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April 5, 2019 Science Journal Highlights

author:ZhongAn Health Bank

Published in the journal Science (April 5, 2019).

April 5, 2019 Science Journal Highlights

Image from the journal Science

1. Chinese scientists have revealed the activation mechanism of plant immune receptor ZAR1 in two Science papers

doi:10.1126/science.aav5868; doi:10.1126/science.aav5870; doi:10.1126/science.aax0174

Although distinguished over more than a billion years of evolution, plants and animals have employed similar immune strategies to protect themselves from pathogens. An important mechanism is determined by cytoplasmic receptors called NLRs, in which NLR recognizes so-called effectors, molecules secreted into plant cells by invading microorganisms. These recognition events involve either direct identification of the effector by the NLR or indirect identification of the effector by the NLR, i.e., the NLR acts as a "guard" to monitor other host proteins modified by the effector, or "guardee" or "guardee" Whether the host recognizes the effector directly or indirectly, it leads to cell death, thereby confining the microorganism to the site of infection. So far, however, we have lacked a detailed understanding of the mechanism of action of plant NFR, and the understanding of how these molecules function in plants is largely based on comparisons with animal NLR molecules.

Now, in two new studies, Hong-Wei Wang's group at Tsinghua University in China, Jijie Chai's group at Tsinghua University's School of Life Sciences, and Jian-Min Zhou's at the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences have pieced together a cascade of molecular events in which inactive NLR molecules are converted into active complexes that provide disease resistance. The findings were published in the April 5, 2019 issue of the journal Science, titled "Ligand-triggered allosteric ADP release primes a plant NLR complex" and "Reconstitution and structure of a plant NLR resistosome conferring immunity, respectively." ”。

The authors focused on an NLR receptor called ZAR1. As an ancient plant molecule, this protein is likely to have broad importance because it interacts with multiple 'protected' in order to identify unrelated bacterial effectors.

By using cryo-EM, the authors observed that in the absence of bacterial effectors, ZAR1, along with the plant protein RKS1, was maintained at rest by interactions involving multiple domains of the ZAR1 protein. Once infected, the bacterial effector modifies the plant protein PBL2, which then activates RKS1, resulting in huge conformational changes that first allow plants to swap ADP for ATP, followed by the assembly of a pentameric rotunda structure, which they call "ZAR1 resistosome."

A notable feature of this structure is its similarity to animal NLR proteins: once activated, animal NLR proteins are also assembled into a wheel-like structure that acts as a signaling platform for cell death execution and immune signal transduction. However, an important difference between the rotisserie structure assembled by plant NLR and animal NLR provides tantalizing clues as to how ZAR1 induces cell death. The authors were able to identify a highly ordered funnel-like structure in ZAR1. This funnel-like structure tethers ZAR1 disease-resistant bodies to the plasma membrane are also necessary for cell death and disease resistance. They speculate that ZAR1 may form pores in the plasma membrane and disrupt cell function in this way, leading to immune signaling and cell death.

2.Science: Discovered a small peptide that prevents cannibalism--- SELF-1

doi:10.1126/science.aav9856

The nematode's favorite food to eat is its larvae, and it must be very careful not to accidentally eat its offspring. In a new study, researchers from the Max Planck Institute for Developmental Biology in Germany have discovered how these tiny nematodes, which are only one millimeter long, can distinguish their offspring from those of other nematodes and thus avoid cannibalism. They found that the Pristionchus nematode identifies its offspring through a complex mechanism. These nematodes carry a smaller, highly variable protein on their surface that appears to be detectable by the nematode's nose. The variable part of the protein may act as a self-identifying code, and even a change in amino acids can lead to cannibalism. The findings were published in the April 5, 2019 issue of the journal Science, titled "Small peptide–mediated self-recognition prevents cannibalism in predatory nematodes."

Corresponding author Ralf Sommer, chief scientist at the Max Planck Institute for Developmental Biology, said, "Self-identification is everywhere in the animal and plant kingdom. It is at the heart of numerous biological processes--- from the aggregation of single-celled organisms to the social or aggressive behavior of various animals--- and is a key part of the human immune system responsible for defending against pathogens. However, although self-identification is widespread, such organism self-identification has not been described in Nematodes before. Sommer established pristionchus nematodes as model organisms that were compared to the famous Caenorhabditis elegans.

3.Science: The new ALS gene expression atlas provides unprecedented detail for disease progression

doi:10.1126/science.aav9776

In a new study, researchers from the New York Genome Center, the Broad Institute, Columbia University, Stanford University, New York University, the Flatiron Institute, and the Royal Swedish Institute of Technology used the new technique to map gene expression in spinal cord samples, providing new insights into the mechanisms of disease occurrence and progression in patients with muscle lateral sclerosis (ALS). They combined spatial transcriptomics with a new computational method to obtain measurements of gene expression in time and space for nearly 12,000 genes in the spinal cord. The result is a new multidimensional gene expression map. This gene expression map provides unprecedented detail and scale, and provides a previously unobtainable view of ALS disease progression. The findings were published in the April 5, 2019 issue of the journal Science, titled "Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis." The corresponding authors are Dr. Hemali Phatnani of the New York Genome Center, Professor Richard Bonneau of New York University, and Dr. Joakim Lundeberg of the Royal Institute of Technology in Sweden.

The researchers describe how this spatiotemporal gene expression map reveals early changes in ALS disease that cannot be observed using traditional sequencing methods. They have also developed new computational methods to reveal changes in the activity of many signaling pathways for all cell types in the disease-driven central nervous system, which could provide new targets for the development of therapeutic and diagnostic approaches.

What makes this study unique compared to previous transcriptome analysis studies is the spatial transcriptomics method used by these researchers, which is capable of generating RNAseq profiles at many locations in tissue slices simultaneously. As a result, they were able to precisely record the expression location of almost every gene in the tissue. Based on this, they were able to accurately record the expression location of almost every gene in the tissue. They examined four time points in disease development in an ALS mouse model, from the earliest to the end of adulthood. In addition, they tested spinal cord samples from ALS patients after death.

In the new study, the researchers collected 76,136 spatial gene expression measurements (SGEM) from 1,165 mouse tissue slices and 61,031 SGEM from 80 human tissue slices (for the background, the next maximum comparable spatial resolution transcriptomics study considered only about 12 tissue slices at the same point in time). By combining data from many tissue slices, they were able to simultaneously detect the expression of nearly 12,000 genes in the tissue region to be detected. This is the first time als has been studied at this depth and scale using this spatial resolution method.

4. Two sciences reveal the mechanism of NLRP1B inflammatory body activation

doi:10.1126/science.aau1330; doi:10.1126/science.aau1208

The inflammatory body is a polyprotein complex that coordinates pro-inflammatory cytokine secretion and cell death. Proteases such as anthrax lethal factor are able to activate an inflammatory body called NLRP1B, but the mechanism of this activation remains unclear. Chui et al. found that the proteolysis of NLRP1B by lethal factors induces proteasome degradation and eventual cell death in the NLRP1B amino terminal domain through genome-wide knockout screening. Sandstrom et al. found that degradation of the amino-terminal domain of NLRP1B leads to the release of a carboxyl-terminal fragment that activates caspase-1 (caspase-1). This process, called "functional degradation," allows the immune system to detect pathogen-related activity as if it recognized pathogen-associated antigens.

5.Science: Tracking meiosis in maize

doi:10.1126/science.aav6428

Plants do not leave germ cell lineages from early development, as animals do, but produce germ cells as needed. Nelms and Walbot used corn as the subject of the study, using the difference in size between somatic cells and developing germ cells in the anthers at the top of the maize plant to isolate individual germ cells during meiosis for pollen development. They used single-cell RNA sequencing to study transcriptome changes during meiosis. These studies show that the degree of specialization of meiosis increases as it progresses, while at the same time, during the transitional phase of the meiosis fine line phase, this transcriptome recombines.

6.Science: Reveals that phosphatidylserine regulates the aggregation of ROP6 in plant plasma membranes

doi:10.1126/science.aav9959

Some lipid variants rare in the plasma membrane act as signal transduction components. By studying the root tip cells of the model plant Arabidopsis thaliana, Platre et al. found that phosphatidylserine, which is relatively abundant in the plasma membrane, also regulates signaling pathways. In response to signals from auxins, phosphatidylserine is required for ROP6 ( a small guanosine triphosphatase ) to aggregate in the membrane. Changes in phosphatidylserine concentrations alter the aggregation of ROP6, thereby altering the auxin signaling response.

7.Science: Flocks of birds that have lost their flight multiple times have convergent evolution in flight-related gene-regulated regions

doi:10.1126/science.aat7244

Species from very different taxa groups undergo similar changes in traits. Which underlying genetic factors cause these parallel changes remains an open question. Sackton et al. observed flocks of birds that had lost their flight multiple times--- ratites and tinamous (a type of walking bird native to South America) and found that there was convergence in the regulatory regions associated with flight-related genes, but not in the protein-coding regions. Changes that occur within these regulatory regions affect limb development and may represent a rapid pathway to convergent changes across taxa.

8.Science: Invasive birds can also spread seeds of native plants

doi:10.1126/science.aau8751

When humans introduce alien species into sensitive ecosystems, invasions of alien species and extinction of native species often follow. The resulting ecological communities can create unusual interactions between survivors and new invaders. Vizentin-Bugoni et al. analyzed the structure of seed propagation networks in Hawaii, where native birds were mostly replaced by invaders. They found that native plants now rely on invasive birds for seed propagation. This propagation interaction network is complex and stable, which is also characteristic of indigenous seed propagation networks in other parts of the world. In some cases, it seems that the introduced species may be integrated into the local ecosystem.

April 5, 2019 Science Journal Highlights
April 5, 2019 Science Journal Highlights