bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of flavone and its derivatives as potential inhibitors of transcriptional regulator LasR of Pseudomonasaeruginosausing virtual screening
Authors: Abelyan Narek , Grabski Hovakim , Tiratsuyan Susanna 
Published: January 2019

AbstractAntibiotic resistance is a global problem nowadays and in 2017 the World Health Organization published the list of bacteria for which treatment are urgently needed, wherePseudomonas aeruginosais of critical priority. Current therapies lack efficacy because this organism creates biofilms conferring increased resistance to antibiotics and host immune responses. The strategy is to “not kill, but disarm” the pathogen and resistance will be developed slowly. It has been shown that LasI/LasR system is the main component of the quorum sensing system inP. aeruginosa. LasR is activated by the interaction with its native autoinducer. A lot flavones and their derivatives are used as antibacterial drug compounds. The purpose is to search compounds that will inhibit LasR. This leads to the inhibition of the synthesis of virulence factors thus the bacteria will be vulnerable and not virulent. We performed virtual screening using multiple docking programs for obtaining consensus predictions. The results of virtual screening suggest benzamides which are synthetical derivatives of flavones as potential inhibitors of transcriptional regulator LasR. These are consistent with recently published experimental data, which demonstrate the high antibacterial activity of benzamides. The compounds interact with the ligand binding domain of LasR with higher binding affinity than with DNA binding domain. Among the selected compounds, by conformational analysis, it was found that there are compounds that bind to the same amino acids of ligand binding domain as the native autoinducer. This could indicate the possibility of competitive interaction of these compounds. A number of compounds that bind to other conservative amino acids ligand binding domain have also been discovered, which will be of interest for further study. Selected compounds meet the criteria necessary for their consideration as drugs and can serve as a basis for conducting furtherin vitro / in vivoexperiments. It could be used for the development of modern anti-infective therapy based on the quorum sensing system ofP. aeruginosa.HighlightsVirtual screening using multiple docking programs for consensus predictions.Virtual screening reveal benzamides as potential inhibitors of LasR.Selected compounds bind to the same amino acids of LBD as the native autoinducer.Selected compounds meet the criteria necessary for their consideration as drugs.GRAPHICAL ABSTRACT1: N- (1,3-benzodioxol-5-ylmethyl) -4- (6,8-dimethyl-4-oxochromen-2-yl) benzamide docking with LBD of LasR, A — ligand conformation predicted by AutoDock, B - by rDock and C - by LeDock,D - binding of CID 108754330 with LBD of LasR predicted by rDock.2: Four types of P. aeruginosa quorum sensing signaling systems I. Las, II. Rhl, III. Pqs and IV. IQS.
Health workers’ perspectives on the outcomes, enablers, and barriers to the implementation of HIV “Treat All” guidelines in Abuja Nigeria
Authors: Odafe Solomon , Stafford Kristen A. , Gambo Aliyu , Onotu Dennis , Swaminathan Mahesh , Dalhatu Ibrahim , Ene Uzoma , Oladipo Ademola , Mukhtar Ahmed , Ibrahim Ramat , Ehoche Akipu , Debem Henry , Boyd Andrew T. , Aboje Sunday , Gobir Bola , Charurat Manhattan 
Published: January 2019

AbstractIntroductionTo improve access to lifesaving treatment for all people living with HIV (PLHIV), Nigeria implemented the Treat All guidelines in 2016. However, health workers’ perspectives on the implementation of the guidelines have not been evaluated.MethodsWe conducted in-depth interviews to explore health workers’ perspectives on the Treat All guidelines. Using purposive sampling, 20 health workers providing HIV patient care were recruited from six primary health care hospitals in Abuja to participate in semi-structured interviews. Data exploration was conducted using thematic content analysis.ResultsThe five main themes that emerged were (1) the perceived benefits of guidelines use, (2) the perceived disadvantages of using the guidelines, (3) reported patients’ response to guideline change, (4) perceived barriers/enablers to guideline use and (5) health workers’ recommendations for improvement. Health workers perceived that the implementation of the Treat All guidelines has considerably improved patient care, particularly in increasing access to skilled health care, reducing stress on patients, and increasing hope for a better health outcome among patients. Other perceived benefits were reduced mortality, reduced pre-treatment attrition, reduction in delays between case detection and initiation on treatment. Perceived major disadvantages were increased workload and overcrowded clinics. Health workers reported that most patients were willing to start treatment early. Perceived key factors enabling guidelines use were health workers’ interest, patient benefits, training and availability of tools for implementation of guidelines, government supervisory visits and hospital management support. Perceived key barriers were poverty, inadequate human resources, lack of familiarity with guidelines, and lack of consistent supply of HIV test kits at some sites.ConclusionsImplementation of the Treat All guidelines led to perceived improvement in patient care. Further improvements could be achieved by implementing an efficient supply chain system for HIV rapid test kits, and through guidelines distribution and training. Additionally, implementing differentiated approaches that decongest clinics, and programs that economically empower patients could improve access to treatment.
A molecular phylogeny of Schizothoracinae (Teleostei: Cypriniformes: Cyprinidae) based on 12 protein-coding mitochondrial genes and RAG1 gene analysis
Authors: Du Yurong , Wang Ting , Qi Delin , Qi Desheng , Li Weilin , Zhong Jiangbin , Chen Juan , Guo Songchang , Ma Jianbin 
Published: January 2019

AbstractThe ever-increasing interest in the investigation of origin and speciation of schizothoracine fishes can be dated to 20th century. However, molecular phylogeny of Schizothoracinae and their phylogenetic relationships, as well as the divergence times still remain controversial. In this study, two DNA sets consisting of 12 protein-coding mitochondrial genes from 254 individuals and RAG1 gene from 106 individuals were used to reconstruct the phylogenetic relationships and calculate the divergence times among the subfamily schizothoracinae. Our results indicated that both of the data sets supported a non-monophyletic relationship due to involving of species of Barbinae. However, the phylogenetic relationships based on mtDNA genes were more reliable than that inferred from RAG1 gene. The highly specialized grade formed a monophyletic group, together with Ptychobarbus as a sister group of Diptychus and Gymnodiptychus, which was belonging to specialized grade, indicating that Ptychobarbus may be transition species to involve to highly specialized schizothoracianae. In addition, the primitive grade clustered with Percocypris pingi, a species of Barbinae. Based on mtDNA gene, the speciation time of Schizothoracinae was 66 Ma, and the divergence time of the primitive grade and Percocypris pingi was 64 Ma. The speciation times of the three grades Schizothoracinae were 57 Ma, 51 Ma and 43 Ma, respectively; and the divergence time of specialized and highly specialized grade was 46 Ma. The divergence times of three grades were not consistent with the three stages of uplift of Qinghai-Tibet Plateau, which is older than the times.
Genetically distinct behavioral modules underlie natural variation in thermal performance curves
Authors: Stegeman Gregory W. , Baird Scott E. , Ryu William S. , Cutter Asher D. 
Published: January 2019

AbstractThermal reaction norms pervade organismal traits as stereotyped responses to temperature, a fundamental environmental input into sensory and physiological systems. Locomotory behavior represents an especially plastic read-out of animal response, with its dynamic dependence on environmental stimuli presenting a challenge for analysis and for understanding the genomic architecture of heritable variation. Here we characterize behavioral reaction norms as thermal performance curves for the nematodeCaenorhabditis briggsae, using a collection of 23 wild isolate genotypes and 153 recombinant inbred lines to quantify the extent of genetic and plastic variation in locomotory behavior to temperature changes. By reducing the dimensionality of the multivariate phenotypic response with a function-valued trait framework, we identified genetically distinct behavioral modules that contribute to the heritable variation in the emergent overall behavioral thermal performance curve. Quantitative trait locus mapping isolated regions on Chromosome II associated with locomotory activity at benign temperatures and Chromosome V loci related to distinct aspects of sensitivity to high temperatures, with each quantitative trait locus explaining up to 28% of trait variation. These findings highlight how behavioral responses to environmental inputs as thermal reaction norms can evolve through independent changes to genetically distinct modular components of such complex phenotypes.Article SummaryPlastic responses to environmental inputs, reaction norm phenotypes that can be summarized with parameters of fits to a mathematical function, are pervasive across diverse organismal traits and crucial to organismal fitness. We quantified the nematodeCaenorhabditis briggsae’s behavioral thermal performance curves as function-valued traits for 23 wild isolate genotypes and 153 recombinant inbred lines. We identified quantitative trait loci on multiple chromosomes that define genetically distinct behavioral modules contributing to the emergent overall behavioral thermal performance curve. These findings highlight how dynamic behavioral responses to environmental inputs can evolve through independent changes to genetically distinct modular components of such complex phenotypes.
The symmetrical pattern of base-pair substitutions rates across the chromosome inEscherichia colihas multiple causes
Authors: Niccum Brittany A. , Lee Heewook , MohammedIsmail Wazim , Tang Haixu , Foster Patricia L. 
Published: January 2019

AbstractMutation accumulation experiments followed by whole-genome sequencing have revealed that for several bacterial species the rate of base-pair substitutions is not constant across the chromosome but varies in a wave-like pattern symmetrical about the origin of replication. The experiments reported here demonstrate that inEscherichia coliseveral interacting factors determine the wave. Perturbing replication timing, progression, or the structure of the terminus disrupts the pattern. Biases in error-correction by proofreading and mismatch repair are major factors. The activities of the nucleoid binding proteins, HU and Fis, are important, suggesting that mutation rates increase when highly structured DNA is replicated. These factors should apply to most bacterial, and possibly eukaryotic, genomes, and imply that different areas of the genome evolve at different rates.
Eco-Evolutionary Feedbacks Between Predator’s Linkage Disequilibrium and Prey Densities Maintain Diversity
Authors: Patel Swati , Bürger Reinhard 
Published: January 2019

ABSTRACTDiversity occurs at multiple scales. Within a single population, there is diversity in genotypes and phenotypes. At a larger scale, within ecological communities, there is diversity in species. There have been a number of studies to investigate how diversity at these two scales influence each other through what has been termed eco-evolutionary feedbacks. Here we study a three-species ecological module called apparent competition, in which the predator is evolving in a trait that determines its interaction with two prey species. Unlike previous studies on apparent competition, which employed evolutionary frameworks with greatly simplified genetics, we study a multilocus eco-evolutionary model in which the predator’s evolving trait is determined by two diallelic loci. We ask how eco-evolutionary feedbacks with these two loci affect the coexistence of the prey species and the maintenance of polymorphisms within the predator species. In doing so, we uncover a novel eco-evolutionary feedback between the prey species and the linkage disequilibrium of the two loci of the predator. Through a stability analysis, we demonstrate how these feedbacks affect polymorphisms at both loci and, among others, may generate stable cycling.
Replicating Arabidopsis Model Leaf Surfaces for Phyllosphere Microbiology
Authors: Soffe Rebecca , Bernach Michal , Remus-Emsermann Mitja , Nock Volker 
Published: January 2019

AbstractArtificial surfaces are commonly used in place of leaves in phyllosphere microbiology to study microbial behaviour on plant leaf surfaces. Studies looking into individual environmental factors influencing microorganisms are routinely carried out using artificial surfaces. Commonly used artificial surfaces include nutrient agar, isolated leaf cuticles, and reconstituted leaf waxes. However, interest is growing in using microstructured surfaces mimicking the complex topography of leaf surfaces for phyllosphere microbiology. As such replica leaf surfaces, produced by microfabrication, are appearing in literature. Replica leaf surfaces have been produced in agar, epoxy, polystyrene, and polydimethylsiloxane (PDMS). However, these protocols are not suitable for replicating fragile leaves such as of the model plant Arabidopsis thaliana. This is of importance as A. thaliana is a model system for molecular plant genetics, molecular plant biology, and microbial ecology. Here we present a versatile replication protocol for replicating fragile leaf surfaces into PDMS. We display the capacity of our replication process using optical microscopy, atomic force microscopy (AFM), and contact angle measurements to compare living and PDMS replica A. thaliana leaf surfaces. To highlight the use of our replica leaf surfaces for phyllosphere microbiology, we visualised bacteria on the replica leaf surfaces in comparison to living leaf surfaces.
SWI/SNF component BAF250a coordinates OCT4 and WNT signaling pathway to control cardiac lineage differentiation
Authors: Lei Ienglam , Tian Shuo , Chen Victor , Zhao Yong , Wang Zhong 
Published: January 2019

AbstractDissecting epigenetic mechanisms controlling early cardiac differentiation will provide insights into heart regeneration and heart disease treatment. SWI/SNF complexes remodel nucleosomes to regulate gene expression and play a key role in organogenesis. Here we reported a unique function of BAF250a in regulating the physical interaction of OCT4 and β-CATENIN during cardiac lineage differentiation from human ESCs. BAF250a deletion greatly reduced the physical interaction between OCT4 and β-CATENIN but did not alter the expression of β-CATENIN and OCT4 in the mesodermal progenitor cells. BAF250a ablation led to decreased recruitment of OCT4 and β-CATENIN at promoters of key mesodermal lineage genes, such as MESP1 and EOMES. Subsequently, the expression of lineage specific genes was down-regulated whereas the expression of pluripotent genes was up-regulated. In parallel, BAF250a ablation also altered recruitments of OCT4 and β-CATENIN to the promoter of CCND2 and CCND3, two key genes for S phase entry during cell cycle. Consequently, BAF250a deletion led to prolonged S phase in Mesp1+ cardiac progenitor cells, which in turn inhibited efficient differentiation of Mesp1+ to Isl1+ cells. Furthermore, BAF250a deletion abolished the interaction of OCT4 and BRG1 in mesoderm, suggesting that BAF250a is the key component in SWI/SNF complex that determines the interaction of Oct4/β-catenin in mesoderm. In contrast, we found that BAF250a did not regulate the OCT4/β-CATENIN interaction during neuroectoderm differentiation. Altogether, our results suggest that BAF250a specifically controls proper cardiac mesoderm differentiation by reorganizing the binding of OCT4/β-CATENIN and regulates both key lineage differentiation genes and cell cycle genes coincided in response to WNT/β-CATENIN signal.HighlightsBAF250a is required for hESC cardiac differentiationBAF250a is required for the assembly of Brg1/OCT4/β-CATENIN complex and the recruitment of OCT4/β-CATENIN to cardiac genesBAF250a is dispensable for the interaction of OCT4/β-CATENIN interaction in neuroectoderm differentiationBAF250a interacts with OCT4/β-CATENIN to promote cardiac differentiation by regulating cell cycle.
MicroRNA-222 regulates fluid shear stress-induced human nucleus pulposus cells degeneration through affecting c-Fos expression
Authors: Miao Haixiong , Yao Yicun , Ye Baoqing , Dai Libing , Liang Weiguo 
Published: January 2019

AbstractIntervertebral disc degeneration (IVDD) is a chronic disease that correlates with the deterioration of the nucleus pulposus (NP) cells. However, the molecular mechanism of IVDD remains unclear. In this study, we investigated the function of microRNA-222 in IVDD and the potential molecular mechanism. NP cells treated with fluid shear stress (FSS) were used to simulate a model of IVDD in vitro. MicroRNA-222 was significantly downregulated in NP cells stimulated with FSS compared with that in unstimulated NP cells. Human NP cells were also treated with FSS to induce their degeneration. The mRNA and protein levels of C-FOS, MEK, phosphorylated MEK5 (pMEK5), ERK5, and pERK5 were evaluated with RT-PCR and western blotting, respectively. Enzyme-linked immunosorbent assays were used to investigate type II collagen and Aggrecan expression. NP cell proliferation was determined with the Cell Counting Kit-8. MicroRNA-222 was significantly downregulated in NP cells treated with FSS. The production of c-Fos and MEK5 were markedly reduced or increased in NP cells transfected with the has-microRNA-222 mimic or inhibitor, respectively, whether or not they were stimulated with FSS. The overexpression or inhibition of microRNA-222 markedly accelerated or suppressed the apoptosis of FSS-stimulated NP cells, respectively. In the NP cells, the overexpression or inhibition of microRNA-222 massively inhibited or strengthened Aggrecan and type II collagen expression. Together, our data indicated that c-Fos was a target of microRNA-222, and was negatively regulated by microRNA-222 in NP cells. Our findings also suggested that microRNA-222 is a possible therapeutic target for IVDD because it regulates c-Fos.
Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes
Authors: Kumar Vikas , Doharey Pawan K. , Gulati Shelly , Meehan Joshua , Martinez Mary G. , Hughes Karrisa , Mooers Blaine H.M. , Cruz-Reyes Jorge 
Published: January 2019

AbstractUridylate insertion/deletion RNA editing inTrypanosoma bruceiis a complex system that is not found in humans, so there is interest in targeting this system for drug development. This system uses hundreds of small non-coding guide RNAs (gRNAs) to modify the mitochondrial mRNA transcriptome. This process occurs in holo-editosomes that assemble several macromoleculartransfactors around mRNA including the RNA-free RNA editing core complex (RECC) and auxiliary ribonucleoprotein (RNP) complexes. Yet, the regulatory mechanisms of editing remain obscure. The enzymatic accessory RNP complex, termed the REH2C, includes mRNA substrates and products, the multi-domain 240 kDa RNA Editing Helicase 2 (REH2) and an intriguing 8-zinc finger protein termed REH2-Associated Factor 1 (H2F1). Both of these proteins are essential in editing. REH2 is a member of the DExH/RHA subfamily of RNA helicases with a conserved C-terminus that includes a regulatory OB-fold domain. In trypanosomes,H2F1 recruits REH2 to the editing apparatus, andH2F1 downregulation causes REH2 fragmentation. Our systematic mutagenesis dissected determinants in REH2 andH2F1 for the assembly of REH2C, the stability of REH2, and the RNA-mediated association of REH2C with other editingtransfactors. We identified functional OB-fold amino acids in eukaryotic DExH/RHA helicases that are conserved in REH2 and that impact the assembly and interactions of REH2C.H2F1 upregulation stabilized REH2in vivo. Mutation of the core cysteines or basic amino acids in individual zinc fingers affected the stabilizing property ofH2F1 but not its interactions with other examined editing components. This result suggests that most, if not all, fingers may contribute to REH2 stabilization. Finally, a recombinant REH2 (240 kDa) established that the full-length protein is abona fideRNA helicase with ATP-dependent unwinding activity. REH2 is the only DExH/RHA-type helicase in kinetoplastid holo-editosomes.
Joints realized by sintering of pressureless Ag paste
Authors: Pietrikova Alena , Girasek Tomas , Livovsky Lubomir , Durisin Juraj , Saksl Karel 
Published: January 2019

PurposeThe purpose of this paper was to investigate an influence of a low temperature pressureless sintering process of silver paste on the quality of sintered joints.Design/methodology/approachThe authors analyzed various curing conditions of the paste during its sintering process: 175°C/90 min, 200°C/60 min, 250°C/30 min, 250°C/60 min, 350°C/30 min and 350°C/60 min. They analyzed an influence of the surface plating applied on a ceramic substrate/layer (Cu, Ag, AgPt and Au thick film) on the joints quality. The authors analyzed microstructure and electrical resistance of the joints. They evaluated these properties from the point of view of thermal aging process and changing resistance, after a constant current loading of the sintered joints.FindingsThe nanoscale pressureless silver paste can be applied for replacing a pressure-assisted micro-sized silver paste. It was found that the quality of the metal plating applied on the ceramic substrate/layer has a significant impact on the quality of the sintered joints. Copper and AgPt plating have better impact on quality of sintered joints in compare with Ag plating.Originality/valueThis investigation of the quality of the pressureless sintered joints at the silver-silver interface reveals an evident cracking immediately after the silver paste curing. Rapid sintering process typical for silver-based films on the substrate is because of the inter-diffusion between the micro and nanoparticles of silver at interfacial interface.
Optimal stable gait for nonlinear uncertain humanoid robot using central force optimization algorithm
Authors: Huan Tran Thien , Anh Ho Pham Huy 
Published: January 2019

Purpose
The purpose of this paper is to design a novel optimized biped robot gait generator which plays an important role in helping the robot to move forward stably. Based on a mathematical point of view, the gait design problem is investigated as a constrained optimum problem. Then the task to be solved is closely related to the evolutionary calculation technique.

Design/methodology/approach
Based on this fact, this paper proposes a new way to optimize the biped gait design for humanoid robots that allows stable stepping with preset foot-lifting magnitude. The newly proposed central force optimization (CFO) algorithm is used to optimize the biped gait parameters to help a nonlinear uncertain humanoid robot walk robustly and steadily. The efficiency of the proposed method is compared with the genetic algorithm, particle swarm optimization and improved differential evolution algorithm (modified differential evolution).

Findings
The simulated and experimental results carried out on the small-sized nonlinear uncertain humanoid robot clearly demonstrate that the novel algorithm offers an efficient and stable gait for humanoid robots with respect to accurate preset foot-lifting magnitude.

Originality/value
This paper proposes a new algorithm based on four key gait parameters that enable dynamic equilibrium in stable walking for nonlinear uncertain humanoid robots of which gait parameters are initiatively optimized with CFO algorithm.