keyword
https://read.qxmd.com/read/38481677/neutralization-of-sars-cov-2-and-intranasal-protection-of-mice-with-a-nanoclamp-antibody-mimetic
#21
JOURNAL ARTICLE
Quentin Pagneux, Nathalie Garnier, Manon Fabregue, Sarah Sharkaoui, Sophie Mazzoli, Ilka Engelmann, Rabah Boukherroub, Mary Strecker, Eric Cruz, Peter Ducos, Sabine Szunerits, Ana Zarubica, Richard Suderman
Intranasal treatment, combined with vaccination, has the potential to slow mutational evolution of viruses by reducing transmission and replication. Here, we illustrate the development of a SARS-CoV-2 receptor-binding domain (RBD) nanoCLAMP and demonstrate its potential as an intranasally administered therapeutic. A multi-epitope nanoCLAMP was made by fusing a pM affinity single-domain nanoCLAMP (P2710) to alternate epitope-binding nanoCLAMP, P2609. The resulting multimerized nanoCLAMP P2712 had sub-pM affinity for the Wuhan and South African (B...
March 8, 2024: ACS Pharmacology & Translational Science
https://read.qxmd.com/read/38476948/high-prevalence-of-pre-treatment-and-acquired-hiv-1-drug-resistance-mutations-among-non-citizens-living-with-hiv-in-botswana
#22
JOURNAL ARTICLE
Patrick T Mokgethi, Wonderful T Choga, Dorcas Maruapula, Natasha O Moraka, Kaelo K Seatla, Ontlametse T Bareng, Doreen D Ditshwanelo, Graceful Mulenga, Terence Mohammed, Pearl M Kaumba, Moses Chihungwa, Tafireyi Marukutira, Sikhulile Moyo, Catherine K Koofhethile, Diana Dickinson, Sununguko W Mpoloka, Simani Gaseitsiwe
BACKGROUND: Approximately 30,000 non-citizens are living with HIV in Botswana, all of whom as of 2020 are eligible to receive free antiretroviral treatment (ART) within the country. We assessed the prevalence of HIV-1 mutational profiles [pre-treatment drug resistance (PDR) and acquired drug resistance (ADR)] among treatment-experienced (TE) and treatment-naïve (TN) non-citizens living with HIV in Botswana. METHODS: A total of 152 non-citizens living with HIV were enrolled from a migrant HIV clinic at Independence Surgery, a private practice in Botswana from 2019-2021...
2024: Frontiers in Microbiology
https://read.qxmd.com/read/38474086/epigenetic-switches-in-retinal-homeostasis-and-target-for-drug-development
#23
REVIEW
Kalpana Rajanala, Arun Upadhyay
Retinal homeostasis, a tightly regulated process maintaining the functional integrity of the retina, is vital for visual function. Emerging research has unveiled the critical role of epigenetic regulation in controlling gene expression patterns during retinal development, maintenance, and response to mutational loads and injuries. Epigenetic switches, including DNA methylation, histone modifications, and non-coding RNAs, play pivotal roles in orchestrating retinal gene expression and cellular responses through various intracellular, extracellular, and environmental modulators...
February 29, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38474014/targeting-atr-pathway-in-solid-tumors-evidence-of-improving-therapeutic-outcomes
#24
REVIEW
Dimitra Mavroeidi, Anastasia Georganta, Emmanouil Panagiotou, Konstantinos Syrigos, Vassilis L Souliotis
The DNA damage response (DDR) system is a complicated network of signaling pathways that detects and repairs DNA damage or induces apoptosis. Critical regulators of the DDR network include the DNA damage kinases ataxia telangiectasia mutated Rad3-related kinase (ATR) and ataxia-telangiectasia mutated (ATM). The ATR pathway coordinates processes such as replication stress response, stabilization of replication forks, cell cycle arrest, and DNA repair. ATR inhibition disrupts these functions, causing a reduction of DNA repair, accumulation of DNA damage, replication fork collapse, inappropriate mitotic entry, and mitotic catastrophe...
February 27, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38471043/licorice-extract-inhibits-porcine-epidemic-diarrhea-virus-in-vitro-and-in-vivo
#25
JOURNAL ARTICLE
Wenfei Bai, Qinghe Zhu, Jun Wang, Limin Jiang, Donghua Guo, Chunqiu Li, Xiaoxu Xing, Dongbo Sun
Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and even death in piglets, resulting in significant economic losses to the pig industry. Because of the ongoing mutation of PEDV, there might be variations between the vaccine strain and the prevailing strain, causing the vaccine to not offer full protection against different PEDV variant strains. Therefore, it is necessary to develop anti-PEDV drugs to compensate for vaccines. This study confirmed the anti-PEDV effect of licorice extract (Le) in vitro and in vivo ...
March 2024: Journal of General Virology
https://read.qxmd.com/read/38470143/complex-n-glycans-are-important-for-interspecies-transmission-of-h7-influenza-a-viruses
#26
JOURNAL ARTICLE
Cindy M Spruit, Diana I Palme, Tiehai Li, María Ríos Carrasco, Alba Gabarroca García, Igor R Sweet, Maryna Kuryshko, Joshua C L Maliepaard, Karli R Reiding, David Scheibner, Geert-Jan Boons, Elsayed M Abdelwhab, Robert P de Vries
Influenza A viruses (IAVs) can overcome species barriers by adaptation of the receptor-binding site of the hemagglutinin (HA). To initiate infection, HAs bind to glycan receptors with terminal sialic acids, which are either N -acetylneuraminic acid (NeuAc) or N -glycolylneuraminic acid (NeuGc); the latter is mainly found in horses and pigs but not in birds and humans. We investigated the influence of previously identified equine NeuGc-adapting mutations (S128T, I130V, A135E, T189A, and K193R) in avian H7 IAVs in vitro and in vivo ...
March 12, 2024: Journal of Virology
https://read.qxmd.com/read/38464327/the-effect-of-molnupiravir-and-nirmatrelvir-on-sars-cov-2-genome-diversity-in-infected-and-immune-suppressed-mice
#27
Rebekah Penrice-Randal, Eleanor G Bentley, Parul Sharma, Adam Kirby, I'ah Donovan-Banfield, Anja Kipar, Daniele F Mega, Chloe Bramwell, Joanne Sharp, Andrew Owen, Julian A Hiscox, James P Stewart
OBJECTIVES: Immunocompromised individuals are susceptible to severe COVID-19 and potentially contribute to the emergence of variants with altered pathogenicity due to persistent infection. This study investigated the impact of immunosuppression on SARS-CoV-2 infection in k18-hACE2 mice and the effectiveness of antiviral treatments in this context. METHODS: Mice were immunosuppressed using cyclophosphamide and infected with a B lineage of SARS-CoV-2. Molnupiravir and nirmatrelvir, alone and in combination, were administered and viral load and viral sequence diversity was assessed...
February 28, 2024: bioRxiv
https://read.qxmd.com/read/38464277/rapid-in-situ-mutation-detection-in-extracellular-vesicle-dna
#28
Md Mofizur Rahman, Lixue Wang, Md Motiar Rahman, Yundi Chen, Wenlong Zhang, Jing Wang, Luke P Lee, Yuan Wan
A PCR- and sequencing-free mutation detection assay facilitates cancer diagnosis and reduces over-reliance on specialized equipment. This benefit was highlighted during the pandemic when high demand for viral nucleic acid testing often sidelined mutation analysis. This shift led to substantial challenges for patients on targeted therapy in tracking mutations. Here, we report a 30-minute DNA mutation detection technique using Cas12a-loaded liposomes in a microplate reader, a fundamental laboratory tool. CRISPR-Cas12a complex and fluorescence-quenching (FQ) probes are introduced into tumor-derived extracellular vesicles (EV) through membrane fusion...
February 29, 2024: bioRxiv
https://read.qxmd.com/read/38463985/constraining-models-of-dominance-for-nonsynonymous-mutations-in-the-human-genome
#29
Christopher C Kyriazis, Kirk E Lohmueller
UNLABELLED: Dominance is a fundamental parameter in genetics, determining the dynamics of natural selection on deleterious and beneficial mutations, the patterns of genetic variation in natural populations, and the severity of inbreeding depression in a population. Despite this importance, dominance parameters remain poorly known, particularly in humans or other non-model organisms. A key reason for this lack of information about dominance is that it is extremely challenging to disentangle the selection coefficient ( s ) of a mutation from its dominance coefficient ( h )...
February 26, 2024: bioRxiv
https://read.qxmd.com/read/38457199/comparison-of-genomic-alterations-in-epstein-barr-virus-positive-and-epstein-barr-virus-negative-diffuse-large-b-cell-lymphoma
#30
JOURNAL ARTICLE
Fang Liu, Sufang Tian, Qing Liu, Yuanfei Deng, Qingyan He, Qianyun Shi, Gang Chen, Xiuli Xu, Jiayin Yuan, Shigeo Nakamura, Kennosuke Karube, Zhe Wang
BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV-posDLBCL) is an aggressive B-cell lymphoma that often presents similar morphological and immune phenotype features to that of EBV-negative DLBCL (EBV-negDLBCL). AIMS AND METHODS: To better understand their difference in genomic landscape, we performed whole-exome sequencing (WES) of EBV-posDLBCL and EBV-negDLBCL. RESULTS: This analysis revealed a new mutational signature 17 (unknown) and signature 29 (smoking) in EBV-posDLBCL as well as a specific mutational signature 24 (associated with aflatoxin) in EBV-negDLBCL...
February 2024: Cancer Medicine
https://read.qxmd.com/read/38454733/ultra-short-term-forecasting-model-of-power-load-based-on-fusion-of-power-spectral-density-and-morlet-wavelet
#31
JOURNAL ARTICLE
Lihe Liang, Jinying Cui, Juanjuan Zhao, Yan Qiang, Juanjuan Zhao
An accurate ultra-short-term time series prediction of a power load is an important guarantee for power dispatching and the safe operation of power systems. Problems of the current ultra-short-term time series prediction algorithms include low prediction accuracy, difficulty capturing the local mutation features, poor stability, and others. From the perspective of series decomposition, a multi-scale sequence decomposition model (TFDNet) based on power spectral density and the Morlet wavelet transform is proposed that combines the multidimensional correlation feature fusion strategy in the time and frequency domains...
February 4, 2024: Mathematical Biosciences and Engineering: MBE
https://read.qxmd.com/read/38453960/observational-retrospective-clinical-study-on-clinical-features-of-macrolide-resistant-mycoplasma-pneumoniae-pneumonia-in-chinese-pediatric-cases
#32
JOURNAL ARTICLE
Peng Li, Wei Wang, Xianhui Zhang, Jie Pan, Lina Gong
This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene...
March 7, 2024: Scientific Reports
https://read.qxmd.com/read/38453914/pla2g12b-drives-expansion-of-triglyceride-rich-lipoproteins
#33
JOURNAL ARTICLE
James H Thierer, Ombretta Foresti, Pradeep Kumar Yadav, Meredith H Wilson, Tabea O C Moll, Meng-Chieh Shen, Elisabeth M Busch-Nentwich, Margaret Morash, Karen L Mohlke, John F Rawls, Vivek Malhotra, M Mahmood Hussain, Steven A Farber
Vertebrates transport hydrophobic triglycerides through the circulatory system by packaging them within amphipathic particles called Triglyceride-Rich Lipoproteins. Yet, it remains largely unknown how triglycerides are loaded onto these particles. Mutations in Phospholipase A2 group 12B (PLA2G12B) are known to disrupt lipoprotein homeostasis, but its mechanistic role in this process remains unclear. Here we report that PLA2G12B channels lipids within the lumen of the endoplasmic reticulum into nascent lipoproteins...
March 7, 2024: Nature Communications
https://read.qxmd.com/read/38451227/emergence-and-dissemination-of-equine-like-g3p-8-rotavirus-a-in-brazil-between-2015-and-2021
#34
JOURNAL ARTICLE
Meylin Bautista Gutierrez, Ighor Arantes, Gonzalo Bello, Lúcia Helena Berto, Leonardo Hermes Dutra, Rodrigo Bentes Kato, Tulio Machado Fumian
Rotavirus A (RVA) is a major cause of acute gastroenteritis globally that is classically genotyped by its two immunodominant outer capsid proteins, VP7 (G-) and VP4 (P-). Recent evidence suggests that the reassortant equine-like G3P[8] strain played a substantial role in RVA transmission in Brazil since 2015. To understand its global emergence and dissemination in Brazilian territory, stool samples collected from 11 Brazilian states ( n = 919) were genotyped by RT-qPCR and proceeded to sequence the VP7 gene ( n = 102, 79 being newly generated) of the G3P[8] samples with pronounced viral loads...
March 7, 2024: Microbiology Spectrum
https://read.qxmd.com/read/38447754/heavily-treatment-experienced-persons-living-with-hiv-currently-in-care-in-italy-characteristics-risk-factors-and-therapeutic-options-the-icona-foundation-cohort-study
#35
JOURNAL ARTICLE
Sergio Lo Caputo, Mariacristina Poliseno, Alessandro Tavelli, Roberta Gagliardini, Stefano Rusconi, Giuseppe Lapadula, Andrea Antinori, Daniela Francisci, Loredana Sarmati, Andrea Gori, Vincenzo Spagnuolo, Francesca Ceccherini-Silberstein, Antonella d'Arminio Monforte, Alessandro Cozzi-Lepri
OBJECTIVES: Heavily Treatment-Experienced (HTE) People Living with HIV (PLWH) pose unique challenges due to limited antiretroviral treatment (ART) options. Our study aimed to investigate the prevalence and features of HTE individuals followed up inthe ICONA cohort as of December 31, 2021. METHODS: HTE were defined based on meeting specific conditions concerning their current ART and their ART history up to December 31, 2021.Descriptive statistics were performed by HTE status...
March 4, 2024: International Journal of Infectious Diseases: IJID
https://read.qxmd.com/read/38447647/a-virus-like-particle-candidate-vaccine-based-on-crispr-cas9-gene-editing-technology-elicits-broad-spectrum-protection-against-sars-cov-2
#36
JOURNAL ARTICLE
Weiqi Wang, Shen Wang, Xianyong Meng, Yongkun Zhao, Nan Li, Tiecheng Wang, Na Feng, Feihu Yan, Xianzhu Xia
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with frequent mutations has seriously damaged the effectiveness of the 2019 coronavirus disease (COVID-19) vaccine. There is an urgent need to develop a broad-spectrum vaccine while elucidating the underlying immune mechanisms. Here, we developed a SARS-CoV-2 virus-like particles (VLPs) vaccine based on the Canarypox-virus vector (ALVAC-VLPs) using CRISPR/Cas9. Immunization with ALVAC-VLPs showed the effectively induce SARS-CoV-2 specific T and B cell responses to resist the lethal challenge of mouse adaptive strains...
March 4, 2024: Antiviral Research
https://read.qxmd.com/read/38446423/a-biotinylated-cpfit-pna-platform-for-the-facile-detection-of-drug-resistance-to-artemisinin-in-plasmodium-falciparum
#37
JOURNAL ARTICLE
Odelia Tepper, Daniel H Appella, Hongchao Zheng, Ron Dzikowski, Eylon Yavin
The evolution of drug resistance to many antimalarial drugs in the lethal strain of malaria ( Plasmodium falciparum ) has been a great concern over the past 50 years. Among these drugs, artemisinin has become less effective for treating malaria. Indeed, several P. falciparum variants have become resistant to this drug, as elucidated by specific mutations in the pfK13 gene. This study presents the development of a diagnostic kit for the detection of a common point mutation in the pfK13 gene of P. falciparum , namely, the C580Y point mutation...
March 6, 2024: ACS Sensors
https://read.qxmd.com/read/38443114/a-role-for-snu66-in-maintaining-5-splice-site-identity-during-spliceosome-assembly
#38
JOURNAL ARTICLE
Kenna Sarka, Sol Katzman, Alan M Zahler
In spliceosome assembly, the 5' splice site is initially recognized by U1snRNA. U1 leaves the spliceosome during the assembly process, therefore other factors contribute to maintenance of 5' splice site identity as it is loaded into the catalytic site. Recent structural data suggest that human tri-snRNP 27K (SNRP27) M141 and SNU66 H734 interact to stabilize the U4/U6 quasi-pseudo knot at the base of the U6 snRNA ACAGAGA box in pre-B complex. Previously, we found that mutations in C. elegans at SNRP-27 M141 promote changes in alternative 5'ss usage...
March 5, 2024: RNA
https://read.qxmd.com/read/38442240/impact-of-cftr-modulation-on-pseudomonas-aeruginosa-infection-in-people-with-cystic-fibrosis
#39
JOURNAL ARTICLE
Emma L Ledger, Daniel J Smith, Jing Jie Teh, Michelle E Wood, Page E Whibley, Mark Morrison, Joanna B Goldberg, David W Reid, Timothy J Wells
BACKGROUND: Pseudomonas aeruginosa is a multidrug-resistant pathogen causing recalcitrant pulmonary infections in people with cystic fibrosis (pwCF). Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been developed that partially correct the defective chloride channel driving disease. Despite the many clinical benefits, studies in adults have demonstrated that while P. aeruginosa sputum load decreases, chronic infection persists. Here, we investigate how P. aeruginosa in pwCF may change in the altered lung environment after CFTR modulation...
March 5, 2024: Journal of Infectious Diseases
https://read.qxmd.com/read/38435811/immunogenicity-of-an-adjuvanted-broadly-active-influenza-vaccine-in-immunocompromised-and-diverse-populations
#40
JOURNAL ARTICLE
Dylan A Hendy, Erik S Pena, Luis Ontiveros-Padilla, Timothy A Dixon, Denzel D Middleton, Grace L Williamson, Nicole Rose Lukesh, Sean R Simpson, Rebeca T Stiepel, Md Jahirul Islam, Michael A Carlock, Ted M Ross, Eric M Bachelder, Kristy M Ainslie
Influenza virus outbreaks are a major burden worldwide each year. Current vaccination strategies are inadequate due to antigenic drift/shift of the virus and the elicitation of low immune responses. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) immunogens subvert the constantly mutating viruses; however, they are poorly immunogenic on their own. To increase the immunogenicity of subunit vaccines such as this, adjuvants can be delivered with the vaccine. For example, agonists of the stimulator of interferon genes (STING) have proven efficacy as vaccine adjuvants...
March 2024: Bioengineering & Translational Medicine
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