November 29, 2019 Science journal essence

December 12, 2019 / BIOON / - -- a new issue of Science Journal (November 29, 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: using machine-guided design method to optimize the coat of AAV virus doi: 10.1126/science.aaw2900 natural AAV does not specifically target the diseased cells and tissues, they can be recognized by the immune system, thus limiting their therapeutic success In order to improve AAV, synthetic biologists have been using the "directed evolution" method, that is, random mutation of specific amino acids of capsid proteins that directly contact the target cells By assessing which amino acid changes can deliver AAV to the target tissue, and iterating the mutations in turn, they aim to improve the required AAV characteristics Now, in a new study, researchers from the Weiss Institute of bioengineering and Harvard Medical School at Harvard University report a way to speed up the process of making such improved AAV shells and develop better AAV viruses Relevant research results were recently published in the journal Science The title of the paper is "comprehensive AAV capped fitness landscape reveals a virtual gene and enables machine guided design" Using a different and more systematic method of capsid protein engineering, the researchers mutated 735 amino acids in AAV-2 capsid one by one, including all possible codon substitutions, insertions and deletions at each site They produced a library of about 200000 virus variants and identified coat changes that both maintained the viability of AAV-2 and improved its "homing" potential (i.e., sex preference) to specific organs in mice Unexpectedly, they also found a novel helper protein hidden in the capsid encoded DNA sequence, which binds to the cell membrane of the target cell 2 Science: new research reveals the mechanism of lactose promoting the production of graft-versus-host disease doi: 10.1126/science.aax3760; Doi: 10.1126/science.aaz7595 in a new study, researchers from the United States, Germany and Japan conducted a large-scale analysis of more than 1300 patients receiving allogeneic hematopoietic cell transplantation from four clinical centers, and found several high-level enterococci, especially Enterococcus faecalis Faecium) - associated with higher GVHD incidence and mortality in these patients The relevant research results were recently published in the journal Science, and the title of the paper is "lactose drives Enterococcus expansion to promote grant versus host disease" They found that after allogeneic hematopoietic cell transplantation, Enterococcus also proliferated in the gastrointestinal tract of mice, and aggravated the severity of the disease in sterile animal models The growth of Enterococcus depends on a disaccharide called lactose, and the elimination of lactose in diet will weaken the growth of Enterococcus, reduce the severity of GVHD in mice, and improve their survival rate Patients with lactose malabsorption genotype had higher enterococcal abundance, and the ability to eliminate enterococci after antibiotic treatment was poor after allogeneic hematopoietic cell transplantation It can be seen that as a common nutrient, lactose can promote the proliferation of Enterococcus, which will play an important role in intestinal and systemic inflammatory diseases 3 Science: reveal that VGLUT2 neurons play a key role in remembering and dealing with negative experiences doi: 10.1126/science.aay8746; doi: 10.1126/science.aaz8638 in a new study, researchers from the Hungarian Academy of Sciences and the University of semelvis found that a central part of the brain stem of mice regulates their ability to evaluate, process and remember negative experiences The related research results were recently published in the Journal of science, and the title of the paper was "medical raph controls acquisition of negative experience in the mouse" In this paper, they describe the experiments they carried out using mice to stimulate neurons and what they learned from them Satoshi ikemoto of the National Institutes of Health (NIH) published an opinion type article in the same issue of science, outlining the history of research on how mammalian brains respond to threats and other negative experiences To learn more about how mice deal with negative experiences and then respond to them, the researchers conducted a series of experiments involving neuronal stimulation More specifically, they used a set of neuroscience tools they described to study the neural circuits associated with negative experiences in mice, with an emphasis on the medial raphe region (MRR) located in the lower part of the brainstem The researchers reported that they found that a previously unknown group of MRR neurons (called VGLUT2 neurons) in mice are the main centers for remembering and processing negative experiences and the behaviors that occur when they experience them again They also found that stimulation of these neurons in the brains of experimental mice led to avoidance type behavior and anxiety related symptoms Inhibition of this group of neurons has the opposite effect - mice no longer respond to experiences that usually scare them 4 Science: enhancer genetic variation in brain cell type or predictable disease risk doi: 10.1126/science.aay0793 In a new study, researchers from the University of California, San Diego School of medicine and the shack Institute of biology and other research institutions now find specific genetic variations in some enhancers that determine whether proteins are expressed in specific cell types in the brain and may play a role in people's risk of mental or neurological disease Using healthy tissue extracted from six patients, they isolated four different types of brain cells - neurons, microglia, oligodendrocytes and astrocytes Then they studied the genetic variation related to disease in enhancers of each cell type to find the variation possibly related to disease risk The related research results were published online in the journal Science on November 14, 2019 The paper title is "brain cell type – specific enhancer promoter interface maps and disease risk association" By using new molecular technology, they can further determine the relationship between enhancer regions and their target genes, thus providing new insights on how the variation of enhancer regions affects the expression of downstream genes in specific cell types "The brain is very complex and there are many different cell types in different brain regions," said Dr Inge holtman, CO lead author of the paper and a postdoctoral researcher in the Department of cell and molecular medicine at the University of California, San Diego School of medicine At present, our understanding of regulatory landscape is still largely unknown Previous studies have tried to create a consistent regulatory picture of the whole brain, but until now we have not really understood what it looks like in a single cell type This study gives us a better understanding of how genes are regulated, which enhancers exist, and which enhancers loop back to specific genes and affect their expression, especially the specific cell types in the brain " These results show that although many genes are expressed in many different cell types, enhancer regions differ from cell to cell, and disease risk is usually related to specific enhancer regions in specific cell types 5 Science: reveal the amazing details of mammalian cerebral cortex doi: 10.1126/science.aay3134 mammalian cerebral cortex is a very complex network of neuronal processes, which are long and thin, with branches and highly dense accumulation This high packing density makes the reconstruction of cortical neural network challenging Motta et al Used advanced automated imaging and analysis tools to reconstruct the morphological characteristics of 89 neurons and their connections in the barrel cortex of mice at high spatial resolution The area covered by this reconstruction is two orders of magnitude larger than the early attempts of neuroanatomical mapping This method reveals the connectivity information of inhibitory synapses and excitatory synapses of cortex cortex connection and excitatory thalamic cortex connection 6 Science: ParB protein catalyzed CTP hydrolysis promotes chromosome assembly doi: 10.1126/science.aay3965; doi: 10.1126/science.aaz8632 pars sequence in bacterial centromere recruits ParB protein to bacterial chromosomes SOH et al Found that the widely distributed ParB protein family not only binds DNA, but also binds and hydrolyzes cytidine triphosphate (CTP) The hydrolysis of CTP by ParB is activated by pars and regulates the diffusion of ParB protein to the flanking region of pars, which is crucial for the assembly of bacterial chromosomes The cytidine triphosphatase domain of ParB protein is conserved in many protein sequences, which indicates that it plays a potential role in other cell processes 7 Science: reveal the folding process of helix membrane protein doi: 10.1126/science.aaw8208 membrane protein will be inserted into cell membrane during translation, and may fold into their secondary and tertiary structures at the same time Choi et al described a single molecular force microscopy technique that allows them to monitor the folding of spiral membrane proteins in vesicles and bicells Two kinds of helix membrane proteins, E.coli GlpG and human β 2- adrenergic receptor, all fold from N to C and have the structure of helix hairpin In cells, this will allow these proteins to begin to fold during translation (BIOON Com)