27, 2020 in the journal Science

Nov 30, 2020 // --- This week, a new issue of Science (November 27, 2020) was published. Let the little editor come with us.
images from the Journal of Science.
1.Science: The development of "intelligent" cell therapy for cancer with big data doi:10.1126/science.abc6270 The search for drugs that kill cancer cells while keeping normal tissues unsalted is the top goal of oncology research.
in two new papers, researchers from the University of California, San Francisco, and Princeton University suggest complementary strategies for solving this conundrum with "smart" cell therapy: these live cell drugs remain inert unless activated by a group of proteins that appear only in cancer cells at the same time.
the biology of this universal approach has been explored for several years by Dr. Wendell Lim and his colleagues in the labs of the University of California, San Francisco's Cell Design Program and the National Cancer Institute-sponsored Synthetic Immunology Center.
, however, adds a powerful new dimension to this by combining cutting-edge therapeutic cell engineering with advanced computational methods.
in the first paper, published In the September 23, 2020 issue of cell Systems, entitled "Grady Power of Combinatorial Antigen Acknowledge in Cancer T Cell Therapies," members of Lim Labs teamed up with Dr. Olga G. Troyanskaya, a computer scientist at Princeton University's Louis-Sigler Institute for Integrated Genomics.
using machine learning, they analyzed a large database of thousands of proteins found in cancer and normal cells.
, they screened millions of possible protein combinations to create a list of protein combinations that could be used to precisely target only cancer cells, not normal cells.
In a second paper, published in the November 27, 2020 issue of Science, entitled "Precise T cell system programs designed by transcriptionally linking multiple receptors," Lim and his colleagues then demonstrated how these calculated protein data can be used to drive the design of effective and highly selective cancer cell therapies.
2. Science: An in-depth analysis of the body's antibody response to the new coronavirus lays the foundation for the development of a new and more effective vaccine doi:10.1126/science.abd4250 A tool designed to detect the history of viral infection from a drop of blood was upgraded in the COVID-19 era.
VirScan is a technique that can determine which of the more than 1,000 different viruses have infected people, and can now detect evidence of coronavirus infection, including SARS-CoV-2.
In a new study, researchers from Briggan Women's Hospital and Harvard Medical School in the United States provided a wealth of details about human antibody responses to SARS-CoV-2 and how the response might be different in individuals infected with more severe COVID-19.
results were published online September 29, 2020 in the journal Science under the title "Viral epitope profiling of COVID-19 patients reveals cross-react and correlates of severity".
analysis, Elledge and his colleagues analyzed blood samples from 232 COVID-19 patients and 190 controls prior to COVID-19 using VirScan to study the antibody response to SARS CoV-2.
identified 800 viral bits called epitopes that the immune system can identify.
not all of the tables are the same, and some of them may be identified by the antibody, which can lead to a response to the elimination of infection.
, however, if the body produces antibodies against other cousins, it may initiate a less effective response, giving the virus an advantage.
, viruses, including sars-CoV virus, can even benefit from the body's antibody response, using antibodies to enter cells, a phenomenon known as antibody-dependent enhancement.
in the case of SARS-CoV-2, the Elledge team detected a series of antibody frequencies for different tables.
many of these epitopes are public epitopes that are --- by the immune system of a large number of patients.
one of the common tables was identified by 79% of COVID-19 patients.
other tables are considered private and are recognized by only a few people or even one person's immune system.
10 tables are present in key areas necessary for the virus to enter the host cell and may be identified by the antibody.
team developed a rapid diagnostic test using the most discernable tables.
3.Science: Structural analysis of the full-length hedgehog protein doi:10.1126/science.abe1502 in the NVAX-CoV2373 of the candidate new crown vaccine In a new study, researchers from the Scripps Institute in the United States described an advanced candidate, SARS-Co. The structure of the V-2 S vaccine (NVAX-CoV2373), a candidate vaccine, was developed based on a full-length S protein (amino acid residue 1 to 1273) that includes cross-membrane domain (TM) and cytoplasmic tail region (cytoplasmic tail, CT).
study was recently published in the Journal of Science under the title "Structural analysis of full-length SARS-CoV-2 Spike protein from an advanced vaccine candidate".
as the final builder of this candidate vaccine, SARS-CoV-2-3Q-2P is also at the S1/S2 polybasic cleavage site, which contains multiple ammonia residues, The arginine is an alkaline amino acid modified to mutate from the original RRAR to QQAQ, thus making it protease resistant, while at the same time in the S2 fusion core K986 and V987 residue at the K986 and V987 residue to enhance its stability, resulting in SARS-CoV-2 3Q-2P-FL protein.
3Q-2P-FL protein expressed and purified from insect cells and made in a 0.01% (v/v) polysorbital 80 (PS 80) detergent.
To show the structural integrity of 3Q-2P-FL immunogens, the researchers performed negative staining electroscopic imaging of 3Q-2P-FL reconstructed under PS 80 in the presence of Matrix-M adele, recreating the vaccine formulation being tested in humans.
This image shows that this trimer 3Q-2P-FL protein exists in the form of a free trimer or multi-triumer rosette, which contains up to 14 trimers and whose cross-membrane domain is enclosed in the micellar core of the PS 80 detergent.
Tight clustering of 3Q-2P-FL proteins in NVAX-CoV2373 nanoparticle vaccine formulations may lead to a stronger immune response than individual soluble tripolymers, similar to other viral glycoprotein immunogens (HA proteins for influenza viruses and F proteins for RSV viruses).
4.Science: Revealing that the antibody mixture REN-COV2 promises to prevent and treat new coronary pneumonia doi:10.1126/science.abe2402 Now, in a new study that builds on these two papers, researchers have found that this antibody cocktail, whether preventive or therapeutic, benefits to animal models of different pathology that simulate SARS-CoV-2 infection.
results were published online October 9, 2020 in the journal Science under the title "REGN-COV2 antibodies prevent and treat SARS-CoV-2 infect in rhesus macaques and hamsters".
Based on two papers published in the Journal of Science in June by Johanna Hansen et al. and Alina Baum et al. identifying and presenting a double antibody therapy, Baum and colleagues tested the antibody cocktail called REGN-COV2 in rhesus monkeys showing mild COVID-19 symptoms and golden hamsters showing more severe COVID-19 symptoms, including rapid weight loss.
the researchers say the treatment almost completely stopped viral infections in rhesus monkeys when regency regency three days before the SARS-CoV-2 virus challenge.
that this capability "is equivalent to or exceeds the effects shown in recent vaccine efficacy studies using the same animal models."
5.Science: Chinese scientists have revealed that the dual-enzyme complex INTAC dephosphatization mechanism doi:10.1126/science.abb5872 transzoa requires coordination of multiple factors to control the progression of polymerases and the integrity of their RNA products.
now, in a new study, scientists in China have discovered a new dual-enzyme complex called INTAC, which consists of the protein phosphatase 2A (PP2A) core enzyme and the multi-sub-RNA endoenzyme Integrator.
and functional studies show that INTAC functions as a non-classical PP2A all-enzyme that enables the C-side domain of RNA polymerase II to dephosphate to reduce transcription.
the study provides a direct link between PP2A-mediated dephosphate and transcriptional regulation of these two basic cellular processes.
6.Science: Mechanical conduction Doi:10.1126/science.aba5528 at the three-cell connection between Abl and Canoe/Afadin; Doi:10.1126/science.abf2782 cells exist in different environments and must respond to specific stimuli.
in the development process, the skin cells need to be rapidly recombined under stress without affecting the integrity of the skin.
Yu et al. have shown that fruit fly endocal cells do this by temporarily stabilizing adhesion at three-cell junctions where three cells meet.
conservative adhesion regulator Canoe/Afadin was recruited to a three-cell connection within seconds and separated by a mechanism that required Abl-dependent tyrosine phosphate when the pressure was released.
these results identify a mechanical conduction pathway in the body that dynamically couples three cell adhesions with physiological forces, enabling cells to quickly regulate their behavior in response to mechanical changes in their environment.
7.Science: Analysis of autism risk gene doi: 10.1126/science.aaz6063; Doi:10.1126/science.abf3661 When trying to determine the effects of a single gene, CRISPR targeting in the body, especially in mammals, can be difficult and time-consuming.
, however, such studies may be needed to identify pathological genetic variants that affect specific cells in the development trajectory.
to study the function of genes associated with autism spectrum disorder (ASD), Jin et al. used the gene editing and single-cell sequencing system Perturb-Seq to knock out 35 ASD candidate genes in multiple mouse embryos.
method identifies gene expression networks in neurons and glial cells, suggesting new features of ASD-related genes.
8.Science: Increased photolysal productivity during the growing season leads to early aging of temperat autumn leaves doi:10.1126/science.abd8911; Doi:10.1126/science.abf4481 Under recent climate change, the length of the growing season in tempered forests has been increasing because leaves appear earlier and leaves age later.
, However, Zani et al. have found that this trend may reverse as increased photolysal productivity begins to push autumn leaves to age earlier.
combined with experimental, observational and modelling studies based on forest trees in Europe, the researchers concluded that by the end of the 21st century, leaf aging would be three to six days ahead of schedule, rather than extending by 1-