RNA delivery by extracellular vesicles in mammalian cells and its applications.

The term 'extracellular vesicles' refers to a heterogeneous population of vesicular bodies of cellular origin that derive either from the endosomal compartment (exosomes) or as a result of shedding from the plasma membrane (microvesicles, oncosomes and apoptotic bodies). Extracellular vesicles carry a variety of cargo, including RNAs, proteins, lipids and DNA, which can be taken up by other cells, both in the direct vicinity of the source cell and at distant sites in the body via biofluids, and elicit a variety of phenotypic responses. Owing to their unique biology and roles in cell-cell communication, extracellular vesicles have attracted strong interest, which is further enhanced by their potential clinical utility. Because extracellular vesicles derive their cargo from the contents of the cells that produce them, they are attractive sources of biomarkers for a variety of diseases. Furthermore, studies demonstrating phenotypic effects of specific extracellular vesicle-associated cargo on target cells have stoked interest in extracellular vesicles as therapeutic vehicles. There is particularly strong evidence that the RNA cargo of extracellular vesicles can alter recipient cell gene expression and function. During the past decade, extracellular vesicles and their RNA cargo have become better defined, but many aspects of extracellular vesicle biology remain to be elucidated. These include selective cargo loading resulting in substantial differences between the composition of extracellular vesicles and source cells; heterogeneity in extracellular vesicle size and composition; and undefined mechanisms for the uptake of extracellular vesicles into recipient cells and the fates of their cargo. Further progress in unravelling the basic mechanisms of extracellular vesicle biogenesis, transport, and cargo delivery and function is needed for successful clinical implementation. This Review focuses on the current state of knowledge pertaining to packaging, transport and function of RNAs in extracellular vesicles and outlines the progress made thus far towards their clinical applications

A second update on mapping the human genetic architecture of COVID-19

Matters Arising From: COVID-19 Host Genetics Initiative. Nature https://doi.org/10.1038/s41586-021-03767-x (2021)Data availability: Summary statistics generated by the COVID-19 HGI are available online, including per-ancestry summary statistics for African, admixed American, East Asian, European and South Asian ancestries (https://www.covid19hg.org/results/r7/). The analyses described here used the data release 7. If available, individual-level data can be requested directly from contributing studies, listed in Supplementary Table 1. We used publicly available data from GTEx (https://gtexportal.org/home/), the Neale laboratory (http://www.nealelab.is/uk-biobank/), the Finucane laboratory (https://www.finucanelab.org), the FinnGen Freeze 4 cohort (https://www.finngen.fi/en/access_results) and the eQTL catalogue release 3 (http://www.ebi.ac.uk/eqtl/).Code availability: The code for summary statistics lift-over, the projection PCA pipeline including precomputed loadings and meta-analyses (https://github.com/covid19-hg/); for heritability estimation (https://github.com/AndrewsLabUCSF/COVID19_heritability); for Mendelian randomization and genetic correlation (https://github.com/marcoralab/MRcovid); and subtype analyses (https://github.com/mjpirinen/covid19-hgi_subtypes) are available at GitHub.Reporting summary: Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article online at: https://www.nature.com/articles/s41586-023-06355-3#MOESM2 .Supplementary information is available online at: https://www.nature.com/articles/s41586-023-06355-3#Sec4 .Copyright © The Author(s) 2023. Investigating the role of host genetic factors in COVID-19 severity and susceptibility can inform our understanding of the underlying biological mechanisms that influence adverse outcomes and drug development1,2. Here we present a second updated genome-wide association study (GWAS) on COVID-19 severity and infection susceptibility to SARS-CoV-2 from the COVID-19 Host Genetic Initiative (data release 7). We performed a meta-analysis of up to 219,692 cases and over 3 million controls, identifying 51 distinct genome-wide significant loci—adding 28 loci from the previous data release2. The increased number of candidate genes at the identified loci helped to map three major biological pathways that are involved in susceptibility and severity: viral entry, airway defence in mucus and type I interferon

Heterodyne-Detected Sum Frequency Generation Study of Adsorption of I- at Model Paint-Water Interface and Its Relevance to Post-Nuclear Accident Scenario

Organic iodides constitute a significant fraction of radioactive iodine released into the environment in the event of a nuclear power plant accident. The painted surfaces inside the reactor containment play a key role in the formation of organic iodides. In this study, heterodyne detected vibrational sum frequency generation (HD-VSFG) spectroscopy has been used to gain insight into the origin of organic iodides from paint surfaces. Model polymeric compounds dimethylhexadecyl amine (DHDA) and Nylon6, which resemble the constituents of containment paints, are selected for this study. Our investigations on the DHDAwater interface and Nylon6-water interface reveal the existence of positive surface field at acidic conditions (bulk pH: 2, 6) due to protonation at amine functional group and adsorption of H+ at amide groups; and a negative surface field at pH 11 due to adsorption of OH ions at both amine and amide functional groups. In the presence of CsI in the aqueous phase, this surface field is altered by the counterion effect of I- (at pH 6 and pH 2) and Cs+ ions (at pH 11) at the DHDAwater and Nylon6-water interfaces. These studies highlight that at acidic bulk pH (pH < 7), both DHDA and Nylon6 participate in adsorption of I at the interface, and compared to Nylon6, DHDA is more effective in adsorbing I-. On the other hand, at bulk pH = 11, I- is repelled from both the Nylon6-water interface and the DHDA-water interface, suggesting the lower probability of organic iodide formation at alkaline condition

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Not AvailableICAR-National Rice Research Institute (NRRI), Cuttack, India had taken up two tiny villages namely Gurujanga & Guali in Odisha state for developing as model villages and dissemination of improved rice production technologies. Adoption of few land mark rice varieties developed by ICAR-NRRI, Cuttack resulted huge yield advantage over varieties grown earlier. Non-farm income and labour force participation rate were key factors together with other improved traits for adoption of varieties and technologies. However, un-matching convergence, recurrent drought, low liquidity due to lack of financial inclusions, etc. were major impediments for reaping the benefits of technology transfer through model village programmes.Not Availabl

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