bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibroblast Activation Protein Inhibitor PET/CT
Authors: Sharma Punit , Singh Shashank Shekhar , Gayana Shankaramurthy 
Published: December 2020

Purpose
Fibroblast activation protein (FAP) is a cell membrane–bound serine peptidase, overexpressed in cancer-associated fibroblasts and activated fibroblasts at wound healing/inflammatory sites. Recently, molecular PET/CT imaging with radiolabeled FAP inhibitor (FAPI) has been evaluated in different diseases. We aimed to assess its potential role based on the available literature.

Patients and Methods
We conducted a comprehensive review of the available preclinical and clinical data on FAPI PET/CT in an attempt to summarize its current status and potential future role. Based on that, we have discussed the pathophysiology behind FAP-based imaging, followed by a discussion of FAPI radiopharmaceuticals including their synthesis, biodistribution, and dosimetry. Next, we have discussed studies evaluating FAPI PET/CT in different oncological and nononcological pathologies. The potential of FAPI PET/CT in theranostics has also been addressed.

Results
Based on the early scientific evidence available, including preclinical and clinical studies, FAPI PET/CT seems to be a promising molecular imaging tool, especially in oncology. It can be used for imaging different types of cancers and outperforms 18F-FDG PET/CT in some of these. Its potential as a theranostic tool warrants special attention.

Conclusions
Fibroblast activation protein inhibitor PET/CT has the potential to emerge as a powerful molecular imaging tool in the future. However, as of yet, the available evidence is limited, warranting further research and trials in this field.
Antimalarial andPlasmodium falciparumserpentine receptor 12 targeting effect of a purinergic receptor antagonist FDA approved drug
Authors: Gupta Sonal , Joshi Nishant , Saini Monika , Singh Shailja 
Published: December 2020

AbstractIntraerythrocytic stages ofPlasmodium falciparumresponsible for all clinical manifestations of malaria are regulated by array of signaling cascades and effector molecules that represents attractive targets for antimalarial therapy. G-protein coupled receptors (GPCRs) are druggable targets in treatment of various pathological conditions however there is limited understanding about the role of GPCRs in malaria pathogenesis. InPlasmodium,serpentine receptors (PfSR1, PfSR10, PfSR12 and PfSR25) with GPCR like membrane topology have been reported with the finite knowledge about their potential as antimalarial targets. Herein we evaluated the druggability of PfSR12 using FDA approved P2Y type of purinergic signaling antagonist, Prasugrel. Blocking of purinergic receptor signaling resulted in inhibition of growth and development ofP. falciparum. Progression studies indicated the inhibitory effect of purinergic signalling inhibitor begins in late erythrocyte stages predominantly in the schizonts. Furthermore, purinoreceptor inhibitor blockedin vivogrowth of malaria parasite in mouse experimental model. The localization of PfSR1, PfSR10, PfSR12 and PfSR25 was analyzed by immunofluorescence assays. The putative purinergic receptor PfSR12 is found to be expressed in late intraerythrocytic stages. Prasugrel, a generic purinoreceptor inhibitor and agonist ATP showed specific binding to recombinant PfSR12 confirming it as purinergic receptor. This study indicates the presence of P2Y type of purinergic signaling in growth and development of malaria parasite and suggests PfSR12 as putative purinergic receptor.
Random forest model for feature-based Alzheimer’s disease conversion prediction from early mild cognitive impairment subjects
Authors: Velazquez Matthew , Lee Yugyung ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

AbstractAlzheimer’s Disease (AD) conversion prediction from the mild cognitive impairment (MCI) stage has been a difficult challenge. This study focuses on providing an individualized MCI to AD conversion prediction using a balanced random forest model that leverages clinical data. In order to do this, 383 Early Mild Cognitive Impairment (EMCI) patients were gathered from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Of these patients, 49 would eventually convert to AD (EMCI_C), whereas the remaining 335 did not convert (EMCI_NC). All of these patients were split into training and testing data sets with 95 patients reserved for testing. Nine clinical features were selected, comprised of a mix of demographic, brain volume, and cognitive testing variables. Oversampling was then performed in order to balance the initially imbalanced classes. Our results showed that a random forest model was effective (93.6% accuracy) at predicting the conversion of EMCI patients to AD based on these clinical features. Additionally, we assessed the importance of each clinical feature at both the individual and model level for interpretation of the prediction itself. Our model could impact the clinical environment as a tool to predict the conversion to AD from a prodromal stage or to identify ideal candidates for clinical trials.
Messenger RNA cap methylation by PCIF1 attenuates the interferon-β induced antiviral state
Authors: Tartell Michael A. , Boulias Konstantinos , Hoffmann Gabriela Brunsting , Greer Eric Lieberman , Whelan Sean P. J. 
Published: December 2020

AbstractInterferons induce cell intrinsic responses associated with resistance to viral infection. To overcome the suppressive action of interferons and their downstream effectors viruses have evolved diverse mechanisms. Working with vesicular stomatitis virus (VSV) we report a role for the host cell N6-adenosine mRNA cap-methylase, phosphorylated C-terminal domain interacting factor 1 (PCIF1), in attenuating the antiviral activity of interferon-β. Using cell based andin vitrobiochemical assays we demonstrate that PCIF1 efficiently modifies VSV mRNA cap structures to m7Gpppm6Am, and we identify thecis-acting elements required for this modification. Under basal conditions, N6-methylation of VSV mRNA cap structures is functionally inert with regard to mRNA stability, translation and viral infectivity. Induction of an antiviral state by treatment of cells with interferon-β prior to infection uncovered a functional role for PCIF1 in attenuation of the antiviral response. Cells lacking PCIF1 or expressing a catalytically inactive PCIF1, exhibit an augmented effect of interferon-β in the inhibition of viral replication and gene expression. This work identifies a function of PCIF1 and cap-proximal m6Amin attenuation of the host response to VSV infection that likely extends to other viruses.SignificanceThe cap structure present at the 5’ end of eukaryotic mRNAs regulates RNA stability, translation, and marks mRNA as self, thereby impeding recognition by the innate immune system. Cellular transcripts beginning with adenosine are additionally modified at the N6 position of the 2’-O methylated cap-proximal residue by the methyltransferase PCIF1 to m7Gpppm6Am. We define a function for this N6-adenosine methylation in attenuating the interferon-β mediated suppression of viral infection. Cells lacking PCIF1, or defective in its enzymatic activity, augment the cell intrinsic suppressive effect of interferon-β treatment on vesicular stomatitis virus gene expression. VSV mRNAs are efficiently methylated by PCIF1, suggesting this contributes to viral evasion of innate immune suppression.
HUMAN ADENOVIRUS TYPE 4 COMPRISES TWO MAJOR PHYLOGROUPS WITH DISTINCT REPLICATIVE FITNESS AND VIRULENCE PHENOTYPES
Authors: Bair Camden R. , Zhang Wei , Gonzalez Gabriel , Kamali Arash , Stylos Daniel , Blanco Jorge C. G. , Kajon Adriana E. 
Published: December 2020

ABSTRACTHuman adenovirus type 4 (HAdV-E4) is the only type (and serotype) classified within speciesHuman mastadenovirus Ethat has been isolated from a human host to the present. Recent phylogenetic analysis of whole genome sequences of strains representing the spectrum of intratypic genetic diversity described to date identified two major evolutionary lineages designated phylogroups (PG) I, and II, and validated the early clustering of HAdV-E4 genomic variants into two major groups by low resolution restriction fragment length polymorphism analysis. In this study we expanded our original analysis of intra- and inter-PG genetic variability, and used a panel of viruses representative of the spectrum of genetic diversity described for HAdV-E4 to examine the magnitude of inter- and intra-PG phenotypic diversity using an array of cell-based assays and a cotton rat model of HAdV respiratory infection. Our proteotyping of HAdV-E strains using concatenated protein sequences in selected coding regions including E1A, E1B-19K and −55K, DNA polymerase, L4-100K, various E3 proteins, and E4-34K confirmed that the two clades encode distinct variants/proteotypes at most of these loci. Ourin vitroandin vivostudies demonstrated that PG I and PG II differ in their growth, spread, and cell killing phenotypes in cell culture and in their pulmonary pathogenic phenotypes. Surprisingly, the differences in replicative fitness documentedin vitrobetween PGs did not correlate with the differences in virulence observed in the cotton rat model. This body of work is the first reporting phenotypic correlates of naturally occurring intratypic genetic variability for HAdV-E4.IMPORTANCEHuman adenovirus type 4 (HAdV-E4) is a prevalent causative agent of acute respiratory illness of variable severity and of conjunctivitis and comprises two major phylogroups that carry distinct coding variations in proteins involved in viral replication and modulation of host responses to infection. Our data show that PG I and PG II are intrinsically different regarding their ability to grow and spread in culture and to cause pulmonary disease in cotton rats.This is the first report of phenotypic divergence among naturally occurring known genetic variants of a HAdV type of medical importance. This research reveals readily detectable phenotypic differences between strains representing phylogroups I and II, and it introduces a unique experimental system for the elucidation of the genetic basis of adenovirus fitness and virulence and thus for increasing our understanding of the implications of intratypic genetic diversity in the presentation and course of HAdV-E4-associated disease.
PySCNet: A tool for reconstructing and analyzing gene regulatory network from single-cell RNA-Seq data
Authors: Wu Ming , Kacprowski Tim , Zehn Dietmar 
Published: December 2020

AbstractSummaryThe Advanced capacities of high throughput single cell technologies have facilitated a great understanding of complex biological systems, ranging from cell heterogeneity to molecular expression kinetics. Several pipelines have been introduced to standardize the scRNA-seq analysis workflow. These include cell population identification, cell marker detection and cell trajectory reconstruction. Yet, establishing a systematized pipeline to capture regulatory relationships among transcription factors (TFs) and genes at the cellular level still remains challenging. Here we present PySCNet, a python toolkit that enables reconstructing and analyzing gene regulatory networks (GRNs) from single cell transcriptomic data. PySCNet integrates competitive gene regulatory construction methodologies for cell specific or trajectory specific GRNs and allows for gene co-expression module detection and gene importance evaluation. Moreover, PySCNet offers a user-friendly dashboard website, where GRNs can be customized in an intuitive way.AvailabilitySource code and documentation are available:https://github.com/MingBit/PySCNetContactming.wu@tum.de
Structural and biophysical characterization of the tandem substrate-binding domains of the ABC importer GlnPQ
Authors: Ploetz Evelyn , Schuurman-Wolters Gea K. , Zijlstra Niels , Jager Amarins W. , Griffith Douglas A. , Guskov Albert , Gouridis Giorgos , Poolman Bert , Cordes Thorben 
Published: December 2020

ABSTRACTThe ATP-binding cassette transporter GlnPQ is an essential uptake system that transports glutamine, glutamic acid, and asparagine in Gram-positive bacteria. It features two extracytoplasmic substrate-binding domains (SBDs) that are linked in tandem to the transmembrane domain of the transporter. The two SBDs differ in their ligand specificities, binding affinities and their distance to the transmembrane domain. Here, we elucidate the effects of the tandem arrangement of the domains on the biochemical, biophysical and structural properties of the protein. For this, we determined the crystal structure of the ligand-free tandem SBD1-2 protein fromL. lactisin the absence of the transporter and compared the tandem to the isolated SBDs. We also used isothermal titration calorimetry to determine the ligand-binding affinity of the SBDs and single-molecule Förster-resonance energy transfer (smFRET) to relate ligand binding to conformational changes in each of the domains of the tandem. We show that substrate binding and conformational changes are not notably affected by the presence of the adjoining domain in the wild-type protein, and changes only occur when the linker between the domains is shortened. In a proof-of-concept experiment, we combine smFRET with protein-induced fluorescence enhancement and show that a decrease in SBD linker length is observed as a linear increase in donor-brightness for SBD2 while we can still monitor the conformational states (open/closed) of SBD1. These results demonstrate the feasibility of PIFE-FRET to monitor protein-protein interactions and conformational states simultaneously.HIGHLIGHTSResolved crystal structure of tandem SBD1-2 of GlnPQ fromLactococcus lactisConformational states and ligand binding affinities of individual domains SBD1 and SBD2 are similar to tandem SBD1-2No cooperative effects are seen for different ligands for SBDs in the tandemProof of concept experiments show that PIFE-FRET can monitor SBD conformations and protein-protein interaction simultaneously
Genetic Conservation of SARS-CoV-2 RNA Replication Complex in Globally Circulating Isolates and Recently Emerged Variants from Humans and Minks Suggests Minimal Pre-Existing Resistance to Remdesivir
Authors: Martin Ross , Li Jiani , Parvangada Aiyippa , Perry Jason , Cihlar Tomas , Mo Hongmei , Porter Danielle , Svarovskaia Evguenia 
Published: December 2020

AbstractRemdesivir (RDV) exhibits potent antiviral activity against SARS-CoV-2 and is currently the only drug approved for the treatment of COVID-19. However, little is currently known about the potential for pre-existing resistance to RDV and the possibility of SARS-CoV-2 genetic diversification that might impact RDV efficacy as the virus continue to spread globally. In this study, >90,000 SARS-CoV-2 sequences from globally circulating clinical isolates, including sequences from recently emerged United Kingdom and South Africa variants, and >300 from mink isolates were analyzed for genetic diversity in the RNA replication complex (nsp7, nsp8, nsp10, nsp12, nsp13, and nsp14) with a focus on the RNA-dependent RNA polymerase (nsp12), the molecular target of RDV. Overall, low genetic variation was observed with only 12 amino acid substitutions present in the entire RNA replication complex in ≥0.5% of analyzed sequences with the highest overall frequency (82.2%) observed for nsp12 P323L that consistently increased over time. Low sequence variation in the RNA replication complex was also observed among the mink isolates. Importantly, the coronavirus Nsp12 mutations previously selected in vitro in the presence of RDV were identified in only 2 isolates (0.002%) within all the analyzed sequences. In addition, among the sequence variants observed in ≥0.5% clinical isolates, including P323L, none were located near the established polymerase active site or sites critical for the RDV mechanism of inhibition. In summary, the low diversity and high genetic stability of the RNA replication complex observed over time and in the recently emerged SARS-CoV-2 variants suggests a minimal global risk of pre-existing SARS-CoV-2 resistance to RDV.
Downtown Diet: a global meta-analysis of urbanization on consumption patterns of vertebrate predators
Authors: Gámez Siria , Potts Abigail , Mills Kirby L. , Allen Aurelia A. , Holman Allyson , Randon Peggy , Linson Olivia , Harris Nyeema C. 
Published: December 2020

AbstractPredation is a fundamental ecological process that shapes communities and drives long-term evolutionary dynamics. As the world rapidly urbanizes, it is critical to understand how the built environment and other human perturbations alter predation across taxa. We conducted a meta-analysis to quantify the effects of urban environments on three components of trophic ecology in predators: dietary species richness (DSR), dietary evenness (DEV), and stable isotopic ratios (δ13C and δ15N IR). We then evaluated whether intensity of anthropogenic pressure, using the human footprint index (HFI), explained variation in the effect sizes of dietary attributes using a meta-regression. We calculated Hedges’ g effect sizes from 44 studies including 11,986 samples across 40 predatory species in 39 cities globally. The direction and magnitude of effect sizes varied between predator taxonomic groups with reptile diets exhibiting the most sensitivity to urbanization. Effect sizes revealed that predators in cities had comparable DSR, DEV, and nitrogen ratios, though carbon consumption was significantly higher. We found that HFI did not explain variation in effect sizes, a result consistent between the 1993 and 2009 editions of this metric. Our study provides the first assessment of how urbanization has perturbed predator-prey interactions for multiple taxa at a global scale, revealing that the functional role of predators is conserved in cities and urbanization does not inherently relax predation.
XlinkCyNET: a Cytoscape application for visualization of protein interaction networks based on cross-linking mass-spectrometry identifications
Authors: Lima Diogo Borges , Zhu Ying , Liu Fan 
Published: December 2020

ABSTRACTSoftware tools that allow visualization and analysis of protein interaction networks are essential for studies in systems biology. One of the most popular network visualization tools in biology is Cytoscape, which offers a large selection of plugins for interpretation of protein interaction data. Chemical cross-linking coupled to mass spectrometry (XL-MS) is an increasingly important source for such interaction data, but there are currently no Cytoscape tools to analyze XL-MS results. In light of the suitability of Cytoscape platform but also to expand its toolbox, here we introduceXlinkCyNET, an open-source Cytoscape Java plugin for exploring large-scale XL-MS-based protein interaction networks. XlinkCyNET offers rapid and easy visualization of intra and intermolecular cross-links and the locations of protein domains in a rectangular bar style, allowing subdomain-level interrogation of the interaction network. XlinkCyNET is freely available from the Cytoscape app store:http://apps.cytoscape.org/apps/xlinkcynetand athttps://www.theliulab.com/software/xlinkcynet.
PhylUp: phylogenetic alignment building with custom taxon sampling
Authors: Kandziora Martha 
Published: December 2020

AbstractIn recent years it has become easier to reconstruct large-scale phylogenies with more or less automated workflows. However, they do not permit to adapt the taxon sampling strategy for the clade of interest. While most tools permit a single representative per taxon, PhylUp – the workflow presented here - enables to use different sampling strategies for different taxonomic ranks, as often needed for molecular dating analyses or for a large outgroup sampling. While PhylUp focuses on user-defined sampling strategies, it also facilitates the updating of alignments with new sequences from local and online sequence databases and their incorporation into existing alignments. To start a PhylUp run at least one sequence per locus has to be provided, PhylUp then adds new sequences to the existing one by internally using BLAST to find similar sequences and filters them according to user settings. Taxonomic sampling is increased compared to available tools and the custom taxonomic sampling allows to use automated workflows for new research fields. The workflow is presented in detail and I demonstrate the usability.
easyMF: A Web Platform for Matrix Factorization-based Biological Discovery from Large-scale Transcriptome Data
Authors: Ma Wenlong , Chen Siyuan , Zhai Jingjing , Qi Yuhong , Xie Shang , Song Minggui , Ma Chuang 
Published: December 2020

AbstractWith the development of high-throughput experimental technologies, large-scale RNA sequencing (RNA-Seq) data have been and continue to be produced, but have led to challenges in extracting relevant biological knowledge hidden in the produced high-dimensional gene expression matrices. Here, we present easyMF, a user-friendly web platform that aims to facilitate biological discovery from large-scale transcriptome data through matrix factorization (MF). The easyMF platform enables users with little bioinformatics experience to streamline transcriptome analysis from raw reads to gene expression and to decompose expression matrix from thousands of genes to a handful of metagenes. easyMF also offers a series of functional modules for metagene-based exploratory analysis with an emphasis on functional gene discovery. As a modular, containerized and open-source platform, easyMF can be customized to satisfy users’ specific demands and deployed as a web server for broad applications. easyMF is freely available athttps://github.com/cma2015/easyMF. We demonstrated the application of easyMF with four case studies using 940 RNA sequencing datasets from maize (Zea maysL.).
Evaluation of a polymeric composite bone filler scaffold for local antibiotic delivery to preventStaphylococcus aureusinfection in a contaminated bone defect
Authors: Beenken Karen E. , Campbell Mara J. , Ramirez Aura M. , Alghazali Karrar , Walker Christopher M. , Jackson Bailey , Griffin Christopher , King William , Bourdo Shawn E. , Rifkin Rebecca , Hecht Silke , Meeker Daniel G. , Anderson David E. , Biris Alexandru S. , Smeltzer Mark S. 
Published: December 2020

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane (dPU), nano-sized hydroxyapatite (nHA), and decellularized bovine bone particles (DBP). In this report we describe the results of studies aimed at evaluating the use of this scaffold as a means of local antibiotic delivery for the prevention of infection in a segmental bone defect contaminated withStaphylococcus aureus. We evaluated two different scaffold formulations that contained the same components in the same ratios but differed from each other with respect to overall porosity and therefore surface area. Studies done with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity was correlated with increased uptake and prolonged release of all three antibiotics. Vancomycin could be passively loaded into either scaffold formulation in an amount sufficient to prevent infection, as evidenced by the complete eradication of viable bacteria from the surgical site of most animals in a rabbit model of a contaminated mid-radial segmental bone defect. Even in those few cases in which complete eradication was not achieved, the number of viable bacteria present in the bone was significantly reduced comparison to untreated controls. There was also no radiographic evidence of osteomyelitis in any rabbit treated with vancomycin-loaded scaffold. Microcomputed tomography (μCT) of bone defects up to 84 days of exposure to scaffolds with and without vancomycin also demonstrated that the addition of vancomycin even in the highest concentration did not significantly diminish the osteogenic properties of either scaffold formulation. Together, these results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery.