bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis
Authors: Hammond Jennetta W. , Bellizzi Matthew J. , Ware Caroline , Qiu Wen Q. , Saminathan Priyanka , Li Herman , Luo Shaopeiwen , Li Yuanhao , Gelbard Harris A. 
Published: August 2019

AbstractMultiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the CNS characterized by both grey and white matter injury. Microglial activation and a reduction in synaptic density are key features of grey matter pathology that can be modeled with experimental autoimmune encephalomyelitis (EAE). Complement deposition combined with microglial engulfment has been shown during normal development and in disease as a mechanism for pruning synapses. We tested whether there is excess complement production in the EAE hippocampus and whether complement-dependent synapse loss is a source of degeneration in EAE using C1qa and C3 knockout mice. We found that C1q and C3 protein levels were elevated in EAE mice. Genetic loss of C1qa provided a small degree of protection from EAE-induced decreases in synaptic density. However, C1qa knockout EAE mice had similar levels of microglial activation and identical clinical scores as WT EAE mice. C3 knockout mice were largely protected from EAE-induced synapse loss and microglial activation, results that correlated with a reduction in the EAE clinical score. Thus, pathologic expression and activation of the early complement pathway drives a portion of the synapse elimination observed in the EAE grey matter.
Translocational unfolding in clostridial binary iota toxin complex
Authors: Yamada Tomohiro , Yoshida Toru , Kawamoto Akihiro , Mitsuoka Kaoru , Iwasaki Kenji , Tsuge Hideaki 
Published: August 2019

AbstractProtein translocation across the membrane is critical for microbial pathogenesis and various cellular functions. Bacterial binary toxins such as anthrax toxin are composed of enzyme components and a translocation channel, which catalyses substrate unfolding and translocation. Here we report the structures of the clostridial binary toxin (iota toxin) translocation channel Ib-pore and its complex with ADP-ribosyltransferase Ia. The Ib-pore structure at atomic resolution provides a similar structural framework as observed for the catalytic ϕ-clamp of the anthrax protective antigen pore. However, the Ia-bound Ib-pore structure showed a unique binding mode of Ia: one Ia binds to the Ib-pore, and the Ia N-terminal domain interacts with Ib via two other Ib-pore bottlenecks with multiple weak interactions. Furthermore, Ib-binding induces Ia N-terminal α-helix tilting and partial unfolding, whereupon the unfolded N-terminus continues to the ϕ-clamp gate. This study reveals the novel mechanism of N-terminal unfolding, which is crucial for protein translocation.
Functional characterization ofRalstonia insidiosa, a bona fide resident at the maternal-fetal interface
Authors: Parnell Lindsay A. , Willsey Graham G. , Joshi Chetanchandra S. , Yin Yin , Wargo Matthew J. , Mysorekar Indira U. 
Published: August 2019

AbstractControversy about whether there are microbes in the placenta and if they have any functional importance during pregnancy and for neonatal health is ongoing. Previous work has demonstrated that the basal plate (BP), comprising maternal and fetal derived cells harbors intracellular bacteria. 16S sequencing and bacterial species-specific analysis of term placentas revealed that the gram-negative bacillusRalstonia insidiosa, native to aqueous environments and an effective biofilm promoter, comprises the most abundant species in the BP. Here, we demonstrate whetherR. insidiosacells home to a particular niche in the BP, how they may arrive there, and whether they are associated with adverse outcomes. We developed methods to detect and study cell-specific localization ofR. insidiosausing ex vivo and in vitro models. Additionally, we studied potential routes ofR. insidiosaentry into the placenta. We show thatR. insidiosais a bona fide resident in human placental BP. It can access trophoblast cells in culture and within basal plate tissues where it localizes to intracellular single-membrane vacuoles and can replicate. However, the presence ofR. insidiosadoes not cause cell death and does not induce a pro-inflammatory immune response suggesting that it is not harmful in and of itself. Finally, we show that in a pregnant mouse model,R. insidiosatraffics to the placenta via the intrauterine route but does not induce preterm labor or preterm birth. Together, our findings provide a foundation for understanding non-pathogenic placental cell-microbe interactions and the functional importance ofR. insidiosain placental health and physiology.
Statistical inference for the evolutionary history of cancer genomes
Authors: Dinh K. N. , Jaksik R. , Kimmel M. , Lambert A. , Tavaré S. 
Published: August 2019

AbstractRecent years have produced a large amount of work on inference about cancer evolution from mutations identified in cancer samples. Much of the modeling work has been based on classical models of population genetics, generalized to accommodate time-varying cell population size. Reverse-time genealogical views of such models, commonly known as coalescents, have been used to infer aspects of the past of growing populations. Another approach is to use branching processes, the simplest scenario being the linear birth-death process (lbdp), a binary fission Markov age-dependent branching process. A genealogical view of such models is also available. The two approaches lead to similar but not identical results. Inference from evolutionary models of DNA often exploits summary statistics of the sequence data, a common one being the so-called Site Frequency Spectrum (SFS). In a sequencing experiment with a known number of sequences, we can estimate for each site at which a novel somatic mutation has arisen, the number of cells that carry that mutation. These numbers are then grouped into sites which have the same number of copies of the mutant. SFS can be computed from the statistics of mutations in a sample of cells, in which DNA has been sequenced. In this paper, examine how the SFS based on birth-death processes differ from those based on the coalescent model. This may stem from the different sampling mechanisms in the two approaches. However, we also show mathematically and computationally that despite this, they can be made quantitatively comparable at least for the range of parameters typical for tumor cell populations. We also present a model of tumor evolution with selective sweeps, based on coalescence, and demonstrate how it may help in understanding the past history of tumor as well the influence of data pre-processing. We illustrate the theory with applications to several examples of The Cancer Genome Atlas tumors.
Validating the Cyc2 neutrophilic Fe oxidation pathway using meta-omics of Zetaproteobacteria iron mats at marine hydrothermal vents
Authors: McAllister Sean M. , Polson Shawn W. , Butterfield David A. , Glazer Brian T. , Sylvan Jason B. , Chan Clara S. 
Published: August 2019

AbstractZetaproteobacteria create extensive iron (Fe) oxide mats at marine hydrothermal vents, making them an ideal model for microbial Fe oxidation at circumneutral pH. Comparison of neutrophilic Fe-oxidizer isolate genomes has revealed a hypothetical Fe oxidation pathway, featuring a homolog of the Fe oxidase Cyc2 from Acidithiobacillus ferrooxidans. However, Cyc2 function is not well verified in neutrophilic Fe-oxidizers, particularly in Fe-oxidizing environments. Toward this, we analyzed genomes and metatranscriptomes of Zetaproteobacteria, using 53 new high-quality metagenome assembled genomes reconstructed from Fe mats at Mid-Atlantic Ridge, Mariana Backarc, and Loihi Seamount (Hawaii) hydrothermal vents. Phylogenetic analysis demonstrated conservation of Cyc2 sequences among most neutrophilic Fe-oxidizers, suggesting a common function. We confirmed the widespread distribution of cyc2 and other model Fe oxidation pathway genes across all represented Zetaproteobacteria lineages. High expression of these genes was observed in diverse Zetaproteobacteria under multiple environmental conditions, and in incubations. The putative Fe oxidase gene, cyc2, was highly expressed in situ, often as the top expressed gene. The cyc2 gene showed increased expression in Fe(II)-amended incubations, with corresponding increases in carbon fixation and central metabolism gene expression. These results substantiate the Cyc2-based Fe oxidation pathway in neutrophiles and demonstrate its significance in marine Fe-mineralizing environments.
Intraspecific difference among herbivore lineages and their host-plant specialization drive the strength of trophic cascades
Authors: Sentis Arnaud , Bertram Raphaël , Dardenne Nathalie , Simon Jean-Christophe , Magro Alexandra , Pujol Benoit , Danchin Etienne , Hemptinne Jean-Louis 
Published: August 2019

AbstractTrophic cascades—the indirect effect of predators on non-adjacent lower trophic levels—are important drivers of the structure and dynamics of ecological communities. However, the influence of intraspecific trait variation on the strength of trophic cascade remains largely unexplored, which limits our understanding of the mechanisms underlying ecological networks. Here we experimentally investigated how intraspecific difference among herbivore lineages specialized on different host plants influences the strength of trophic cascade in a terrestrial tritrophic system. We found that the occurrence and strength of the trophic cascade are strongly influenced by herbivores’ lineage and host-plant specialization but are not associated with density-dependent effects mediated by the growth rate of herbivore populations. Our findings stress the importance of intraspecific heterogeneities and evolutionary specialization as drivers of the strength of trophic cascades and underline that intraspecific variation should not be overlooked to decipher the joint influence of evolutionary and ecological factors on the functioning of multi-trophic interactions.
Predictive coding account of action perception: Evidence from effective connectivity in the Action Observation Network
Authors: Urgen Burcu A. , Saygin Ayse P. 
Published: August 2019

AbstractVisual perception of actions is supported by a network of brain regions in the occipito-temporal, parietal, and premotor cortex in the primate brain, known as the Action Observation Network (AON). Although there is a growing body of research that characterizes the functional properties of each node of this network, the communication and direction of information flow between the nodes is unclear. According to the predictive coding account of action perception, this network is not a purely feedforward system but has feedback connections through which prediction error signals are communicated between the regions of the AON. In the present study, we investigated the effective connectivity of the AON in an experimental setting where the human subjects’ predictions about the observed agent were violated, using fMRI and Dynamical Causal Modeling (DCM). We specifically examined the influence of the lowest and highest nodes in the AON hierarchy, pSTS and ventral premotor cortex, respectively, on the middle node, inferior parietal cortex during prediction violation. Our DCM results suggest that the influence on the inferior parietal node is through a feedback connection from ventral premotor cortex during perception of actions that violate people’s predictions.
Assembly methods for nanopore-based metagenomic sequencing: a comparative study
Authors: Latorre-Pérez Adriel , Villalba-Bermell Pascual , Pascual Javier , Porcar Manuel , Vilanova Cristina 
Published: August 2019

ABSTRACTBackgroundMetagenomic sequencing has lead to the recovery of previously unexplored microbial genomes. In this sense, short-reads sequencing platforms often result in highly fragmented metagenomes, thus complicating downstream analyses. Third generation sequencing technologies, such as MinION, could lead to more contiguous assemblies due to their ability to generate long reads. Nevertheless, there is a lack of studies evaluating the suitability of the available assembly tools for this new type of data.FindingsWe benchmarked the ability of different short-reads and long-reads tools to assembly two different commercially available mock communities, and observed remarkable differences in the resulting assemblies depending on the software of choice. Short-reads metagenomic assemblers proved unsuitable for MinION data. Among the long-reads assemblers tested, Flye and Canu were the only ones performing well in all the datasets. These tools were able to retrieve complete individual genomes directly from the metagenome, and assembled a bacterial genome in only two contigs in the best scenario. Despite the intrinsic high error of long-reads technologies, Canu and Flye lead to high accurate assemblies (~99.4-99.8 % of accuracy). However, errors still had an impact on the prediction of biosynthetic gene clusters.ConclusionsMinION metagenomic sequencing data proved sufficient for assembling low-complex microbial communities, leading to the recovery of highly complete and contiguous individual genomes. This work is the first systematic evaluation of the performance of different assembly tools on MinION data, and may help other researchers willing to use this technology to choose the most appropriate software depending on their goals. Future work is still needed in order to assess the performance of Oxford Nanopore MinION data on more complex microbiomes.
MADS-box factor AGL16 negatively regulates drought resistance via stomatal density and stomatal movement
Authors: Zhao Ping-Xia , Miao Zi-Qing , Zhang Jing , Liu Qian-Qian , Xiang Cheng-Bin 
Published: August 2019

ABSTRACTDrought is one of the most severe environmental factors limiting plant growth and productivity. Plants respond to drought by closing stomata to reduce water loss. The molecular mechanisms underlying plant drought resistance are very complex and yet to be fully understood. While much research attention has been focused on the positive regulation of stomatal closure, less is known about its negative regulation, equally important in this reversible process. Here we show that the MADS-box transcriptional factor AGL16 acts as a negative regulator in drought resistance by regulating both stomatal density and movement. Loss-of-function mutantagl16was more resistant to drought stress with higher relative water content, which was attributed to a reduced leaf stomatal density and more sensitive stomatal closure due to a higher leaf ABA level compared with wild type, whileAGL16overexpression lines displayed the opposite phenotypes.AGL16is preferentially expressed in guard cells and down regulated in response to drought stress. The expression ofCYP707A3andAAO3in ABA metabolism andSDD1in stomatal development was altered by AGL16 as shown inagl16and overexpression lines. Chromatin immunoprecipitation, transient transactivation, and yeast-one-hybrid assays demonstrated that AGL16 bound the CArG motif in the promoter of theCYP707A3,AAO3, andSDD1to regulate their transcription, and therefore alter leaf stomatal density and ABA level. Taken together, AGL16 acts as a negative regulator of drought resistance by modulating leaf stomatal density and ABA accumulation.
Screening the MMV Open Access Pathogen box unveils novel and potent inhibitors of Amoebiasis agent: Entamoeba histolytica
Authors: Toghueo Rufin Marie Kouipou , Dize Darline , Laleu Benoît , Fokou Patrick Valere Tsouh , Kemgne Eugenie Aimee Madiesse , Boyom Fabrice Fekam 
Published: August 2019

AbstractAmoebiasis caused by the protozoan parasite Entamoeba histolytica remains a major public health hazard, as being the second cause of death among parasitic infections. Although currently prescribed drugs have shown to be effective in the treatment of amoebiasis, side effects and emergence of parasites resistance prompted the search for novel drug to control this disease. In this regard, the Medicines for Malaria Venture (MMV) Pathogen Box library of selected compounds was screened to identify anti-Entamoeba histolytica agents using the resazurin based fluorescence assay. Overall, the results revealed three novel anti-Entamoeba histolytica scaffolds with low micromolar activity including MMV675968 (IC50 = 2.10 µM), MMV688179 (IC50 = 2.38 µM) and MMV688844 (IC50 = 5.63 µM). Structure-Activity-Relationship (SAR) studies led to identification of two analogs ∼100 fold more potent and selective than the original hit compound 1 (MMV675968): 1k (IC50 = 0.043 µM) and 1l (IC50 = 0.055 µM). Predictive analysis using Maestro 11.6 suggested that these hit compounds possess acceptable physicochemical and metabolism properties. These lead compounds are therefore good starting points for lead optimization studies towards identification of drug candidate against amoebiasis.Author SummaryDiarrhoea is a leading cause of death for millions of children worldwide. One of the top 15 causes of severe diarrhoea is Entamoeba histolytica, causing amoebiasis. What makes E. histolytica dangerous is its ability to disseminate easily through a given population via contaminated food and water supplies. Moreover, E. histolytica is quite comfortable in the environment, difficult to kill with chorine and infect people at a very low dose, making it a priority pathogen to eradicate. Many drugs have been developed so far to cure this infection. However, they are not efficient enough to control the disease due to pathogen resistance that is becoming a big issue. In addition to that, almost all the drugs in use are highly toxic to human causing several side effects upon medications. Therefore, new, more efficient and less toxic drugs are urgently needed for the better management of amoebiasis. Since the development of a new drug takes years, repurposing existing drugs has been shown to shortcut the process and boost the discovery rate of new medicines. Using this same approach, we have identified two compounds that potently inhibit E. histolytica and are nontoxic that can enter the drug discovery pipeline for new amoebicidal drug development. Moreover, these new inhibitors could also serve as starting points for the synthesis of a library of amoebicidal compounds.
Case-Base-Control designs
Authors: Elhezzani Najla Saad , Bergsma Wicher , Weale Mike 
Published: August 2019

AbstractMost genome-wide association studies (GWASs) use randomly selected samples from the population (hereafter bases) as the control set. This approach is successful when the trait of interest is rare; otherwise, a loss in the statistical power to detect disease-associated variants is expected. To address this, a proposal to combine the three sample types, cases, controls and bases is introduced, for instances when the disease under study is prevalent. This is done by modelling the bases as a mixture of multinomial logistic functions of cases and controls, according to the disease prevalence. The maximum likelihood method is used to estimate the underlying parameters using the EM algorithm. Three classical tests of association; score, Walds, and likelihood ratio tests are derived and their power of detecting genetic associations under different designs is compared. Simulations show that combining the three samples can increase the power to detect disease-associated variants, though a very large base sample set can compensate for the lack of controls.
Investigation of diffusion alloying time on electrochemical behavior and conductivity of Nb-modified AISI 430 SS as PEMFC bipolar plate
Authors: Cheng Fupeng , Cui Jinglong , Xu Shuai , Wang Hongyu , Zhang Pengchao , Sun Juncai 
Published: August 2019

Purpose
The purpose of this paper is to improve the surface electrical conductivity and corrosion resistance of AISI 430 stainless steel (430 SS) as bipolar plates for proton exchange membrane fuel cells (PEMFCs), a protective Nb-modified layer is formed onto stainless steel via the plasma surface diffusion alloying method. The effect of diffusion alloying time on electrochemical behavior and surface conductivity is evaluated.

Design/methodology/approach
In this work, the surface electrical conductivity and corrosion resistance of modified specimen are evaluated by the potentiodynamic and potentionstatic polarization tests. Moreover, the hydrophobicity is also investigated by contact angle measurement.

Findings
The Nb-modified 430 SS treated by 1.5 h (1.5Nb) presented a lower passivation current density, lower interfacial contact resistance and a higher hydrophobicity than other modified specimens. Moreover, the 1.5 Nb specimen presents a smoother surface than other modified specimens after potentionstatic polarization tests.

Originality/value
The effect of diffusion alloying time on electrochemical behavior, surface conductivity and hydrophobicity of modified specimen is evaluated. The probable anti-corrosion mechanism of Nb-modified specimen in simulated acid PEMFC cathode environment is presented.
Influence of Big Data in managing cyber assets
Authors: Mitra Amit , Munir Kamran 
Published: August 2019

Purpose
Today, Big Data plays an imperative role in the creation, maintenance and loss of cyber assets of organisations. Research in connection to Big Data and cyber asset management is embryonic. Using evidence, the purpose of this paper is to argue that asset management in the context of Big Data is punctuated by a variety of vulnerabilities that can only be estimated when characteristics of such assets like being intangible are adequately accounted for.

Design/methodology/approach
Evidence for the study has been drawn from interviews of leaders of digital transformation projects in three organisations that are within the insurance industry, natural gas and oil, and manufacturing industries.

Findings
By examining the extant literature, the authors traced the type of influence that Big Data has over asset management within organisations. In a context defined by variability and volume of data, it is unlikely that the authors will be going back to restricting data flows. The focus now for asset managing organisations would be to improve semantic processors to deal with the vast array of data in variable formats.

Research limitations/implications
Data used as evidence for the study are based on interviews, as well as desk research. The use of real-time data along with the use of quantitative analysis could lead to insights that have hitherto eluded the research community.

Originality/value
There is a serious dearth of the research in the context of innovative leadership in dealing with a threatened asset management space. Interpreting creative initiatives to deal with a variety of risks to data assets has clear value for a variety of audiences.