bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biology and taxonomy of crAss-like bacteriophages, the most abundant virus in the human gut
Authors: Guerin Emma , Shkoporov Andrey , Stockdale Stephen R. , Clooney Adam G. , Ryan Feargal J. , Sutton Thomas D. S. , Draper Lorraine A. , Gonzalez-Tortuero Enrique , Ross R. Paul , Hill Colin 
Published: April 2018

AbstractCrAssphage is yet to be cultured even though it represents the most abundant virus in the gut microbiota of humans. Recently, sequence based classification was performed on distantly related crAss-like phages from multiple environments, leading to the proposal of a familial level taxonomic group [Yutin N, et al. (2018) Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut. Nat Microbiol 3(1):38–46]. Here, we assembled the metagenomic sequencing reads from 702 human faecal virome/phageome samples and obtained 98 complete circular crAss-like phage genomes and 145 contigs ≥70kb. In silico comparative genomics and taxonomic analysis was performed, resulting in a classification scheme of crAss-like phages from human faecal microbiomes into 4 candidate subfamilies composed of 10 candidate genera. Moreover, laboratory analysis was performed on faecal samples from an individual harbouring 7 distinct crAss-like phages. We achieved propagation of crAss-like phages in ex vivo human faecal fermentations and visualised Podoviridae virions by electron microscopy. Furthermore, detection of a crAss-like phage capsid protein could be linked to metagenomic sequencing data confirming crAss-like phage structural annotations.SignificanceCrAssphage is the most abundant biological entity in the human gut, but it remains uncultured in the laboratory and its host(s) is unknown. CrAssphage was not identified in metagenomic studies for many years as its sequence is so different from anything present in databases. To this day, it can only be detected from sequences assembled from metagenomics or viromic datasets (crAss – cross Assembly). In this study, we identified 243 new crAss-like phages from human faecal metagenomic studies. Taxonomic analysis of these crAss-like phages highlighted their extensive diversity within the human microbiome. We also present the first propagation of crAssphage in faecal fermentations and provide the first electron micrographs of this extraordinary bacteriophage.
Using the residual bootstrap to quantify uncertainty in mean apparent propagator MRI
Authors: Gu Xuan , Eklund Anders , Özarslan Evren , Knutsson Hans 
Published: April 2018

AbstractEstimation of noise-induced variability in MAP-MRI is needed to properly characterize the amount of uncertainty in quantities derived from the estimated MAP-MRI coefficients. Bootstrap metrics, such as the standard deviation, provides additional valuable diffusion information in addition to common MAP-MRI parameters, and can be incorporated in MAP-MRI studies to provide more extensive insight. To the best of our knowledge, this is the first paper to study the uncertainty of MAP-MRI derived metrics. The noise variability of quantities of MAP-MRI have been quantified using the residual bootstrap, in which the residuals are resampled using two sampling schemes. The residual bootstrap method can provide empirical distributions for MAP-MRI derived quantities, even when the exact distributions are not easily derived. The residual bootstrap methods are applied to SPARC data and HCP-MGH data, and empirical distributions are obtained for the zero-displacement probabilities. Here, we compare and contrast the residual bootstrap schemes using all shells and within the same shell. We show that residual resampling within each shell generates larger uncertainty than using all shells for the HCP-MGH data. Standard deviation and quartile coefficient maps of the estimated variability are provided.
Flexible coding of memory and space in the primate hippocampus during virtual navigation
Authors: Gulli Roberto A. , Duong Lyndon , Corrigan Ben , Doucet Guillaume , Williams Sylvain , Fusi Stefano , Martinez-Trujillo Julio C. 
Published: April 2018

AbstractHippocampal maps of space change across tasks. The mechanisms of this effect remain unclear. To examine this, we recorded activity of hippocampal neurons in monkeys navigating the same virtual maze during two different tasks: a foraging task requiring only cue guided navigation, and a memory task also requiring context-object association. Within each task, individual neurons had spatially-selective response fields, enabling a linear classifier to decode position in the virtual environment in each task. However, the population code did not generalize across tasks. This was due to sensory and mnemonic coding of non-spatial features and their associations by single neurons during each period of the associative memory task. Thus, sensory and mnemonic representations of non-spatial features shape maps of space in the primate hippocampus during virtual navigation. This may reflect a fundamental role of the hippocampus in compressing information from a variety of sources for efficient memory storage.
Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription
Authors: Gilbertson Sarah , Federspiel Joel D. , Hartenian Ella , Cristea Ileana M. , Glaunsinger Britt 
Published: April 2018

AbstractAlterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.
Spontaneous mutations conferring antibiotic resistance to antitubercular drugs at a range of concentrations in Mycobacterium smegmatis
Authors: Nyinoh Iveren W , McFadden Johnjoe 
Published: April 2018

AbstractMycobacteria population can undergo mutations in their DNA sequence during replication, which if not repaired, would be transferred to future generations. In this study, in vitro spontaneous mutations in Mycobacterium smegmatis mc2155 (Msm) conferring resistance to isoniazid (INHr), rifampicin (RIFr), kanamycin (KANr) and streptomycin (STRr) were determined at several concentrations in a fluctuation assay. Mutation rate was estimated using the P₀ method, and estimates were then compared with the Lea-Coulson method of the median and Ma-Sandri-Sarkar Maximum Likelihood Estimator (MSS-MLE) method available on the Fluctuation analysis calculator (FALCOR). The mutation rates of RIFr ranged from 9.24 × 10-8 - 2.18 × 10-10, INHr 1.2 × 10-7 - 1.20×10-9, STRr 2.77 × 10-8 - 5.31 × 10-8 and KANr 1.7 × 10-8 mutations per cell division. This study provides mutation rate estimates to key antitubercular drugs at a range of concentrations.
EWI-2 Inhibits Cell-Cell Fusion at the Virological Presynapse
Authors: Whitaker Emily E. , Symeonides Menelaos , Munson Phillip B. , Thali Markus 
Published: April 2018

AbstractCell-to-cell transfer of virus particles through the virological synapse (VS) is a highly efficient mode of HIV-1 transmission. Formation of the VS, a transient multiform adhesion structure, is mediated through an interaction between the HIV-1 envelope glycoprotein (Env) and the viral receptor CD4 on the surface of infected cell and target cell, respectively. Given that Env, unlike many other viral fusogens, can mediate the merger of membranes at neutral pH, the close encounter of infected and uninfected cells would seem prone to result in cell-cell fusion and thus the formation of syncytia. However, while it is being recognized now that small, T cell-based syncytia are indeed a defining feature of the natural history of HIV-1, the majority of VSs nevertheless resolve without fusion, thus securing continued virus spread. Gag, the main viral structural component, is partially responsible for restraining Env and preventing it from becoming fusogenic before being incorporated into particles. In addition, a few cellular factors, including tetraspanins and ezrin, have also been shown to inhibit Env’s activity while this fusogen is still part of the producer cell.Here, we identify EWI-2, a protein that was previously shown to associate with the tetraspanins CD9 and CD81 and also with ezrin, as a host factor that contributes to the inhibition of Env­mediated cell-cell fusion. Using fluorescence microscopy, flow cytometry, and TZM-bl fusion assays, we show that EWI-2, comparable to tetraspanins, while overall being downregulated upon HIV-1 infection, accumulates at the producer cell side of the VS (i.e. the presynapse), where it contributes to the fusion-preventing activities of the other viral and cellular components.
Population structure ofBorrelia gariniifromIxodes uriaecollected in seabird colonies of the northwestern Atlantic Ocean
Authors: Munro Hannah J. , Ogden Nicholas H. , Mechai Samir , Lindsay L. Robbin , Robertson Gregory J. , Whitney Hugh , Lang Andrew S. 
Published: April 2018

AbstractThe occurrence ofBorrelia gariniiin seabird ticks,Ixodes uriae, associated with different species of colonial seabirds has been studied since the early 1990s. Research on the population structure of this bacterium in ticks from seabird colonies in the northeastern Atlantic Ocean has revealed admixture between marine and terrestrial tick populations. We studiedB. gariniipopulation structure inI. uriaecollected from seabird colonies in the northwestern Atlantic Ocean, in Newfoundland and Labrador, Canada. We applied a multi-locus sequence typing (MLST) scheme toB. gariniifound in ticks from four species of seabirds. TheB. gariniistrains found in this seabird colony ecosystem were diverse. Some were very similar to strains from Asia and Europe, including some obtained from human clinical samples, while others formed a divergent group specific to this region of the Atlantic Ocean.ImportanceThis study provides the firstB. gariniisequences from North American seabird ticks that were characterized using an MLST approach. This revealed new MLST sequence types and alleles, enhancing our knowledge ofB. gariniidiversity. Our findings highlight the genetic complexity ofB. gariniicirculating among seabird ticks and their avian hosts but also demonstrate surprisingly close connections betweenB. gariniiin this ecosystem and terrestrial sources in Eurasia. Genetic similarities amongB. gariniifrom seabird ticks and humans indicate the possibility thatB. gariniicirculating within seabird tick-avian host transmission cycles could directly, or indirectly via connectivity with terrestrial transmission cycles, have consequences for human health.
Conversion of iPS derived hepatic progenitors into scalable, functional and developmentally relevant human organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold engineered from collagen-coated pores of defined size
Authors: Seng Ng Soon , Saeb-Parsy Kourosh , Segal Joe M , Serra Maria Paola , Blackford Samuel J I , Lopez Marta Horcas , No Da Yoon , Frank Curtis W , Cho Nam Joon , Nakauchi Hiromitsu , Glenn Jeffrey S , Rashid S Tamir 
Published: April 2018

AbstractGeneration of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 µm diameter pores coated with Collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularize and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications.
Cold acclimation ofTrogoderma granariumEverts is tightly linked to regulation of enzyme activity, energy content and ion concentration
Authors: Mohammadzadeh Mozhgan , Izadi Hamzeh 
Published: April 2018

ABSTRACTIn this study, cold hardiness and some physiological characteristics ofT. granariumlarvae were investigated under different thermal regimes, i.e. warm-acclimated (WA), cold-acclimated (CA), fluctuating-acclimated (FA) and rapid cold-hardened (RCH). In all regimes, the survival rate of the larvae decreased with a decrease in temperature and raise in exposure time. Cold acclimated larvae showed the highest cold hardiness in -15 and -20 ºC. Control larvae had the highest glycogen content (34.4 ± 2.3 µg/gdw). In contrast, cold acclimation larvae had the lowest glycogen content (23.0 ± 1.6 µg/gdw). Change in trehalose content was reversely proportional to change in glycogen content. The greatest myo-inositol and glucose contents were detected in larvae cold acclimation treatment (10.7 ± 0.4 µg/gdw) and control (0.49 ± 0.03 µg/gdw), respectively. In control and treated larvae, the concentration of Na+decreased, though the concentration of K+rose, with rising the exposure time. The shape of the thermal reaction of AMP-depended protein kinase and protein phosphatase IIC followed the same norm, which is different from protein phosphatase I and protein phosphatase IIA. Protein phosphatase IIA and IIC showed a complete difference in thermal reaction norms. In did, thermal fluctuation caused the highest changes in the activity of the enzymes, whereas the RCH showed the lowest changes in the activity of the enzyme. Our results showed a significant enhancement of larval cold tolerance under CA regime that is related to the level of low molecular weight carbohydrates, protein kinase, and phosphatases activity, and hemolymph ions concentration.SUMMARY STATEMENTInTrogoderma granarium, cold acclimation enhances the larval cold tolerance that is related to change in the level of low molecular weight carbohydrates, protein kinase, and phosphatases activity, and hemolymph ions concentration.
Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with Adverse Drug Reactions
Authors: Ramsbottom Kerry A , Carr Dan , Jones Andrew R , Rigden Daniel J 
Published: April 2018

AbstractAdverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters such as including receptor flexibility affected the docking performance, were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles. It was found that the programmes investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results.
Observing fear enables plasticity of the dmPFC-BLA pathway during subsequent learning of inhibitory avoidance
Authors: Ito Wataru , Morozov Alexei 
Published: April 2018

AbstractObserving fear in others is a form of social distress. In mice, it leads to the formation of silent synapses in the prefrontal-amygdala pathway and enhances inhibitory avoidance learning at a later time. Here, we report that observing fear enabled ex vivo LTP. The unsilencing of silent synapses was the prevailing mechanism and the plasticity was occluded by inhibitory avoidance training. In free moving mice with OF experience, the inhibitory avoidance training transiently facilitated local field potentials evoked in BLA by stimulating the prefrontal afferents. The facilitation persisted during the first 4 hours after IA training, which is the time when IA memories consolidate. Thus, the OF-generated silent synapses enable plasticity that may enhance consolidation of IA memories.
Novel functions for integrin-associated proteins revealed by myofibril attachment inDrosophila
Authors: Green Hannah J. , Griffiths Annabel G. M. , Brown Nicholas H. 
Published: April 2018

AbstractWe use the myotendinous junction ofDrosophilaflight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.Graphical abstract
Axin proteolysis by Iduna is required for the regulation of stem cell proliferation and intestinal homeostasis in Drosophila
Authors: Gultekin Yetis , Steller Hermann 
Published: April 2018

AbstractThe self-renewal of intestinal stem cell is controlled by Wingless/Wnt-β catenin signaling both in Drosophila and mammals. Since Axin is a rate-limiting factor in Wingless signaling its regulation is essential. Iduna is an evolutionarily conserved ubiquitin E3 ligase that has been identified as a critical regulator for degradation of ADP-ribosylated Axin and thus of Wnt/β-catenin signaling. However, its physiological significance remains to be demonstrated. Here, we generated loss-of-function mutants of Iduna to investigate its physiological role in Drosophila. Genetic depletion of Iduna causes the accumulation of both Tankyrase and Axin. Increase of Axin protein in enterocytes non-autonomously enhanced stem cell divisions in the Drosophila midgut. Enterocytes secreted Unpaired and thereby stimulated the activity of the JAK-STAT pathway in intestinal stem cells. A decrease in Axin gene expression suppressed both the over-proliferation of stem cells and restored their numbers to normal levels in Iduna mutants. These findings suggest that Iduna-mediated regulation of Axin proteolysis is essential to maintain tissue homeostasis in the Drosophila midgut.
Digital preservation: some underlying issues for long-term preservation
Authors: Tripathi Sneha 
Published: April 2018

Purpose
The purpose of this study is to investigate the concept of digital preservation and traditional preservation per se and discusses various issues related to long-term preservation in a digital environment.

Design/methodology/approach
The study attempts to look into the various aspects of preservation in context of digital objects (borne or digitalized) especially. Bundling of an object (digital), digital storage, quality control and risk preparedness are some of the pointers studied to perceive an overall scenario for long-term preservation of an object.

Findings
Various methods have been suggested to deal with the issues related to long-term preservation of an object which can be used to frame an organization’s policy for long-term preservation.

Originality/value
The study emphasizes on collective measures incorporating traditional and digital means to ensure long-term preservation. It lists down various checklists to deal with various issues pertinent to long-term digital preservation.
Diagnosis and management of ADA2 deficient polyarteritis nodosa
Authors: Human Andrea , Pagnoux Christian 
Published: April 2018

AbstractDeficiency of ADA2 (DADA2) is a recently described systemic inflammatory vasculopathy caused by mutations in the CERC1 gene that often, but not always, clinically resembles polyarteritis nodosa (PAN). The condition was originally characterized by livedoid rash, systemic inflammation, variable hypogammaglobulinemia, and early‐onset stroke. The phenotypic spectrum has expanded to include patients with immunodeficiency syndromes and bone marrow dysfunction, which are not typical features of PAN. Exploration into the pathogenesis and treatment options of DADA2 has added to our understanding of this condition, but more studies are needed. The purpose of this article is to review the various clinical phenotypes of DADA2, and raise awareness among rheumatologists to consider DADA2 when evaluating patients presenting with PAN‐like disease.