bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting transmission blocking potential of anti-malarial compounds in the Mosquito Feeding Assay using Plasmodium falciparum Male Gamete Inhibition Assay
Authors: Colmenarejo Gonzalo , Lozano Sonia , González-Cortés Carolina , Calvo David , Sanchez-Garcia Juliana , Matilla Jesús-Luís Presa , Leroy Didier , Rodrigues Janneth 
Published: May 2018

AbstractPlasmodium falciparum Standard Membrane Feeding Assay (PfSMFA) is the current gold standard mosquito based confirmatory transmission blocking (TrB) assay for human malaria. However, owing to its complexity only selected gametocytocidal molecules are progressed into SMFA. Predictive tools for evaluation of TrB behavior of compounds in SMFA would be extremely beneficial, but lack of substantially large data sets from many mosquito feeds preempts the ability to perform correlations between outcomes from in vitro assays and SMFA. Here, a total of 44 different anti-malarial compounds were screened for inhibitory effect on male gamete formation in exflagellation inhibition assay (EIA) and the same drug-treated parasites were fed to mosquitoes in SMFA. Regression analysis was performed between outcomes of the two assays and regression models were applied to a randomly selected validation set of four compounds indicating no overfitting and good predictive power. In addition, the pIC50 for 11 different compounds obtained in the EIA was also correlated with pIC50’s in SMFA. Resulting regression models provided pIC50 predictions in SMFA with reasonably good accuracy thereby demonstrating the use of a simple in vitro assay to predict TrB of molecules in a complex mosquito based assay.
Experimental investigation of radiobiology in head and neck cancer cell lines as a function of HPV status, by MTT assay
Authors: Reid Paul , Wilson Puthenparampil , Li Yanrui , Marcu Loredana G. , Staudacher Alexander H. , Brown Michael P. , Bezak Eva 
Published: May 2018

AbstractHead and neck cancers (HNCs) are aggressive epithelial tumours frequently treated using radiation. HNC biology shows distinctions dependent on the oncologic involvement of the human papilloma virus (HPV). Clinically, HPV positive HNCs respond better to radiotherapy but few in vitro data demonstrate radiobiological differences explaining differences in clinical outcomes. This pilot study examined radiobiological responses to irradiation and subsequent regeneration in two HNC cell lines (HPV positive and negative). A novel approach was taken to develop generational cultures of HNC cell lines, UM-SCC-1 (HPV negative) and UM-SCC-47 (HPV positive). MTT assays were used to determine surviving metabolic activity as a function of dose following 6 MV X-ray irradiation. Parallel cultures surviving 4 Gy irradiation (not analysed) were re-cultured and passaged to develop subsequent generations which were re-irradiated and analysed for generational change in radiation response. Second and 3rd generations of UM-SCC-1 showed decreasing metabolic activity with dose but little difference was evident in surviving fractions between these generations. Significantly lower metabolic activity in the 3rd generation at <6 Gy, compared to the 2nd generation, showed UM-SCC-47 becoming progressively more radiosensitive. HPV positive UM-SCC-47 showed generational progression in radiosensitisation not seen in the HPV negative UM-SCC-1.
RNA-Seq and UHPLC-Q-TOF/MS Based Lipidomics Study in Lysiphlebia japonica
Authors: Gao Xueke , Luo Junyu , Lü Limin , Zhang LiJuan , Zhang Shuai , Cui Jinjie 
Published: May 2018

AbstractLipids play an important role in energy storage, membrane structure stabilization and signaling. Parasitoids are excellent models to study lipidomics because a majority of them do not accumulate during their free-living life-stage. Studies on parasitoids have mostly focused on the changes in the lipids and gene transcripts in hosts and little attention has been devoted to lipidomics and transcriptomics changes in parasitoids. In this study, a relative quantitative analysis of lipids and their gene transcripts in 3-days-old Lysiphlebia japonica larva (3 days after spawning) and pupae were performed using liquid chromatography, mass spectrometry and RNA-seq. Thirty-three glycerolipids and 250 glycerophospholipids were identified in this study; all triglycerides and the vast majority of phospholipids accumulated in the pupal stage. This was accompanied by differentially regulated lipid uptake and remolding. Furthermore, our data showed that gene transcription was up-regulated in key nutrient metabolic pathways involved in lipid synthesis in 3-days-old larvae. Finally, our data suggests that larva and pupa of L. japonica may lack the ability for fatty acids synthesis. A comprehensive, quantitative, and expandable resource was provided for further studies of metabolic regulation and molecular mechanisms underlying parasitic response to hosts defense.
Modeling Transcriptional Rewiring in Neutrophils Through the Course of Treated Juvenile Idiopathic Arthritis
Authors: Hu Zihua , Jiang Kaiyu , Frank Mark Barton , Chen Yanmin , Jarvis James N. 
Published: May 2018

AbstractNeutrophils in children with the polyarticular form of juvenile idiopathic arthritis (JIA) display abnormal transcriptional patterns linked to fundamental metabolic derangements. In this study, we sought to determine the effects of therapy on mRNA and miRNA expression networks in polyarticular JIA. Using exon and miRNA microarrays, we studied children with untreated active JIA (ADU, n = 35), children with active disease on therapy with methotrexate ± etanercept (ADT, n = 26), and children with inactive disease also on therapy (ID, n = 14). We compared the results to findings from healthy control children (HC, n = 35). We found substantial re-ordering of mRNA and miRNA expression networks after the initiation of therapy. Each disease state was associated with a distinct transcriptional profile, with the ADT state differing the most from HC, and ID more strongly resembling HC. Changes at the mRNA level were mirrored in changes in miRNA expression patterns. The analysis of the expression dynamics from differentially expressed genes across three disease states indicated that therapeutic response is a complex process. This process does not simply involve genes slowly correcting in a linear fashion over time. Computational modeling of miRNA and transcription factor (TF) co-regulatory networks demonstrated that combinational regulation of miRNA and TF might play an important role in dynamic transcriptome changes.
Development and evaluation of a novel system for inducing orthostatic challenge by tilt tests and lower body negative pressure
Authors: Dziuda Łukasz , Krej Mariusz , Śmietanowski Maciej , Sobotnicki Aleksander , Sobiech Mariusz , Kwaśny Piotr , Brzozowska Anna , Baran Paulina , Kowalczuk Krzysztof , Skibniewski Franciszek W. 
Published: May 2018

AbstractLower body negative pressure (LBNP) is a method derived from space medicine, which in recent years has been increasingly used by clinicians to assess the efficiency of the cardiovascular regulatory mechanisms. LBNP with combined tilt testing is considered as an effective form of training to prevent orthostatic intolerance. We have developed a prototype system comprising a tilt table and LBNP chamber, and tested it in the context of the feasibility of the device for assessing the pilots’ efficiency. The table allows for controlled tilting in the range from −45 to +80° at the maximum change rate of 45°/s. The LBNP value can smoothly be adjusted down to −100 mmHg at up to 20 mmHg/s. 17 subjects took part in the pilot study. A 24-minute scenario included −100 mmHg supine LBNP, head up tilt (HUT) and −60 mmHg LBNP associated with HUT, separated by resting phases. The most noticeable changes were observed in stroke volume (SV). During supine LBNP, HUT and the combined stimulus, a decrease of the SV value by 20%, 40% and below 50%, respectively, were detected. The proposed system can map any pre-programed tilt and LBNP profiles, and the pilot study confirmed the efficiency of performing experimental procedures.
Nanofocusing of structured light for quadrupolar light-matter interactions
Authors: Sakai Kyosuke , Yamamoto Takeaki , Sasaki Keiji 
Published: May 2018

AbstractThe spatial structure of an electromagnetic field can determine the characteristics of light-matter interactions. A strong gradient of light in the near field can excite dipole-forbidden atomic transitions, e.g., electric quadrupole transitions, which are rarely observed under plane-wave far-field illumination. Structured light with a higher-order orbital angular momentum state may also modulate the selection rules in which an atom can absorb two quanta of angular momentum: one from the spin and another from the spatial structure of the beam. Here, we numerically demonstrate a strong focusing of structured light with a higher-order orbital angular momentum state in the near field. A quadrupole field was confined within a gap region of several tens of nanometres in a plasmonic tetramer structure. A plasmonic crystal surrounding the tetramer structure provides a robust antenna effect, where the incident structured light can be strongly coupled to the quadrupole field in the gap region with a larger alignment tolerance. The proposed system is expected to provide a platform for light-matter interactions with strong multipolar effects.
Novel pathway of 3-hydroxyanthranilic acid formation in limazepine biosynthesis reveals evolutionary relation between phenazines and pyrrolobenzodiazepines
Authors: Pavlikova Magdalena , Kamenik Zdenek , Janata Jiri , Kadlcik Stanislav , Kuzma Marek , Najmanova Lucie 
Published: May 2018

AbstractNatural pyrrolobenzodiazepines (PBDs) form a large and structurally diverse group of antitumour microbial metabolites produced through complex pathways, which are encoded within biosynthetic gene clusters. We sequenced the gene cluster of limazepines and proposed their biosynthetic pathway based on comparison with five available gene clusters for the biosynthesis of other PBDs. Furthermore, we tested two recombinant proteins from limazepine biosynthesis, Lim5 and Lim6, with the expected substrates in vitro. The reactions monitored by LC-MS revealed that limazepine biosynthesis involves a new way of 3-hydroxyanthranilic acid formation, which we refer to as the chorismate/DHHA pathway and which represents an alternative to the kynurenine pathway employed for the formation of the same precursor in the biosynthesis of other PBDs. The chorismate/DHHA pathway is presumably also involved in the biosynthesis of PBD tilivalline, several natural products unrelated to PBDs, and its part is shared also with phenazine biosynthesis. The similarities between limazepine and phenazine biosynthesis indicate tight evolutionary links between these groups of compounds.
Comparative genomic analysis of Acinetobacter spp. plasmids originating from clinical settings and environmental habitats
Authors: Salto Ileana P. , Torres Tejerizo Gonzalo , Wibberg Daniel , Pühler Alfred , Schlüter Andreas , Pistorio Mariano 
Published: May 2018

AbstractBacteria belonging to the genus Acinetobacter have become of clinical importance over the last decade due to the development of a multi-resistant phenotype and their ability to survive under multiple environmental conditions. The development of these traits among Acinetobacter strains occurs frequently as a result of plasmid-mediated horizontal gene transfer. In this work, plasmids from nosocomial and environmental Acinetobacter spp. collections were separately sequenced and characterized. Assembly of the sequenced data resulted in 19 complete replicons in the nosocomial collection and 77 plasmid contigs in the environmental collection. Comparative genomic analysis showed that many of them had conserved backbones. Plasmid coding sequences corresponding to plasmid specific functions were bioinformatically and functionally analyzed. Replication initiation protein analysis revealed the predominance of the Rep_3 superfamily. The phylogenetic tree constructed from all Acinetobacter Rep_3 superfamily plasmids showed 16 intermingled clades originating from nosocomial and environmental habitats. Phylogenetic analysis of relaxase proteins revealed the presence of a new sub-clade named MOBQAci, composed exclusively of Acinetobacter relaxases. Functional analysis of proteins belonging to this group showed that they behaved differently when mobilized using helper plasmids belonging to different incompatibility groups.
Terahertz-driven polymerization of resists in nanoantennas
Authors: Park Woongkyu , Lee Youjin , Kang Taehee , Jeong Jeeyoon , Kim Dai-Sik 
Published: May 2018

AbstractPlasmon-mediated polymerization has been intensively studied for various applications including nanolithography, near-field mapping, and selective functionalization. However, these studies have been limited from the near-infrared to the ultraviolet regime. Here, we report a resist polymerization using intense terahertz pulses and various nanoantennas. The resist is polymerized near the nanoantennas, where giant field enhancement occurs. We experimentally show that the physical origin of the cross-linking is a terahertz electron emission from the nanoantenna, rather than multiphoton absorption. Our work extends nano-photochemistry into the terahertz frequencies.
ERCC1 rs11615 polymorphism increases susceptibility to breast cancer: a meta-analysis of 4547 individuals
Authors: Li Bingjie , Shi Xiaoqing , Yuan Yingying , Peng Mengle , Jin Huifang , Qin Dongchun 
Published: May 2018

Excision repair cross-complementation group 1 (ERCC1), a DNA repair protein, is vital for maintaining genomic fidelity and integrity. Despite the fact that a mounting body of case–control studies has concentrated on investigating the association of the ERCC1 rs11615 polymorphism and breast cancer risk, there is still no consensus on it. We conducted the current meta-analysis of all eligible articles to reach a much more explicit conclusion on this ambiguous association. A total of seven studies involving 2354 breast cancer cases and 2193 controls were elaborately selected for this analysis from the Embase, EBSCO, PubMed, WanFang, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated in our meta-analysis. We found that the ERCC1 rs11615 polymorphism was significantly associated with breast cancer risk under all genetic models. When excluded, the studies that deviated from Hardy–Weinberg equilibrium (HWE), the pooled results of what remained significantly increase the risk of breast cancer under the allele model (OR = 1.14, 95% CI = 1.02–1.27, P=0.02), heterozygote model (OR = 1.24, 95% CI = 1.06–1.44, P=0.007), and dominant model (OR = 1.21, 95% CI = 1.05–1.41, P=0.01). This increased breast cancer risk was found in Asian population as well as under the heterozygote model (OR = 1.24, 95% CI = 1.05–1.48, P=0.013) and dominant model (OR = 1.20, 95% CI = 1.02–1.42, P=0.03). Our results suggest that the ERCC1 rs11615 polymorphism is associated with breast cancer susceptibility, and in particular, this increased risk of breast cancer existence in Asian population.
Support for the value 5/2 for the spin glass lower critical dimension at zero magnetic field
Authors: Maiorano Andrea , Parisi Giorgio 
Published: May 2018

Significance
Glassy systems at low temperature may stay in many equilibrium configurations quite different from one another. An important quantity is the (free) energy difference for going from an equilibrium configuration to another one: Its properties dominate the dynamics at large times. The analytic computation of these differences is notoriously difficult. For spin glasses a clean computation can be done, using uncontrolled approximations. Here we use numerical simulations to show that this theory predicts the correct properties of the differences in three and four dimensions. The same theory predicts also that the spin glass transition disappears at dimensions 5/2 and our verification of the predictions of the theory brings support to this result.
Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria
Authors: Belliveau Nathan M. , Barnes Stephanie L. , Ireland William T. , Jones Daniel L. , Sweredoski Michael J. , Moradian Annie , Hess Sonja , Kinney Justin B. , Phillips Rob 
Published: May 2018

SignificanceOrganisms must constantly make regulatory decisions in response to a change in cellular state or environment. However, while the catalog of genomes expands rapidly, we remain ignorant about how the genes in these genomes are regulated. Here, we show how a massively parallel reporter assay, Sort-Seq, and information-theoretic modeling can be used to identify regulatory sequences. We then use chromatography and mass spectrometry to identify the regulatory proteins that bind these sequences. The approach results in quantitative base pair-resolution models of promoter mechanism and was shown in both well-characterized and unannotated promoters inEscherichia coli. Given the generality of the approach, it opens up the possibility of quantitatively dissecting the mechanisms of promoter function in a wide range of bacteria.
Invasion biology: searching for predictions and prevention, and avoiding lost causes.
Authors: Cassey P. , García-Díaz P. , Lockwood J. L. , Blackburn T. M. 
Published: May 2018

Abstract

The introduction and establishment of alien species is one of the many profound influences of ongoing anthropogenic global environmental change. Invasion biology has emerged as the interdisciplinary study of the patterns, processes and consequences of the redistribution of biodiversity across all environments and spatio-temporal scales. The modern discipline hinges on the knowledge that biological invasions cannot be defined and studied solely by their final outcome of establishing alien species but rather as a sequential series of stages, or barriers, that all alien species transit: the 'invasion pathway'. Some of the most important influences for a species transiting these sequential stages (i.e. transport, introduction, establishment and spread) are event-level effects, which vary independently of species and location, such as the number of individuals released in any given location (propagule pressure). The number of studies of biological invasions has increased exponentially over the past two decades, and we now have a significant body of research on different aspects of the invasion process. In particular, the hierarchical nature of the invasion pathway has lent itself strongly to modern statistical methods in hierarchical modelling. Now, the science behind invasive species management must continue to develop innovative ways of using this accumulated knowledge for delivering actionable management procedures.
The hierarchy-of-hypotheses approach.
Authors: Heger T. , Jeschke J. M. 
Published: May 2018

Abstract

Reviewing empirical evidence for major hypotheses in ecology is connected to two methodological challenges. First, all available empirical tests for a given hypothesis should be identified, collected and organized. This can be difficult due to divergent formulations of the hypothesis in the literature and divergent empirical approaches to address it. Second, the entire body of available data should be used to systematically assess the overall level of support of the hypothesis. Many approaches (e.g. formal meta-analyses) typically use only a fraction of the available data, often because of inconsistencies in the data. In this chapter, we show how the new hierarchy-of-hypotheses (HoH) approach can be used to overcome these challenges.
Hierarchy of hypotheses or hierarchy of predictions? Clarifying key concepts in ecological research.
Authors: Farji-Brener A. G. , Amador-Vargas S. 
Published: May 2018

Abstract

Hypotheses and predictions are the core of scientific research, and are fundamentally different. Nonetheless, predictions are constantly confused with hypotheses in the scientific literature. The hypothetic-deductive method starts with a question to which potential explanations - hypotheses - are proposed. Each hypothesis has expected outcomes - predictions - that are deduced assuming the hypothesis was true. In this chapter, we point out that the hierarchy-of-hypotheses (HoH) approach is confusing the terms hypothesis and prediction, and further explain why the so-called sub-hypotheses of the HoH approach are in fact predictions. We also propose an alternative approach inspired by the HoH approach to help arrange predictions by their potential to disprove the hypothesis.
Mapping theoretical and evidential landscapes in ecological science: Levins' virtue trade-off and the hierarchy-of-hypotheses approach.
Authors: Griesemer J. 
Published: May 2018

Abstract

According to Richard Levins, there is no single, best all-purpose model in ecology, nor can useful models simultaneously maximize theoretical virtues of generality, realism and precision (Levins, 1966, 1968a,b). A 'virtue trade-off' must be made if models are to be useful for understanding, explanation, prediction or control. Recently, large-scale data synthesis projects have aimed to systematically review many empirical studies to evaluate major hypotheses. A specific version of systematic review called the 'hierarchy-of-hypotheses' approach has been proposed (Jeschke et al., 2012; Heger and Jeschke, 2014; and Chapter 2, this volume). I argue that investigation of the patchwork of models organized by Levins' theoretical 'virtue space' and discovery of robust theorems across a theoretical landscape could be enhanced by recent efforts to manage evidential complexity in a patchwork of empirical studies by the hierarchy-of-hypotheses approach.
A hierarchy of hypotheses or a network of models.
Authors: Scheiner S. M. , Fox G. A. 
Published: May 2018

Abstract

Many different explanations for biological invasions have been proposed, yet there is little evidence that any of them are general. Invasion biologists are increasingly favouring a multicausal outlook rather than seeking single explanations of invasions, or seeking to identify a list of characteristics of invasive species. The time is ripe for systematization of ideas in invasion biology. The hierarchy-of-hypotheses (HoH) framework proposed by Jeschke and Heger thus comes at an opportune moment but we believe that it must be modified substantially to be useful. A principal problem is the notion that science proceeds simply by testing hypotheses, which neglects the roles of models (the source of hypotheses) and of the broader constitutive theories that give rise to models. Accepting or rejecting hypotheses seems to us a doomed approach for complex phenomena like invasions, in which multiple causes are likely to account for the differences between invading and native populations. This multicausality also means that explanations for invasions are not likely to be strictly hierarchical. Finally, the criteria proposed for retaining hypotheses in the HoH - support by a majority of empirical studies - is ad hoc and beset by severe statistical problems. We argue that examination of a network of models - rather than a hierarchy of hypotheses - is needed to move the field forward.
The hierarchy-of-hypotheses approach updated - a toolbox for structuring and analysing theory, research and evidence.
Authors: Heger T. , Jeschke J. M. 
Published: May 2018

Abstract

In Chapters 3, 4 and 5, three groups of authors have commented on the hierarchy-of-hypotheses (HoH) approach as introduced in Chapter 2. Here, we make suggestions on how to account for the issues raised in Chapters 3-5, whilst also considering several comments by other colleagues that we received during discussions or in response to our presentations on this topic. We focus on five issues and address each in a separate section of this chapter. In the concluding section, we suggest treating the HoH approach as a toolbox; we describe its core as well as an array of modules that can be chosen.