bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic Removal of False Connections in Diffusion MRI Tractography Using Topology-Informed Pruning (TIP)
Authors: Yeh Fang-Cheng , Panesar Sandip , Barrios Jessica , Fernandes David , Abhinav Kumar , Meola Antonio , Fernandez-Miranda Juan C. 
Published: June 2018

AbstractDiffusion MRI fiber tracking provides a non-invasive method for mapping the trajectories of human brain connections, but its false connection problem has been a major challenge. This study introduces topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve the tracking accuracy. The accuracy of the tractography with and without TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine whether TIP could improve the accuracy. The results showed that TIP improved the tracking accuracy by 11.93% in the single-shell scheme and by 3.47% in the grid scheme. The improvement is significantly different from a random pruning (p-value < 0.001). The diagnostic agreement between TIP and neuroanatomists was comparable to the agreement between neuroanatomists. The proposed TIP algorithm can be used to automatically clean up noisy fibers in deterministic tractography, with a potential to confirm the existence of a fiber connection in basic neuroanatomical studies or clinical neurosurgical planning.
Migration through a small pore disrupts inactive chromatin organization in neutrophil-like cells
Authors: Jacobson Elsie C. , Perry Jo K. , Long David S. , Olins Ada L. , Olins Donald E. , Wright Bryon E. , Vickers Mark H. , O’Sullivan Justin M. 
Published: June 2018

AbstractBackgroundMammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. Their nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through constricted space, where the nuclear shape must change in order to fit through the constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration.ResultsTotal RNA-sequencing identified that neutrophil migration through 5 or 14μm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes, when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling.Hi-C was used to capture the genome organization in control and migrated cells. Minimal switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin.ConclusionShort range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in human health and disease.
Improved performance of microbial fuel cells through addition of trehalose lipids
Authors: Cheng Peng , Shan Rui , Yuan Hao-Ran , Dong Ge , Deng Li-fang , Chen Yong 
Published: June 2018

AbstractElectron transfer from microorganisms to the electrode is the key process in microbial fuel cells (MFCs). In this study, a trehalose lipid was added to a Rhodococcus pyridinivorans-inoculated MFC to improve the power output by enhancing electron transfer. Upon trehalose lipid addition, the current density and maximum power density were increased by 1.83 times and 5.93 times, respectively. Cyclic voltammetry analysis revealed that the addition of trehalose lipid increased the electron transfer performance, while electrochemical impedance spectroscopy results proved a decrease in internal resistance. Microscopy images showed that the trehalose lipid-treated bacteria interacted more closely with various fagellum-like contacts, while in the pure trehalose lipid (200 mg/L), pores were obviously observed in the cell surface.ImportanceImproving the power output of microbial fuel cells by the addition of bio-surfactants have been proved to be a novel method. However, only rhamnolipid and sophorolipid are certified to be effective. Trehalose lipid is a common material in cosmetic and bio-medicine industry. Our research broaden the application of bio-surfactant in MFC and preliminarily explain the mechanism.HighlightsTrehalose lipid enhanced MFC power generationTrehalose lipid decrease MFC internal resistancePores were observed with the addition of trehalose lipidAddition of bio-surfactant is a promising way to increase MFC performance
A command-like descending neuron that coordinately activates backward and inhibits forward locomotion
Authors: Carreira-Rosario Arnaldo , Zarin Aref Arzan , Clark Matthew Q. , Manning Laurina , Fetter Richard , Cardona Albert , Doe Chris Q. 
Published: June 2018

AbstractCommand-like descending neurons can induce many behaviors, such as backward locomotion, escape, feeding, courtship, egg-laying, or grooming. In most animals it remains unknown how neural circuits switch between these antagonistic behaviors: via top-down activation/inhibition of antagonistic circuits or via reciprocal inhibition between antagonistic circuits. Here we use genetic screens, intersectional genetics, circuit reconstruction by electron microscopy, and functional optogenetics to identify a bilateral pair of larval “mooncrawler descending neurons” (MDNs) with command-like ability to coordinately induce backward locomotion and block forward locomotion; the former by activating a backward-specific premotor neuron, and the latter by disynaptic inhibition of a forward-specific premotor neuron. In contrast, direct reciprocal inhibition between forward and backward circuits was not observed. Thus, MDNs coordinate a transition between antagonistic larval locomotor behaviors. Interestingly, larval MDNs persist into adulthood, where they can trigger backward walking. Thus, MDNs induce backward locomotion in both limbless and limbed animals.HighlightsMDN command-like descending neuron induces backward larval locomotionMDN neurons coordinately regulate antagonistic behaviors (forward/backward locomotion)MDN-motor circuit validated at structural (TEM) and functional (optogenetic) levelsMDN neurons induce backward locomotion in both limbless larva and limbed adult
AQ-seq: Accurate quantification of microRNAs and their variants
Authors: Kim Haedong , Kim Jimi , Kim Kijun , Chang Hyeshik , You Kwontae , Kim V. Narry 
Published: June 2018

AbstractMicroRNAs (miRNAs) modulate diverse biological and pathological processes via post-transcriptional gene silencing. High-throughput small RNA sequencing (sRNA-seq) has been widely adopted to investigate the functions and regulatory mechanisms of miRNAs. However, accurate quantification has been limited owing to the severe ligation bias in conventional sRNA-seq methods. Here we present a high-throughput protocol, termed AQ-seq (accurate quantification by sequencing), that utilizes adapters with terminal degenerate sequences and a high concentration of polyethylene glycol (PEG), which removes the ligation bias during library preparation. By accurately measuring miRNAs and their variants (known as isomiRs), we identify alternatively processed miRNAs and correct the 5′ end usage and strand preference that have been misannotated. We also uncover highly modified miRNAs that are uridylated and adenylated. Taken together, AQ-seq reveals the complexity of the miRNA isoform landscape, allowing us to refine miRNA annotation and to advance our understanding of miRNA regulation. Furthermore, AQ-seq can be adopted to improve other ligation-based sequencing methods including crosslinking-immunoprecipitation-sequencing (CLIP-seq) and ribosome profiling (Ribo-seq).
How adaptive plasticity evolves when selected against
Authors: Rago Alfredo , Kouvaris Kostas , Uller Tobias , Watson Richard 
Published: June 2018

AbstractAdaptive plasticity allows organisms to cope with environmental change, thereby increasing the population’s long-term fitness. However, individual selection can only compare the fitness of individuals within each generation: if the environment changes more slowly than the generation time (i.e., a coarse-grained environment) a population will not experience selection for plasticity even if it is adaptive in the long-term. How does adaptive plasticity then evolve? One explanation is that, if competing alleles conferring different degrees of plasticity persist across multiple environments, natural selection between lineages carrying those alleles could select for adaptive plasticity (lineage selection).We show that adaptive plasticity can evolve even in the absence of such lineage selection. Instead, we propose that adaptive plasticity in coarse-grained environments evolves as a by-product of inefficient short-term natural selection. In our simulations, populations that can efficiently respond to selective pressures follow short-term, local, optima and have lower long-term fitness. Conversely, populations that accumulate limited genetic change within each environment evolve long-term adaptive plasticity even when plasticity incurs short-term costs. These results remain qualitatively similar regardless of whether we decrease the efficiency of natural selection by increasing the rate of environmental change or decreasing mutation rate, demonstrating that both factors act via the same mechanism. We demonstrate how this mechanism can be understood through the concept of learning rate.Our work shows how plastic responses that are costly in the short term, yet adaptive in the long term, can evolve as a by-product of inefficient short-term selection, without selection for plasticity at either the individual or lineage level.
Phosphorylation of a Toxoplasma gondii tyrosine transporter by calcium-dependent kinase 3 is important for parasite fitness
Authors: Wallbank Bethan A. , Dominicus Caia S. , Broncel Malgorzata , Legrave Nathalie , MacRae James I. , Staines Henry M. , Treeck Moritz 
Published: June 2018

AbstractToxoplasma gondii parasites rapidly exit their host cell when exposed to calcium ionophores. The calcium-dependent protein kinase 3 (TgCDPK3) was previously identified as a key mediator in this process, as TgCDPK3 knockout (Δcdpk3) parasites fail to egress in a timely manner. Phosphoproteomic analysis comparing WT with Δcdpk3 parasites revealed changes in the TgCDPK3-dependent phosphoproteome that included proteins important for regulating motility, but also metabolic enzymes, indicating that TgCDPK3 controls processes beyond egress. Here we have investigated a predicted direct target of TgCDPK3, a putative transporter of the major facilitator superfamily (MFS) and show that it is rapidly phosphorylated after induction of calcium signalling. Conditional knockout (KO) of the transporter reveals an essential role in the lytic cycle during intracellular growth with a transcriptome signature of amino acid-starved parasites. Using a combination of metabolomics and heterologous expression, we confirmed a primary role in tyrosine import. Complementation with phosphorylation site mutants shows that phosphorylation of serine 56 (S56) by TgCDPK3 gives the parasites a growth benefit in competition assays. Collectively, these findings validate an important, albeit non-essential role for TgCDPK3 in the regulation of metabolic processes, in addition to motility.Author summaryToxoplasma gondii is an obligate intracellular parasite. To survive and spread throughout the host it must repeatedly infect, replicate within and exit, host cells. These recurring cycles of infection and egress rely on signalling pathways that allow the parasites to sense and respond rapidly to their environment. While some key kinases and secondary messengers within these pathways have been identified, functional analysis of non-kinases has been very limited. This is especially true for candidates that are not predicted to play a role in active motility or are not known to function in established signalling pathways. Here we have followed up on an unexpected target of the T. gondii calcium-dependent kinase 3 (TgCDPK3), a plant-like calcium dependent kinase, that was previously shown to play an important role in calcium-mediated exit from the host cell. We show that, in addition to controlling motility of the parasite (as previously shown), TgCDPK3 phosphorylates an essential tyrosine transporter in the plasma membrane. Mutational analysis of the phosphorylation sites demonstrates an important role in maintaining parasite fitness, thus demonstrating that TgCDPK3 plays a pleiotropic role in controlling both egress and metabolism.
Computational algorithms and neural circuitry for compressed sensing in the mammalian main olfactory bulb
Authors: Kepple Daniel , Cazakoff Brittany N. , Demmer Heike S. , Eckmeier Dennis , Shea Stephen D. , Koulakov Alexei A. 
Published: June 2018

ABSTRACTA major challenge for many sensory systems is the representation of stimuli that vary along many dimensions. This problem is particularly acute for chemosensory systems because they require sensitivity to a large number of molecular features. Here we use a combination of computational modeling andin vivoelectrophysiological data to propose a solution for this problem in the circuitry of the mammalian main olfactory bulb. We model the input to the olfactory bulb as an array of chemical features that, due to the vast size of chemical feature space, is sparsely occupied. We propose that this sparseness enables compression of the chemical feature array by broadly-tuned odorant receptors. Reconstruction of stimuli is then achieved by a supernumerary network of inhibitory granule cells. The main olfactory bulb may therefore implement a compressed sensing algorithm that presents several advantages. First, we demonstrate that a model of synaptic interactions between the granule cells and the mitral cells that constitute the output of the olfactory bulb, can store a highly efficient representation of odors by competitively selecting a sparse basis set of “expert” granule cells. Second, we further show that this model network can simultaneously learn separable representations of each component of an odor mixture without exposure to those components in isolation. Third, our model is capable of independent and odor-specific adaptation, which could be used by the olfactory system to perform background subtraction or sensitively compare a sample odor with an internal expectation. This model makes specific predictions about the dynamics of granule cell activity during learning. Usingin vivoelectrophysiological recordings, we corroborate these predictions in an experimental paradigm that stimulates memorization of odorants.
Fold-change detection of NF-κB at target genes with different transcript outputs
Authors: Wong V. C. , Ramji R. , Gaudet S. , Miller-Jensen K. 
Published: June 2018

AbstractThe transcription factor NF-κB promotes inflammatory and stress-responsive gene transcription across a range of cell types in response to the cytokine tumor necrosis factor-α (TNF). Although NF-κB signaling exhibits significant variability across single cells, some target genes exhibit fold-change detection of NF-κB, which may buffer against stochastic variation in signaling molecules. However, this observation was made at target genes supporting high levels of TNF-inducible transcription. It is unknown if fold-change detection is maintained at NF-κB target genes with low levels of TNF-inducible transcription, for which stochastic promoter events may be more pronounced. Here we used a microfluidic cell-trapping device to measure how TNF-induced activation of NF-κB controls transcription in single Jurkat T cells at the promoters of integratedHIVand the endogenous cytokine geneIL6, which produce only a few transcripts per cell. We tracked TNF-stimulated NF-κB RelA nuclear translocation by live-cell imaging and then quantified transcript number by RNA FISH in the same cell. We found that TNF-induced transcription correlates with fold change in nuclear NF-κB with similar strength at low versus high abundance target genes. A computational model of TNF-NF-κB signaling, which implements fold-change detection from competition for binding to κB motifs, was sufficient to reproduce fold-change detection across the experimentally measured range of transcript outputs. Nevertheless, we found that gene-specific trends in transcriptional noise and levels of promoter-bound NF-κB predicted by the model were inconsistent with our experimental observations at low abundance gene targets. Our results reveal a gap in our understanding of RelA-mediated transcription for low abundance transcripts and suggest that cells use additional biological mechanisms to maintain robustness of NF-κB fold-change detection while tuning transcriptional output.
Oxygen restriction generates difficult-to-culture pathogens
Authors: Kvich Lasse , Fritz Blaine G. , Crone Stephanie , Kragh Kasper N. , Kolpen Mette , Sønderholm Majken , Andersson Mikael , Koch Anders , Jensen Peter Ø. , Bjarnsholt Thomas 
Published: June 2018

AbstractInduction of a non-culturable state has been demonstrated for many bacteria. In a clinical perspective, the lack of growth due to these non-culturable bacteria can have major consequences for the diagnosis and treatment of patients. Here we show how anoxic conditioning (restriction of molecular oxygen, O2) generates difficult-to-culture (DTC) bacteria during biofilm growth. A significant subpopulation ofPseudomonas aeruginosaentered a DTC state after anoxic conditioning, ranging from five to 90 % of the total culturable population, in both planktonic and biofilm models. Anoxic conditioning also generated DTC subpopulations ofStaphylococcus aureusandStaphylococcus epidermidis. Growth of the DTC populations were achieved by substituting O2with 10 mM NO3-as an alternative electron acceptor for anaerobic respiration or, in the case ofP. aeruginosa, by adding sodium pyruvate or catalase as scavengers against reactive oxygen species (ROS) during aerobic respiration. An increase in normoxic plating due to addition of catalase suggests the molecule hydrogen peroxide as a possible mechanism for induction of DTCP. aeruginosa.Anoxic conditioning also generated a true viable but non-culturable (VBNC) population ofP. aeruginosathat was not resurrected by substituting O2with NO3-during anaerobic respiration. Moreover, bacterial detection in clinical samples was improved significantly by supplementing 10 mM NO3-to LB plates and incubating under anoxic conditions. These results demonstrate that habituation to an infectious anoxic micro-environment complicates diagnostic culturing of bacteria, especially in the case of chronic infections where oxygen is restricted due to the host immune response.ImportanceDiagnostics of bacteria from chronic infections by standard culture-based methods is challenging. Bacteria in a non-culturable state may contribute to the lack of culturing from these infections. Many stressors are known to induce a non-culturable state, among others the absence of molecular oxygen, which is evident in chronic infections due to high rates of oxygen consumption by the host response. In this study, we have shown thatPseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidiscan enter a difficult-to-culture state after oxygen restriction. Regrowth was not possible using conventional normoxic plating where oxygen served as electron acceptor. Instead, regrowth was enabled during anoxic conditions with added nitrate as alternative electron acceptor. Our findings show that bacteria can habituate to their environment and that it has to be taken into consideration especially when culturing clinical samples e.g. from chronic infections.
Research on the construction of seamless learning platform based on open education
Authors: Xin Yongrong , Zuo Xiuping , Huang Qingping 
Published: June 2018

Purpose
The implementation of the national education and lifelong education should break through the traditional learning mode in the digital era. A seamless learning environment is the intelligent form of deep integration of digital learning environment and physical learning environment. The development and construction of seamless learning space and platform is a new trend of international mobile learning research and practice. So, the purpose of this paper is to build a seamless learning platform of the open education system by expanding and improving the connotation and extension of seamless learning, based on the theories of mobile learning, ubiquitous learning and open education, combining with the characteristics of the big data era.

Design/methodology/approach
A seamless learning platform model will be constructed through constructing five modules including resource integration module, requirement module, management module, teacher integration module, and carrier module, using interdisciplinary research methods (combined with economics), functional analysis, model methods and exploratory research methods. Finally, this paper attempts to realize the application of a seamless learning platform in open education through the strategic path of public-private partnership (PPP).

Findings
Seamless learning platform model given by this paper can effectively eliminate the problem of information asymmetry between learner-demander and educational manager through the effective management of carrier fusion module. Furthermore, it can effectively integrate the learning resources and teachers of the open education system and social individual education system, and provide high-quality shared learning resources and diverse stratification teachers to students and social workers through PPP project cooperation ways.

Originality/value
There are many papers on the study of open education and resource construction. However, few papers have studied how to effectively integrate and optimize various existing scattered online resources, including various system courses, teachers and platform systems. The paper provides an effective way to solve the above sub-problems and the realization path/model reference for the effective and accurate promotion of lifelong sustainable learning for all.