bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Abundant New Saponin-Polybromophenol Antibiotic (CU1) fromCassia fistulaBark Against Multi-Drug Resistant Bacteria Targeting RNA Polymerase
Authors: Chakraborty Asit Kumar , Saha Sourajit , Poria Kousik , Samanta Tanmoy , Gautam Sudhanshu , Mukhopadhyay Jayanta 
Published: November 2020

AbstractSpread of multidrug-resistant infections is a threat to human race and need for new drug development is great. Bark ethanol extract ofCassia fistulainhibited MDR bacteria isolated from Ganga River water, human and animal. On TLC, a gray colour major band ran fast (CU1; 6.6% of bark and ~30% of crude extract) which quickly purified on HPLC C18column at 3 min. Chemical assays suggested a triterpene linked to polyphenol known as saponin. CHN Elements analysis (35.9% C; 5.5% H) did not identified nitrogen suggesting a polyphenol or glycoside. VU-Vis spectra gave high peak at below 200nm with a secondary peak at 275nm with minor hinge at 578nm indicating a fused ring with bromo-polyphenol. CU1 Mass (897 Daltons) with fragments of 515, 325, 269, 180 daltons and six halogen substitutions reflected by 82 molecular mass of DBr deviate six larger fragments. FT-IR suggested broad band at 3500-3000 cm−1for −OH where as two strong peaks at 1552cm−1for aromatic C=C and 1408cm−1for phenol. Proton-NMR confirmed polymeric phenol at δ 4.86-4.91 ppm and tetratet at δ3.57-3.618 ppm with phenolic bromo-substituents. Carbon-NMR identified a strong peak at δ=23.7ppm for many C-Br and at 165ppm for a polybenzoid compound. CU1 inhibited the RNA Polymerase ofE. coli(IC50=23μg/ml) andM. tuberculosis(IC50=34μg/ml) but not DNA polymerase. Gel shift assays demonstrated that CU1 drug interacted with enzyme and inhibited its binding to open promoter complex. Thus, CU1 phyto-chemical is an alternative safer and low cost drug against MDR-TB as well as other MDR pathogens.
IRIS-FGM: an integrative single-cell RNA-Seq interpretation system for functional gene module analysis
Authors: Chang Yuzhou , Allen Carter , Wan Changlin , Chung Dongjun , Zhang Chi , Li Zihai , Ma Qin 
Published: November 2020

AbstractSummarySingle-cell RNA-Seq (scRNA-Seq) data is useful in discovering cell heterogeneity and signature genes in specific cell populations in cancer and other complex diseases. Specifically, the investigation of functional gene modules (FGM) can help to understand gene interactive networks and complex biological processes. QUBIC2 is recognized as one of the most efficient and effective tools for FGM identification from scRNA-Seq data. However, its limited availability to a C implementation restricted its application to only a few downstream analyses functionalities. We developed an R package named IRIS-FGM (Integrative scRNA-Seq Interpretation System for Functional Gene Module analysis) to support the investigation of FGMs and cell clustering using scRNA-Seq data. Empowered by QUBIC2, IRIS-FGM can effectively identify co-expressed and co-regulated FGMs, predict cell types/clusters, uncover differentially expressed genes, and perform functional enrichment analysis. It is noteworthy that IRIS-FGM can also takes Seurat objects as input, which facilitate easy integration with existing analysis pipeline.Availability and ImplementationIRIS-FGM is implemented in R environment (as of version 3.6) with the source code freely available athttps://github.com/OSU-BMBL/IRIS-FGMContactqin.ma@osumc.eduSupplementary informationSupplementary data are available atBioinformaticsonline.
Spatiotemporal Variations in Growth Rate and Virulence Plasmid Copy Number duringYersinia pseudotuberculosisInfection
Authors: Schneiders Stephan , Hechard Tifaine , Edgren Tomas , Avican Kemal , Fällman Maria , Fahlgren Anna , Wang Helen 
Published: November 2020

AbstractPathogenicYersinia spp.depend on the activity of a potent virulence plasmid-encodedysc/yoptype 3 secretion system (T3SS) to colonize hosts and cause disease. It was recently shown thatY. pseudotuberculosisup-regulates the virulence plasmid copy number (PCN) during infection and the resulting elevated gene dose of plasmid-encoded T3SS genes is essential for virulence. When and how this novel regulatory mechanism is deployed and regulates the replication of the virulence plasmid during infection is unknown. In the current study, we applied droplet digital PCR (ddPCR) to investigate the dynamics ofY. pseudotuberculosisvirulence PCN variations and growth rates in infected mouse organs. We demonstrated that both PCN and growth varied in different tissues and over time throughout the course of infection, indicating that the bacteria adapted to discrete microenvironments during infection. The PCN was highest in Peyer’s Patches and caecum during the clonal invasive phase of the infection, while the fastest growth rates were found in the draining mesenteric lymph nodes. In deeper, systemic organs, the PCN was lower and more modest growth rates were recorded. Our study indicates that increased gene dosage of the plasmid-encoded T3SS genes is most important early in the infection during invasion of the host. The described ddPCR approach will greatly simplify analyses of PCN, growth dynamics, and bacterial loads in infected tissues, and will be readily applicable to other infection models.ImportanceStudying pathogenic bacteria proliferating inside infected hosts is challenging using traditional methods, especially the transit and reversible genetic events. The bacteria are effectively diluted by the overwhelming number of host cells present in infected tissues. Using an innovative droplet digital PCR (ddPCR) approach, we have determined the virulence plasmid copy number (PCN) variations and growth rates ofYersiniaduring the course of infection in a mouse model. Here, we show that both the virulence plasmid copy number and bacterial growth rates display spatiotemporal variations in mice during infection. We demonstrate that the peak-to-trough ratio can be used as a proxy for determining the growth rate of invasive bacterial pathogen during infection, and ddPCR as the method of choice for quantifying DNA in host-pathogen interaction context. This proof-of-concept ddPCR approach can be easily applied for any bacterial pathogens and any infection models, for analysis of PCN, growth dynamics and bacterial loads.
In situ3D comparison ofChlorella pyrenoidosawith nuclear-irradiated mutagenic strains by using focused ion beam milling and cryo-electron tomography
Authors: Guo Wangbiao , Feng Lingchong , Wang Zhenyi , Guo Jiansheng , Park Donghyun , Carroll Brittany L. , Zhang Xing , Liu Jun , Cheng Jun 
Published: November 2020

AbstractMicroalgae are highly efficient photosynthetic organisms that hold enormous potential as sources of renewable energy. In particular,Chlorella pyrenoidosadisplays a rapid growth rate, high tolerance to light, and high lipid content, making it especially valuable for applications such as flue gas CO2fixation, biofuel production, and nutritional extracts. In order to unveil its full potential, it is necessary to characterize its subcellular architecture. Here, we achieved three-dimensional (3D) visualization of the architectures ofC. pyrenoidosacells, by combining focused ion beam scanning electron microscopy (FIB/SEM), cryo-FIB milling, and cryo-electron tomography (cryo-ET). These high-resolution images bring to light intricate features of intact organelles, including thylakoid membranes, pyrenoid, starch granules, mitochondria, nucleus, lipid droplets and vacuoles, as well as the fine architectures within the chloroplast, including the concave-convex pyrenoid, plastoglobules, thylakoid tips, and convergence zones. Significantly, comparative analysis of wild-type and nuclear-irradiated mutagenic strains determined that cell volume and surface area of mutant cells have increased substantially to 2.2-fold and 1.7-fold, respectively, consistent with up-regulation of the enzyme Rubisco and enhanced photosynthetic metabolic processes. Moreover, quantitative analysis established that the thylakoid membrane width in mutant cells increased to 1.3-fold, while the membrane gap decreased to 0.8-fold, possibly contributing to the higher biomass growth rate of mutant cells. Our work reveals the first 3D subcellular architectures ofC. pyrenoidosacell and provides a structural framework for unlocking the higher growth rate in microalgae relevant to a wide range of industrial applications.
“Dimerization of the Mineralocorticoid Receptor Ligand Binding Domain by helix 9, 10 and the F-domain”
Authors: Bianchetti Laurent , Sinar Deniz , Depenveiller Camille , Dejaegere Annick 
Published: November 2020

AbstractIn vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear receptor (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to the group of oxo-steroidian NRs, together with the glucocorticoid (GR), progesterone (PR), and androgen (AR) receptors. Classically, these oxo-steroidian NRs homodimerize and bind to specific genomic sequences to activate gene expression. NRs are multi-domain proteins, and dimerization is mediated by both the DNA (DBD) and ligand binding (LBD) domains, with the latter thought to provide the largest dimerization interface. However, at the structural level, the LBD dimerization of oxo-steroidian receptors has remained largely a matter of debate. This is linked to the receptor refractory expression, purification and crystallization. As a result, there is currently no consensus on a common homodimer assembly across the 4 receptors,i.e. GR, PR, AR and MR, despite their sequence homology. Examining the available MR LBD crystals and using widely plebiscited tools such as PISA, PRISM and EPPIC, and the MM/PBSA method, we have determined that an interface mediated by the helices H9 and H10 of the LBD as well as by the F domain presents the features of a biological protein-protein interaction surface. This interface which has been observed in both GRα and MR crystals, distinguished itself among other contacts and provided for the first time a homodimer architecture that is common to both oxo-steroidian receptors.
Multi-resolution characterization of molecular taxonomies in bulk and single-cell transcriptomics data
Authors: Reed Eric R. , Monti Stefano 
Published: November 2020

AbstractAs high-throughput genomics assays become more efficient and cost effective, their utilization has become standard in large-scale biomedical projects. These studies are often explorative, in that relationships between samples are not explicitly defineda priori, but rather emerge from data-driven discovery and annotation of molecular subtypes, thereby informing hypotheses and independent evaluation. Here, we presentK2Taxonomer, a novel unsupervised recursive partitioning algorithm and associated R package that utilize ensemble learning to identify robust subgroups in a “taxonomy-like” structure (https://github.com/montilab/K2Taxonomer).K2Taxonomerwas devised to accommodate different data paradigms, and is suitable for the analysis of both bulk and single-cell transcriptomics data. For each of these data types, we demonstrate the power ofK2Taxonomerto discover known relationships in both simulated and human tissue data. We conclude with a practical application on breast cancer tumor infiltrating lymphocyte (TIL) single-cell profiles, in which we identified co-expression of translational machinery genes as a dominant transcriptional program shared by T cells subtypes, associated with better prognosis in breast cancer tissue bulk expression data.
Deletion ofCrtc1leads to hippocampal neuroenergetic impairments associated with depressive-like behavior
Authors: Cherix Antoine , Poitry-Yamate Carole , Lanz Bernard , Zanoletti Olivia , Grosse Jocelyn , Sandi Carmen , Gruetter Rolf , Cardinaux Jean-René 
Published: November 2020

AbstractMood disorders (MD) are a major burden on society as their biology remains poorly understood, challenging both diagnosis and therapy. Among many observed biological dysfunctions, homeostatic dysregulation, such as metabolic syndrome (MeS), shows considerable comorbidity with MD. Recently, CREB-regulated transcription coactivator 1 (CRTC1), a regulator of brain metabolism, was proposed as a promising factor to understand this relationship. Searching for imaging biomarkers and associating them with pathophysiological mechanisms using preclinical models, can provide significant insight into these complex psychiatric diseases and help the development of personalized healthcare. Here, we used neuroimaging technologies to show that deletion ofCrtc1in mice leads to an imaging fingerprint of hippocampal metabolic impairment related to depressive-like behavior. By identifying the underlying molecular/physiological origin, we could assign an energy-boosting mood-stabilizing treatment, ebselen, which rescued behavior and neuroimaging markers. Finally, our results point towards the GABAergic system as a potential therapeutic target for behavioral dysfunctions related to metabolic disorders. This study provides new insights onCrtc1’sand MeS’s relationship to MD and establishes depression-related markers with clinical potential.
An Oatp transporter-mediated steroid sink promotes tumor-induced cachexia inDrosophila
Authors: Santabárbara-Ruiz Paula , Léopold Pierre 
Published: November 2020

SummaryCancer cachexia is a multifactorial syndrome associated with many types of tumors and characterized by a combination of anorexia, loss of body weight, catabolic alterations and systemic inflammation. We developed a tumor model inDrosophilalarvae causing a cachexia-like syndrome, and used it to evaluate the role of steroid hormone imbalance in cachectic alterations. Cachectic larvae show reduced levels of the circulating steroid ecdysone. Artificially importing ecdysone in the tumor using the Oatp74D importer aggravates cachexia, while feeding animals with ecdysone rescues cachectic defects. This suggests that a steroid sink induced by the tumor promotes catabolic alterations in healthy tissues. We find that Oatp33Eb, another member of this family of transporters, is specifically induced in tumors promoting cachexia. Blocking Oatp33Eb in cachectic tumors restores circulating ecdysone and reverses cachectic alterations. Oatp transporters are induced in several types of hormone-dependent tumors, suggesting that a similar sink effect could modify hormonal balance in cachectic cancer patients.Highlights-We used theDrosophilalarva as a model to study hormonal imbalance in tumor-induced cachexia.-Steroid (ecdysone) levels are reduced in cachectic tumor-bearing larvae.-Steroid import by the tumor reduces circulating hormone levels and induces cachexia.-The Oatp33Eb transporter is specifically upregulated in cachectic tumors and its inhibition rescues both circulating steroid levels and metabolic/tissue homeostasis.-SpecificOatpgenes are found upregulated in human tumors with high prevalence of cachexia.
G1 Phase Lengthening During Neural Tissue Development Involves CDC25B Induced G1 Heterogeneity
Authors: Molina Angie , Bonnet Frédéric , Lobjois V. , Bel-Vialar Sophie , Gautrais Jacques , Pituello Fabienne , Agius Eric 
Published: November 2020

ABSTRACTWhile lengthening of the cell cycle and G1 phase is a generic feature of tissue maturation during development, the underlying mechanism remains still poorly understood. Here we develop a time lapse imaging strategy to measure the four phases of the cell cycle in single neural progenitor cells in their endogenous environment. Our results show that neural progenitors possess a great heterogeneity of the cell cycle length. This duration variability is distributed over all phases of the cell cycle, with the G1 phase being the one contributing primarily to cell cycle variability. Within one cell cycle, each phase duration appears stochastic and independent except for a surprising correlation between S and M phase. Lineage analysis indicates that the majority of daughter cells display longer G1 phase than their mother’s suggesting that at each cell cycle a mechanism lengthens the G1 phase. We identify an actor of the core cell cycle machinery, the CDC25B phosphatase known to regulate G2/M transition, as an indirect regulator of the duration of the G1 phase. We propose that CDC25B acts via a cell to cell increase in G1 phase heterogeneity revealing a novel mechanism of G1 lengthening associated with tissue development.
Do congruent lip movements facilitate speech processing in a dynamic audiovisual multi-talker scenario? An ERP study with older and younger adults
Authors: Begau Alexandra , Klatt Laura-Isabelle , Wascher Edmund , Schneider Daniel , Getzmann Stephan 
Published: November 2020

AbstractIn natural conversations, visible mouth and lip movements play an important role in speech comprehension. There is evidence that visual speech information improves speech comprehension, especially for older adults and under difficult listening conditions. However, the neurocognitive basis is still poorly understood. The present EEG experiment investigated the benefits of audiovisual speech in a dynamic cocktail-party scenario with 22 (aged 20 to 34 years) younger and 20 (aged 55 to 74 years) older participants. We presented three simultaneously talking faces with a varying amount of visual speech input (still faces, visually unspecific and audiovisually congruent). In a two-alternative forced-choice task, participants had to discriminate target words (“yes” or “no”) among two distractors (one-digit number words). In half of the experimental blocks, the target was always presented from a central position, in the other half, occasional switches to a lateral position could occur. We investigated behavioral and electrophysiological modulations due to age, location switches and the content of visual information, analyzing response times and accuracy as well as the P1, N1, P2, N2 event-related potentials (ERPs) and the contingent negative variation (CNV) in the EEG. We found that audiovisually congruent speech information improved performance and modulated ERP amplitudes in both age groups, suggesting enhanced preparation and integration of the subsequent auditory input. In the older group, larger amplitude measures were found in early phases of processing (P1-N1). Here, amplitude measures were reduced in response to audiovisually congruent stimuli. In later processing phases (P2-N2) we found decreased amplitude measures in the older group, while an amplitude reduction for audiovisually congruent compared to visually unspecific stimuli was still observable. However, these benefits were only observed as long as no location switches occurred, leading to enhanced amplitude measures in later processing phases (P2-N2). To conclude, meaningful visual information in a multi-talker setting, when presented from the expected location, is shown to be beneficial for both younger and older adults.
Vitamin D – contrary to vitamin K – does not associate with clinical outcome in hospitalized COVID-19 patients
Authors: Walk Jona , Dofferhoff Anton S.M. , van den Ouweland Jody M.W. , van Daal Henny , Janssen Rob 
Published: November 2020

AbstractSARS-CoV-2 causes remarkably variable disease from asymptomatic individuals to respiratory insufficiency and coagulopathy. Vitamin K deficiency was recently found to associate with clinical outcome in a cohort of COVID-19 patients. Vitamin D has been hypothesized to reduce disease susceptibility by modulating inflammation, yet little is known about its role in disease severity. Considering the critical interaction between vitamin K and vitamin D in calcium and elastic fiber metabolism, we determined vitamin D status in the same cohort of 135 hospitalized COVID-19 patients by measuring blood 25(OH)D levels. We found no difference in vitamin D status between those with good and poor outcome (defined as intubation and/or death). Instead, we found vitamin D sufficient persons (25(OH)D >50 nmol/L) had accelerated elastic fiber degradation compared to those with mild deficiency (25(OH)D 25-50 nmol/L). Based on these findings, we hypothesize that vitamin D might have both favorable anti-inflammatory and unfavorable pro-calcification effects during COVID-19 and that vitamin K might compensate for the latter.
Strategic management accounting practices: a literature review and opportunity for future research
Authors: Rashid Md. Mamunur , Ali Md. Mohobbot , Hossain Dewan Mahboob 
Published: November 2020

PurposeThe purpose of this study is to review the empirical studies that have focused on the adoption, benefits and contingencies of strategic management accounting (SMA) practices and the effects of adoption on firm performance.Design/methodology/approachThe study has highlighted empirical studies conducted on SMA practices in the context of both developed [1] and developing economies. In reviewing the literature, the study focuses on the findings of developed economy separately from that of developing economy to get more insight into the differences in the practices of the two set of economies. Based on the review, avenues for future research studies are outlined.FindingsThe review of extant literature reveals that several SMA techniques such as competitor accounting, strategic pricing, benchmarking and customer accounting have been highly or moderately adopted in several developed countries while majority of other techniques remained at the bottom line of the adoption status. However, the review demonstrates substantial differences in the SMA practices between the two set of economies in terms of the level of adoption, contingent factors and the effects of adoption.Originality/valueThe study attempts to focus on empirical studies that have concentrated exclusively on SMA practices. The adoption status, benefits derived, contingent factors affecting the adoption decision and the effect of adopting a package of SMA techniques on several aspects of firm performance are presented in the context of both developed and developing economies.
The multi-objective optimization of tunneling boring machine control based on geological conditions identification
Authors: Wang Hongyuan , Wang Jingcheng 
Published: November 2020

PurposeThe purpose of this paper aims to design an optimization control for tunnel boring machine (TBM) based on geological identification. For unknown geological condition, the authors need to identify them before further optimization. For fully considering multiple crucial performance of TBM, the authors establish an optimization problem for TBM so that it can be adapted to varying geology. That is, TBM can operate optimally under corresponding geology, which is called geology-adaptability.Design/methodology/approachThis paper adopted k-nearest neighbor (KNN) algorithm with modification to identify geological conditions. The modification includes adjustment of weights in voting procedure and similarity distance measurement, which at suitable for engineering and enhance accuracy of prediction. The authors also design several key performances of TBM during operation, and built a multi-objective function. Further, the multi-objective function has been transformed into a single objective function by weighted-combination. The reformulated optimization was solved by genetic algorithm in the end.FindingsThis paper provides a support for decision-making in TBM control. Through proposed optimization control, the advance speed of TBM has been enhanced dramatically in each geological condition, compared with the results before optimizing. Meanwhile, other performances are acceptable and the method is verified by in situ data.Originality/valueThis paper fulfills an optimization control of TBM considering several key performances during excavating. The optimization is conducted under different geological conditions so that TBM has geological-adaptability.