bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide identification of binding sites of GRHL2 in luminal-like and basal A subtypes of breast cancer
Authors: Wang Zi , Wu Haoyu , Daxinger Lucia , Danen Erik HJ 
Published: February 2020

AbstractGrainyhead like 2 (GRHL2) is one of three mammalian homologues of the grainyhead (GRH) gene. It suppresses the oncogenic epithelial-mesenchymal transition (EMT), acting as a tumor suppressor. On the other hand, GHRL2 promotes cell proliferation by increasing human telomerase reverse transcriptase (hTERT) activity, serving as a tumor promoter. According to gene expression profiling, breast cancer can be divided into basal-like (basal A and basal B), luminal-like, HER2 enriched, claudin-low and normal-like subtypes. To identify common and subtype-specific genomic binding sites of GRHL2 in breast cancer, GRHL2 ChIP-seq was performed in three luminal-like and three basal A human breast cancer cell lines. Most binding sites of GRHL2 were found in intergenic and intron regions. 13,351 common binding sites were identified in basal A cells, which included 551 binding sites in gene promoter regions. For luminal-like cells, 6,527 common binding sites were identified, of which 208 binding sites were found in gene promoter regions. Basal A and luminal-like breast cancer cells shared 4711 GRHL2 binding sites, of which 171 binding sites were found in gene promoter regions. The identified GRHL2-binding motifs are all identical to a motif reported for human ovarian cancer, indicating conserved GRHL2 DNA-binding among human cancer cells. Notably, no binding sites of GRHL2 were detected in the promoter regions of several established EMT-related genes, including CDH1, ZEB1, ZEB2 and CDH2 genes. Collectively, this study provides a comprehensive overview of interactions of GRHL2 with DNA and lays the foundation for further understanding of common and subtype-specific signaling pathways regulated by GRHL2 in breast cancer.
mzMLb: a future-proof raw mass spectrometry data format based on standards-compliant mzML and optimized for speed and storage requirements
Authors: Bhamber Ranjeet S. , Jankevics Andris , Deutsch Eric W , Jones Andrew R , Dowsey Andrew W 
Published: February 2020

AbstractWith ever-increasing amounts of data produced by mass spectrometry (MS) proteomics and metabolomics, and the sheer volume of samples now analyzed, the need for a common open format possessing both file size efficiency and faster read/write speeds has become paramount to drive the next generation of data analysis pipelines. The Proteomics Standards Initiative (PSI) has established a clear and precise XML representation for data interchange, mzML, receiving substantial uptake; nevertheless, storage and file access efficiency has not been the main focus. We propose an HDF5 file format ‘mzMLb’ that is optimised for both read/write speed and storage of the raw mass spectrometry data. We provide extensive validation of write speed, random read speed and storage size, demonstrating a flexible format that with or without compression is faster than all existing approaches in virtually all cases, while with compression, is comparable in size to proprietary vendor file formats. Since our approach uniquely preserves the XML encoding of the metadata, the format implicitly supports future versions of mzML and is straightforward to implement: mzMLb’s design adheres to both HDF5 and NetCDF4 standard implementations, which allows it to be easily utilised by third parties due to their widespread programming language support. A reference implementation within the established ProteoWizard toolkit is provided.
Pharmacologic activation of the mitochondrial phosphoenolpyruvate cycle enhances islet function in vivo
Authors: Abulizi Abudukadier , Stark Romana , Cardone Rebecca L. , Lewandowski Sophie L. , Zhao Xiaojian , Alves Tiago C. , Thomas Craig , Kung Charles , Wang Bei , Siebel Stephan , Andrews Zane B. , Merrins Matthew J. , Kibbey Richard G. 
Published: February 2020

SummaryThe mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle is an anaplerotic-cataplerotic mitochondrial shuttle utilizing mitochondrial PEPCK (PCK2) and pyruvate kinase (PK). PEP cycling stimulates insulin secretion via OxPhos-independent lowering of ADP by PK. We assessin vivowhether islet PCK2 is necessary for glucose sensing and if speeding the PEP cycle via pharmacological PK activators amplifies insulin secretion.Pck2-/-mice had severely impaired insulin secretion during islet perifusion, oral glucose tolerance tests and hyperglycemic clamps. Acute and chronic pharmacologic PK activator therapy improved islet insulin secretion from normal, high-fat diet (HFD) fed, or Zucker diabetic fatty (ZDF) rats, and glucolipotoxic or diabetic humans. A similar improvement in insulin secretion was observed in regular chow and HFD ratsin vivo. Insulin secretion and cytosolic Ca2+during PK activation were dependent on PCK2. These data provide a preclinical rationale for strategies, such as PK activation, that target the PEP cycle to improve glucose homeostasis.HighlightsLoss of mitochondrial phosphoenolpyruvate (PEP) impairs insulin releasein vivo.Pyruvate kinase (PK) activators stimulate beta-cells in preclinical diabetes models.PEP cyclingin vivodepends on PK and mitochondrial PEPCK (PCK2) for insulin release.Acute and 3-week oral PK activator amplifies insulin release during hyperglycemia.eTOC BlurbAbudukadier et al. show that small molecule pyruvate kinase activationin vivoandin vitroincreases insulin secretion in rodent and human models of diabetes. The phosphoenolpyruvate (PEP) cycling mechanism and its amplification are dependent on mitochondrial PEPCK (PCK2).
Photoreceptor progenitor dynamics in the zebrafish embryo retina and its modulation by primary cilia and N-cadherin
Authors: Aparicio Gonzalo , Rodao Magela , Badano José L. , Zolessi Flavio R. 
Published: February 2020

AbstractBackgroundPhotoreceptors of the vertebrate neural retina are originated from the neuroepithelium, and like other neurons, must undergo cell body translocation and polarity transitions to acquire their final functional morphology, which includes features of neuronal and epithelial cells.MethodsWe analyzed this process in detail on zebrafish embryos usingin vivoconfocal microscopy and electron microscopy. Photoreceptor progenitors were labeled by the transgenic expression of EGFP under the regulation of the photoreceptor-specific promotercrx, and genes of interest were knocked-down using morpholino oligomers.ResultsPhotoreceptor progenitors detached from the basal retina at pre-mitotic stages, rapidly retracting a short basal process as the cell body translocated apically. They remained at an apical position indefinitely to form the outer nuclear layer (ONL), initially extending and retracting highly dynamic neurite-like processes, tangential to the apical surface. Many photoreceptor progenitors presented a short apical primary cilium. The number and length of these cilia was gradually reduced until nearly disappearing around 60 hpf. Their disruption by knocking-down IFT88 and Elipsa caused a notorious defect on basal process retraction. Time-lapse analysis of N-cadherin knock-down, a treatment known to cause a severe disruption of the ONL, showed that the ectopic photoreceptor progenitors initially migrated in an apparent random manner, profusely extending cell processes, until they encountered other cells to establish cell rosettes in which they stayed acquiring the photoreceptor-like polarity.ConclusionAltogether, our observations indicate a complex regulation of photoreceptor progenitor dynamics to form the retinal ONL, previous to the post-mitotic maturation stages.
G4C2repeat RNA mediates the disassembly of the nuclear pore complex in C9orf72 ALS/FTD
Authors: Coyne Alyssa N , Zaepfel Benjamin L , Hayes Lindsey , Fitchman Boris , Salzberg Yuval , Bowen Kelly , Trost Hannah , Rigo Frank , Harel Amnon , Svendsen Clive N , Sareen Dhruv , Rothstein Jeffrey D 
Published: February 2020

AbstractNucleocytoplasmic transport, controlled by the nuclear pore complex, has recently emerged as a pathomechanism underlying neurodegenerative diseases including C9orf72 ALS/FTD. However, little is known about the underlying molecular events and the underlying biology in human neurons. Using super resolution structured illumination microscopy of twenty three nucleoporins in nuclei from C9orf72 iPSC derived neurons and postmortem human tissue we identify a unique subset of eight nucleoporins lost from human neuronal nuclei. POM121, an integral transmembrane nucleoporin, appears to coordinate the composition of the nucleoporins within human neuronal nuclei ultimately impacting nucleocytoplasmic transport, and subsequent cellular toxicity in C9orf72 iPSNs. These data suggest that POM121 is a critical nucleoporin in the maintenance of the nuclear localization of specific nucleoporins in human neurons. Moreover, loss of nuclear POM121, as a result of expanded C9orf72 ALS/FTD repeat RNA, initiates a pathological cascade affecting nucleoporin composition within neuronal nuclei, nuclear pore complex function, and overall downstream neuronal survival.
β-L-1-[5-(E-2-Bromovinyl)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)] uracil (L-BHDU) effectiveness against varicella-zoster virus and herpes simplex virus type 1 depends on thymidine kinase activity
Authors: De Chandrav , Liu Dongmei , Depledge Daniel , Breuer Judith , Singh Uma S. , Hartline Caroll , Prichard Mark N. , Chu Chung K. , Moffat Jennifer F. 
Published: February 2020

Abstractß-L-1-[5-(E-2-bromovinyl)-2-(hydroxymethyl)-1,3-(dioxolan-4-yl)] uracil (L-BHDU) prevents varicella-zoster virus (VZV) replication in cultured cells andin vivo. Its mechanism of action was investigated by evaluating its activity against related herpesviruses and by analyzing resistant VZV strains. L-BHDU was effective against herpes simplex virus type 1 (HSV-1) with an EC50of 0.22µM in human foreskin fibroblast (HFF) cells. L-BHDU also inhibited HSV-2 and simian varicella virus (SVV) to a lesser extent. VZV mutants resistant to L-BHDU and other antiviral compounds were obtained by serial passage of the wild type VZV pOka and VZV Ellen strains in the presence of increasing drug concentrations. VZV strains resistant to L-BHDU (L-BHDUR) were cross-resistant to acyclovir (ACV) and brivudin (BVdU) but not to foscarnet (PFA) and cidofovir (CDV). Conversely, ACV-resistant strains were also resistant to L-BHDU. Whole genome sequencing of L-BHDURstrains identified mutations in ATP-binding (G22R) and nucleoside binding (R130Q) domains of VZV thymidine kinase (TK). The wild type and mutant forms of VZV TK were cloned as GST fusion proteins and expressed inE. coli. The partially purified TKG22R-GST and TKR130Q- GST proteins failed to convert thymidine to thymidine monophosphate whereas the wild type TK-GST protein was enzymatically active. Similarly, L-BHDURvirus TK did not phosphorylate the drug. As expected, wild type VZV converted L-BHDU to L-BHDU monophosphate and diphosphate forms. In conclusion, L-BHDU effectiveness against VZV and HSV-1 depends on thymidine kinase activity.
Phenotypic associations among cell cycle genes inSaccharomyces cerevisiae
Authors: Bermudez-Cruz María , Wu Peter I. , Callerame Deanna , Hammer Staci , Hu James C. , Polymenis Michael 
Published: February 2020

ABSTRACTA long-standing effort in biology is to precisely define and group phenotypes that characterize a biological process, and the genes that underpin them. InSaccharomyces cerevisiaeand other organisms, functional screens have generated rich lists of phenotypes associated with individual genes. However, it is often challenging to identify sets of phenotypes and genes that are most closely associated with a given biological process. Here, we focused on the 166 phenotypes arising from loss-of-function and the 86 phenotypes from gain-of-function mutations in 571 genes currently assigned to cell cycle-related ontologies inS. cerevisiae. To reduce this complexity, we applied unbiased, computational approaches of correspondence analysis to identify a minimum set of phenotypic variables that accounts for as much of the variability in the data as possible. Loss-of-function phenotypes can be reduced to 20 dimensions, while gain-of-function ones to 14 dimensions. We also pinpoint the contributions of phenotypes and genes in each set. The approach we describe not only simplifies the categorization of phenotypes associated with cell cycle progression but can also serve as a discovery tool for gene function.
Chronic wireless streaming of invasive neural recordings at home for circuit discovery and adaptive stimulation
Authors: Gilron Ro’ee , Little Simon , Perrone Randy , Wilt Robert , de Hemptinne Coralie , Yaroshinsky Maria S. , Racine Caroline A. , Wang Sarah , Ostrem Jill L. , Larson Paul S. , Wang Doris D. , Galifianakis Nick B. , Bledsoe Ian , San Luciano Marta , Dawes Heather E. , Worrell Gregory A. , Kremen Vaclav , Borton David , Denison Timothy , Starr Philip A. 
Published: February 2020

AbstractInvasive neural recording in humans shows promise for understanding the circuit basis of brain disorders. Most recordings have been done for short durations from externalized brain leads in hospital settings, or from first-generation implantable sensing devices that offer only intermittent brief streaming of time series data. Here we report the first human use of an implantable neural interface for wireless multichannel streaming of field potentials over long periods, with and without simultaneous therapeutic neurostimulation, untethered to receiving devices. Four Parkinson’s disease patients streamed bilateral 4-channel motor cortical and basal ganglia field potentials at home for over 500 hours, paired with wearable monitors that behaviorally categorize states of inadequate or excessive movement. Motor state during normal home activities was efficiently decoded using either supervised learning or unsupervised clustering algorithms. This platform supports adaptive deep brain stimulation, and may be widely applicable to brain disorders treatable by invasive neuromodulation.
Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy
Authors: Madar A.D. , Pfammatter J.A. , Bordenave J. , Plumley E.I. , Ravi S. , Cowie M. , Wallace E.P. , Hermann B.P. , Maganti R.K. , Jones M.V. 
Published: February 2020

AbstractIn temporal lobe epilepsy, the ability of the dentate gyrus to limit excitatory cortical input to the hippocampus breaks down, leading to seizures. The dentate gyrus is also thought to help discriminate between similar memories by performing pattern separation, but whether epilepsy leads to a breakdown in this neural computation, and thus to mnemonic discrimination impairments, remains unknown. Here we show that temporal lobe epilepsy is characterized by behavioral deficits in mnemonic discrimination tasks, in both humans (females and males) and mice (C57Bl6 males, systemic low-dose kainate model). Using a recently developed assay in brain slices of the same epileptic mice, we reveal a decreased ability of the dentate gyrus to perform certain forms of pattern separation. This is due to a subset of granule cells with abnormal bursting that can develop independently of early EEG abnormalities. Overall, our results linking physiology, computation and cognition in the same mice advance our understanding of episodic memory mechanisms and their dysfunction in epilepsy.Significance StatementPeople with temporal lobe epilepsy (TLE) often have learning and memory impairments, sometimes occurring earlier than the first seizure, but those symptoms and their biological underpinnings are poorly understood. We focused on the dentate gyrus, a brain region that is critical to avoid confusion between similar memories and is anatomically disorganized in TLE. We show that both humans and mice with TLE experience confusion between similar situations. This impairment coincides with a failure of the dentate gyrus to disambiguate similar input signals because of pathological bursting in a subset of neurons. Our work bridges seizure-oriented and memory-oriented views of the dentate gyrus function, suggests a mechanism for cognitive symptoms in TLE and supports a long-standing hypothesis of episodic memory theories.
Machine Learning Algorithms for Predicting Coronary Artery Disease: Efforts Toward an Open Source Solution
Authors: Akella Aravind , Kaushik Vibhor 
Published: February 2020

AbstractThe development of Coronary Artery Disease (CAD), one of the most prevalent diseases in the world, is heavily influenced by several modifiable risk factors. Predictive models built using machine learning (ML) algorithms may assist healthcare practitioners in timely detection of CAD, and ultimately, may improve outcomes. In this study, we have applied six different ML algorithms to predict the presence of CAD amongst patients listed in an openly available dataset provided by the University of California Irvine (UCI) Machine Learning Repository, named “the Cleveland dataset.” All six ML algorithms achieved accuracies greater than 80%, with the “Neural Network” algorithm achieving accuracy greater than 93%. The recall achieved with the “Neural Network” model is also highest of the six models (0.93). Additionally, five of the six algorithms resulted in very similar AUC-ROC curves. The AUC-ROC curve corresponding to the “Neural Network” algorithm is slightly steeper implying higher “true positive percentage” achieved with this model. We also extracted the variables of importance in the “Neural Network” model to help in the risk assessment. We have released the full computer code generated in this study in the public domain as a preliminary effort toward developing an open solution for predicting the presence of coronary artery disease in a given population and present a workflow model for implementing a possible solution.
A one-tube method for rapid and reliable plant genomic DNA isolation for PCR analysis
Authors: Hu Wei , Lagarias J. Clark 
Published: February 2020

AbstractBackgroundConsistent isolation of high quality plant genomic DNA is a prerequisite for successful PCR analysis. Time consumption, ease of operation and procedure cost are important secondary considerations for selecting an effective DNA extraction method. The simple, reliable and rapid DNA extraction method developed by Edwards and colleagues in 1991 [1] has proven to be the gold standard.ResultsThrough modification of the Edwards method of extraction, we have developed a one-tube protocol that greatly improves the efficiency of plant DNA extraction and reduces the potential for sample contamination while simultaneously yielding high quality DNA suitable for PCR analysis. We further show that DNA extracts prepared with this method are stable at room temperature for at least three months.ConclusionThe one-tube extraction method yields high quality plant DNA with improved efficiency while greatly minimizing the potential for cross contamination. This low-cost and environment-friendly method is widely applicable for plant molecular biology research.
Comparison of the two up-to-date sequencing technologies for genome assembly: HiFi reads of Pacbio Sequel II system and ultralong reads of Oxford Nanopore
Authors: Lang Dandan , Zhang Shilai , Ren Pingping , Liang Fan , Sun Zongyi , Meng Guanliang , Tan Yuntao , Hu Jiang , Li Xiaokang , Lai Qihua , Han Lingling , Wang Depeng , Hu Fengyi , Wang Wen , Liu Shanlin 
Published: February 2020

AbstractThe availability of reference genomes has revolutionized the study of biology. Multiple competing technologies have been developed to improve the quality and robustness of genome assemblies during the last decade. The two widely-used long read sequencing providers – Pacbio (PB) and Oxford Nanopore Technologies (ONT) – have recently updated their platforms: PB enable high throughput HiFi reads with base-level resolution with >99% and ONT generated reads as long as 2 Mb. We applied the two up-to-date platforms to one single rice individual, and then compared the two assemblies to investigate the advantages and limitations of each. The results showed that ONT ultralong reads delivered higher contiguity producing a total of 18 contigs of which 10 were assembled into a single chromosome compared to that of 394 contigs and three chromosome-level contigs for the PB assembly. The ONT ultralong reads also prevented assembly errors caused by long repetitive regions for which we observed a total 44 genes of false redundancies and 10 genes of false losses in the PB assembly leading to over/under-estimations of the gene families in those long repetitive regions. We also noted that the PB HiFi reads generated assemblies with considerably less errors at the level of single nucleotide and small InDels than that of the ONT assembly which generated an average 1.06 errors per Kb assembly and finally engendered 1,475 incorrect gene annotations via altered or truncated protein predictions.
Reconstruction of cell spatial organization based on ligand-receptor mediated self-assembly
Authors: Ren Xianwen , Zhong Guojie , Zhang Qiming , Zhang Lei , Sun Yujie , Zhang Zemin 
Published: February 2020

AbstractSingle-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such asin situsequencing show great promise, technical difficulties currently limit their wide usage. Since cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, here we present CSOmap, a computational strategy to infer cellular interaction from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of tumor microenvironments for multiple cancers and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be widely applicable to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems.
Bile acid supplementation improves murine pancreatitis in association with the gut microbiota
Authors: Wan You-Dong , Zhu Rui-Xue , Pan Xin-Ting 
Published: February 2020

ABSTRACTDisorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. Similar results were found in microbiota-depleted AP without BA treatment. However, we did not observe further downregulation of the FXR signaling pathway in microbiota-depleted AP mice given TUDCA, indicating that improvement of pancreatitis by TUDCA may be associated with gut microbiota. Our analysis of changes to the gut microbiota in AP indicated thatLactobacillimay be the key contributors. Taken together, our study shows that supplementation with BAs could improve bile acid-FXR-FGF15 signaling, and reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.