bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis hydathodes are sites of intense auxin metabolism and nutrient scavenging
Authors: Routaboul Jean-Marc , Bellenot Caroline , Clément Gilles , Citerne Sylvie , Remblière Céline , Charvin Magali , Franke Lars , Chiarenza Serge , Vasselon Damien , Jardinaud Marie-Françoise , Carrère Sébastien , Nussaume Laurent , Laufs Patrick , Leonhardt Nathalie , Navarro Lionel , Schattat Martin , Noël Laurent D. 
Published: December 2022

AbstractHydathodes are small organs located on the leaf margins of all vascular plants. They release excess xylem sap through guttation when stomata are closed or when the humidity level is high. Many promoter analyses have suggested other hydathode functions in metabolite transport and auxin metabolism, but experimental demonstration is still lacking. Here, we compared the transcriptomic and metabolomic features of mature Arabidopsis hydathodes to the leaf blade. 1460 differentially-expressed genes were identified revealing that genes related to auxin metabolism, transport, stress, DNA, plant cell wall, RNA or wax were on average more expressed in hydathodes. On the other hand, genes involved in glucosinolate metabolism, sulfation pathway, metal handling or photosynthesis were downregulated in hydathodes. In hydathodes, there are an increased expression of auxin transcriptional regulators and biosynthetic genes, a lower expression of auxin transport genes and a differential expression of genes related to its vacuolar storage that is consistent with increased contents of free and conjugated auxin. We also found that ca. 78% of the total content of 52 xylem sap metabolites were removed from guttation fluid at the hydathode level. Using reverse genetics, we showed that the capture of nitrate and phosphate in the guttation fluid relies on theNRT2.1andPHT1;4transporters, respectively. Thus, hydathodes absorb a significant part of xylem sap nutrients, limiting the loss of valuable chemicals during guttation. Our transcriptomic and metabolomic analyses reveal an organ with its own transcriptomic and physiological identity and highlight hydathode biological processes that may impact the whole plant.One sentence summaryTranscriptome and physiological analysis of mature and healthy hydathodes of Arabidopsis demonstrates that those organs are sites of intense auxin metabolism and nutrient scavenging
Investigating the origin of subtelomeric and centromeric AT-rich elements inAspergillus flavus
Authors: Lustig Arthur J. 
Published: December 2022

AbstractAn in silico study ofAspergillus flavusgenome stability uncovered significant variations in both coding and non-coding regions. The non-coding insertions uniformly consisted of AT-rich sequences that are evolutionarily maintained, albeit distributed at widely different sites in an array ofA. flavusstrains. A survey of ≥ 2kb AT-rich elements (AT ≥ 70%; ATEs) uncovered three classes. The first class is composed of homologous insertions at ectopic, non-allelic sites that contain homology to transposable elements (TEs). Strains differed significantly in frequency, position, and TE type, but displayed a common enrichment in subtelomeric regions. The TEs were heavily mutated, with patterns consistent with the ancestral activity of repeat-induced point mutations (RIP). The second class consists of ∼100 kb regions at each centromere. Centromeric ATEs and TE clusters within these centromeres display a high level of sequence identity between strains. The third class consists of a conserved set of novel subtelomeric ATE repeats which lack discernible TEs and, unlike TEs, display a constant polarity relative to the telomere. Members of one of these classes are derivatives of a progenitor ATE that is predicted to have undergone extensive homologous recombination during evolution. These studies suggest that transposition and RIP are forces in the evolution of subtelomeric and centromeric structure and function.
Metabolomic comparison usingStreptomycesspp. as a factory of secondary metabolites
Authors: Flores Clavo Rene , Kelyene Pereira Alana , Ruiz Quiñones Nataly , Henrique Costa Jonas , Pacheco Fill Taícia , Fantinatti Garboggini Fabiana 
Published: December 2022

AbstractUnderstanding extremophiles and their usefulness in biotechnology involves studying their habitat, physiology and biochemical adaptations, as well as their ability to produce biocatalysts, in environments that are still poorly explored. In northwestern Peru, which has saline lagoons of marine origin Pacific Ocean, the other site is from the coast of Brazil of the Atlantic Ocean. Both environments are considered extreme. The objective of the present work was to compare two different strains isolated from these extreme environments at the metabolic level using molecular network methodology through the Global Natural Products Molecular Social Network (GNPS). In our study, the MS/MS spectra from the network were compared with GNPS spectral libraries, where the metabolites were annotated. Differences were observed in the molecular network presented in the two strains ofStreptomycesspp. coming from these two different environments. Within the an-notated compounds from marine bacteria, the metabolites characterized forStreptomycessp. B-81 from Peruvian marshes were lobophorins A (1) and H (2), as well as divergolides A (3), B (4) and C (5).Streptomycessp. 796.1 produced different compounds, such as glucopiericidin A (6) and dehy-dro-piericidin A1a (7). The search for new metabolites in underexplored environments may therefore reveal new metabolites with potential application in different areas of biotechnology.
GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program
Authors: Lewis Michael , Terre Berta , Knobel Philip A. , Cheng Tao , Lu Hao , Attolini Camille Stephan-Otto , Smak Jordann , Coyaud Etienne , Garcia-Cao Isabel , Querol Jessica , Gil-Gomez Gabriel , Piergiovanni Gabrielle , Costanzo Vincenzo , Peiró Sandra , Raught Brian , Zhao Haotian , Salvatella Xavier , Roy Sudipto , Mahjoub Moe , Stracker Travis H. 
Published: December 2022

AbstractMulticiliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains.
Cell coupling compensates for changes in single-cell Her6 dynamics and provides phenotypic robustness
Authors: Doostdar Parnian , Hawley Joshua , Marinopoulou Elli , Lea Robert , Biga Veronica , Papalopulu Nancy , Rodriguez Ximena Soto 
Published: December 2022

Abstracther6is a zebrafish ortholog ofHes1, known for its role in maintaining neural progenitors during neural development. Here, we characterise the population-level effect of altering Her6 protein expression dynamics at the single-cell level in the embryonic zebrafish telencephalon. Using an endogenousHer6:Venusreporter and 4D single-cell tracking, we show that Her6 oscillates in neural telencephalic progenitors and that fusion of a protein destabilisation domain (PEST) to Her6:Venus alters its expression dynamics causing most cells to downregulate Her6 prematurely. However, in PEST mutants, a higher proportion of cells exhibit Her6 oscillations and while expression is reduced in most cells, some cells express Her6 at wild-type levels resulting in increased heterogeneity of Her6 expression in the population. Despite the profound differences in the single-cell Her6 dynamics, differentiation markers do not exhibit major differences early on, while an increase in differentiation is observed at later developmental stages (vglut2a, gad1andgad2). At the same time, at late stage the overall size of the telencephalon remains the same. Computational modelling that simulates changes in Her6 protein stability reveals that the increase in population Her6 expression heterogeneity is an emergent property of finely tuned Notch signalling coupling between single cells. Our study suggests that such cell coupling provides a compensation strategy whereby a normal phenotype is maintained while single-cell dynamics are abnormal, although the limit of this compensation is reached at late developmental stages. We conclude that in the neural progenitor population, cell coupling controls Her6 expression heterogeneity and in doing so, it provides phenotypic robustness when individual cells lose Her6 expression prematurely.
ExpressUrself: A spatial model for predicting recombinant expression from mRNA sequence
Authors: Dunne Michael P. , Caceres-Delpiano Javier 
Published: December 2022

AbstractMaximising the yield of recombinantly expressed proteins is a critical part of any protein engineering pipeline. In most cases, the expression of a given protein can be tuned by adjusting its DNA coding sequence, however finding coding sequences that optimise expression is a nontrivial task. The 3-dimensional structure of mRNA is known to strongly influence the expression levels of proteins, due to its effect on the efficiency of ribosome attachment. While correlations between mRNA structure and expression are well established, no model to date has succeeded in effectively utilising this information to accurately predict expression levels. Here we present ExpressUrself, a model designed to capture spatial characteristics of the sequence surrounding the start codon of an mRNA transcript, and intended to be used for optimising protein expression. The model is trained and tested on a large data set of variant DNA sequences and is able to predict the expression of previously unseen transcripts to a high degree of accuracy.
Dynamically regulated transcription factors are encoded by highly unstable mRNAs in theDrosophilalarval brain
Authors: Thompson Mary Kay , Ceccarelli Arianna , Ish-Horowicz David , Davis Ilan 
Published: December 2022

AbstractThe level of each RNA species depends on the balance between its rates of production and decay. Although previous studies have measured RNA decay across the genome in tissue culture and single-celled organisms, few experiments have been performed in intact complex tissues and organs. It is therefore unclear whether the determinants of RNA decay found in cultured cells are preserved in an intact tissue, and whether they differ between neighboring cell types and are regulated during development. To address these questions, we measured RNA synthesis and decay rates genome wide via metabolic labeling of whole culturedDrosophilalarval brains using 4-thiouridine. Our analysis revealed that decay rates span a range of more than 100-fold, and that RNA stability is linked to gene function, with mRNAs encoding transcription factors being much less stable than mRNAs involved in core metabolic functions. Surprisingly, among transcription factor mRNAs there was a clear demarcation between more widely used transcription factors and those that are expressed only transiently during development. mRNAs encoding transient transcription factors are among the least stable in the brain. These mRNAs are characterized by epigenetic silencing in most cell types, as shown by their enrichment with the histone modification H3K27me3. Our data suggests the presence of an mRNA destabilizing mechanism targeted to these transiently expressed transcription factors to allow their levels to be regulated rapidly with high precision. Our study also demonstrates a general method for measuring mRNA transcription and decay rates in intact organs or tissues, offering insights into the role of mRNA stability in the regulation of complex developmental programs.
Novel Complete Methanogenic Pathways in Longitudinal Genomic Study of Monogastric Age-Associated Archaea
Authors: Feehan Brandi , Ran Qinghong , Dorman Victoria , Rumback Kourtney , Pogranichniy Sophia , Ward Kaitlyn , Goodband Robert , Niederwerder Megan C , Lee Sonny T M 
Published: December 2022

AbstractBackgroundArchaea perform critical roles in the microbiome system, including utilizing hydrogen to allow for enhanced microbiome member growth and influencing overall host health. With the majority of microbiome research focussing on bacteria, the functions of archaea are largely still under investigation. Understanding methanogenic functions during the host lifetime will add to the limited knowledge on archaeal influence on gut and host health. In our study, we determined lifelong archaea detection and methanogenic functions while assessing global and host distribution of our novel archaeal metagenome assembled genomes (MAGs). We followed 7 monogastric swine throughout their life, from birth to adult (1-156 days of age), and collected feces at 22 time points. The samples underwent gDNA extraction, Illumina sequencing, bioinformatic quality and assembly processes, and MAG taxonomic assignment and functional annotation.ResultsWe generated 1,130 non-redundant MAGs with 8 classified as methanogenic archaea. The taxonomic classifications were as follows: ordersMethanomassiliicoccales(5) andMethanobacteriales(3); generaUBA71(3),Methanomethylophilus(1),MX-02(1), andMethanobrevibacter(3). We recovered the first US swineMethanobrevibacter UBA71 sp006954425andMethanobrevibacter gottschalkiiMAGs. TheMethanobacterialesMAGs were identified primarily during the young, preweaned host whereasMethanomassiliicoccalesprimarily in the adult host. Moreover, we identified our methanogens in metagenomic sequences from Chinese swine, US adult humans, Mexican adult humans, Swedish adult humans, and paleontological humans, indicating that methanogens span different hosts, geography and time. We determined complete metabolic pathways for all three methanogenic pathways: hydrogenotrophic, methylotrophic, and acetoclastic. This study provided the first evidence of acetoclastic methanogenesis in monogastric archaea which indicated a previously unknown capability for acetate utilization in methanogenesis for monogastric methanogens. Overall, we hypothesized that the age-associated detection patterns were due to differential substrate availability via the host diet and microbial metabolism, and that these methanogenic functions are likely crucial to methanogens across hosts. This study provided a comprehensive, genome-centric investigation of monogastric-associated methanogens which will further our understanding of microbiome development and functions.
Activation loop phosphorylation tunes conformational dynamics underlying Pyk2 tyrosine kinase activation
Authors: Palhano Zanela TM , Woudenberg A , Romero Bello KG , Underbakke ES 
Published: December 2022

AbstractPyk2 is a multidomain non-receptor tyrosine kinase that undergoes a multistage activation mechanism. Activation is instigated by conformational rearrangements relieving autoinhibitory FERM domain interactions. The kinase autophosphorylates a central linker residue to recruit Src kinase. Pyk2 and Src mutually phosphorylate activation loops to confer full activation. While the mechanisms of autoinhibition are established, the conformational dynamics associated with autophosphorylation and Src recruitment remain unclear. We employ hydrogen/deuterium exchange mass spectrometry (HDX-MS) and kinase activity profiling to map the conformational dynamics associated with substrate binding and Src-mediated activation loop phosphorylation. Nucleotide engagement stabilizes the autoinhibitory interface, while phosphorylation deprotects both FERM and kinase regulatory surfaces. Phosphorylation organizes active site motifs linking catalytic loop with activation segment. Dynamics of the activation segment anchor propagate to EF/G-helices to prevent reversion of the autoinhibitory FERM interaction. We employ targeted mutagenesis to dissect how phosphorylation-induced conformational rearrangements elevate kinase activity above the basal autophosphorylation rate.
A decrease in fatty acid synthesis rescues cells with limited peptidoglycan synthesis capacity
Authors: Willdigg Jessica R. , Patel Yesha , Helmann John D. 
Published: December 2022

AbstractProper synthesis and maintenance of a multilayered cell envelope is critical for bacterial fitness. However, whether mechanisms exist to coordinate synthesis of the membrane and peptidoglycan layers is unclear. InBacillus subtilis, synthesis of peptidoglycan (PG) during cell elongation is mediated by an elongasome complex acting in concert with class A PBPs (aPBPs). We previously described mutant strains limited in their capacity for PG synthesis due to a loss of aPBPs and an inability to compensate by upregulation of elongasome function. Growth of these PG-limited cells can be restored by suppressor mutations predicted to decrease membrane synthesis. One suppressor mutation leads to an altered function repressor, FapR*, that functions as a super-repressor and leads to decreased transcription of fatty acid synthesis (FAS) genes. Consistent with fatty acid limitation mitigating cell wall synthesis defects, inhibition of FAS by cerulenin also restored growth of PG-limited cells. Moreover, cerulenin can counteract the inhibitory effect of β-lactams in some strains. These results imply that limiting PG synthesis results in impaired growth, in part, due to an imbalance of PG and cell membrane synthesis and thatB. subtilislacks a robust physiological mechanism to reduce membrane synthesis when PG synthesis is impaired.ImportanceUnderstanding how a bacterium coordinates cell envelope synthesis is essential to fully appreciate how bacteria grow, divide, and resist cell envelope stresses such as β-lactam antibiotics. Balanced synthesis of the peptidoglycan cell wall and the cell membrane is critical for cells to maintain shape, turgor pressure and resist external cell envelope threats. UsingBacillus subtilis, we show that cells deficient in peptidoglycan synthesis can be rescued by compensatory mutations that decrease the synthesis of fatty acids. Further, we show that inhibiting fatty acid synthesis with cerulenin is sufficient to restore growth of cells deficient in peptidoglycan synthesis. Understanding the coordination of cell wall and membrane synthesis may provide insights relevant to antimicrobial treatment.
Low Dimensional Chaotic Attractors in Daily Hospital Occupancy from COVID-19 in the USA and Canada
Authors: Gonçalves Carlos Pedro 
Published: December 2022

AbstractEpidemiological application of chaos theory methods have uncovered the existence of chaotic markers in SARS-CoV-2’s epidemiological data, including low dimensional attractors with positive Lyapunov exponents, and evidence markers of a dynamics that is close to the onset of chaos for different regions. We expand on these previous works, performing a comparative study of United States of America (USA) and Canada’s COVID-19 daily hospital occupancy cases, applying a combination of chaos theory, machine learning and topological data analysis methods. Both countries show markers of low dimensional chaos for the COVID-19 hospitalization data, with a high predictability for adaptive artificial intelligence systems exploiting the recurrence structure of these attractors, with more than 95%R2scores for up to 42 days ahead prediction. The evidence is favorable to the USA’s hospitalizations being closer to the onset of chaos and more predictable than Canada, the reasons for this higher predictability are accounted for by using topological data analysis methods.
Non-targeted metabolomics identifies erythronate accumulation in cancer cells
Authors: Zhang Jie , Keibler Mark A. , Dong Wentao , Ghelfi Jenny , Cordes Thekla , Kanashova Tamara , Pailot Arnaud , Linster Carole , Dittmar Gunnar , Metallo Christian M. , Lautenschlaeger Tim , Hiller Karsten , Stephanopoulos Gregory 
Published: December 2022

AbstractUsing a non-targeted isotope-assisted metabolomics approach, we identified erythronate as a metabolite that accumulates in several human cancer cell lines. Erythronate has been reported to be a detoxification product derived from off-target glycolytic metabolism. We provide data supporting a possible alternative route to erythronate production involving the dephosphorylation of the pentose phosphate pathway intermediate erythrose-4-phosphate to form erythrose, followed by the oxidation of erythrose by an aldehyde dehydrogenase. Finally, we detected increased erythronate concentrations in tumors relative to adjacent normal tissues from lung cancer patients. These findings suggest the accumulation of erythronate to be an example of metabolic reprogramming in cancer cells, raising the possibility that elevated level of erythronate may serve as a biomarker of certain types of cancer.
Conformational dynamics of cohesin/Scc2 loading complex are regulated by Smc3 acetylation and ATP binding
Authors: Kaushik Aditi , Than Thane , Petela Naomi J , Voulgaris Menelaos , Percival Charlotte , Daniels Peter , Rafferty John B , Nasmyth Kim A , Hu Bin 
Published: December 2022

AbstractThe ring-shaped cohesin complex is the key player in sister chromatid cohesion, DNA repair, and gene transcription. The loading of cohesin to chromosomes requires the loader Scc2 and is regulated by ATP. This process is also hindered by Smc3 acetylation. However, the molecular mechanism underlying this inhibition remains mysterious. Here we identify a novel configuration of Scc2 with pre-engaged cohesin and reveal dynamic conformations of the cohesin/Scc2 complex in the loading reaction. We demonstrate that Smc3 acetylation blocks the association of Scc2 with pre-engaged cohesin by impairing the interaction of Scc2 with Smc3’s head. Lastly, we show that ATP binding induces the cohesin/Scc2 complex to clamp DNA by promoting the interaction between Scc2 and Smc3 coiled coil. Our results illuminate a dynamic reconfiguration of the cohesin/Scc2 complex during loading and indicate how Smc3 acetylation and ATP regulate this process.