keyword
https://read.qxmd.com/read/38546111/functional-characterization-of-the-niemann-pick-c2-protein-bdionpc2b-in-the-parasitic-wasp-baryscapus-dioryctriae-chalcidodea-eulophidae
#1
JOURNAL ARTICLE
Qi Chen, Qingxin Liu, Yuanxu Chen, Lin Du, Xiaoyan Zhu, Yi Yang, Jingyi Zhao, Zizhuo Wang, Liwen Song, Jing Li, Bingzhong Ren
Reverse chemical ecology has been widely applied for the functional characterization of olfactory proteins in various arthropods, but few related studies have focused on parasitic wasps. Here, the odorant carrier Niemann-Pick C2 protein of Baryscapus dioryctriae (BdioNPC2b) was studied in vitro and in vivo. Ligand binding analysis revealed that BdioNPC2b most strongly bound to 2-butyl-2-octenal and which compound could elicit an EAG response and attracted B. dioryctriae adults. Moreover, this odorant attractant significantly improved the reproductive efficiency of B...
March 28, 2024: Journal of Agricultural and Food Chemistry
https://read.qxmd.com/read/38545858/interlaboratory-validation-of-the-toxtracker-assay-an-in-vitro-reporter-assay-for-mechanistic-genotoxicity-assessment
#2
JOURNAL ARTICLE
Giel Hendriks, Els Adriaens, Ashley Allemang, Julie Clements, Gabrielle Cole, Remco Derr, Maria Engel, Annie Hamel, Darren Kidd, Stephanie Kellum, Tomomi Kiyota, Abby Myhre, Valerie Naëssens, Stefan Pfuhler, Marise Roy, Raja Settivari, Maik Schuler, Andreas Zeller, Jan van Benthem, Philippe Vanparys, David Kirkland
ToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode-of-action (MoA), thereby supporting discrimination of direct-acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non-genotoxic compounds...
March 28, 2024: Environmental and Molecular Mutagenesis
https://read.qxmd.com/read/38543745/deciphering-the-role-of-post-translational-modifications-and-cellular-location-of-hepatitis-delta-virus-hdv-antigens-in-hdv-mediated-liver-damage-in-mice
#3
JOURNAL ARTICLE
Sheila Maestro, Nahia Gomez-Echarte, Gracian Camps, Carla Usai, Cristina Olagüe, Africa Vales, Rafael Aldabe, Gloria Gonzalez-Aseguinolaza
Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adeno-associated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investigate the molecular aspects of HDV and associated liver damage. For the purpose of this study, we generated HDV genomes modified by site-directed mutagenesis aimed to (i) prevent some post-translational modifications of HDV antigens (HDAgs) such as large-HDAg (L-HDAg) isoprenylation or short-HDAg (S-HDAg) phosphorylation; (ii) alter the localization of HDAgs within the subcellular compartments; and (iii) inhibit the right conformation of the delta ribozyme...
February 28, 2024: Viruses
https://read.qxmd.com/read/38543569/enhanced-heat-resistance-in-morchella-eximia-by-atmospheric-and-room-temperature-plasma
#4
JOURNAL ARTICLE
Qin Zhang, Junbin Lin, Junjie Yan, Renyun Miao, Rencai Feng, Ying Gan, Bingcheng Gan
This study focuses on optimizing the mutagenesis process for Morchella eximia (Mel-7) mycelia through atmospheric and room temperature plasma (ARTP) mutation and explores the resultant thermal adaptability and physiological responses of mutant strains. This research demonstrated a clear relationship between ARTP mutagenesis exposure duration and lethality rate, indicating that an exposure time of 40 s resulted in the optimal balance of inducing mutations without causing excessive mortality. Additionally, this study established 43 °C as the ideal screening temperature for identifying mutant strains with enhanced heat resistance, as this temperature significantly challenges the mycelia while allowing thermotolerant strains to be distinguishable...
March 5, 2024: Microorganisms
https://read.qxmd.com/read/38543064/demethyleneberberine-alleviates-pulmonary-fibrosis-through-disruption-of-usp11-deubiquitinating-grem1
#5
JOURNAL ARTICLE
Chuang Ge, Mengsheng Huang, Yanhong Han, Chang Shou, Dongyin Li, Yubin Zhang
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic interstitial lung disease. Intricate pathogenesis of pulmonary fibrosis and only two approved medications with side effects and high cost bring us the challenge of fully understanding this lethal disease and urgency to find more safe and low-cost therapeutic alternatives. PURPOSE: Demethyleneberberine (DMB) has been demonstrated to have various anti-inflammatory, antioxidant, antifibrosis and anti-cancer bioactivities...
February 22, 2024: Pharmaceuticals
https://read.qxmd.com/read/38543033/characterisation-of-modular-polyketide-synthases-designed-to-make-pentaene-analogues-of-amphotericin-b
#6
JOURNAL ARTICLE
Yuhao Song, Mark Hogan, Jimmy Muldoon, Paul Evans, Patrick Caffrey
Glycosylated polyene macrolides are important antifungal agents that are produced by many actinomycete species. Development of new polyenes may deliver improved antibiotics. Here, Streptomyces nodosus was genetically re-programmed to synthesise pentaene analogues of the heptaene amphotericin B. These pentaenes are of interest as surrogate substrates for enzymes catalysing unusual, late-stage biosynthetic modifications. The previous deletion of amphotericin polyketide synthase modules 5 and 6 generated S. nodosus M57, which produces an inactive pentaene...
March 21, 2024: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/38542484/rationally-designed-novel-antimicrobial-peptides-targeting-chitin-synthase-for-combating-soybean-phytophthora-blight
#7
JOURNAL ARTICLE
Yue Ran, Kiran Shehzadi, Jian-Hua Liang, Ming-Jia Yu
Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens' quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact...
March 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38540936/aviation-mutagenesis-alters-the-content-of-volatile-compounds-in-dahongpao-camellia-sinensis-leaves-and-improves-tea-quality
#8
JOURNAL ARTICLE
Jianghua Ye, Qi Zhang, Pengyuan Cheng, Yuhua Wang, Jishuang Zou, Shaoxiong Lin, Mingzhe Li, Miao Jia, Yiling Chen, Xiaoli Jia, Haibin Wang
Aviation mutagenesis is a fast and efficient breeding method. In this study, we analyzed the effect of aviation mutagenesis on volatile compounds and odor characteristics in Dahongpao fresh leaves and gross tea for the first time. The results showed that aviation mutagenesis significantly increased the total volatile compounds of Dahongpao fresh leaves and gross tea. Aviation mutagenesis most critically significantly increased the content of beta-myrcene in Dahongpao fresh leaves, prompting its conversion to beta-pinene, cubebol, beta-phellandrene, zingiberene, ( Z , Z )-3,6-nonadienal, and 6-pentyloxan-2-one after processing, which in turn enhanced the fruity, green, spicy, and woody odor characteristics of the gross tea...
March 20, 2024: Foods (Basel, Switzerland)
https://read.qxmd.com/read/38540914/-lactiplantibacillus-plantarum-a72-a-strain-with-antioxidant-properties-obtained-through-artp-mutagenesis-affects-caenorhabditis-elegans-anti-aging
#9
JOURNAL ARTICLE
Sibo Zou, Qi Wu, Zhigao Li, Sufang Zhang, Liang Dong, Yingxi Chen, Yiwei Dai, Chaofan Ji, Huipeng Liang, Xinping Lin
This research endeavored to elucidate the antioxidant attributes of lactic acid bacteria, specifically their impact on anti-aging and lifespan augmentation in Caenorhabditis elegans . The study focused on Lactiplantibacillus plantarum A72, identified through ARTP mutagenesis for its potent antioxidant properties. In vitro analysis affirmed its free radical neutralizing capacity. In C. elegans , the strain not only extended the lifespan by 25.13% and amplified motility 2.52-fold, but also maintained reproductive capabilities...
March 19, 2024: Foods (Basel, Switzerland)
https://read.qxmd.com/read/38539865/8-oxog-dependent-regulation-of-global-protein-responses-leads-to-mutagenesis-and-stress-survival-in-bacillus-subtilis
#10
JOURNAL ARTICLE
Lissett E Martínez, Gerardo Gómez, Norma Ramírez, Bernardo Franco, Eduardo A Robleto, Mario Pedraza-Reyes
The guanine oxidized (GO) system of Bacillus subtilis , composed of the YtkD (MutT), MutM and MutY proteins, counteracts the cytotoxic and genotoxic effects of the oxidized nucleobase 8-OxoG. Here, we report that in growing B. subtilis cells, the genetic inactivation of GO system potentiated mutagenesis (HPM), and subsequent hyperresistance, contributes to the damaging effects of hydrogen peroxide (H2 O2 ) (HPHR). The mechanism(s) that connect the accumulation of the mutagenic lesion 8-OxoG with the ability of B...
March 8, 2024: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/38537722/high-throughput-mutagenesis-and-screening-approach-for-the-identification-of-drug-resistant-mutations-in-the-rifampicin-resistance-determining-region-of-mycobacteria
#11
JOURNAL ARTICLE
Hui Zhao, Jiachen Li, Siyuan Feng, Lin Xu, Bin Yan, Chengjuan Li, Meisong Li, Yaxuan Wang, Yaxin Li, Lujie Liang, Dianrong Zhou, Jia Wan, Wenli Wang, Guo-Bao Tian, Bing Gu, Xi Huang
Rifampicin is the most powerful first-line antibiotic for tuberculosis, which is caused by Mycobacterium tuberculosis. Although accumulating evidence from sequencing data of clinical M. tuberculosis isolates suggested that mutations in the rifampicin-resistance-determining region (RRDR) are strongly associated with rifampicin resistance, the comprehensive characterization of RRDR polymorphisms that confer this resistance remains challenging. By incorporating I-SceI sites for I-SceI-based integrant removal and utilizing an L5 swap strategy, we efficiently replaced the integrated plasmid with alternative alleles, making mass allelic exchange feasible in mycobacteria...
March 25, 2024: International Journal of Antimicrobial Agents
https://read.qxmd.com/read/38537598/ph-dependence-of-hsf1-trimerization-is-shaped-by-intramolecular-interactions
#12
JOURNAL ARTICLE
Bo-Hee Choi, Chang-Ju Lee, Tae Hwan Kim, David Nahm-Joon Kim, Young-Shang Park, Jeong-Mo Choi, Jang-Su Park
Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. Previous studies have shown that low pH within the physiological range directly activates HSF1 function in vitro. However, the detailed molecular mechanisms remain unclear. This study proposes a molecular mechanism based on the trimerization behavior of HSF1 at different pH values. Extensive mutagenesis of human and goldfish HSF1 revealed that the optimal pH for trimerization depended on the identity of residue 103. In particular, when residue 103 was occupied by tyrosine, a significant increase in the optimal pH was observed, regardless of the rest of the sequence...
March 25, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38536879/comprehensive-mutagenesis-maps-the-effect-of-all-single-codon-mutations-in-the-aav2-rep-gene-on-aav-production
#13
JOURNAL ARTICLE
Nina K Jain, Pierce J Ogden, George M Church
Recombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single-codon mutations to the AAV2 rep gene on AAV2 production...
March 27, 2024: ELife
https://read.qxmd.com/read/38536788/a-dual-computational-and-experimental-strategy-to-enhance-tslp-antibody-affinity-for-improved-asthma-treatment
#14
JOURNAL ARTICLE
Yitong Lv, He Gong, Xuechao Liu, Jia Hao, Lei Xu, Zhiwei Sun, Changyuan Yu, Lida Xu
Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis...
March 2024: PLoS Computational Biology
https://read.qxmd.com/read/38535230/hsp90-mediated-multi-drug-resistance-in-dna-polymerase-defective-strains-of-candida-albicans
#15
JOURNAL ARTICLE
Bhabasha Gyanadeep Utkalaja, Satya Ranjan Sahu, Sushree Subhashree Parida, Narottam Acharya
The incidence of infections caused by Candida species, specifically by drug-resistant isolates, is a major health concern as they can disseminate to and colonize most vital organs, enhancing morbidity and mortality. Several molecular mechanisms have been reported to be involved in drug resistance. These are mostly drug- and isolate-specific. Here, we characterized three different genetically modified strains of C. albicans that were multi-drug-resistant (MDR) and deciphered a uniform mechanism responsible for resistance...
March 19, 2024: Journal of Fungi (Basel, Switzerland)
https://read.qxmd.com/read/38534113/exploring-the-links-between-sos-response-mutagenesis-and-resistance-during-the-recovery-period
#16
JOURNAL ARTICLE
Sreyashi Ghosh, Mehmet A Orman
Although the mechanistic connections between SOS-induced mutagenesis and antibiotic resistance are well established, our current understanding of the impact of SOS response levels, recovery durations, and transcription/translation activities on mutagenesis remains relatively limited. In this study, when bacterial cells were exposed to mutagens like ultraviolet light for defined time intervals, a compelling connection between the rate of mutagenesis and the RecA-mediated SOS response levels became evident. Our observations also indicate that mutagenesis primarily occurs during the subsequent recovery phase following the removal of the mutagenic agent...
March 27, 2024: Antimicrobial Agents and Chemotherapy
https://read.qxmd.com/read/38533084/forward-genetic-screen-using-a-gene-breaking-trap-approach-identifies-a-novel-role-of-grin2bb-associated-rna-transcript-grin2bbart-in-zebrafish-heart-function
#17
JOURNAL ARTICLE
Ramcharan Singh Angom, Adita Joshi, Ashok Patowary, Ambily Sivadas, Soundhar Ramasamy, Shamsudheen K V, Kriti Kaushik, Ankit Sabharwal, Mukesh Kumar Lalwani, Subburaj K, Naresh Singh, Vinod Scaria, Sridhar Sivasubbu
LncRNA-based control affects cardiac pathophysiologies like myocardial infarction, coronary artery disease, hypertrophy, and myotonic muscular dystrophy. This study used a gene-break transposon (GBT) to screen zebrafish ( Danio rerio ) for insertional mutagenesis. We identified three insertional mutants where the GBT captured a cardiac gene. One of the adult viable GBT mutants had bradycardia (heart arrhythmia) and enlarged cardiac chambers or hypertrophy; we named it "bigheart." Bigheart mutant insertion maps to grin2bb or N-methyl D-aspartate receptor (NMDAR2B) gene intron 2 in reverse orientation...
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38532652/recent-progress-of-atmospheric-and-room-temperature-plasma-as-a-new-and-promising-mutagenesis-technology
#18
REVIEW
Dongao Li, Jie Shen, Qiang Ding, Jinyong Wu, Xiangsong Chen
At present, atmospheric and room-temperature plasma (ARTP) is regarded as a new and powerful mutagenesis technology with the advantages of environment-friendliness, operation under mild conditions, and fast mutagenesis speed. Compared with traditional mutagenesis strategies, ARTP is used mainly to change the structure of microbial DNA, enzymes, and proteins through a series of physical, chemical, and electromagnetic effects with the organisms, leading to nucleotide breakage, conversion or inversion, causing various DNA damages, so as to screen out the microbial mutants with better biological characteristics...
April 2024: Cell Biochemistry and Function
https://read.qxmd.com/read/38532137/machine-learning-guided-engineering-of-genetically-encoded-fluorescent-calcium-indicators
#19
JOURNAL ARTICLE
Sarah J Wait, Marc Expòsit, Sophia Lin, Michael Rappleye, Justin Daho Lee, Samuel A Colby, Lily Torp, Anthony Asencio, Annette Smith, Michael Regnier, Farid Moussavi-Harami, David Baker, Christina K Kim, Andre Berndt
Here we used machine learning to engineer genetically encoded fluorescent indicators, protein-based sensors critical for real-time monitoring of biological activity. We used machine learning to predict the outcomes of sensor mutagenesis by analyzing established libraries that link sensor sequences to functions. Using the GCaMP calcium indicator as a scaffold, we developed an ensemble of three regression models trained on experimentally derived GCaMP mutation libraries. The trained ensemble performed an in silico functional screen on 1,423 novel, uncharacterized GCaMP variants...
March 2024: Nature computational science
https://read.qxmd.com/read/38531363/the-hisrs-like-domain-of-gcn2-is-a-pseudoenzyme-that-can-bind-uncharged-trna
#20
JOURNAL ARTICLE
Jay Z Yin, Alexander F A Keszei, Scott Houliston, Frantisek Filandr, Jonah Beenstock, Salima Daou, Julia Kitaygorodsky, David C Schriemer, Mohammad T Mazhab-Jafari, Anne-Claude Gingras, Frank Sicheri
GCN2 is a stress response kinase that phosphorylates the translation initiation factor eIF2α to inhibit general protein synthesis when activated by uncharged tRNA and stalled ribosomes. The presence of a HisRS-like domain in GCN2, normally associated with tRNA aminoacylation, led to the hypothesis that eIF2α kinase activity is regulated by the direct binding of this domain to uncharged tRNA. Here we solved the structure of the HisRS-like domain in the context of full-length GCN2 by cryoEM. Structure and function analysis shows the HisRS-like domain of GCN2 has lost histidine and ATP binding but retains tRNA binding abilities...
March 22, 2024: Structure
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