bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node
Authors: Barber-Axthelm Isaac M , Kelly Hannah G , Esterbauer Robyn , Wragg Kathleen , Gibbon Anne , Lee Wen Shi , Wheatley Adam K , Kent Stephen J , Tan Hyon-Xhi , Juno Jennifer A 
Published: August 2020

AbstractCharacterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between individual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models.
Age and gender dependence of liver diffusion parameters and the evidence of intravoxel incoherent motion modelling of perfusion component is constrained by diffusion component
Authors: Huang Hua , Zheng Cun-Jing , Wang Li-Fei , Che-Nordin Nazmi , Wáng Yì Xiáng J. 
Published: August 2020

AbstractObjectivesTo establish reference values for middle aged subjects and investigate age and gender dependence of liver diffusion MRI parameters.MethodsThe IVIM type of liver diffusion scan was based on a single-shot spin-echo type echo-planar sequence using a 1.5-T magnet with 16b-values. DDVD (diffusion-derived vessel density) was the signal difference betweenb=0 andb=2 s/mm2images after removing visible vessels. IVIM analysis was performed with full-fitting and segmented-fitting, and with threshold b-value of 60 or 200 s/mm2, and fitting started fromb=2 s/mm2. 32 men (age range: 25-71 years) and 26 men (age: 22-69 years) had DDVD and IVIM analysis respectively, while 36 women (age: 20-71 years) had DDVD and IVIM analysis.ResultsDDVD had an age-related reduction noted for women. IVIM results of full fitting had good agreement with segmented fitting with thresholdbof 60 s/mm2results, but less so with results of thresholdbof 200 s/mm2. As age increases, female subjects’ Dslowmeasure had significant reduction, and PF and Dfastmeasure had significant increase. For the age group of 40-55 years, DDVD, Dslow, PF, and Dfast were 12.27±3.90, 1.072±0.067 (10−3mm2/s), 0.141±0.025, 61.0±14.0 (10−3mm2/s), and 13.4±3.6, 1.069±0.074 mm2/s, 0.119±0.014, 57.1±13.2 mm2/s, for men and women, respectively.ConclusionDDVD measure suggest that aging may be associated with reduction in liver perfusion. Lower Dslowmeasurement can lead to artificial higher PF and Dfastmeasurement, providing the evidence of IVIM modeling of perfusion component is constrained by diffusion component.
Future carbon emissions from global mangrove forest loss
Authors: Adame M.F. , Connolly R.M. , Turschwell M.P. , Lovelock C.E. , Fatoyinbo L. , Lagomasino D. , Goldberg L.A. , Holdorf J. , Friess D.A. , Sasmito SD. , Sanderman J. , Sievers M. , Buelow C. , Kauffman B.J. , Bryan-Brown D. , Brown C.J. 
Published: August 2020

AbstractMangroves have among the highest carbon densities of any tropical forest. These “blue carbon” ecosystems can store large amounts of carbon for long periods, and their protection reduces greenhouse gas emissions and supports climate change mitigation. The incorporation of mangroves into Nationally Determined Contributions to the Paris Agreement and their valuation on carbon markets requires predicting how the management of different land-uses can prevent future greenhouse gas emissions and increase CO2sequestration. Management actions can reduce CO2emissions and enhance sequestration, but should be guided by predictions of future emissions, not just carbon storage. We project emissions and forgone soil carbon sequestration potential caused by mangrove loss with comprehensive global datasets for carbon stocks, mangrove distribution, deforestation rates, and drivers of land-use change. Emissions from mangrove loss could reach 2,397 Tg CO2eqby the end of the century, or 3,401 Tg CO2eqwhen considering forgone carbon sequestration. The highest emissions were predicted in southeast and south Asia (West Coral Triangle, Sunda Shelf, and the Bay of Bengal) due to conversion to aquaculture or agriculture, followed by the Caribbean (Tropical Northwest Atlantic) due to clearing and erosion, and the Andaman coast (West Myanmar) and north Brazil due to erosion. Together, these six regions accounted for 90% of the total potential CO2eqfuture emissions. We highlight hotspots for future emissions and the land-use specfic management actions that could avoid them with appropriate policies and regulation.
Genetics of phosphorus use efficiency in a MAGIC wheat population grown in the field
Authors: Wasson Anton P. , Zwart Alexander B. , Verbyla Arunas P. , Permalloo Gilbert , Weligama Chandrakumara , Ryan Peter R. , Delhaize Emmanuel 
Published: August 2020

AbstractPhosphorus (P) is an essential plant nutrient and regular applications are essential in most farming systems to maintain high yields. Yet the P fertilizers applied to crops and pastures are derived from non-renewable resources. It is therefore important to find agronomic and genetic strategies for using this resource efficiently, especially since only a proportion of the applied P is absorbed by crops. The aim of this study was to identify Quantitative Trait Loci (QTL) for P use efficiency (PUE) in wheat using a Multiparent Advanced Generation InterCross (MAGIC) population grown in the field. The 357 genotypes were arranged in paired plots with and without P fertilization. Yield and biomass were measured and PUE was calculated as either the performance of the genotype relative to the average response to fertilization, or the performance of the genotype relative to the average resilience in the absence of fertilization. Five trials were conducted over three years in Australia at three sites with contrasting clay and sandy soil types.Genotypic variation for response and resilience were identified in all trials with moderate to strong correlation with productivity with and without P between trials. Multiparent Whole Genome Average Interval Mapping (WGAIM) QTL analyses were conducted on the four traits (Biomass / Yield × P Response / Resilience) across the five trials and identified 130 QTL in total. QTL within 10 cM of each other were clustered into 56 groups that were likely to represent identical or linked loci. Of the clusters 27 (48%) contained only a single QTL but 17 (31%) contained 3 or more in different trials or traits. This suggests multiple biological mechanisms driving PUE in different environments. Eight of the 56 groups collocated with QTL for seedling root hair length identified in the same MAGIC population in an earlier study.HighlightIdentification of genetic loci for phosphorus use efficiency in a multigenic population of Australian wheats grown on contrasting soils.
Lung Immune Tone Regulation by the Gut-Lung Immune Axis: Short-chain Fatty Acid Receptors FFAR2 and FFAR3, and IL-1β Expression Profiling in Mouse and Human Lung
Authors: Liu Qing , Tian Xiaoli , Maruyama Daisuke , Arjomandi Mehrdad , Prakash Arun 
Published: August 2020

ABSTRACTMicrobial metabolites produced by the gut microbiome, such as short-chain fatty acids (SCFA), can influence both local intestinal and distant lung physiology and response to injury. However, how lung immune activity is regulated by SCFAs is unknown. We examined fresh human lung tissue and observed the presence of SCFAs with large inter-individual and even intra-lobe variability.In vitro, SCFAs were capable of modifying the metabolic programming in both resting and LPS-exposed alveolar macrophages (AM). Additionally, since we hypothesized that lung immune tone could be defined through priming of the inflammasome (aka signal 1), we interrogated naïve mouse lungs for pro-IL-1β message and localized its presence within the alveolar spacein situ, specifically in AM subsets, and in close proximity to alveolar type 2 epithelial (AT2) cells. We established that metabolically active gut microbiota, that produce SCFAs, can transmit LPS and SCFAs to the lung (potential sources of signal 1), and thereby could regulate lung immune tone and metabolic programming. To understand how murine lung cells sensed and upregulated IL-1β in response to gut-microbiome factors, we determined thatin vitro, AM and AT2 cells expressed SCFA receptors, FFAR2, FFAR3, and IL-1β but with different expression patterns and LPS-inducibility. Finally, we observed that IL-1β, FFAR2 and FFAR3 were expressed both in isolated human AM and AT2 cellsex-vivo, but in fresh human lung sectionsin situ, only AM expressed IL-1β at rest and after LPS challenge. Together, this translational study using mouse and human lung tissue and cells supports an important role for the gut microbiome and SCFAs in regulating lung immune tone.
Genomic diversity ofEscherichia coliisolates from healthy children in rural Gambia
Authors: Foster-Nyarko Ebenezer , Alikhan Nabil-Fareed , Ikumapayi Usman Nurudeen , Golam Sarwar , Hossain M Jahangir , Okoi Catherine , Tientcheu Peggy-Estelle , Defernez Marianne , O’Grady Justin , Antonio Martin , Pallen Mark J. 
Published: August 2020

AbstractLittle is known about the genomic diversity ofEscherichia coliin healthy children from sub-Saharan Africa, even though this is pertinent to understanding bacterial evolution and ecology and their role in infection. We isolated and whole-genome sequenced up to five colonies of faecalE. colifrom 66 asymptomatic children aged three-to-five years in rural Gambia (n=88 isolates from 21 positive stools). We identified 56 genotypes, with an average of 2.7 genotypes per host. These were spread over 37 seven-allele sequence types and theE. coliphylogroups A, B1, B2, C, D, E, F andEscherichiacryptic clade I. Immigration events accounted for three-quarters of the diversity within our study population, while one-quarter of variants appeared to have arisen from within-host evolution. Several study strains were closely related to isolates that caused disease in humans or originated from livestock. Our results suggest that within-host evolution plays a minor role in the generation of diversity than independent immigration and the establishment of strains among our study population. Also, this study adds significantly to the number of commensalE. coligenomes, a group that has been traditionally underrepresented in the sequencing of this species.
Transcriptional network involving ERG and AR orchestrates Distal-Less Homeobox 1 mediated prostate cancer progression
Authors: Goel Sakshi , Bhatia Vipul , Carskadon Shannon , Gupta Nilesh , Asim Mohammad , Palanisamy Nallasivam , Ateeq Bushra 
Published: August 2020

AbstractNearly half of the prostate cancer (PCa) cases show elevated levels of ERG oncoprotein due toTMPRSS2-ERGgene fusion. Here, we demonstrate ERG mediated upregulation of Distal-less homeobox-1 (DLX1), an established PCa biomarker. Using series of functional assays, we show DLX1 elicits oncogenic properties in prostate epithelial cells, and abrogating its function leads to reduced tumor burden in mouse xenografts. Clinically, ∼60% of the PCa patients exhibit high DLX1 levels, while ∼50% of these cases also harbor elevated ERG associated with aggressive disease and poor survival probability. Mechanistically, we show that ERG gets recruited ontoDLX1promoter and interacts with its enhancer-bound androgen receptor (AR) and FOXA1 to regulateDLX1expression inTMPRSS2-ERGpositive cases. Alternatively, in ERG-negative cases, DLX1 is regulated by AR/AR-V7 and FOXA1. Importantly, BET bromodomain inhibitors disrupt the transcriptional regulators ofDLX1and its associated oncogenic properties, signifying their efficacy in treatment of DLX1-positive PCa patients.
Different combinations of insect Na,K-ATPase α- and β-subunit paralogs enable fine tuning of toxin resistance and enzyme kinetics
Authors: Herbertz Marlena , Dalla Safaa , Wagschal Vera , Turjalei Rohin , Heiser Marlies , Dobler Susanne 
Published: August 2020

AbstractBackgroundCardiac glycosides are known to fatally inhibit the Na,K-ATPase throughout the animal kingdom. Several animals, however, evolved target-site insensitivity by substitutions in the otherwise highly conserved cardiac glycoside binding pocket located on the Na,K-ATPase α-subunit. The minimal functional enzyme consist of an α- and a β-subunit, the latter considered mainly as a chaperone responsible for correct folding and membrane integration. We here analyze resistance to cardiac glycosides and kinetic properties of different Na,K-ATPase α/β-combinations of the large milkweed bug,Oncopeltus fasciatus. These insects have adapted to high concentrations of cardiac glycosides in their food plants via several rounds of Na,K-ATPase gene duplications followed by differential resistance conferring substitutions and subfunctionalization of the enzymes.ResultsTo investigate their characteristics we expressed nine combinations ofO. fasciatusNa,K-ATPase α/β-sunbunits (three each) inSf9 cells and tested them with two structurally distinct cardiac glycosides, calotropin, a host plant compound, and ouabain, a commonly used toxin. Differences in the number and identity of amino acid substitutions in the cardiac glycoside binding site resulted in large differences in activity and toxin resistance of the three α-subunits. The enzymes’ kinetics were also influenced by the β-subunits leading to increased activities (αCβ3) or altered resistances. The host plant toxin calotropin proved to be a much more potent inhibitor than ouabain for the phylogenetically oldest αC based enzymes. This effect was compensated for in the αB and αA based enzymes with αAβ1 having higher resistance against calotropin than against ouabain.ConclusionThe originally higher inhibitory potency of the host compound calotropin supports a coevolutionary escalation of plant defenses and herbivore tolerance mechanisms. For the bugs the possession of multiple paralogs improved adaptation to plant toxins in a stepwise manner and mitigates pleiotropic effects by a compromise between ion pumping activity and resistance.
H2O2/ABA signal pathway participates in the regulation of stomata opening of cucumber leaves under salt stress by putrescine
Authors: Ma Siguang , Jahan Mohammad Shah , Guo Shirong , Tian Mimi , Zhou Ranran , Liu Hongyuan , Feng Bingjie , Shu Sheng 
Published: August 2020

AbstractThe stomatal-aperture is imperative for plant physiological metabolism. The function of polyamines (PAs) in stomatal regulation under stress environment largely remains elucidate. Herein, we investigated the regulatory mechanism of exogenous putrescine (Put) on the stomatal opening of cucumber leaves under salt stress. The results revealed that Put relieved the salt-induced photosynthetic inhibition of cucumber leaves by regulating stomatal-apertures. Put application increased hydrogen peroxide (H2O2) and decreased abscisic acid (ABA) content in leaves under salt stress. The inhibitors of diamine oxidase (DAO), polyamine oxidase (PAO), nicotinamide adenine dinucleotide phosphate oxidase (NADPH) are AG, 1,8-DO and DPI, respectively and pre-treatment with these inhibitors up-regulated key gene NCED of ABA synthase and down-regulated key gene GSHS of reduced glutathione (GSH) synthase. The content of H2O2 and GSH were decreased and ABA content was increased and its influenced trend is AG>1,8-DO>DPI. Moreover, the Put induced down-regulation of ABA content under salt stress blocked by treatment with H2O2 scavenger (DMTU) and GSH scavenger (CNDB). Additionally, the application of DMTU also blocked the increase of GSH content. Collectively, these results suggest that Put can regulate GSH content by promoting H2O2 generation through polyamine metabolic pathway, which inhibits ABA accumulation to achieve stomatal regulation under salt stress.HighlightExogenous putrescine alleviates photosynthesis inhibition in salt-stressed cucumber seedlings by regulating stomatal-aperture.
Predicting the tension in actin cytoskeleton from the nucleus shape
Authors: Balakrishnan Sreenath , Raju Shilpa R , Barua Anwesha , Ananthasuresh G.K. 
Published: August 2020

AbstractTension in actin cytoskeleton regulates many cellular processes and nuclear morphology. Here, we demonstrate a simple computational method for estimating actin cytoskeletal tension from nucleus shape. We first note that mechanics-based modeling defines a relationship among the volume, surface area, and projected area of the nucleus and hence a specific surface in the three-parameter space of the aforementioned geometric quantities. Data of nuclei from multiple cell types lie on such a surface. Furthermore, nuclei from a given cell population lie on a straight line on the surface. The location and orientation of the line varies with cell type. By using a mechanical model, we present two non-dimensional parameters, namely, the flatness and stretch indicators, which serve as curvilinear coordinates on the surface. Flatness indicator defines the extent of nuclear flattening due to actin cytoskeletal tension and the stretch indicator captures the effect of the elastic modulus of the nuclear envelope. We validate our assertions by modulating the actin cytoskeletal tension using three independent mechanisms: (i) direct downregulation by Cytochalasin D, (ii) indirect upregulation using Nocodazole, and (iii) mechanical stimulation by varying substrate stiffness. We also infer that the flatness indicator is equivalent to the ratio of the height to diameter of the nucleus and is related to the Vogel number. By using this geometric insight, we validate the predictions of our model with data from many previous studies. Finally, we present an analytical formula and a correlation for estimating actin cytoskeletal tension from nuclear projected area and volume.
Transcription coordinates histone amounts and genome content
Authors: Claude Kora-Lee , Bureik Daniela , Adarska Petia , Singh Abhyudai , Schmoller Kurt M. 
Published: August 2020

AbstractBiochemical reactions typically depend on the concentrations of the molecules involved, and cell survival therefore critically depends on the concentration of proteins. To maintain constant protein concentrations during cell growth, global mRNA and protein synthesis rates are tightly linked to cell volume. While such regulation is appropriate for most proteins, certain cellular structures do not scale with cell volume. The most striking example of this is the genomic DNA, which doubles during the cell cycle and increases with ploidy, but is independent of cell volume.Here, we show that the amount of histone proteins is coupled to the DNA content, even though mRNA and protein synthesis globally increase with cell volume. As a consequence, and in contrast to the global trend, histone concentrations (i.e. amounts per volume) decrease with cell volume but increase with ploidy. We find that this distinct coordination of histone homeostasis and genome content is already achieved at the transcript level, and is an intrinsic property of histone promoters that does not require direct feedback mechanisms. Mathematical modelling and histone promoter truncations reveal a simple and generalizable mechanism to control the cell volume- and ploidy-dependence of a given gene through the balance of the initiation and elongation rates.
An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation
Authors: Harms Mirja , Habib Monica MW , Nemska Simona , Nicolò Antonella , Gilg Andrea , Preising Nico , Sokkar Pandian , Carmignani Sara , Raasholm Martina , Weidinger Gilbert , Kizilsavas Gönül , Wagner Manfred , Ständker Ludger , Abadi Ashraf , Jumaa Hassan , Kirchhoff Frank , Frossard Nelly , Sanchez-Garcia Elsa , Münch Jan 
Published: August 2020

AbstractBackgroundAberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes including chronic inflammatory diseases. Thus, the chemokine receptor CXCR4 is a promising target for the therapy of inflammatory disorders, such as atopic dermatitis or allergic asthma. A natural fragment of serum albumin, named EPI-X4, has previous been identified as endogenous peptide antagonist and inverse agonist of CXCR4. The endogenous CXCR4 antagonist provides a promising basis for the development of improved analogues for the therapy of inflammatory diseases.ObjectiveTo increase the anti-CXCR4 activity of EPI-X4 and to evaluate the therapeutic potential of optimized analogs in mouse models of atopic dermatitis and asthma.MethodsMolecular docking analysis of the interaction of EPI-X4 with CXCR4 was performed to define critical interaction motifs and to rationally design analogs with increased activity. EPI-X4 derivatives were synthesized and CXCR4 binding and antagonizing activity determined in assays for antibody competition, inhibition of CXCR4-mediated HIV-1 infection, CXCL12-dependent Ca2+mobilization, ERK and AKT phosphorylation and cell migration. Toxicity of peptides was evaluated in zebrafish embryos. The therapeutic efficacy of the lead peptide EPI-X4 JM#21 was determined in mouse models of atopic dermatitis and asthma.ResultsDocking analysis identified key interaction motifs of EPI-X4/CXCR4. Rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4 and resulted in the generation of the lead analog JM#21, which bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. JM#21 did not exert toxic effects in zebrafish embryos and efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Moreover, EPI-X4 and its improved derivative suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model.ConclusionThe rationally designed EPI-X4 derivative JM#21 is a potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.Graphical Abstract
Different evolutionary pathways of HIV-1 between fetus and mother perinatal transmission pairs indicate unique immune selection pressure in fetuses
Authors: Marichannegowda Manukumar Honnayakanahalli , Mengual Michael , Kumar Amit , Giorgi Elena E. , Tu Joshua J. , Martinez David R. , Li Xiaojun , Feng Liping , Permar Sallie R , Gao Feng 
Published: August 2020

SummaryStudy of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1envgene from 12in uterotransmission pairs show that most infections (67%) occur within two months from childbirth. In addition, envsequences from long-term infected fetuses were highly divergent and formed separate phylogenetic lineages from their cognate maternal viruses. Host selection sites unique to infant viruses were identified in regions frequently targeted by broadly neutralizing antibodies and T cell immune responses. The identification of unique selection sites in theenvgene of fetal viruses indicates that the immune system in fetuses is capable of exerting selection pressure on viral evolution. Studying selection and evolution of HIV-1 or other viruses in fetuses can be an alternative approach to investigate adaptive immunity in fetuses.