Chen Minyong , Assis Diego M. , Benet Matthieu , McClung Colleen M. , Gordon Elizabeth , Ghose Shourjo , Dupard Steven J. , Willetts Matthew , Taron Christopher H. , Samuelson James C. 
Published: July 2022

AbstractN-glycoproteomic analyses provide valuable resources for investigation of cancer mechanisms, biomarkers, and therapeutic targets. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 display hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells.
Genetic and physiological insights into the diazotrophic activity of a non-cyanobacterial marine diazotroph
Authors: Joublin-Delavat Aurélie , Touahri Katia , Crétin Pauline , Morot Amandine , Rodrigues Sophie , Jesus Bruno , Trigodet Florian , Delavat François 
Published: July 2022

AbstractNitrogen (N2) fixation, or diazotrophy, supports a large part of primary production in oceans. Culture-independent approaches highlighted the presence in abundance of marine non-cyanobacterial diazotrophs (NCD) but their ecophysiology remains elusive, mostly because of the low number of isolated NCD and because of the lack of available genetic tools for these isolates. Here, a dual genetic and functional approach allowed unveiling the ecophysiology of a marine NCD affiliated to the speciesVibrio diazotrophicus. Physiological characterization of the first marine NCD mutant obtained so far was performed using a soft-gellan assay, demonstrating that a ΔnifHmutant in not able to grow in nitrogen-deprived media. Furthermore, we demonstrated thatV. diazotrophicusproduces a thick biofilm under diazotrophic conditions, suggesting biofilm production as an adaptive response of this NCD to cope with the inhibition of nitrogen-fixation by molecular oxygen. Finally, the genomic signature ofV. diazotrophicusis essentially absent from metagenomic data ofTara Oceanexpeditions, despite having been isolated from various marine environments. We think that the genetically tractableV. diazotrophicusstrain used in this study may serve as an ideal model to study the ecophysiology of these overlooked procaryotic group.
Ionic control of porin permeability in bacteria
Authors: Caño Muñiz Santiago E. , Hagting Anja , Evans Ieuan E. , Alsulami Ali F , Summers David , Blundell Tom L , Floto R. Andres 
Published: July 2022

AbstractBacterial porins permit permeation of hydrophilic nutrients and antibiotics across the outer membrane but also contribute to proton leak from the periplasmic space, suggesting that their activity might be dynamically regulated. Here we show, in Escherichia coli, that porin permeability is controlled by changes in periplasmic ions, inhibited by periplasmic acidification, thereby limiting proton loss during electron transport chain activity, and enhanced during starvation, promoting nutrient uptake. Growth in glucose increases periplasmic potassium through activating the voltage-gated channel Kch, triggering enhanced porin permeation and membrane action potentials. This metabolic control of porin permeability explains the recognized decrease in antibiotic susceptibility when bacteria are grown in lipid media and the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics.One sentence summaryThe permeability of bacterial porin is dynamically regulated by periplasmic pH and potassium levels, altering antibiotic resistance.
Sugar sensation and mechanosensation in the egg-laying preference shift of Drosophila suzukii
Authors: Wang Wanyue , Dweck Hany K M , Talross Gaëlle J S , Zaidi Ali , Gendron Joshua M. , Carlson John R 
Published: July 2022

AbstractThe agricultural pest Drosophila suzukii differs from most other Drosophila species in that it lays eggs in ripe, rather than overripe, fruit. Previously we showed that changes in bitter taste sensation accompanied this adaptation (Dweck et al., 2021). Here we show that D. suzukii has also undergone a variety of changes in sweet taste sensation. D. suzukii has a weaker preference than D. melanogaster for laying eggs on substrates containing all three primary fruit sugars: sucrose, fructose, and glucose. Major subsets of D. suzukii taste sensilla have lost electrophysiological responses to sugars. Expression of several key sugar receptor genes is reduced in the taste organs of D. suzukii. By contrast, certain mechanosensory channel genes, including nompC, are expressed at higher levels in the taste organs of D. suzukii, which has a higher preference for stiff substrates. Finally, we find that D. suzukii responds differently from D. melanogaster to combinations of sweet and mechanosensory cues. Thus, the two species differ in sweet sensation, mechanosensation, and their integration, which are all likely to contribute to the differences in their egg-laying preferences in nature.
Cryopreservation of mosquito microbiota for use in microcosm experiments
Authors: Zhao Serena Y. , Hughes Grant L. , Coon Kerri L. 
Published: July 2022

AbstractMosquitoes develop in a wide range of aquatic habitats containing highly diverse and variable bacterial communities that shape both larval and adult traits, including the capacity of adult females of some mosquito species to vector disease-causing organisms to humans. However, while most mosquito studies control for host genotype and environmental conditions, the impact of microbiota variation on phenotypic outcomes of mosquitoes is often unaccounted for. The inability to conduct reproducible intra- and inter-laboratory studies of mosquito-microbiota interactions has also greatly limited our ability to identify microbial targets for mosquito-borne disease control. Here, we developed an approach to isolate and cryopreserve microbial communities derived from mosquito larval rearing environments in the lab and field. We then validated the use of our approach to generate experimental microcosms colonized by standardized lab- and field-derived microbial communities. Our results overall reveal minimal effects of cryopreservation on the recovery of bacteria when directly compared with isolation from non-cryopreserved fresh material. Our results also reveal improved reproducibility of microbial communities in replicate microcosms generated using cryopreserved stocks over fresh material. Altogether, these results provide a critical next step toward the standardization of mosquito studies to include larval rearing environments colonized by defined microbial communities. They also lay the foundation for long-term studies of mosquito-microbe interactions and the identification and manipulation of taxa with potential to reduce mosquito vectorial capacity.
ProteinSGM: Score-based generative modeling forde novoprotein design
Authors: Lee Jin Sub , Kim Jisun , Kim Philip M. 
Published: July 2022

ABSTRACTThe generation ofde novoprotein structures with predefined function and properties remains a challenging problem in protein design. Diffusion models, a novel state-of-the-art class of generative models, have recently shown astounding empirical performance in image synthesis. Here we use image-based representations of protein structure to develop ProteinSGM, a score-based diffusion model that produces realisticde novoproteins and can inpaint plausible backbones and domains into structures of predefined length. Withunconditional generation, we show that ProteinSGM can generate native-like protein structures, surpassing the performance of previously reported generative models. We experimentally validate somede novodesigns and observe strong structural consistency with generated backbones. Finally, we applyconditional generationtode novoprotein design by formulating it as an image inpainting problem, allowing precise and modular design of protein structure.
Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory
Authors: Ibrahim Kirolos , Bennett Ilana J. 
Published: July 2022

AbstractSeparate unimodal magnetic resonance imaging (MRI) literatures have shown that hippocampal gray matter macrostructure (volume) and microstructure (diffusion) decline in aging and relate to episodic memory performance, with multimodal MRI studies reporting that episodic memory may be better explained by a combination of these metrics. However, these effects are often assessed independent of age or only within older adults and therefore do not address whether these distinct modalities mediate the effect of age on episodic memory. Here, we simultaneously examined the unique and joint contribution of hippocampal volume and diffusion to age-related differences in episodic memory in 83 younger and 61 older adults who underwent a T1-and diffusion-weighted MRI and completed the Rey Auditory Verbal Learning Test. As expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that the structural metrics did not jointly mediate the age-memory relationship. Together, these findings indicate that hippocampal microstructure uniquely contributes to age-related differences in episodic memory and suggest that volume and diffusion capture distinct neurobiological properties of hippocampal gray matter.
Novel Viral and Microbial Species in a Translocated Toutouwai (Petroica longipes) Population from Aotearoa/New Zealand
Authors: French Rebecca K. , Stone Zoë L. , Parker Kevin A. , Holmes Edward C. 
Published: July 2022

AbstractBackgroundTranslocation is a common tool in wildlife management and been responsible for many conservation successes. During translocations, any associated infectious agents are moved with their wildlife hosts. Accordingly, translocations can present a risk of infectious disease emergence, although they also provide an opportunity to restore natural infectious communities (‘infectome’) and mitigate the long-term risks of reduced natural resistance.MethodsWe used metatranscriptomic sequencing to characterise the infectome of 41 toutouwai (North Island robin, Petroica longipes) that were translocated to establish a new population within the North Island of New Zealand. We also screened for pathogenic bacteria, fungi and parasites.ResultsAlthough we did not detect any known avian diseases, which is a positive outcome for the translocated toutouwai population, we identified a number of novel viruses of interest, including a novel avian hepatovirus, as well as a divergent calici-like virus and four hepe-like viruses of which the host species is unknown. We also revealed a novel spirochete bacterium and a coccidian eukaryotic parasite.ConclusionsThe presumably non-pathogenic viruses and microbial species identified here support the idea that the majority of microorganisms likely do not cause disease in their hosts, and that translocations could serve to help restore and maintain native infectious communities. We advise greater surveillance of infectious communities of both native and non-native wildlife before and after translocations to better understand the impact, positive or negative, that such movements may have on both host and infectome ecology.
Comprehensive analysis identifies histone 2A ubiquitination as a marker for aging and pan-cancer prognosis
Authors: Zhang Fen , Wang Zhan , Zhang Jiahang , Zhou Menghao , Chen Yongxia , Zhang Sainan , Sun Zeyu , Ji Feiyang 
Published: July 2022

AbstractUbiquitination is a post-translational modification (PTM) that induces protein degradation or function alteration and plays crucial roles in aging and cancer. Previous ubiquitinomes of aging mainly focused on how ubiquitination changes in drosophila and other lower animals, but how ubiquitination changes during the aging of higher animals and what causes these changes remain unclear. Here, we profiled whole-life ubiquitinome data of mouse brain, heart, liver, muscle, and spleen, and integratively analyzed the ubiquitinome data with RNA sequencing data. The results showed that the ubiquitination of protein, especially histone 2A (H2A), changed intensely during aging due to the regulated expression of E3 ligases (E3s) and deubiquitylating enzymes (DUBs). Then we developed two distinct H2A’ E3s/DUBs expression subtypes with different prognosis, DNA damage response (DDR), and tumor microenvironment cell infiltration degrees based on an unsupervised method in pan-cancer. In conclusion, our study provided temporal resolution ubiquitinome data of mouse aging and revealed the vital role of H2A ubiquitination in aging and tumor progression.