bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperbolic disc embedding of functional human brain connectomes using resting state fMRI
Authors: Whi Wonseok , Ha Seunggyun , Kang Hyejin , Lee Dong Soo 
Published: March 2021

AbstractThe brain presents a real complex network of modular, small-world, and hierarchical nature, which are features of non-Euclidean geometry. Using resting-state functional magnetic resonance imaging (rs-fMRI), we constructed a scale-free binary graph for each subject, using internodal time-series correlation of regions-of-interest (ROIs) as a proximity measure. The resulted network could be embedded onto manifolds of various curvature and dimensions. While maintaining the fidelity of embedding (low distortion, high mean average precision), functional brain networks were found to be best represented in the hyperbolic disc. Usingmodel, we reduced the dimension of the network into 2-D hyperbolic space and were able to efficiently visualize the internodal connections of the brain, preserving proximity as distances and angles on the hyperbolic discs. Each individual disc revealed decentralized nature of information flow and anatomic relevance. Using the hyperbolic distance on themodel, we could detect the anomaly of network in autistic spectrum disorder (ASD) subjects. This procedure of embedding grants us a reliable new framework for studying functional brain networks and the possibility of detecting anomalies of the network in the hyperbolic disc on an individual scale.
Pellaea zygophylla, a new combination for a distinctive & well-known but neglected fern
Authors: Alexander Patrick J. 
Published: March 2021

AbstractPellaea ovatais a widespread species, sexual diploid in Texas &northeastern Mexico but an apogamous triploid in northwestern Mexico, south to northern Argentina, &on Hispaniola. The type belongs to the southern, apogamous triploid form. Although these two forms have been discussed repeatedly in the literature, morphological distinctions between them have been overlooked and they have not been recognized taxonomically. However, they are distinct.Pellaea ovatas.s. has puberulent rachides & costae; pinnae usually 2-pinnate with a well-defined main axis &pinnules borne singly; fertile pinnules ovate, cordate basally &rounded apically. The sexual diploid form has rachides &costae glabrous; pinnae pseudo-dichotomously branched &pinnules usually paired; fertile pinnules narrowly rounded-trapeziform, obliquely truncate to cordate basally &truncate apically. Riddell named the sexual diploid formPteris zygophylla, from which I give it the new combinationPellaea zygophylla.
TOWARDS QUANTITATIVE FORECASTING OF SPECIES YIELDS WITH INCOMPLETE INFORMATION ON MODEL PARAMETERS
Authors: Fort Hugo 
Published: March 2021

AbstractPredicting both the absolute and the relative abundance of species in a spatial patch is of paramount interest in areas like, agriculture, ecology and environmental science.The linear Lotka-Volterra generalized equations (LLVGE) serve for describing the dynamics of communities of species connected by negative as well as positive interspecific interactions.Here we particularize these LLVGE to the case of single trophic ecological communities, like mixtures of plants, withS>2 species. Thus, by estimating the LLVGE parameters from the yields in monoculture and biculture experiments, the LLVGE are able to produce decently accurate predictions for species yields.However, a common situation we face is that we don’t know all the parameters appearing in the LLVGE. Indeed, for large values ofS, only a fraction of the experiments necessary for estimating the model parameters is commonly carried out. We then analyze which quantitative predictions are possible with an incomplete knowledge of the parameters.
Copper intoxication in group BStreptococcustriggers transcriptional activation of thecopoperon that contributes to enhanced virulence during acute infection
Authors: Sullivan Matthew J. , Goh Kelvin G. K. , Gosling Dean , Katupitiya Lahiru , Ulett Glen C. 
Published: March 2021

AbstractBacteria can utilize Copper (Cu) as a trace element to support cellular processes; however, excess Cu can intoxicate bacteria. Here, we characterize thecopoperon in group B streptococcus (GBS), and establish its role in evasion of Cu intoxication and the response to Cu stress on virulence. Growth of GBS mutants deficient in either thecopACu exporter, or thecopYrepressor, were severely compromised in Cu-stress conditions. GBS survival of Cu stress reflected a mechanism of CopY de-repression of the CopA efflux system. However, neither mutant was attenuated for intracellular survival in macrophages. Analysis of global transcriptional responses to Cu by RNA-sequencing revealed a stress signature encompassing homeostasis of multiple metals. Genes induced by Cu stress included putative metal transporters for manganese import, whereas a system for iron export was repressed. In addition,copApromoted the ability of GBS to colonize the blood, liver and spleen of mice following disseminated infection. Together, these findings show that GBScopAmediates resistance to Cu intoxication, via regulation by the Cu-sensing transcriptional repressor,copY. Cu stress responses in GBS reflect a transcriptional signature that heightens virulence and represents an important part of the bacteria’s ability to survive in different environments.ImportanceUnderstanding how bacteria manage cellular levels of metal ions, such as copper, helps to explain how microbial cells can survive in different stressful environments. We show how the opportunistic pathogen group B Streptococcus (GBS) achieves homeostasis of intracellular copper through the activities of the genes that comprise the cop operon, and describe how this helps GBS survive in stressful environments, including in the mammalian host during systemic disseminated infection.
IL-18 and Lower Risk for Lung Cancer: Triangulated Evidence from Germline Predictions, Pre-Diagnostic Measurements, and Tumor Expression
Authors: Smith-Byrne Karl , Chen Yan , Kachuri Linda , Kapoor Pooja M. , Guida Florence , Zahed Hana , Alcala Karine , Amos Christopher , Atkins Joshua , Bodinier Barbara , Ferreiro-Iglesia Aida , Hung Rayjean J. , Johansson Mikael , Koh Woon-Puay , Kyrø Cecilie , Langhammer Arnulf , Pietzner Maik , Sala Núria , Sandanger Torkjel M. , Travis Ruth C. , Tsilidis Kostas , Yuan Jian-Min , Robbins Hilary , Brennan Paul , McKay James , Johansson Mattias , Mälarstig Anders 
Published: March 2021

AbstractLung cancer remains the most common cause of cancer death globally. Dysregulation of immune response and inflammatory signaling is known to play an important role in lung tumorigenesis, but the causal drivers of this process have yet to be elucidated. To identify circulating inflammatory and immune-related proteins that influence risk for lung cancer we related genetically predicted plasma levels for 85 inflammation and immune proteins with susceptibility to lung cancer. Mendelian randomization (MR) analyses in 29,266 cases and 56,450 controls identified a candidate causal marker, IL-18, which conferred lower risk of lung cancer (OR per standard deviation increase: 0.85 [95% CI: 0.79-0.92]), in particular for adenocarcinoma (OR: 0.80 [95% CI: 0.72-0.89]). We subsequently validated this association using polygenic IL-18 predictions in the UK Biobank (HR highest vs. lowest quartile: 0.83 [95% CI: 0.72-0.95]) and using pre-diagnostic blood concentrations of IL-18 in 732 cases and 732 controls after controlling for the inhibitory role of IL-18BP (OR highest vs. lowest quartile: 0. 63 [95% CI: 0. 41-0.91]). Genetic colocalization suggested that IL-18 may act on lung cancer risk locally via lung tissue expression, and joint MR and tumor microenvironment analyses highlight CD8 T cells and NK cells as potential mediators. In addition to risk, IL-18 expression in adenocarcinoma tumor tissue was found to be associated with all-cause mortality in 480 TCGA samples after controlling for IL-18BP (HR per SD: 0.87 [95% CI: 0.78, 0.98]), which is in line with recent studies showing anti-tumor effects of IL-18. Our comprehensive genomic triangulation study thus highlights the potential for IL-18 as an aetiological biomarker and targetable for immune-oncology therapies.
Immunoinformatic approach to design a vaccine against SARS-COV-2 membrane glycoprotein
Authors: Ravindran Radhika , Gunasekaran Shoba , Easwaran Murugesh , Lulu Sajitha , Unni P. Ambili , Vino S. , Doble Mukesh 
Published: March 2021

ABSTRACTSARS-COV-2 is a pandemic virus causing COVID-19 disease which affects lungs and upper respiratory tract leading to progressive increase in the death rate worldwide. Currently, there are more than 123 million cases and over 2.71 million confirmed death caused by this virus. In this study, by utilizing an immunoinformatic approach, multiepitope-based vaccine is designed from the membrane protein which plays a vital role in the virion assembly of the novel-CoV. A total of 19 MHC class- I binders with HLA-A and HLA-B alleles have been selected with NetMHC pan EL 4.0 method from IEDB MHC-I prediction server. Four epitopes candidates from M-protein were selected based on the antigenicity, stability, immunogenicity, Ramachandran plot and scores with 100 % was taken for docking analysis with alleles HLA-A (PDB ID: 1B0R) and HLA-B (PDB ID: 3C9N) using ClusPro server. Among the four epitopes, the epitope FVLAAVYRI has the least binding energy and forms electrostatic, hydrogen and hydrophobic interactions with HLA-A (−932.8 Kcal/mol) and HLA-B (−860.7 Kcal/mol) which induce the T-cell response. Each HLA-A and HLA-B complex in the system environment achieves stable backbone configuration between 45-100 ns of MD simulation. This study reports a potent antigenic and immunogenic profile of FVLAAVYRI epitope from M-protein and furtherin vitroandin vivovalidation is needed for its adaptive use as vaccine against COVID-19.
A simple micropreparative gel electrophoresis technique for purification of proteins, nucleic acids, and bioconjugates
Authors: Sajjadi Sayyed Hashem , Wu Shang-Jung , Zubkovs Vitalijs , Ahmadzadeh Hossein , Goharshadi Elaheh K. , Boghossian Ardemis A. 
Published: March 2021

AbstractThe biochemical and biomedical fields hinge on the ability to effectively separate and purify biological macromolecules. Though this need is largely addressed with a variety of chromatographic and electrophoretic purification techniques, such techniques are usually laborious, time-consuming, and often require complex and costly instalments that are inaccessible to most laboratories. In this work, we introduce a simple micro-preparative (MP) method based on polyacrylamide gel electrophoresis (PAGE) to purify biological samples containing proteins, nucleic acids, and complex bioconjugates. Using a conventional vertical slab system, we demonstrate the extraction of purified DNA, proteins, and DNA-protein bioconjugates from their respective mixtures using MP-PAGE. We apply this system to recover DNA from a ladder mixture with yields of up to 90%, compared to the 58% yield obtained using specialized commercial devices. We also demonstrate the purification of folded enhanced yellow fluorescence protein (EYFP) from crude cell extract with 90% purity, comparable to purities achieved using a two-step size exclusion and immobilized metal-ion affinity chromatography purification procedure. Finally, we demonstrate the successful isolation of an EYFP-DNA bioconjugate sample that otherwise could not be processed using the two-step chromatography procedure. MP-PAGE thus offers a rapid and versatile means of purifying a variety of biomolecules without the need for specialized equipment.
Recurrent chromosomal translocations in sarcomas create a mega-complex that mislocalizes NuA4/TIP60 to Polycomb target loci
Authors: Sudarshan Deepthi , Avvakumov Nikita , Lalonde Marie-Eve , Alerasool Nader , Joly-Beauparlant Charles , Jacquet Karine , Mameri Amel , Lambert Jean-Philippe , Rousseau Justine , Lachance Catherine , Paquet Eric , Herrmann Lara , Setty Samarth Thonta , Loehr Jeremy , Bernardini Marcus Q. , Rouzbahman Marjan , Gingras Anne-Claude , Coulombe Benoit , Droit Arnaud , Taipale Mikko , Doyon Yannick , Côté Jacques 
Published: March 2021

ABSTRACTChromosomal translocations frequently promote carcinogenesis by producing gain-of-function fusion proteins. Recent studies have identified highly recurrent chromosomal translocations in patients with Endometrial Stromal Sarcomas (ESS) and Ossifying FibroMyxoid Tumors (OFMT) leading to an in-frame fusion of PHF1 (PCL1) to six different subunits of the NuA4/TIP60 complex. While NuA4/TIP60 is a co-activator that acetylates chromatin and loads the H2A.Z histone variant, PHF1 is part of the Polycomb repressive complex 2 (PRC2) linked to transcriptional repression of key developmental genes through methylation of histone H3 on lysine 27. In this study, we characterize the fusion protein produced by theEPC1-PHF1translocation. The chimeric protein assembles a mega-complex harboring both NuA4/TIP60 and PRC2 activities and leads to mislocalization of chromatin marks in the genome, in particular over an entire topologically- associating domain including part of theHOXDcluster. This is linked to aberrant gene expression, most notably increased expression of PRC2 target genes. Furthermore, we show that JAZF1, implicated with a PRC2 component in the most frequent translocation in ESS,JAZF1-SUZ12, is a potent transcription activator that physically associates with NuA4/TIP60, its fusion creating similar outcomes asEPC1-PHF1. Importantly, the specific increased expression of PRC2 targets/HOXgenes was also confirmed with ESS patient samples. Altogether, these results indicate that most chromosomal translocations linked to these sarcomas employ the same molecular oncogenic mechanism through a physical merge of NuA4/TIP60 and PRC2 complexes leading to mislocalization of histone marks and aberrant polycomb target gene expression.
Massive loss of transcription factors and the initial diversification of placental mammals
Authors: Zhao Xin-Wei , Wu Jiaqi , Kishino Hirohisa 
Published: March 2021

ABSTRACTAs one of the most successful categories of organisms, mammals occupy a variety of niches on earth as a result of macroevolution. Transcription factors (TFs), the basic regulators of gene expression, may also evolve during mammalian phenotypic diversification and macroevolution. To examine the relationship between TFs and mammalian macroevolution, we analyzed 140,821de novo-identified TFs and their birth and death histories from 96 mammalian species. Gene tree vs. species tree reconciliation revealed that mammals experienced an upsurge in TF losses around 100 million years ago and also near the K–Pg boundary, thus implying a relationship with the divergence of placental animals. From approximately 100 million years ago to the present, losses dominated TF events without a significant change in TF gains. To quantify the effects of this TF pruning on mammalian macroevolution, we analyzed rates of molecular evolution and expression profiles of regulated target genes. Surprisingly, TF loss decelerated, rather than accelerated, molecular evolutionary rates of their target genes, suggesting increased functional constraints. Furthermore, an association study revealed that massive TF losses are significantly positively correlated with solitary behavior, nocturnality, reproductive-seasonality and insectivory life history traits, possibly through rewiring of regulatory networks.
Green Fluorescent Carbon Dots as Targeting Probes for LED-Dependent Bacterial Killing
Authors: Samphire Jenny , Takebayashi Yuiko , Hill Stephen A. , Hill Nicholas , Heesom Kate J. , Lewis Philip A. , Alibhai Dominic , Bragginton Eilis C. , Dorh Josephine , Dorh Neciah , Spencer James , Galan M. Carmen 
Published: March 2021

ABSTRACTThe emergence of antimicrobial resistance represents a significant health and economic challenge worldwide. The slow pace of antibacterial discovery necessitates strategies for optimal use of existing agents, including effective diagnostics able to drive informed prescribing; and development of alternative therapeutic strategies that go beyond traditional small-molecule approaches. Thus, the development of novel probes able to target bacteria for detection and killing, and that can pave the way to effective theranostic strategies, is of great importance. Here we demonstrate that metal-free green-emitting fluorescent carbon dots (FCDs) synthesized from glucosamine HCl andm-phenylenediamine, and featuring 2,5-deoxyfructosazine on a robust amorphous core, can label both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) bacterial pathogens within 10 minutes of exposure. Moreover, effective killing of Gram-positive and -negative bacteria can be induced by combining FCD treatment with irradiation by LED light in the visible range. Cell-based, electron microscopy and Tandem Mass Tag (TMT) proteomic experiments indicate that FCD administration in combination with LED exposure gives rise to local heating, ROS production, and membrane- and DNA-damage, suggesting multiple routes to FCD-mediated bacterial killing. Our data identify FCDs as materials that combine facile synthesis from low-cost precursors with labelling and light-dependent killing of clinically important bacterial species, and that thus warrant further exploration as the potential bases for novel theranostics.
Sex differences in concentrations of HMGB1 and numbers of pigmented monocytes in infants with malaria
Authors: Kanoi Bernard N. , Egwang Thomas G. 
Published: March 2021

AbstractFemales generally mount more robust innate and adaptive immune responses and demonstrate a higher rate of morbidity, and prevalence of autoimmune diseases by comparison with males. In malaria, females demonstrate higher concentrations of antibodies and rates of severe adverse events and mortality following natural infections and malaria vaccination. Although monocytes/macrophages play a crucial role in disease and protection in malaria, no studies have investigated sex differences in their functions in production of proinflammatory cytokines and chemokines in malaria-infected subjects. Here, we show significant sex differences in serum concentrations of HMGB1, a non-histone chromatin-associated protein, and numbers of pigmented monocytes, which are both markers of severe malaria, in infants <5 years old from a malaria endemic region in Northern Uganda. Female infants with clinical malaria had significantly higher HMGB1 concentrations than male infants, and female infants with asymptomatic malaria had significantly lower numbers of pigmented monocytes than male infants with asymptomatic malaria. There was (1) a significant correlation between HMGB1 concentrations and pigmented monocyte numbers in female but not male infants; and (2) a significant correlation between HMGB1 concentrations and parasite densities in female but not male infants. These findings suggest that female infants with clinical malaria might be at a greater risk of morbidity characterized by higher serum HMGB1 levels.
Higher phage virulence accelerates the evolution of host resistance
Authors: Wendling Carolin C. , Lange Janina , Liesegang Heiko , Sieber Michael , Pöhlein Anja , Bunk Boyke , Rajkov Jelena , Goehlich Henry , Roth Olivia , Brockhurst Michael A. 
Published: March 2021

AbstractParasites and pathogens vary strikingly in their virulence and the resulting selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and as of now mainly based on observations and theoretical predictions with few experimental tests. Increased virulence can increase selection for host resistance evolution if resistance costs are outweighed by the benefits of avoiding infection. To test this, we experimentally evolved the bacteriumVibrio alginolyticusin the presence of two variants of the filamentous phage, VALGΦ8, that differ in their virulence. The bacterial host exhibited two alternative defence strategies against future phage infection: (1) super infection exclusion (SIE) whereby phage-infected cells were immune to subsequent infection at a cost of reduced growth, and (2) surface receptor mutations (SRM) in genes encoding the MSHA type-IV pilus providing resistance to infection by preventing phage attachment. While SIE emerged rapidly against both phages, SRM evolved faster against the high virulence compared to the low virulence phage. Using a mathematical model of our system we show that increasing virulence strengthens selection for SRM due to the higher costs of infection suffered by SIE immune hosts. In both the experiments and the model, higher levels of SRM in the host population drove more rapid phage extinction. Thus, by accelerating the evolution of host resistance, more virulent phages caused shorter epidemics.
A Statistical Model for Describing and Simulating Microbial Community Profiles
Authors: Ma Siyuan , Ren Boyu , Mallick Himel , Moon Yo Sup , Schwager Emma , Maharjan Sagun , Tickle Timothy L. , Lu Yiren , Carmody Rachel N. , Franzosa Eric A. , Janson Lucas , Huttenhower Curtis 
Published: March 2021

AbstractMany methods have been developed for statistical analysis of microbial community profiles, but due to the complex nature of typical microbiome measurements (e.g. sparsity, zero-inflation, nonindependence, and compositionality) and of the associated underlying biology, it is difficult to compare or evaluate such methods within a single systematic framework. To address this challenge, we developed SparseDOSSA (Sparse Data Observations for the Simulation of Synthetic Abundances): a statistical model of microbial ecological population structure, which can be used to parameterize real-world microbial community profiles and to simulate new, realistic profiles of known structure for methods evaluation. Specifically, SparseDOSSA’s model captures marginal microbial feature abundances as a zero-inflated log-normal distribution, with additional model components for absolute cell counts and the sequence read generation process, microbemicrobe, and microbe-environment interactions. Together, these allow fully known covariance structure between synthetic features (i.e. “taxa”) or between features and “phenotypes” to be simulated for method benchmarking. Here, we demonstrate SparseDOSSA’s performance for 1) accurately modeling human-associated microbial population profiles; 2) generating synthetic communities with controlled population and ecological structures; 3) spiking-in true positive synthetic associations to benchmark analysis methods; and 4) recapitulating an end-to-end mouse microbiome feeding experiment. Together, these represent the most common analysis types in assessment of real microbial community environmental and epidemiological statistics, thus demonstrating SparseDOSSA’s utility as a general-purpose aid for modeling communities and evaluating quantitative methods. An open-source implementation is available athttp://huttenhower.sph.harvard.edu/sparsedossa2.