keyword
https://read.qxmd.com/read/38506509/restoration-of-virulence-in-the-attenuated-candid-1-vaccine-virus-requires-reversion-at-both-positions-168-and-427-in-the-envelope-glycoprotein-gpc
#21
JOURNAL ARTICLE
Jack H Nunberg, Jonna B Westover, Joanne York, Kie Hoon Jung, Kevin W Bailey, Kirsten M Boardman, Minghao Li, Rachel S Furnell, Samantha R Wasson, Justin S Murray, Rakesh Kaundal, Aaron J Thomas, Brian B Gowen
Live-attenuated virus vaccines provide long-lived protection against viral disease but carry inherent risks of residual pathogenicity and genetic reversion. The live-attenuated Candid#1 vaccine was developed to protect Argentines against lethal infection by the Argentine hemorrhagic fever arenavirus, Junín virus. Despite its safety and efficacy in Phase III clinical study, the vaccine is not licensed in the US, in part due to concerns regarding the genetic stability of attenuation. Previous studies had identified a single F427I mutation in the transmembrane domain of the Candid#1 envelope glycoprotein GPC as the key determinant of attenuation, as well as the propensity of this mutation to revert upon passage in cell culture and neonatal mice...
March 20, 2024: Journal of Virology
https://read.qxmd.com/read/38506170/long-term-immunogenicity-and-safety-of-heterologous-boosting-with-a-sars-cov-2-mrna-vaccine-sys6006-in-chinese-participants-who-had-received-two-or-three-doses-of-inactivated-vaccine
#22
JOURNAL ARTICLE
Jianying Huang, Yuanzheng Qiu, Lin Luo, Jianyuan Wu, Di Hu, Xiang Zhong, Jiawei Lin, Lixian Guo, Hanyu Yang, Chunlei Li, Xinghuan Wang
The emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs booster vaccination. We evaluated the long-term safety and immunogenicity of heterologous boosting with a SARS-CoV-2 messenger RNA vaccine SYS6006. A total of 1000 participants aged 18 years or more who had received two (Group A) or three (Group B) doses of SARS-CoV-2 inactivated vaccine were enrolled and vaccinated with one dose of SYS6006 which was designed based on the prototype spike protein and introduced mutation sites...
March 2024: Journal of Medical Virology
https://read.qxmd.com/read/38502371/impact-of-resistance-on-therapeutic-design-a-moran-model-of-cancer-growth
#23
JOURNAL ARTICLE
Mason S Lacy, Adrianne L Jenner
Resistance of cancers to treatments, such as chemotherapy, largely arise due to cell mutations. These mutations allow cells to resist apoptosis and inevitably lead to recurrence and often progression to more aggressive cancer forms. Sustained-low dose therapies are being considered as an alternative over maximum tolerated dose treatments, whereby a smaller drug dosage is given over a longer period of time. However, understanding the impact that the presence of treatment-resistant clones may have on these new treatment modalities is crucial to validating them as a therapeutic avenue...
March 19, 2024: Bulletin of Mathematical Biology
https://read.qxmd.com/read/38501598/sensitive-detection-of-sars-cov-2-main-protease-3cl-pro-with-an-engineered-ribonuclease-zymogen
#24
JOURNAL ARTICLE
Evans C Wralstad, Ronald T Raines
Alongside vaccines and antiviral therapeutics, diagnostic tools are a crucial aid in combating the COVID-19 pandemic caused by the etiological agent SARS-CoV-2. All common assays for infection rely on the detection of viral sub-components, including structural proteins of the virion or fragments of the viral genome. Selective pressure imposed by human intervention of COVID-19 can, however, induce viral mutations that decrease the sensitivity of diagnostic assays based on biomolecular structure, leading to an increase in false-negative results...
April 2024: Protein Science
https://read.qxmd.com/read/38501170/cross-species-human-disease-modeling-using-patient-derived-extracellular-vesicles
#25
JOURNAL ARTICLE
Rewayd Shalash, Mor Levi-Ferber, Coral Cohen, Amir Dori, Chaya Brodie, Sivan Henis-Korenblit
Reliable disease models are critical for medicine advancement. Here, we established a versatile human disease model system using patient derived extracellular vesicles (EVs), which transfer a pathology-inducing cargo from a patient to a recipient naïve model organism. As a proof of principle, we applied extracellular vesicles from serum of muscular dystrophy patients to C. elegans and demonstrated their capability to induce a spectrum of muscle pathologies including lifespan shortening and robust impairment of muscle organization and function...
March 19, 2024: Disease Models & Mechanisms
https://read.qxmd.com/read/38501136/the-origin-and-the-genetic-regulation-of-the-self-compatibility-mechanism-in-clementine-citrus-clementina-hort-ex-tan
#26
JOURNAL ARTICLE
Stefania Bennici, Lara Poles, Mario Di Guardo, Lawrence Percival-Alwyn, Mario Caccamo, Concetta Licciardello, Alessandra Gentile, Gaetano Distefano, Stefano La Malfa
Self-incompatibility (SI) is a genetic mechanism common in flowering plants to prevent self-fertilization. Among citrus species, several pummelo, mandarin, and mandarin-like accessions show SI behavior. In these species, SI is coupled with a variable degree of parthenocarpy ensuring the production of seedless fruits, a trait that is highly appreciated by consumers. In Citrus , recent evidences have shown the presence of a gametophytic SI system based on S-ribonucleases ( S-RNases ) ability to impair self-pollen tube growth in the upper/middle part of the style...
2024: Frontiers in Plant Science
https://read.qxmd.com/read/38500034/generalizability-of-machine-learning-in-predicting-antimicrobial-resistance-in-e-coli-a-multi-country-case-study-in-africa
#27
JOURNAL ARTICLE
Mike Nsubuga, Ronald Galiwango, Daudi Jjingo, Gerald Mboowa
BACKGROUND: Antimicrobial resistance (AMR) remains a significant global health threat particularly impacting low- and middle-income countries (LMICs). These regions often grapple with limited healthcare resources and access to advanced diagnostic tools. Consequently, there is a pressing need for innovative approaches that can enhance AMR surveillance and management. Machine learning (ML) though underutilized in these settings, presents a promising avenue. This study leverages ML models trained on whole-genome sequencing data from England, where such data is more readily available, to predict AMR in E...
March 18, 2024: BMC Genomics
https://read.qxmd.com/read/38496645/a-tale-of-two-fusion-proteins-understanding-the-metastability-of-human-respiratory-syncytial-virus-and-metapneumovirus-and-implications-for-rational-design-of-uncleaved-prefusion-closed-trimers
#28
Yi-Zong Lee, Jerome Han, Yi-Nan Zhang, Garrett Ward, Keegan Braz Gomes, Sarah Auclair, Robyn L Stanfield, Linling He, Ian A Wilson, Jiang Zhu
UNLABELLED: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we designed uncleaved prefusion-closed (UFC) trimers for the fusion (F) proteins of both viruses by examining mutations critical to F metastability. For RSV, we assessed four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identified key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38496487/interpretable-atomistic-prediction-and-functional-analysis-of-conformational-ensembles-and-allosteric-states-in-protein-kinases-using-alphafold2-adaptation-with-randomized-sequence-scanning-and-local-frustration-profiling
#29
Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Hao Tian, Sian Xiao, Peng Tao, Gennady Verkhivker
The groundbreaking achievements of AlphaFold2 (AF2) approaches in protein structure modeling marked a transformative era in structural biology. Despite the success of AF2 tools in predicting single protein structures, these methods showed intrinsic limitations in predicting multiple functional conformations of allosteric proteins and fold-switching systems. The recent NMR-based structural determination of the unbound ABL kinase in the active state and two inactive low-populated functional conformations that are unique for ABL kinase presents an ideal challenge for AF2 approaches...
February 20, 2024: bioRxiv
https://read.qxmd.com/read/38496431/antigenic-determinants-of-hastv-va1-neutralization-and-their-relevance-in-the-human-immune-response
#30
Inci Ramírez-Bello, Tomás López, Rafaela Espinosa, Anisa Ghosh, Kassidy Green, Lidia Riaño-Umbarila, Carlos Gaspar-Castillo, Celia M Alpuche-Aranda, Susana López, Rebecca M DuBois, Carlos F Arias
UNLABELLED: Astroviruses are highly divergent and infect a wide variety of animal hosts. In 2009, a genetically divergent human astrovirus (HAstV) strain VA1 was first identified in an outbreak of acute gastroenteritis. This strain has also been associated with fatal central nervous system disease. In this work, we report the isolation of three high-affinity neutralizing monoclonal antibodies (Nt-MAbs) targeting the capsid spike domain of HAstV-VA1. These antibodies (7C8, 2A2, 3D8) were used to select individual HAstV-VA1 mutants resistant to their neutralizing activity and also select a HAstV-VA1 triple mutant that escapes neutralization from all three Nt-MAbs...
March 5, 2024: bioRxiv
https://read.qxmd.com/read/38496410/rapid-degradation-of-the-human-ace2-receptor-upon-binding-and-internalization-of-sars-cov-2-spike-rbd-protein
#31
Paul Feinstein
It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain (RBD). Robust interactions are shown using a novel cell-based assay between an RBD membrane tethered-GFP fusion protein and the membrane bound ACE2-Cherry fusion protein...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38494848/the-cell-death-related-genes-machine-learning-model-for-precise-therapy-and-clinical-drug-selection-in-hepatocellular-carcinoma
#32
JOURNAL ARTICLE
Mingyang Du, Yonggang Qu, Lingshan Qin, Jiahe Zheng, Wei Sun
Hepatocellular carcinoma (HCC) is the prevailing subtype of hepatocellular malignancy. While previous investigations have evidenced a robust link with programmed cell death (PCD) and tumorigenesis, a comprehensive inquiry targeting the relationship between multiple PCDs and HCC remains scant. Our aim was to develop a predictive model for different PCD patterns in order to investigate their impact on survival rates, prognosis and drug response rates in HCC patients. We performed functional annotation and pathway analysis on identified PCD-related genes (PCDRGs) using multiple bioinformatics tools...
April 2024: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/38492185/an-advanced-intrahepatic-cholangiocarcinoma-patient-benefits-from-personalized-immunotherapy
#33
JOURNAL ARTICLE
Sihui Zhu, Chenxi Liu, Yunchen Jin, Hailong Zhang, Mingzhen Zhou, Chen Xu, Jie Shao, Qin Liu, Jia Wei, Jie Shen, Baorui Liu
Advanced intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy characterized by limited response to standard therapeutic modalities, such as radiotherapy, chemotherapy, and targeted therapy. The prognosis for patients with advanced ICC is exceedingly bleak, with an overall survival of less than 1 year. In recent years, personalized neoantigen vaccines have emerged as a promising approach to augment the immune response against tumors. Clinical investigations are currently underway to evaluate the efficacy of neoantigen-based peptide, DNA, and dendritic cell vaccines...
March 16, 2024: Inflammation
https://read.qxmd.com/read/38491858/dietary-restriction-fails-to-extend-lifespan-of-drosophila-model-of-werner-syndrome
#34
JOURNAL ARTICLE
Eileen Sember, Ranga Chennakesavula, Breanna Beard, Mubaraq Opoola, Dae-Sung Hwangbo
Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in the WRN gene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS. In this study, using the null mutant flies (WRNexoΔ) for the gene WRNexo (CG7670), homologous to the exonuclease domain of WRN in humans, we examined how diets affect the lifespan, stress resistance, and sleep/wake patterns of a Drosophila model of WS...
March 16, 2024: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/38491510/sex-disparities-revealed-by-single-cell-and-bulk-sequencing-and-their-impacts-on-the-efficacy-of-immunotherapy-in-esophageal-cancer
#35
JOURNAL ARTICLE
Huimeng Yan, Jinyuan Huang, Yingying Li, Bin Zhao
BACKGROUND: There is an ongoing debate on whether sex affects immune-suppressive tumor microenvironment and immunotherapy. Here, we explored the underlying molecular bases for sex dimorphisms and their impact on the efficacy of immunotherapy in esophageal cancer (EC). METHODS: 2360 EC patients from phase 3 trials were pooled to compare overall survivals by calculating hazard ratios (HRs) and their 95% confidence intervals (CIs). Genomic data of 1425 samples were integrated to depict the genomic landscapes and antigenic features...
March 15, 2024: Biology of Sex Differences
https://read.qxmd.com/read/38490361/recombination-and-repeat-induced-point-mutation-landscapes-reveal-trade-offs-between-the-sexual-and-asexual-cycles-of-magnaporthe-oryzae
#36
JOURNAL ARTICLE
Xifang Zong, Yaxin Lou, Mengshuang Xia, Kunyang Zhao, Jingxuan Chen, Ju Huang, Sihai Yang, Long Wang
The fungal disease caused by Magnaporthe oryzae is one of the most devastating diseases that endangers many crops worldwide. Evidences show that sexual reproduction can be advantageous for fungal diseases as hybridization facilitates host-jumping. However, the pervasive clonal lineages of M. oryzae observed in natural fields contradict this expectation. A better understanding of the roles of recombination and the fungi-specific repeat-induced point (RIP) mutation in shaping its evolutionary trajectory is essential to bridge this knowledge gap...
March 13, 2024: Journal of Genetics and Genomics
https://read.qxmd.com/read/38489040/adaptive-responses-of-erythritol-producing-yarrowia-lipolytica-to-thermal-stress-after-evolution
#37
JOURNAL ARTICLE
Kai Xia, Yuqing Chen, Fangmei Liu, Xuequn Zhao, Ruyi Sha, Jun Huang
Elucidation of the thermotolerance mechanism of erythritol-producing Yarrowia lipolytica is of great significance to breed robust industrial strains and reduce cost. This study aimed to breed thermotolerant Y. lipolytica and investigate the mechanism underlying the thermotolerant phenotype. Yarrowia lipolytica HT34, Yarrowia lipolytica HT36, and Yarrowia lipolytica HT385 that were capable of growing at 34 °C, 36 °C, and 38.5 °C, respectively, were obtained within 150 days (352 generations) by adaptive laboratory evolution (ALE) integrated with 60 Co-γ radiation and ultraviolet ray radiation...
March 15, 2024: Applied Microbiology and Biotechnology
https://read.qxmd.com/read/38488266/rapid-identification-of-sars-cov-2-variants-using-stable-high-frequency-mutation-sites
#38
JOURNAL ARTICLE
Yu Fu, Xiaobai He, Quan Fang, Fei Kong, Yan Zhang, Ting Fu, Liang Chen, YanXin Liu, Zhen Wang, Jianxin Lyu, Linjie Chen
Respiratory infectious viruses, including SARS-CoV-2, undergo rapid genetic evolution, resulting in diverse subtypes with complex mutations. Detecting and differentiating these subtypes pose significant challenges in respiratory virus surveillance. To address these challenges, we integrated ARMS-PCR with molecular beacon probes, allowing selective amplification and discrimination of subtypes based on adjacent mutation sites. The method exhibited high specificity and sensitivity, detecting as low as 104 copies/mL via direct fluorescence analysis and ~106 copies/mL using real-time PCR...
March 15, 2024: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://read.qxmd.com/read/38485995/the-landscape-of-immune-checkpoint-related-long-non-coding-rnas-core-regulatory-circuitry-reveals-implications-for-immunoregulation-and-immunotherapy-responses
#39
JOURNAL ARTICLE
Changfan Qu, Hao Cui, Song Xiao, Longlong Dong, Qianyi Lu, Lei Zhang, Peng Wang, Mengyu Xin, Hui Zhi, Chenyu Liu, Shangwei Ning, Yue Gao
Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions...
March 14, 2024: Communications Biology
https://read.qxmd.com/read/38485709/repurposing-crispr-cas13-systems-for-robust-mrna-trans-splicing
#40
JOURNAL ARTICLE
David N Fiflis, Nicolas A Rey, Harshitha Venugopal-Lavanya, Beatrice Sewell, Aaron Mitchell-Dick, Katie N Clements, Sydney Milo, Abigail R Benkert, Alan Rosales, Sophia Fergione, Aravind Asokan
Type VI CRISPR enzymes have been developed as programmable RNA-guided Cas proteins for eukaryotic RNA editing. Notably, Cas13 has been utilized for site-targeted single base edits, demethylation, RNA cleavage or knockdown and alternative splicing. However, the ability to edit large stretches of mRNA transcripts remains a significant challenge. Here, we demonstrate that CRISPR-Cas13 systems can be repurposed to assist trans-splicing of exogenous RNA fragments into an endogenous pre-mRNA transcript, a method termed CRISPR Assisted mRNA Fragment Trans-splicing (CRAFT)...
March 14, 2024: Nature Communications
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