Tim23–Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import

Mitochondrial protein traffic requires coordinated operation of protein translocator complexes in the mitochondrial membrane. The TIM23 complex translocates and inserts proteins into the mitochondrial inner membrane. Here we analyze the intermembrane space (IMS) domains of Tim23 and Tim50, which are essential subunits of the TIM23 complex, in these functions. We find that interactions of Tim23 and Tim50 in the IMS facilitate transfer of precursor proteins from the TOM40 complex, a general protein translocator in the outer membrane, to the TIM23 complex. Tim23–Tim50 interactions also facilitate a late step of protein translocation across the inner membrane by promoting motor functions of mitochondrial Hsp70 in the matrix. Therefore, the Tim23–Tim50 pair coordinates the actions of the TOM40 and TIM23 complexes together with motor proteins for mitochondrial protein import

ガクガンメン リョウイキ ニオケル コツチユ ニ タイスル テイシュツリョク チョウオンパ パルス ショウシャ ノ シヨウ ケイケン

Fracture healing has traditionally been thought to be a naturally optimized process with predetermined time-course for bone metabolism, and no one had had an idea that fracture healing may be manipulated to occur at a faster rate. In 1980s, the use of low-intensity pulsed ultrasound (LIPUS) was demonstrated with a significant promotion of bone healing and LIPUS has been used extensively for bone fractures in the limbs. On the other hand, the effectiveness of LIPUS for maxillofacial bone fractures has not been studied yet. In clinical orthodontics, there are many cases closely related to bone healing: the traumatic bone fracture in maxillofacial region, the osteotomy of jaw deformity, and the bone grafting in to alveolar cleft. The purpose of this study was to examine the benefit of LIPUS to the acceleration of maxillofacial bone healing. Thirty-five patients received LIPUS after surgery served as subjects. Of total subjects, 11 patients had surgery for maxillofacial bone fracture fixation, 7 patients with jaw deformity had orthognathic surgery, and 17 patients affected by cleft lip and palate underwent alveolar cleft bone grafting. Five-seven days after surgery, the patient received 15 minutes of LIPUS (BR sonic-pro, ITO Co., Tokyo, Japan) per day for 14 days. A LIPUS signal was transmitted at a frequency of 1.0 MHz with a spatial-average intensity of 160 mW and pulsed 1: 4. In addition, we used the visual analogue scale (VAS) for pain assessment, and simple radiographs and computed tomography (CT) for evaluation of the bone healing. In most cases, pain disappeared within one week after surgery. In the patients with bone fracture fixation or jaw osteotomy, bone healing was validated by plain radiographs and/or CT taken at 3 months after surgery, leading to stable occlusion. In the cases with alveolar bone grafting, early bone formation was observed from CT taken at 3 months after surgery. In addition, the catabolic effects of LIPUS exposure were not found at all. In conclusion, LIPUS application might involve in acceleration of maxillofacial bone healing after surgery. Therefore, LIPUS may be a promising therapeutic tool for bone healing in maxillofacial region

C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers

Nuclear import receptors (NIRs) not only transport RNA-binding proteins (RBPs) but also modify phase transitions of RBPs by recognizing nuclear localization signals (NLSs). Toxic arginine-rich poly-dipeptides from C9orf72 interact with NIRs and cause nucleocytoplasmic transport deficit. However, the molecular basis for the toxicity of arginine-rich poly-dipeptides toward NIRs function as phase modifiers of RBPs remains unidentified. Here we show that arginine-rich poly-dipeptides impede the ability of NIRs to modify phase transitions of RBPs. Isothermal titration calorimetry and size-exclusion chromatography revealed that proline:arginine (PR) poly-dipeptides tightly bind karyopherin-β2 (Kapβ2) at 1:1 ratio. The nuclear magnetic resonances of Kapβ2 perturbed by PR poly-dipeptides partially overlapped with those perturbed by the designed NLS peptide, suggesting that PR poly-dipeptides target the NLS binding site of Kapβ2. The findings offer mechanistic insights into how phase transitions of RBPs are disabled in C9orf72-related neurodegeneration

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Mitochondrial biogenesis: cell-cycle-dependent investment in making mitochondria

SummaryMitochondria cannot be made de novo, so pre-existing mitochondria must be inherited at each cell division. A new study demonstrates cell-cycle-dependent regulation of the activity of the TOM translocase complex to induce mitochondrial biogenesis during the M phase of the cell cycle

Complete Photochromic Structural Changes in Ruthenium(II)Diimine Complexes, Based on Control of the Excited States by Metalation

The thermal and photochemical reactions of a newly synthesized complex, [RuII(TPA)(tpphz)]2+ (1; TPA=tris(2-pyridylmethyl)amine, tpphz=tetrapyrido[3,2-a:2,3-c:3,2-h: 2,3-j]phenazine), and its derivatives have been investigated. Heating a solution of complex 1 (closed form) and its derivatives in MeCN caused the partial dissociation of one pyridylmethyl moiety of the TPA ligand and the resulting vacant site on the RuII center was occupied by a molecule of MeCN from the solvent to give a dissociated complex, [RuII(3-TPA)(tpphz)(MeCN)]2+ (1, open form), and its derivatives, respectively, in quantitative yields. The thermal dissociation reactions were investigated on the basis of kinetics analysis, which indicated that the reactions proceeded through a seven-coordinate transition state. Although the backwards reaction was induced by photoirradiation of the MLCT absorption bands, the photoreaction of complex 1 reached a photostationary state between complexes 1 and 1 and, hence, the recovery of complex 1 from complex 1 was 67%. Upon protonation of complex 1 at the vacant site of the tpphz ligand, the efficiency of the photoinduced recovery of complex 1+H+ from complex 1+H+ improved to 83%. In contrast, dinuclear -tpphz complexes 2 and 3, which contained the RuII(TPA)(tpphz) unit and either a RuII(bpy)2 or PdIICl2 moiety on the other coordination edge of the tpphz ligand, exhibited 100% photoconversion from their open forms into their closed forms (22 and 33). These results are the first examples of the complete photochromic structural change of a transition-metal complex, as represented by complete interconversion between its open and closed forms. Scrutinization by performing optical and electrochemical measurements allowed us to propose a rationale for how metal coordination at the vacant site of the tpphz ligand improves the efficiency of photoconversion from the open form into the closed form. It is essential to lower the energy level of the triplet metal-to-ligand charge-transfer excited state (3MLCT*) of the closed form relative to that of the triplet metal-centered excited state (3MC*) by metal coordination. This energy-level manipulation hinders the transition from the 3MLCT* state into the 3MC* state in the closed form to block the partial photodissociation of the TPA ligand.X1165sciescopu