bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep single-cell RNA sequencing data of individual T cells from treatment-naïve colorectal cancer patients
Authors: Zhang Yuanyuan , Zheng Liangtao , Zhang Lei , Hu Xueda , Ren Xianwen , Zhang Zemin 
Published: July 2019

AbstractT cells, as a crucial compartment of the tumour microenvironment, play vital roles in cancer immunotherapy. However, the basic properties of tumour-infiltrating T cells (TILs) such as the functional state, migratory capability and clonal expansion remain elusive. Here, using Smart-seq2 protocol, we have generated a RNA sequencing dataset of 11,138 T cells isolated from peripheral blood, adjacent normal and tumour tissues of 12 colorectal cancer (CRC) patients, including 4 with microsatellite instability (MSI). The dataset contained an expression profile of 10,805 T cells, as well as the full-length T cell receptor (TCR) sequences of 9,878 cells after quality control. To facilitate data mining of our T cell dataset, we developed a web-based application to deliver systematic interrogations and customizable functionalities (http://crctcell.cancer-pku.cn/). Functioning with our dataset, the web tool enables the characterization of TILs based on both transcriptome and assembled TCR sequences at the single cell level, which will help unleash the potential value of our CRC T cell data resource.
Temporally replicated DNA methylation patterns in great tit using reduced representation bisulfite sequencing
Authors: Mäkinen Hannu , Viitaniemi Heidi M. , Visser Marcel E. , Verhagen Irene , van Oers Kees , Husby Arild 
Published: July 2019

AbstractSeasonal timing of reproduction is an important fitness trait in many plants and animals but the underlying molecular mechanism for this trait is poorly known. DNA methylation is known to affect timing of reproduction in various organisms and is therefore a potential mechanism also in birds. Here we describe genome wide data aiming to detect temporal changes in methylation in relation to timing of breeding using artificial selection lines of great tits (Parus major) exposed to contrasting temperature treatments. Methylation levels of DNA extracted from erythrocytes were examined using reduced representation bisulfite sequencing (RRBS). In total, we obtained sequencing data from 63 libraries over four different time points from 16 birds with on average 20 million quality filtered reads per library. These data describe individual level temporal variation in DNA methylation throughout the breeding season under experimental temperature regimes and provides a resource for future studies investigating the role of temporal changes in DNA methylation in timing of reproduction.
Space-time clustering of recently-diagnosed tuberculosis and impact of ART scale-up: Evidence from an HIV hyper-endemic rural South African population
Authors: Tomita Andrew , Smith Catherine M. , Lessells Richard J. , Pym Alexander , Grant Alison D. , de Oliveira Tulio , Tanser Frank 
Published: July 2019

AbstractIn HIV hyperendemic sub-Saharan African communities, particularly in southern Africa, the likelihood of achieving the Sustainable Development Goal of ending the tuberculosis (TB) epidemic by 2030 is low, due to lack of cost-effective and practical interventions in population settings. We used one of Africa’s largest population-based prospective cohorts from rural KwaZulu-Natal Province, South Africa, to measure the spatial variations in the prevalence of recently-diagnosed TB disease, and to quantify the impact of community coverage of antiretroviral therapy (ART) on recently-diagnosed TB disease. We collected data on TB disease episodes from a population-based sample of 41,812 adult individuals between 2009 and 2015. Spatial clusters (‘hotspots’) of recently-diagnosed TB were identified using a space-time scan statistic. Multilevel logistic regression models were fitted to investigate the relationship between community ART coverage and recently-diagnosed TB. Spatial clusters of recently-diagnosed TB were identified in a region characterized by a high prevalence of HIV and population movement. Every percentage increase in ART coverage was associated with a 2% decrease in the odds of recently-diagnosed TB (aOR = 0.98, 95% CI:0.97–0.99). We identified for the first time the clear occurrence of recently-diagnosed TB hotspots, and quantified potential benefit of increased community ART coverage in lowering tuberculosis, highlighting the need to prioritize the expansion of such effective population interventions targeting high-risk areas.
The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice
Authors: Haug Michael , Meyer Charlotte , Reischl Barbara , Prölß Gerhard , Vetter Kristina , Iberl Julian , Nübler Stefanie , Schürmann Sebastian , Rupitsch Stefan J. , Heckel Michael , Pöschel Thorsten , Winter Lilli , Herrmann Harald , Clemen Christoph S. , Schröder Rolf , Friedrich Oliver 
Published: July 2019

AbstractMutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17–23 wks), adult (25–45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates. We used a novel automated biomechatronics platform, the MyoRobot, to perform coherent quantitative recordings of passive (resting length-tension curves, visco-elasticity) and active (caffeine-induced force transients, pCa-force, ‘slack-tests’) parameters to determine age-dependent effects of the R349P desmin mutation in slow-twitch soleus and fast-twitch extensor digitorum longus small fiber bundles. We demonstrate that active force properties are not affected by this mutation while passive steady-state elasticity is vastly altered in R349P desmin fiber bundles compatible with a pre-aged phenotype exhibiting stiffer muscle preparations. Visco-elasticity on the other hand, was not altered. Our study represents the first systematic age-related characterization of small muscle fiber bundle preparation biomechanics in conjunction with inherited desminopathy.
Trade-offs between parameter constraints and model realism: a case study
Authors: Jehn Florian U. , Chamorro Alejandro , Houska Tobias , Breuer Lutz 
Published: July 2019

AbstractTightly constraint parameter ranges are seen as an important goal in constructing hydrological models, a difficult task in complex models. However, many studies show that complex models are often good at capturing the behaviour of a river. Therefore, this study explores the trade-offs between tightly constrained parameters and the ability to predict hydrological signatures, that capture the behaviour of a river. To accomplish this we built five models of differing complexity, ranging from a simple lumped model to a semi-lumped model with eight spatial subdivisions. All models are built within the same modelling framework, use the same data, and are calibrated with the same algorithm. We also consider two different methods for the potential evapotranspiration. We found that that there is a clear trade-off along the axis of complexity. While the more simple models can constrain their parameters quite well, they fail to get the hydrological signatures right. It is the other way around for the more complex models. The method of evapotranspiration only influences the parameters directly related to it. This study highlights that it is important to focus not only on parametric uncertainty. Tightly constrained parameters can be misguiding as they give credibility to oversimplified model structures.
Unified Theory of Ultimate Hydrocarbon Recovery for Primary and Cyclic Injection Processes in Ultratight Reservoirs
Authors: Cronin Michael , Emami-Meybodi Hamid , Johns Russell T. 
Published: July 2019

AbstractThis paper presents a simple method to estimate ultimate recovery factors (URF) of ultratight reservoirs based on equilibrium by diffusion in which URF is only a function of changes in hydrocarbon density between initial and final states. URF is defined at infinite time and therefore does not depend on the transient behavior. Although URF may not be achievable during the life-cycle of the field development and production, it provides valuable insights on the role of phase behavior. We show that equilibrium phase behavior defines the absolute upper-bound for URF during primary production and explains the poor recovery from shale oil reservoirs compared to the high recovery factor in shale gas reservoirs in a unifying way. Further, we quantify how injected solvent compositions (CH4, CO2, N2, and C2H6) during huff’n’puff enhanced oil recovery (EOR) improve recovery based on density reduction and compositional dilution, and show that the largest percentage increase in recovery occurs for heavier oils. Our calculations provide a practical means to define the URF from primary production as a function of reservoir fluid composition, temperature, and pressure drawdown. In addition, our calculations articulate incremental URF (IURF) of solvent huff‘n’puff based on net solvent transfer into ultratight rock, which is a key design consideration. The results illustrate that solvent transfer dilutes the hydrocarbons in place, thus maximizing long-term hydrocarbon recovery. Net mass transfer can be improved by enhancing the diffusion of solvent into the matrix based on the huff‘n’puff design parameters including solvent composition, drawdown pressure, and the net amount of solvent injected based on optimal frequency and cycle duration.
Prevention of urinary catheter-associated infections by coating antimicrobial peptides from crowberry endophytes
Authors: Monteiro Claudia , Costa Fabíola , Pirttilä Anna Maria , Tejesvi Mysore V. , Martins M. Cristina L. 
Published: July 2019

AbstractUrinary catheters are extensively used in hospitals, being responsible for about 75% of hospital-acquired infections. In this work, a de novo designed antimicrobial peptide (AMP) Chain201D was studied in the context of urinary catheter-associated infections. Chain201D showed excellent antimicrobial activity against relevant ATCC strains and clinical isolates of bacteria and yeast and demonstrated high stability in a wide range of temperatures, pH and salt concentrations. Moreover, the bactericidal activity of Chain201D immobilized on a model surface was studied against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), some of the most prevalent strains found in urinary catheter-associated infections. Chain201D was successfully tethered to ((1-mercapto-11-undecyl)-(tetra(ethylene glycol) (EG4)) terminated self-assembled monolayers (SAMs), (EG4-SAMs), activated by 1,1′-Carbonyldiimidazole (CDI) at different concentrations. Chain201D surfaces can bind and kill by contact a high percentage of adherent bacteria. These achievements are obtained without any peptide modification (for chemoselective conjugation) and without the use of a spacer. Moreover, increased amounts of immobilized AMP lead to higher numbers of adhered/dead bacteria, revealing a concentration-dependent behaviour and demonstrating that Chain201D has excellent potential for developing antimicrobial urinary catheters.
Comparative Genomics Analysis in Grass Species Reveals Two Distinct Evolutionary Strategies Adopted by R Genes
Authors: Zhang Yinan , Guo Meijun , Shen Jie , Song Xie , Dong Shuqi , Wen Yinyuan , Yuan Xiangyang , Guo Pingyi 
Published: July 2019

AbstractResistance genes play an important role in the defense of plants against the invasion of pathogens. In Setaria italica and closely related grass species, R genes have been identified through genetic mapping and genome-wide homologous/domain searching. However, there has been to date no systematic analysis of the evolutionary features of R genes across all sequenced grass genomes. Here, we determined and comprehensively compared R genes in all 12 assembled grass genomes and an outgroup species (Arabidopsis thaliana) through synteny and selection analyses of multiple genomes. We found that the two groups of nucleotide binding site (NBS) domains containing R genes—R tandem duplications (TD) and R singletons—adopted different strategies and showed different features in their evolution. Based on Ka/Ks analysis between syntenic R loci pairs of TDs or singletons, we conclude that R singletons are under stronger purifying selection to be conserved among different grass species than R TDs, while R genes located at TD arrays have evolved much faster through diversifying selection. Furthermore, using the variome datasets of S. italica populations, we scanned for selection signals on genes and observed that a part of R singleton genes have been under purifying selection in populations of S. italica, which is consistent with the pattern observed in syntenic R singletons among different grass species. Additionally, we checked the synteny relationships of reported R genes in grass species and found that the functionally mapped R genes for novel resistance traits are prone to appear in TDs and are heavily divergent from their syntenic orthologs in other grass species, such the black streak R gene Rxo1 in Z. mays and the blast R gene Pi37 in O. sativa. These findings indicate that the R genes from TDs adopted tandem duplications to evolve faster and accumulate more mutations to facilitate functional innovation to cope with variable threats from a fluctuating environment, while R singletons provide a way for R genes to maintain sequence stability and retain conservation of function.
Impact of the Madden-Julian oscillation on Antarctic sea ice and its dynamical mechanism
Authors: Lee Hyun-Ju , Seo Kyong-Hwan 
Published: July 2019

AbstractThe influence of the Madden-Julian oscillation (MJO) on Antarctic sea ice extent has not been extensively explored. This study investigates intraseasonal variability of the sea ice extent induced by the MJO and its physical mechanism. During austral winter, the sea ice extent anomaly exhibits considerable melting and freezing as the MJO evolves. Numerical experiments and the Rossby wave theory show that the high-latitude circulation anomalies in response to the MJO are responsible for the sea ice change. The MJO-induced Rossby waves propagate into the Southern Hemisphere through the northerly ducts over the western Indian Ocean–central Africa and the Maritime Continent. The MJO-induced circulation anomalies reach high latitudes and lead to anomalous meridional temperature advection, causing changes in the sea ice extent. The time difference between the meridional wind and sea ice anomalies is ~5 days. As the MJO moves, the sea ice extent anomaly also exhibits eastward-migrating behavior. Strong sea ice melting in the total anomaly is synchronous to the evolution of the MJO, suggesting the practical usefulness of the location of the MJO for the prediction of the sea ice decrease.
Histo-blood group antigens and rotavirus vaccine shedding in Nicaraguan infants
Authors: Bucardo Filemón , Reyes Yaoska , Rönnelid Ylva , González Fredman , Sharma Sumit , Svensson Lennart , Nordgren Johan 
Published: July 2019

AbstractABO, Lewis and secretor histo-blood group antigens (HBGA) are susceptibility factors for rotavirus in a P-genotype dependent manner and can influence IgA seroconversion rates following rotavirus vaccination. To investigate the association between HBGA phenotypes and rotavirus vaccine shedding fecal samples (n = 304) from a total of 141 infants vaccinated with Rotarix (n = 71) and RotaTeq (n = 70) were prospectively sampled in three time frames (≤3, 4–7 and ≥8 days) after first vaccination dose. Rotavirus was detected with qPCR and genotypes determined by G/P multiplex PCR and/or sequencing. HBGAs were determined by hemagglutination and saliva based ELISA. Low shedding rates were observed, with slightly more children vaccinated with RotaTeq (19%) than Rotarix (11%) shedding rotavirus at ≥4 days post vaccination (DPV). At ≥4 DPV no infant of Lewis A (n = 6) or nonsecretor (n = 9) phenotype in the Rotarix cohort shed rotavirus; the same observation was made for Lewis A infants (n = 7) in the RotaTeq cohort. Putative in-vivo gene reassortment among RotaTeq strains occurred, yielding mainly G1P[8] strains. The bovine derived P[5] genotype included in RotaTeq was able to replicate and be shed at long time frames (>13 DPV). The results of this study are consistent with that HBGA phenotype influences vaccine strain shedding as similarly observed for natural infections. Due to the low overall shedding rates observed, additional studies are however warranted.
Functional importance of the oligomer formation of the cyanobacterial H+ pump Gloeobacter rhodopsin
Authors: Iizuka Azusa , Kajimoto Kousuke , Fujisawa Tomotsumi , Tsukamoto Takashi , Aizawa Tomoyasu , Kamo Naoki , Jung Kwang-Hwan , Unno Masashi , Demura Makoto , Kikukawa Takashi 
Published: July 2019

AbstractMany microbial rhodopsins self-oligomerize, but the functional consequences of oligomerization have not been well clarified. We examined the effects of oligomerization of a H+ pump, Gloeobacter rhodopsin (GR), by using nanodisc containing trimeric and monomeric GR. The monomerization did not appear to affect the unphotolyzed GR. However, we found a significant impact on the photoreaction: The monomeric GR showed faint M intermediate formation and negligible H+ transfer reactions. These changes reflected the elevated pKa of the Asp121 residue, whose deprotonation is a prerequisite for the functional photoreaction. Here, we focused on His87, which is a neighboring residue of Asp121 and conserved among eubacterial H+ pumps but replaced by Met in an archaeal H+ pump. We found that the H87M mutation removes the “monomerization effects”: Even in the monomeric state, H87M contained the deprotonated Asp121 and showed both M formation and distinct H+ transfer reactions. Thus, for wild-type GR, monomerization probably strengthens the Asp121-His87 interaction and thereby elevates the pKa of Asp121 residue. This strong interaction might occur due to the loosened protein structure and/or the disruption of the interprotomer interaction of His87. Thus, the trimeric assembly of GR enables light-induced H+ transfer reactions through adjusting the positions of key residues.
Enhancement of Single Molecule Raman Scattering using Sprouted Potato Shaped Bimetallic Nanoparticles
Authors: William R. V. , Das G. M. , Dantham V. R. , Laha R. 
Published: July 2019

AbstractHerein, for the first time, we report the single molecule surface enhanced resonance Raman scattering (SERRS) and surface enhanced Raman scattering (SERS) spectra with high signal to noise ratio (S/N) using plasmon-active substrates fabricated by sprouted potato shaped Au-Ag bimetallic nanoparticles, prepared using a new one-step synthesis method. This particular shape of the nanoparticles has been obtained by fixing the amount of Au and carefully adjusting the amount of Ag. These nanoparticles have been characterized using scanning electron microscopy, extinction spectroscopy, and glancing angle X-ray diffraction. The single molecule sensitivity of SERS substrates has been tested with two different molecular Raman probes. The origin of the electromagnetic enhancement of single molecule Raman scattering in the presence of sprouted shape nanoparticles has been explained using quasi-static theory as well as finite element method (FEM) simulations. Moreover, the role of (i) methods for binding Raman probe molecules to the substrate, (ii) concentration of molecules, and (iii) Au-Ag ratio on the spectra of molecules has been studied in detail.
Circular RNAs are differentially expressed in prostate cancer and are potentially associated with resistance to enzalutamide
Authors: Greene John , Baird Anne-Marie , Casey Orla , Brady Lauren , Blackshields Gordon , Lim Marvin , O’Brien Odharnaith , Gray Steven G. , McDermott Raymond , Finn Stephen P. 
Published: July 2019

AbstractMost forms of castration-resistant prostate cancer (CRPC) are dependent on the androgen receptor (AR) for survival. While, enzalutamide provides a substantial survival benefit, it is not curative and many patients develop resistance to therapy. Although not yet fully understood, resistance can develop through a number of mechanisms, such as AR copy number gain, the generation of splice variants such as AR-V7 and mutations within the ligand binding domain (LBD) of the AR. circular RNAs (circRNAs) are a novel type of non-coding RNA, which can regulate the function of miRNA, and may play a key role in the development of drug resistance. circRNAs are highly resistant to degradation, are detectable in plasma and, therefore may serve a role as clinical biomarkers. In this study, AR-V7 expression was assessed in an isogenic model of enzalutamide resistance. The model consisted of age matched control cells and two sub-line clones displaying varied resistance to enzalutamide. circRNA profiling was performed on the panel using a high throughout microarray assay. Bioinformatic analysis identified a number of differentially expressed circRNAs and predicted five miRNA binding sites for each circRNA. miRNAs were stratified based on known associations with prostate cancer, and targets were validated using qPCR. Overall, circRNAs were more often down regulated in resistant cell lines compared with control (588 vs. 278). Of particular interest was hsa_circ_0004870, which was down-regulated in enzalutamide resistant cells (p ≤ 0.05, vs. sensitive cells), decreased in cells that highly express AR (p ≤ 0.01, vs. AR negative), and decreased in malignant cells (p ≤ 0.01, vs. benign). The associated parental gene was identified as RBM39, a member of the U2AF65 family of proteins. Both genes were down-regulated in resistant cells (p < 0.05, vs. sensitive cells). This is one of the first studies to profile and demonstrate discrete circRNA expression patterns in an enzalutamide resistant cell line model of prostate cancer. Our data suggests that hsa_circ_0004870, through RBM39, may play a critical role in the development of enzalutamide resistance in CRPC.
Increased similarity of neural responses to experienced and empathic distress in costly altruism
Authors: O’Connell Katherine , Brethel-Haurwitz Kristin M. , Rhoads Shawn A. , Cardinale Elise M. , Vekaria Kruti M. , Robertson Emily L. , Walitt Brian , VanMeter John W. , Marsh Abigail A. 
Published: July 2019

AbstractEmpathy—affective resonance with others’ sensory or emotional experiences—is hypothesized to be an important precursor to altruism. However, it is not known whether real-world altruists’ heightened empathy reflects true self-other mapping of multi-voxel neural response patterns. We investigated this relationship in adults who had engaged in extraordinarily costly real-world altruism: donating a kidney to a stranger. Altruists and controls completed fMRI testing while anticipating and experiencing pain, and watching as a stranger anticipated and experienced pain. Machine learning classifiers tested for shared representation between experienced and observed distress. Altruists exhibited more similar representations of experienced and observed fearful anticipation spontaneously and following an empathy prompt in anterior insula and anterior/middle cingulate cortex, respectively, suggesting heightened empathic proclivities and abilities for fear. During pain epochs, altruists were distinguished by spontaneous empathic responses in anterior insula, anterior/mid-cingulate cortex and supplementary motor area, but showed no difference from controls after the empathy prompt. These findings (1) link shared multi-voxel representations of the distress of self and others to real-world costly altruism, (2) reinforce distinctions between empathy for sensory states like pain and anticipatory affective states like fear, and (3) highlight the importance of differentiating between the proclivity and ability to empathize.