bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Scentsor”: A Whole-Cell Yeast Biosensor with an Olfactory Reporter for Low-Cost and Equipment-Free Detection of Pharmaceuticals
Authors: Miller Rachel A. , Lee Seryeong , Fridmanski Ethan J. , Barron Elsa , Pence Julia , Lieberman Marya , Goodson Holly V. 
Published: July 2020

ABSTRACTPortable and inexpensive analytical tools are required to monitor pharmaceutical quality in technology limited settings including low- and middle-income countries (LMICs). Whole cell yeast biosensors have the potential to help meet this need. However, most of the read-outs for yeast biosensors require expensive equipment or reagents. To overcome this challenge, we have designed a yeast biosensor that produces a unique scent as a readout. This inducible scent biosensor, or “scentsor,” does not require the user to administer additional reagents for reporter development and utilizes only the user’s nose to be “read.” In this manuscript, we describe a scentsor that is responsive to the hormone estradiol (E2). The best estimate threshold (BET) for E2 detection with a panel of human volunteers (n = 49) is 39 nM E2 (15 nM when “non-smellers” are excluded). This concentration of E2 is sensitive enough to detect levels of E2 that would be found in dosage forms. This manuscript provides evidence that scent has potential for use in portable yeast biosensors as a read out, particularly for use in technology-limited environments.
Immediate and long-term effects of transcranial direct-current stimulation in the mouse primary somatosensory cortex
Authors: Sánchez-León Carlos A. , Cordones Isabel , Ammann Claudia , Ausín José M. , Gómez-Climent María A. , Carretero-Guillén Alejandro , Campos Guillermo Sánchez-Garrido , Gruart Agnès , Delgado-García José M. , Cheron Guy , Medina Javier F. , Márquez-Ruiz Javier 
Published: July 2020

AbstractTranscranial direct-current stimulation (tDCS) is a non-invasive brain stimulation technique consisting in the application of weak electric currents on the scalp. Although previous studies have demonstrated the clinical value of tDCS for modulating sensory, motor, and cognitive functions, there are still huge gaps in the knowledge of the underlying physiological mechanisms. To define the immediate impact as well as the after-effects of tDCS on sensory processing, we first performed electrophysiological recordings in primary somatosensory cortex (S1) of alert mice during and after administration of S1-tDCS, and followed up with immunohistochemical analysis of the stimulated brain regions. During the application of cathodal and anodal transcranial currents we observed polarity-specific bidirectional changes in the N1 component of the sensory-evoked potentials (SEPs) and associated gamma oscillations. Regarding the long-term effects observed after 20 min of tDCS, cathodal stimulation produced significant after-effects including a decreased SEP amplitude for up to 30 min, a power reduction in the 20-80 Hz range and a decrease in gamma event related synchronization (ERS). In contrast, no significant long-term changes in SEP amplitude or power analysis were observed after anodal stimulation except for a significant increase in gamma ERS after tDCS cessation. The polarity-specific differences of these long-term effects were corroborated by immunohistochemical analysis, which revealed an unbalance of GAD 65-67 immunoreactivity between the stimulated vs. non-stimulated S1 region only after cathodal tDCS. These results highlight the differences between immediate and long-term effects of tDCS, as well as the asymmetric long-term changes induced by anodal and cathodal stimulation.Significance StatementHere we provide a first glimpse at the immediate and long-term impact of tDCS on neural processing in alert animals. The obtained results highlight the complexity of tDCS-associated effects, which include both bidirectional as well as asymmetrical modulation depending on the polarity of the stimulation. This asymmetry suggests the implication of different mechanisms underlying the long-term effects induced by anodal and cathodal transcranial currents. Identifying and defining these effects and its associated mechanisms is crucial to help design effective protocols for clinical applications.
ANTAGONISTIC ROLES FOR ATAXIN-2 STRUCTURED AND DISORDERED DOMAINS IN RNP CONDENSATION
Authors: Singh Amanjot , Huelsmeier Joern , Kandi Arvind Reddy , Pothapragada Sai Shruti , Hillebrand Jens , Petrauskas Arnas , Agrawal Khushboo , Krishnan RT , Thiagarajan Devasena , VijayRaghavan K. , Ramaswami Mani , Bakthavachalu Baskar 
Published: July 2020

ABSTRACTAtaxin-2 is a conserved translational control protein associated with spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS) as well as an important target for ALS therapeutics under development. Despite its clinical and biological significance, Ataxin-2’s activities, mechanisms and functions are not well understood. WhileDrosophilaAtaxin-2 (Atx2) mediates mRNP condensation via a C-terminal intrinsically disordered domain (cIDR), how Ataxin-2 IDRs work with structured (Lsm, Lsm-AD and PAM2) domains to enable positive and negative regulation of target mRNAs remains unclear. Using TRIBE (Targets of RNA-Binding Proteins Identified by Editing) technology, we identified and analysed Atx-2 target mRNAs in theDrosophilabrain. We show that Atx2 preferentially interacts with AU-rich elements (AREs) in 3’UTRs and plays a broad role in stabilization of identified target mRNAs. Strikingly, Atx2 interaction with its targets is dependent on the cIDR domain required for neuronal-granule formation. In contrast, Atx2 lacking its Lsm domain not only interacts more efficiently with the target mRNA identified, but also forms larger RNP granules. Providing an extensive dataset of Atx2-interacting brain mRNAs, our results demonstrate that Atx2: (a) interacts with target mRNAs within RNP granules; (b) modulates the turnover of these target mRNAs; (c) has an additional essential role outside of mRNP granules; and (d) contains distinct protein domains that drive or oppose RNP-granule assembly. These findings increase understanding of neuronal translational control mechanisms and inform Ataxin-2-based interventions in development for SCA2 and ALS.
KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma
Authors: D’Oto Alexandra , Fang Jie , Jin Hongjian , Xu Beisi , Singh Shivendra , Mullasseril Anoushka , Jones Victoria , Abu-Zaid Ahmed , von Buttlar Xinyu , Cooke Bailey , Hu Dongli , Shohet Jason , Murphy Andrew J , Davidoff Andrew M , Yang Jun 
Published: July 2020

ABSTRACTThe H3K27me2/me3 histone demethylase KDM6B is over-expressed in neuroblastoma and is essential to neuroblastoma cell survival. While the KDM6B inhibitor, GSK-J4, has shown activity inin vitroandin vivopreclinical models, the mechanism of action remains poorly defined. We demonstrate that genetic and pharmacologic inhibition of KDM6B downregulates the pRB-E2F transcriptome andMYCNexpression. Chemical genetic analyses show that high expression of the E2F transcriptome is positively correlated with sensitivity of cancer cells to GSK-J4. Mechanistically, inhibition of KDM6B activity 1) reduces the chromatin accessibility of E2F target genes andMYCN, 2)selectively leads to an increase of H3K27me3 but a decrease of the enhancer mark H3K4me1 at the CTCF and BORIS binding sites, which may, consequently, disrupt the long-range chromatin interaction ofMYCNand E2F target genes, and 3) phenocopies the transcriptome induced by the specific CDK4/6 inhibitor palbociclib. Overexpression of CDK4/6 orRb1knockout confers neuroblastoma cell resistance to both palbociclib and GSK-J4. A gene signature targeted by KDM6B inhibition is associated with poor survival of patients with neuroblastoma regardless of theMYCNstatus. These data indicate that KDM6B activity promotes an oncogenic CDK4/6-pRB-E2F pathway in neuroblastoma cells via H3K27me3-dependent enhancer-promoter interactions, providing a rationale to target KDM6B for high-risk neuroblastoma.
An open-source experimental framework for automation of high-throughput cell biology experiments
Authors: Katunin Pavel , Cadby Ashley , Nikolaev Anton 
Published: July 2020

AbstractModern data analysis methods, such as optimisation algorithms or machine and deep learning, have been successfully applied to a number of biological, biotechnological and medical questions. For these methods to be efficient, a large number of high quality experiments need to be conducted, which requires a high degree of automation. Here we report an open-source hardware that allows for automatic high-throughput generation of large amounts of cell biology data. The hardware consists of an automatic XY-stage for moving a multiwell plate containing growing cells; a perfusion manifold allowing application of up to 8 different solutions; and a small epifluorescent microscope. It is extremely cheap (approximately £400 without and £2500 with a fluorescent microscope) and is easily customizable for individual experimental needs. We demonstrate the usability of this platform with high-throughput Ca2+ imaging and large-scale labelling experiments.Key points-We present an open source framework for automation of cell biology experiments-The framework consists of an XY platform, application of up to 8 solutions and a small epifluorescent microscope with autofocusing-Very cheap (£400 without a fluorescent microscope and £2500 with a fluorescent microscope), customisable,-Can be used in a variety of biological applications such as imaging of fluorescent reporters, optimisation of treatment conditions and fluorescent labelling
Relationships between macro-fungal dark diversity and habitat parameters using LiDAR
Authors: Valdez Jose W. , Brunbjerg Ane Kirstine , Fløjgaard Camilla , Dalby Lars , Clausen Kevin K. , Pärtel Meelis , Pfeifer Norbert , Hollaus Markus , Wimmer Michael H. , Ejrnæs Rasmus , Moeslund Jesper Erenskjold 
Published: July 2020

AbstractDespite the important role of fungi for ecosystems, relatively little is known about the factors underlying the dynamics of their diversity. Moreover, studies do not typically consider their dark diversity: the species absent from an otherwise suitable site. Here, we examined potential drivers of local fungal dark diversity in temperate woodland and open habitats using LiDAR and in-situ field measurements, combined with a systematically collected and geographically comprehensive macro-fungi and plant data set. For the first time, we also estimated species pools of fungi by considering both plant and fungi co-occurrences. The most important LiDAR variables for modelling fungal dark diversity were amplitude and echo ratio, which are both thought to represent vegetation structure. These results suggest that the local fungal dark diversity is highest in production forests like plantations and lowest in more open forests and in open habitats with little woody vegetation. Plant species richness was the strongest explanatory factor overall and negatively correlated with local fungal dark diversity. Soil fertility showed a positive relationship with dark diversity in open habitats. These findings may indicate that the local dark diversity of macro-fungi is highest in areas with a relatively high human impact (typically areas with low plant species richness and high soil fertility). Overall, this study brings novel insights into local macro-fungi dark diversity patterns, suggesting that a multitude of drivers related to both soil and vegetation act in concert to determine fungal dark diversity.
Development of a free radical scavenging probiotic to mitigate coral bleaching
Authors: Dungan Ashley M. , Bulach Dieter , Lin Heyu , van Oppen Madeleine J. H. , Blackall Linda L. 
Published: July 2020

ABSTRACTCorals are colonized by symbiotic microorganisms that exert a profound influence on the animal’s health. One noted symbiont is a single-celled alga (from the familySymbiodiniaceae), which provides the coral with most of its fixed carbon. During thermal stress, hyperactivity of photosynthesis results in a toxic accumulation of reactive oxygen species (ROS). If not scavenged by the antioxidant network, ROS may trigger a signaling cascade ending with the coral host and algal symbiont disassociating; this process is known as bleaching. Our goal was to construct a probiotic comprised of host-associated bacteria able to neutralize free radicals such as ROS. Using the coral model, the anemoneExaiptasia diaphana, and pure bacterial cultures isolated from the model animal, we identified six strains with high free radical scavenging ability belonging to the familiesAlteromonadaceae, Rhodobacteraceae, Flavobacteriaceae, andMicrococcaceae. In parallel, we established a “negative” probiotic consisting of genetically related strains with poor free radical scavenging capacities. From their whole genome sequences, we explored genes of interest that may contribute to their potential beneficial roles, which may help facilitate the therapeutic application of a bacterial probiotic. In particular, the occurrence of key pathways that are known to influence ROS in each of the strains has been inferred from the genomes sequences and are reported here.IMPORTANCECoral bleaching is tightly linked to the production of reactive oxygen species (ROS), which accumulates to a toxic level in algae-harboring host cells leading to coral-algal dissociation. Interventions targeting ROS accumulation, such as the application of exogenous antioxidants, have shown promise for maintaining the coral-algal partnership. With the feasibility of administering antioxidants directly to corals being low, we aim to develop a probiotic to neutralize toxic ROS during a thermal stress event. This probiotic can be tested with corals or a coral model to assess its efficacy in improving coral resistance to environmental stress.
Efficient and stable metabarcoding sequencing from DNBSEQ-G400 sequencer examined by large fungal community analysis
Authors: Sun Xiaohuan , Wang Jingjing , Fang Chao , Li Jiguang , Han Mo , Wei Xiaofang , Zheng Haotian , Luo Xiaoqing , Gong Meihua , Xiao Liang , Hu Yuehua , Song Zewei 
Published: July 2020

ABSTRACTMetabarcoding has become the de facto method for characterizing the structure of microbial communities in complex environmental samples. To determine how sequencing platform may influence microbial community characterization, we present a large-scale comparison of two sequencing platforms; Illumina MiSeq and a new platform DNBSEQ-G400 developed by MGI Tech. The accuracy of DNBSEQ-G400 on bacterial and fungal mock samples and compared sequencing consistency and precision between DNBSEQ-G400 and MiSeq platforms by sequencing the fungal ITS2 region from 1144 soil samples with 3 technical replicates. The DNBSEQ-G400 showed a high accuracy in reproducing mock communities containing different proportions of bacteria and fungi, respectively. The taxonomic profiles of the 1144 soil samples generated by the two DNBSEQ-G400 modes closely resembled each other and were highly correlated with those generated by the MiSeq platform. Analyses of technical replicates demonstrated a run bias against certain taxa on the MiSeq but not DNBSEQ-G400 platform. Based on lower cost, greater capacity, and less bias, we conclude that DNBSEQ-G400 is an optimal platform for short-term metabarcoding of microbial communities.IMPORTANCEExperimental steps that generate sequencing bias during amplicon sequencing have been intensively evaluated, including the choice of primer pair, polymerase, PCR cycle and technical replication. However, few studies have assessed the accuracy and precision of different sequencing platforms. Here, we compared the performance of newly released DNBSEQ-G400 sequencer with that of the commonly used Illumina MiSeq platform by leveraging amplicon sequencing of a large number of soil samples. Significant sequencing bias among major fungal genera was found in parallel MiSeq runs, which can be easily neglected without the use of sequencing controls. We emphasize the importance of technical controls in large-scale sequencing efforts and provide DNBSEQ-G400 as an alternative with increased sequencing capacity and more stable reproducibility for amplicon sequencing.
Modeling COVID-19 for lifting non-pharmaceutical interventions
Authors: Koehler Matt , Slater David M. , Jacyna Garry , Thompson James R. 
Published: July 2020

AbstractAs a result of the COVID-19 worldwide pandemic, the United States instituted various non-pharmaceutical interventions (NPIs) in an effort to the slow the spread of the disease. Although necessary for public safety, these NPIs can also have deleterious effects on the economy of a nation. State and federal leaders need tools that provide insight into which combination of NPIs will have the greatest impact on slowing the disease and at what point in time it is reasonably safe to start lifting these restrictions to everyday life. In the present work, we outline a modeling process that incorporates the parameters of the disease, the effects of NPIs, and the characteristics of individual communities to offer insight into when and to what degree certain NPIs should be instituted or lifted based on the progression of a given outbreak of COVID-19.
The Ceratodon purpureus genome uncovers structurally complex, gene rich sex chromosomes
Authors: Carey Sarah B. , Jenkins Jerry , Lovell John T. , Maumus Florian , Sreedasyam Avinash , Payton Adam C. , Shu Shenqiang , Tiley George P. , Fernandez-Pozo Noe , Barry Kerrie , Chen Cindy , Wang Mei , Lipzen Anna , Daum Chris , Saski Christopher A. , McBreen Jordan C. , Conrad Roth E. , Kollar Leslie M. , Olsson Sanna , Huttunen Sanna , Landis Jacob B. , Burleigh J. Gordon , Wickett Norman J. , Johnson Matthew G. , Rensing Stefan A. , Grimwood Jane , Schmutz Jeremy , McDaniel Stuart F. 
Published: July 2020

AbstractNon-recombining sex chromosomes, like the mammalian Y, often lose genes and accumulate transposable elements, a process termed degeneration1,2. The correlation between suppressed recombination and degeneration is clear in animal XY systems1,2, but the absence of recombination is confounded with other asymmetries between the X and Y. In contrast, UV sex chromosomes, like those found in bryophytes, experience symmetrical population genetic conditions3,4. Here we test for degeneration in the bryophyte UV sex chromosome system through genomic comparisons with new female and male chromosome-scale reference genomes of the mossCeratodon purpureus. We show that the moss sex chromosomes evolved over 300 million years ago and expanded via two chromosomal fusions. Although the sex chromosomes show signs of weaker purifying selection than autosomes, we find suppressed recombination alone is insufficient to drive gene loss on sex-specific chromosomes. Instead, the U and V sex chromosomes harbor thousands of broadly-expressed genes, including numerous key regulators of sexual development across land plants.
Epitope-Based Peptide Vaccine Design Against Fructose Bisphosphate Aldolase of Candida Glabrata: An Immunomics Approach
Authors: Elhasan LM Elamin , Hassan Mohamed B. , Elhassan Reham M. , Abdelrhman Fatima A. , Salih Essam A. , Ibrahim. H Asma , Mohamed Amna A. , Osman Hozaifa S. , Khalil Marwa Saad M. , Alsafi Athar A. , Idris Abeer Babiker , Hassan Mohamed A. 
Published: July 2020

AbstractBackgroundCandida glabratais a human opportunistic pathogen that can cause life-threatening systemic infections. Although, there are multiple effective vaccines against fungal infections, and some of these vaccines were engaged in different stages of clinical trials, none of them yet approved by (FDA).AimTo predict the most conserved and immunogenic B- and T-cell epitopes from the Fructose Bisphosphate aldolase (Fba1) protein ofC. glabrata.Materials and Methods13C. glabrataFructose bisphosphate aldolase protein sequences (361amino acid) were retrieved from NCBI and several in silico tools presented in the IEDB server for predicting peptides were used and homology modeling and molecular docking were performed.ResultThe promising B-cell Epitopes were AYFKPH, VDKESLYTK, and HVDKESLYTK. While, promising peptides which have the high affinity to MHC I binding were: AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL and YFKEHGEPL. Two peptides (LFSSHMLDL and YIRSIAPAY) were noted to have the highest affinity to MHC class II that interact with 9 MHC class II alleles. The molecular Docking revealed the epitopes QTSNGGAAY and LFSSHMLDL have the high binding energy to MHC moleculesConclusionThe epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines that they are more specific, less time consuming, safe, less allergic and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidates epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cells epitopes from Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine againstC. galabrata.
Predicting Tumor Response to Drugs based on Gene-Expression Biomarkers of Sensitivity Learned from Cancer Cell Lines
Authors: Li Yuanyuan , Umbach David M. , Krahn Juno , Shats Igor , Li Xiaoling , Li Leping 
Published: July 2020

SUMMARYHuman cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs and their possible mechanisms of action. The goal of those studies is to translate the findings fromin vitrostudies of cancer cell lines intoin vivotherapeutic relevance and, eventually, patients’ care. Tremendous progress has been made. In this work, we built predictive models for 453 drugs using data on gene expression and drug sensitivity (IC50) from cancer cell lines. We identified many known drug-gene interactions and uncovered several potentially novel drug-gene associations. Importantly, we further applied these predictive models to ∼17,000 bulk RNA-seq samples from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to predict drug sensitivity for both normal and tumor tissues. We created a web site for users to visualize and download our predicted data (https://edelgene.niehs.nih.gov/cancerRxTissue). Using trametinib as an example, we showed that our approach can faithfully recapitulate the known tumor specificity of the drug. We further demonstrated that our approach can predict drugs that 1) are tumor-type specific; 2) elicit higher sensitivity from tumor compared to corresponding normal tissue; 3) elicit differential sensitivity across breast cancer subtypes. If validated, our predictions could have clinical relevance for patients’ care.