bluuebunny/crossref_metadata_2025_split huggingface dataset:
CosR is a repressor of compatible solute biosynthesis and transporter systems
Authors: Gregory Gwendolyn J. , Morreale Daniel P. , Boyd E. Fidelma 
Published: November 2019

AbstractBacteria accumulate small, organic compounds, called compatible solutes, via uptake from the environment or biosynthesis from available precursors to maintain the turgor pressure of the cell in response to osmotic stress.Vibrio parahaemolyticushas biosynthesis pathways for the compatible solutes ectoine (ectABCasp_ect)and glycine betaine (betIBAproXWV), four betaine-carnitine-choline transporters (bcct1-bcct4) and a second ProU transporter (proVWX).Most of these systems are induced in high salt. CosR, a MarR-type regulator, which is divergently transcribed frombcct3, was previously shown to be a direct repressor ofectABCasp_ectinVibriospecies. In this study, we investigated the role of CosR in glycine betaine biosynthesis and compatible solute transporter gene regulation. Expression analyses demonstrated thatbetIBAproXWV,bcct1,bcct3, andproVWXare repressed in low salinity. Examination of an in-framecosRdeletion mutant shows induced expression of these systems in the mutant at low salinity compared to wild-type. DNA binding assays demonstrate that purified CosR binds directly to the regulatory region of each system. InEscherichia coliGFP reporter assays, we demonstrate that CosR directly represses transcription ofbetIBAproXWV,bcct3, andproVWX. Similar toV. harveyi, we showbetIBAproXWVis positively regulated by the LuxR homolog OpaR. Bioinformatics analysis demonstrates that CosR is widespread within the genus, present in over 50 species. In several species, thecosRhomolog was clustered with thebetIBAproXWVoperon, which again suggests the importance of this regulator in glycine betaine biosynthesis. Incidentally, in fourAliivibriospecies that contain ectoine biosynthesis genes, we identified another MarR-type regulator,ectR, clustered with these genes, which suggests the presence of a novel ectoine regulator. Homologs of EctR in this genomic context were present inA. fischeri, A. finisterrensis, A. sifiaeandA. wodanis.ImportanceVibrio parahaemolyticuscan accumulate compatible solutes via biosynthesis and transport, which allow the cell to survive in high salinity conditions. There is little need for compatible solutes under low salinity conditions, and biosynthesis and transporter systems are repressed. However, the mechanism of this repression is not fully elucidated. CosR plays a major role in the repression of multiple compatible solute systems inV. parahaemolyticusas a direct negative regulator of ectoine and glycine betaine biosynthesis systems and four transporters. Homology analysis suggests that CosR functions in this manner in many otherVibriospecies. InAliivibriospecies, we identified a new MarR family regulator EctR that clusters with the ectoine biosynthesis genes.
Spectrum of protein localization in proteomes captures evolutionary relation between species
Authors: Marot-Lassauzaie Valérie , Goldberg Tatyana , Rost Burkhard 
Published: November 2019

AbstractThe native subcellular localization or cellular compartment of a protein is the one in which it acts most often; it is one aspect of protein function. Do ten eukaryotic model organisms differ in theirlocation spectrum, i.e. the fraction of its proteome in each of its seven major compartments? As experimental annotations of locations remain biased and incomplete, we need prediction methods to answer this question. To gauge the bias of prediction methods, we merged all available experimental annotations for the human proteome. In doing so, we found important values in both Swiss-Prot and the Human Protein Atlas (HPA). After systematic bias corrections, the complete but faulty prediction methods appeared to be more appropriate to compare location spectra between species than the incomplete more accurate experimental data. This work compared the location spectra for ten eukaryotes:Homo sapiens, Gorilla gorilla, Pan troglodytes, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Anopheles gambiae, Caenorhabitis elegans, Saccharomyces cerevisiaeandSchizosaccharomyces pombe. Overall, the predicted location spectra were similar. However, the detailed differences were significant enough to plot trees and 2D (PCA) maps relating the ten organisms using a simple Euclidean distance in seven states, corresponding to the seven studied localization classes. The relations based on the simple predicted location spectra captured aspects of cross-species comparisons usually revealed only by much more detailed evolutionary comparisons.
Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites
Authors: Miller Helen L. , Contera Sonia , Wollman Adam J.M. , Hirst Adam , Dunn Katherine E. , Schröter Sandra , O’Connell Deborah , Leake Mark C. 
Published: November 2019

AbstractIntercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.
Optogeneticlacoperon to control chemical and protein production inEscherichia coliwith light
Authors: Lalwani Makoto A. , Ip Samantha S. , Carrasco-Lopez Cesar , Zhao Evan M. , Kawabe Hinako , Avalos José L. 
Published: November 2019

AbstractControl of thelacoperon with IPTG has been used for decades to regulate gene expression inE. colifor countless applications, including metabolic engineering and recombinant protein production. However, optogenetics offers unique capabilities such as easy tunability, reversibility, dynamic induction strength, and spatial control that are difficult to obtain with chemical inducers. We developed an optogeneticlacoperon in a series of circuits we call OptoLAC. With these circuits, we control gene expression from various IPTG-inducible promoters using only blue light. Applying them to metabolic engineering improves mevalonate and isobutanol production by 24% and 27% respectively, compared to IPTG induction, in light-controlled fermentations scalable to at least 2L bioreactors. Furthermore, OptoLAC circuits enable light control of recombinant protein production, reaching yields comparable to IPTG induction, but with enhanced tunability of expression and spatial control. OptoLAC circuits are potentially useful to confer light controls over other cell functions originally engineered to be IPTG-inducible.
Graph-Theoretical Formulation of the Generalized Epitope-based Vaccine Design Problem
Authors: Dorigatti Emilio , Schubert Benjamin 
Published: November 2019

AbstractEpitope-based vaccines have revolutionized vaccine research in the last decades. Due to their complex nature, bioinformatics plays a pivotal role in their development. However, existing algorithms address only specific parts of the design process or are unable to provide formal guarantees on the quality of the solution. Here we present a unifying formalism of the general epitope vaccine design problem that tackles all phases of the design process simultaneously and combines all prevalent design principles. We then demonstrate how to formulate the developed formalism as an integer linear program which guarantees optimality of the designs. This makes it possible to explore new regions of the vaccine design space, analyze the trade-offs between the design phases, and balance the many requirements of vaccines.
Global transcriptome analysis reveals circadian control of splicing events in Arabidopsis thaliana
Authors: Romanowski Andrés , Schlaen Rubén G. , Perez-Santangelo Soledad , Mancini Estefanía , Yanovsky Marcelo J. 
Published: November 2019

SUMMARYThe circadian clock of Arabidopsis thaliana controls many physiological and molecular processes, allowing plants to anticipate daily changes in their environment. However, developing a detailed understanding of how oscillations in mRNA levels are connected to oscillations in post-transcriptional processes, such as splicing, has remained a challenge.Here we applied a combined approach using deep transcriptome sequencing and bioinformatics tools to identify novel circadian regulated genes and splicing events.Using a stringent approach, we identified 300 intron retention, 8 exon skipping, 79 alternative 3’ splice site usage, 48 alternative 5’ splice site usage, and 350 multiple (more than one event type) annotated events under circadian regulation. We also found 7 and 721 novel alternative exonic and intronic events. Depletion of the circadian regulated splicing factor AtSPF30 homolog, resulted in the disruption of a subset of clock controlled splicing events.Altogether, our global circadian RNA-seq coupled with an in silico, event centred, splicing analysis tool offers a new approach for studying the interplay between the circadian clock and the splicing machinery at a global scale. The identification of many circadian regulated splicing events broadens our current understanding of the level of control that the circadian clock has over this posttranscriptional regulatory layer.
Using MAP-Elites to Optimize Self-Assembling Behaviors in a Swarm of Bio-micro-robots
Authors: Cazenille Leo , Bredeche Nicolas , Aubert-Kato Nathanael 
Published: November 2019

AbstractWe are interested in programming a swarm of molecular robots that can perform self-assembly to form specific shapes at a specific location. Programming such robot swarms is challenging for two reasons. First, the goal is to optimize both the parameters and the structure of chemical reaction networks. Second, the search space is both high-dimensional and deceptive. In this paper, we show that MAP-Elites, an algorithm that searches for both high-performing and diverse solutions, outperforms previous state-of-the-art optimization methods.
Behavioral traits that define social dominance are the same that reduce social influence in a consensus task
Authors: Rodriguez-Santiago Mariana , Nührenberg Paul , Derry James , Deussen Oliver , Garrison Linda K , Garza Sylvia F , Francisco Fritz , Hofmann Hans A , Jordan Alex 
Published: November 2019

AbstractIn many species, cultures, and contexts, social dominance reflects the ability to exert influence over others, and the question of what makes an effective leader is pertinent to a range of disciplines and contexts. While dominant individuals are often assumed to be most influential, the behavioral traits that make them dominant may also make them socially aversive and thereby reduce their influence. Here we examine the influence of dominant and subordinate males on group behavior in different social contexts using the cichlid fish Astatotilapia burtoni. We find that phenotypically dominant males display behavioral traits that typify leadership across taxonomic systems – aggressive, social centrality, and movement leadership, while subordinate males are passive, socially peripheral, and have little influence over movement. However, in a more complex group-consensus task involving visual cue associations, subordinate males become the most effective agents of social change. We find that dominant males are spatially distant and have lower signal-to-noise ratios of informative behavior in the association task, potentially interfering with their ability to generate group-consensus. In contrast, subordinate males are physically close to other group members, have high signal-to-noise behaviors in the association task, and visual connectivity to other group members equal to that of dominant males. The attributes that define effective social influence are therefore highly context-specific, with socially and phenotypically dominant males being influential in routine but not complex social scenarios. These results demonstrate that behavioral traits that are typical of socially dominant individuals may actually reduce their social influence in other contexts.Significance StatementThe attributes that allow individuals to attain positions of social power and dominance are common across many vertebrate social systems – aggression, intimidation, coercion. Yet these traits are socially aversive, and can make dominant individuals poor agents of social change. In a vertebrate system (social cichlid fish) we show that dominant males are aggressive, socially central, and lead group movement. Yet dominant males are poor effectors of consensus in an more sophisticated association task compared with passive, socially-peripheral subordinate males. The most effective agents of social influence possess behavioral traits opposite of those typically found in position of social dominance, suggesting the behavioral processes that generate social dominance may simultaneously place the most ineffective leaders in positions of power.
Full Water‐Cycle Monitoring in an Urban Catchment Reveals Unexpected Water Transfers (Detroit MI, USA)
Authors: Hoard Christopher J. , Haefner Ralph J. , Shuster William D. , Pieschek Rachel L. , Beeler Stephanie 
Published: November 2019

AbstractA goal in urban water management is to reduce the volume of stormwater runoff in urban systems and the effect of combined sewer overflows into receiving waters. Effective management of stormwater runoff in urban systems requires an accounting of various components of the urban water balance. To that end, precipitation, evapotranspiration (ET), sewer flow, and groundwater in a 3.40‐hectare sewershed in Detroit, Michigan were monitored to capture the response of the sewershed to stormwater flow prior to implementation of stormwater control measures. Monitoring results indicate that stormflow in sewers was not initiated unless rain depth was 3.6 mm or greater. ET removed more than 40% of the precipitation in the sewershed, whereas pipe flow accounted for 19%–85% of the losses. Flows within the sewer that could not be associated with direct precipitation indicate an unexpected exchange of water between the leaky sewer and the groundwater system, pathways through abandoned or failing residential infrastructure, or a combination of both. Groundwater data indicate that groundwater flows into the leaky combined sewer rather than out. This research demonstrates that urban hydrologic fluxes can modulate the local water cycle in complex ways which affect the efficiency of the wastewater system, effectiveness of stormwater management, and, ultimately, public health.
Paracetamol is a centrally acting analgesic using mechanisms located in the periaqueductal grey
Authors: Barrière David André , Boumezbeur Fawzi , Dalmann Romain , Cadeddu Roberto , Richard Damien , Pinguet Jérémy , Daulhac Laurence , Sarret Philippe , Whittingstall Kevin , Keller Matthieu , Mériaux Sébastien , Eschalier Alain , Mallet Christophe 
Published: November 2019

Background and PurposeWe previously demonstrated that paracetamol has to be metabolised in the brain by fatty acid amide hydrolase enzyme into AM404 (N‐(4‐hydroxyphenyl)‐5Z,8Z,11Z,14Z‐eicosatetraenamide) to activate CB1 receptors and TRPV1 channels, which mediate its analgesic effect. However, the brain mechanisms supporting paracetamol‐induced analgesia remain unknown.Experimental ApproachThe effects of paracetamol on brain function in Sprague‐Dawley rats were determined by functional MRI. Levels of neurotransmitters in the periaqueductal grey (PAG) were measured using in vivo 1H‐NMR and microdialysis. Analgesic effects of paracetamol were assessed by behavioural tests and challenged with different inhibitors, administered systemically or microinjected in the PAG.Key ResultsParacetamol decreased the connectivity of major brain structures involved in pain processing (insula, somatosensory cortex, amygdala, hypothalamus, and the PAG). This effect was particularly prominent in the PAG, where paracetamol, after conversion to AM404, (a) modulated neuronal activity and functional connectivity, (b) promoted GABA and glutamate release, and (c) activated a TRPV1 channel‐mGlu5 receptor‐PLC‐DAGL‐CB1 receptor signalling cascade to exert its analgesic effects.Conclusions and ImplicationsThe elucidation of the mechanism of action of paracetamol as an analgesic paves the way for pharmacological innovations to improve the pharmacopoeia of analgesic agents.
IFN‐γ +874T/A polymorphism increases susceptibility to post‐traumatic osteomyelitis
Authors: Zhao Xing‐qi , Jiang Nan , Hu Yan‐jun , Yu Bin 
Published: November 2019

AbstractImmunological inflammatory reaction is one of the key links in the occurrence and development of post‐traumatic osteomyelitis after microbial invasion. Growing evidence suggests complex interactions between IFN‐γ and bone remodelling cells. However, potential association of IFN‐γ gene polymorphism with susceptibility to post‐traumatic osteomyelitis remains unclear. This study aimed to investigate the potential link between IFN‐γ +874T/A polymorphism and risk of developing post‐traumatic osteomyelitis. A total of 189 patients with post‐traumatic osteomyelitis and 200 healthy controls were enrolled for genotyping using the SNaPshot genotyping method. Statistically significant associations were found between the gene polymorphism and the risk of post‐traumatic osteomyelitis by dominant model (AA + AT vs. TT, OR = 1.820, p = .017) and heterozygous model (AT vs. TT, OR = 1.781, p = .029). Moreover, the frequency of mutant allele A was significantly higher in the patients than that in the healthy controls (15.07% vs. 9.25%, OR = 1.742, p = .013). IFN‐γ +874T/A polymorphism may contribute to the increased susceptibility to post‐traumatic osteomyelitis.
Artesunate inhibits the mevalonate pathway and promotes glioma cell senescence
Authors: Wei Shupei , Liu Lili , Chen Zhiyu , Yin Wenli , Liu Yingzi , Ouyang Qianying , Zeng Feiyue , Nie Yingjie , Chen Tao 
Published: November 2019

AbstractGlioma is a common brain malignancy for which new drug development is urgently needed because of radiotherapy and drug resistance. Recent studies have demonstrated that artemisinin (ARS) compounds can display antiglioma activity, but the mechanisms are poorly understood. Using cell lines and mouse models, we investigated the effects of the most soluble ARS analogue artesunate (ART) on glioma cell growth, migration, distant seeding and senescence and elucidated the underlying mechanisms. Artemisinin effectively inhibited glioma cell growth, migration and distant seeding. Further investigation of the mechanisms showed that ART can influence glioma cell metabolism by affecting the nuclear localization of SREBP2 (sterol regulatory element‐binding protein 2) and the expression of its target gene HMGCR (3‐hydroxy‐3‐methylglutaryl coenzyme A reductase), the rate‐limiting enzyme of the mevalonate (MVA) pathway. Moreover, ART affected the interaction between SREBP2 and P53 and restored the expression of P21 in cells expressing wild‐type P53, thus playing a key role in cell senescence induction. In conclusion, our study demonstrated the new therapeutic potential of ART in glioma cells and showed the novel anticancer mechanisms of ARS compounds of regulating MVA metabolism and cell senescence.
Fundic gland polyp prevalence according toHelicobacter pyloriinfection status
Authors: Notsu Takumi , Adachi Kyoichi , Mishiro Tomoko , Ishimura Norihisa , Ishihara Shunji 
Published: November 2019

AbstractBackground and AimThe prevalence of fundic gland polyp (FGP) occurrence has not been clarified in individuals withHelicobacter pyloriinfection post‐eradicated status. This study was performed to examine the relationship between FGP prevalence andH.pyloriinfection status.MethodsWe enrolled 3400 subjects (2185 male subjects and 1215 female subjects; mean age 54.7 ± 9.5 years) with knownH. pyloriinfection status and who underwent an upper gastrointestinal endoscopy examination as part of an annual check‐up. Subjects without and withH.pyloriinfection numbered 1617 and 239, respectively, while 1544 had a post‐eradication status. The presence of FGP and degree of gastric mucosal atrophy were determined in each subject using an endoscopic method.ResultsEndoscopy findings showed FGPs in 1029 (30.3%) of all subjects. The prevalence ratio of FGP positivity inH.pylori‐negative,H.pylori‐positive, and post‐eradicated subjects was 51.9%, 1.7%, and 12.0%, respectively. Multiple logistic regression analysis revealed that female gender, older age, milder gastric mucosal atrophy, and anti‐secretory therapy were significant risk factors for FGP occurrence. As compared withH.pylori‐positive subjects, the odds ratios forH.pylori‐negative and post‐eradication status were 48.3 and 6.6, respectively (P< 0.001). In the post‐eradication status subjects, longer duration following bacterial eradication was a significant risk factor for occurrence of FGPs.ConclusionThe risk of FGP occurrence in individuals who have undergoneH.pylorieradication treatment is lower as compared with those who have never been infected. However, that risk increases over time following eradication.