bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lamprey Lecticans Link New Vertebrate Genes to the Origin and Elaboration of Vertebrate Tissues
Authors: Root Zachary D. , Jandzik David , Allen Cara , Brewer Margaux , Romášek Marek , Square Tyler , Medeiros Daniel M. 
Published: September 2020

ABSTRACTThe evolution of vertebrates from an invertebrate chordate ancestor involved the evolution of new organs, tissues, and cell types. It was also marked by the origin and duplication of new gene families. If, and how, these morphological and genetic innovations are related is an unresolved question in vertebrate evolution. Hyaluronan is an extracellular matrix (ECM) polysaccharide important for water homeostasis and tissue structure. Vertebrates possess a novel family of hyaluronan binding proteins called Lecticans, and studies in jawed vertebrates (gnathostomes) have shown they function in many of the cells and tissues that are unique to vertebrates. This raises the possibility that the origin and/or expansion of this gene family helped drive the evolution of these vertebrate novelties. In order to better understand the evolution of thelecticangene family, and its role in the evolution of vertebrate morphological novelties, we investigated the phylogeny, genomic arrangement, and expression patterns of alllecticansin the sea lamprey (Petromyzon marinus), a jawless vertebrate. Though bothP. marinusand gnathostomes have fourlecticans, our phylogenetic and syntenic analyses suggest lampreylecticansare the result of one or more cyclostome-specific duplications. Despite the independent expansion of the lamprey and gnathostomelecticanfamilies, we find highly conserved expression oflecticansin vertebrate-specific and mesenchyme-derived tissues. We also find that, unlike gnathostomes, lamprey expresses itslecticanparalogs in distinct subpopulations of head skeleton precursors, potentially reflecting an ancestral diversity of skeletal tissue types. Together, these observations suggest that the ancestral pre-duplicationlecticanhad a complex expression pattern, functioned to support mesenchymal histology, and likely played a role in the evolution of vertebrate-specific cell and tissue types.
Single-cell characterization of transcriptomic heterogeneity in lymphoblastoid cell lines
Authors: SoRelle Elliott D. , Dai Joanne , Zhou Jeffrey Y. , Giamberardino Stephanie N. , Bailey Jeffrey A. , Gregory Simon G. , Chan Cliburn , Luftig Micah A. 
Published: September 2020

AbstractLymphoblastoid Cell Lines (LCLs) are generated by transforming primary B cells with Epstein-Barr Virus (EBV) and are used extensively as model systems in viral oncology, immunology, and human genetics research. In this study, we characterized single-cell transcriptomic profiles of five LCLs and present a simple discrete-time simulation to explore the influence of stochasticity on LCL clonal evolution. Single-cell RNA sequencing revealed substantial phenotypic heterogeneity within and across LCLs with respect to immunoglobulin isotype; virus-modulated host pathways involved in survival, proliferation, and differentiation; viral replication state; and oxidative stress. This heterogeneity is likely attributable to intrinsic variance in primary B cells and host-pathogen dynamics. Stochastic simulations demonstrate that initial primary cell heterogeneity, random sampling, time in culture, and even mild differences in phenotype-specific fitness can contribute substantially to dynamic diversity in populations of nominally clonal cells.
Molecular characterization revealed the role of thaumatin-like proteins in stress response in bread wheat
Authors: Sharma Alok , Sharma Himanshu , Rajput Ruchika , Pandey Ashutosh , Upadhyay Santosh Kumar 
Published: September 2020

ABSTRACTThaumatin-like proteins (TLPs) are related to the pathogenesis-related-5 (PR-5) family and involved in stress response. Herein, a total of 93TLPgenes were identified in the genome ofTriticum aestivum.Further, we identified 26, 27, 39 and 37TLPgenes in theBrachypodium distachyon,Oryza sativa,Sorghum bicolorandZea maysgenomes for comparative characterization, respectively. They could be grouped into small and long TLPs with conserved thaumatin signature motif. Tightly clustered genes exhibited conserved gene and protein structure. The physicochemical analyses suggested significant differences between small and long TLPs. Evolutionary analyses suggested the role of duplication events and purifying selection in the expansion of the TLP gene family. Expression analyses revealed the possible roles ofTLPsin plant development and abiotic and fungal stress response. Recombinant expression ofTaTLP2-BinSaccharomyces cerevisiaeprovided significant tolerance against cold, heat, drought and salt stresses. The results depicted the importance of TLPs in cereal crops that would be highly useful in future crop improvement programs.
Primary saturation of α, β-unsaturated carbonyl containing fatty acids does not abolish electrophilicity
Authors: Snyder Nathaniel W. , O’Brien James , Singh Bhupinder , Buchan Gregory , Arroyo Alejandro D. , Liu Xiaojing , Bostwick Anna , Varner Erika L. , Angajala Anusha , Sobol Robert W. , Blair Ian A. , Mesaros Clementina , Wendell Stacy G. 
Published: September 2020

AbstractMetabolism of polyunsaturated fatty acids results in the formation of hydroxylated fatty acids that can be further oxidized by dehydrogenases, often resulting in the formation of electrophilic, α,β-unsaturated ketone containing fatty acids. As electrophiles are associated with redox signaling, we sought to investigate the metabolism of the oxo-fatty acid products in relation to their double bond architecture. Using an untargeted liquid chromatography mass spectrometry approach, we identified mono- and di-saturated products of the arachidonic acid-derived 11-oxoeicosatetraenoic acid (11-oxoETE) and mono-saturated metabolites of 15-oxoETE and docosahexaenoic acid-derived 17-oxodocosahexaenoinc acid (17-oxoDHA) in both human A549 lung carcinoma and umbilical vein endothelial cells. Notably, mono-saturated oxo-fatty acids maintained their electrophilicity as determined by nucleophilic conjugation to glutathione while a second saturation of 11-oxoETE resulted in a loss of electrophilicity. These results would suggest that prostaglandin reductase (PTGR1), known for its reduction of the α,β-unsaturated double bond, was not responsible for the saturation of oxo-fatty acids. Surprisingly, knockdown of PTGR1 expression by shRNA confirmed its participation in the formation of 15-oxoETE and 17-oxoDHA mono-saturated metabolites. Furthermore, overexpression of PTGR1 in A549 cells increased the rate and total amount of oxo-fatty acid saturation. These findings will further facilitate the study of electrophilic fatty acid metabolism and signaling in the context of inflammatory diseases and cancer where they have been shown to have anti-inflammatory and anti-proliferative signaling properties.HighlightsPrimary saturation of electrophilic fatty acids does not abolish biological activity.Prostaglandin reductase 1 reduces double bonds in fatty acids that are structurally similar to 15-keto-prostaglandin E2.Prostaglandin reductase 1 reduces non-carbonyl adjacent double bonds.
Three-Dimensional Impedance Tomographic Mapping of Metabolically Active Endolumen
Authors: Abiri Parinaz , Luo Yuan , Huang Zi-Yu , Roustaei Mehrdad , Duarte-Vogel Sandra , Cui Quinyu , Sevag Packard René R. , Ebrahimi Ramin , Benharash Peyman , Tai Yu-Chong , Hsiai Tzung K. 
Published: September 2020

AbstractReal-time detection of vulnerable atherosclerotic lesions, characterized by a high content of oxidized low-density lipoprotein (oxLDL)-laden macrophages or foam cells, remains an unmet clinical need. While fractional flow reserve (FFR)-guided revascularization in angiographically intermediate stenoses is utilized to assess hemodynamic significance,in vivodetection of oxLDL-rich plaques may provide a new paradigm for treating metabolically unstable lesions. Herein, we have demonstrated endoluminal mapping of lipid-laden lesions using 3-D electrical impedance spectroscopy-derived impedance tomography (EIT) in a pre-clinical swine model. We performed surgical banding of the right carotid arteries of Yucatan mini-pigs, followed by 16 weeks of high-fat diet, to promote the development of lipid-rich lesions. We implemented an intravascular sensor combining an FFR pressure transducer with a 6-point micro-electrode array for electrical impedance spectroscopy (EIS) measurements. 3-D EIT mapping was achieved using an EIS-based reconstruction algorithm. We demonstrated that EIT mapping corresponds to endoluminal histology for oxLDL-laden lesions. We further used computational models to theoretically predict and validate EIS measurements. Thus, our 3-D EIS-derived EIT providesin vivodetection of metabolically active plaques with the goal of guiding optimal intravascular intervention.One Sentence SummaryThis work demonstratesin vivomapping of oxidized LDL-laden endolumen by deploying an intravascular dual-sensor to a swine model of atherosclerosis.
Development of antibody-dependent cell cytotoxicity function in HIV-1 antibodies
Authors: Doepker Laura E. , Danon Sonja , Harkins Elias , Ralph Duncan , Yaffe Zak , Dhar Amrit , Wagner Cassia , Stumpf Megan M. , Arenz Dana , Williams James A. , Jaoko Walter , Mandaliya Kishor , Lee Kelly K. , Matsen Frederick A. , Overbaugh Julie M. 
Published: September 2020

AbstractA prerequisite for the design of an HIV vaccine that elicits protective antibodies is understanding the developmental pathways that result in desirable antibody features. The development of antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) is particularly relevant because such antibodies have been associated with HIV protection in humans. We reconstructed the developmental pathways of six human HIV-specific ADCC antibodies using longitudinal antibody sequencing data. Most of the inferred naïve antibodies did not mediate detectable ADCC. Gain of antigen binding and ADCC function typically required mutations in complementarity determining regions of one or both chains. Enhancement of ADCC potency often required additional mutations in framework regions. Antigen binding affinity and ADCC activity were correlated, but affinity alone was not sufficient to predict ADCC potency. Thus, elicitation of human ADCC antibodies may require mutations that first enable high affinity antigen recognition, followed by mutations that optimize factors contributing to functional ADCC activity.
Intelligence-associated Polygenic Scores Predict g, Independent of Ancestry, Parental Educational Levels, and Color among Hispanics in comparison to European, European- African, and African Americans
Authors: Pesta Bryan J. , Fuerst John G. R. , Piffer Davide , Kirkegaard Emil O. W. 
Published: September 2020

AbstractPolygenic scores for educational attainment and intelligence (eduPGS), genetic ancestry, and cognitive ability have been found to be inter-correlated in some admixed American populations. We argue that this could either be due to causally-relevant genetic differences between ancestral groups or be due to population stratification-related confounding. Moreover, we argue that it is important to determine which scenario is the case so to better assess the validity of eduPGS. We investigate the confounding vs. causal concern by examining, in detail, the relation between eduPGS, ancestry, and general cognitive ability in East Coast Hispanic and non-Hispanic samples. European ancestry was correlated withgin the admixed Hispanic (r= .30,N= 506), European-African (r= .26,N= 228), and African (r= .084,N= 2,179) American samples. Among Hispanics and the combined sample, these associations were robust to controls for racial / ethnic self-identification, genetically predicted color, and parental education. Additionally, eduPGS predictedgamong Hispanics (B= 0.175,N= 506) and all other groups (European:B= 0.230,N= 4914; European-African:B= 0.215,N= 228; African:B= 0.126,N= 2179) with controls for ancestry. Path analyses revealed that eduPGS, but not color, partially statistically explained the association betweengand European ancestry among both Hispanics and the combined sample. Of additional note, we were unable to account for eduPGS differences between ancestral populations using common tests for ascertainment bias and confounding related to population stratification. Overall, our results suggest that eduPGS derived from European samples can be used to predictgin American populations. However, owing to the uncertain cause of the differences in eduPGS, it is not yet clear how the effect of ancestry should be handled. We argue that more research is needed to determine the source of the relation between eduPGS, genetic ancestry, and cognitive ability.
Representational drift in primary olfactory cortex
Authors: Schoonover Carl E. , Ohashi Sarah N. , Axel Richard , Fink Andrew J.P. 
Published: September 2020

SummaryRepresentations of the external world in sensory cortices may define the identity of a stimulus and should therefore vary little over the life of the organism. In the olfactory system the primary olfactory cortex, piriform, is thought to determine odor identity1–6. We have performed electrophysiological recordings of single units maintained over weeks to examine the stability of odor representations in the mouse piriform cortex. We observed that odor representations drift over time, such that the performance of a linear classifier trained on the first recording day approaches chance levels after 32 days. Daily exposure to the same odorant slows the rate of drift, but when exposure is halted that rate increases once again. Moreover, behavioral salience does not stabilize odor representations. Continuous drift poses the question of the role of piriform in odor identification. This instability may reflect the unstructured connectivity of piriform7–15and may be a property of other unstructured cortices.
JIB-04 has broad-spectrum antiviral activity and inhibits SARS-CoV-2 replication and coronavirus pathogenesis
Authors: Son Juhee , Huang Shimeng , Zeng Qiru , Bricker Traci L. , Case James Brett , Zhou Jinzhu , Zang Ruochen , Liu Zhuoming , Chang Xinjian , Harastani Houda H. , Chen Lu , Gomez Castro Maria Florencia , Zhao Yongxiang , Kohio Hinissan P. , Hou Gaopeng , Fan Baochao , Niu Beibei , Guo Rongli , Rothlauf Paul W. , Bailey Adam L. , Wang Xin , Shi Pei-Yong , Martinez Elisabeth D. , Whelan Sean P.J. , Diamond Michael S. , Boon Adrianus C.M. , Li Bin , Ding Siyuan 
Published: September 2020

AbstractPathogenic coronaviruses represent a major threat to global public health. Here, using a recombinant reporter virus-based compound screening approach, we identified several small-molecule inhibitors that potently block the replication of the newly emerged severe acute respiratory syndrome virus 2 (SARS-CoV-2). Among them, JIB-04 inhibited SARS-CoV-2 replication in Vero E6 cells with an EC50of 695 nM, with a specificity index of greater than 1,000. JIB-04 showedin vitroantiviral activity in multiple cell types against several DNA and RNA viruses, including porcine coronavirus transmissible gastroenteritis virus. In anin vivoporcine model of coronavirus infection, administration of JIB-04 reduced virus infection and associated tissue pathology, which resulted in improved weight gain and survival. These results highlight the potential utility of JIB-04 as an antiviral agent against SARS-CoV-2 and other viral pathogens.
Genome-wide analyses point to differences in genetic architecture of BMI between tall and short people
Authors: Lin Bochao D. , Mullin Benjamin H. , Wilson Scott G. , Walsh John P. , Li Yue , Adan Roger , Luykx Jurjen J. 
Published: September 2020

AbstractTo examine differences in the genetic architecture of BMI between tall and short people, we conducted genome-wide and follow-up analyses using UK Biobank data. We identify 57 loci as height-specific, detect differences in SNP-based heritability between tall and short people and show how genetic correlations between the two rises during the lifespan. Using phenome-wide analyses (PHEWAS), a significant association between a short people-specific locus onMC4Rand energy portion size was detected. We identify one locus (GPC5-GPC6)with different effect directions on BMI in short and tall people. PHEWAS indicates this locus is associated with bone mineral density. Transcriptome-wide analyses hint that genes differentially associated with BMI in short vs tall people are enriched in brain tissue. Our findings highlight the role of height in the genetic underpinnings of BMI, provide biological insight into mechanisms underlying height-dependent differences in BMI and show that in short and tall people obesity is a risk factor that differentially increases susceptibility for disease.
Field testing of biohybrid robotic jellyfish to demonstrate enhanced swimming speeds
Authors: Xu Nicole W. , Townsend James P. , Costello John H. , Colin Sean P. , Gemmell Bradford J. , Dabiri John O. 
Published: September 2020

ABSTRACTBiohybrid robotic designs incorporating live animals and self-contained microelectronic systems can leverage the animals’ own metabolism to reduce power constraints and act as natural chassis and actuators with damage tolerance. Previous work established that biohybrid robotic jellyfish can exhibit enhanced speeds up to 2.8 times their baseline behavior in laboratory environments. However, it remains unknown if the results could be applied in natural, dynamic ocean environments and what factors can contribute to large animal variability. Deploying this system in the coastal waters of Massachusetts, we validate and extend prior laboratory work by demonstrating increases in jellyfish swimming speeds up to 2.3 times greater than their baseline, with absolute swimming speeds up to 6.6 ± 0.3 cm s-1. These experimental swimming speeds are predicted using a hydrodynamic model with morphological and time-dependent input parameters obtained from field experiment videos. The theoretical model can provide a basis to choose specific jellyfish with desirable traits to maximize enhancements from robotic manipulation. With future work to increase maneuverability and incorporate sensors, biohybrid robotic jellyfish can potentially be used track environmental changes in applications for ocean monitoring.
Sequence dependence of biomolecular phase separation
Authors: Weiner Benjamin G. , Meir Yigal , Wingreen Ned S. 
Published: September 2020

AbstractCells are home to a wide variety of biomolecular condensates - phase-separated droplets that lack a membrane. In addition to nonspecific interactions, phase separation depends on specific binding motifs between constituent molecules. Nevertheless, few rules have been established on how these specific, heterotypic interactions drive phase separation. Using lattice-polymer simulations and mean-field theory, we show that the sequence of binding motifs strongly affects a polymer’s ability to phase separate, influencing both phase boundaries and condensate properties (e.g. viscosity and polymer diffusion). We find that sequences with large blocks of a single motif typically form more inter-polymer bonds which promote phase separation. Notably, the sequence of binding motifs influences phase separation primarily by determining the conformational entropy of self-bonding by single polymers. This contrasts with systems where the molecular architecture primarily affects the energy of the dense phase, providing a new entropy-based mechanism for the biological control of phase separation.
Evolution of ST-4821 clonal complex hyperinvasive and quinolone-resistant meningococci: the next meningococcal pandemic?
Authors: Chen Mingliang , Harrison Odile B. , Bratcher Holly B. , Bo Zhiyan , Jolley Keith A. , Rodrigues Charlene M.C. , Bray James E. , Guo Qinglan , Zhang Xi , Chen Min , Maiden Martin C.J. 
Published: September 2020

AbstractThe expansion of quinolone-resistantNeisseria meningitidisclone ChinaCC4821-R1-C/Bfrom ST-4821 clonal complex (cc4821) caused a serogroup shift from serogroup A to C in invasive meningococcal disease (IMD) in China. To establish the relationship among globally distributed cc4821 meningococci, we analysed whole genome sequence data from 173 cc4821 meningococci isolated in four continents from 1972-2019. These meningococci clustered into four sub-lineages (1-4), with sub-lineage 1 primarily comprising serogroup C IMD isolates (82%, 41/50). Most isolates from outside China formed a distinct sub-lineage (81.6%, 40/49, the Europe-USA cluster), with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(cc4821) and harbouring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/Bhas expanded to other countries. The increasing global distribution of B:cc4821 meningococci raises concern that cc4821 has the potential to cause a global pandemic and, this would be challenging to control though there is indirect evidence that Trumenba®vaccine might afford some protection.
Hits-Based Quantitative Characterization of SOBI-Recovered P3 Network Configuration: an EEG Source-Imaging Study
Authors: Privitera Adam John , Fung Renee , Hua Yunqing , Tang Akaysha C. 
Published: September 2020

AbstractOne frequently studied biomarker for health and disease conditions is the P3 component extracted from scalp recorded electroencephalography (EEG). The spatial origin of this significant neural signal is known to be distributed, typically involving large regions of the cerebral cortex as well as subcortical structures. Unlike the temporal characterization of the P3 by amplitude or latency measures from event-related potentials (ERPs), the spatial characterization of the P3 component is relatively rare, typically qualitative, and often reported as differences between populations (group differences between healthy controls and clinical groups). Here we introduce a novel approach to quantitatively characterize the spatial origin of the P3 component by (1) applying second-order blind identification (SOBI) to continuous, high-density EEG data to extract the P3 component, (2) modeling the underlying generators of the SOBI P3 component as a set of equivalent current dipoles (ECDs) in Talairach space using BESA; (3) using the application Talairach Client to determine the “hits” associated with the anatomical structures at three level of resolution (lobe, gyrus, and cell type). We show that the hits information provided by Talairach Client can enable a quantitative characterization of the spatial configuration of the network underlying the P3 component (P3N) via two quantities: cross-individual reliability (or consistency) of a given brain structure as a part of the P3N, and within-individual contribution of a given brain structure to the whole P3N network. We suggest that this method may be used to further differentiate individuals in the absence of differences in P3 amplitude or latency, or when scientific questions or practical application cannot be supported by a yes-no answer regarding the source of a P3 component. Finally, application of our method to a group of 13 participants revealed that frontal structures, particularly BA10, play a special role in the function of a global cortical network underlying novelty processing.