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https://www.readbyqxmd.com/read/29141238/rationale-redesign-of-type-iii-secretion-systems-toward-the-development-of-non-pathogenic-e-coli-for-in-vivo-delivery-of-therapeutic-payloads
#1
REVIEW
Coral González-Prieto, Cammie F Lesser
Transkingdom secretion systems that bacteria use to inject proteins directly into the cytosol of mammalian host cells play an essential role in the virulence of many Gram-negative bacterial pathogens. Current efforts are underway to repurpose these machines as novel therapeutics; type III secretion systems as vectors for the delivery of proteins of therapeutic value including heterologous antigens for vaccine development and type IV secretion systems as vectors for DNA. While initial studies focused on the use of attenuated or replication incompetent pathogens, the recent development of non-pathogenic Escherichia coli that encode programmable type III secretion systems expands possibilities for the in vivo directed delivery of therapeutic payloads...
November 12, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29141206/role-of-the-pif1-pcna-complex-in-pol-%C3%AE-dependent-strand-displacement-dna-synthesis-and-break-induced-replication
#2
Olga Buzovetsky, Youngho Kwon, Nhung Tuyet Pham, Claire Kim, Grzegorz Ira, Patrick Sung, Yong Xiong
The S. cerevisiae Pif1 helicase functions with DNA polymerase (Pol) δ in DNA synthesis during break-induced replication (BIR), a conserved pathway responsible for replication fork repair and telomere recombination. Pif1 interacts with the DNA polymerase processivity clamp PCNA, but the functional significance of the Pif1-PCNA complex remains to be elucidated. Here, we solve the crystal structure of PCNA in complex with a non-canonical PCNA-interacting motif in Pif1. The structure guides the construction of a Pif1 mutant that is deficient in PCNA interaction...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29139595/structure-and-electronic-properties-of-unnatural-base-pairs-role-of-dispersion-interactions
#3
Ayan Datta, Sk Jahiruddin, Nilangshu Mandal
Recent report of the success of unnatural base pairs (UBPs) like d5SICS-dNaM to be incorporated within the gene sequence and get replicated with DNA is an important milestone in synthetic biology. Followed by this, several other UBPs like dTPT3-dNaM, dTPT3-dFIMO, dTPT3-IMO, dTPT3-FEMO, FTPT3-NaM, FTPT3-FIMO, FTPT3-IMO, FTPT3-FEMO, have demonstrated similar or better retention and fidelity inside cell. Among these base pairs, dNaM-dTPT3 has been optimized to be a better fit inside a pAIO plasmid. Based on both implicit and explicit dispersion corrected density functional theory (DFT) calculations, we show that although the set of UBPs are significantly diverse in their elemental and structural configuration they do share a common trait of favoring a slipped parallel stacked dimer arrangement...
November 15, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29139335/shprh-as-a-new-player-in-ribosomal-rna-transcription-and-its-potential-role-in-homeostasis-of-ribosomal-dna-repeats
#4
Deokjae Lee, Jun Hong Park, Shinseog Kim, Seon-Gyeong Lee, Kyungjae Myung
There are hundreds of copies of rDNA repeats in mammalian chromosomes and the ratio of active, poised, or inactive rDNA is regulated in epigenetic manners. Recent studies demonstrated that a post-DNA replication repair enzyme, SHPRH affects rRNA transcription by recognizing epigenetic markers on rDNA promoters and unveiled potential links between DNA repair and ribosome biogenesis (1) . This study suggests that SHPRH could be a link between mTOR-mediated epigenetic regulations and rRNA transcription, while concomitantly affecting genomic integrity...
November 15, 2017: Transcription
https://www.readbyqxmd.com/read/29139200/allosteric-mechanism-of-quinoline-inhibitors-for-hiv-rt-associated-rnase-with-md-simulation-and-dynamics-fluctuation-network
#5
Yi Cai, Hao Liu, Haifeng Chen
The human immunodeficiency virus (HIV) is a retrovirus which infects T lymphocyte of human body and causes Immunodeficiency. Reverse transcriptase inhibitors (RTIs) can inhibit some functions of RT, preventing virus synthesis (double-stranded DNA), so that HIV virus replication can be reduced. Experimental results indicate a series of benzimidazole-based inhibitors which target HIV RT-associate RNase to inhibit the reverse transcription of HIV virus. However, the allosteric mechanism is still unclear. Here, molecular dynamics simulations and dynamics fluctuation network analysis were used to reveal the binding mode between the inhibitors and RT-associate RNase...
November 15, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29139108/a-3-untranslated-region-polymorphism-rs2304277-in-the-dna-repair-pathway-gene-ogg1-is-a-novel-risk-modulator-for-urothelial-bladder-carcinoma
#6
Tayyaba Ahmed, Saira Nawaz, Rabia Noreen, Kashif Sardar Bangash, Abdur Rauf, Muhammad Younis, Khursheed Anwar, Muhammad Athar Khawaja, Maleeha Azam, Abid Ali Qureshi, Saeed Akhter, Lambertus A Kiemeney, Raheel Qamar, Syeda Hafiza Benish Ali
Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)GG = 3...
November 15, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/29138946/semiotic-systems-with-duality-of-patterning-and-the-issue-of-cultural-replicators
#7
Gerhard Schaden, Cédric Patin
Two major works in recent evolutionary biology have in different ways touched upon the issue of cultural replicators in language, namely Dawkins' Selfish Gene and Maynard Smith and Szathmáry's Major Transitions in Evolution. In the latter, the emergence of language is referred to as the last major transition in evolution (for the time being), a claim we argue to be derived from a crucial property of language, called Duality of Patterning. Prima facie, this property makes natural language look like a structural equivalent to DNA, and its peer in terms of expressive power...
November 14, 2017: History and Philosophy of the Life Sciences
https://www.readbyqxmd.com/read/29138843/investigation-of-candidate-genes-and-mechanisms-underlying-postmenopausal-osteoporosis-using-bioinformatics-analysis
#8
Xiaozhong Zhu, Zhiyuan Wang, Yanxun Zhao, Chao Jiang
The present study aimed to determine candidate genes, chemicals and mechanisms underlying postmenopausal osteoporosis (PMOP). A gene expression profile (accession no. GSE68303), which included 12 tissue samples from ovariectomized mice (OVX group) and 11 normal tissue samples from sham surgery mice (control group), was downloaded from the Gene Expression Omnibus database. The identification of differentially expressed genes (DEGs), and Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses, was performed, followed by an investigation of protein‑protein interactions (PPI), PPI modules, transcription factors (TFs) and chemicals...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138440/structural-basis-for-dna-recognition-of-a-single-stranded-dna-binding-protein-from-enterobacter-phage-enc34
#9
Elina Cernooka, Janis Rumnieks, Kaspars Tars, Andris Kazaks
Modern DNA sequencing capabilities have led to the discovery of a large number of new bacteriophage genomes, which are a rich source of novel proteins with an unidentified biological role. The genome of Enterobacter cancerogenus bacteriophage Enc34 contains several proteins of unknown function that are nevertheless conserved among distantly related phages. Here, we report the crystal structure of a conserved Enc34 replication protein ORF6 which contains a domain of unknown function DUF2815. Despite the low (~15%) sequence identity, the Enc34 ORF6 structurally resembles the gene 2...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138305/manipulating-the-bacterial-cell-cycle-and-cell-size-by-titrating-the-expression-of-ribonucleotide-reductase
#10
Manlu Zhu, Xiongfeng Dai, Weilun Guo, Zengxiang Ge, Mingxuan Yang, Haikuan Wang, Yi-Ping Wang
Understanding how bacteria coordinate growth with cell cycle events to maintain cell size homeostasis remains a grand challenge in biology. The period of chromosome replication (C period) is a key stage in the bacterial cell cycle. However, the mechanism of in vivo regulation of the C period remains unclear. In this study, we found that titration of the expression of ribonucleotide reductase (RNR), which changes the intracellular deoxynucleoside triphosphate (dNTP) pools, enables significant perturbations of the C period, leading to a substantial change in cell size and DNA content...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29138037/genetic-predisposition-to-preeclampsia-is-conferred-by-fetal-dna-variants-near-flt1-a-gene-involved-in-the-regulation-of-angiogenesis
#11
Kathryn J Gray, Richa Saxena, S Ananth Karumanchi
Preeclampsia risk is influenced by both the mother's genetic background, as well as the genetics of her fetus; however, the specific genes responsible for conferring preeclampsia risk have largely remained elusive. Evidence that preeclampsia has a genetic predisposition was first detailed in the early 1960's, and overall preeclampsia heritability is estimated at ∼55%. Many traditional gene discovery approaches have been employed to investigate the specific genes that contribute to preeclampsia risk, but these have largely not been successful or reproducible...
November 11, 2017: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29137822/dnmt1-is-associated-with-cell-cycle-and-dna-replication-gene-sets-in-diffuse-large-b-cell-lymphoma
#12
Suet Kee Loo, Suzina Sheikh Ab Hamid, Mustaffa Musa, Kah Keng Wong
Dysregulation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) is associated with the pathogenesis of various types of cancer. It has been previously shown that DNMT1 is frequently expressed in diffuse large B-cell lymphoma (DLBCL), however its functions remain to be elucidated in the disease. In this study, we gene expression profiled (GEP) shRNA targeting DNMT1(shDNMT1)-treated germinal center B-cell-like DLBCL (GCB-DLBCL)-derived cell line (i.e. HT) compared with non-silencing shRNA (control shRNA)-treated HT cells...
October 9, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#13
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#14
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136422/transmission-as-a-basic-process-in-microbial-biology-lwoff-award-prize-lecture
#15
Fernando Baquero
Transmission is a basic process in biology and evolution, as it communicates different biological entities within and across hierarchical levels (from genes to holobionts) both in time and space. Vertical descent, replication, is transmission of information across generations (in the time dimension), and horizontal descent is transmission of information across compartments (in the space dimension). Transmission is essentially a communication process that can be studied by analogy of the classic information theory, based on 'emitters', 'messages' and 'receivers'...
November 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/29135113/minichromosome-maintenance-mcm-protein-4-overexpression-is-a-potential-prognostic-marker-for-laryngeal-squamous-cell-carcinoma
#16
Jianfeng Han, Meng Lian, Jugao Fang, Honggang Liu, Ru Wang, Jie Zhai, Yi Fan Yang, Ling Fen, Qian Shi, Hong Zhi Ma, Juan Sun, Zhihong Ma
PURPOSE: The minichromosomal maintenance (MCM) proteins are involved in the initiation and DNA replication. The role of MCM4 remains to be elucidated. The purpose of this study was to investigate the effects of MCM4 in laryngeal squamous cell carcinoma (LSCC) cell growth and apoptosis. METHODS: LSCC cell line UMSCC 5 was used in this study. The small interfering RNA (siRNA) of MCM 4 gene was used to identify the effects of MCM4 on the proliferation and apoptosis using methylimidazole tetrazolium (MTT) assay and flow-cytometry, respectively...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29135110/pathway-cross-talk-network-strategy-reveals-key-pathways-in-non-small-cell-lung-cancer
#17
Meng-Li Zheng, Nai-Kang Zhou, De-Liang Huang, Cheng-Hua Luo
PURPOSE: The purpose of this study was to explore the pathway cross-talks and key pathways in non-small cell lung cancer (NSCLC) to better understand the underlying pathological mechanism. METHODS: Integrated gene expression data, pathway data and protein-protein interaction (PPI) data were assessed to identify the pathway regulatory interactions in NSCLC, and constructed the background and disease pathway crosstalk networks, respectively. In this work, the attractor method was implemented to identified the differential pathways, and the rank product (RP) algorithm was used to determine the importance of pathways...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29134604/muprints-and-whole-genome-insertion-scans-methods-for-investigating-chromosome-accessibility-and-dna-dynamics-using-bacteriophage-mu
#18
N Patrick Higgins
Bacteriophage Mu infects a broad range of gram-negative bacteria. After infection, Mu amplifies its DNA through a coupled transposition/replication cycle that inserts copies of Mu throughout all domains of the folded chromosome. Mu has the most relaxed target specificity of the known transposons (Manna et al., J Bacteriol 187: 3586-3588, 2005) and the Mu DNA packaging process, called "headful packaging", incorporates 50-150 bp of host sequences covalently bound to its left end and 2 kb of host DNA linked to its right end into a viral capsid...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29134599/phage-genome-annotation-using-the-rast-pipeline
#19
Katelyn McNair, Ramy Karam Aziz, Gordon D Pusch, Ross Overbeek, Bas E Dutilh, Robert Edwards
Phages are complex biomolecular machineries that have to survive in a bacterial world. Phage genomes show many adaptations to their lifestyle such as shorter genes, reduced capacity for redundant DNA sequences, and the inclusion of tRNAs in their genomes. In addition, phages are not free-living, they require a host for replication and survival. These unique adaptations provide challenges for the bioinformatics analysis of phage genomes. In particular, ORF calling, genome annotation, noncoding RNA (ncRNA) identification, and the identification of transposons and insertions are all complicated in phage genome analysis...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29134476/aminoglycoside-damage-and-hair-cell-regeneration-in-the-chicken-utricle
#20
Mirko Scheibinger, Daniel C Ellwanger, C Eduardo Corrales, Jennifer S Stone, Stefan Heller
In this study, we present a systematic characterization of hair cell loss and regeneration in the chicken utricle in vivo. A single unilateral surgical delivery of streptomycin caused robust decline of hair cell numbers in striolar as well as extrastriolar regions, which in the striola was detected very early, 6 h post-insult. During the initial 12 h of damage response, we observed global repression of DNA replication, in contrast to the natural, mitotic hair cell production in undamaged control utricles...
November 13, 2017: Journal of the Association for Research in Otolaryngology: JARO
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