bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive evaluation of module detection methods for gene expression data
Authors: Saelens Wouter , Cannoodt Robrecht , Saeys Yvan 
Published: March 2018

AbstractA critical step in the analysis of large genome-wide gene expression datasets is the use of module detection methods to group genes into co-expression modules. Because of limitations of classical clustering methods, numerous alternative module detection methods have been proposed, which improve upon clustering by handling co-expression in only a subset of samples, modelling the regulatory network, and/or allowing overlap between modules. In this study we use known regulatory networks to do a comprehensive and robust evaluation of these different methods. Overall, decomposition methods outperform all other strategies, while we do not find a clear advantage of biclustering and network inference-based approaches on large gene expression datasets. Using our evaluation workflow, we also investigate several practical aspects of module detection, such as parameter estimation and the use of alternative similarity measures, and conclude with recommendations for the further development of these methods.
Enabling Controlling Complex Networks with Local Topological Information
Authors: Li Guoqi , Deng Lei , Xiao Gaoxi , Tang Pei , Wen Changyun , Hu Wuhua , Pei Jing , Shi Luping , Stanley H. Eugene 
Published: March 2018

AbstractComplex networks characterize the nature of internal/external interactions in real-world systems including social, economic, biological, ecological, and technological networks. Two issues keep as obstacles to fulfilling control of large-scale networks: structural controllability which describes the ability to guide a dynamical system from any initial state to any desired final state in finite time, with a suitable choice of inputs; and optimal control, which is a typical control approach to minimize the cost for driving the network to a predefined state with a given number of control inputs. For large complex networks without global information of network topology, both problems remain essentially open. Here we combine graph theory and control theory for tackling the two problems in one go, using only local network topology information. For the structural controllability problem, a distributed local-game matching method is proposed, where every node plays a simple Bayesian game with local information and local interactions with adjacent nodes, ensuring a suboptimal solution at a linear complexity. Starring from any structural controllability solution, a minimizing longest control path method can efficiently reach a good solution for the optimal control in large networks. Our results provide solutions for distributed complex network control and demonstrate a way to link the structural controllability and optimal control together.
A Mathematical Model for the Sounds Produced by Knuckle Cracking
Authors: Chandran Suja V. , Barakat A. I. 
Published: March 2018

AbstractThe articular release of the metacarpophalangeal joint produces a typical cracking sound, resulting in what is commonly referred to as the cracking of knuckles. Despite over sixty years of research, the source of the knuckle cracking sound continues to be debated due to inconclusive experimental evidence as a result of limitations in the temporal resolution of non-invasive physiological imaging techniques. To support the available experimental data and shed light onto the source of the cracking sound, we have developed a mathematical model of the events leading to the generation of the sound. The model resolves the dynamics of a collapsing cavitation bubble in the synovial fluid inside a metacarpophalangeal joint during an articular release. The acoustic signature from the resulting bubble dynamics is shown to be consistent in both magnitude and dominant frequency with experimental measurements in the literature and with our own experiments, thus lending support for cavitation bubble collapse as the source of the cracking sound. Finally, the model also shows that only a partial collapse of the bubble is needed to replicate the experimentally observed acoustic spectra, thus allowing for bubbles to persist following the generation of sound as has been reported in recent experiments.
The mode and dynamics of glioblastoma cell invasion into a decellularized tissue-derived extracellular matrix-based three-dimensional tumor model
Authors: Koh IlKyoo , Cha Junghwa , Park Junseong , Choi Junjeong , Kang Seok-Gu , Kim Pilnam 
Published: March 2018

AbstractGlioblastoma multiforme (GBM) is the most common brain tumor with very aggressive and infiltrative. Extracellular matrix (ECM) plays pivotal roles in the infiltrative characteristics of GBM. To understand the invasive characteristic of GBM, it is necessary to study cell-ECM interaction in the physiologically relevant biomimetic model that recapitulates the GBM-specific ECM microenvironment. Here, we propose biomimetic GBM-specific ECM microenvironment for studying mode and dynamics of glioblastoma cell invasion. Using tissue decellularization process, we constructed a patient tissue-derived ECM (pdECM)-based three-dimensional in vitro model. In our model, GBM cells exhibited heterogeneous morphology and altered the invasion routes in a microenvironment-adaptive manner. We further elucidate the effects of inhibition of ECM remodeling-related enzymatic activity (Matrix metalloproteinase (MMP) 2/9, hyaluronan synthase (HAS)) on GBM cell invasion. Interestingly, after blocking both enzyme activity, GBM cells underwent morphological transition and switch the invasion mode. Such adaptability could render cell invasion resistant to anti-cancer target therapy. There results provide insight of how organ-specific matrix differentially regulates cancer cell phenotype, and have significant implications for the design of matrix with appropriate physiologically relevant properties for in vitro tumor model.
Seasonal bacterial community succession in four typical wastewater treatment plants: correlations between core microbes and process performance
Authors: Zhang Bo , Yu Quanwei , Yan Guoqi , Zhu Hubo , Xu Xiang yang , Zhu Liang 
Published: March 2018

AbstractTo understand the seasonal variation of the activated sludge (AS) bacterial community and identify core microbes in different wastewater processing systems, seasonal AS samples were taken from every biological treatment unit within 4 full-scale wastewater treatment plants. These plants adopted A2/O, A/O and oxidation ditch processes and were active in the treatment of different types and sources of wastewater, some domestic and others industrial. The bacterial community composition was analyzed using high-throughput sequencing technology. The correlations among microbial community structure, dominant microbes and process performance were investigated. Seasonal variation had a stronger impact on the AS bacterial community than any variation within different wastewater treatment system. Facing seasonal variation, the bacterial community within the oxidation ditch process remained more stable those in either the A2/O or A/O processes. The core genera in domestic wastewater treatment systems were Nitrospira, Caldilineaceae, Pseudomonas and Lactococcus. The core genera in the textile dyeing and fine chemical industrial wastewater treatment systems were Nitrospira, Thauera and Thiobacillus.
Cascaded neural networks improving fish species prediction accuracy: the role of the biotic information
Authors: Franceschini Simone , Gandola Emanuele , Martinoli Marco , Tancioni Lorenzo , Scardi Michele 
Published: March 2018

AbstractSpecies distribution is the result of complex interactions that involve environmental parameters as well as biotic factors. However, methodological approaches that consider the use of biotic variables during the prediction process are still largely lacking. Here, a cascaded Artificial Neural Networks (ANN) approach is proposed in order to increase the accuracy of fish species occurrence estimates and a case study forLeucos aulain NE Italy is presented as a demonstration case. Potentially useful biotic information (i.e. occurrence of other species) was selected by means of tetrachoric correlation analysis and on the basis of the improvements it allowed to obtain relative to models based on environmental variables only. The prediction accuracy of theL.aulamodel based on environmental variables only was improved by the addition of occurrence data forA.arborellaandS.erythrophthalmus. While biotic information was needed to train the ANNs, the final cascaded ANN model was able to predictL.aulabetter than a conventional ANN using environmental variables only as inputs. Results highlighted that biotic information provided by occurrence estimates for non-target species whose distribution can be more easily and accurately modeled may play a very useful role, providing additional predictive variables to target species distribution models.
Functional analysis of the Drosophila RhoGAP Cv-c protein and its equivalence to the human DLC3 and DLC1 proteins
Authors: Sotillos Sol , Aguilar-Aragon Mario , Hombría James Castelli-Gair 
Published: March 2018

AbstractRhoGAP proteins control the precise regulation of the ubiquitous small RhoGTPases. The Drosophila Crossveinless-c (Cv-c) RhoGAP is homologous to the human tumour suppressor proteins Deleted in Liver Cancer 1–3 (DLC1-3) sharing an identical arrangement of SAM, GAP and START protein domains. Here we analyse in Drosophila the requirement of each Cv-c domain to its function and cellular localization. We show that the basolateral membrane association of Cv-c is key for its epithelial function and find that the GAP domain targeted to the membrane can perform its RhoGAP activity independently of the rest of the protein, implying the SAM and START domains perform regulatory roles. We propose the SAM domain has a repressor effect over the GAP domain that is counteracted by the START domain, while the basolateral localization is mediated by a central, non-conserved Cv-c region. We find that DLC3 and Cv-c expression in the Drosophila ectoderm cause identical effects. In contrast, DLC1 is inactive but becomes functional if the central non-conserved DLC1 domain is substituted for that of Cv-c. Thus, these RhoGAP proteins are functionally equivalent, opening up the use of Drosophila as an in vivo model to analyse pharmacologically and genetically the human DLC proteins.
Cardiac Actions of a Small Molecule Inhibitor Targeting GATA4–NKX2-5 Interaction
Authors: Kinnunen Sini M. , Tölli Marja , Välimäki Mika J. , Gao Erhe , Szabo Zoltan , Rysä Jaana , Ferreira Mónica P. A. , Ohukainen Pauli , Serpi Raisa , Correia Alexandra , Mäkilä Ermei , Salonen Jarno , Hirvonen Jouni , Santos Hélder A. , Ruskoaho Heikki 
Published: March 2018

AbstractTranscription factors are fundamental regulators of gene transcription, and many diseases, such as heart diseases, are associated with deregulation of transcriptional networks. In the adult heart, zinc-finger transcription factor GATA4 is a critical regulator of cardiac repair and remodelling. Previous studies also suggest that NKX2-5 plays function role as a cofactor of GATA4. We have recently reported the identification of small molecules that either inhibit or enhance the GATA4–NKX2-5 transcriptional synergy. Here, we examined the cardiac actions of a potent inhibitor (3i-1000) of GATA4–NKX2-5 interaction in experimental models of myocardial ischemic injury and pressure overload. In mice after myocardial infarction, 3i-1000 significantly improved left ventricular ejection fraction and fractional shortening, and attenuated myocardial structural changes. The compound also improved cardiac function in an experimental model of angiotensin II -mediated hypertension in rats. Furthermore, the up-regulation of cardiac gene expression induced by myocardial infarction and ischemia reduced with treatment of 3i-1000 or when micro- and nanoparticles loaded with 3i-1000 were injected intramyocardially or intravenously, respectively. The compound inhibited stretch- and phenylephrine-induced hypertrophic response in neonatal rat cardiomyocytes. These results indicate significant potential for small molecules targeting GATA4–NKX2-5 interaction to promote myocardial repair after myocardial infarction and other cardiac injuries.
Rare variants in drug target genes contributing to complex diseases, phenome-wide
Authors: Verma Shefali Setia , Josyula Navya , Verma Anurag , Zhang Xinyuan , Veturi Yogasudha , Dewey Frederick E. , Hartzel Dustin N. , Lavage Daniel R. , Leader Joe , Ritchie Marylyn D. , Pendergrass Sarah A. 
Published: March 2018

AbstractThe DrugBank database consists of ~800 genes that are well characterized drug targets. This list of genes is a useful resource for association testing. For example, loss of function (LOF) genetic variation has the potential to mimic the effect of drugs, and high impact variation in these genes can impact downstream traits. Identifying novel associations between genetic variation in these genes and a range of diseases can also uncover new uses for the drugs that target these genes. Phenome Wide Association Studies (PheWAS) have been successful in identifying genetic associations across hundreds of thousands of diseases. We have conducted a novel gene based PheWAS to test the effect of rare variants in DrugBank genes, evaluating associations between these genes and more than 500 quantitative and dichotomous phenotypes. We used whole exome sequencing data from 38,568 samples in Geisinger MyCode Community Health Initiative. We evaluated the results of this study when binning rare variants using various filters based on potential functional impact. We identified multiple novel associations, and the majority of the significant associations were driven by functionally annotated variation. Overall, this study provides a sweeping exploration of rare variant associations within functionally relevant genes across a wide range of diagnoses.
Assessment of intrinsic and extrinsic signaling pathway in excitotoxic retinal ganglion cell death
Authors: Fahrenthold Berkeley K. , Fernandes Kimberly A. , Libby Richard T. 
Published: March 2018

AbstractExcitotoxicity leads to the activation of a cytotoxic cascade that causes neuronal death. In the retina, retinal ganglion cells (RGCs) die after an excitotoxic insult. Multiple pathways have been proposed to contribute to RGC death after an excitotoxic insult, including TNF signaling, JNK activation, and ER stress. To test the importance of these pathways in RGC death after excitotoxic injury, the excitotoxin N-methyl-D-aspartate (NMDA) was intravitreally injected into mice deficient in components of these pathways. Absence ofTnfor its canonical downstream mediator,Bid, did not confer short- or long-term protection to RGCs. Despite known activation in RGCs and a prominent role in mediating RGC death after other insults, attenuating JNK signaling did not prevent RGC death after excitotoxic insult. Additionally, deficiency of the ER stress protein DDIT3 (CHOP), which has been shown to be involved in RGC death, did not lessen NMDA induced RGC death. Furthermore, absence of bothJun(JNK’s canonical target) andDdit3, which together provide robust, long-term protection to RGC somas after axonal insult, did not lessen RGC death. Collectively, these results indicate that the drivers of excitotoxic injury remain to be identified and/or multiple cell death pathways are activated in response to injury.
Fusion of a highly N-glycosylated polypeptide increases the expression of ER-localized proteins in plants
Authors: Kang Hyangju , Park Youngmin , Lee Yongjik , Yoo Yun-Joo , Hwang Inhwan 
Published: March 2018

AbstractPlants represent promising systems for producing various recombinant proteins. One key area of focus for improving this technology is developing methods for producing recombinant proteins at high levels. Many methods have been developed to increase the transcript levels of recombinant genes. However, methods for increasing protein production involving steps downstream of transcription, including translation, have not been fully explored. Here, we investigated the effects of N-glycosylation on protein production and provide evidence that N-glycosylation greatly increases the expression levels of ER-targeted recombinant proteins. Fusion of the extracellular domain (M domain) of protein tyrosine phosphatase receptor type C (CD45), which contains four putative N-glycosylation sites to a model protein, leptin at the C-terminus, increased recombinant protein levels by 6.1 fold. This increase was specific to ER-targeted proteins and was dependent on N-glycosylation. Moreover, expression levels of leptin, leukemia inhibitory factor and GFP were also greatly increased by fusion of M domain at either the N or C-terminus. Furthermore, the increase in protein levels resulted from enhanced translation, but not transcription. Based on these results, we propose that fusing a small domain containing N-glycosylation sites to target proteins is a powerful technique for increasing the expression levels of recombinant proteins in plants.
Exploring Ugi-Azide Four-Component Reaction Products for Broad-Spectrum Influenza Antivirals with a High Genetic Barrier to Drug Resistance
Authors: Zhang Jiantao , Hu Yanmei , Foley Christopher , Wang Yuanxiang , Musharrafieh Rami , Xu Shuting , Zhang Yongtao , Ma Chunlong , Hulme Christopher , Wang Jun 
Published: March 2018

AbstractInfluenza viruses are respiratory pathogens that are responsible for seasonal influenza and sporadic influenza pandemic. The therapeutic efficacy of current influenza vaccines and small molecule antiviral drugs is limited due to the emergence of multidrug-resistant influenza viruses. In response to the urgent need for the next generation of influenza antivirals, we utilized a fast-track drug discovery platform by exploring multi-component reaction products for antiviral drug candidates. Specifically, molecular docking was applied to screen a small molecule library derived from the Ugi-azide four-component reaction methodology for inhibitors that target the influenza polymerase PAC-PB1N interactions. One hit compound 5 was confirmed to inhibit PAC-PB1N interactions in an ELISA assay and had potent antiviral activity in an antiviral plaque assay. Subsequent structure-activity relationship studies led to the discovery of compound 12a, which had broad-spectrum antiviral activity and a higher in vitro genetic barrier to drug resistance than oseltamivir. Overall, the discovery of compound 12a as a broad-spectrum influenza antiviral with a high in vitro genetic barrier to drug resistance is significant, as it offers a second line of defense to combat the next influenza epidemics and pandemics if vaccines and oseltamivir fail to confine the disease outbreak.
In situ immobilisation of toxic metals in soil using Maifan stone and illite/smectite clay
Authors: Ou Jieyong , Li Hong , Yan Zengguang , Zhou Youya , Bai Liping , Zhang Chaoyan , Wang Xuedong , Chen Guikui 
Published: March 2018

AbstractClay minerals have been proposed as amendments for remediating metal-contaminated soils owing to their abundant reserves, high performance, simplicity of use and low cost. Two novel clay minerals, Maifan stone and illite/smectite clay, were examined in the in situ immobilisation of soil metals. The application of 0.5% Maifan stone or illite/smectite clay to field soils significantly decreased the fractions of diethylenetriaminepentaacetic acid (DTPA)-extractable Cd, Ni, Cr, Zn, Cu and Pb. Furthermore, reductions of 35.4% and 7.0% in the DTPA-extractable fraction of Cd were obtained with the Maifan stone and illite/smectite clay treatments, respectively, which also significantly reduced the uptake of Cd, Ni, Cr, Zn, Cu and Pb in the edible parts of Brassica rapa subspecies pekinensis, Brassica campestris and Spinacia oleracea. Quantitatively, the Maifan stone treatment reduced the metal uptake in B. rapa ssp. Pekinensis, B. campestris and S. oleracea from 11.6% to 62.2%, 4.6% to 41.8% and 11.3% to 58.2%, respectively, whereas illite/smectite clay produced reductions of 8.5% to 62.8% and 4.2% to 37.6% in the metal uptake in B. rapa ssp. Pekinensis and B. campestris, respectively. Therefore, both Maifan stone and illite/smectite clay are promising amendments for contaminated soil remediation.
The evolution of insecticide resistance in the brown planthopper (Nilaparvata lugens Stål) of China in the period 2012–2016
Authors: Wu Shun-Fan , Zeng Bin , Zheng Chen , Mu Xi-Chao , Zhang Yong , Hu Jun , Zhang Shuai , Gao Cong-Fen , Shen Jin-Liang 
Published: March 2018

AbstractThe brown planthopper,Nilaparvata lugens, is an economically important pest on rice in Asia. Chemical control is still the most efficient primary way for rice planthopper control. However, due to the intensive use of insecticides to control this pest over many years, resistance to most of the classes of chemical insecticides has been reported. In this article, we report on the status of eight insecticides resistance inNilaparvata lugens(Stål) collected from China over the period 2012–2016. All of the field populations collected in 2016 had developed extremely high resistance to imidacloprid, thiamethoxam, and buprofezin. Synergism tests showed that piperonyl butoxide (PBO) produced a high synergism of imidacloprid, thiamethoxam, and buprofezin effects in the three field populations, YA2016, HX2016, and YC2016. Functional studies using both double-strand RNA (dsRNA)-mediated knockdown in the expression ofCYP6ER1and transgenic expression ofCYP6ER1inDrosophila melanogastershowed thatCYP6ER1confers imidacloprid, thiamethoxam and buprofezin resistance. These results will be beneficial for effective insecticide resistance management strategies to prevent or delay the development of insecticide resistance in brown planthopper populations.
Analytical prediction of the piezoelectric d33 response of fluoropolymer arrays with tubular air channels
Authors: Zhukov Sergey , Eder-Goy Dagmar , Fedosov Sergey , Xu Bai-Xiang , von Seggern Heinz 
Published: March 2018

AbstractThe present study is focused on tubular multi-channel arrays composed of commercial fluoropolymer (FEP) tubes with different wall thickness. After proper charging in a high electric field, such tubular structures exhibit a large piezoelectric $${{\boldsymbol{d}}}_{{\bf{33}}}$$

d

33

coefficient significantly exceeding the values of classical polymer ferroelectrics and being even comparable to conventional lead-free piezoceramics. The quasistatic piezoelectric $${{\boldsymbol{d}}}_{{\bf{33}}}$$

d

33

coefficient was theoretically derived and its upper limits were evaluated considering charging and mechanical properties of the arrays. In order to optimize the $${{\boldsymbol{d}}}_{{\bf{33}}}$$

d

33

coefficient the remanent polarization and the mechanical properties were taken into account, both being strongly dependent on the air channel geometry as well as on the wall thickness of the FEP tubes. The model predictions are compared with experimental d33 coefficients for two particular arrays with equal air gaps of 250 μm, but with different wall thickness of utilized FEP tubes of 50 μm and 120 μm, respectively. Analytical modeling allows for the prediction that arrays made of FEP tubes with a wall thickness of 10 μm are foreseen to exhibit a superb piezoelectric response of up to 600 pC/N if the height of stadium-like shaped air channels is reduced down to 50 μm, making them potentially interesting for application as highly sensitive sensors and energy harvesting.