2019 Science journal last issue, December 20, 2019 Science journal essence

December 31, 2019 / BIOON / - -- another issue of Science Journal (December 20, 2019) will be published this week What are the highlights of its research? Let Xiaobian come together The picture is from science journal 1 Science: genome wide transcriptome analysis of all protein coding genes in human blood cells doi: 10.1126/science.aax9198 in clinical and research environment, blood is the main source of molecular analysis for human beings, and is the target of many treatment strategies, which highlights the need for a comprehensive molecular map construction of the cells that make up human blood The human protein atlas project ( ORG) is an open database designed to map all human proteins by integrating a variety of genomic techniques, including antibody based imaging Previously, the human protein map included gene expression information from peripheral blood monocytes, but not from many other blood cell subsets In order to improve the resolution, people need to deeply characterize the cells in the blood to provide detailed details of gene expression in human blood cells and associate them with other tissues in the body For this reason, in a new study, researchers from Karolinska Institute and other research institutions in Sweden conducted transcriptome based expression analysis on 18 classical immune cell populations separated by flow cytometry They combined blood cell expression profiles with tissue expression profiles, including transcriptome data from external sources to expand the number of tissue types and brain regions included in this open database Based on the expression specificity and distribution in blood cells and tissues, they classified the whole genome of protein coding genes The relevant research results were recently published in the journal Science, and the title of the paper is "a genome wide transcription analysis of protein coding genes in human blood cells" These researchers provided the expression map of all protein coding genes in human blood cells and classified them according to the specificity and distribution of all protein coding genes in all major tissues and organs of the human body The whole genome analysis of RNA expression profile of blood cells can identify genes up-regulated in various immune cells, thus confirming previously known protein markers, and identifying new targets for further analysis There are 1448 protein coding genes expressed in a large number of single immune cell types It will be interesting to further study the corresponding proteins to explore the biological functions related to each cell phenotype 2 Science: host cells use aromatics receptors to detect bacterial quorum sensing signals doi: 10.1126/science.aaw1629 bacterial infection will not automatically lead to disease; many bacteria only become dangerous in large numbers In a new study, researchers from institutions such as the Max Planck Institute of infection biology in Germany found that host cells have a receptor that can't recognize the bacteria itself, but can detect communication between bacteria When there are a large number of bacteria, the host will use this receptor to record the pathogenic substances they secrete called virulence factors The related research results were recently published in the journal Science, and the title of the paper was "host monitoring of quorum sensing during Pseudomonas aeruginosa infection" Stefan Kaufmann of the Max Planck Institute of infectious biology and his team found that host cells can observe the communication between Pseudomonas aeruginosa by means of a receptor called the aryl hydrocarbon receptor The receptors detect quorum sensing molecules, allowing host cells to detect when the bacteria are ready to attack "Through this kind of spying behavior, host cells can activate the immune system when they need to resist this bacterial attack," explains Pedro Moura Alves, the first author of the paper In fact, before Pseudomonas aeruginosa reached their quorum sensing level, the receptor eavesdropped the conversation between the bacteria; the early stage of quorum sensing was detected to inhibit the aromatics receptor, thus blocking the early start of host immune defense "It works for the host because it saves energy and allows a small number of bacteria to exist alone, if they don't cause any damage," Kaufmann said Only when they reach a critical number can they have enough energy to defend " It also helps to prevent collateral damage caused by the immune system response 3 Science: challenge the routine! In a new study, under the leadership of David Bartel, Professor of biology, Sean mcgeary, and Kathy Lin, a former graduate student of the Whitehead Institute of Biomedical Sciences, researchers collected six kinds of miRNAs On this basis, an improved prediction model for all single miRNAs was developed Their findings provide unprecedented accuracy and granularity for miRNA target prediction The relevant research results were recently published in the journal Science, and the title of the paper was "the biological basis of microRNA targeting efficiency" In order to understand the targeting effect of miRNA, people need to identify specific sites that can bind to miRNA in miRNA sequence, and they also need to know the interaction intensity binding affinity on each site Generally, miRNA will bind to mRNA when at least six of the first eight nucleotides of miRNA match the complementary nucleotide sequence at a certain location of mRNA These two sequences are like rows of puzzle pieces pushed together: if each puzzle piece is inserted into the corresponding puzzle piece, then these rows of puzzle pieces can be combined into a locked puzzle -- miRNA can be combined with its target If the pieces can't be put together, the rows of pieces can't be connected together These binding sites are exactly matched with the first eight nucleotides of miRNA, which are called canonical sites In the past, it was thought that there was an obvious hierarchical relationship between them Regardless of the identity of miRNA, each site would produce a similar amount of inhibition However, mcgeary did not observe this Mcgeary studied six miRNAs and developed a method to measure the relative binding affinity of each miRNA to a large number of RNA sequences These measurements and mcgeary's further calculations from them form a new and rich database that can be used to improve miRNA targeting prediction Through these experiments, the researchers found that the expected target hierarchy of classical sites is not suitable for all miRNAs In fact, a single miRNA has a stronger affinity for a lower classical site in this desired hierarchy In addition, they found that each miRNA has a unique nonclassical binding site, some of which contain at least one base mismatch but can still bind miRNA They found that in many cases, although the pairing of nonclassical sites was imperfect or abnormal, the binding of miRNA to a nonclassical site was stronger than that to some classical sites "As humans, we like to classify things according to different characteristics," Lin said But to build a quantitative model, you have to realize that the interaction between each miRNA and the target is different " 4 Science: heavy weight! Cancer cells evade treatment by increasing DNA mutations doi: 10.1126/science.aav4474; doi: 10.1126/science.aba1748 as a response to antibiotic therapy, bacteria improve their survival probability by increasing the mutation rate in their genome, so that they have more opportunities to develop drug resistance This strategy is not limited to bacteria In a new study, Italian researchers found that colorectal cancer cells also increase their mutation rate, thereby avoiding death from targeted therapies The relevant research results were published online in the journal Science on November 7, 2019, and the title of the paper is "adaptive portability of color cancers in response to targeted therapies" They first treated colorectal cancer cell lines with cetuximab Cetuximab is an antibody that blocks the epidermal growth factor receptor on the surface of colorectal cancer cells, thus preventing their proliferation The drug is approved for the treatment of patients with metastatic colorectal cancer After 96 hours of treatment, most cancer cells died, but some resistant cells survived two weeks after cetuximab treatment After stopping the drug treatment two weeks later, previously resistant cells grew rapidly and became sensitive to the drug again But if the researchers continue to use the drug for more than two weeks, the cells will become permanently resistant The researchers found that both the mismatch repair gene and the homologous recombination gene were down regulated during the treatment, but returned to normal expression level after the treatment stopped These findings point to a decline in the ability to repair faulty DNA in cancer cells treated with the drug, as well as recurrence in other colorectal cancer cell lines and in pre - and post-treatment tumor samples from patients The authors also determined that cetuximab causes a large increase in error prone DNA polymerases, which are more likely to make mistakes in replicating genetic material, which subsequently leads to a decrease in gene expression encoding high fidelity polymerases This treatment did lead to increased markers of DNA damage and genomic changes in colorectal cancer cells: increased mutations and increased genomic instability The drug also causes stress reactions in bacteria that evade antibiotic eradication by activating mutations 5 Science: challenge the routine! In a new study, researchers from Monash University, Australian Research Council, advanced molecular imaging center of excellence and Doherty Institute of the University of Melbourne redefined our understanding of T cell recognition in the past 20 years The related research results were recently published in the journal Science, and the title of the paper is "a class of γ δ T cell receivers recognize the understanding of the anti retaining mobile MR1" In order to interact with other cells in the body, T cells rely on specialized receptors called T cell receptors that recognize viral or bacterial fragments that bind to specific molecules called major histocompatibility complexes (MHCs) or MHC like molecules In the past 20 years, it has been widely accepted that T cell receptors bind to MHC and MHC like molecules for recognition In this new study, the researchers describe a cell population in a little-known group of T cells called delta T cells that recognize an MHC like molecule called MR1 By using high-intensity x-ray beams at the Australian synchrotron, they obtained detailed three-dimensional images of the interaction between the γ δ T cell receptor and MR1, and obtained interesting results: the γ δ T cell receptor binds under the MHC like molecule for recognition This highly unusual recognition mechanism reshapes our understanding of how T cell receptors interact with their target molecules and represents T cell growth