bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of miRNA signatures for kidney renal clear cell carcinoma using the tensor-decomposition method
Authors: Ng Ka-Lok , Taguchi Y-h 
Published: November 2019

AbstractCancer is a highly complex disease caused by multiple genetic factors. MicroRNA (miRNA) and mRNA expression profiles are useful for identifying prognostic biomarkers for cancer. Kidney renal clear cell carcinoma (KIRC), which accounts for more than 70% of all renal malignant tumour cases, was selected for our analysis.Traditional methods of identifying cancer prognostic markers may not be accurate. Tensor decomposition (TD) is a useful method uncovering the underlying low-dimensional structures in the tensor. The TD-based unsupervised feature extraction method was applied to analyse mRNA and miRNA expression profiles. Biological annotations of the prognostic miRNAs and mRNAs were examined utilizing the pathway and oncogenic signature databases DIANA-miRPath and MSigDB.TD identified the miRNA signatures and the associated genes. These genes were found to be involved in cancer-related pathways, and 23 genes were significantly correlated with the survival of KIRC patients. We demonstrated that the results are robust and not highly dependent upon the databases we selected. Compared with traditional supervised methods tested, TD achieves much better performance in selecting prognostic miRNAs and mRNAs.These results suggest that integrated analysis using the TD-based unsupervised feature extraction technique is an effective strategy for identifying prognostic signatures in cancer studies.
RIPK3 inhibition prevents KRAS mutant p53 deficient lung tumor progression by impeding MDSCs
Authors: Jayakumar Asha 
Published: November 2019

AbstractKRAS mutant p53 deficient (KP) non-small cell lung carcinoma (NSCLC) lacks targeted therapies. Existing treatments for lung cancer cause resistance and result in toxicities requiring novel effective therapies. By targeting mechanisms causing resistance such as myeloid derived suppressor cells (MDSCs), KP tumors could be inhibited. MDSCs are functionally diverse and suppress T cells in many cancers. RIPK3, a cell death inducing enzyme, also functions as a signaling component producing cytokines that mediate the suppressive function of MDSCs. Partial deletion of RIPK3 in myeloid cells reduced KP tumor growth. This also reduced accumulation of MDSCs with a consistent increase in antigen specific IFNγ producing CD8 T cells. Inhibiting RIPK3 with a small molecule inhibitor such as GSK 872 effectively reduces RIPK3 activity in myeloid cells including MDSCs and reduces growth of small and large KP tumors. GSK 872 in combination with checkpoint inhibitors such as anti PD-1 and anti CTLA-4 further decreased KP tumor size. Together, our findings show that inhibiting RIPK3 in MDSCs is effective in inhibiting KP NSCLC and is a viable therapeutic option for improving existing immunotherapeutic treatments.
Addition of insoluble fiber to isolation media allows for increased metabolite diversity of lab-cultivable microbes derived from zebrafish gut samples
Authors: Condren Alanna R. , Costa Maria S , Sanchez Natalia Rivera , Konkapaka Sindhu , Gallik Kristin L , Saxena Ankur , Murphy Brian T , Sanchez Laura M 
Published: November 2019

AbstractThere is a gap in measured microbial diversity when comparing genomic sequencing techniques versus cultivation from environmental samples in a laboratory setting. Standardized methods in artificial environments may not recapitulate the environmental conditions that native microbes require for optimal growth. For example, the intestinal tract houses microbes at various pH values as well as minimal oxygen and light environments. These microbes are also exposed to an atypical source of carbon: dietary fiber compacted in fecal matter. To investigate how the addition of insoluble fiber to isolation media could affect the cultivation of microbes from zebrafish intestines, an isolate library was built and analyzed using the bioinformatics pipeline IDBac. The addition of fiber led to an increase in bacterial growth and encouraged the growth of species from several phyla. Furthermore, fiber addition altered the metabolism of the cultivated gut-derived microbes and induced the production of unique metabolites that were not produced when microbes were otherwise grown on standard isolation media. Addition of this inexpensive carbon source to media supported the cultivation of a diverse community whose specialized metabolite production may more closely replicate their metabolite productionin vivo.
Extended Recognition of the Histone H3 Tail by Histone Demethylase KDM5A
Authors: Petronikolou Nektaria , Longbotham James E. , Fujimori Danica Galonić 
Published: November 2019

ABSTRACTHuman lysine demethylase KDM5A is a chromatin modifying enzyme associated with transcriptional regulation due to its ability to catalyze removal of methyl groups from methylated lysine 4 of histone H3 (H3K4me3). Amplification of KDM5A is observed in a number of cancers, including breast cancer, prostate cancer, hepatocellular carcinoma, lung cancer and gastric cancer. In this study, we employed alanine scanning mutagenesis to investigate substrate recognition of KDM5A and identify the H3 tail residues necessary for KDM5A-catalyzed demethylation. Our data show that the H3Q5 residue is critical for substrate recognition by KDM5A. Our data also reveal that the protein-protein interactions between KDM5A and the histone H3 tail extend beyond the amino acids proximal to the substrate mark. Specifically, demethylation activity assays show that deletion or mutation of residues at positions 14-18 on the H3 tail results in an 8-fold increase in the KMapp compared to wild-type 18mer peptide, suggesting this distal epitope is important in histone engagement. Finally, we demonstrate that post-translational modifications on this distal epitope can modulate KDM5A-dependent demethylation. Our findings provide insights into H3K4-specific recognition by KDM5A as well as how chromatin context can regulate KDM5A activity and H3K4 methylation status.
CiteFuse enables multi-modal analysis of CITE-seq data
Authors: Kim Hani Jieun , Lin Yingxin , Geddes Thomas A. , Yang Jean , Yang Pengyi 
Published: November 2019

AbstractMulti-modal profiling of single cells represents one of the latest technological advancements in molecular biology. Among various single-cell multi-modal strategies, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) allows simultaneous quantification of two distinct species: RNA and surface marker proteins (ADT). Here, we introduce CiteFuse, a streamlined package consisting of a suite of tools for pre-processing, modality integration, clustering, differential RNA and ADT expression analysis, ADT evaluation, ligand-receptor interaction analysis, and interactive web-based visualization of CITE-seq data. We show the capacity of CiteFuse to integrate the two data modalities and its relative advantage against data generated from single modality profiling. Furthermore, we illustrate the pre-processing steps in CiteFuse and in particular a novel doublet detection method based on a combined index of cell hashing and transcriptome data. Collectively, we demonstrate the utility and effectiveness of CiteFuse for the integrative analysis of transcriptome and epitope profiles from CITE-seq data.
Investigation of the quorum-sensing regulon of the biocontrol bacterium Pseudomonas chlororaphis strain PA23
Authors: Shah Nidhi , Gislason April , Becker Michael , Belmonte Mark F. , Fernando W.G. Dilantha , de Kievit Teresa R. 
Published: November 2019

AbstractPseudomonas chlororaphis strain PA23 is a biocontrol agent capable of protecting canola from stem rot disease caused by the fungal pathogen Sclerotinia sclerotiorum. PA23 produces several of inhibitory compounds that are under control of a complex regulatory network. Included in this cascade is the PhzRI quorum sensing (QS) system, which plays an essential role in PA23 biocontrol. The focus of the current study was to employ RNA sequencing to explore the spectrum of PA23 genes under QS control. Transcriptomic profiling revealed 545 differentially expressed genes (365 downregulated; 180 upregulated) in the phzR mutant and 534 genes (382 downregulated; 152 upregulated) in the AHL-deficient PA23-6863. In both strains, decreased expression of phenazine, pyrrolnitrin, and exoprotease biosynthetic genes was observed. We have previously reported that QS activates expression of these genes and their encoded products. In addition, elevated siderophore and decreased chitinase gene expression was observed in the QS-deficient stains, which was confirmed by phenotypic analysis. Inspection of the promoter regions revealed the presence of “phz-box” sequences in only 58 of the 807 differentially expressed genes, suggesting that much of the QS regulon is indirectly regulated. Consistent with this notion, 41 transcriptional regulators displayed altered expression in one or both of the QS-deficient strains. Collectively, our findings indicate that QS governs expression of approximately 13% of the PA23 genome affecting diverse functions ranging from secondary metabolite production to general metabolism. To the best of our knowledge, this represents the first global transcriptomic analysis of the QS regulon of a biocontrol pseudomonad.
A Partially Phase-Separated Genome Sequence Assembly of the Vitis Rootstock ‘Börner’ (Vitis riparia x Vitis cinerea) and its Exploitation for Marker Development and Targeted Mapping
Authors: Holtgräwe Daniela , Sörensen Thomas Rosleff , Hausmann Ludger , Pucker Boas , Viehöver Prisca , Töpfer Reinhard , Weisshaar Bernd 
Published: November 2019

AbstractGrapevine breeding becomes highly relevant due to upcoming challenges like climate change, a decrease in the number of available fungicides, increasing public concern about plant protection, and the demand for a sustainable production. Downy mildew caused by Plasmopara viticola is one of the most devastating diseases worldwide of cultivated Vitis vinifera. Therefore, in modern breeding programs genetic marker technologies and genomic data are used to develop new cultivars with defined and stacked resistance loci. Potential sources of resistance are wild species of American or Asian origin. The interspecific hybrid of Vitis riparia Gm 183 x V. cinerea Arnold, available as the rootstock cultivar ‘Börner’, carries several relevant resistance loci. We applied next generation sequencing to enable the reliable identification of simple sequence repeats (SSR) and also generated a draft genome sequence assembly of ‘Börner’ to access genome wide sequence variations in a comprehensive and highly reliable way. These data were used to cover the ‘Börner’ genome with genetic marker positions. A subset of these marker positions was used for targeted mapping of the P. viticola resistance locus, Rpv14, to validate the marker position list. Based on the reference genome sequence PN40024, the position of this resistance locus can be narrowed down to less than 0.5 Mbp on chromosome 5.
The role of host phenology for parasite transmission
Authors: MacDonald Hannelore , Akçay Erol , Brisson Dustin 
Published: November 2019

AbstractPhenology is a fundamental determinant of species distributions, abundances, and interactions. In host-parasite interactions, host phenology can affect parasite fitness due to the temporal constraints it imposes on host contact rates. However, it remains unclear how parasite transmission is shaped by the wide range of phenological patterns observed in nature. We develop a mathematical model of the Lyme disease system to study the consequences of differential tick developmental-stage phenology for the transmission ofB. burgdorferi. Incorporating seasonal tick activity can increaseB. burgdorferifitness compared to continuous tick activity but can also prevent transmission completely.B. burgdorferifitness is greatest when the activity period of the infectious nymphal stage slightly precedes the larval activity period. Surprisingly,B. burgdorferiis eradicated if the larval activity period begins long after the end of nymphal activity due to a feedback with mouse population dynamics. These results highlight the importance of phenology, a common driver of species interactions, for the fitness of a parasite.
Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan McDermid syndrome and autism
Authors: Breen Michael S. , Browne Andrew , Hoffman Gabriel E. , Stathopoulos Sofia , Brennand Kristen , Buxbaum Joseph D. , Drapeau Elodie 
Published: November 2019

ABSTRACTBackgroundPhelan-McDermid syndrome (PMS) is a rare genetic disorder with high risk of autism spectrum disorder (ASD), intellectual disability and language delay, and is caused by 22q13.3 deletions or mutations in the SHANK3 gene. To date, the molecular and pathway changes resulting from SHANK3 haploinsufficiency in PMS remain poorly understood. Uncovering these mechanisms is critical for understanding pathobiology of PMS and, ultimately, for the development of new therapeutic interventions.MethodsWe developed human induced pluripotent stem cell (hiPSC)-based models of PMS by reprogramming peripheral blood samples from individuals with PMS (n=7) and their unaffected siblings (n=6). For each participant, up to three hiPSC clones were generated and differentiated into induced neural progenitor cells (iNPCs; n=32) and induced forebrain neurons (iNeurons; n=42). Genome-wide RNA-sequencing was applied to explore transcriptional differences between PMS probands and unaffected siblings.ResultsTranscriptome analyses identified 391 differentially expressed genes (DEGs) in iNPCs and 82 DEGs in iNeurons, when comparing cells from PMS probands and unaffected siblings (FDR <5%). Genes under-expressed in PMS were implicated in Wnt signaling, embryonic development and protein translation, while over-expressed genes were enriched for pre- and post-synaptic density genes, regulation of synaptic plasticity, and G-protein-gated potassium channel activity. Gene co-expression network analysis identified two modules in iNeurons that were over-expressed in PMS, implicating postsynaptic signaling and GDP binding, and both modules harbored a significant enrichment of genetic risk loci for developmental delay and intellectual disability. Finally, PMS-associated genes were integrated with other ASD iPSC transcriptome findings and several points of convergence were identified, indicating altered Wnt signaling, extracellular matrix and glutamatergic synapses.LimitationsGiven the rarity of the condition, we could not carry out experimental validation in independent biological samples. In addition, functional and morphological phenotypes caused by loss of SHANK3 were not characterized here.ConclusionsThis is the largest human neural sample analyzed in PMS. Genome-wide RNA-sequencing in hiPSC-derived neural cells from individuals with PMS revealed both shared and distinct transcriptional signatures across iNPCs and iNeurons, including many genes implicated in risk for ASD, as well as specific neurobiological pathways, including the Wnt pathway.
The Oscillatory ReConstruction Algorithm (ORCA) adaptively identifies frequency bands to improve spectral decomposition in human and rodent neural recordings
Authors: Watrous Andrew J , Buchanan Robert 
Published: November 2019

AbstractNeural oscillations are routinely analyzed using methods that measure activity in canonical frequency bands (e.g. alpha, 8-12 Hz), though the frequency of neural signals is not fixed and varies within and across individuals based on numerous factors including neuroanatomy, behavioral demands, and species. Further, band-limited activity is an often assumed, typically unmeasured model of neural activity and band definitions vary considerably across studies. These factors together mask individual differences and can lead to noisy spectral estimates and interpretational problems when linking electrophysiology to behavior. We developed the Oscillatory ReConstruction Algorithm (“ORCA”), an unsupervised method to measure the spectral characteristics of neural signals in adaptively identified bands which incorporates two new methods for frequency band identification. ORCA uses the instantaneous power, phase, and frequency of activity in each band to reconstruct the signal and directly quantify spectral decomposition performance using each of four different models. To reduce researcher bias, ORCA provides spectral estimates derived from the best model and requires minimal hyperparameterization. Analyzing human scalp EEG data during eyes open and eyes-closed “resting” conditions, we first identify variability in the frequency content of neural signals across subjects and electrodes. We demonstrate that ORCA significantly improves spectral decomposition compared to conventional methods and captures the well-known increase in low-frequency activity during eyes closure in electrode- and subject-specific frequency bands. We further illustrate the utility of our method in rodent CA1 recordings. ORCA is a novel analytic tool that will allow researchers to investigate how non-stationary neural oscillations vary across behaviors, brain regions, individuals, and species.
RiboFlow, RiboR and RiboPy: An ecosystem for analyzing ribosome profiling data at read length resolution
Authors: Ozadam Hakan , Geng Michael , Cenik Can 
Published: November 2019

AbstractSummaryRibosome occupancy measurements enable protein abundance estimation and infer mechanisms of translation. Recent studies have revealed that sequence read lengths in ribosome profiling data are highly variable and carry critical information. Consequently, data analyses require the computation and storage of multiple metrics for a wide range of ribosome footprint lengths. We developed a software ecosystem including a new efficient binary file format named ‘ribo’. Ribo files store all essential data grouped by ribosome footprint lengths. Users can assemble ribo files using our RiboFlow pipeline that processes raw ribosomal profiling sequencing data. RiboFlow is highly portable and customizable across a large number of computational environments with built-in capabilities for parallelization. We also developed interfaces for writing and reading ribo files in the R (RiboR) and Python (RiboPy) environments. Using RiboR and RiboPy, users can efficiently access ribosome profiling quality control metrics, generate essential plots, and carry out analyses. Altogether, these components create a complete software ecosystem for researchers to study translation through ribosome profiling.Availability and ImplementationFor a quickstart, please see https://ribosomeprofiling.github.io. Source code, installation instructions and links to documentation are available on GitHub: https://github.com/ribosomeprofiling
Wolbachiapromote successful sex with siblings
Authors: Bagheri Zeynab , Talebi Ali Asghar , Asgari Sassan , Mehrabadi Mohammad 
Published: November 2019

AbstractWolbachiaare intracellular α-proteobacteria that have a wide distribution among various arthropods and nematodes. They affect the host reproduction favoring their maternal transmission, which sets up a potential conflict in inbreeding situations when the host avoids sexual reproduction preventing inbreeding depression, whileWolbachiapushes it. In this study, we used the waspHabrobracon hebetorto test the hypothesis thatWolbachiamodulate inbreeding avoidance behaviour and promote sib mating. To test this, we first cured wasps ofWolbachiausing tetracycline treatment and produced infected and uninfected isolines. Then, we paired the uninfected and infected females with sibling (inbred) and non-sibling (outbred) males in choice and non-choice experiments. Our results showed no obvious precopulatory inbreeding avoidance in this wasp as brother-sister mating rates (in both choice and nonchoice experiments) were not significantly different form non-sibling pairs, regardless ofWolbachiainfection. However, our results indicated thatH. hebetorshows a strong postcopulatory inbreeding avoidance behaviour that results in a low fertilization rate of uninfected siblings and therefore high rate of production of male progeny was obtained. We observed higher rates of fertilization success in theWolbachia-infected lines that resulted in significantly higher female progeny production compared to the uninfected sib mates. Since diploid females are the result of successful fertilization due to haplodiploidy sex determination system in this insect, our results indicate thatWolbachiapromoted fertile sib mating inH. hebetor.Interestingly, the rate of adult emergence in the progeny ofWolbachia-infected sib mates were almost similar to the non-sib mate crosses and significantly more than those observed in the uninfected sib mate crosses. We support the idea thatWolbachiamodulate inbreeding avoidance and promote sib mating and also mitigate inbreeding depression. The waspHabrobracon hebetorsiblings infected withWolbachiashow higher rates of fertilization success and higher adult emergence rates compared to the uninfected sib mates. By promoting successful sex with siblings and increasing the probability of female progeny,Wolbachiaenhance their transmission to the next generation and also mitigate inbreeding depression. This is an undescribed effect ofWolbachia(symbiont) on the host reproduction.
Presence of orange tubercles does not always indicate accelerated low water corrosion
Authors: Phan Hoang C. , Wade Scott A. , Blackall Linda L. 
Published: November 2019

ABSTRACTThe rapid degradation of marine infrastructure at the low tide level due to accelerated low water corrosion (ALWC) is a problem encountered worldwide. Despite this, there is limited understanding of the microbial communities involved in this process. We obtained samples of the orange-coloured tubercles commonly associated with ALWC from two different types of steel sheet piling, located adjacent to each other but with different levels of localised corrosion, at a seaside harbour. The microbial communities from the outer and inner layers of the orange tubercles, and from adjacent seawater, were studied by pure culture isolation and metabarcoding of the 16S rRNA genes. A collection of 119 bacterial isolates was obtained from one orange tubercle sample, using a range of media with anaerobic and aerobic conditions. The metabarcoding results showed that sulfur and iron oxidisers were more abundant on the outer section of the orange tubercles compared to the inner layers, where Deltaproteobacteria (which includes many sulfate reducers) were more abundant. The microbial communities varied significantly between the inner and outer layers of the orange tubercles and also with the seawater, but overall did not differ significantly between the two steel sheet types. Metallurgical analysis found differences in composition, grain size, ferrite-pearlite ratio and the extent of inclusions present between the two steel types investigated.IMPORTANCEThe presence of orange tubercles on marine steel pilings is often used as an indication that accelerated low water corrosion is taking place. We studied the microbial communities in attached orange tubercles on two closely located sheet pilings that were of different steel types. The attached orange tubercles were visually similar, but the extent of underlying corrosion on the different steel surfaces were substantially different. No clear difference was found between the microbial communities present on the two different types of sheet piling. However, there were clear differences in the microbial communities in the corrosion layers of tubercles, which were also different to the microbes present in adjacent seawater. The overall results suggest that the presence of orange tubercles, a single measurement of water quality, or the detection of certain general types of microbes (e.g. sulfate reducing bacteria) should not be taken alone as definitive indications of accelerated corrosion.