The Essence of Science Journal in December 2018

1.Science: Pro-Linked Protein 2 Cutting Can Prevent Heart Failure

doi:10.1126/science.aan3303; doi:10.1126/science.aav8956


Dr. Long-Sheng Song, a researcher at the University of Iowa in the United States, and his team have confirmed in a previous study that a structural protein called junctophilin-2 (JP2) is essential for the heartbeat. Heart failure is associated with this protein loss or destruction.


Now, in a new study, researchers from the University of Iowa, Shanghai Jiaotong University, and Nantong University focus on JP2. They used mice as a research object, revealing that under pressure, JP2 was cut into two fragments. This cutting of JP2 destroys the structure and function of heart cells. They were surprised to find that one of these two newly produced JP2 fragments protects the heart from damage by going to the nucleus of heart cells and turning off gene expression that promotes heart failure. Related research was published online in the journal Science, entitled “E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator”.


Heart disease such as high blood pressure, arterial occlusion or heart attack can put stress on the heart. At the cellular level, this type of stress activates a calcium ion-dependent protease, calpain, which cleaves JP2 into two fragments. The new study suggests that the amino-terminal fragment of JP2 migrates into the nucleus of heart cells and initiates genetic alterations that prevent heart failure. DNA sequences that allow this fragment to enter the nucleus and regulate gene expression are highly conserved in many species from mouse to human.


To confirm the beneficial effects of the JP2 amino-terminal fragment, these researchers genetically engineered mice to express higher levels of the JP2 amino-terminal fragment. These mice did not develop heart failure when subjected to cardiac stress. Conversely, mice that have been genetically engineered to lose this function of the JP2 amino-terminal fragment in the nucleus of heart cells develop heart failure at a faster rate after suffering from cardiac stress.



2.Science: Revealing the Gating Mechanism of Human TRPM2 from the Structure



Adenosine diphosphate ribose (ADPR) mediates calcium release by activating the transient receptor potential M2 channel (TRPM2). There are three structures that clarify the conformational regulation mechanism of TRPM2 gated. Longfei Wang et al. describe the low-temperature electron microscopy structure of human TRPM2 in the state where ADPR binds but calcium ions are not bound and in both combined state of ADPR and calcium ions. In the unbound state of calcium ions, the interaction between the internal of the subunit and subunits appears to lock TRPM2 in a closed, auto-suppressed state. ADPR binding disrupts some interactions and significantly changes the TRPM2 conformation. Calcium ion binding further triggers the opening of this channel.



3.Science: Structurally Reveals the Mechanism by Which Human TFIID Loads RNA Polymerase II onto a DNA Promoter



To initiate transcription, RNA polymerase II is recruited to the DNA promoter by the universal transcription factor IID (TFIID). Patel et al. used a variety of experimental methods to elucidate the complete molecular structure of human TFIID and its complete conformation during promoter recognition. They proposed how TFIID is exactly loaded onto this promoter, which involves multiple defined steps, including promoter recognition and transcription initiation, and results in regulated gene expression.



4.Science: Combined Use of Two Small Molecule Drugs Leads to Natural Killer Cell-Mediated Cancer Cell Killing

doi:10.1126/science.aas9090; doi:10.1126/science.aav7871


Immunotherapy is an effective treatment for certain cancers. However, for those who do not respond, strategies to stimulate the immune system and directly target malignant cells may be more effective. Ruscetti et al. reported the use of two clinically approved anticancer drugs to promote immune surveillance in mice and to kill lung cancer with KRAS mutations. These two small molecule drugs – a mitogen-activated protein kinase inhibitor and a CDK4 / 6 inhibitor recruit natural killer (NK) cells to eliminate aging lung cancer cells, but for both drugs, only use one of the drugs, this effect does not occur.



5.Science: Revealing the Mechanism of Cutting Membrane of ESCRT Protein Complex



The ESCRT protein complex plays a crucial role in cell division, the release of HIV from infected cells by budding, and other processes involving the cutting of narrow necks from their inner surfaces. This unusual, inward-facing membrane cut makes it difficult to reproduce this process and understand its mechanisms. Schöneberg et al. encapsulated the ESCRT protein complex inside the lipid vesicles and used optical tweezers to pull the membrane nanotubes outward. In the presence of adenosine triphosphate, clustered ESCRTs generate forces and shrink the membrane nanotubes, eventually cutting them. This approach provides a window to study the molecular mechanisms involved in ESCRT activity.



6.Science: Revealing the Mechanism of Plant Lateral Root Asymmetry

doi:10.1126/science.aau3956; doi:10.1126/science.aav9375


The growth of plant roots is not a response to the overall architectural blueprint, but rather to finding scarce resources in the soil. Orosa-Puente et al. showed why new lateral roots appear on the wet side of the root rather than on the dry side. The transcription factor ARF7 is distributed throughout the root, but post-translational modification occurs on the dry side of the root, which inhibits its function. The ARF7, located on the wet side of the root, remains functional, thus enabling the initiation of a signal cascade that leads to the formation of new lateral roots.



7.Science: Exploring the Strength of Long-Range Connections in Social Networks of Population Size



We seem to make sense by establishing the closest and strongest connection with people in our direct social networks, and the links between different social networks are weaker. However, Park et al. found a powerful network across non-geographical distances in 11 culturally diverse population networks on four continents, including 56 million Twitter users and 58 million mobile phone users. Although this is very rare, the close connection between different social networks can be very important for the spread of thoughts or diseases.

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