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September 30, 2019 / BIOON / -- September 2019 is coming to an end What are the highlights of cell journal in September worth learning? Xiaobian has sorted this out and shared it with you 1 Cell: rethink how cholesterol is integrated into cells Doi: 10.1016/j.cell.2019.08.038 NPC (Niemann pick type C) protein is essential for sterol homeostasis such as cholesterol NPC proteins are thought to promote the integration of sterols into lysosomal membranes before redistribution to other cell membranes In a new study, the researchers proposed a framework for the integration of sterol membranes by using crystallography and cryoelectron microscopy in combination with in vivo studies of the NPC system of Saccharomyces cerevisiae (ncr1 and NPC2) The relevant research results were published online in the journal Cell on September 19, 2019, under the title of "structural insight into eukaryotic steel transport through Niemann pick type C proteins" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.08.038 Sterols were transferred between the hydrophobic pocket of vacuole NPC2 and membrane protein NCR1 The N-terminal domain (NTD) of ncr1 is located to deliver sterols to a tunnel that connects NTD to the lumen leaflets at a distance of 50 Å In the process of transport, sterols are trapped in the inner part of the tunnel The proton relay network composed of charged amino acid residues in the transmembrane region is connected with the tunnel, thus supporting a proton driven transport mechanism These researchers proposed a sterol integration model, which elucidated the role of NPC protein in this essential eukaryotic pathway, and rationalized the mutations in patients with Niemann Pick disease type C 2 Cell: new research shows that intestinal bacteria can improve the efficacy of influenza vaccine in clinical trials doi: 10.1016/j.cell.2019.08.010 in animal models and human related research more and more evidence shows that the presence of microorganisms in the gut can shape immune response In a new study, researchers from Stanford University in the United States confirmed the association in humans They found that for people who had not been vaccinated against influenza or who had not been infected with the virus in the past three years, antibiotic treatment regimens prior to vaccination resulted in fewer antibodies being immunized than the study participants who had not been treated with antibiotics The related research results were recently published in the journal Cell, and the title of the paper is "antiotics driven gut microbiome perfusion alters immunity to vaccines in humans" "It's very important to do this kind of research in humans because a lot of research has been done in animal models," said Dan Littman, who studies flora immune system interactions at the New York University School of medicine Although this is valuable, especially in understanding how the immune system reacts to flora, vaccinations, and fatal microbial infections, there are significant differences in the human body, and we know very little about how the human body reacts " 3 Cell: using proteomics technology to reveal why patients with metastatic melanoma do not respond to immunotherapy? doi:10.1016/j.cell.2019.08.012
In a recent study published in the international journal Cell, researchers from the University of Tel Aviv explained why more than half of patients with metastatic melanoma did not respond to cancer immunotherapy In this paper, the researchers used proteomics technology (protein mapping) to answer a question they urgently want to know, that is He immunotherapy is very helpful for melanoma patients, but it has no effect on 60% of patients with metastatic melanoma The researchers compared the response of 116 melanoma patients to immunotherapy (including those who were successfully treated and those who were not) Using proteomics technology, the researchers could find the difference in metabolism of cancer cells between the two groups Professor markel said that in recent years, scientists have used a variety of cancer immunotherapies, that is, these therapies can enhance the anti-cancer activity of the body's immune system These therapies can effectively treat some cancer patients, but some patients have no response to immunotherapy, and the current researchers do not know the molecular mechanism In this study, the researchers focused on the study of metastatic melanoma In order to better understand the molecular mechanism of cancer cells' tolerance to therapy, the researchers analyzed tumor samples from 116 patients using proteomics technology; the researchers used a mass spectrometer to map a variety of proteins in the cells, and then carried out a lot of calculation and analysis to identify them The comparison of proteome can help to identify the main differences between the two groups In the responder body, the high level of protein expression is closely related to lipid metabolism, which may be better recognized by the immune system Then the researchers validated their results in the mouse model of metastatic melanoma and melanoma tissue culture Using genetic engineering technology, they silenced the cellular mechanism responsible for lipid metabolism The researchers found that after silencing the metabolic pathway, the cancer cells could try to hide to avoid being recognized and damaged by the host body's T cells Therefore, the mouse body The cancer cells developed faster than those in the control group 4 Cell: successfully mapped the connection map of 1000 neurons in mouse brain doi: 10.1016/j.cell.2019.07.042 In a new study, researchers from the Jennifer Research Center at the Howard Hughes Institute of medicine carefully unraveled more than 1000 entangled neurons, tracking each cell's branching path in the brain to determine where it went and which cells it was connected to If placed end-to-end, the neurons would stretch more than 80 meters, about the length of two school buses, they report Relevant research results were recently published in the Journal of cell, and the title of the paper is "reconstruction of 1000 project neurons reviews new cell types and organization of long range connectivity in the mouse brain" When jayaram chandrashekar and his colleagues started their neuromapping two years ago, neuroscientists had a general idea of which areas of the mammalian brain talk to each other But the structure of information transfer in the brain is largely a mystery A complete neural circuit map can help scientists better understand how the brain is connected and how information is transmitted through this neural circuit In October 2017, the neuron tracking project team mouselight released the data of the first 300 neurons Today, they've expanded the data set dramatically, adding more than 700 neurons "This is the largest number set of such neurons to date," chandrashekar said 5 Cell: new research reveals the regulatory effect of selective promoter in tumor doi: 10.1016/j.cell.2019.08.018 In a new study, researchers from research institutions such as the Singapore Genomics Institute (GIS) found that many human cancers show a wide range of changes in gene activation, and the same gene uses different starting positions to produce selective gene products These changes have not been detected by early analytical methods, and may be used to identify new biomarkers and new therapeutic targets for predicting the survival of cancer patients The related research results were recently published in cell journal, and the title of the paper was "a pan cancer transcription analysis revels pervasive regulation through alternative promoters" Picture from cell, 2019, DOI: 10.1016/j.cell.2019.08.018 The human genome contains all our genes The region that controls where the gene starts is called the promoter, or the "switch" that turns on the gene in the genome Many genes have multiple promoters, which can even lead to different functions of the same gene The researchers designed a special software called Proactiv, which is used to detect the activated promoter in the whole genome The basic algorithm in Proactiv is applicable to RNA analysis data, which is usually generated by hundreds of cancer research laboratories around the world They applied Proactiv to a large number of open data collected from more than 18000 cancer samples, and found that the promoters in cancer genes are often different from those in human without cancer They also found specific activation promoters associated with survival in cancer patients, which represent a new class of biomarkers 6 Cell: targeted activation of PV neurons in the critical time window is expected to treat schizophrenia doi: 10.1016/j.cell.2019.07.023 although the induction process occurs earlier, schizophrenia appears in early adulthood, which indicates that it may involve pathological changes in the late brain development of susceptible individuals In a new study, using a genetic mouse model of schizophrenia, pico Caroni and his team from the Swiss Institute of Friedrich Mitchell (FMI) found that, like human patients, characteristic network and cognitive deficits only occur in adult mice They then confirmed that during the sensitive time window of late adolescence, these defects could be permanently prevented by specific treatment The relevant research results were recently published in the journal Cell, and the title of the paper is "long lasting rescue of network and coherent dysfunction in a genetic schizophrenia model" In order to study the underlying causes of a complex genetic disease, people need to focus on the simpler genetic model as much as possible, that is, carrying a clearly defined mutation of human or animal, and / or they show a higher incidence rate In schizophrenia, such genetic models include people with 22q11DS syndrome, which is caused by partial deletion of chromosome 22 The risk of schizophrenia in these people increases 20-30 times This led the researchers to develop mice that carried the corresponding deletions in order to use them as models of schizophrenia for laboratory research (these mice are called "lgdel mice," but for simplicity, they are called "schizophrenic mice" here.) Using a schizophrenic mouse model, the Caroni team set out to study the defects that schizophrenic mice showed and how to treat and prevent them They found that what is known to exist in human patients also exists in schizophrenic mice: network and cognitive dysfunction in late adolescence Like human patients, adult mice show severe dysfunction in specific types of neurons called PV neurons, in which PV neurons are important mediators of neural networks This dysfunction leads to network synchronization defects, which is a sign of schizophrenia It is worth noting that the antipsychotics Department temporarily suppresses the Internet and cognitive deficits in adult schizophrenic mice 7 Cell: the long-standing problem of cell development is finally solved! It is revealed that neural crest cells clear dead cells in early embryonic development doi: 10.1016/j.cell.2019.08.001 no matter it is human, fish or any other