April 21, 2020  |  

Precise temporal regulation of Dux is important for embryo development.

Zygotic genome activation (ZGA) following fertilization is accomplished through a process termed the maternal-to-zygotic transition, during which the maternal RNAs and proteins are degraded and zygotic genome is transcriptionally activated.1 In mice, minor ZGA occurs from S phase of the zygote to G1 phase of the two-cell (2C) embryo, while major ZGA takes place during the middle-to-late 2C stage with a burst of transcription of totipotent cleavage stage-specific genes and retrotransposons.2Dux has been recently identified and considered as a master inducer that regulates the ZGA process.3–5Dux can directly bind and robustly activate 2C stage-specific ZGA transcripts and convert mouse embryonic stem cells (mESCs) to a 2C-like state with unique features that resembles the 2C embryos.4Intriguingly, ~20% embryos with zygotic depletion of Dux unexpectedly reached morula or blastocyst stage even though defective ZGA program was detected.


April 21, 2020  |  

Chryseobacterium mulctrae sp. nov., isolated from raw cow’s milk.

A Gram-stain-negative bacterial strain, designated CA10T, was isolated from bovine raw milk sampled in Anseong, Republic of Korea. Cells were yellow-pigmented, aerobic, non-motile bacilli and grew optimally at 30?°C and pH 7.0 on tryptic soy agar without supplementation of NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain CA10T belonged to the genus Chryseobacterium, family Flavobacteriaceae, and was most closely related to Chryseobacterium indoltheticum ATCC 27950T (98.75?% similarity). The average nucleotide identity and digital DNA-DNA hybridization values of strain CA10T were 94.4 and 56.9?%, respectively, relative to Chryseobacterium scophthalmum DSM 16779T, being lower than the cut-off values of 95-96?and 70?%, respectively. The predominant respiratory quinone was menaquinone-6; major polar lipid, phosphatidylethanolamine; major fatty acids, iso-C15?:?0, summed feature 9 (iso-C17?:?1?9c and/or C16?:?0 10-methyl), summed feature 3 (iso-C15?:?0 2-OH and/or C16?:?1?7c) and iso-C17?:?0 3-OH. The results of physiological, chemotaxonomic and biochemical analyses suggested that strain CA10T is a novel species of genus Chryseobacterium, for which the name Chryseobacterium mulctrae sp. nov. is proposed. The type strain is CA10T (=KACC 21234T=JCM 33443T).


April 21, 2020  |  

Allopseudarcicella aquatilis gen. nov., sp. nov., isolated from freshwater.

A Gram-stain-negative, rod-shaped and red-pigmented strain, HME7025T, was isolated from freshwater sampled in the Republic of Korea. Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain HME7025T formed a lineage within the family Cytophagaceae of the phylum Bacteroidetes. Strain HME7025T was closely related to the genera Pseudarcicella, Arcicella and Flectobacillus. The 16S rRNA gene sequence similarity values of strain HME7025T were under 94.5?% to its closest phylogenetic neighbours. The major fatty acids of strain HME7025T were iso-C15?:?0 (41.9?%), summed feature 3 (comprising C16?:?1?7c and/or C16?:?1?6c; 12.2?%) and anteiso-C15?:?0 (10.8?%). The major respiratory quinone was menaquinone-7. The major polar lipids were phosphatidylethanolamine, two unidentified aminophospholipids and one unidentified polar lipid. The DNA G+C content of strain HME7025T was 37.9?mol%. On the basis of the evidence presented in this study, strain HME7025T represents a novel species of a novel genus within the family Cytophagaceae, for which the name Allopseudarcicella aquatilis gen. nov., sp. nov. is proposed. The type strain is HME7025T (=KCTC 23617T=CECT 7957T).


April 21, 2020  |  

The complete genome sequence and comparative genome analysis of the multi-drug resistant food-borne pathogen Bacillus cereus.

Bacillus cereus is an opportunistic human pathogen causing food-borne gastrointestinal infections and non-gastrointestinal infections worldwide. The strain B. cereus FORC_013 was isolated from fried eel. Its genome was completely sequenced by PacBio technology, analyzed and compared with other complete genome sequences of Bacillus to elucidate the distinct pathogenic features of the strain isolated in South Korea. Genomic analysis revealed pathogenesis and host immune evasion-associated genes encoding tissue-destructive exoenzymes, and pore-forming toxins. In particular, tissue-destructive (hemolysin BL, nonhaemolytic enterotoxins) and cytolytic proteins (cytolysin) were observed in the genome, which damage the plasma membrane of the epithelial cells of the small intestine causing diarrhea in humans. Capsule biosynthesis gene found in both chromosome and plasmid, which might be responsible for protecting the pathogen from the host cell immune defense system after host cell invasion. Additionally, multidrug resistance operon and efflux pumps were identified in the genome, which play a prominent role in multi-antibiotic resistance. Comparative phylogenetic tree analysis of the strain FORC_013 and other B. cereus strains revealed that the closest strains are ATCC 14579 and B4264. This genome data can be used to identify virulence factors that can be applied for the development of novel biomarkers for the rapid detection of this pathogen in foods.Copyright © 2018. Published by Elsevier Inc.


April 21, 2020  |  

A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild-derived and classical inbred mouse strains.

The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic diversity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflect differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ), and diversity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ, and PWD/PhJ), and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the International Immunogenetics Information System. In contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. In contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of diversity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand inter-strain variation in models of antibody-mediated disease. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.


April 21, 2020  |  

Potent LpxC Inhibitors with In Vitro Activity Against Multi-Drug Resistant Pseudomonas aeruginosa.

New drugs with novel mechanisms of resistance are desperately needed to address both community and nosocomial infections due to Gram-negative bacteria. One such potential target is LpxC, an essential enzyme that catalyzes the first committed step of Lipid A biosynthesis. Achaogen conducted an extensive research campaign to discover novel LpxC inhibitors with activity against Pseudomonas aeruginosa We report here the in vitro antibacterial activity and pharmacodynamics of ACHN-975, the only molecule from these efforts and the first ever LpxC inhibitor to be evaluated in Phase 1 clinical trials. In addition, we describe the profile of three additional LpxC inhibitors that were identified as potential lead molecules. These efforts did not produce an additional development candidate with a sufficiently large therapeutic window and the program was subsequently terminated.Copyright © 2019 American Society for Microbiology.


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