bluuebunny/crossref_metadata_2025_split huggingface dataset:
CMTM6 drives cisplatin resistance in OSCC by regulating AKT mediated Wnt signaling
Authors: Mohapatra Pallavi , Shriwas Omprakash , Mohanty Sibasish , Kaushik Sandeep Rai , Arya Rakesh , Rath Rachna , Majumdar Saroj Kumar Das , Muduly Dillip Kumar , Nanda Ranjan K , Dash Rupesh 
Published: March 2020

AbstractChemoresistance is one of the important factors for treatment failure in OSCC, which can culminate in progressive tumor growth and metastatic spread. Rewiring tumor cells to undergo drug-induced apoptosis is a promising way to overcome chemoresistance, which can be achieved by identifying the causative factors for acquired chemoresistance. In this study, to explore the key cisplatin resistance triggering factors, we performed global proteomic profiling of OSCC lines representing with sensitive, early and late cisplatin-resistant patterns. The top ranked up-regulated protein appeared to be CMTM6. We found CMTM6 to be elevated in both early and late cisplatin-resistant cells with respect to the sensitive counterpart. Analyses of OSCC patient samples indicate that CMTM6 expression is upregulated in chemotherapy-non-responder tumors as compared to chemotherapy-naïve tumors. Stable knockdown of CMTM6 restores cisplatin-mediated cell death in chemoresistant OSCC lines. Similarly, upon CMTM6 overexpression in CMTM6KD lines, the cisplatin resistant phenotype was efficiently rescued. Mechanistically, it was found that CMTM6 interacts with membrane bound Enolase-1 and stabilized its expression, which in turn activates the AKT-GSK3β mediated Wnt signaling. CMTM6 triggers the translocation of β-catenin into the nucleus, which elevates the Wnt target pro-survival genes like Cyclin D, c-Myc and CD44. Moreover, incubation with lithium chloride, a Wnt signaling activator, efficiently rescued the chemoresistant phenotype in CMTM6KD OSCC lines. In a patient-derived cell xenograft model of chemoresistant OSCC, knock-down of CMTM6 restores cisplatin induced cell death and results in significant reduction of tumor burden. CMTM6 has recently been identified as a stabilizer of PD-L1 and henceforth it facilitates immune evasion by tumor cells. Herewith for the first time, we uncovered another novel role of CMTM6 as one of the major driver of cisplatin resistance.
Host shifting and host sharing in a genus of specialist flies diversifying alongside their sunflower hosts
Authors: Hippee Alaine C. , Beer Marc A. , Bagley Robin K. , Condon Marty A. , Kitchen Andrew , Lisowski Edward A. , Norrbom Allen L. , Forbes Andrew A. 
Published: March 2020

AbstractCongeneric parasites are unlikely to specialize on the same tissues of the same host species, likely because of strong multifarious selection against niche overlap. Exceptions where multiple congeneric species overlap on the same tissues may therefore reveal important insights into the ecological factors underlying the origins and maintenance of diversity. Larvae of sunflower maggot flies in genusStrauziafeed on the pith of plants in the family Asteraceae. AlthoughStrauziatend to be host specialists, some species overlap in their host use. To resolve the origins of host sharing among these specialist flies, we used reduced representation genomic sequencing to infer the first multi-locus phylogeny of genusStrauzia.Our results show thatHelianthus tuberosusandHelianthus grosseserratuseach host three different fly species, and that the flies co-occurring on a host are not one another’s closest relatives. Though this pattern implies that host sharing is most likely the result of host shifts, these may not be host shifts in the conventional sense of an insect moving onto an entirely new plant. Many hosts ofStrauziabelong to a young (1-2 MYA) clade of perennial sunflowers noted for their frequent introgression and hybrid speciation events. In at least one case, flies may have converged upon a host after their respective ancestral host plants hybridized to form a new sunflower species (H. tuberosus). Broadly, we suggest that rapid and recent adaptive introgression and speciation in this group of plants may have instigated the diversification of their phytophagous fly associates, including the convergence of >1 species onto the same shared host plants.
Direct Measurement of Trunk Volume in Forest Trees: Focus on White Pine and Comparison to a Statistical Method
Authors: Leverett Robert T. , Ruskin David N. , Masino Susan A. 
Published: March 2020

AbstractAccurate measurement of tree volume and associated carbon storage are necessary to determine ongoing sequestration as well as site productivity and changes in growth of individual tree species. Standard statistical methods vary their estimations of tree volume, and thus carbon storage and sequestration, particularly in larger, older trees in a forest setting. Here, we describe a detailed direct measurement method that combines traditional trunk taper models with state-of-the-art instrumentation and the best mathematical models for producing more accurate measurements of trunk volume. A stand-grown Eastern White Pine (Pinus strobus) is used as an example; the method is compared with a commonly used statistics-based Forest Service method. This latter method is shown to over- or underestimate volume if the trunk form factor deviates sufficiently from the average value for this species. Direct measurement modeling can be used to validate or choose among existing simple statistical volume models, especially for local applications. It can also assist in widespread recalibration of other standards and models used to estimate volume and carbon storage over time.
Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation
Authors: Liu Zilei , Li Jie P. , Chen Mingkuan , Wu Mengyao , Shi Yujie , Li Wei , Teijaro John R. , Wu Peng 
Published: March 2020

SummaryRe-activation and clonal expansion of tumor specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL) based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. Here we introduce FucoID as a general platform to detect endogenous antigen-specific T cells and study their biology. Through this interaction dependent labeling approach, TSA-reactive T cells can be detected and separated from bystander T cells in primary tumor digests based on their cell-surface enzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possess a distinct TCR repertoire and unique gene features. Though exhibiting a dysfunctional phenotype, this subset of TILs possesses substantial capabilities of proliferation and tumor specific killing. FucoID features genetic manipulation-free procedures and a quick turnover cycle, and therefore should have the potential of accelerating the pace of personalized cancer treatment.HighlightsInteraction dependent fucosylation enables the detection and isolation ofbona fideintratumoral tumor specific antigen-reactive T cellsTumor specific antigen-reactive CD8+T cells possess capabilities to be expanded and adoptively transferred for tumor controlTumor specific antigen-reactive CD8+T cells feature oligoclonal expansion and upregulate genes for the steroid biosynthesis and metabolic processIntratumoral bystander CD8+T cells can be separated into two groups based on PD-1 expression that feature distinct gene modules
Austropuccinia psidii, causing myrtle rust, has a gigabase-sized genome shaped by transposable elements
Authors: Tobias Peri A , Schwessinger Benjamin , Deng Cecilia H , Wu Chen , Dong Chongmei , Sperschneider Jana , Jones Ashley , Lou Zhenyan , Zhang Peng , Sandhu Karanjeet , Smith Grant R , Tibbits Josquin , Chagné David , Park Robert F 
Published: March 2020

AbstractAustropuccinia psidii, originating in South America, is a globally invasive fungal plant pathogen that causes rust disease on Myrtaceae. Several biotypes are recognized, with the most widely distributed pandemic biotype spreading throughout the Asia-Pacific and Oceania regions over the last decade.Austropuccinia psidiihas a broad host range with more than 480 myrtaceous species. Since first detected in Australia in 2010, the pathogen has caused the near extinction of at least three species and negatively affected commercial production of several Myrtaceae. To enable molecular and evolutionary studies intoA. psidiipathogenicity, we assembled a highly contiguous genome for the pandemic biotype. With an estimated haploid genome size of just over 1 Gb (gigabases), it is the largest assembled fungal genome to date. The genome has undergone massive expansion via distinct transposable element (TE) bursts. Over 90% of the genome is covered by TEs predominantly belonging to the Gypsy superfamily. These TE bursts have likely been followed by deamination events of methylated cytosines to silence the repetitive elements. This in turn led to the depletion of CpG sites in transposable elements and a very low overall GC content of 33.8%. The overall gene content is highly conserved, when compared to other closely related Pucciniales, yet the intergenic distances are increased by an order of magnitude indicating a general insertion of TEs between genes. Overall, we show how transposable elements shaped the genome evolution ofA. psidiiand provide a greatly needed resource for strategic approaches to combat disease spread.
Intracellular Delivery of NanoparticlesviaMicroelectrophoresis Technique: Feasibility demonstration
Authors: Han Mengke , Zhao Jiangbo , Fabian Joseph Mahandas , Mustafa Sanam , Ruan Yinlan , Wiederman Steven , Ebendorff-Heidepriem Heike 
Published: March 2020

ABSTRACTNanoparticles with desirable properties and functions have been actively developed for various bio-medical research, such asin vivoandin vitrosensors, imaging agents and delivery vehicles of therapeutics. However, an effective method to deliver nanoparticles into the intracellular environment is a major challenge and critical to many biological studies. Current techniques, such as intracellular uptake, electroporation and microinjection, each have their own set of benefits and associated limitations (e.g., aggregation and endosomal degradation of nanoparticles, high cell mortality and low throughput). Here, the well-established microelectrophoresis technique is applied for the first time to deliver nanoparticles into target cells, which overcomes some of these delivery difficulties. Semiconductive quantum dots, with average hydrodynamic diameter of 24.4 nm, have been successfully ejectedviasmall electrical currents (−0.2 nA) through fine-tipped glass micropipettes as an example, into living human embryonic kidney cells (roughly 20 - 30μm in length). As proposed by previous studies, micropipettes were fabricated to have an average tip inner diameter of 206 nm for ejection but less than 500 nm to minimize the cell membrane damage and cell distortion. In addition, delivered quantum dots were found to stay monodispersed within the cells for approximately one hour. We believe that microelectrophoresis technique may serve as a simple and general strategy for delivering a variety of nanoparticles intracellularly in various biological systems.
Reverse transcriptase enzyme and priming strategy affect quantification and diversity of environmental transcripts
Authors: Cholet Fabien , Ijaz Umer Z. , Smith Cindy J. 
Published: March 2020

SummaryRT-Q-PCR, and RT-PCR amplicon sequencing, provide a convenient, target-specific, high-sensitivity approach for gene expression studies and are widely used in environmental microbiology. Yet, the effectiveness and reproducibility of the reverse transcription step has not been evaluated. Therefore, we tested a combination of four commercial reverse transcriptases with two priming techniques to faithfully transcribe16S rRNAandamoAtranscripts from marine sediments. Both enzyme and priming strategy greatly affected quantification of the exact same target with differences of up to 600-fold. Furthermore, the choice of RT system significantly changed the communities recovered. For16S rRNA, both enzyme and priming had a significant effect with enzyme having a stronger impact than priming. Inversely, foramoAonly the change in priming strategy resulted in significant differences between the same sample. Specifically, more OTUs and better coverage ofamoAtranscripts diversity were obtained with GS priming indicating this approach was better at recovering the diversity ofamoAtranscripts. Moreover, sequencing of RNA mock communities revealed that, even though transcript α diversities (i.e.OTU counts within a sample) can be biased by the RT, the comparison of β diversities (i.e.differences in OTU counts between samples) is reliable as those biases are reproducible between environments.Originality-Significance StatementIs the complementary DNA (cDNA) produced after Reverse Transcription (RT) a faithful representation of the starting RNA? This is a fundamental and important question for transcriptomic-based studies in environmental microbiology that aim to quantify and/or examine the diversity of transcripts via RT approaches. Yet little is known about the reliability and reproducibility of this step. Here, we evaluated the effect of the two main components of the RT reaction – the retro transcriptase enzyme and priming strategy (gene specific vs random priming), on the quantification and diversity of cDNA. We found that both have a significant impact. We further provide evidence to enable informed choices as to the enzyme and priming combinations to improve the performance of RT-PCR approaches. Taken together, this work will improve the reliability and reproducibility of transcript-based studies in environmental microbiology.
The genetic basis for PRC1 complex diversity emerged early in animal evolution
Authors: Gahan James M , Rentzsch Fabian , Schnitzler Christine E 
Published: March 2020

AbstractPolycomb group proteins are essential regulators of developmental processes across animals. Despite their importance, studies on Polycomb are often restricted to classical model systems and, as such, little is known about the evolution of these important chromatin regulators. Here we focus on Polycomb Repressive Complex 1 (PRC1) and trace the evolution of core components of canonical and non-canonical PRC1 complexes in animals. Previous work suggested that a major expansion in the number of PRC1 complexes occurred in the vertebrate lineage. Here we show that the expansion of the PCGF protein family, an essential step for the establishment of the large diversity of PRC1 complexes found in vertebrates, predates the bilaterian-cnidarian ancestor. This means that the genetic repertoire necessary to form all major vertebrate PRC1 complexes emerged early in animal evolution, over 550 million years ago. We further show thatPCGF5, a gene conserved in cnidarians and vertebrates but lost in all other studied groups, is expressed in the nervous system in the sea anemoneNematostella vectensis, similar to its mammalian counterpart. Together this work provides an evolutionary framework to understand PRC1 complex diversity and evolution and establishesNematostellaas a promising model system in which this can be further explored.
Active Listening
Authors: Friston Karl J. , Sajid Noor , Quiroga-Martinez David Ricardo , Parr Thomas , Price Cathy J. , Holmes Emma 
Published: March 2020

AbstractThis paper introduces active listening, as a unified framework for synthesising and recognising speech. The notion ofactive listeninginherits from active inference, which considers perception and action under one universal imperative: to maximise the evidence for our (generative) models of the world. First, we describe a generative model of spoken words that simulates (i) how discrete lexical, prosodic, and speaker attributes give rise to continuous acoustic signals; and conversely (ii) how continuous acoustic signals are recognised as words. The ‘active’ aspect involves (covertly) segmenting spoken sentences and borrows ideas from active vision. It casts speech segmentation as the selection of internal actions, corresponding to the placement of word boundaries. Practically, word boundaries are selected that maximise the evidence for an internal model of how individual words are generated. We establish face validity by simulating speech recognition and showing how the inferred content of a sentence depends on prior beliefs and background noise. Finally, we consider predictive validity by associating neuronal or physiological responses, such as the mismatch negativity and P300, with belief updating under active listening, which is greatest in the absence of accurate prior beliefs about what will be heard next.
Computational vaccinology based development of multi-epitope subunit vaccine for protection against the Norovirus’ infections
Authors: Ahmad Irfan , Ali Syed Shujait , Shah Ismail , Khan Shahzeb , Khan Mazhar , Ullah Saif , Ali Shahid , Khan Jafar , Ali Mohammad , Khan Abbas , Wei Dong-Qing 
Published: March 2020

AbstractHuman Norovirus belong to familyCalciviridae, it was identified in the outbreak of gastroenteritis in Norwalk, due to its seasonal prevalence known as “winter vomiting disease”. Treatment of Norovirus infection is still mysterious because there is no effective antiviral drugs or vaccine developed to protect against the infection, to eradicate the infection an effective vaccine should be developed. In this study capsid protein (A7YK10), small protein (A7YK11) and polyprotein (A7YK09) were utilized. These proteins were subjected to B and T cell epitopes prediction by using reliable immunoinformatics tools. The antigenic and non-allergenic epitopes were selected for subunit vaccine, which can activate cellular and humoral immune responses. Linkers joined these epitopes together. The vaccine structure was modelled and validated by using Errat, ProSA and rampage servers. The modelled vaccine was docked with TLR-7. Stability of the docked complex was evaluated by MD simulation. In order to apply the concept in a wet lab, the reverse translated vaccine sequence was cloned in pET28a (+). The vaccine developed in this study requires experimental validation to ensure its effectiveness against the disease.
Revealing 29 sets of independently modulated genes inStaphylococcus aureus, their regulators and role in key physiological responses
Authors: Poudel Saugat , Tsunemoto Hannah , Seif Yara , Sastry Anand , Szubin Richard , Xu Sibei , Machado Henrique , Olson Connor , Anand Amitesh , Pogliano Joe , Nizet Victor , Palsson Bernhard O. 
Published: March 2020

AbstractThe ability ofStaphylococcus aureusto infect many different tissue sites is enabled, in part, by its Transcriptional Regulatory Network (TRN) that coordinates its gene expression to respond to different environments. We elucidated the organization and activity of this TRN by applying Independent Component Analysis (ICA) to a compendium of 108 RNAseq expression profiles from twoS. aureusclinical strains (TCH1516 and LAC). ICA decomposed theS. aureustranscriptome into 29 independently modulated sets of genes (i-modulons) that revealed (1) high confidence associations between 21 i-modulons and known regulators; (2) an association between an i-modulon and σS, whose regulatory role was previously undefined; (3) the regulatory organization of 65 virulence factors in the form of three i-modulons associated with AgrR, SaeR and Vim-3, (4) the roles of three key transcription factors (codY, Fur and ccpA) in coordinating the metabolic and regulatory networks; and (5) a low dimensional representation, involving the function of few transcription factors, of changes in gene expression between two laboratory media (RPMI, CAMHB) and two physiological media (blood and serum). This representation of the TRN covers 842 genes representing 76% of the variance in gene expression that provides a quantitative reconstruction of transcriptional modules inS. aureus, and a platform enabling its full elucidation.Significance StatementStaphylococcus aureusinfections impose an immense burden on the healthcare system. To establish a successful infection in a hostile host environment,S. aureusmust coordinate its gene expression to respond to a wide array of challenges. This balancing act is largely orchestrated by the Transcriptional Regulatory Network (TRN). Here, we present a model of 29 independently modulated sets of genes that form the basis for a segment of the TRN in clinical USA300 strains ofS. aureus. Using this model, we demonstrate the concerted role of various cellular systems (e.g. metabolism, virulence and stress response) underlying key physiological responses, including response during blood infection.
Pixel-based machine learning and image reconstitution for dot-ELISA pathogen serodiagnosis
Authors: Anastassopoulou Cleo , Tsakris Athanasios , Patrinos George P. , Manoussopoulos Yiannis 
Published: March 2020

AbstractSerological methods serve as a direct or indirect means of pathogen infection diagnosis in plant and animal species, including humans. Dot-ELISA (DE) is an inexpensive and sensitive, solid-state version of the microplate enzyme-linked immunosorbent assay, with a broad range of applications in epidemiology. Yet, its applicability is limited by uncertainties in the qualitative output of the assay due to overlapping dot colorations of positive and negative samples, stemming mainly from the inherent color discrimination thresholds of the human eye. Here, we report a novel approach for unambiguous DE output evaluation by applying machine learning-based pattern recognition of image pixels of the blot using an impartial predictive model rather than human judgment. Supervised machine learning was used to train a classifier algorithm through a built multivariate logistic regression model based on the RGB (“Red”, “Green”, “Blue”) pixel attributes of a scanned DE output of samples of known infection status to a model pathogen (Lettuce big-vein associated virus). Based on the trained and cross-validated algorithm, pixel probabilities of unknown samples could be predicted in scanned DE output images which would then be reconstituted by pixels having probabilities above a cutoff that may be selected at will to yield desirable false positive and false negative rates depending on the question at hand, thus allowing for proper dot classification of positive and negative samples and, hence, accurate diagnosis. Potential improvements and diagnostic applications of the proposed versatile method that translates unique pathogen antigens to the universal basic color language are discussed.
Natural selection has preserved and enhanced the phase-separation properties of FUS during 160 million years of mammalian evolution
Authors: Dasmeh Pouria , Wagner Andreas 
Published: March 2020

AbstractProtein phase separation is essential for the self-assembly of non-membraneous organelles. However, we know little about its ability to change in evolution. Here we studied the evolution of the mammalian RNA binding protein FUS, a protein whose prion-like domain (PLD) is essential for the formation of stress granules through liquid-liquid phase separation. Although the prion-like domain evolves three times as rapidly as the remainder of FUS, it harbors absolutely conserved tyrosine residues that are crucial for phase separation. Ancestral reconstruction shows that the phosphorylation sites within the PLD are subject to stabilizing selection. They toggle among a small number of amino acid states. One exception to this pattern are primates, where the number of such phosphosites has increased through positive selection. In addition, we find frequent glutamine to proline changes that help maintain the unstructured state of FUS that is necessary for phase separation. In summary, natural selection has stabilized the liquid-forming potential of FUS and minimized the propensity of cytotoxic liquid-to-solid phase transitions during 160 million years of mammalian evolution.