Viral RNA recognition by LGP2 and MDA5, and activation of signaling through step-by-step conformational changes

細胞内のウイルスを認識する蛋白質の仕組みを解明 --ウイルスから我々の体を守る影のヒーロー--. 京都大学プレスリリース. 2020-12-04.Cytoplasmic RIG-I-like receptor (RLR) proteins in mammalian cells recognize viral RNA and initiate an antiviral response that results in IFN-β induction. Melanoma differentiation-associated protein 5 (MDA5) forms fibers along viral dsRNA and propagates an antiviral response via a signaling domain, the tandem CARD. The most enigmatic RLR, laboratory of genetics and physiology (LGP2), lacks the signaling domain but functions in viral sensing through cooperation with MDA5. However, it remains unclear how LGP2 coordinates fiber formation and subsequent MDA5 activation. We utilized biochemical and biophysical approaches to observe fiber formation and the conformation of MDA5. LGP2 facilitated MDA5 fiber assembly. LGP2 was incorporated into the fibers with an average inter-molecular distance of 32 nm, suggesting the formation of hetero-oligomers with MDA5. Furthermore, limited protease digestion revealed that LGP2 induces significant conformational changes on MDA5, promoting exposure of its CARDs. Although the fibers were efficiently dissociated by ATP hydrolysis, MDA5 maintained its active conformation to participate in downstream signaling. Our study demonstrated the coordinated actions of LGP2 and MDA5, where LGP2 acts as an MDA5 nucleator and requisite partner in the conversion of MDA5 to an active conformation. We revealed a mechanistic basis for LGP2-mediated regulation of MDA5 antiviral innate immune responses

看護師のアピアランスに関する認識

This study aimed to clarify recognition about the appearance of nurses in an acute stage hospital and contribute to effective spread and enlightenment for maintenance of the appearance support system. The authors performed a questionnaire survey with the items such as interest in appearance care, start period, participants for care, enforcers, support resource and so on for １８３ nurses with cancer nursing experience who worked at hospitals in local cities that were bases for cancer treatment cooperation. The result revealed that a number of participants interested in appearance care and most of them recognized that appearance care should start at the time of cancer examination or before treatment. Moreover, it has been indicated that the nurses who were highly concerned with appearance care from a wider perspective including patients’ psychological conditions. The result has suggested that it is necessary to promote “care to prepare in anticipation of change in physical appearance” on the basis of the characteristic of acute stage hospitals and establish an individual support system in accordance with the conditions of the nurses’ interest in appearance for maintenance of the appearance support system

Direct Observation of Strand Passage by DNA-Topoisomerase and Its Limited Processivity

Type-II DNA topoisomerases resolve DNA entanglements such as supercoils, knots and catenanes by passing one segment of DNA duplex through a transient enzyme-bridged double-stranded break in another segment. The ATP-dependent passage reaction has previously been demonstrated at the single-molecule level, showing apparent processivity at saturating ATP. Here we directly observed the strand passage by human topoisomerase IIα, after winding a pair of fluorescently stained DNA molecules with optical tweezers for 30 turns into an X-shaped braid. On average 0.51±0.33 µm (11±6 turns) of a braid was unlinked in a burst of reactions taking 8±4 s, the unlinked length being essentially independent of the enzyme concentration between 0.25–37 pM. The time elapsed before the start of processive unlinking decreased with the enzyme concentration, being ∼100 s at 3.7 pM. These results are consistent with a scenario where the enzyme binds to one DNA for a period of ∼10 s, waiting for multiple diffusional encounters with the other DNA to transport it across the break ∼10 times, and then dissociates from the binding site without waiting for the exhaustion of transportable DNA segments

Vector meson dominance and the rho meson

We discuss the properties of vector mesons, in particular the rho^0, in the context of the Hidden Local Symmetry (HLS) model. This provides a unified framework to study several aspects of the low energy QCD sector. Firstly, we show that in the HLS model the physical photon is massless, without requiring off field diagonalization. We then demonstrate the equivalence of HLS and the two existing representations of vector meson dominance, VMD1 and VMD2, at both tree level and one loop order. Finally the S matrix pole position is shown to provide a model and process independent means of specifying the rho mass and width, in contrast to the real axis prescription currently used in the Particle Data Group tables.Comment: 18 pages, REVTE