bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of metabolic niche occupancy dynamics in a Baltic Sea bacterial community
Authors: Massing Jana C. , Fahimipour Ashkaan , Bunse Carina , Pinhassi Jarone , Gross Thilo 
Published: August 2022

AbstractProgress in molecular methods has enabled the monitoring of bacterial populations in time. Nevertheless, understanding community dynamics and its links with ecosystem functioning remains challenging due to the tremendous diversity of microorganisms. Conceptual frameworks that make sense of time-series of taxonomically-rich bacterial communities, regarding their potential ecological function, are needed. A key concept for organizing ecological functions is the niche, the set of strategies that enable a population to persist and define its impacts on the surroundings. Here we present a framework based on manifold learning, to organize genomic information into potentially occupied bacterial metabolic niches over time. We apply the method to re-construct the dynamics of putatively occupied metabolic niches using a long-term bacterial time-series from the Baltic Sea, the Linnaeus Microbial Observatory (LMO). The results reveal a relatively low-dimensional space of occupied metabolic niches comprising groups of taxa with similar functional capabilities. Time patterns of occupied niches were strongly driven by seasonality. Some metabolic niches were dominated by one bacterial taxon whereas others were occupied by multiple taxa, and this depended on season. These results illustrate the power of manifold learning approaches to advance our understanding of the links between community composition and functioning in microbial systems.ImportanceThe increase in data availability of bacterial communities highlights the need for conceptual frameworks to advance our understanding of these complex and diverse communities alongside the production of such data. To understand the dynamics of these tremendously diverse communities, we need tools to identify overarching strategies and describe their role and function in the ecosystem in a comprehensive way. Here, we show that a manifold learning approach can coarse grain bacterial communities in terms of their metabolic strategies and that we can thereby quantitatively organize genomic information in terms of potentially occupied niches over time. This approach therefore advances our understanding of how fluctuations in bacterial abundances and species composition can relate to ecosystem functions and it can facilitate the analysis, monitoring and future predictions of the development of microbial communities.
Timing and Delivery route effects of Cecal Microbiome transplants on Salmonella Typhimurium infections in Chickens
Authors: Pottenger Sian , Watts Amyleigh , Wedley Amy , Jopson Sue , Darby Alistair C , Wigley Paul 
Published: August 2022

AbstractBackgroundExposure to microbes early in life has long-lasting effects on microbial community structure and function of the microbiome. However, in commercial poultry settings chicks are reared as a single-age cohort with no exposure to adult birds which can have profound effects on microbiota development and subsequent pathogen challenge. Microbiota manipulation is a proven and promising strategy to help reduce pathogen load and transmission within broiler flocks.ResultsManipulation of the microbiota between 4 and 72 hours of hatch markedly reduces faecal shedding and colonisation with the foodborne pathogen Salmonella enterica serovar Typhimurium (ST4/74). Administration route has minimal effect on the protection conferred with fewer birds in transplant groups shown to shed ST4/74 in the faeces compared to PBS-gavaged control birds. Analysis of the microbiome following transplantation demonstrated that the relative abundance of the anti-inflammatory bacterium Faecalibacterium prausnitzii was significantly higher in CMT groups compared to PBS controls. The presence of F. prausnitzii was also shown to increase in PBS-challenged birds compared to unchallenged birds potentially indicating a role of this bacterium in limiting Salmonella infections.ConclusionsThis study highlights the efficacy of using microbiome transplants as a means to reduce colonisation and shedding of Salmonella in chickens. Effective protection can be conferred during the first few days of a chick’s life regardless of time point and traditional hatchery delivery systems are sufficient to alter the microbiome and transfer donor material. Early microbiota intervention in chickens is a promising route of pathogen control in broiler flocks in the fight to control food-borne outbreaks in the human population.
Distribution of the gyromitrin mycotoxin in the lorchel family assessed by a pre-column-derivatization and ultra high-performance liquid chromatography method
Authors: Dirks Alden C. , Mohamed Osama G. , Schultz Pamela , Miller Andrew N. , Tripathi Ashootosh , James Timothy Y. 
Published: August 2022

ABSTRACTGyromitrin (acetaldehyde N-methyl-N-formylhydrazone) and its homologs are deadly mycotoxins produced most infamously by the lorchel (also known as false morel) Gyromitra esculenta, which is paradoxically consumed as a delicacy in some parts of the world. There is much speculation about the presence of gyromitrin in other species of the lorchel family (Discinaceae), but no studies have broadly assessed its distribution. Given the history of poisonings associated with the consumption of G. esculenta and G. ambigua, we hypothesized that gyromitrin evolved in the last common ancestor of these taxa and would be present in their descendants with adaptive loss of function in the nested truffle clade, Hydnotrya. To investigate this hypothesis, we developed a sensitive analytical derivatization method for the detection of gyromitrin using 2,4-dinotrobenzaldehyde as the derivatization reagent. In total, we analyzed 66 specimens for the presence of gyromitrin over 105 tests. Moreover, we sequenced the nuc rDNA ITS1-5.8S-ITS2 region (ITS barcode) and nuc 28S rDNA to assist in species identification and to infer a supporting phylogenetic tree. We detected gyromitrin in all tested specimens from the G. esculenta group as well as G. leucoxantha. This distribution is consistent with a model of rapid evolution coupled with horizontal transfer, which is typical for secondary metabolites. We clarified that gyromitrin production in Discinaceae is both discontinuous and more limited than previously thought. Further research is required to elucidate the gyromitrin biosynthesis gene cluster and its evolutionary history in lorchels. KEYWORDS: 2,4-dinitrobenzaldehyde, Gyromitra spp., Hydnotrya spp., Discinaceae, Pezizales, Schiff bases, UHPLC-DAD analysis
Validation of an engineered Zika virus-like particle vaccine candidate in a mosquito-mouse transmission model
Authors: Mancini Maria Vittoria , Tandavanitj Rapeepat , Ant Thomas H. , Murdochy Shivan M. , Gingell Daniel D. , Setthapramote Chayanee , Natsrita Piyatida , Kohl Alain , Sinkins Steven P. , Patel Arvind H. , De Lorenzo Giuditta 
Published: August 2022

AbstractThe primary route of Zika virus (ZIKV) transmission is through the bite of an infected Aedes mosquito, when it probes the skin of a vertebrate host during a blood meal. Viral particles are injected into the bite site together with mosquito saliva and a complex mixture of other components. Some of them are shown to play a key role in the augmentation of the arbovirus infection in the host, with increased viremia and/or morbidity. This vector-derived contribution to the infection is not usually considered when vaccine candidates are tested in preclinical animal models. In this study, we performed a preclinical validation of a promising ZIKV vaccine candidate in a mosquito-mouse transmission model using both Asian and African ZIKV lineages. Mice were immunized with engineered ZIKV virus-like particles and subsequently infected through the bite of ZIKV-infected Ae. aegypti mosquitoes. Despite a mild increase in viremia in mosquito-infected mice compared to those infected through traditional needle injection, the vaccine protected the animals from developing the disease and strongly reduced viremia. In addition, during peak viremia, naïve mosquitoes were allowed to feed on infected vaccinated and non-vaccinated mice. Our analysis of viral titers in mosquitos showed that the vaccine was able to inhibit virus transmission from the host to the vector.Author summaryZika is a mosquito-borne viral disease, causing acute debilitating symptoms and complications in infected individuals and irreversible neuronal abnormalities in newborn children. The primary vectors of ZIKV are generally considered to be mosquitoes of the genus Aedes, in particular Aedes aegypti. Despite representing a significant public health burden with a widespread transmission in many regions of the world, Zika remains a neglected disease with no effective antiviral therapies or approved vaccines to control and prevent infections. The efficacy of several promising candidate vaccines is however under investigation, mainly through artificial infections (i.e. needle-mediated injections of the virus) in animal models, while it is known that components of the mosquito bite lead to an enhancement of viral infection and spread. In this study, we have also included mosquitoes as viral vectors, demonstrating that the ability of a promising candidate vaccine to protect animals against ZIKV infections after the bite of an infected mosquito, and to also prevent its further transmission. These findings represent an additional crucial step for the development of an effective prevention tool for clinical use.Graphical abstract
TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
Authors: Shetty Sunil , Hofstetter Jon , Battaglioni Stefania , Ritz Danilo , Hall Michael N. 
Published: August 2022

AbstractTarget of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells preserve a small pool of dormant ribosomes under nutrient-limited conditions. The regulation of dormant ribosomes is poorly characterized. Here, we show that upon inhibition of TORC1 by rapamycin or nitrogen starvation, Stm1 (suppressor of target of Myb protein 1) forms non-translating, dormant 80S ribosomes. Furthermore, Stm1-bound 80S ribosomes are protected from proteasomal degradation. Upon re-feeding, TORC1 directly phosphorylates and inhibits Stm1, thereby reactivating translation. Finally, SERBP1 (SERPINE1 mRNA binding protein), a mammalian ortholog of Stm1, forms dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. Thus, TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner via a ribosome preservation factor.
Sex differences in early and term placenta are conserved in adult tissues
Authors: Olney Kimberly C. , Plaisier Seema B. , Phung Tanya N. , Silasi Michelle , Perley Lauren , O’Bryan Jane , Ramirez Lucia , Kliman Harvey J. , Wilson Melissa A. 
Published: August 2022

AbstractBackgroundPregnancy complications vary based on the fetus’s genetic sex, which may, in part, be modulated by the placenta. Further, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different time points throughout pregnancy and comparisons to adult tissues remains poorly characterized.MethodsHere, we collect and characterize sex differences in gene expression in term placentas ( ≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx.ResultsWe identify 268 and 53 sex differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex differentially expressed genes observed in the term placentas, 31 are also sex differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males.ConclusionsWe find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.HighlightsSex differences in gene expression in late first trimester placentas are positively correlated with sex differences in gene expression in full term placentas; sex differences develop early and are maintained.Sex differences in gene expression on the sex chromosomes in the placenta are correlated to sex differences in adult tissues.Sex-linked gametolog genes require additional methodological approaches for accurate quantification.
Comprehensive chromatin proteomics resolves functional phases of pluripotency
Authors: Ugur Enes , de la Porte Alexandra , Bultmann Sebastian , Drukker Micha , Mann Matthias , Wierer Michael , Leonhardt Heinrich 
Published: August 2022

AbstractThe establishment of cellular identity is driven by transcriptional and epigenetic regulation exerted by the components of the chromatin proteome - the chromatome. However, chromatome composition and its dynamics in functional phases of pluripotency have not been comprehensively analyzed thus limiting our understanding of these processes. To address this problem, we developed an accurate mass spectrometry (MS)-based proteomic method called Chromatin Aggregation Capture (ChAC) followed by Data-Independent Acquisition (DIA) to analyze chromatome reorganizations during the transition from ground to formative and primed pluripotency states. This allowed us to generate a comprehensive atlas of proteomes, chromatomes, and chromatin affinities for the three pluripotency phases, revealing the specific binding and rearrangement of regulatory complexes. The technical advances, the comprehensive chromatome atlas, and the extensive analysis reported here provide a foundation for an in-depth understanding of mechanisms that govern the phased progression of pluripotency and changes of cellular identities in development and disease.
Auditory corticofugal neurons transmit auditory and non-auditory information during behavior
Authors: Ford Alexander N. , Czarny Jordyn E. , Rogalla Meike M. , Quass Gunnar L. , Apostolides Pierre F. 
Published: August 2022

AbstractLayer 5 pyramidal neurons of sensory cortices project “corticofugal” axons to myriad sub-cortical targets, thereby broadcasting high-level signals important for perception and learning. Recent studies suggestdendritic Ca2+spikesas key biophysical mechanisms supporting corticofugal neuron function: These long-lasting events drive burst firing, thereby initiating uniquely powerful signals to modulate sub-cortical representations and trigger learning-related plasticity. However, the behavioral relevance of corticofugal dendritic spikes is poorly understood. We shed light on this issue using 2-photon Ca2+imaging of auditory corticofugal dendrites as mice of either sex engage in a GO/NO-GO sound-discrimination task.Unexpectedly, only a minority of dendritic spikes were triggered by behaviorally relevant sounds under our conditions. Task related dendritic activity instead mostly followed sound cue termination and co-occurred with mice’s instrumental licking during the answer period of behavioral trials, irrespective of reward consumption. Temporally selective, optogenetic silencing of corticofugal neurons during the trial answer period impaired auditory discrimination learning. Thus, auditory corticofugal systems’ contribution to learning and plasticity may be partially non-sensory in nature.Significance StatementThe auditory cortex sends a massive “feedback” projection to the inferior colliculus (IC) which controls IC neuron plasticity and some types of perceptual learning. Precisely what signals are fed back during behavior is unclear. Using multiphoton imaging of auditory cortico-collicular neurons as mice engage in a sound discrimination task, we find that activity coincides more with mice’s instrumental actions rather than sound cues. Dendritic Ca2+spikes and burst firing contributed to this non-auditory activity, which is notable given that dendritic spikes instruct synaptic plasticity in many other circuits. Accordingly, optogenetic silencing of corticofugal neurons during mice’s instrumental actions impaired discriminative learning. Auditory corticofugal neurons may thus transmit significant non-auditory information that contributes to learning-related plasticity.
Dnmt3bascoordinates transcriptional induction and alternative exon inclusion to promote catalytically active Dnmt3b expression
Authors: Dar Mohd Saleem , Mensah Isaiah K , He Ming , McGovern Sarah , Hall Mark C , Whitlock Hannah Christian , Bippus Nina Elise , Ceminsky Madison , Emerson Martin L , Tan Hern J , Gowher Humaira 
Published: August 2022

SummaryDuring mammalian embryogenesis, DNMT3B activity is critical for the genome-wide establishment of DNA methylation. Using naïve ESC differentiation as a model, we elucidated the mechanism by which lncRNA,Dnmt3bas,controls the inducible expression and alternative splicing ofDnmt3b. Our data showed thatDnmt3basknockdown increased transcriptional induction and decreased H3K27me3 at Dnmt3b cis-regulatory elements post-differentiation. Notably, transcriptional induction ofDnmt3bwas accompanied by exon inclusion, switching the major isoform from catalytically inactiveDnmt3b6to the activeDnmt3b1. WhileDnmt3basoverexpression attenuatedDnmt3binduction, it increased theDnmt3b1:Dnmt3b6ratio. This observation was explained by a specific interaction ofDnmt3baswith hnRNPL, which promotes exon inclusion. These data suggest thatDnmt3bascoordinates alternative splicing and transcriptional induction of Dnmt3b by facilitating the interaction of hnRNPL and RNA Pol II at the Dnmt3b promoter. This two-pronged mechanism would tightly control DNMT3B activity, ensuring the fidelity and specificity ofde novoDNA methylation during development.
Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic marks
Authors: Cassiano Larissa M. G. , Silva Vanessa C. , Oliveira Marina S. , Prado Bárbara V. O. , Cardoso Cristianne G. , Salim Anna C. M. , Franco Gloria R. , D’Almeida Vânia , Francisco Saionara C. , Coimbra Roney S. 
Published: August 2022

AbstractCOVID-19 induces chromatin remodeling in host immune cells, and it had previously been shown that vitamin B12 downregulates some inflammatory genes via methyl-dependent epigenetic mechanisms. In this work, whole blood cultures from moderate or severe COVID-19 patients were used to assess the potential of B12 as adjuvant drug. The vitamin normalized the expression of a panel of inflammatory genes still dysregulated in the leukocytes despite glucocorticoid therapy during hospitalization. B12 also increased the flux of the sulfur amino acid pathway, raising the bioavailability of methyl. Accordingly, B12-induced downregulation of CCL3 strongly and negatively correlated with the hypermethylation of CpGs in its regulatory regions. Transcriptome analysis revealed that B12 attenuates the effects of COVID-19 on most inflammation-related pathways affected by the disease. As far as we are aware, this is the first study to demonstrate that pharmacological modulation of epigenetic marks in leukocytes favorably regulates central components of COVID-19 physiopathology.TeaserB12 has great potential as an adjuvant drug for alleviating inflammation in COVID-19.
Acetylsalicylic acid and Salicylic acid inhibit SARS-CoV-2 replication in precision-cut lung slices
Authors: Geiger Nina , König Eva-Maria , Oberwinkler Heike , Roll Valeria , Diesendorf Viktoria , Fähr Sofie , Obernolte Helena , Seewald Katherina , Wronski Sabine , Steinke Maria , Bodem Jochen 
Published: August 2022

AbstractAspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses and at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analyzed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and in a patient-near replication system using human precision-cut lung slices by two orders of magnitude. The compounds did not interfere with viral entry but led to lower viral RNA expression after 24 h.
Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism
Authors: Bussi Claudio , Heunis Tiaan , Pellegrino Enrica , Bernard Elliott M. , Bah Nourdine , dos Santos Mariana Silva , Santucci Pierre , Aylan Beren , Rodgers Angela , Fearns Antony , Mitschke Julia , Moore Christopher , MacRae James I. , Greco Maria , Reinheckel Thomas , Trost Matthias , Gutierrez Maximiliano G. 
Published: August 2022

SummaryTransient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required lysosomal leakage of Cathepsin B and Cathepsin L and was independent of proteasome degradation and mitophagy. In a mouse model of endomembrane damage, metabolic analysis confirmed that in vivo, live lung macrophages that internalised crystals displayed impaired mitochondrial function and increased glycolytic and lipid metabolism. Single-cell RNA-sequencing analysis of bronchoalveolar lavage revealed that lysosomal damage skewed metabolic and immune responses primarily in CD36+/LIPA+ and Krt79+/Car4+ subsets of alveolar macrophages. Importantly, modulation of macrophage metabolism with 2-Deoxy- d- glucose and oxamate impacted the host response to Mycobacterium tuberculosis (Mtb) infection in an endomembrane damage dependent manner. This work uncovers a new inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.