October 11, 2019 Science journal essence

October 27, 2019 / BIOON / - -- a new issue of Science Journal (October 11, 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: great progress! It is revealed that the gene shisa7 controls the tranquilizing effect of benzodiazepines Doi: 10.1126/science.aax5719; doi: 10.1126/science.aaz3176 between 1999 and 2017, the number of deaths due to excessive use of Valium (also known as benzodiazepine, or diazepam) and other benzodiazepines in the United States increased tenfold For many years, scientists have believed that these powerful tranquilizers, used to treat anxiety, muscle spasms and sleep disorders, alone play a role in calming nerves Now, in a new study, researchers from the National Institutes of Health (NIH) in the United States have found that this view of the neural circuits of such drugs and their effects may have to change By studying mice, they found that this might require the help of a "sticky" gene named shisa7 The relevant research results were published in the Science Journal on October 11, 2019 The title of the paper is "shisa7 is a GABAA receiver auxiliary subunit controlling benzodiazepine actions" "We found that shisa7 plays a key role in the regulation of inhibitory neural circuits and the sedative effect of some benzodiazepines on the activity of neural circuits," said Wei Lu, Ph.D., co-author of the paper and researcher at the National Institutes of Neurology and stroke (NINDS), National Institutes of health We hope that these results will help scientists design more effective treatments for various neurological and neuropsychiatric diseases caused by problems in these circuits " 2.! In the same research group, two back-to-back articles of science were published: revealing the relationship between sleep and synaptic rhythm doi: 10.1126/science.aav3617; doi: 10.1126/science.aav2642; Doi:10.1126/science.aay5304, a time biologist at Ludwig-Maximilians-Universitaet (LMU) in Germany, pointed out in the two articles of Science that sleep wakefulness cycles are crucial to the protein and phosphorylation kinetics regulating the activity of synapses in synapses Ludwig-Maximilians-Universitaet The biological clock controls almost all the physiological processes of human body and predicts the environmental changes of daily cycle such as day and night The molecular mechanism of how circadian rhythm and sleep affect the level of brain cells remains unclear Professor Maria Robles, group leader of LMU medical psychology research team, recently published two articles in the journal Science, revealed how sleep and wakefulness cycles (rather than biological clocks) drive protein abundance in the brain and the cycle of synaptic protein phosphorylation to organize synaptic activity "Our research shows that sleep wake cycle plays a central role in time regulation of many aspects of synaptic function," said Maria Robles Maria Robles, a time biologist at LMU, and her team used quantitative proteomics based on mass spectrometry to map the daily dynamics of protein and phosphorylation in isolated synapses in the mouse forebrain In these studies, the team investigated how synaptoproteins and phosphoproteomes form dynamically during the day, and the effects of sleep deprivation on them In one study, the team found that a quarter of the 8000 key synaptic proteins phosphorylated on a normal day had two major peaks: one when the mice woke up and the other before they went to bed "This suggests that synaptic phosphorylation plays a key role in regulating synaptic function, especially during the sleep wake sleep transition," said Maria Robles "The pattern of phosphorylation of this feature seems to reflect the accumulation and dissipation of sleep and waking pressure, as sleep deprivation almost completely eliminates the synaptic phosphorylation rhythm "Our research shows that key synaptic processes are regulated by phosphorylation when it comes to sleep and wake-up stress," said Maria Robles "In the second study, published in the same issue of science, the same team worked with a team at the University of Zurich (Steve Brown) to show that synaptic protein abundance is also controlled rhythmically by the sleep wake cycle In particular, they showed that synaptic activity triggers the cycle of messenger proteins, which gather at the synapse in a rhythmic fashion throughout the day Although the production of proteins depends entirely on the awake sleep cycle, the travel and accumulation of messenger molecules in synapses are mainly in response to the mechanism of circadian rhythm 3 Major discovery of science! Migrating dendritic cells activate TGF - β to regulate CD8 T cell doi: 10.1126/science.aav5728; Doi: 10.1126/science.aaz3289 a group of researchers from the United States and the United Kingdom found that migratory dendritic cells (DCS) can activate transforming growth factor - β (TGF - β) before regulating the non sensitized CD8 + T cells, which can transform T cells into tissue-resident T cells (TRM) implanted in the skin In their paper, published in the journal Science, the team described their work on these cells and how they were pretreated before entering the epidermis Donna Farber of Irvine Medical Center at Columbia University published an outlook on the team's work in the same issue of the journal Previous studies have found that memory T cells exist in tissues, rather than circulating in the body This TRM is produced when the human body successfully defeats an invading factor (such as a virus), which is an important mediator for the human body to remember how to fight the same virus the next time it encounters it One of the TRM is CD8 + epithelial TRM (ETRM) cells in the skin Previous studies have also shown that when T cells are generated in bone marrow, they enter the lymph nodes, where they are trained to form the T cells the body needs to support normal immune responses These specialized T cells rely on TGF - β to mature normally But the details of this process are still under study In this new work, the researchers looked at the role of DCS expressing α V integrin in the transformation process This work involves knockout of the α V integrin of CD11c + DCS in mouse model to detect the maturation process of non sensitized CD8 + T cells This resulted in a significant reduction of CD8 + T cells in the skin, but had no effect on T cells in the lymph nodes This suggests that migratory DCs play an important role in the activation of CD8 + T cells pretreated by TGF - β In addition, this suggests that the distribution of pre immune T cells in tissues may not be as uniform as previously thought 4 Science: the three-dimensional structure of human RAGA / ragc heterodimer doi: 10.1126/science.aax3939 the target of rapamycin complex 1 (mTORC1) is called master kinase, which plays a key role in integrating multiple signals to regulate cell growth As a class of ornithine triphosphatase, rag's heterodimer binds to mTORC1 and recruits it into lysosomes when it is nutritious Here, other signal transduction pathways converge on mTORC1 complex Anandapadamanaban et al Analyzed the low temperature electron microscope structure and crystal structure of RAGA / ragc heterodimer These structural and dynamic studies explain the nucleotide states required for binding to mTORC1 and support the mechanism of conformational communication between RAGA and ragc subunits in this heterodimer Raga / ragc binding does not cause conformational changes in mTORC1, which is consistent with the view that mTORC1 must detect other growth regulators before being activated 5 Science: lowering the glun3a receptor subunit level in the medial habenular nucleus can prevent conditioned position aversion doi: 10.1126/science.aax1522 glycine is considered to be a major inhibitory neurotransmitter However, it can also be used as a coagonist for the excitatory N-methyl-D-aspartic acid (NMDA) receptor Otsu et al Studied the function of NMDA receptor subunit combination glun1 / glun3a in the medial habenula (MHB) of adult mice This combination of NMDA receptor subunits in MHB neurons is activated by glycine released by astrocytes Activation of glun1 / glun3a NMDA receptor results in depolarization and spike increase of MHB neurons Decreasing glun3a receptor subunit level in MHB can prevent conditioned place aversion 6 Science: build a global model to explore the contribution of nature to human beings doi: 10.1126/science.aaw3372; Doi: 10.1126/science.aaz1433 a recent global assessment of the Intergovernmental science policy platform on biodiversity and ecosystem services highlighted the urgent need to determine where nature's contribution is and how it is most important to mankind Chaplin Kramer et al developed a global ecosystem service model focusing on water quality regulation, coastal protection and crop pollination By 2050, up to 5 billion people could face the risk of reduced ecosystem services, particularly in Africa and South Asia (BIOON Com)