bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a novel NDM-5-harboring plasmid from a carbapenem-resistantEscherichia coliisolate from China
Authors: Yin Dongdong , Lin Yanfeng , Li Zhonghong , Ma Hui , Lu Lanfen , Wang Kaiying , Yang Lang , Du Xinying , Song Hongbin , Li Peng , Qi Kezong 
Published: January 2020

ABSTRACTA carbapenem-resistantEscherichia coli(sequence type 5415) strain was isolated from a male patient. S1-PFGE and Southern blotting showed that theblaNDM-5gene was located on a novel 66-kb IncFII [F2:A-:B-] plasmid. Conjugation assays revealed that theblaNDM-5-bearing plasmid was self-transferrable. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and theblaNDM-5flanking genetic elements. This study highlights the genetic complexity of an NDM-5 carbapenemase and the urgent need for continuous active monitoring.IMPORTANCECarbapenem resistance due to the NDM enzyme has become a serious clinical problem in medical care and public health. We here identified ablaNDM-5-positiveE. colistrain ST5414. TheblaNDM-5gene was located on a novel self-transferrable IncFII type plasmid p2947-NDM5. Genomic sequencing and comparative analysis suggested that plasmid p2947-NDM5 likely originated from a combination of an IncFII-type backbone and the blaNDM-5 flanking genetic elements. The genetic context of NDM-5 is highly similar to that of animal origins, and we speculate that theblaNDM-harboring IncFII plasmid has a potential risk of being transmitted from animals to humans and should be paid more attention. Our findings highlight the threat of NDM-5 carbapenemase circulation and the urgency of stringent surveillance and control measures.
Human stem cell derived sensory neurons are positioned to support varicella zoster virus latency
Authors: Sadaoka Tomohiko , Rajbhandari Labchan , Shukla Priya , Jagdish Balaji , Lee Hojae , Lee Gabsang , Venkatesan Arun 
Published: January 2020

ABSTRACTThe neuropathogenesis of varicella-zoster virus (VZV) has been challenging to study due to the strict human tropism of the virus and the resultant difficulties in establishing tractable experimental models.In vivo, sensory neurons of the dorsal root ganglia and trigeminal ganglia serve as cellular niches that support viral latency, and VZV can subsequently reactivate from these cells to cause disease. Whether sensory neurons possess intrinsic properties that position them to serve as a reservoir of viral latency remains unknown. Here, we utilize a robust human sensory neuron system to investigate lytic infection and viral latency. We find that sensory neurons exhibit resistance to lytic infection by VZV. On the other hand, latent infection in sensory neurons is associated with an episomal-like configuration of viral DNA and expression of the VZV latency-associated transcript (VLT), thus closely mirroring thein vivostate. Moreover, despite the relative restriction in lytic infection, we demonstrate that viral reactivation is possible from latently infected sensory neurons. Taken together, our data suggest that human sensory neurons possess intrinsic properties that serve to facilitate their role as a latent reservoir of VZV.IMPORTANCEVaricella-zoster virus (VZV) has infected over 90% of people worldwide. Following primary infection, the virus can remain dormant in the nervous system and may reactivate later in life, with potentially severe consequences. Here, we develop a model of VZV infection in human sensory neurons in order to determine whether these cells are intrinsically positioned to support latency and reactivation. We find that human sensory neurons are relatively resistant to lytic infection, but can support latency and reactivation. Moreover, duringin vitrolatency human sensory neurons, but not other neurons, express the newly discovered VZV latency-associated transcript (VLT), thus closely mirroring thein vivolatent state. Taken together, these data indicate that human sensory neurons are uniquely positioned to support latency. We anticipate that this human sensory neuron model will serve to facilitate further understanding of the mechanisms of VZV latency and reactivation.
Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice
Authors: Shi Shuai , Ji Xin-Yu , Shi Jing-Jing , Shi Shu-Qing , Jia Qiu-Lei , Yuan Guo-Zhen , Zhang Qiu-Yan , Dong Yu , Lu Ying-Dong , Cui Han-Ming , Hu Yuan-Hui 
Published: January 2020

AbstractMechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.ImportanceHFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.
A susceptibility locus on chromosome 13 profoundly impacts the stability of genomic imprinting in mouse pluripotent stem cells
Authors: Swanzey Emily , McNamara Thomas F. , Apostolou Effie , Tahiliani Mamta , Stadtfeld Matthias 
Published: January 2020

SummaryCultured pluripotent cells accumulate detrimental epigenetic alterations, including DNA methylation changes at imprinted genes known as loss-of-imprinting (LOI). Despite the substantial biomedical relevance of this phenomenon, the molecular cause of this epigenetic instability in pluripotent cells remains unknown. While the occurrence of LOI is generally considered a stochastic phenomenon, here we document a strong genetic determinant that segregates mouse pluripotent cells into epigenetically stable and unstable cell lines. Unstable lines exhibit hypermethylation atDlk1-Dio3and select other imprinted loci, which is associated with impaired developmental potential. Stimulation of demethylases by ascorbic acid prevents LOI and can preserve developmental potential. Susceptibility to LOI greatly differs between commonly used mouse strains, which we utilize to map a causal region on chromosome 13 with Quantitative Trait Locus (QTL) analysis. Our observations identify a strong genetic determinant of locus-specific epigenetic abnormalities in pluripotent cells and provide a non-invasive way to suppress them. This highlights the importance of considering genetics in conjunction with culture conditions for assuring the quality of pluripotent cells for biomedical applications.
Time dependent stress relaxation and recovery in mechanically strained 3D microtissues
Authors: Walker Matthew , Godin Michel , Harden James L. , Pelling Andrew E. 
Published: January 2020

AbstractCharacterizing the time-dependent mechanical properties of cells is not only necessary to determine how they deform, but also to fully understand how external forces trigger biochemical-signaling cascades to govern their behavior. Presently mechanical properties are largely assessed by applying local shear or compressive forces on single cells in isolation grown on non-physiological 2D surfaces. In comparison, we developed the microfabricated vacuum actuated stretcher to measure tensile loading of 3D multicellular ‘microtissue’ cultures. With this approach, we assessed here the time-dependent stress relaxation and recovery responses of microtissues, and quantified the spatial remodeling that follows step length changes. Unlike previous results, stress relaxation and recovery in microtissues measured over a range of step amplitudes and pharmacological treatments followed a stretched exponential behavior describing a broad distribution of inter-related timescales. Furthermore, despite a performed compendium of experiments, all responses led to a single linear relationship between the residual elasticity and degree of stress relaxation, suggesting that these mechanical properties are coupled through interactions between structural elements and the association of cells with their matrix. Lastly, although stress relaxation could be quantitatively and spatially linked to recovery, they differed greatly in their dynamics; while stress recovery behaved as a linear process, relaxation time constants changed with an inverse power law with step size. This assessment of microtissues offers insights into how the collective behavior of cells in a 3D collagen matrix generate the dynamic mechanical properties of tissues, which is necessary to understanding how cells deform and sense mechanical forces in the body.
Mechanical stretch sustains myofibroblast phenotype and function in microtissues through latent TGF-β1 activation
Authors: Walker Matthew , Godin Michel , Pelling Andrew E. 
Published: January 2020

AbstractFibrosis is a leading cause of death in developed countries that is characterized by a progressive deterioration of tissue mechanical behavior. Developing methods to study tissue mechanics and myofibroblast activation may lead to new targets for therapeutic treatments that are urgently needed. Microtissue arrays are a promising approach to conduct relatively high throughput research into fibrosis as they recapitulate key biomechanical aspects of the disease through a relevant 3D extracellular environment. In early work, our group developed a device called the MVAS-force to stretch microtissues while enabling simultaneous assessment of their dynamic mechanical behavior. Here we investigated TGF-β1 induced fibroblast to myofibroblast differentiation in microtissue cultures using our MVAS-force device through assessing α-SMA expression, contractility and stiffness. By doing so, we linked cell-level phenotypic changes to functional changes that characterize the clinical manifestation of fibrotic disease. As expected, TGF-β1 treatment promoted a myofibroblastic phenotype and microtissues became stiffer and possessed increased contractility. Furthermore, these changes were partially reversible upon TGF-β1 withdrawal. In contrast, however, long-term cyclic stretching maintained myofibroblast activation. Furthermore stretching had no effect compared static cultures when TGF-β1 receptors were inhibited and stretching promoted myofibroblast differentiation when given latent TGF-β1. Together these results suggest that external mechanical stretch may activate latent TGF-β1 and might be a powerful stimulus for continued myofibroblast activation to progress fibrosis. Further exploration of this pathway with our approach may yield new insights into myofibroblast activation and more effective therapeutic treatments for fibrosis.Insight boxUsing a novel high-throughput approach, we quantified the effects of dynamic mechanical stretching on the phenotype and function of cells in 3D microtissue cultures during myofibroblast activation with TGF-β1 treatment and subsequent withdrawal. Our findings show that mechanical stretch may activate endogenously produced latent TGF-β1 to maintain the presence and activity of myofibroblasts after tissue injury. Importantly, through this feed forward mechanism, mechanical stretch might be a powerful stimulus that directs tissues away from recovery and towards the development of fibrosis.
Atomistic Molecular Dynamics Simulations of Trioleoylglycerol – Phospholipid Membrane Systems
Authors: Hammad Mirza Ahmed , Akram Hafiza Minal , Raza Muhammad Sohail 
Published: January 2020

AbstractAdiposomes are phospholipid coated triacylglyceride particles that serve as structural models of the fat storage compartments of cells, known as lipid droplets (LDs); however, unlike LDs, they do not carry proteins. There is a deficit of available methods and experimental data regarding the internal packing of the adiposomes, and computer simulations offer a promising way to pinpoint the molecular arrangements within these structures. However, in the absence of a triacylglycerol-specific atomic forcefield, thus far, all adiposome/LD simulations have been performed with the coarse grained/united atom forcefields. Yet it is desirable to model the phospholipid/triacylglycerol interface with atomic resolution. In the present study, we first prepared a 2-monooleoylglycerol (MOG) forcefield which was then used to build a trioleoylglycerol (TOG) forcefield by the modular approach of the AMBER software suite. TOG bilayer membrane (2L) systems were modelled from two different initial conformations; TOG3 and TOG2:1. The simulations revealed that TOG2:1 is the most populated conformation in TOG membranes, irrespective of the starting conformation. Some other parameter optimizations were performed for TOG membranes based on which adiposome mimicking tetralayer membrane system (4L) was prepared with a TOG bilayer at core surrounded by two DOPC leaflets. The 4L membranes were stable throughout the simulations, however it was observed that a small amount of cations and water diffused from surface to the TOG core of the membrane. Based on these results a TAG-packing model was also developed. It is expected that the availability of MOG forcefield will equip future studies with a framework for molecular dynamics simulations of adiposomes/LDs.
A theory of the use of information by enemies in the predator-prey space race
Authors: Patin Rémi , Fortin Daniel , Chamaillé-Jammes Simon 
Published: January 2020

AbstractWe currently lack a comprehensive theory about how behaviourally responsive predators and prey use the information they acquire about the environment and each other’s presence while engaged in the ‘space race’. This limits our understanding of the role of behaviour in trophic relationships and our ability to predict predators and prey distributions. Here we combined a simulation model with a genetic algorithm to discover how predators and prey behaving optimally should use information in environments with different levels of heterogeneity in prey forage distribution and prey vulnerability. Our results demonstrate the key role of movement unpredictability in successful strategies for both predators and prey, supporting the ‘shell-game’ hypothesis. We however reveal striking differences between predators and prey in the magnitude of this unpredictability, and in how it varies with the environment. Our work offers a robust theoretical framework to better understand predator-prey space use and interpret empirical studies.
Functional diversity metrics using kernel densityn-dimensional hypervolumes
Authors: Mammola Stefano , Cardoso Pedro 
Published: January 2020

SummaryThe use ofn-dimensional hypervolumes in trait-based ecology is rapidly increasing. By representing the functional space of a species or community as a Hutchinsonian niche, the abstract Euclidean space defined by a set of independent axes corresponding to individuals or species traits, these multidimensional techniques show great potential for the advance of functional ecology theory.In the panorama of existing methods for delineating multidimensional spaces, the R packagehypervolume[Glob. Ecol. Biogeogr.(2014) 23:595–609] is currently the most used. However, functions for calculating the standard set of functional diversity (FD) indices—richness, divergence, and regularity—have not been developed within thehypervolumeframework yet. This gap is delaying its full exploitation in functional ecology, meanwhile preventing the possibility to compare its performance with that of other methods.We develop a set of functions to calculate FD indices based onn-dimensional hypervolumes, including alpha (richness), beta (and respective components), dispersion, evenness, contribution, and originality. Altogether, these indices provide a coherent framework to explore the primary mathematical components of FD within a multidimensional setting. These new functions can work either with hypervolume objects or raw data (species presence or abundance and their traits) as input data, and are versatile in terms of input parameters and options.These functions are implemented withinBAT(Biodiversity Assessment Tools), an R package for biodiversity assessments. As a coherent corpus of functional indices based on a common algorithm, it opens the possibility to fully explore the strengths of the Hutchinsonian niche concept in community ecology research.
Logarithmic encoding of ensemble time intervals
Authors: Ren Yue , Allenmark Fredrik , Müller Hermann J. , Shi Zhuanghua 
Published: January 2020

AbstractAlthough time perception is based on the internal representation of time, whether the subjective timeline is scaled linearly or logarithmically remains an open issue. Evidence from previous research is mixed: while the classical internal-clock model assumes a linear scale with scalar variability, there is evidence that logarithmic timing provides a better fit to behavioral data. A major challenge for investigating the nature of the internal scale is that the retrieval process required for time judgments may involve a remapping of the subjective time back to the objective scale, complicating any direct interpretation of behavioral findings. Here, we used a novel approach, requiring rapid intuitive ‘ensemble’ averaging of a whole set of time intervals, to probe the subjective timeline. Specifically, observers’ task was to average a series of successively presented, auditory or visual, intervals in the time range 300-1300 ms. Importantly, the intervals were taken from three sets of durations, which were distributed such that the arithmetic mean (from the linear scale) and the geometric mean (from the logarithmic scale) were clearly distinguishable. Consistently across the three sets and the two presentation modalities, our results revealed subjective averaging to be close to the geometric mean, indicative of a logarithmic timeline underlying time perception.
Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets
Authors: Piran Mehran , Piran Mehrdad , Sepahi Neda , Ghanbariasad Ali , Rahimi Amir 
Published: January 2020

AbstractColorectal cancer (CRC) is one of the major causes of cancer deaths across the world. Patients survival time at time of diagnosis depends largely on stage of the tumor. Therefore, understanding the molecular mechanisms promoting cancer progression from early stages to high-grade stages is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary and metastatic samples in some test datasets. DEGs were employed to construct a protein-protein interaction (PPI) network. Then, a smaller network containing 39 DEGs were extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis. A number of these DEGs were then verified by gene expression profiling, survival analysis and a number of validation datasets from different genomic repositories. They were involved in cell proliferation, energy production under hypoxic conditions, epithelial to mesenchymal transition (EMT) and angiogenesis. Multiple combination targeting of these DEGs were proposed to have high potential in preventing cancer progression. Some genes were also presented as diagnostic biomarkers for colorectal cancer. Finally, TMEM131, DARS and SORD genes were identified in this study which had never been associated with any kind of cancer neither as a biomarker nor curative target.
Functional specialization of the medial temporal lobes in human recognition memory: dissociating effects of hippocampal vs parahippocampal damage
Authors: Argyropoulos Georgios P. D. , Dell’Acqua Carola , Butler Emily , Loane Clare , Roca-Fernandez Adriana , Almozel Azhaar , Drummond Nikolas , Lage-Martinez Carmen , Cooper Elisa , Henson Richard N. , Butler Christopher R. 
Published: January 2020

AbstractA central debate in the systems neuroscience of memory concerns whether different medial temporal lobe (MTL) structures support different processes or material-types in recognition memory. We tested a rare patient (Patient MH) with a perirhinal lesion that appeared to spare the hippocampus, using two recognition memory paradigms, each run separately with faces, scenes and words. Replicating reports of a previous case, Patient MH showed impaired familiarity and preserved recollection, relative to controls, with no evidence for any effect of material-type. Moreover, when compared with other amnesic patients, who had hippocampal lesions that appeared to spare the perirhinal cortex, Patient MH showed greater impairment on familiarity and less on recollection, forming a double dissociation. However, when replacing this traditional, binary categorization of patients with a parametric analysis that related memory performance to continuous measures of brain damage across all patients, we found a different pattern: while hippocampal damage predicted recollection, it was parahippocampal instead of perirhinal (or entorhinal) cortex volume that predicted familiarity. Furthermore, there was no evidence that these brain-behavior relationships were moderated by material-type, nor by laterality of damage. Thus, while our data provide the most compelling support yet for dual-process models of recognition memory, in which recollection and familiarity depend on different MTL structures, they suggest that familiarity depends more strongly upon the parahippocampal rather than perirhinal cortex. More generally, our study reinforces the need to go beyond single-case and group studies, and instead examine continuous brain-behavior relationships across larger patient groups.