Top 10 Biorxiv Papers Today in Molecular Biology


2.01 Mikeys
#1. CtIP -mediated alternative mRNA splicing finetunes the DNA damage response
Rosario Prados-Carvajal, Guillermo Rodriguez-Real, Gabriel Gutierrez-Pozo, Pablo Huertas
In order to survive to the exposure of DNA damaging agents, cells activate a complex response that coordinates the cellular metabolism, cell cycle progression and DNA repair. Among many other events, recent evidence has described global changes in mRNA splicing in cells treated with genotoxic agents. Here, we explore further this DNA damage-dependent alternative splicing. Indeed, we show that both the splicing factor SF3B2 and the repair protein CtIP contribute to the global pattern of splicing both in cells treated or not to DNA damaging agents. Additionally, we focus on a specific DNA damage- and CtIP-dependent alternative splicing event of the helicase PIF1 and explore its relevance for the survival of cells upon exposure to ionizing radiation. Indeed, we described how the nuclear, active form of PIF1 is substituted by a splicing variant, named vPIF1, in a fashion that requires both the presence of DNA damage and CtIP. Interestingly, timely expression of vPIF1 is required for optimal survival to exposure to DNA damaging agents,...
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biorxivpreprint: CtIP -mediated alternative mRNA splicing finetunes the DNA damage response https://t.co/zGJnc3QNM2 #bioRxiv
NZthRzXeiplAQA6: RT @biorxivpreprint: CtIP -mediated alternative mRNA splicing finetunes the DNA damage response https://t.co/zGJnc3QNM2 #bioRxiv
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Authors: 4
Total Words: 15339
Unqiue Words: 3888

2.007 Mikeys
#2. A highly sensitive and specific SYBR Green quantitative polymerase chain reaction (qPCR) method for rapid detection of scale drop disease virus in Asian sea bass, Lates calcarifer
Sukhontip Sriisan, Chuenchit Boonchird, Siripong Thitamadee, Ha Thanh Dong, Saengchan Senapin
Scale drop disease virus (SDDV) is a novel Megalocytivirus causing scale drop disease (SDD) in Asian sea bass in Southeast Asia. In order to support disease diagnosis and surveillance, the present study developed a highly sensitive and specific SYBR Green qPCR assay for rapid detection of SDDV. Specific primers targeting a 135-bp fragment of ATPase coding gene of the SDDV genome were newly designed and subsequent gradient PCR assays were conducted to investigate their optimal annealing temperature. The optimized qPCR assay could detect as low as 2 viral copies per reaction and showed no cross amplification with DNA extracted from 12 viruses and bacteria commonly found in aquatic animals. The SDDV ATPase qPCR method was subsequently validated with field samples (n=86). The results revealed that all clinically sick fish (n=34) from 5 affected farms gave positive results. Interestingly, 30/52 samples of apparently healthy fish from 8 unaffected farms which previously tested negative for SDDV by semi-nested PCR assay were positive by...
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biorxivpreprint: A highly sensitive and specific SYBR Green quantitative polymerase chain reaction (qPCR) method for rapid detection of scale drop disease virus in Asian sea bass, Lates calcarifer https://t.co/GpN2i8lNMn #bioRxiv
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Authors: 5
Total Words: 0
Unqiue Words: 0

2.004 Mikeys
#3. Role of microRNA-21 in hypertrophic cardiac remodeling
Ken Watanabe, Taro Narumi, Tetsu Watanabe, Yoichiro Otaki, Tetsuya Takahashi, Tomonori Aono, Jun Goto, Taku Toshima, Takayuki Sugai, Masahiro Wanezaki, Daisuke Kutsuzawa, Shigehiko Kato, Harutoshi Tamura, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Tetsuro Shishido, Masafumi Watanabe
Hypertension is a major public health problem among with aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its impact on hypertrophic cardiac remodeling in hypertension is not known. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of...
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biorxivpreprint: Role of microRNA-21 in hypertrophic cardiac remodeling https://t.co/4atdui5qNu #bioRxiv
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Authors: 18
Total Words: 0
Unqiue Words: 0

2.004 Mikeys
#4. Loss of family with sequence similarity 13, member A exacerbates pulmonary hypertension through accelerating endothelial-to-mesenchymal transition
Pranindya Rinastiti, Koji Ikeda, Elda Putri Rahardini, Kazuya Miyagawa, Naoki Tamada, Yuko Kuribayashi, Ken-ichi Hirata, Noriaki Emoto
Pulmonary hypertension is a progressive lung disease with poor prognosis due to the consequent right heart ventricular failure. Pulmonary artery remodeling and dysfunction are culprits for pathologically increased pulmonary arterial pressure, but their underlying molecular mechanisms remain to be elucidated. Previous genome-wide association studies revealed a significant correlation between the genetic locus of family with sequence similarity 13, member A (FAM13A) and various lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis; however whether FAM13A is also involved in the pathogenesis of pulmonary hypertension remained unknown. Here, we identified a significant role of FAM13A in the development of pulmonary hypertension. FAM13A expression was reduced in mouse lungs of hypoxia-induced pulmonary hypertension model. We identified that FAM13A was expressed in lung vasculatures, especially in endothelial cells. Genetic loss of FAM13A exacerbated pulmonary hypertension in mice exposed to chronic hypoxia...
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biorxivpreprint: Loss of family with sequence similarity 13, member A exacerbates pulmonary hypertension through accelerating endothelial-to-mesenchymal transition https://t.co/6s2kIlo5K8 #bioRxiv
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Authors: 8
Total Words: 0
Unqiue Words: 0

2.003 Mikeys
#5. Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD)
Álvaro Rol, Toni Todorovski, Pau Martin-Malpartida, Anna Escolà, Elena González-Rey, Eric Aragon, Xavier Verdaguer, Mariona Vallès-Miret, Josep Farrera-Sinfreu, Eduard Puig, Jimena Fernández-Carneado, Berta Ponsati, Mario Delgado, Antoni Riera, Maria J. Macias
Ulcerative colitis and Crohn's disease are inflammatory bowel diseases (IBD) that lead to chronic inflammations of the gastrointestinal tract due to an abnormal response of the immune system. Finding new effective drugs to tackle IBD represents a major therapeutic concern since IBD incidence and prevalence is increasing worldwide. Recent studies positioned Cortistatin (CST) as a candidate for IBD treatment due to its anti-inflammatory and immunomodulatory activity. Here, we studied the structural properties of CST using NMR and synthesized and characterized new analogs displaying enriched populations of some native conformations. One of them, Analog 5, preserved the activity against IBD with an increased half-life in serum, overcoming the native hormone limitation and opening the door for the use of CST analogs as therapeutic agents. This work represents a new approach to the rational design of molecules to treat IBD and a possibility for patients that fail to respond to other therapies.
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biorxivpreprint: Structure-based design of a Cortistatin analog with improved immunoregulatory activity against inflammatory bowel disease (IBD) https://t.co/wnN6EnzW4h #bioRxiv
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Authors: 15
Total Words: 0
Unqiue Words: 0

2.001 Mikeys
#6. BET inhibition disrupts transcription but retains enhancer-promoter contact
Nicholas T. Crump, Erica Ballabio, Laura Godfrey, Ross Thorne, Emmanouela Repapi, Jon Kerry, Marta Tapia, Peng Hua, Panagis Filippakopoulos, James O. J Davies, Thomas Milne
In higher eukaryotes, enhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. The formation of phase condensates is thought to be an essential component of enhancer function. Here, we show that pharmacological targeting of cells with inhibitors of BET (Bromodomain and Extra-Terminal domain) proteins can have a strong impact on transcription but very little impact on enhancer-promoter interactions. Treatment with 1,6-hexanediol, which dissolves phase condensate structures and reduces BET and Mediator protein binding at enhancers, can also have a strong effect on gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable...
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biorxivpreprint: BET inhibition disrupts transcription but retains enhancer-promoter contact https://t.co/wUeeMNCghs #bioRxiv
PromPreprint: BET inhibition disrupts transcription but retains enhancer-promoter contact https://t.co/kR7IaKCXCQ
IchiroNakanoNS: RT @biorxivpreprint: BET inhibition disrupts transcription but retains enhancer-promoter contact https://t.co/wUeeMNCghs #bioRxiv
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Authors: 11
Total Words: 16077
Unqiue Words: 3445

1.998 Mikeys
#7. Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage
Bo Cao, Xiaolin Wu, Jieliang Zhou, Hang Wu, Michael S. DeMott, Chen Gu, Lianrong Wang, Delin You, Peter C. Dedon
Here we present the Nick-seq platform for quantitative mapping of DNA modifications and damage at single-nucleotide resolution across genomes. Pre-existing breaks are blocked and DNA structures converted to strand-breaks for 3'-extension by nick-translation to produce nuclease-resistant oligonucleotides, and 3'-capture by terminal transferase tailing. Libraries from both products are subjected to NGS sequencing. Nick-seq is a generally applicable method illustrated with quantitative profiling of single-strand breaks, phosphorothioate modifications, and DNA oxidation.
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zTiredScientist: RT @biorxivpreprint: Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage https://t.co/ygKiudAKFH #bioRx…
brian_tenner: RT @biorxivpreprint: Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage https://t.co/ygKiudAKFH #bioRx…
NZthRzXeiplAQA6: RT @biorxivpreprint: Nick-seq for single-nucleotide resolution genomic maps of DNA modifications and damage https://t.co/ygKiudAKFH #bioRx…
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Authors: 9
Total Words: 0
Unqiue Words: 0

1.997 Mikeys
#8. Translational regulation of Pmt1 and Pmt2 by Bfr1 affects unfolded protein O-mannosylation
Joan Castells-Ballester, Natalie Rinis, Ilgin Kotan, Lihi Gal, Daniela Bausewein, Ilia Kats, Ewa Zatorska, Günter Kramer, Bernd Bukau, Maya Schuldiner, Sabine Strahl
O-mannosylation is implicated in protein quality control in Saccharomyces cerevisiae due to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile folding cycles and saves cellular resources is mainly mediated by protein O-mannosyltransferases Pmt1 and Pmt2. Here we describe a genetic screen for factors that influence O-mannosylation in yeast, using slow-folding GFP as a reporter. Our screening identifies the RNA binding protein brefeldin A resistance factor 1 (Bfr1) that has not been linked to O-mannosylation and ER protein quality control before. We find that Bfr1 affects O-mannosylation through changes in Pmt1 and Pmt2 protein abundance, but has no effect on PMT1 and PMT2 transcript levels, mRNA localization to the ER membrane or protein stability. Ribosome profiling reveals that Bfr1 is a crucial factor for Pmt1 and Pmt2 translation thereby affecting unfolded protein...
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biorxivpreprint: Translational regulation of Pmt1 and Pmt2 by Bfr1 affects unfolded protein O-mannosylation https://t.co/1amc1k4qZw #bioRxiv
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Sample Sizes : [3]
Authors: 11
Total Words: 18781
Unqiue Words: 5625

1.997 Mikeys
#9. Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency
Mateusz Stoszko, Abdullah MS Al-Hatmi, Anton Skriba, Michael Roling, Enrico Ne, Yvonne M Mueller, Mohammad Javad Najafzadeh, Raquel Crespo, Joyce Kang, Renata Ptackova, Pritha Biswas, Alessia Bertoldi, Tsung Wai Kan, Elisa de Crignis, Miroslav Sulc, Joyce Lebbink, Casper Rokx, Annelies Verbon, Wilfred van Ijcken, Robert-Jan Palstra, Peter D Katsikis, Vladimir Havlicek, Sybren de Hoog, Tokameh Mahmoudi
A leading pharmacological strategy towards HIV cure requires 'shock' or activation of HIV gene expression in latently infected cells with Latency Reversal Agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs we used fungal secondary metabolites (extrolites) as a source of bio-active molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the P-TEFb inhibitory 7SK snRNP complex to be significantly reduced upon GTX treatment of independent donor CD4+T cells. GTX disrupted 7SK snRNP, releasing active P-TEFb, which then phosphorylated RNA Pol II CTD, inducing HIV transcription. Our data highlight the power of combining a medium throughput bioassay, mycology and orthogonal mass spectrometry to identify novel potentially therapeutic compounds.
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Authors: 24
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1.997 Mikeys
#10. RNA-guided Retargeting of Sleeping Beauty Transposition in Human Cells
Adrian Kovač, Csaba Miskey, Michael Menzel, Esther Grueso, Andreas Gogol-Döring, Zoltán Ivics
Two different approaches of genomic modification are currently used for genome engineering and gene therapy: integrating vectors, which can efficiently integrate large transgenes but are unspecific with respect to their integration sites, and nuclease-based approaches, which are highly specific but not efficient at integrating large genetic cargoes. Here we demonstrate biased genome-wide integration of the Sleeping Beauty (SB) transposon by combining it with components of the CRISPR/Cas9 system. We provide proof-of-concept that it is possible to influence the target site selection of SB by fusing it to a catalytically inactive Cas9 (dCas9) and by providing a single guide RNA (sgRNA) against the human Alu retrotransposon. Enrichment of transposon integrations was dependent on the sgRNA, occurred in a relatively narrow, ~200 bp window around the targeted sites and displayed an asymmetric pattern with a bias towards sites that are downstream of the sgRNA targets. Our data indicate that the targeting mechanism specified by CRISPR/Cas9...
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biorxivpreprint: RNA-guided Retargeting of Sleeping Beauty Transposition in Human Cells https://t.co/x7jW5mm0Yf #bioRxiv
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Authors: 6
Total Words: 0
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