bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic markers and tree properties predicting wood biorefining potential in aspen (Populus tremula) bioenergy feedstock
Authors: Escamez Sacha , Robinson Kathryn M. , Luomaranta Mikko , Gandla Madhavi Latha , Mähler Niklas , Yassin Zakiya , Grahn Thomas , Scheepers Gerhard , Stener Lars-Göran , Jansson Stefan , Jönsson Leif J. , Street Nathaniel R. , Tuominen Hannele 
Published: July 2021

AbstractBackgroundWood represents the majority of the biomass on land and constitutes a renewable source of biofuels and other bioproducts. However, wood is recalcitrant to bioconversion, raising a need for feedstock improvement in production of, for instance, biofuels. We investigated the properties of wood that affect bioconversion, as well as the underlying genetics, to help identify superior tree feedstocks for biorefining.ResultsWe recorded 65 wood-related and growth traits in a population of 113 natural aspen genotypes from Sweden. These traits included three growth and field performance traits, 20 traits for wood chemical composition, 17 traits for wood anatomy and structure, and 25 wood saccharification traits as indicators of bioconversion potential. Glucose release after saccharification with acidic pretreatment correlated positively with tree stem height and diameter and the carbohydrate content of the wood, and negatively with the content of lignin and the hemicellulose sugar units. Most of these traits displayed extensive natural variation within the aspen population and high broad-sense heritability, supporting their potential in genetic improvement of feedstocks towards improved bioconversion. Finally, a genome wide association study (GWAS) revealed 13 genetic loci for saccharification yield (on a whole tree biomass basis), with six of them intersecting with associations for either height or stem diameter of the trees.ConclusionsThe simple growth traits of stem height and diameter were identified as good predictors of wood saccharification yield in aspen trees. GWAS elucidated the underlying genetics, revealing putative genetic markers for bioconversion of bioenergy tree feedstocks.
MSNovelist: De novo structure generation from mass spectra
Authors: Stravs Michael A. , Dührkop Kai , Böcker Sebastian , Zamboni Nicola 
Published: July 2021

AbstractStructural elucidation of small molecules de novo from mass spectra is a longstanding, yet unsolved problem. Current methods rely on finding some similarity with spectra of known compounds deposited in spectral libraries, but do not solve the problem of predicting structures for novel or poorly represented compound classes. We present MSNovelist that combines fingerprint prediction with an encoder-decoder neural network to generate structures de novo from fragment spectra. In evaluation, MSNovelist correctly reproduced 61% of database annotations for a GNPS reference dataset. In a bryophyte MS2 dataset, our de novo structure prediction substantially outscored the best database candidate for seven features, and a potential novel natural product with a flavonoid core was identified. MSNovelist allows predicting structures solely from MS2 data, and is therefore ideally suited to complement library-based annotation in the case of poorly represented analyte classes and novel compounds.
Isoform resolved measurements of absolute translational efficiency define interplay of HIF and mTOR dysregulation in kidney cancer
Authors: Sugimoto Yoichiro , Ratcliffe Peter J. 
Published: July 2021

AbstractHypoxia inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways orchestrate responses to oxygen and nutrient availability. These pathways are frequently dysregulated in cancer, but their interplay is poorly understood, in part because of difficulties in simultaneous measurement of global and mRNA-specific translation. Here we describe a workflow for measurement of absolute translational efficiency of mRNAs resolved by their transcription start sites (TSSs). Its application to kidney cancer cells revealed a remarkable extent of translational reprogramming by mTOR, strongly affecting many metabolic enzymes and pathways. By contrast, global effects of HIF on translation were limited, and we did not observe reported translational activation by HIF2A. In contrast, HIF-dependent alterations in TSS usage were associated with robust changes in translational efficiency in a subset of genes. Analyses of the interplay of HIF and mTOR revealed that specific classes of HIF1A and HIF2A transcriptional target gene manifest markedly different sensitivity to mTOR, in a manner that supports combined use of HIF2A and mTOR inhibitors in treatment of kidney cancer.
Outer membrane vesicles derived from Klebsiella pneumoniae are a driving force for horizontal gene transfer
Authors: Dell’Annunziata Federica , Dell’Aversana Carmela , Doti Nunzianna , Donadio Giuliana , Dal Piaz Fabrizio , Izzo Viviana , De Filippis Anna , Galdiero Marilena , Altucci Lucia , Boccia Giovanni , Galdiero Massimiliano , Folliero Veronica , Franci Gianluigi 
Published: July 2021

AbstractGram-negative bacteria release outer membrane vesicles (OMVs) into the extracellular environment. Recent studies recognized these vesicles as vectors to horizontal gene transfer, however the parameters that mediate OMVs transfer within bacterial communities remain unclear. The present study highlights for the first time the transfer of plasmids containing resistance genes via OMVs derived from Klebsiella pneumoniae (K. pneumoniae). This mechanism confers DNA protection and it is plasmid copy number dependent with a ratio of 3.6 time among high copy-number plasmid (pGR) versus low copy number plasmid (PRM) and the transformation efficiency was 3.6 times greater. Therefore, the DNA amount in the vesicular lumen and the efficacy of horizontal gene transfer was strictly dependent on the identity of the plasmid. Moreover, the role of K. pneumoniae-OMVs in interspecies transfer was described. The transfer ability was not related to the phylogenetic characteristics between the donor and the recipient species. K. pneumoniae-OMVs transferred plasmid to Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa and Burkholderia cepacia. These findings address the pivotal role of K. pneumoniae-OMVs as vectors for antimicrobial resistance genes spread, contributing to the development of antibiotic resistance in the microbial communities.Author summaryK. pneumoniae is an important opportunistic pathogen that affects several host districts, in particular respiratory and urinary tracts. Hospital-acquired K. pneumoniae infections lead to a 50% mortality rate correlated with rapid acquisition of antibiotic resistance. Currently, the increasing rate of antibiotic resistance among K. pneumoniae isolates is a major concern worldwide. The spread of multidrug-resistant K. pneumoniae strains renders current therapeutic options ineffective. Like all Gram-negative bacteria, K. pneumoniae secretes OMVs. OMVs are spherical structures, with a diameter between 50-250 nm, originating from the outer membrane. OMVs biogenesis allows bacteria to interact with the external environment, increasing bacterial survival under stressful conditions and regulating microbial interactions within bacterial communities. Few evidence recognized OMVs as vectors for horizontal gene transfer, contributing to the spread of resistance. In this scenario, the present study examines the potential role of K. pneumoniae-OMVs in inter- and intra-species diffusion of ß-lactam resistance.
Inhibition of Ras1-MAPK pathways for hypha formation by novel drug candidates in Candida albicans
Authors: Park Young Kwang , Shin Jisoo , Lee Hee-Yoon , Kim Hag Dong , Kim Joon 
Published: July 2021

AbstractThe opportunistic human fungal pathogen Candida albicans has morphogenesis as a virulence factor. The morphogenesis of C. albicans is closely related to pathogenicity (1). Ras1 in C. albicans is an important switch in the MAPK pathway for morphogenesis (2, 3). The MAPK pathway is important for the virulence, such as cell growth, morphogenesis, and biofilm formation (4, 5). Ume6 is a well-known transcriptional factor for hyphal-specific genes (6). Despite numerous studies, as a recent issue, it is necessary to develop a new drug that uses a different pathway mechanism to inhibit resistant C. albicans strains caused by chronic prescription of azole or echinocandin drugs, which are mainly used. Here, we show that the small carbazole derivatives attenuated the pathogenicity of C. albicans through inhibition of the Ras1/MAPK pathway. We found that the small molecules inhibit morphogenesis through repressing protein and RNA levels in Ras/MAPK related genes including UME6 and NRG1. Furthermore, we found the antifungal effect of the small molecules in vivo using a candidiasis murine model. We anticipate our findings are that the small molecules are the promising compounds for the development of new antifungal agents for the treatment of systemic candidiasis and possibly for other fungal diseases.Author summaryThe infection by the opportunistic human fungal pathogen Candida albicans occurs mainly in immunocompetent and immunocompromised humans, such as AIDS patients, immunosuppressant-treated organ transplant patients, and recent COVID-19 patients. Morphogenesis which the ability to switch between yeast and hyphal growth forms is one of the representative virulence factors of C. albicans. Here, we describe novel small molecules that show antifungal effects such as the inhibition of the morphogenesis and the biofilm formation, and maintenance of biofilm. Moreover, we found that these small molecules had antifungal activity in mouse experiments, and confirmed that they were also effective in drug-resistant C. albicans strains. Studies of some small molecules with structures similar to ours have already been reported to exhibit growth inhibitory activity against bacteria and Candida species. However, the mechanism of action of these molecules has not been elucidated. In this study, we demonstrated, for the first time, the mechanism by which these two small molecules inhibit C. albicans pathogenicity through inhibition of specific pathways. Our study, through the research of the mechanism of action of novel small molecules, provides new insights into the development of drug candidates not only for wild-type C. albicans, but also for strains resistant to existing drugs.
Individual history of winning and hierarchy landscape influence stress susceptibility in mice
Authors: LeClair Katherine B , Chan Kenny L , Kaster Manuella P , Parise Lyonna F , Burnett C. Joseph , Russo Scott J 
Published: July 2021

ABSTRACTSocial hierarchy formation is strongly evolutionarily conserved. Across species, rank within social hierarchy has large effects on health and behavior. To investigate the relationship between social rank and stress susceptibility, we exposed ranked male and female mice to social and non-social stressors and manipulated social hierarchy position. We found that rank predicts same sex social stress outcomes: dominance in males and females confers resilience while subordination confers susceptibility. Pre-existing rank does not predict non-social stress outcomes in females and weakly does so in males, but rank emerging under stress conditions reveals social interaction deficits in male and female subordinates. Both history of winning and rank of cage mates affect stress susceptibility in males: rising to the top rank through high mobility confers resilience and mice that lose dominance lose stress resilience, though gaining dominance over a subordinate animal does not confer resilience. Overall, we have demonstrated a relationship between social status and stress susceptibility, particularly when taking into account individual history of winning and the overall hierarchy landscape in male and female mice.
Parafoveal words can modulate sentence meaning: Electrophysiological evidence from an RSVP-with-flanker task
Authors: Li Nan , Dimigen Olaf , Sommer Werner , Wang Suiping 
Published: July 2021

ABSTRACTDuring natural reading, readers also take up some visual information from not-yet-fixated words to the right of the current fixation and it is well-established that this parafoveal preview facilitates the subsequent foveal processing of the word. However, the extraction and integration of word meaning from the parafoveal word and its possible influence on the semantic sentence context are controversial. In the current study, we recorded event-related potentials (ERPs) in the RSVP-with-flankers paradigm to test whether and how updates of sentential meaning that are based only on parafoveal information influence the subsequent foveal processing. Using Chinese sentences, the sentence congruency of parafoveal and foveal target words were orthogonally manipulated. In contrast to previous research, we also controlled for potentially confounding effects of parafoveal-to-foveal repetition priming (identity preview effects) on the N400. Crucially, we found that the classic effect of foveal congruency on the N400 component only appeared when the word in preview had been congruent with sentence meaning; in contrast, there was no N400 when the preview word had been incongruent. These results indicate that sentence meaning rapidly adapts to parafoveal preview, which already changes the context for the then fixated word. We also show that a correct parafoveal preview generally attenuates the N400 once a word is fixated, regardless of congruency. Taken together, our findings underline the highly generative and adaptive framework of language comprehension.
A native mass spectrometry-based assay for rapid assessment of the empty/full capsid ratio in AAV gene therapy products
Authors: Strasser Lisa , Morgan Tomos E. , Guapo Felipe , Füssl Florian , Forsey Daniel , Anderson Ian , Bones Jonathan 
Published: July 2021

ABSTRACTAdeno-associated virus (AAV)-based cell and gene therapy is a rapidly developing field, requiring analytical methods for detailed product characterization. One important quality attribute of AAV products that requires monitoring is the amounts of residual empty capsids following downstream processing. Traditionally, empty and full particles are quantified via analytical ultracentrifugation as well as anion exchange chromatography using ultraviolet or fluorescence detection. Here, we present a native mass spectrometry-based approach to assess the ratio of empty to full AAV-capsids without the need for excessive sample preparation. We report rapid determination of the amount of empty particles in AAV5 and AAV8 samples, with results correlating well with more conventional analysis strategies, demonstrating the potential of state-of-the-art mass spectrometry for the characterization of viral particles.
DynaTMT: A user-friendly tool to process combined SILAC/TMT data
Authors: Klann Kevin , Krause David , Münch Christian 
Published: July 2021

ABSTRACTThe measurement of protein dynamics by proteomics to study cell remodeling has seen increased attention over the last years. This development is largely driven by a number of technological advances in proteomics methods. Pulsed stable isotope labeling in cell culture (SILAC) combined with tandem mass tag (TMT) labeling has evolved as a gold standard for profiling protein synthesis and degradation. While the experimental setup is similar to typical proteomics experiments, the data analysis proves more difficult: After peptide identification through search engines, data extraction requires either custom scripted pipelines or tedious manual table manipulations to extract the TMT-labeled heavy and light peaks of interest. To overcome this limitation, which deters researchers from using protein dynamic proteomics, we developed a user-friendly, browser-based application that allows easy and reproducible data analysis without the need for scripting experience. In addition, we provide a python package that can be implemented in established data analysis pipelines. We anticipate that this tool will ease data analysis and spark further research aimed at monitoring protein translation and degradation by proteomics.
Investigating the Impact of Offer Frame Manipulations On Responders Playing The Ultimatum Game
Authors: Fabre Eve Florianne , Rumiati Rino , Cacciari Cristina , Borau Sylvie , Causse Mickael , Lotto Lorella 
Published: July 2021

AbstractThe present study was designed to test the impact of frame manipulations on the decision-making of responders playing the ultimatum game. Experiment 1 investigated responders’ event-related potentials (ERPs) measured in response to the offers as a function of the frame (i.e., negative: “the proposerkeeps”versuspositive “the proposer offers”). While no difference in acceptation rate was found as a function of the offer’s frame, electrophysiological results suggest that the stronger negative affective response to the offers in the negative frame (N400) was successfully reappraised by the responders (P600), possibly explaining why the offer frame manipulation did not modulate acceptation rates. No framing effect was found when the ultimatum game was played in its one-shot version (Experiment 2), suggesting that repeated measurements did not affect responders’ behavior. However, an offer framing effect was found in female (but not in male) responders, when the players’ cognitive charge was increased using more complex game rules (Experiment 3), presumably reflecting women’s greater affective responses to negative outcomes. Taken together, these results suggest that framing manipulations are associated with complex affective and cognitive processes, supporting the cognitive–affective tradeoff model.
Gut-derived metabolites influence neurodevelopmental gene expression and Wnt signalling events in a germ-free zebrafish model
Authors: Rea Victoria , Bell Ian , Van Raay Terence 
Published: July 2021

ABSTRACTSmall molecule metabolites produced by the microbiome are known to be neuroactive and are capable of directly impacting the brain and central nervous system, yet there is little data on the contribution of these metabolites to the earliest stages of neural development and neural gene expression. Here, we explore the impact of rearing zebrafish embryos in the absence of microbes on early neural development as well as investigate whether any potential changes can be rescued with treatment of metabolites derived from the zebrafish gut microbiota. Overall, we did not observe any gross morphological changes between treatments but did observe a significant decrease in neural gene expression in embryos raised germ-free, which was rescued with the addition of zebrafish metabolites. Specifically, we identified 361 genes significantly down regulated in GF embryos compared to conventionally raised embryos via RNA-Seq analysis. Of these, 42 were rescued with the treatment of zebrafish gut-derived metabolites to GF embryos. Gene ontology analysis revealed that these genes are involved in prominent neurodevelopmental pathways including transcriptional regulation and Wnt signalling. Consistent with the ontology analysis, we found alterations in the development of Wnt dependent events which is rescued in the GF embryos treated with metabolites.
The EEG spectral fingerprints of meditation and mind wandering differ between experienced meditators and novices
Authors: Rodriguez-Larios Julio , Bracho Montes de Oca Eduardo A. , Alaerts Kaat 
Published: July 2021

AbstractPrevious literature suggests that meditation training is associated with changes in participants’ experience during meditation practice. In this study, we assess whether putative differences in the experience of meditation between meditators and non-meditators are reflected in EEG spectral modulations. For this purpose, we recorded electroencephalography (EEG) during rest and two breath focus meditations (with and without experience sampling) in a group of 29 adult participants with more than 3 years of meditation experience and a control group of 29 participants without any meditation experience. Experience sampling in one of the meditation conditions allowed us to disentangle periods of breath focus from mind wandering (i.e. moments of distraction driven by task-irrelevant thoughts) during meditation practice. Overall, meditators reported a greater level of focus and reduced mind wandering during meditation practice than controls. In line with these reports, EEG spectral modulations associated to meditation and mind wandering also differed significantly between meditators and controls. While meditators (but not controls) showed a significant decrease in individual alpha frequency and amplitude and a steeper 1/f slope during meditation relative to rest, controls (but not meditators) showed a relative increase in individual alpha amplitude during mind wandering relative to breath focus periods. Together, our results show that the experience of meditation changes with training and that this is reflected in oscillatory and non-oscillatory components of brain activity.
Cdt1 inhibits CMG helicase in early S phase to separate origin licensing from DNA synthesis
Authors: Ratnayeke Nalin , Chung Mingyu , Meyer Tobias 
Published: July 2021

AbstractA fundamental concept in eukaryotic DNA replication is the temporal separation of G1 origin licensing from S phase origin firing. Re-replication and genome instability ensue if licensing occurs after DNA synthesis has started. In humans and other vertebrates, the E3 ubiquitin ligase CRL4Cdt2 starts to degrade the licensing factor Cdt1 after origins fire, raising the question of how cells prevent re-replication in early S phase. Here, using quantitative microscopy, we show that Cdt1 inhibits DNA synthesis during an overlap period when cells fire origins while Cdt1 is still present. Cdt1 inhibits DNA synthesis by suppressing CMG helicase progression at replication forks through the MCM-binding domain of Cdt1, and DNA synthesis commences once Cdt1 is degraded. Thus, instead of separating licensing from firing to prevent re-replication in early S phase, cells separate licensing from DNA synthesis through Cdt1-mediated inhibition of CMG helicase after firing.Highlights– Cdt1 is present together with fired origins of replication at the start of S phase– Cdt1 delays DNA synthesis by inhibiting CMG helicase progression after origins fire– Cdt1 inhibits CMG helicase progression through the MCM-binding domain of Cdt1