bluuebunny/crossref_metadata_2025_split huggingface dataset:
Larval microbiota primes theDrosophilaadult gustatory response
Authors: Montanari Martina , Manière Gérard , Berthelot-Grosjean Martine , Dusabyinema Yves , Gillet Benjamin , Grosjean Yaël , Kurz C. Léopold , Royet Julien 
Published: March 2023

AbstractThe survival of animals depends, among other things, on their ability to identify threats in their surrounding environment. Senses such as olfaction, vision and taste play an essential role in sampling their living environment, including microorganisms, some of which are potentially pathogenic. This study focuses on the mechanisms of detection of bacteria by theDrosophilagustatory system. We demonstrate that the peptidoglycan (PGN) that forms the cell wall of bacteria triggers an immediate feeding aversive response when detected by the gustatory system of adult flies. Although we identify ppk23+ and Gr66a+ gustatory neurons as necessary to transduce fly response to PGN, we demonstrate that they play very different roles in the process. Time-controlled functional inactivation andin vivocalcium imaging demonstrate that while ppk23+ neurons are required in the adult flies to directly transduce PGN signal, Gr66a+ neurons must be functional in larvae to allow future adults to become PGN sensitive. Furthermore, the ability of adult flies to respond to bacterial PGN is lost when they hatch from larvae reared under axenic conditions. Recolonization of axenic larvae, but not adults, with a single bacterial species,Lactobacillus brevis,is sufficient to restore the ability of adults to respond to PGN. Our data demonstrate that the genetic and environmental characteristics of the larvae are essential to make the future adults competent to respond to certain sensory stimuli such as PGN.
In Need of Age-Appropriate Cardiac Models: Impact of Cell Age on Extracellular Matrix Therapy Outcomes
Authors: Ozcebe S. Gulberk , Zorlutuna Pinar 
Published: March 2023

ABSTRACTAging is the main risk factor for cardiovascular disease (CVD). As the world’s population ages rapidly and CVD rates rise, there is a growing need for physiologically relevant models of aging hearts to better understand cardiac aging. Translational research relies heavily on young animal models, however, these models correspond to early ages in human life, therefore cannot fully capture the pathophysiology of age-related CVD. Here, we chronologically aged human induced pluripotent stem cell-derived cardiomyocytes (iCMs) and compared in vitro iCM aging to native human cardiac tissue aging. We showed that 14-month-old advanced aged iCMs had an aging profile similar to the aged human heart and recapitulated age-related disease hallmarks. We then used aged iCMs to study the effect of cell age on the young extracellular matrix (ECM) therapy, an emerging approach for myocardial infarction (MI) treatment and prevention. Young ECM decreased oxidative stress, improved survival, and post-MI beating in aged iCMs. In the absence of stress, young ECM improved beating and reversed aging-associated expressions in 3-month-old iCMs while causing the opposite effect on 14-month-old iCMs. The same young ECM treatment surprisingly increased SASP and impaired beating in advanced aged iCMs. Overall, we showed that young ECM therapy had a positive effect on post-MI recovery, however, cell age was determinant in the treatment outcomes without any stress conditions. Therefore, “one-size-fits-all” approaches to ECM treatments fail, and cardiac tissue engineered models with age-matched human iCMs are valuable in translational basic research for determining the appropriate treatment, particularly for the elderly.
Mycobacteriumtrehalose polyphleates are required for infection by therapeutically useful mycobacteriophages BPs and Muddy
Authors: Wetzel Katherine S. , Illouz Morgane , Abad Lawrence , Aull Haley G. , Russell Daniel A. , Garlena Rebecca A. , Cristinziano Madison , Malmsheimer Silke , Chalut Christian , Hatfull Graham F. , Kremer Laurent 
Published: March 2023

AbstractMycobacteriophages are good model systems for understanding their bacterial hosts and show promise as therapeutic agents for nontuberculous mycobacterium infections. However, little is known about phage recognition ofMycobacteriumcell surfaces, or mechanisms of phage resistance. We show here that surface-exposed trehalose polyphleates (TPPs) are required for infection ofMycobacterium abscessusandMycobacterium smegmatisby clinically useful phages BPs and Muddy, and that TPP loss leads to defects in adsorption, infection, and confers resistance. Transposon mutagenesis indicates that TPP loss is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss, and someM. abscessusclinical isolates are phage-insensitive due to TPP absence. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, andM. abscessusmutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.
Persistence of SARS-CoV-2 and its surrogate, bacteriophage Phi6, on surfaces and in water
Authors: Pitol Ana K. , Venkatesan Samiksha , Hoptroff Michael , Hughes Grant L. 
Published: March 2023

ABSTRACTThe COVID-19 pandemic has motivated research on the persistence of infectious SARS-CoV-2 in environmental reservoirs such as surfaces and water. Viral persistence data has been collected for SARS-CoV-2 and its surrogates, including bacteriophage Phi6. Despite its wide use, no side-by-side comparisons between Phi6 and SARS-CoV-2 exist. Here, we quantified the persistence of SARS-CoV-2 and Phi6 on surfaces (plastic and metal) and in water and evaluated the influence that the deposition solution has on viral persistence by using four commonly used deposition solutions: two culture media (DMEM and Tryptone Soya Broth (TSB)), Phosphate Buffered Saline (PBS), and human saliva. Phi6 remained infectious in water significantly longer than SARS-CoV-2, having a half-life of 27 hours as compared with 15 hours for SARS-CoV-2. The persistence of viruses on surfaces was significantly influenced by the virus used and the deposition solution, but not by the surface material. Phi6 remained infectious significantly longer than SARS-CoV-2 when the inoculation solution was culture media (DMEM, TSB) and saliva. Using culture media and saliva led to half-lives between 9 hours and 2 weeks for Phi6, as compared to 0.5 to 2 hours for SARS-CoV-2. Using PBS as a deposition solution led to half-lives shorter than 4 hours for both viruses on all surfaces. Our results showed that, although it has been frequently used as a surrogate for coronaviruses, bacteriophage Phi6 is not an adequate surrogate for studies quantifying SARS-CoV-2 persistence, as it over-estimates infectiousness. Additionally, our findings reveal the need of using adequate deposition solutions when evaluating viral persistence on surfaces.
Brain fingerprinting using fMRI spectral signatures on high-resolution cortical graphs
Authors: Ferritto Carlo , Preti Maria Giulia , Moia Stefano , Van De Ville Dimitri , Behjat Hamid 
Published: March 2023

ABSTRACTResting-state fMRI has proven to entail subject-specific signatures that can serve as a fingerprint to identify individuals. Conventional methods are based on building a connectivity matrix based on correlation between the average time course of pairs of brain regions. This approach, first, disregards the exquisite spatial detail manifested by fMRI due to working on average regional activities, second, cannot disentangle correlations associated to cognitive activity and underlying noise, and third, does not account for cortical morphology that spatially constraints function. Here we propose a method to address these shortcomings via leveraging principles from graph signal processing. We build high spatial resolution cortical graphs that encode each individual’s cortical morphology and treat region-specific, whole-hemisphere fMRI maps as signals that reside on the graphs. fMRI graph signals are then decomposed using systems of graph spectral kernels to extract structure-informed functional signatures, which are in turn used for fingerprinting. Results on 100 subjects showed the overall superior subject differentiation power of the proposed signatures over the conventional method. Moreover, placement of the signatures within canonical functional brain networks revealed the greater contribution of high-level cognitive networks in subject identification.
Endophyte genomes support greater metabolic gene cluster diversity compared with non-endophytes inTrichoderma
Authors: Scott Kelsey , Konkel Zachary , Gluck-Thaler Emile , David Guillermo E. Valero , Simmt Coralie Farinas , Grootmyers Django , Chaverri Priscila , Slot Jason 
Published: March 2023

ABSTRACTTrichodermais a cosmopolitan genus with diverse lifestyles and nutritional modes, including mycotrophy, saprophytism, and endophytism. Previous research has reported greater metabolic gene repertoires in endophytic fungal species compared to closely-related non-endophytes. However, the extent of this ecological trend and its underlying mechanisms are unclear. Some endophytic fungi may also be mycotrophs and have one or more mycoparasitism mechanisms. Mycotrophic endophytes are prominent in certain genera likeTrichoderma, therefore, the mechanisms that enable these fungi to colonize both living plants and fungi may be the result of expanded metabolic gene repertoires. Our objective was to determine what, if any, genomic features are overrepresented in endophytic fungi genomes in order to undercover the genomic underpinning of the fungal endophytic lifestyle. Here we compared metabolic gene cluster and mycoparasitism gene diversity across a dataset of thirty-eightTrichodermagenomes representing the full breadth of environmentalTrichoderma’s diverse lifestyles and nutritional modes. We generated four newTrichoderma endophyticumgenomes to improve the sampling of endophytic isolates from this genus. As predicted, endophyticTrichodermagenomes contained, on average, more total biosynthetic and degradative gene clusters than non-endophytic isolates, suggesting that the ability to create/modify a diversity of metabolites potential is beneficial or necessary to the endophytic fungi. Still, once the phylogenetic signal was taken in consideration, no particular class of metabolic gene cluster was independently associated with theTrichodermaendophytic lifestyle. Several mycoparasitism genes, but no chitinase genes, were associated with endophyticTrichodermagenomes. Most genomic differences betweenTrichodermalifestyles and nutritional modes are difficult to disentangle from phylogenetic divergences among species, suggesting that Trichoderma genomes maybe particularly well-equipped for lifestyle plasticity. We also consider the role of endophytism in diversifying secondary metabolism after identifying the horizontal transfer of the ergot alkaloid gene cluster toTrichoderma.
Epithelial galectin-3 induces mitochondrial complex inhibition and cell cycle arrest of CD8+T Cells in severe/critical ill COVID-19
Authors: Wang Yudie , Yang Cheng , Wang Zhongyi , Wang Yi , Yan Qing , Feng Ying , Liu Yanping , Zhang Xiaolan , Zhao Jingwei , Huang Juan , Zhou Jingjiao 
Published: March 2023

AbstractSeveral studies have identified the presence of functionally depleted CD8+T cells in COVID-19 patients, and particularly abnormally reduced CD8+T cells in severe/critical patients, which may be a major cause of disease progression and poor prognosis. In this study, a proliferating-depleted CD8+T cell phenotype was observed in severe/critical COVID-19 patients through scRNA-seq and scTCR-seq analysis. These CD8+T cells were subsequently found to be characterized by cell cycle arrest and downregulation of mitochondrial biogenesis and respiratory chain complex genes. Cellchat analysis revealed that the Galectin signaling pathways between infected lung epithelial cells and CD8+T cells play the key role in inducing CD8+T cell reduction and dysfunction in severe/critical COVID-19. We used SARS-COV-2 ORF3a to transfect A549 epithelial cells, and co-cultured with CD8+T cells. The ex vivo experiments confirmed that galectin-3 inhibited the transcription of mitochondrial respiratory chain complex III/IV genes in CD8+T cells by suppressing the nuclear translocation of nuclear respiratory factor 1 (NRF1). In addition, the regulatory effect of galectin-3 was correlated with the activation of ERK signaling and/or the inhibition of Akt signaling. Galectin-3 inhibitor, TD-139, promoted nuclear translocation of NRF1, and enhanced mitochondrial respiratory chain complex III/IV gene expression and mitochondrial biogenesis, then restore the expansion ability of CD8+T cells. Our study improved the understanding the immunopathogenesis and provided new target for the prevention and treatment of severe/critical COVID-19.
A bi-kinase module sensitizes and potentiates plant immune signaling
Authors: Köster Philipp , He Gefeng , Dong Qiuyan , Hake Katarina , Schmitz-Thom Ina , Heinkow Paulina , Eirich Jürgen , Wallrad Lukas , Hashimoto Kenji , Schültke Stefanie , Finkemeier Iris , Romeis Tina , Kudla Jörg 
Published: March 2023

AbstractSystemic signaling is an essential hallmark of multicellular life. Pathogen encounter occurs locally but triggers organ-scale and organismic immune responses. In plants, elicitor perception provokes systemically expanding Ca2+and H2O2signals conferring immunity. Here, we identify a Ca2+sensing bi-kinase module as becoming super-activated through mutual trans-phosphorylation and imposing synergistically enhanced NADPH oxidase activation. A combined two-layer bi-kinase/substrate phospho-code allows for sensitized signaling initiation already by near-resting elevations of Ca2+concentration at the infection site. Subsequently, it facilitates further signal wave proliferation with minimal amplitude requirement, triggering protective defense responses throughout the plant. Our study reveals how plants build and perpetuate trans-cellular immune signal proliferation while avoiding disturbance of ongoing cellular signaling along the path of response dissemination.One sentence summaryMutual trans-activation of a Ca2+sensing bi-kinase module potentiates NADPH oxidase activation to facilitate systemic immunity.
VIP interneurons regulate cortical size tuning and visual perception
Authors: Ferguson Katie A. , Salameh Jenna , Alba Christopher , Selwyn Hannah , Barnes Clayton , Lohani Sweyta , Cardin Jessica A. 
Published: March 2023

AbstractLocal cortical circuit function is regulated by diverse populations of GABAergic interneurons with distinct properties and extensive interconnectivity. Inhibitory-to-inhibitory interactions between interneuron populations may play key roles in shaping circuit operation according to behavioral context. A specialized population of GABAergic interneurons that co-express vasoactive intestinal peptide (VIP-INs) are activated during arousal and locomotion and innervate other local interneurons and pyramidal neurons. Although modulation of VIP-IN activity by behavioral state has been extensively studied, their role in regulating information processing and selectivity is less well understood. Using a combination of cellular imaging, short and long-term manipulation, and perceptual behavior, we examined the impact of VIP-INs on their synaptic target populations in the primary visual cortex of awake behaving mice. We find that loss of VIP-IN activity alters the behavioral state-dependent modulation of somatostatin-expressing interneurons (SST-INs) but not pyramidal neurons (PNs). In contrast, reduced VIP-IN activity disrupts visual feature selectivity for stimulus size in both populations. Inhibitory-to inhibitory interactions thus directly shape the selectivity of GABAergic interneurons for sensory stimuli. Moreover, the impact of VIP-IN activity on perceptual behavior varies with visual context and is more acute for small than large visual cues. VIP-INs thus contribute to both state-dependent modulation of cortical circuit activity and sensory context-dependent perceptual performance.
Sulfide oxidation promotes hypoxic angiogenesis and neovascularization
Authors: Kumar Roshan , Vitvitsky Victor , Seth Proud , Hiraki Harrison L. , Bell Hannah , Andren Anthony , Singhal Rashi , Baker Brendon M. , Lyssiotis Costas A. , Shah Yatrik M. , Banerjee Ruma 
Published: March 2023

AbstractAngiogenic programming in the vascular endothelium is a tightly regulated process to maintain tissue homeostasis and is activated in tissue injury and the tumor microenvironment. The metabolic basis of how gas signaling molecules regulate angiogenesis is elusive. Herein, we report that hypoxic upregulation of NO synthesis in endothelial cells reprograms the transsulfuration pathway and increases H2S biogenesis. Furthermore, H2S oxidation by mitochondrial sulfide quinone oxidoreductase (SQOR) rather than downstream persulfides, synergizes with hypoxia to induce a reductive shift, limiting endothelial cell proliferation that is attenuated by dissipation of the mitochondrial NADH pool. Tumor xenografts in whole-body WBCreSQORfl/flknockout mice exhibit lower mass and reduced angiogenesis compared to SQORfl/flcontrols. WBCreSQORfl/flmice also exhibit reduced muscle angiogenesis following femoral artery ligation, compared to controls. Collectively, our data reveal the molecular intersections between H2S, O2and NO metabolism and identify SQOR inhibition as a metabolic vulnerability for endothelial cell proliferation and neovascularization.HighlightsHypoxic induction of •NO in endothelial cells inhibits CBS and switches CTH reaction specificityHypoxic interruption of the canonical transsulfuration pathway promotes H2S synthesisSynergizing with hypoxia, SQOR deficiency induces a reductive shift in the ETC and restricts proliferationSQOR KO mice exhibit lower neovascularization in tumor xenograft and hind limb ischemia models
Early-adult methionine restriction reduces methionine sulfoxide and extends lifespan inDrosophila
Authors: Kosakamoto Hina , Obata Fumiaki , Kuraishi Junpei , Aikawa Hide , Okada Rina , Johnstone Joshua N. , Onuma Taro , Piper Matthew D. W. , Miura Masayuki 
Published: March 2023

AbstractMethionine restriction (MetR) extends lifespan in various organisms, but its mechanistic understanding remains incomplete. Whether MetR during a specific period of adulthood increases lifespan is not shown. InDrosophila, MetR is reported to extend lifespan only when amino acid levels are low. Here, by using an exome-matched holidic medium, we show that decreasing Met levels to 10% extendsDrosophilalifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life robustly extends lifespan. MetR induces the expression ofMethionine sulfoxide reductase A(MsrA) in young flies, which reduces the oxidatively-damaged Met.MsrAinduction isfoxo-dependent and persists for two weeks after cessation of the MetR diet. Loss ofMsrAattenuates lifespan extension by early-adult MetR. Our study highlights the age-dependency of the organismal response to specific nutrient and suggests that nutrient restriction at a particular period of life is sufficient for healthspan extension.
A computationally informed comparison between the strategies of rodents and humans in visual object recognition
Authors: Schnell Anna Elisabeth , Leemans Maarten , Vinken Kasper , de Beeck Hans Op 
Published: March 2023

AbstractMany species are able to recognize objects, but it has been proven difficult to pinpoint and compare how different species solve this task. Recent research suggested to combine computational and animal modelling in order to obtain a more systematic understanding of task complexity and compare strategies between species. In the present study, we created a large multidimensional stimulus set and designed a visual discrimination task partially based upon modelling with a convolutional deep neural network (CNN). Experiments included rats (N = 11; 1115 daily sessions in total for all rats together) and humans (N = 45). Each species was able to master the task and generalize to a variety of new images. Nevertheless, rats and humans showed very little convergence in terms of which object pairs were associated with high and low performance, suggesting the use of different strategies. There was an interaction between species and whether stimulus pairs favoured early or late processing in a CNN. A direct comparison with CNN representations and visual feature analyses revealed that rat performance was best captured by late convolutional layers and partially by visual features such as brightness and pixel-level similarity, while human performance related more to the higher-up fully connected layers. These findings highlight the additional value of using a computational approach for the design of object recognition tasks. Overall, this computationally informed investigation of object recognition behaviour reveals a strong discrepancy in strategies between rodent and human vision.
Contrasting Response of Microeukaryotic and Bacterial Communities to the Interplay of Seasonality and Stochastic Events in Shallow Soda Lakes
Authors: Márton Zsuzsanna , Csitári Bianka , Felföldi Tamás , Jordán Ferenc , Hidas András , Szabó Attila , Székely Anna J. 
Published: March 2023

AbstractSeasonal environmental variation is a leading driver of microbial planktonic community assembly and interactions. Yet, unexpected departures from general seasonal successional trends are often reported. To understand the role of local stochastic events in modifying seasonal succession, we sampled fortnightly throughout three seasons (spring, summer, and autumn) five nearby shallow soda lakes exposed to the same seasonal meteorological changes. We characterised their microeukaryotic and bacterial communities by 18S and 16S rRNA gene sequencing, respectively. Biological interactions were inferred by the analyses of synchronous and time-shifted interaction networks, and the keystone taxa were topologically identified. The pans showed similar succession patterns during the study period with spring being characterised by high relevance of trophic interactions and certain level of community stability followed by a more dynamic and variable summer-autumn period both in respect of community composition and microbial interactions. Adaptation to general seasonal changes happened through the abundant shared core microbiome of the pans. However, stochastic events such as desiccation and cyanobacterial blooms disrupted common network attributes and introduced shifts from the prevalent seasonal trajectory. These were more pronounced for microeukaryotes than for bacteria which was reflected in increased turnover and contribution of non-core microeukaryotes. Our results demonstrated that despite being extreme and highly variable habitats, shallow soda lakes exhibit certain similarities in the seasonality of their planktonic communities, yet random stochastic events such as droughts can instigate substantial deviations from prevalent trends for the microeukaryotic but not bacterial communities.