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https://www.readbyqxmd.com/read/28934823/comprehensive-analysis-of-non-synonymous-natural-variants-of-g-protein-coupled-receptors
#1
Hee Ryung Kim, Nguyen Minh Duc, Ka Young Chung
G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs...
September 19, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28934500/a-synthetic-dna-binding-inhibitor-of-sox2-guides-human-induced-pluripotent-stem-cells-to-differentiate-into-mesoderm
#2
Junichi Taniguchi, Ganesh N Pandian, Takuya Hidaka, Kaori Hashiya, Toshikazu Bando, Kyeong Kyu Kim, Hiroshi Sugiyama
Targeted differentiation of human induced pluripotent stem cells (hiPSCs) using only chemicals would have value-added clinical potential in the regeneration of complex cell types including cardiomyocytes. Despite the availability of several chemical inhibitors targeting proteins involved in signaling pathways, no bioactive synthetic DNA-binding inhibitors, targeting key cell fate-controlling genes such as SOX2, are yet available. Here, we demonstrate a novel DNA-based chemical approach to guide the differentiation of hiPSCs using pyrrole-imidazole polyamides (PIPs), which are sequence-selective DNA-binding synthetic molecules...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934490/number-of-inadvertent-rna-targets-for-morpholino-knockdown-in-danio-rerio-is-largely-underestimated-evidence-from-the-study-of-ser-arg-rich-splicing-factors
#3
Marine Joris, Marie Schloesser, Denis Baurain, Marc Hanikenne, Marc Muller, Patrick Motte
Although the involvement of Ser/Arg-rich (SR) proteins in RNA metabolism is well documented, their role in vertebrate development remains elusive. We, therefore, elected to take advantage of the zebrafish model organism to study the SR genes' functions using the splicing morpholino (sMO) microinjection and the programmable site-specific nucleases. Consistent with previous research, we revealed discrepancies between the mutant and morphant phenotypes and we show that these inconsistencies may result from a large number of unsuspected inadvertent morpholino RNA targets...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934489/antisense-oligonucleotides-targeting-translation-inhibitory-elements-in-5-utrs-can-selectively-increase-protein-levels
#4
Xue-Hai Liang, Hong Sun, Wen Shen, Shiyu Wang, Joyee Yao, Michael T Migawa, Huynh-Hoa Bui, Sagar S Damle, Stan Riney, Mark J Graham, Rosanne M Crooke, Stanley T Crooke
A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934479/targeted-reconstruction-of-t-cell-receptor-sequence-from-single-cell-rna-seq-links-cdr3-length-to-t-cell-differentiation-state
#5
Shaked Afik, Kathleen B Yates, Kevin Bi, Samuel Darko, Jernej Godec, Ulrike Gerdemann, Leo Swadling, Daniel C Douek, Paul Klenerman, Eleanor J Barnes, Arlene H Sharpe, W Nicholas Haining, Nir Yosef
The T cell compartment must contain diversity in both T cell receptor (TCR) repertoire and cell state to provide effective immunity against pathogens. However, it remains unclear how differences in the TCR contribute to heterogeneity in T cell state. Single cell RNA-sequencing (scRNA-seq) can allow simultaneous measurement of TCR sequence and global transcriptional profile from single cells. However, current methods for TCR inference from scRNA-seq are limited in their sensitivity and require long sequencing reads, thus increasing the cost and decreasing the number of cells that can be feasibly analyzed...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934476/crystal-structure-of-an-engineered-hiv-specific-recombinase-for-removal-of-integrated-proviral-dna
#6
Gretchen Meinke, Janet Karpinski, Frank Buchholz, Andrew Bohm
As part of the HIV infection cycle, viral DNA inserts into the genome of host cells such that the integrated DNA encoding the viral proteins is flanked by long terminal repeat (LTR) regions from the retrovirus. In an effort to develop novel genome editing techniques that safely excise HIV provirus from cells, Tre, an engineered version of Cre recombinase, was designed to target a 34-bp sequence within the HIV-1 LTR (loxLTR). The sequence targeted by Tre lacks the symmetry present in loxP, the natural DNA substrate for Cre...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934464/recruitment-and-delivery-of-the-fission-yeast-rst2-transcription-factor-via-a-local-genome-structure-counteracts-repression-by-tup1-family-corepressors
#7
Ryuta Asada, Miki Umeda, Akira Adachi, Satoshi Senmatsu, Takuya Abe, Hiroshi Iwasaki, Kunihiro Ohta, Charles S Hoffman, Kouji Hirota
Transcription factors (TFs) determine the transcription activity of target genes and play a central role in controlling the transcription in response to various environmental stresses. Three dimensional genome structures such as local loops play a fundamental role in the regulation of transcription, although the link between such structures and the regulation of TF binding to cis-regulatory elements remains to be elucidated. Here, we show that during transcriptional activation of the fission yeast fbp1 gene, binding of Rst2 (a critical C2H2 zinc-finger TF) is mediated by a local loop structure...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934437/group-b-streptococcus-and-the-vaginal-microbiota
#8
Geoffrey H Rosen, Tara M Randis, Purnahamsi V Desai, Katherine J Sapra, Bing Ma, Pawel Gajer, Michael S Humphrys, Jacques Ravel, Shari E Gelber, Adam J Ratner
Background: Streptococcus agalactiae (group B Streptococcus [GBS]) is an important neonatal pathogen and emerging cause of disease in adults. The major risk factor for neonatal disease is maternal vaginal colonization. However, little is known about the relationship between GBS and vaginal microbiota. Methods: Vaginal lavage samples from nonpregnant women were tested for GBS, and amplicon-based sequencing targeting the 16S ribosomal RNA V3-V4 region was performed...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934418/systems-biotechnology-for-protein-production-in-pichia-pastoris
#9
Richard J Zahrl, David A Peña, Diethard Mattanovich, Brigitte Gasser
The methylotrophic yeast Pichia pastoris (syn. Komagataella spp.) is one of the most important production systems for heterologous proteins. After the first genome sequences were published in 2009, tremendous effort was made to establish systems-level analytical methods. Methylotrophic lifestyle was one of the most thoroughly investigated topics, studied at the levels of transcriptome, proteome and metabolic flux. Also the responses of P. pastoris to environmental stress conditions experienced during high cell density production processes were studied...
November 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28934373/formyl-peptide-derived-lipopeptides-disclose-differences-between-the-receptors-in-mouse-and-men-and-call-the-pepducin-concept-in-question
#10
Malene Winther, André Holdfeldt, Martina Sundqvist, Zahra Rajabkhani, Michael Gabl, Johan Bylund, Claes Dahlgren, Huamei Forsman
A pepducin is a lipopeptide containing a peptide sequence that is identical to one of the intracellular domains of the G-protein coupled receptor (GPCR) assumed to be the target. Neutrophils express two closely related formyl peptide receptors belonging to the family of GPCRs; FPR1 and FPR2 in human and their respective orthologue Fpr1 and Fpr2 in mouse. By applying the pepducin concept, we have earlier identified FPR2 activating pepducins generated from the third intracellular loop of FPR2. The third intracellular loop of FPR2 differs in two amino acids from that of FPR1, seven from Fpr2 and three from Fpr1...
2017: PloS One
https://www.readbyqxmd.com/read/28934318/identification-of-lag3-high-affinity-aptamers-by-ht-selex-and-conserved-motif-accumulation-cma
#11
Mario Martínez Soldevilla, Sandra Hervas, Helena Villanueva, Teresa Lozano, Obdulia Rabal, Julen Oyarzabal, Juan José Lasarte, Maurizio Bendandi, Susana Inoges, Ascensión López-Díaz de Cerio, Fernando Pastor
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases...
2017: PloS One
https://www.readbyqxmd.com/read/28934310/sanger-and-next-generation-sequencing-data-for-characterization-of-ctl-epitopes-in-archived-hiv-1-proviral-dna
#12
Camille Tumiotto, Lionel Riviere, Pantxika Bellecave, Patricia Recordon-Pinson, Alice Vilain-Parce, Gwenda-Line Guidicelli, Hervé Fleury
One of the strategies for curing viral HIV-1 is a therapeutic vaccine involving the stimulation of cytotoxic CD8-positive T cells (CTL) that are Human Leucocyte Antigen (HLA)-restricted. The lack of efficiency of previous vaccination strategies may have been due to the immunogenic peptides used, which could be different from a patient's virus epitopes and lead to a poor CTL response. To counteract this lack of specificity, conserved epitopes must be targeted. One alternative is to gather as many data as possible from a large number of patients on their HIV-1 proviral archived epitope variants, taking into account their genetic background to select the best presented CTL epitopes...
2017: PloS One
https://www.readbyqxmd.com/read/28934262/effects-of-eimeria-tenella-infection-on-chicken-caecal-microbiome-diversity-exploring-variation-associated-with-severity-of-pathology
#13
Sarah E Macdonald, Matthew J Nolan, Kimberley Harman, Kay Boulton, David A Hume, Fiona M Tomley, Richard A Stabler, Damer P Blake
Eimeria species cause the intestinal disease coccidiosis, most notably in poultry. While the direct impact of coccidiosis on animal health and welfare is clear, its influence on the enteric microbiota and by-stander effects on chicken health and production remains largely unknown, with the possible exception of Clostridium perfringens (necrotic enteritis). This study evaluated the composition and structure of the caecal microbiome in the presence or absence of a defined Eimeria tenella challenge infection in Cobb500 broiler chickens using 16S rRNA amplicon sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28934251/new-experimental-model-for-single-liver-lobe-hyperthermia-in-small-animals-using-non-directional-microwaves
#14
Ionuț Tudorancea, Vlad Porumb, Alexandru Trandabăţ, Decebal Neaga, Bogdan Tamba, Radu Iliescu, Gabriel M Dimofte
PURPOSE: Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. MATERIALS AND METHODS: A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage...
2017: PloS One
https://www.readbyqxmd.com/read/28934224/identification-and-analysis-of-differentially-expressed-long-non-coding-rnas-between-multiparous-and-uniparous-goat-capra-hircus-ovaries
#15
Yinghui Ling, Lina Xu, Long Zhu, Menghua Sui, Qi Zheng, Wenyong Li, Yong Liu, Fugui Fang, Xiaorong Zhang
Long non-coding RNAs (lncRNAs) play important roles in almost all biological processes. However, there is little information on the effects of lncRNAs on ovulation and lambing rates. In the present study, we used high-throughput RNA sequencing to identify differentially expressed lncRNAs between the ovaries of multiparous (Mul) and uniparous (Uni) Anhui White goats. Among the 107,255,422 clean reads, 183,754 lncRNAs were significantly differentially expressed between the Uni and Mul. Among them, 455 lncRNAs were co-expressed between the two samples, whereas, 157,523 lncRNAs were uniquely expressed in the Uni, and 25,776 uniquely lncRNAs were expressed in the Mul...
2017: PloS One
https://www.readbyqxmd.com/read/28934144/the-recognition-of-calmodulin-to-the-target-sequence-of-calcineurin-a-novel-binding-mode
#16
Chia-Lin Chyan, Deli Irene, Sin-Mao Lin
Calcineurin (CaN) is a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in the presence of minimal levels of Ca(2+), but the enzyme is inactive until activated by CaM. Upon binding to CaM, CaN then undergoes a conformational rearrangement, the auto inhibitory domain is displaced and thus allows for full activity...
September 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28934125/optimized-mtdna-control-region-primer-extension-capture-analysis-for-forensically-relevant-samples-and-highly-compromised-mtdna-of-different-age-and-origin
#17
Mayra Eduardoff, Catarina Xavier, Christina Strobl, Andrea Casas-Vargas, Walther Parson
The analysis of mitochondrial DNA (mtDNA) has proven useful in forensic genetics and ancient DNA (aDNA) studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR) is commonly sequenced using established Sanger-type Sequencing (STS) protocols involving fragment sizes down to approximately 150 base pairs (bp). Recent developments include Massively Parallel Sequencing (MPS) of (multiplex) PCR-generated libraries using the same amplicon sizes...
September 21, 2017: Genes
https://www.readbyqxmd.com/read/28933620/sequential-processing-deficit-as-a-shared-persisting-biomarker-in-dyslexia-and-childhood-apraxia-of-speech
#18
Beate Peter, Hope Lancaster, Caitlin Vose, Kyle Middleton, Carol Stoel-Gammon
The purpose of this study was to investigate the hypothesis that individuals with dyslexia and individuals with childhood apraxia of speech share an underlying persisting deficit in processing sequential information. Levels of impairment (sensory encoding, memory, retrieval, and motor planning/programming) were also investigated. Participants were 22 adults with dyslexia, 10 adults with a probable history of childhood apraxia of speech (phCAS), and 22 typical controls. All participants completed nonword repetition, multisyllabic real word repetition, and nonword decoding tasks...
September 21, 2017: Clinical Linguistics & Phonetics
https://www.readbyqxmd.com/read/28933597/microrna-1297-inhibits-the-growth-and-metastasis-of-colorectal-cancer-by-suppressing-cyclin-d2-expression
#19
Yanan Wang, Jinfang Xue, Haoyu Kuang, Xiaojun Zhou, Liya Liao, Fang Yin
microRNAs (miR) can potentially be used for categorizing the various subtypes of colorectal cancer (CRC) and predicting a patient's response to treatment with traditional anti-CRC therapies. We investigated how miR-1297 and its potential target molecule cyclin D2 (CCND2) might affect the progression of CRC. Thirty-two pairs of CRC specimens and corresponding samples of para-tumor tissue were collected and examined for their levels of miR-1297 and CCND2 expression. We also examined miR-1297 and CCND2 expression in cultured SW480 cells...
September 21, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28933584/circular-rna-hsa_circ_0001982-promotes-breast-cancer-cell-carcinogenesis-through-decreasing-mir-143
#20
Yi-Yin Tang, Ping Zhao, Tian-Ning Zou, Jia-Jun Duan, Rong Zhi, Si-Yuan Yang, De-Chun Yang, Xiao-Li Wang
Circular RNAs (circRNAs) are a type of noncoding RNAs generated from back-splicing, which have been verified to mediate multiple tumorigenesis. With the development of high-throughput sequencing, massive circRNAs are discovered in tumorous tissue. However, the potential physiological effect of circRNAs in breast cancer is still unknown. The purpose of this study is to investigate the expression profile of circRNA in breast cancer tissue and explore the in-depth regulatory mechanism in breast cancer tumorigenesis...
September 21, 2017: DNA and Cell Biology
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