Sunday reading (17.04)
Review of scientific periodicals for April 11-17
Elizaveta Minina, PCR.news
Physiology and space
1. Prolonged stay in space causes changes in the brain and its compartments filled with cerebrospinal fluid, and also affects visual acuity. This set of symptoms is known as spaceflight-associated neuro-ocular syndrome (SANS). The authors of the study published in PNAS analyzed using MRI what changes occur in the perivascular spaces of astronauts who have been on the International Space Station (ISS) for more than six months. They have increased the volume of the perivascular space in the basal ganglia and white matter, as well as the lateral ventricle, the volume of the subarachnoid space has changed.
2. Chinese scientists announced the creation of an atlas of cellular transcriptomes for the crab-eating macaque Macaca fascicularis. The article is published in Nature. The atlas includes transcriptomes of more than a million cells from 45 tissues of an adult macaque. Thus, an annotated set of transcriptomic data was obtained for a species close to humans. To show the usefulness of the atlas from a practical point of view, the scientists reconstructed a network of intercellular interactions that provide transmission via the Wnt signaling pathway, and showed which cells express receptors and coreceptors of viruses that infect humans.
3. The oldest evidence of human infection with the plague bacillus Yersinia pestis belongs to the Neolithic era. An international team of researchers on the pages of PNAS reported the receipt of 17 genomes of Y. pestis, whose age varies from 2500 to 5000 years, from fossils collected throughout Eurasia. The results of the study indicate the existence of a special Y line. pestis, not adapted for flea transport and probably extinct, which existed for thousands of years without significant parallel diversification and at the same time was able to spread rapidly across continents — possibly due to increased human mobility and intensification of animal husbandry. A similar evolutionary history was not previously unknown for any pathogen for which ancient genomes were obtained.
4. The most important event of early embryogenesis is the activation of the zygotic genome: up to this point, the new organism lives only at the expense of proteins and RNA obtained as part of the egg, and after activation begins to produce its own RNA and proteins. Spanish scientists have analyzed at the transcriptomic level how this process occurs in humans, mice and cows; the article is published in Science Advances. At the stage of activation of the zygote genome, there are more acts of exon transmission during splicing of a variety of transcripts than in any previously described cells and tissues. A significant proportion of cases of exon skipping leads to the appearance of non-canonical toxic forms of proteins, but this does not happen at later stages. Exons are especially often omitted in transcripts that encode proteins involved in the cellular response to DNA damage.
5. The authors of a paper published in the journal Alzheimer's & Dementia suggested that high-density lipoproteins (HDL) may protect against Alzheimer's disease. Perhaps this is due to the ability of HDL to participate in lipid metabolism, due to which they can affect the lipid composition of neural membranes, as well as vascular functionality and the efficiency of synaptic transmission. The authors measured HDL concentrations in cerebrospinal fluid in 180 patients over 60 years of age. Their low content correlated with cognitive symptoms of Alzheimer's disease. Scientists have also shown that HDL levels in cerebrospinal fluid and plasma correlate with each other.
6. Scientists from the USA and Canada on the pages of Nature Communications talked about the development of a new approach to the treatment of Alzheimer's disease, the target of which may be microglia cells. They showed that activation of the NF-kB signaling pathway in microglial cells under the action of tau protein leads to its further accumulation in brain tissues, which is provided by microglia, and toxic effects on the surrounding nerve tissue. Constant inactivation of the NF-kB pathway in microglial cells prevents the accumulation and spread of tau protein in brain tissue in young PS19 mice, since microglial cells do not release tau protein outside. And inhibition of NF-kB in the microglia of old mice improved their memory.
Structural Biology, CRISPR-Cas
7. A team of scientists from Australia and the USA, led by Nobel laureate Jennifer Dudnaya, studied in detail the interaction between DNA, guide RNA and Cas9. The results of the study are published in Nature Structural & Molecular Biology. Using cryo–electron microscopy, scientists obtained the structure of DNA – RNA - Cas9. It sheds light on many nuances in the work of CRISPR-Cas9, in particular, on how Cas9 bends and turns DNA so that its sequence is readable.
8. Chinese scientists have developed a method of reprogramming somatic cells into pluripotent cells using small molecules; the article is published in Nature. Reprogramming into pluripotent stem cells, similar in key characteristics to embryonic stem cells, included an intermediate plastic state that corresponded to the stage of cell dedifferentiation. The authors of the work showed that for successful reprogramming along the proposed pathway, preliminary inhibition of the JNK signaling pathway is necessary.
9. Vitamin E increases the effectiveness of anti-cancer immunotherapy by promoting the activation of dendritic cells in the tumor, according to the journal Cancer Discovery. Looking through electronic medical records of patients undergoing checkpoint inhibitor therapy, the researchers noticed that patients taking vitamin E generally showed better survival. Vitamin E enhanced the effect of immunotherapy on the mouse model, and its effect was associated with the activation of dendritic cells. Penetrating into dendritic cells through the SCARB1 receptor, vitamin E increased their antitumor activity by inhibiting tyrosine phosphatase SHP1 (the control point for dendritic cells). Activated dendritic cells contributed to the development of antitumor T-cell immunity.
10. Familial adenomatous polyposis is a hereditary disease that serves as a predisposition factor for colon cancer; it is caused by mutations in the gene encoding the APC tumor suppressor. APC is involved in cytoskeletal rearrangements, provides polarization and migration of cells of different types. According to a study published in Science Advances, T-cells of patients with mutations in APC have impaired adhesion and mobility, and this is due to the role of APC in regulating cytoskeletal rearrangements and integrin-dependent adhesion. Thus, mutations in APC not only directly increase the risk of colon cancer, but also disrupt T-cell immunity, which can also contribute to the development of a tumor.
11. American scientists have developed allosteric EGFR inhibitors to overcome resistance in lung cancer. The results of the study are published in Nature Communications. Existing tyrosine kinase inhibitors compete with ATP for binding to EGFR, however, new inhibitors bind to other sites. One of the inhibitors, JBJ-09-063, is effective both against EGFR forms that respond to tyrosine kinase inhibitors and against forms resistant to them. The authors of the study believe that JBJ-09-063 can be used alone or in combination with tyrosine kinase inhibitors for the treatment of lung cancer caused by mutations in EGFR.
12. The authors of the article in Science found that sphingolipids control the heterogeneity of skin fibroblasts. Comparison of lipidomes and transcriptomes of different fibroblasts showed that the lipid composition determines their transcriptional program and functional specialization. Of particular importance are sphingolipids, which modulate the activity of signaling pathways involving fibroblast growth factor 2 (FGF2), with some sphingolipids acting as positive regulators, and others as negative ones. As a result, sphingolipids determine in which processes the fibroblast will participate — in wound healing, in the restructuring of the extracellular matrix, or will be involved in fibrosis.
Evolution of viruses
13. Zika virus and dengue fever virus are among the pathogenic flaviviruses carried by arthropods, and in many countries both viruses circulate simultaneously. Scientists from the USA and Mexico studied the features of the evolution of the Zika virus and reported the results in Cell Reports. They imitated the evolution of the Zika virus in nature by passing virus particles through the culture of mosquito cells and infecting mice with or without immunity to dengue fever, then isolated the virus from them and repeated everything from the beginning. It turned out that in both cases, the Zika virus evolves very quickly and acquires an I39V replacement in the NS2B protein, which allows it to evade pre-existing immunity to dengue. In addition, such viruses become much more pathogenic and easier to transmit.
14. Codetta Biosciences received a grant of $15 million for the development of a platform for spatial digital PCR with the possibility of multiplex multi-mix studies. According to the company's representatives, the platform is designed for multi-mix quantitative studies of DNA, RNA and proteins, and it will be possible to conduct up to 30 studies simultaneously. This will allow you to use fewer samples and save a lot on the maintenance of many devices used for multiomics at present. Technical details have not been disclosed yet.
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