Jonathon Foos的动态

Unified metagenomic method for rapid detection of microorganisms in clinical samples Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing. https://lnkd.in/gJXfbafJ

Researchers from the Center for Genomic Regulation have discovered that Escherichia coli bacteria modify their #ribosomes in response to certain antibiotics, such as #streptomycin and #kasugamycin, potentially providing a new mechanism of #antibiotic #resistance. The study reveals that #E. #coli sheds chemical modifications in ribosomal RNA at antibiotic binding sites, making it harder for the drugs to inhibit protein synthesis. This adaptive strategy represents a subtle and precise method of resistance, distinct from other mechanisms like DNA mutations or drug expulsion. The findings were made using advanced nanopore sequencing, which preserves and identifies RNA modifications in their natural state. Understanding why and how bacteria shed these modifications could lead to strategies for combating antimicrobial resistance, a growing global health crisis responsible for millions of deaths annually. Further research could pave the way for new drugs or techniques to counteract this bacterial adaptation.

This week we officially opened our #biobank of our trademarked UC San Diego HUMANOID: Human Organoid Center of Research Excellence (CoRE) PDOs to meet the growing demands of researchers (??newsletter). Availability of these #phenotyped (and in some cases, also #genotyped), #PDOs that are #benchmarked in ways to show that they retain the #epigenetic drivers of disease phenotype and inter-patient heterogeneity, are expected to perform better as platforms for #drugdiscovery. We abide by, i.e., "less is more"; that way, the cell-autonomous features that are unique to diseases are likely to be reproducibly maintained. But #wait, there is #more (because we are #expanding #PDO #research to cover from the "#cradle to the #grave"), because it is never too early to impact #wellbeing if we start with the #mother and her #baby. Link to #newsletter: https://lnkd.in/gXUUkzaW #diseasemodeling; #humanoids; #scienceandtechnology; #pharma; #cellculture; #pdo; #organoidresearch; #precisionmedicine; #innovation #3dbiology; #3dcellculture; #organoids; #drugdiscovery; #drugscreening; #drugdevelopment; #biologics; #RNAtherapeutics

Source: (Frontiers in microbiology) Study identifies novel chromosomal mutation linked to cefiderocol resistance in Acinetobacter baumannii, highlighting the need for improved resistance monitoring tools. Two isolates from patients showed differing FDC susceptibility; mutation in a TonB-dependent receptor was found in the resistant strain. Mass spectrometry confirmed reduced antibiotic uptake. Combined genomic and functional analyses enhance resistance detection and tracking.

Impact on Biology Series - Thunder PASEF The paper describes a new, highly sensitive method for identifying Human Leukocyte Antigen (HLA) class I peptide ligands (HLAIps), which are crucial for vaccine and immunotherapy development. This method uses liquid chromatography-ion mobility-tandem mass spectrometry (LC-IMS-MS/MS) and an optimized technique called Thunder-DDA-PASEF on the timsTOF line of systems. It significantly improves the identification and profiling of HLAIps by doubling the coverage of immunopeptidomics analyses and increasing identification rates by up to 41.7%. This advancement allows for detailed profiling of HLAIps from various human cell lines and plasma, including cells expressing the SARS-CoV-2 spike protein, identifying peptides that trigger immune responses. Daniel Hornburg, PhD Rohan Thakur Torsten MüllerPierre-Olivier SchmitDijana Vitko https://lnkd.in/ejQ4NJEc

Hi everyone! I just finished reading an interesting scientific article. Each day I'll share information about research. #science #lifesciences #biology Holze, J., Lauber, F., Soler, S. et al. Label-free biosensor assay decodes the dynamics of Toll-like receptor signaling. Nat Commun 15, 9554 (2024). https://lnkd.in/eABj88Qi The role of toll-like receptors (TLRs) within the innate immune system is essential for activating necessary cellular pathways in response to pathogens. Optical biosensors are promising as they visualize the whole cell response, which assists in monitoring underlying cellular responses. Other reporter systems, such as fluorescent tags are not time efficient and do not capture real time interactions within the signaling pathway. The authors of this study aimed to create an optical biosensor capable of showcasing real time activation of the TLR pathway. Significant findings showed ligand bias, where a specific TLR would be activated in response to bacterial LPS depending on the cell type. Additionally, this method captures how endosomal TLRs are able to interact with various adaptor proteins to activate downstream pathways. The development of label-free optical biosensors is integral to understanding the distinct activation of each TLR pathway and its downstream effects, which may aid in identifying potential drug targets.

LC-MS analysis is crucial for sgRNA due to its sensitivity and specificity. Our new tools, like the waters_connect MAP Sequence App and mRNA Cleaver MicroApp, speed up data processing and visualization, making RNA analysis more efficient. Unique cleavage sites from various enzymes boosts confidence in sequence confirmation, optimizing drug development and RNA product releases. Check out our recently published application note to learn more: #RNA #LCMS #Biopharma

??????Daily article sharing! Estimation of the allelic status of apolipoprotein E4 isoforms with fully automated LUMIPULSE??assays ? Tatsushi Yuri,?Rosina Degrieck,?Dagmara Minczakiewicz,?Hideo Sato,?Jo Kamada,?Takuya Nakazawa,?Ina Vandenbroucke,?Katsumi Aoyagi,?Hisashi Nojima Explor Neurosci. 2023;2:238–244?DOI: https://lnkd.in/g2wesgA5 Academic Editor:?Dirk M. Hermann, University of Duisburg-Essen, Germany Abstract Aim:?Apolipoprotein E (ApoE) isoforms, especially the ApoE4 isoform, are genetic risk factors for Alzheimer’s disease (AD). Moreover, the?APOE ε4?haplotype has a dose-dependent association with an increased risk of amyloid-related imaging abnormalities (ARIA) in individuals receiving disease-modifying therapy for AD. Therefore, the importance of?APOE?genotyping or proteotyping has been highlighted. Here, the authors developed fully automated chemiluminescence enzyme-immunoassay kit for ApoE4 and Pan-ApoE, and evaluated their diagnostic concordance with the?APOE?genotyping. Methods:?One hundred seventy-eight specimens were analyzed using the Lumipulse??G ApoE4 and Pan-ApoE for the ApoE proteotype and evaluated its diagnostic concordance with the?APOE?genotype. Results:?The ApoE4 kit specifically detected the ApoE4 concentration in plasma samples, and the polymorphism could be classified clearly by the ratio of ApoE4 and Pan-ApoE amount in plasma. Conclusions:?The combination of Pan-ApoE and ApoE4-specific chemiluminescent enzyme immunoassay (CLEIA) assay is useful for predicting?APOE ε4?allele status. Welcome to read!

[Resveratrol inhibits expression of EMMPRIN from macrophages] [Article in Chinese] Heng Ge?1,?Jun-feng Zhang,?Bing-shi Guo,?Ben He,?Bin-yao Wang,?Chang-qian Wang Affiliations?Expand PMID:?17007354 Abstract Aim:?To investigate the effect of resveratrol on EMMPRIN expression of macrophages. Methods:?Human monocytic cell line THP-1 cells were co-cultured with EMMPRIN-highly-expressed MCF-7 cells; MMP-9 production was assayed by zymography. THP-1 cells were induced by PMA, expression of EMMPRIN was assayed by Western blotting. Cells were treated with resveratrol or PPARgamma agonist--pioglitazone during differentiation, EMMPRIN expression and MMP-9 activity were assayed. U937 cells were co-transfected with PPARy expression and luciferase-coding reporter vector, then cultured with pioglitazone or resveratrol, the activating capability of resveratrol on PPARgamma was evaluated by measuring the luciferase activity. THP-1 cells were pretreated with PPARgamma antagonist--GW9662 before pioglitazone or resveratrol treatment, then assayed for EMMPRIN expression and MMP-9 production. Results:?EMMPRIN expression was greatly increased during the differentiation from monocytes to macrophages; co-culturing with MCF-7 cells significantly increased MMP-9 production by monocytes. Both resveratrol and pioglitazone markedly inhibited EMMPRIN expression during monocytes differentiation. Resveratrol significantly activated PPARgamma and GW9662 greatly decreased the effect of resveratrol on EMMPRIN and MMP-9. Conclusion:?EMMPRIN expression is greatly up-regulated from monocytes to macrophages, which may play a role in inducing MMPs production by monocytes/macrophages. Resveratrol can significantly inhibit EMMPRIN expression via activating PPARgamma, which may be the underlying mechanism of its inhibitory effect on MMPs production by monocytes/macrophages.

Hi everyone! I just finished reading an interesting scientific article. Each day I'll share information about research. #science #lifesciences #biology Delgado-Tejedor, A., Medina, R., Begik, O. et al. Native RNA nanopore sequencing reveals antibiotic-induced loss of rRNA modifications in the A- and P-sites. Nat Commun 15, 10054 (2024). https://lnkd.in/ehTPF_nZ Understanding the mechanisms of antibiotic resistance within pathogens is essential for developing new antibiotics capable of overcoming these adaptations. Most antibiotics target the ribosome to interfere with protein synthesis and prevent the survival of bacteria. This study investigates the relationship between rRNA modifications and the ability of antibiotics to access ribosomal binding sites. Using Nanopore sequencing, researchers identified significant modifications at the A and P sites of the ribosomal subunit after antibiotic exposure, which disrupt the binding efficiency of certain antibiotics. Additionally, methyltransferase activity is a key area of interest, as mutations in methyltransferase genes were frequently observed in antibiotic-resistant bacteria. Future research directions include exploring the underlying mechanisms of rRNA modifications in bacteria and their direct effects on mRNA translation and gene expression.