bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Murine Lupus with TIGIT-Ig
Authors: Liu Shuowu , Sun Lizhu , Wang Chuqi , Cui Yingshu , Ling Yuee , Li Tian , Lin Fangxing , Fu Wenyan , Ding Min , Zhang Shuyi , Lei Changhai , Hu Shi 
Published: March 2019

AbstractThe TIGIT (T cell immunoreceptor with Ig and ITIM domains) protein is a co-inhibitory receptor that has been reported to suppress autoreactive T and B cells to trigger immunological tolerance. We generated a new recombinant protein by connecting the extracellular domain of murine TIGIT to the Fc region of the rat immunoglobulin IgG2a. The fusion protein was then characterized. The results suggested that among mice with lupus that were treated with the TIGIT-Ig fusion protein, the onset of proteinuria was delayed, serum concentrations of autoantibodies, such as antinuclear antibodies, were reduced without a decrease in the total IgG concentrations, and the survival rate was significantly increased compared to those of the controls. In conclusion, TIGIT-Ig administration showed promising results for both the prevention and treatment of autoimmune diseases in mice. This indicates that treatment with recombinant human TIGIT-Ig shows promise as an effective way to treat human autoimmune diseases.
Phenotyping and molecular marker analysis of WH1105 and Kharchia 65 backcrosses and F4progenies for salinity tolerance
Authors: Varsha  , Yashveer Shikha , Singh Vikram , Pratap Swati 
Published: March 2019

ABSTRACTSoil salinity is a worldwide adverse environmental factor for crop productivity and quality in arid, semiarid and coastal areas. In India, approximately 8.5 million hectare of land area is affected by high salinity (EC ≥ 5 dS m−1). Development of salinity tolerant varieties through marker assisted breeding is most efficient and effective strategy for management of soil salinity. WH 1105 is widely cultivated wheat variety with many agronomically superior qualities but is affected by soil salinity. Two genes (Nax1andNax2) for salinity tolerance were introgressed from Kharchia 65 into the genetic background of WH 1105 through marker assisted backcross breeding. BC1F3, BC2F2and F4generations of the cross WH1105 x Kharchia 65 were evaluated for various morphological traits under initial salt stress condition. On the basis of phenotypic and genotypic variations 44 high yielding plants were selected from the cross. Out of 178 SSRs tested, 30 were found polymorphic for background selection of the foreground selected plants. Cluster tree analysis of parents and all the three generations showed that all the selected plants were inclined toward recurrent parent (WH 1105) indicating higher similarity with the recurrent parent. Four plants were selected as high grain yielding and salt tolerant. These plants could be further backcrossed with the recurrent parent to develop salt tolerant wheat lines.
Enriching hippocampal memory function in older adults through real-world exploration
Authors: Kolarik Branden S. , Stark Shauna M. , Rutledge Samantha M. , Stark Craig E.L. 
Published: March 2019

AbstractAge-related structural and functional changes in the hippocampus can have a severe impact on hippocampally-dependent memory performance. Here we test the hypothesis that a real-world spatial exploration intervention will improve hippocampally-dependent memory performance in healthy older adults. We found that following our intervention, participants’ lure discrimination index (LDI) was significantly higher than it was at baseline, while traditional recognition scores remained relatively unchanged. These results point to the viability of a spatial exploration intervention for improving hippocampally-dependent memory in older adults.
Enriching hippocampal memory function in older adults through video games
Authors: Clemenson Gregory D. , Stark Shauna M. , Rutledge Samantha M. , Stark Craig E.L. 
Published: March 2019

AbstractHealthy aging is accompanied by a steady cognitive decline with clear losses in memory. Animal studies have consistently demonstrated that simply modifying an animal’s living environment (known as environmental enrichment) can have a positive influence on age-related cognitive decline in the hippocampus. Previously, we showed that playing immersive 3D video games can improve hippocampal-based memory in young healthy adults, suggesting that the exploration of the large open worlds of modern-day video games may act as proxy for environmental enrichment in humans. Here, we replicated our previous video game study in older adults and showing that playing video games for 4 weeks can improve hippocampal-based memory in a population that is already experiencing age-related decline in this memory. Furthermore, we showed that the improvements last for up to 4 weeks past the intervention, highlighting the potential of video games as intervention for age-related cognitive decline.
Inhibition of arterivirus RNA synthesis by cyclophilin inhibitors is counteracted by mutations in replicase transmembrane subunits
Authors: de Wilde Adriaan H. , Boomaars-van der Zanden A. Linda , de Jong Anja W. M. , Barcéna Montserrat , Snijder Eric J. , Posthuma Clara C. 
Published: March 2019

AbstractPreviously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse RNA viruses, including arteriviruses and coronaviruses, which both belong to the orderNidovirales. Here we aimed to identify arterivirus proteins involved in the mode-of-action of cyclophilin inhibitors and to investigate how these compounds inhibit arterivirus RNA synthesis in the infected cell. Repeated passaging of the arterivirus prototype equine arteritis virus (EAV) in the presence of CsA revealed that reduced drug sensitivity is associated with the emergence of adaptive mutations in nonstructural protein 5 (nsp5), one of the transmembrane subunits of the arterivirus replicase polyprotein. Introduction of singular nsp5 mutations (nsp5 Q21R, Y113H, or A134V) led to a ∼2-fold decrease in sensitivity to CsA treatment, whereas combinations of mutations further increased EAV’s CsA resistance. The detailed experimental characterization of engineered EAV mutants harboring CsA-resistance mutations implicated nsp5 in arterivirus RNA synthesis. Particularly, in anin vitroassay, EAV RNA synthesis was far less sensitive to CsA treatment when nsp5 contained the adaptive mutations mentioned above. Interestingly, for increased sensitivity to the closely-related drug ALV CsA-resistant nsp5 mutants required the incorporation of an additional adaptive mutation, which resided in nsp2 (H114R), another transmembrane subunit of the arterivirus replicase. Our study provides the first evidence for the involvement of nsp2 and nsp5 in the mechanism underlying the inhibition of arterivirus replication by cyclophilin inhibitors.ImportanceCurrently, no approved treatments are available to combat infections with nidoviruses, a group of plus-stranded RNA viruses including important zoonotic and veterinary pathogens. Previously, the cyclophilin inhibitors cyclosporin A (CsA) and Alisporivir (ALV) were shown to inhibit the replication of diverse nidoviruses (both arteriviruses and coronaviruses), and may thus represent a class of pan-nidovirus inhibitors. Here, using the arterivirus prototype equine arteritis virus, we have established that resistance to CsA and ALV treatment is associated with adaptive mutations in two trans-membrane subunits of the viral replication complex, nonstructural proteins 2 and 5. This is the first evidence for the involvement of specific replicase subunits of nidoviruses in the mechanism underlying the inhibition of their replication by cyclophilin inhibitors. Understanding this mechanism of action is of major importance to guide future drug design, both for nidoviruses and other RNA viruses inhibited by these compounds.
Vesicle-associatedPseudomonas aeruginosaleucine aminopeptidase modulates bacterial biofilms grown on host cellular substrates
Authors: Esoda Caitlin N. , Kuehn Meta J. 
Published: March 2019

AbstractPseudomonas aeruginosa, known as one of the leading causes of morbidity and mortality in cystic fibrosis (CF) patients, secretes a variety of virulence-associated proteases. These enzymes have been shown to contribute significantly toP. aeruginosapathogenesis and biofilm formation in the chronic colonization of CF patient lungs, as well as playing a role in infections of the cornea, burn wounds and chronic wounds. Our lab has previously characterized a secretedP. aeruginosapeptidase, PaAP, that is highly expressed in chronic CF isolates. This leucine aminopeptidase is not only secreted solubly, it also associates with bacterial outer membrane vesicles (OMVs), structures known for their contribution to virulence mechanisms in a variety of Gram-negative species and one of the major components of the biofilm matrix. With this in mind, we hypothesized that PaAP may play a role inP. aeruginosabiofilm formation. Using a lung epithelial cell/bacterial biofilm coculture model, we show that PaAP deletion in a clinicalP. aeruginosabackground leads to increased early biofilm formation. We additionally found that only native vesicle-bound PaAP, as opposed to its soluble forms, could reconstitute the original PaAP-mediated inhibition phenotype, and that the PaAP-containing vesicles could disperse preformed biofilm microcolonies ofKlebsiella pneumoniae, another lung pathogen. These data provide the basis for future work into the mechanism behind PaAP-OMV mediated bacterial microcolony dispersal and the application of these findings to clinical anti-biofilm research.
Global distribution of earthworm diversity
Authors: Phillips Helen R P , Guerra Carlos A , Bartz Marie L. C. , Briones Maria J. I. , Brown George , Ferlian Olga , Gongalsky Konstantin B. , Krebs Julia , Orgiazzi Alberto , Schwarz Benjamin , Bach Elizabeth M. , Bennett Joanne , Brose Ulrich , Decaëns Thibaud , De Vries Franciska T. , König-Ries Birgitta , Loreau Michel , Mathieu Jérôme , Mulder Christian , van der Putten Wim H. , Ramirez Kelly S. , Rillig Matthias C. , Russell David , Rutgers Michiel , Thakur Madhav P. , Wall Diana H. , Wardle David ,   Data Providers (see bulk upload sheet), Cameron Erin , Eisenhauer Nico 
Published: March 2019

AbstractSoil organisms provide crucial ecosystem services that support human life. However, little is known about their diversity, distribution, and the threats affecting them. Here, we compiled a global dataset of sampled earthworm communities from over 7000 sites in 56 countries to predict patterns in earthworm diversity, abundance, and biomass. We identify the environmental drivers shaping these patterns. Local species richness and abundance typically peaked at higher latitudes, while biomass peaked in the tropics, patterns opposite to those observed in aboveground organisms. Similar to many aboveground taxa, climate variables were more important in shaping earthworm communities than soil properties or habitat cover. These findings highlight that, while the environmental drivers are similar, conservation strategies to conserve aboveground biodiversity might not be appropriate for earthworm diversity, especially in a changing climate.One sentence summaryGlobal patterns of earthworm diversity, abundance and biomass are driven by climate but patterns differ from many aboveground taxa.
STATegra: a comprehensive multi-omics dataset of B-cell differentiation in mouse
Authors: Gomez-Cabrero David , Tarazona Sonia , Ferreirós-Vidal Isabel , Ramirez Ricardo N. , Company Carlos , Schmidt Andreas , Reijmers Theo , Saint Paul Veronica von , Marabita Francesco , Rodríguez-Ubreva Javier , Garcia-Gomez Antonio , Carroll Thomas , Cooper Lee , Liang Ziwei , Dharmalingam Gopuraja , van der Kloet Frans , Harms Amy C. , Balzano-Nogueira Leandro , Lagani Vicenzo , Tsamardinos Ioannis , Lappe Michael , Maier Dieter , Westerhuis Johan A. , Hankemeier Thomas , Imhof Axel , Ballestar Esteban , Mortazavi Ali , Merkenschlager Matthias , Tegner Jesper , Conesa Ana 
Published: March 2019

AbstractMulti-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.
Modeling the ballistic-to-diffusive transition in nematode motility reveals variation in exploratory behavior across species
Authors: Helms Stephen J. , Rozemuller W. Mathijs , Costa Antonio Carlos , Avery Leon , Stephens Greg J. , Shimizu Thomas S. 
Published: March 2019

AbstractA quantitative understanding of organism-level behavior requires predictive models that can capture the richness of behavioral phenotypes, yet are simple enough to connect with underlying mechanistic processes. Here we investigate the motile behavior of nematodes at the level of their translational motion on surfaces driven by undulatory propulsion. We broadly sample the nematode behavioral repertoire by measuring motile trajectories of the canonical lab strainC. elegansN2 as well as wild strains and distant species. We focus on trajectory dynamics over timescales spanning the transition from ballistic (straight) to diffusive (random) movement and find that salient features of the motility statistics are captured by a random walk model with independent dynamics in the speed, bearing and reversal events. We show that the model parameters vary among species in a correlated, low-dimensional manner suggestive of a common mode of behavioral control and a trade-off between exploration and exploitation. The distribution of phenotypes along this primary mode of variation reveals that not only the mean but also the variance varies considerably across strains, suggesting that these nematode lineages employ contrasting “bet-hedging” strategies for foraging.
A phenotypically plastic magic trait promoting reproductive isolation in sticklebacks?
Authors: Garduno Paz Monica V. , Huntingford Felicity A. , Garrett Sean , Adams Colin E. 
Published: March 2019

AbstractThis study identifies one possible mechanism whereby gene flow is interrupted in populations undergoing evolutionary divergence in sympatry; this is an important issue in evolutionary biology that remains poorly understood. Variation in trophic morphology was induced in three-spined stickleback by exposing them from an early age either to large benthic or to small pelagic prey. At sexual maturity, females given a choice between two breeding males, showed positive assortative mate choice for males raised on the same diet as themselves. The data indicate that this was mediated through a preference for males with trophic morphology similar to that of fish with which the females were familiar (from their pre-testing holding tanks). In trials where the female did not choose the most familiar male, the evidence suggests that either she had difficulty discriminating between two similar males or was positively choosing males with more extreme morphologies (more benthic-like or pelagic -like). This study has shown for the first time that expression of a plastic trait induced at an early age, not only results in specialisation for local foraging regimes but can also play a significant role in mate choice. This is equivalent to an environmentally induced, plastic version of the “magic traits” that promote ecologically-driven divergence in sympatry, hence the proposed descriptor “plastic magic trait”.
In vivo feasibility study of the use of porous polyhedral oligomeric silsesquioxane implants in partial laryngeal reconstruction
Authors: Birchall Martin A. , Herrmann Peggy , Sibbons Paul 
Published: March 2019

AbstractBackgroundLoss of substantial volumes of laryngeal tissue after trauma or cancer significantly impairs quality of life. We hypothesised that repair of laryngeal defects with a candidate biomaterial, seeded with mesenchymal stem cells (MSC) and epithelial cells, may offer a therapeutic approach to this unmet need.MethodMoulded porous polyhedral oligomeric silsesquioxane polycarbonate-urea (POSS-PCU) scaffolds were seeded with human-derived MSC and epithelial cells, were implanted orthotopically into a defect created in the thyroid cartilage in eight pigs and monitoredin vivofor 2 months.In vivoassessments were performed at 1, 2, 4 and 8 weeks post implantation. Histology was performed following termination.ResultsImplant operations were uncomplicated. One pig was terminated early (2 weeks post-implantation) following expectoration of its implant. No other mortality or morbidity was observed. Endoscopy showed partial extrusion of implants at two weeks and complete extrusion of all implants by termination.ConclusionsPOSS-PCU moulded laryngeal implants, in the present formulation, are extruded from the site of implantation between two- and eight-weeks post-surgery in pigs. In its present formulation and with the present, one-stage, protocol, this material does not appear to provide a suitable scaffold and vehicle for cells intended for partial laryngeal replacement in pigs.
Fully-sensitive Seed Finding in Sequence Graphs Using a Hybrid Index
Authors: Ghaffaari Ali , Marschall Tobias 
Published: March 2019

AbstractMotivationSequence graphs are versatile data structures that are, for instance, able to represent the genetic variation found in a population and to facilitate genome assembly. Read mapping to sequence graphs constitutes an important step for many applications and is usually done by first finding exact seed matches, which are then extended by alignment. Existing methods for finding seed hits prune the graph in complex regions, leading to a loss of information especially in highly polymorphic regions of the genome. While such complex graph structures can indeed lead to a combinatorial explosion of possible alleles, the query set of reads from a diploid individual realizes only two alleles per locus—a property that is not exploited by extant methods.ResultsWe present thePan-genomeSeedIndex (PSI), a fully-sensitive hybrid method for seed finding, which takes full advantage of this property by combining an index over selected paths in the graph with an index over the query reads. This enables PSI to find all seeds while eliminating the need to prune the graph. We demonstrate its performance with different parameter settings on both simulated data and on a whole human genome graph constructed from variants in the 1000 Genome Project data set. On this graph, PSI outperforms GCSA2 in terms of index size, query time, and sensitivity.AvailabilityThe C++ implementation is publicly available at:https://github.com/cartoonist/psi.
Bidirectional FtsZ filament treadmilling transforms lipid membranes via torsional stress
Authors: Ramirez-Diaz Diego A. , Merino-Salomon Adrian , Meyer Fabian , Heymann Michael , Rivas German , Bramkamp Marc , Schwille Petra 
Published: March 2019

AbstractFtsZ is a key component in bacterial cell division, being the primary protein of the presumably contractile Z ring. In vivo and in vitro, it shows two distinctive features that could so far however not be mechanistically linked: self-organization into directionally treadmilling vortices on solid supported membranes, and shape deformation of flexible liposomes. In cells, circumferential treadmilling of FtsZ was shown to recruit septum-building enzymes, but an active force production remains elusive. To gain mechanistic understanding of FtsZ dependent membrane deformations and constriction, we designed an in vitro assay based on soft lipid tubes pulled from FtsZ decorated giant lipid vesicles (GUVs) by optical tweezers. FtsZ actively transformed these tubes into spring-like structures, where GTPase activity promoted spring compression. Operating the optical tweezers in lateral vibration mode and assigning spring constants to FtsZ coated tubes, we found that FtsZ rings indeed exerts 0.14 – 1.09 pN forces upon GTP hydrolysis, through torsional stress induced by bidirectional treadmilling. These directional forces could further be demonstrated to induce membrane budding with constricting necks on both, giant vesicles and E.coli cells devoid of their cell walls.
Multiscale analysis of acne connects molecular subnetworks with disease status
Authors: Hall Jacob B. , Divaraniya Aparna A. , Lee Hao-Chih , Becker Christine E. , McCauley Benjamin , Glowe Patricia K. , Sebra Robert , Pavel Ana B. , Singer Giselle , Nelson Amanda , Thiboutot Diane , Marmur Ellen , Schadt Eric E. , Zeichner Joshua , Guttman-Yassky Emma , Kidd Brian A. , Dudley Joel T. 
Published: March 2019

ABSTRACTAcne vulgaris affects millions of individuals and can lead to psychosocial impairment as well as permanent scarring. Previous studies investigating acne pathogenesis have either examined a targeted set of biological parameters in a modest-sized cohort or carried out high-throughput assays on a small number of samples. To develop a more comprehensive understanding of acne pathophysiology, we conducted an in-depth multi-omic study of 56 acne patients and 20 individuals without acne. We collected whole blood, skin punch biopsies, microbiota from skin follicles, and relevant clinical measurements to understand how multiple factors contribute to acne. We provide an integrative analysis of multi-omics data that results in a molecular network of acne. Comparisons of lesional and non-lesional skin highlighted multiple biological processes, including immune cell and inflammatory responses, response to stress, T cell activation, lipid biosynthesis, fatty acid metabolism, keratinocytes, antimicrobial activity, epithelial cell differentiation, and response to wounding, that are differentially altered in acne lesions compared to non-lesions. Our results suggest baseline differences in the skin that may predispose individuals to develop acne. These datasets and findings offer a framework for new target identification and reference for future studies.