bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rrp6p/Rrp47p constitutes an independent nuclear turnover system of mature small non-coding RNAs inSaccharomyces cerevisiae
Authors: Chaudhuri Anusha , Das Subhadeep , Banerjea Mayukh , Das Biswadip 
Published: December 2020

AbstractInSaccharomyces cerevisiae,the nuclear exosome/Rrp6p/TRAMP participates in the 3’-end processing of several precursor non-coding RNAs. Here we demonstrate that the depletion of nucleus-specific 3’→5’ exoribonuclease Rrp6p and its cofactor, Rrp47p led to the specific and selective enhancement of steady-state levels of mature small non-coding RNAs (sncRNAs) that include 5S and 5.8S rRNAs, snRNAs and snoRNAs, but not 18S and 25S rRNAs. Most importantly, their steady-state enhancement does not require the exosome, TRAMP, CTEXT, or Rrp6p-associated Mpp6p. Rrp6p/47p-dependent enhancement of the steady-state levels of sncRNAs is associated with the diminution of their nuclear decay-rate and requires their polyadenylation before targeting by Rrp6p, which is catalyzed by both the canonical and non-canonical poly(A) polymerases, Pap1p and Trf4p. Consistent with this finding, we also demonstrated that Rrp6p and Rrp47p exist as an exosome-independent complex. Thus, Rrp6p-Rrp47p defines a core nuclear exosome-independent novel turnover system that targets the small non-coding RNAs.
Dietary folic acid deficiency impacts hippocampal morphology and cortical acetylcholine metabolism in adult male and female mice
Authors: Bennett Calli , Green Jacalyn , Ciancio Mae , Goral Joanna , Pitstick Lenore , Pytynia Matthew , Meyer Alice , Kwatra Neha , Jadavji Nafisa M. 
Published: December 2020

AbstractObjectiveOne-carbon metabolism is a metabolic network that integrates nutritional signals with biosynthesis, redox homeostasis, and epigenetics. There are sex differences in hepatic one-carbon metabolism. However, it is unclear whether there are sex differences in dietary deficiencies of one-carbon metabolism in the brain. The aim of this study was to investigate if sex modulates the effects of dietary folic acid deficiency in brain tissue using a mouse model.MethodsMale and female C57Bl/6J mice were placed on a folic acid deficient (FD) or control diet (CD) at six weeks of age. Mice were maintained on these diets for six months, after which animals were euthanized and brain tissue and serum were collected for analysis. Serum folate levels were measured. In brain tissue, hippocampal volume and morphology including Cornu Ammonis 1 and 3 (CA1; CA3), and dentate gyrus thickness were measured. Apoptosis within the hippocampus was assessed using active caspase-3 immunofluorescence staining. Additionally, cortical acetylcholine metabolism was measured in brain tissue using immunofluorescence staining of acetylcholinesterase (AChE), or choline acetyltransferase (ChAT), and neuronal nuclei (NeuN).ResultsMale and female FD mice had reduced serum levels of folate. Both males and females maintained on a FD showed a decrease in the thickness of the hippocampal CA1-CA3 region. Interestingly, there was a sex difference in the levels of active caspase-3 within the CA3 region of the hippocampus. In cortical tissue, there were increased levels of neuronal ChAT and reduced levels of AChE in FD females and male mice.ConclusionsThe results indicated that FD impacts hippocampal morphology and cortical neuronal acetylcholine metabolism. The data from our study indicate that there was only one sex difference and that was in hippocampal apoptosis. Our study provides little evidence that sex modulates the effects of dietary folate deficiency on hippocampal morphology and cortical neuronal acetylcholine metabolism.
Evolutionary rescue can prevent rate-induced tipping
Authors: Vanselow Anna , Halekotte Lukas , Feudel Ulrike 
Published: December 2020

AbstractToday, the transformation of ecosystems proceeds at unprecedented rates. Recent studies suggest that high rates of environmental change can causerate-induced tipping. In ecological models, the associatedrate-induced critical transitionmanifests during transient dynamics in which populations drop to dangerously low densities. In this work, we study howindirect evolutionary rescue- due to the rapid evolution of a predator’s trait - can save a prey population from the rate-induced collapse. Therefore, we explicitly include the time-dependent dynamics of environmental change and evolutionary adaptation in an eco-evolutionary system. We then examine how fast the evolutionary adaptation needs to be to counteract the response to environmental degradation and express this relationship by means of a critical rate. Based on this critical rate, we conclude that indirect evolutionary rescue is more probable if the predator population possesses a high genetic variation and, simultaneously, the environmental change is slow. Hence, our results strongly emphasize that the maintenance of biodiversity requires a deceleration of the anthropogenic degradation of natural habitats.
Plasticity of fibroblast transcriptional response to physical and biochemical cues revealed by dynamic network analysis
Authors: Lee Pilhwa , Decker Joseph , Shea Lonnie , Beard Daniel A. 
Published: December 2020

SummaryData on human skin fibroblast transcriptional responses to external cues were used to reconstruct dynamic gene regulatory networks. The goal of the reconstruction was to determine dynamic network interactions (quantitative predictive relationships of mutual regulatory influences of and on transcription factor expression) from time course data on 56 transcript expression levels obtained following different external cues. The inherently under-determined nature of this problem was addressed in part by excluding putative regulatory motifs that did not appear to be functional in multiple independent experiments from different independent external perturbations. Data were obtained from a previously published experiment in which the 56 transcripts were assayed by bioluminescence in live cells cultured on substrates of varying levels of stiffness and exposed to different levels of arginylglycylaspartic acid (RGD) peptide. The inferred dynamical networks were validated via comparison of predictions toa prioriknown interactions from gene databases. We discovered that exposures to different substrate stiffnesses and to RGD stimulate responses that are mediated throughGATA4, SMAD3/4, ETS-1, andSTAT5and other genes, which can initiate hypertrophic, fibrotic, and inflammatory responses. The developed dynamical system identification method for discovering new mechanotransduction pathways is applicable to the identification of gene regulatory networks in numerous emerging applications where time-series data on multiple state variables and from multiple external perturbations are available.
Surveying the contribution of rare variants to the genetic architecture of human disease through exome sequencing of 177,882 UK Biobank participants
Authors: Wang Quanli , Dhindsa Ryan S. , Carss Keren , Harper Andrew , Nag Abhishek , Tachmazidou Ioanna , Vitsios Dimitrios , Deevi Sri VV , Mackay Alex , Muthas Daniel , Hühn Michael , Monkley Susan , Olsson Henric , Wasilewski Sebastian , Smith Katherine R. , March Ruth , Platt Adam , Haefliger Carolina , Petrovski Slavé ,   AstraZeneca Genomics Initiative
Published: December 2020

SummaryThe UK Biobank (UKB) represents an unprecedented population-based study of 502,543 participants with detailed phenotypic data and linkage to medical records. While the release of genotyping array data for this cohort has bolstered genomic discovery for common variants, the contribution of rare variants to this broad phenotype collection remains relatively unknown. Here, we use exome sequencing data from 177,882 UKB participants to evaluate the association between rare protein-coding variants with 10,533 binary and 1,419 quantitative phenotypes. We performed both a variant-level phenome-wide association study (PheWAS) and a gene-level collapsing analysis-based PheWAS tailored to detecting the aggregate contribution of rare variants. The latter revealed 911 statistically significant gene-phenotype relationships, with a median odds ratio of 15.7 for binary traits. Among the binary trait associations identified using collapsing analysis, 83% were undetectable using single variant association tests, emphasizing the power of collapsing analysis to detect signal in the setting of high allelic heterogeneity. As a whole, these genotype-phenotype associations were significantly enriched for loss-of-function mediated traits and currently approved drug targets. Using these results, we summarise the contribution of rare variants to common diseases in the context of the UKB phenome and provide an example of how novel gene-phenotype associations can aid in therapeutic target prioritisation.
Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment
Authors: Ko J. , Meyer A. N. , Haas M. , Donoghue D. J. 
Published: December 2020

ABSTRACTBackgroundMetastatic castrate-resistant prostate cancer (CRPC) remains uncurable and novel therapies are needed to better treat patients. Aberrant Fibroblast Growth Factor Receptor (FGFR) signaling has been implicated in advanced prostate cancer (PCa), and FGFR1 is suggested to be a promising therapeutic target along with current androgen deprivation therapy.MethodsWe established a novelin vitro3D culture system to study endogenous FGFR signaling in a rare subpopulation of prostate cancer stem cells (CSCs) in the cell lines PC3, DU145, LNCaP, and the induced pluripotent iPS87 cell line.Results3D-propagation of PCa cells generated spheroids with increased stemness markers ALDH7A1 and OCT4, while inhibition of FGFR signaling by BGJ398 or Dovitinib decreased cell survival and proliferation of 3D spheroids. The 3D spheroids exhibited altered expression of EMT markers associated with metastasis such as E-cadherin, vimentin and Snail, compared to 2D monolayer cells. TKI treatment did not result in significant changes of EMT markers, however, specific inhibition of FGFR signaling by BGJ398 showed more favorable molecular-level changes than treatment with the multi-RTK inhibitor Dovitinib.ConclusionsThis study provides evidence for the first time that FGFR1 plays an essential role in the proliferation of PCa CSCs at a molecular and cellular level, and suggests that TKI targeting of FGFR signaling may be a promising strategy for AR-independent CRPC.
A New and Improved Genome Sequence ofCannabis sativa
Authors: Braich Shivraj , Baillie Rebecca C. , Spangenberg German C. , Cogan Noel O.I. 
Published: December 2020

AbstractCannabis is a diploid species (2n = 20), the estimated haploid genome sizes of the female and male plants using flow cytometry are 818 and 843 Mb respectively. Although the genome of Cannabis has been sequenced (from hemp, wild and high-THC strains), all assemblies have significant gaps. In addition, there are inconsistencies in the chromosome numbering which limits their use. A new comprehensive draft genome sequence assembly (~900 Mb) has been generated from the medicinal cannabis strain Cannbio-2, that produces a balanced ratio of cannabidiol and delta-9-tetrahydrocannabinol using long-read sequencing. The assembly was subsequently analysed for completeness by ordering the contigs into chromosome-scale pseudomolecules using a reference genome assembly approach, annotated and compared to other existing reference genome assemblies. The Cannbio-2 genome sequence assembly was found to be the most complete genome sequence available based on nucleotides assembled and BUSCO evaluation inCannabis sativawith a comprehensive genome annotation. The new draft genome sequence is an advancement in Cannabis genomics permitting pan-genome analysis, genomic selection as well as genome editing.
Expression of SSEA4 and TRA1-60 as Marker of Induced Pluripotent Stem Cells by Small Molecule Compound VC6TFZ on Peripheral Blood Mononuclear Cell
Authors: Andrianto A , Basworo Adityo , Dewi Ivana Purnama , Pikir Budi Susetio 
Published: December 2020

IntroductionIt is possible to induce pluripotent stem cells from somatic cells, offering an infinite cell resource with the potential for disease research and use in regenerative medicine. Due to ease of accessibility, minimum invasive treatment, and can be kept frozen, peripheral blood mononuclear cells (PBMC) were an attractive source cell. VC6TFZ, a small molecule compound, has been successfully reprogrammed from mouse fibroblast induced pluripotent stem cells (iPSCs). However, it has not been confirmed in humans.ObjectiveThe aim of this research is to determine whether the small molecule compound VC6TFZ can induced pluripotency of PBMC to generate iPSCs detected with expression of SSEA4 and TRA1-60.MethodsUsing the centrifugation gradient density process, mononuclear cells were separated from peripheral venous blood. Mononuclear cells were cultured for 6 days in the expansion medium. The cells were divided into four groups; group 1 (P1), which was not exposed to small molecules (control group) and groups 2-4 (P2-P4), the experimental groups, subjected to various dosages of the small molecule compound VC6TFZ (VPA, CHIR, Tranylcypromine, FSK, Dznep, and TTNPB). The induction of pluripotency using small molecule compound VC6TFZ was completed within 14 days, then for 7 days the medium shifted to 2i medium. iPSCs identification in based on colony morphology and pluripotent gene expression, SSEA4 and TRA1-60 marker, using immunocytochemistry.ResultsColonies appeared on reprogramming process in day 7th. These colonies had round, large, and cobble stone morphology like ESC. Gene expression of SSEA4 and TRA 1-60 increased statisticaly significant than control group (SSEA4 were P2 p=0.007; P3 p=0.001; P4 p=0.009 and TRA 1-60 were P2 p=0.002; P3 p=0.001; P4 p=0.001).ConclusionSmall molecule compound VC6TFZ could induced pluripotency of human PBMC to generate iPSCs. Pluripotxency marker gene expression, SSEA 4 and TRA 1-60, in the experimental group was statistically significantly higher than in the control group.
Functional Transcriptome Analysis of Bladder Cancer Cell Lines Persistently Infected with Oncolytic Newcastle Disease Virus
Authors: Ahmad Umar , Thirumorthy Arcana , Chau De Ming , Chia Suet Lin , Yusoff Khatijah , Abdullah Syahril , Chan Soon Choy , Veerakumarasivam Abhi 
Published: December 2020

AbstractBackgroundNewcastle disease virus (NDV) has been an attractive virotherapy agent that targets various type of human cancers while leaving normal cells unharmed. Wild-type NDV strain AF2240 has been found to persistently infect subpopulation of cancer cellsin vitro, making the cells less susceptible to NDV-mediated oncolysis. It is proposed that transcriptome profiling of NDV persistently infected bladder cancer cell lines will provide insights to understand such occurrence by identifying specific pathways associated with NDV persistent infection due to transcriptomic dysregulation.ResultsTranscriptome profiling revealed a total of 63 and 134 differentially expressed genes (DEGs) from NDV persistently infected TCCSUPPi and EJ28Pi bladder cancer cells relative to their uninfected controls, respectively. Of the 63 DEGs identified for TCCSUPPi cells, 25 DEGs were upregulated (log2fold-change ≥ 0) and 38 DEGs were downregulated (log2fold-change ≤ 0). These genes were significantly enriched in the molecular function of calcium binding (GO:0005509) and DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227) and the enriched important upregulated pathways were mainly heme metabolism, TGF-beta signaling and spermatogenesis. As for EJ28Pi, 55 DEGs were upregulated (log2fold-change ≥ 0) and 79 DEGs were downregulated (log2fold-change ≤ 0). These DEGs resulted in significantly enriched molecular function such as protein domain specific binding (GO:0019904) and RNA polymerase II regulatory region sequence-specific DNA binding (GO:0000977). The enriched important upregulated pathways were allograft rejection, KRAS signaling up and interferon gamma response. Other important pathways that were downregulated in both the NDV-persistently infected cell lines were angiogenesis, apoptosis, and xenobiotic metabolism.ConclusionThe transcriptome profiles (RNA-Seq) of these cell lines suggest that evasion of apoptosis and increase in TGF-beta signaling and interferon gamma response activities are crucial for establishment of NDV persistent infection in bladder cancer cells. Findings from this study provide the molecular basis that warrant further study on how bladder cancer cells acquired NDV persistent infection. Resolving the mechanism of persistent infection will facilitate the application of NDV for more effective treatment of bladder cancer.
Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors
Authors: Lin Li , Zhou Ning , Kang Le , Wang Qi , Wu Jian , Wang Xiaoyan , Yang Chunjie , Zhang Guoping , Chen Yunqin , Jiang Hong , Chen Ruizhen , Yang Xiangdong , Sun Aijun , Gong Hui , Ren Jun , Aikawa Hiroshi , Issei Komuro , Ge Junbo , Yang Cheng , Zou Yunzeng 
Published: December 2020

AbstractOxidized low-density lipoprotein (Ox-LDL) can induce cardiac hypertrophy, but the mechanism is still unclear. Here we elucidate the role of angiotensin II (AngII) receptor (AT1-R) in Ox-LDL-induced cardiomycyte hypertrophy. Inhibition of Ox-LDL receptor LOX-1 and AT1-R rather than AngII abolished Ox-LDL-induced hypertrophic responses. Similar results were obtained from the heart of mice lacking endogenous Ang II and their cardiomyocytes. Ox-LDL but not AngII induced binding of LOX-1 to AT1-R, and the inhibition of LOX-1 or AT1-R rather than AngII abolished the association of these two receptors. Ox-LDL-induced ERKs phosphorylation in LOX-1 and AT1-R-overexpression cells and the binding of both receptors were suppressed by the mutants of LOX-1 (Lys266Ala/Lys267Ala) or AT1-R (Glu257Ala), however, the AT1-R mutant lacking Gq protein-coupling ability only abolished the ERKs phosphorylation. The phosphorylation of ERKs induced by Ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by Gq protein inhibitor but not by Jak2, Rac1 and RhoA inhibitors. Therefore, the direct interaction between LOX-1 and AT1-R and the downstream Gq protein activation are important mechanisms for Ox-LDL-but not AngII-induced cardiomyocyte hypertrophy.
60 fs, 1030 nm FEL pump–probe laser based on a multi-pass post-compressed Yb:YAG source
Authors: Viotti Anne-Lise , Alisauskas Skirmantas , Bin Wahid Ammar , Balla Prannay , Schirmel Nora , Manschwetus Bastian , Hartl Ingmar , Heyl Christoph M. 
Published: December 2020

This paper reports on nonlinear spectral broadening of 1.1 ps pulses in a gas-filled multi-pass cell to generate sub-100 fs optical pulses at 1030 nm and 515 nm at pulse energies of 0.8 mJ and 225 µJ, respectively, for pump–probe experiments at the free-electron laser FLASH. Combining a 100 kHz Yb:YAG laser with 180 W in-burst average power and a post-compression platform enables reaching simultaneously high average powers and short pulse durations for high-repetition-rate FEL pump–probe experiments.
Turbojet direct-thrust control scheme for full-envelope fuel consumption minimization
Authors: Villarreal-Valderrama Francisco , Santana Delgado Carlos , Zambrano-Robledo Patricia Del Carmen , Amezquita-Brooks Luis 
Published: December 2020

Purpose
Reducing fuel consumption of unmanned aerial vehicles (UAVs) during transient operation is a cornerstone to achieve environment-friendly operations. The purpose of this paper is to develop a control scheme that improves the fuel economy of a turbojet in its full operating envelope.

Design/methodology/approach
A novel direct-thrust linear quadratic integral (LQI) approach, comprised by an optimal observer/controller satisfying specified performance parameters, is presented. The thrust estimator, based in a Wiener model, is validated with the experimental data of a micro-turbojet. Model uncertainty is characterized by analyzing variations between the identified model and measured data. The resulting uncertainty range is used to verify closed-loop stability with the circle criterion. The proposed controller provides stable responses with the specified performance in the whole operating range, even with after considering plant nonlinearities. Finally, the direct-thrust LQI is compared with a standard thrust controller to assess fuel economy and performance.

Findings
The direct-thrust LQI approach reduced the fuel consumption by 2.1090% in the most realistic scenario. The controllers were also evaluated using the environmental effect parameter (EEP) and transient-thrust-specific fuel consumption (T-TSFC). These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy. Controllers were also evaluated using the EEP and T-TSFC. These novel metrics are proposed to evaluate the environmental impact during transient-thrust operations. The direct-thrust LQI approach has a more efficient fuel consumption according to these metrics. The results also show that isolating the thrust dynamics within the feedback loop has an important impact in fuel economy.

Originality/value
This study shows the design of an effective direct-thrust control approach that minimizes fuel consumption, ensures stable responses for the full operation range, allows isolating the thrust dynamics when designing the controller and is compatible with classical robustness and performance metrics. Finally, the study shows that a simple controller can reduce the fuel consumption of the turbojet during transient operation in scenarios that approximate realistic operating conditions.
A novel addressing algorithm of radix-2 FFT using single-bank dual-port memory
Authors: Kaya Zeynep , Seke Erol 
Published: December 2020

Purpose
This paper aims to present a single-block memory-based FFT processor design with a conflict-free addressing scheme for field-programmable gate arrays FPGAs with dual-port block memories. This study aims for a single-block dual-port memory-based N-point radix-2 FFT design that uses memory locations and spending minimum clock cycle.

Design/methodology/approach
A new memory-based Fast Fourier Transform (FFT) design that uses a dual-port memory block is proposed. Dual-port memory allows the design to perform two memory reads and writes in a single clock cycle. This approach achieves low operational clock and smallest memory simultaneously, excluding some small overhead for exceptional address changes. The methodology is to read from while writing to a memory location, eliminating the need for excess memory and additional clock cycles.

Findings
With the minimum memory size and the simplest architecture, radix-2 FFT and single-memory block are used. The number of clock pulses spent for all FFT operations does not provide much advantage for low-point FFT operations but is important for high-point FFT operations. With the developed algorithm, N memory is used, and the number of clock pulses spent for all FFT stages is (N/2 +1)log2N for all FFT operations.

Originality/value
This is an original paper, which has simultaneously in whole or in part been submitted anywhere else.