Top 10 Biorxiv Papers Today in Molecular Biology


2.01 Mikeys
#1. Combinatorial Treatment Increases IKAP Levels in Human Cells Generated from Familial Dysautonomia Patients
Gil Ast, Sivan Yanai, Jonathan Zonszain, Maya Donyo
Familial Dysautonomia (FD) is an autosomal recessive congenital neuropathy that results from a point mutation at the 5′ splice site of intron 20 in the IKBKAP gene. This mutation decreases production of the IKAP protein, and treatments that increase the level of the full-length IKBKAP transcript are likely to be of therapeutic value. We previously found that phosphatidylserine (PS), an FDA-approved food supplement, elevates IKAP levels in cells generated from FD patients. Here we demonstrate that combined treatment of cells generated from FD patients with PS and kinetin or PS and the histone deacetylase inhibitor trichostatin A (TSA) resulted in an additive elevation of IKAP compared to each drug alone. This indicates that the compounds influence different pathways. We also found that pridopidine enhances production of IKAP in cells generated from FD patients. Pridopidine has an additive effect on IKAP levels when used in combination with kinetin or TSA, but not with PS; suggesting that PS and pridopidine influence IKBKAP levels...
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biorxivpreprint: Combinatorial Treatment Increases IKAP Levels in Human Cells Generated from Familial Dysautonomia Patients https://t.co/oaNiM4wj8e #bioRxiv
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Sample Sizes : None.
Authors: 4
Total Words: 7102
Unqiue Words: 2098

2.004 Mikeys
#2. Nascent transcript analysis of glucocorticoid crosstalk with TNF defines primary and cooperative inflammatory repression
Sarah K. Sasse, Margaret Gruca, Mary A. Allen, Vineela Kadiyala, Tengyao Song, Fabienne Gally, Arnav Gupta, Miles A Pufall, Robin D Dowell, Anthony N. Gerber
The glucocorticoid receptor (GR) binds to specific DNA sequences and directly induces transcription of anti-inflammatory genes that contribute to cytokine repression, frequently in cooperation with NF-kB. Whether inflammatory repression also occurs through local interactions between GR and inflammatory gene regulatory elements remains controversial. Here, using Global Run-on Sequencing (GRO-seq) in human airway epithelial cells, we show that glucocorticoid signaling represses transcription within 10 minutes. Many repressed regulatory regions reside within 'hyper-ChIPable' genomic regions that are subject to non-specific interactions with some antibodies. When this was accounted for, we determined that transcriptional repression occurs without local GR occupancy. Instead, widespread transcriptional induction through canonical GR binding sites is associated with reciprocal repression of distal TNF-regulated enhancers through a chromatin-dependent process, as evidenced by chromatin accessibility and enhancer-reporter assays....
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CyrilPedia: 'Here, using Global Run-on Sequencing in human airway epithelial cells, we show that glucocorticoid signaling represses transcription within 10 minutes' https://t.co/HZ5w5a8YzF
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Sample Sizes : [75395, 68278, 251]
Authors: 10
Total Words: 11626
Unqiue Words: 3482

2.003 Mikeys
#3. Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes
Vikas Kumar, Pawan K. Doharey, Shelly Gulati, Joshua Meehan, Mary Grace Martinez, Karissa Hughes, Blaine H.M. Mooers, Jorge Cruz-Reyes
Uridylate insertion/deletion RNA editing in Trypanosoma brucei uses hundreds of small non-coding guide RNAs (gRNAs) to modify the mitochondrial mRNA transcriptome. This process occurs in holo-editosomes that assemble several macromolecular trans factors around mRNA: the RNA-free RNA editing core complex (RECC) and auxiliary RNPs. Yet, the regulatory mechanisms of editing remain obscure. The enzymatic accessory RNP, termed the REH2C, includes mRNA substrates and products, the multi-domain 240 kDa RNA Editing Helicase 2 (REH2) and an intriguing 8-zinc finger protein termed REH2-Associated Factor 1 (H2F1). Both proteins are essential in editing. REH2 is a member of the DExH/RHA subfamily of RNA helicases with a conserved C-terminus that includes a regulatory OB-fold domain. In trypanosomes, H2F1 recruits REH2 to the editing apparatus, and H2F1 downregulation causes REH2 fragmentation. Our systematic mutagenesis dissected determinants in REH2 and H2F1 for the assembly of REH2C, the stability of REH2, and the RNA-mediated association...
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biorxivpreprint: Protein features for assembly of the RNA editing helicase 2 subcomplex (REH2C) in Trypanosome holo-editosomes https://t.co/mliQg7eTUU #bioRxiv
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Sample Sizes : [3, 2, 3, 3, 3, 2, 3, 3]
Authors: 8
Total Words: 13979
Unqiue Words: 3970

1.998 Mikeys
#4. DNA Gap Repair-Mediated Site-Directed Mutagenesis is Different from Mandecki and Recombineering Approaches
George T. Lyozin, Luca Brunelli
Site-directed mutagenesis allows the generation of mutant DNA sequences for downstream functional analysis of genetic variants involved in human health and disease. Understanding the mechanisms of different mutagenesis methods can help select the best approach for specific needs. We compared three different approaches for in vivo site-directed DNA mutagenesis that utilize a mutant single-stranded DNA oligonucleotide (ssODN) to target a wild type DNA sequence in the host Escherichia coli (E. coli). The first method, Mandecki, uses restriction nucleases to introduce a double stranded break (DSB) into a DNA sequence which needs to be denatured prior to co-transformation. The second method, recombineering (recombination-mediated genetic engineering), requires lambda red gene products and a mutant ssODN with homology arms of at least 20 nucleotides. In a third method described here for the first time, DNA gap repair, a mutant ssODN targets a DNA sequence containing a gap introduced by PCR. Unlike recombineering, both DNA gap repair and...
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Sample Sizes : None.
Authors: 2
Total Words: 5864
Unqiue Words: 1705

1.998 Mikeys
#5. Comparative analysis of mitochondrial genome between UG93A and UG93B reveal common feature of 5′- end heterogeneity in mitochondrial genes of kenaf
Xiaofang Liao, Yanhong Zhao, Aziz Khan, Xiangjun Kong, Bujin Zhou, Min Li, Meiling Wei, Shuangshuang Peng, Fazal Munsif, Ruiyang Zhou
Plant cytoplasmic male sterility (CMS) being maternal phenomenon trait that result from pollen abortion and closely linked with mitochondrial DNA rearrangement in many crops including kenaf. However, the molecular mechanism in kenaf is poorly known. In present work, we described the mitochondrial genome in isonuclear CMS line UG93A and its maintainer line UG93B. Findings of the current study revealed that a total of 398 SNPs and 230 InDels were identified in UG93A mtDNA. Total of 26 SNPs variations and three InDels were identified in the coding region of atp6 , indicating its active role in mitochondrial genome re-arrangement. Northern blot analysis showed that the transcripts of atp1, atp4, atp6, cox3 and sdh4 in F1 were consistent with UG93A but different for UG93B. The transcript of atp9 was found similar between UG93B and F1 while different for UG93A, which depict that atp9 may be regulated by nuclear genes in F1 hybrid. The expression of atp9 in UG93A was substantially lower compared with UG93B, suggesting its key role for...
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biorxivpreprint: Comparative analysis of mitochondrial genome between UG93A and UG93B reveal common feature of 5'- end heterogeneity in mitochondrial genes of kenaf https://t.co/hqce6hgsTZ #bioRxiv
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Sample Sizes : [3]
Authors: 10
Total Words: 9531
Unqiue Words: 2479

1.997 Mikeys
#6. A molecular phylogeny of Schizothoracinae (Teleostei: Cypriniformes: Cyprinidae) based on 12 protein-coding mitochondrial genes and RAG1 gene analysis
Yurong Du, Ting Wang, Delin Qi, Desheng Qi, Weilin Li, Jiangbin Zhong, Juan Chen, Songchang Guo, Jianbin Ma
The ever-increasing interest in the investigation of origin and speciation of schizothoracine fishes can be dated to 20th century. However, molecular phylogeny of Schizothoracinae and their phylogenetic relationships, as well as the divergence times still remain controversial. In this study, two DNA sets consisting of 12 protein-coding mitochondrial genes from 254 individuals and RAG1 gene from 106 individuals were used to reconstruct the phylogenetic relationships and calculate the divergence times among the subfamily schizothoracinae. Our results indicated that both of the data sets supported a non-monophyletic relationship due to involving of species of Barbinae . However, the phylogenetic relationships based on mtDNA genes were more reliable than that inferred from RAG1 gene. The highly specialized grade formed a monophyletic group, together with Ptychobarbus as a sister group of Diptychus and Gymnodiptychus , which was belonging to specialized grade, indicating that Ptychobarbus may be transition species to involve to highly...
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biorxivpreprint: A molecular phylogeny of Schizothoracinae (Teleostei: Cypriniformes: Cyprinidae) based on 12 protein-coding mitochondrial genes and RAG1 gene analysis https://t.co/QKKUkH30ot #bioRxiv
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Sample Sizes : None.
Authors: 9
Total Words: 9438
Unqiue Words: 2881

1.997 Mikeys
#7. Induction of an alternative 5′ leader enhances translation of Inpp5e and resistance to oncolytic virus infection
Huy-Dung Hoang, Tyson Graber, Jian-Jun Jia, Nasana Vaidya, Victoria Gilchrist, Wencheng Li, Christos Gkogkas, Maritza Jaramillo, Seyed Mehdi Jafarnejad, Tommy Alain
Residual cell-intrinsic innate immunity in cancer cells hampers infection with oncolytic viruses. mRNA translation is an important component of innate immunity, yet the targeted cellular mRNAs remain ill-defined. We characterized the translatome of resistant murine "4T1" breast cancer cells infected with three of the most clinically advanced oncolytic viruses: Herpes Simplex virus 1, Reovirus and Vaccinia virus. Common among all three infections were translationally de-repressed mRNAs involved in ciliary homeostasis including Inpp5e, encoding an inositol 5-phosphatase that modifies lipid second messenger signalling. Translationally repressed in the uninfected condition, viral infection induced expression of an Inpp5e mRNA variant that lacks repressive upstream open reading frames (uORFs) within its 5′ leader and is consequently efficiently translated. Furthermore, we show that INPP5E contributes to antiviral immunity by altering virus attachment. These findings uncover a role for translational control through alternative 5′ leader...
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TommyAlain3: Induction of an alternative 5′ leader enhances translation of Inpp5e and resistance to oncolytic virus infection | bioRxiv https://t.co/cnLPUWLC0I
rnaguru: Induction of an alternative 5′ leader enhances translation of Inpp5e and resistance to oncolytic virus infection https://t.co/Bqlk6jlmOO
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Sample Sizes : None.
Authors: 10
Total Words: 14541
Unqiue Words: 4252

1.997 Mikeys
#8. A Pipeline for Fecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR
Kuang He, Hideaki Fujiwara, Cynthia Zajac, Erin Sandford, Pavan Reddy, Sung Won Choi, Muneesh Tewari
Stool contains DNA shed from cells of the gastrointestinal (GI) tract and has great potential as a bio-specimen for non-invasive, nucleic acid-based detection of GI diseases. Whereas methods for studying fecal microbiome DNA are plentiful, there is a lack of well-characterized procedures for stabilization, isolation, and quantitative analysis of fecal host DNA. We report an optimized pipeline for fecal host DNA analysis from the point-of-collection to droplet digital PCR (ddPCR) absolute quantification of host-specific gene targets. We evaluated multiple methods for preservation and isolation of host DNA from stool to identify the highest performing methods. To quantify host DNA, we developed sensitive, human-specific ddPCR assays targeting repetitive nuclear genomic elements (LINE-1) and mitochondrial genes. We validated the ability of these optimized methods to perform absolute quantification of short (<100 bp) host DNA in 200 stool DNA extracts from samples that were serially collected from three healthy individuals and three...
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Authors: 7
Total Words: 10965
Unqiue Words: 2891

0.0 Mikeys
#9. Chromatin interactome mapping at 139 independent breast cancer risk signals
Jonathan Beesley, Haran Sivakumaran, Mahdi Moradi Marjaneh, Luize Lima, Kristine Hillman, Susanne Kaufmann, Natasha Tuano, Nehal Hussein, Sunyoung Ham, Pamela Mukhopadhyay, Stephen Kazakoff, Jason Lee, Kyriaki Michailidou, Daniel Barnes, Antonis Antoniou, Laura Fachal, Alison Dunning, Douglas Easton, Nicola Waddell, Joseph Rosenbluh, Andreas Moller, Georgia Chenevix-Trench, Juliet French, Stacey Edwards
Genome-wide association studies have identified 196 high confidence independent signals associated with breast cancer susceptibility. Variants within these signals frequently fall in distal regulatory DNA elements that control gene expression. We designed a Capture Hi-C array to enrich for chromatin interactions between the credible causal variants and target genes in six human mammary epithelial and breast cancer cell lines. We show that interacting regions are enriched for open chromatin, histone marks for active enhancers and transcription factors relevant to breast biology. We exploit this comprehensive resource to identify candidate target genes at 139 independent breast cancer risk signals, and explore the functional mechanism underlying altered risk at the 12q24 risk region. Our results demonstrate the power of combining genetics, computational genomics and molecular studies to rationalize the identification of key variants and candidate target genes at breast cancer GWAS signals.
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EllaMax0912: Our breast Capture Hi-C paper is finally out! @Edwards_Stace. We performed a dual capture to identify target genes of 139 #breastcancer #GWAS signals https://t.co/sIGbJ61fja @FachalLaura @MayaGhoussaini @alison_amd24 @antonis02 @db_1986 @QIMRBerghofer
EllaMax0912: Our Capture Hi-C paper for #breastcancer #postGWAS is finally out @Edwards_Stace. We used Peaky developed by @chr1swallace group to fine-map chromatin contacts and prioritise candidate causal variants at GWAS signals. https://t.co/4SLDYPXJEJ @loops_enhancers @generegulation
vaschetto_luis: Chromatin interactome mapping at 139 independent breast cancer risk signals https://t.co/BrpTQPYTaq
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Repository: pky
User: cqgd
Language: R
Stargazers: 2
Subscribers: 2
Forks: 2
Open Issues: 1
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Sample Sizes : [45]
Authors: 24
Total Words: 14207
Unqiue Words: 3666

0.0 Mikeys
#10. Homology-directed repair using transient CRISPR/Cpf1-geminiviral replicon in tomato
Tien Van Vu, Velu Sivankalyani, Eun-Jung Kim, Mil Thi Tran, Jihae Kim, Yeon Woo Sung, Duong Thi Hai Doan, Jae-Yean Kim
Genome editing via homology-directed repair (HDR) pathway in somatic plant cells was very inefficient compared to illegitimate repair by non-homologous end joining (NHEJ). Here, compared to a Cas9-based replicon system, we improved approximately 3-fold in the HDR-based genome editing efficiency via transient geminiviral replicon system equipping with CRISPR-LbCpf1 in tomato and obtained replicon-free, but with stable HDR alleles. Our work may pave a way for transgene-free rewriting of alleles of interest in asexually as well as sexually reproducing plants.
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biorxivpreprint: Homology-directed repair using transient CRISPR/Cpf1-geminiviral replicon in tomato https://t.co/u33rKEsKrV #bioRxiv
Jae_Yean: Our first MS of HDR project is online in preprint form: https://t.co/WWNoVXbWV0
Tien_V_Vu: RT @Jae_Yean: Our first MS of HDR project is online in preprint form: https://t.co/WWNoVXbWV0
DuongDoanMiche1: RT @biorxivpreprint: Homology-directed repair using transient CRISPR/Cpf1-geminiviral replicon in tomato https://t.co/u33rKEsKrV #bioRxiv
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Sample Sizes : [3]
Authors: 8
Total Words: 4928
Unqiue Words: 1703

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