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Transposon-encoded IscB family proteins are RNA-guided nucleases in the OMEGA (obligate mobile element-guided activity) system, and likely ancestors of the RNA-guided nuclease Cas9 in the type II CRISPR-Cas adaptive immune system. IscB associates with its cognate ωRNA to form a ribonucleoprotein complex that cleaves double-stranded DNA targets complementary to an ωRNA guide segment. Although IscB shares the RuvC and HNH endonuclease domains with Cas9, it is much smaller than Cas9, mainly due to the lack of the α-helical nucleic-acid recognition lobe. Here, we report the cryo-electron microscopy structure of an IscB protein from the human gut metagenome (OgeuIscB) in complex with its cognate ωRNA and a target DNA, at 2.6-Å resolution. This high-resolution structure reveals the detailed architecture of the IscB-ωRNA ribonucleoprotein complex, and shows how the small IscB protein assembles with the ωRNA and mediates RNA-guided DNA cleavage. The large ωRNA scaffold structurally and functionally compensates for the recognition lobe of Cas9, and participates in the recognition of the guide RNA-target DNA heteroduplex. These findings provide insights into the mechanism of the programmable DNA cleavage by the IscB-ωRNA complex and the evolution of the type II CRISPR-Cas9 effector complexes., (© 2022. The Author(s).)

Outer hair cell elecromotility, driven by prestin, is essential for mammalian cochlear amplification. Here, we report the cryo-EM structures of thermostabilized prestin (Pres TS ), complexed with chloride, sulfate, or salicylate at 3.52-3.63 Å resolutions. The central positively-charged cavity allows flexible binding of various anion species, which likely accounts for the known distinct modulations of nonlinear capacitance (NLC) by different anions. Comparisons of these Pres TS structures with recent prestin structures suggest rigid-body movement between the core and gate domains, and provide mechanistic insights into prestin inhibition by salicylate. Mutations at the dimeric interface severely diminished NLC, suggesting that stabilization of the gate domain facilitates core domain movement, thereby contributing to the expression of NLC. These findings advance our understanding of the molecular mechanism underlying mammalian cochlear amplification., (© 2022. The Author(s).)

Objective: Aging of skeletal muscle is characterized not only by a decrease of muscle quantity but also by changes in muscle quality, such as an increase in muscle stiffness. The present study aimed to investigate the effects of supplementation with quercetin glycosides (QGs), well-known polyphenolic flavonoids, combined with resistance exercise on muscle quantity and stiffness., Materials and Methods: A randomized, controlled trial was conducted in community-dwelling, Japanese people aged 50-74 years who were randomly allocated to exercise with placebo or 200 or 500 mg of QG supplementation. All participants performed low-intensity resistance training mainly targeting thigh muscles with 40% of 1-repetition maximum, 3 days per week for 24 weeks. Muscle cross-sectional area (CSA), lean mass, and vastus lateralis (VL) muscle stiffness were measured before and after the 24-week intervention., Results: Forty-eight subjects completed the 24-week intervention. There were no significant group × time interactions in thigh CSA for primary outcome, as well as lean mass. VL muscle stiffness in the stretched position was significantly lower in both the 200 mg and 500 mg QG groups than in the placebo group after the 24-week intervention ( p < 0.05). No significant correlation was observed between changes of VL muscle CSA and stiffness during the 24-week intervention., Conclusion: Quercetin glycoside supplementation combined with low-intensity resistance exercise improved passive muscle stiffness independently of muscle quantity., Clinical Trial Registration: [www.umin.ac.jp/ctr/], identifier [UMIN000037633]., Competing Interests: This study received funding from Suntory Wellness Ltd. YO, AN, TI, and MN Were employees of Suntory Wellness Ltd., which manufactures and sells health food products. The funder had the following involvement with the study: the study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Otsuka, Miyamoto, Nagai, Izumo, Nakai, Fukuda, Arimitsu, Yamada and Hashimoto.)

As per the International Commission on Radiological Protection 2010 recommendation, it was stated that "interventional radiologists performing difficult procedures with high workloads may be exposed to high doses" and that education and training of medical staffs in radiation exposure is "an urgent priority." There are many reports on the textbook aspects of radiation protection, but reports on the practical aspects of radiation protection have remained to be scarce. Various methods of reducing radiation exposure are described as "useful" or "can be reduced," but the priority of these methods and the "extent" to which they contribute to reducing radiation exposure are not clear. Thus, in this article, we will look into the protection of interventional radiologist from radiation exposure in a practical way, giving priority to clarity rather than academic accuracy., Competing Interests: None, (© 2022 Japanese Society of Interventional Radiology.)

Necrotizing fasciitis is a rare and severe infectious disease that is often fatal and is characterized by the extensive necrosis of subcutaneous tissue and fascial planes. A number of clinical parameters have been intensively investigated to diagnose and assess the severity and prognosis of necrotizing fasciitis. Since it currently remains unclear whether these parameters are also abnormal before disease onset, the present study investigated this issue. We retrospectively recruited 38 patients, including 12 and 26 patients with necrotizing fasciitis and cellulitis, respectively. The results of routine blood examinations were collected at disease onset and also at baseline, which was defined as the time point before disease onset. No significant differences were observed in age or sex between the necrotizing fasciitis and cellulitis groups. However, significant differences were noted in the levels of hemoglobin, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio, sodium, creatinine, albumin, D-dimer, and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score at disease onset. Significant differences were also observed in the levels of hemoglobin, lymphocyte count, monocyte count, platelet count, creatinine, D-dimer, and LRINEC score at baseline. Hemoglobin, platelet count, C-reactive protein, creatinine, albumin, and D-dimer levels were already abnormal at baseline in the necrotizing fasciitis group. In conclusion, the present results revealed precritical abnormalities in routine blood parameters in patients with necrotizing fasciitis. Therefore, individuals predisposed to necrotizing soft tissue infection may be identified prior to disease onset., (© 2022 Japanese Dermatological Association.)

Background: A sarcopenia diagnosis is confirmed by the presence of low muscle quantity or quality under the 2018 revised definition by the European Working Group on Sarcopenia in Older People 2. Imaging methods [i.e. magnetic resonance imaging (MRI)], dual-energy X-ray absorptiometry (DXA), and bioelectrical impedance analysis are tools to evaluate muscle quantity or quality. The present study aimed to investigate whether and how low-intensity and moderate-intensity resistance training improved both muscle quantity and quality measured by MRI, DXA, and segmental bioelectrical impedance spectroscopy (S-BIS) in middle-aged and older people., Methods: A single-blind, randomized, controlled trial was conducted. Community-dwelling people aged 50-79 years were randomly allocated to no exercise (no-Ex), low-intensity exercise (low-Ex), and moderate-intensity exercise (moderate-Ex) groups. Participants in the exercise groups performed resistance training for 24 weeks, with loads of 40% and 60% of one repetition maximum in the low-Ex and moderate-Ex groups, respectively. Cross-sectional area (CSA), lean mass, and muscle electrical properties on S-BIS were used to determine the effects of training interventions on muscle quantity and quality of the lower limbs., Results: Fifty participants (no-Ex 17, age 63.5 ± 8.5 years, women 47.1%; low-Ex 16, age 63.6 ± 8.1 years, women 50.0%; moderate-Ex 17, age 63.5 ± 8.3 years, women 52.9%) completed the 24 week exercise intervention. For the primary outcome, significant intervention effects were found in thigh muscle CSA on MRI between the moderate-Ex and no-Ex groups (+6.8 cm 2 , P < 0.01). Low-Ex for 24 weeks only increased quadriceps CSA (+2.3 cm 2 , P < 0.05). The per cent change of thigh muscle CSA (+7.0%, P < 0.01) after 24 week moderate-Ex was higher than that of leg lean mass on DXA (+2.3%, P = 0.088). Moderate-Ex for 24 weeks also improved S-BIS electrical properties related to muscle quantity and quality, including the intracellular resistance index (+0.1 cm 2 /Ω, P < 0.05), membrane capacitance (+0.7 nF, P < 0.05), and phase angle (+0.3 deg, P < 0.05); their changes were positively correlated with that of thigh muscle CSA (P < 0.01)., Conclusions: Resistance exercise with moderate intensity improved muscle quantity and quality measured by MRI and S-BIS, whereas that with low intensity only increased muscle quantity in middle-aged and older people. The comparisons among the responses to exercise between the assessment methods indicate the greater value of MRI and S-BIS to measure changes of muscle quantity and quality than of lean mass measured by DXA for assessing the local effects of resistance training., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Remarkably high mixed proton and electron conduction arising from oxidized single-wall carbon nanotubes at room temperature is demonstrated. The respective proton and electronic conductivities are 1.40 and 8.0 × 10 -2 S cm -1 in the in-plane direction, and 3.1 × 10 -2 and 1.1 × 10 -3 S cm -1 in the out-of-plane direction, indicating their potential in a wide range of solid electrolyte membranes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 Å resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology., Competing Interests: Declaration of interests The ChRmine antibody (Fab02) and ChRmine variants are described in the pending patent application material; these tools and all methods, protocols, clones, and sequences are freely available to nonprofit institutions and investigators. K.D. is a member of the Cell advisory board., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to investigate the association between level of impaired consciousness and severe hypothermia (<28°C) and to evaluate the association between level of impaired consciousness and inhospital mortality among accidental hypothermia patients., Methods: This was a multicenter retrospective study using the J-Point registry database, which includes data regarding patients whose core body temperature was 35.0°C or less and who were treated as accidental hypothermia in emergency departments between April 1, 2011 and March 31, 2016. We estimated adjusted odds ratios of the level of impaired consciousness for severe hypothermia less than 28°C and inhospital mortality using a logistic regression model., Results: The study included 505 of 572 patients in the J-Point registry. Relative to mildly impaired consciousness (Glasgow Coma Scale [GCS] 13-15), the adjusted odds ratios for severe hypothermia less than 28°C were: moderate (GCS 9-12), 3.26 (95% confidence interval [CI], 1.69-6.25); and severe (GCS < 9), 4.68 (95% CI, 2.40-9.14). Relative to mildly impaired consciousness (GCS 13-15), the adjusted odds ratios for inhospital mortality were: moderate (GCS9-12), 1.65 (95% CI, 0.95-2.88); and severe (GCS < 9), 2.10 (95% CI, 1.17-3.78)., Conclusion: The level of impaired consciousness in patients with accidental hypothermia was associated with severe hypothermia and inhospital mortality., (© 2022 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

The key challenges for converting chitin to 5-hydroxymethylfurfural (5-HMF) include the low 5-HMF yield. Moreover, the disadvantages of traditional acid-base catalysts including complex post-treatment processes, the production of by-products, and severe equipment corrosion also largely limit the large-scale conversion of chitin to 5-HMF. In this view, herein we have demonstrated a microwave aided efficient and green conversion of chitin to 5-HMF while using polyoxometalate (POM) as a catalyst and DMSO/water as solvent. Chitin treated with H 2 SO 4 followed by ball-milling (chitin-H 2 SO 4 -BM) was selected as the starting compound for the conversion process. Four different POMs including H 3 [PW 12 O 40 ], H 3 [PMo 12 O 40 ], H 4 [SiW 12 O 40 ] and H 4 [SiMo 12 O 40 ] were used as catalysts. Various reaction parameters including reaction temperature, amount of catalyst, mass ratios of water/DMSO and reaction time have been investigated to optimize the 5-HMF conversion. The H 4 [SiW 12 O 40 ] catalyst exhibited the highest catalytic performance with 23.1% HMF yield at optimum operating conditions which is the highest among the literature for converting chitin to 5-HMF. Significantly, the disadvantages of the state of the art conversion routes described earlier can be overcome using POM-based catalysts, which makes the process more attractive to meet the ever-increasing energy demands, in addition to helping consume crustacean waste., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The interlayer spaces in two dimensional (2D) layered materials such as graphene, metal oxides and metal chalcogenides can be used in a number of roles that include the trapping of gases, for ion transfer and for water purification applications. In such spaces, "inner" pressure occurs on guest species enclosed between the layers and its variation can, in principal, be used for precisely controlling particular guest properties. In this study, a mixture of two 2D materials including graphene oxide (GO) and nickel hydroxide (Ni(OH) 2 ), was employed to yield an anisotropic GO-Ni(OH) 2 hybrid 2D sheet. The inner pressure associated with this material was able to be tuned by reduction of the GO (to yield rGO) and this in turn was shown to affect the magnetic behaviour of Ni(OH) 2 . The ferromagnetic transition temperature ( T c ) for Ni(OH) 2 decreases as the interlayer distance became shorter, which is opposite to the behaviour observed for the application of hydrostatic pressure to the hybrid sheet. The uniaxial pressure affecting the interlayer of the 2D material, and generated by the reduction of GO to rGO, has the potential to not only influence the behaviour of a range of magnetic materials, but also individual properties of other types of functional materials.

The viability of biorefining technology primarily depends on the facile cellulose conversion route with adequate conversion efficiency. Here we have demonstrated the microwave-assisted hydrolysis of cellulose to glucose using polyoxometalate (POM) clusters as acid catalysts. Two different types of POM, including Wells-Dawson and Keggin were justified as catalysts in the cellulose conversion process. In particular, the cellulose to glucose catalytic conversion using Wells-Dawson type POMs has not been reported to date. Also, even though there have been some previous reports about the catalytic biomass conversion of Keggin type POMs, the systematic study to optimize the conversion efficiency in terms of catalyst amount, reaction temperature, reaction time, and the amount of solvent is lacking. Under the experimental conditions employed, the Keggin-type catalyst showed higher cellulose conversion and glucose yield than the Wells-Dawson-type catalyst. Furthermore, the cellulose conversion efficiency and glucose yields were optimized by tuning the reaction conditions including temperature, reaction time, and the amount of solvent. Under optimized conditions, the Keggin-type POM catalyst shows a remarkably high glucose yield of 77.2% and a cellulose conversion of 90.1%. The unique complex properties of the POM catalyst, including being (i) strong acids with extremely high Brønsted and Lewis acidity and (ii) efficient microwave adsorbants which enhanced interaction between substrate and the catalyst can be attributed to the outstanding efficacy of the conversion process., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The rapid transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-driven infection signifies an ultimate challenge to global health, and the development of effective strategies for preventing and/or mitigating its effects are of the utmost importance. In the current study, an in-depth investigation for the understanding of the SARS-CoV-2 inactivation route using graphene oxide (GO) is presented. We focus on the antiviral effect of GO nanosheets on three SARS-CoV-2 strains: Wuhan, B.1.1.7 (U.K. variant), and P.1 (Brazilian variant). Plaque assay and real-time reverse transcription - polymerase chain reaction (RT-PCR) showed that 50 and 98% of the virus in a supernatant could be cleared following incubation with GO (100 μg/mL) for 1 and 60 min, respectively. Transmission electron microscopy (TEM) analysis and protein (spike (S) and nucleocapsid (N) proteins) decomposition evaluation confirm a two-step virus inactivation mechanism that includes (i) adsorption of the positively charged spike of SARS-CoV-2 on the negatively charged GO surface and (ii) neutralization/inactivation of the SARS-CoV-2 on the surface of GO through decomposition of the viral protein. As the interaction of S protein with human angiotensin-converting enzyme 2 (ACE2) is required for SARS-CoV-2 to enter into human cells, the damage to the S protein using GO makes it a potential candidate for use in contributing to the inhibition of the worldwide spread of SARS-CoV-2. Specifically, our findings provide the potential for the construction of an effective anti-SARS-CoV-2 face mask using a GO nanosheet, which could contribute greatly to preventing the spread of the virus. In addition, as the effect of surface contamination can be severe in the spreading of SARS-CoV-2, the development of efficient anti-SARS-CoV-2 protective surfaces/coatings based on GO nanosheets could play a significant role in controlling the spread of the virus through the utilization of GO-based nonwoven cloths, filters, and so on., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Channelrhodopsins (ChRs) are microbial light-gated ion channels utilized in optogenetics to control neural activity with light . Light absorption causes retinal chromophore isomerization and subsequent protein conformational changes visualized as optically distinguished intermediates, coupled with channel opening and closing. However, the detailed molecular events underlying channel gating remain unknown. We performed time-resolved serial femtosecond crystallographic analyses of ChR by using an X-ray free electron laser, which revealed conformational changes following photoactivation. The isomerized retinal adopts a twisted conformation and shifts toward the putative internal proton donor residues, consequently inducing an outward shift of TM3, as well as a local deformation in TM7. These early conformational changes in the pore-forming helices should be the triggers that lead to opening of the ion conducting pore., Competing Interests: KO, TN, TN, KY, KI, SI, JV, KH, AM, KK, TI, II, TI, RU, RE, SO, GK, TK, TK, WS, HS, TT, MT, RT, AT, RN, MF, HM, YL, EN, RT, TT, MS, TK, TS, TF, YY, SO, YJ, KT, RI, SH, HK, PH, SI, MK, TN, ON No competing interests declared, (© 2021, Oda et al.)

Bifunctional electrocatalytic properties of freeze-dried Ni/NiOx, freeze-dried NiO, and freeze-dried Ni(OH)2 are reported. Freeze-dried Ni(OH)2 was synthesized by the freeze-drying method. Freeze-dried Ni/NiOx and freeze-dried Ni were obtained from the thermal annealing of the material. Both Ni(OH)2 and Ni/NiOx could sustain with freestanding freeze-dried 3D structures without any carbon support. Freeze-dried Ni/NiOx exhibited excellent bifunctional electrocatalytic properties with the ORR performance at 0.62 V (half-wave potential) and OER at 1.47 V (η = 10 mA cm-2). Using freeze-dried metal hydroxides can be considered useful in a wide range of carbon-free applications and can improve the electrocatalytic performance. The bifunctional catalytic activities were calculated to be 0.86, 0.98 and 1.14 V for freeze-dried Ni/NiOx, freeze-dried NiO and freeze-dried Ni(OH)2, respectively. The stacking of 2D sheets into 3D mass seemed to play a vital role behind this excellent bifunctionality of freeze-dried Ni/NiOx. The material reveals possible applications in Zn-air batteries. Besides, the strategy developed herein could be justified to obtain other transition metal-oriented bifunctional electrocatalysts as alternatives to Pt- and Ir/Ru-based expensive benchmark catalysts.

We revisit the densest binary sphere packings (DBSPs) under periodic boundary conditions and present an updated phase diagram, including newly found 12 putative densest structures over the x-α plane, where x is the relative concentration and α is the radius ratio of the small and large spheres. To efficiently explore the DBSPs, we develop an unbiased random search approach based on both the piling-up method to generate initial structures in an unbiased way and the iterative balance method to optimize the volume of a unit cell while keeping the overlap of hard spheres minimized. With those two methods, we have discovered 12 putative DBSPs and thereby the phase diagram is updated, while our results are consistent with those of a previous study [Hopkins et al., Phys. Rev. E 85, 021130 (2012)]PLEEE81539-375510.1103/PhysRevE.85.021130 with a small correction for the case of 12 or fewer spheres in the unit cell. Five of the discovered 12 DBSPs are identified in the small radius range of 0.42≤α≤0.50, where several structures are competitive to each other with respect to packing fraction. Through the exhaustive search, diverse dense packings are discovered and, accordingly, we find that packing structures achieve high packing fractions by introducing distortion and/or combining a few local dense structural units. Furthermore, we investigate the correspondence of the DBSPs with crystals based on the space group. The result shows that many structural units in real crystals, e.g., LaH&#95;{10} and SrGe&#95;{2-δ} being high-pressure phases, can be understood as DBSPs. The correspondence implies that the densest sphere packings can be used effectively as structural prototypes for searching complex crystal structures, especially for high-pressure phases.

This pilot study aimed to examine the effect of pre-meal tasteless calorie-free gum chewing on post-meal blood levels of glucose, insulin, glucagon, and gastrointestinal hormones. This was an open-label, randomized, 2-sequence, 3-period, 2-treatment crossover trial with a 1:1 allocation. Sixteen Japanese adult male volunteers aged between 30 and 49 years without diagnosed glucose metabolism disorder were enrolled. Ingestion of 200-g cooked rice after 15-min tasteless calorie-free gum chewing (GUM+ treatment) was compared to that without preceding gum chewing (GUM- treatment). Cooked rice was divided into twelve equally sized portions and consumed by chewing each portion 30 times before swallowing. Treatment sessions were separated by an at least 1-week interval and attended after an overnight fast. Circulating levels of glucose, insulin, glucagon, active glucagon-like peptide (GLP)-1 and ghrelin were measured at baseline (before treatment) and 0, 15, 30, 60, and 120 min after completion of the meal ingestion, and the postprandial change from baseline was assessed. As a result, the change in glucose levels at 0 min was significantly lower in the GUM+ treatment than in the GUM- treatment ( P  = 0.004). Furthermore, the GUM+ treatment demonstrated higher incremental insulin levels at 15 min ( P  = 0.041) and higher incremental active GLP-1 levels at 30 and 60 min ( P  = 0.018 and 0.021, respectively); whereas, postprandial glucagon and ghrelin levels were not significantly different. In conclusion, the current pilot study demonstrated that tasteless calorie-free gum chewing before rice eating had a significant but limited impact on the increase of postprandial active GLP-1 levels in male individuals without diagnosed glucose metabolism disorder., Competing Interests: Conflict of interestMitsuyoshi Takahara is a staff member of the endowed chair (Department of Diabetes Care Medicine) which received funds from AstraZeneca K.K., Mitsubishi Tanabe Pharma Co., MSD K.K., Nippon Boehringer Ingelheim Co., Novo Nordisk Pharma, Ono Pharmaceutical Co., and Taisho Toyama Pharmaceutical Co.. Masahiro Fukuda has received honoraria from Mitsubishi Tanabe Pharma Co., MSD K.K., Ono Pharmaceutical Co., Sanofi K.K., and Takeda Pharmaceutical Co., and has received research funding from Astellas Pharma, LOTTE Co., Novo Nordisk Pharma, and Sanofi K.K.. Yuji Matsuzawa declares that he has no conflict of interest. Iichiro Shimomura has received honoraria from Astellas Pharma, Eli Lilly Japan K.K., Kowa Co., Mitsubishi Tanabe Pharma Co., MSD K.K., Nippon Boehringer Ingelheim Co., Novo Nordisk Pharma, Ono Pharmaceutical Co., Sanofi K.K., Sanwa Kagaku Kenkyusho Co., and Takeda Pharmaceutical Co., and has received subsides or donations from Astellas Pharma, AstraZeneca K.K., Daiichi Sankyo Co., Kowa Co., Kyowa Kirin Co., Mitsubishi Tanabe Pharma Co., MSD K.K., Novartis Pharmaceuticals Corp., Novo Nordisk Pharma, Ono pharmaceutical Co., Sanofi K.K., Sumitomo Dainippon Pharma., Takeda Pharmaceutical Co., Teijin Pharma, and Terumo Corporation., (© The Japan Diabetes Society 2020.)

Disruptions in the ubiquitin protein ligase E3A ( UBE3A ) gene cause Angelman syndrome (AS). Whereas AS model mice have associated synaptic dysfunction and altered plasticity with abnormal behavior, whether similar or other mechanisms contribute to network hyperactivity and epilepsy susceptibility in AS patients remains unclear. Using human neurons and brain organoids, we demonstrate that UBE3A suppresses neuronal hyperexcitability via ubiquitin-mediated degradation of calcium- and voltage-dependent big potassium (BK) channels. We provide evidence that augmented BK channel activity manifests as increased intrinsic excitability in individual neurons and subsequent network synchronization. BK antagonists normalized neuronal excitability in both human and mouse neurons and ameliorated seizure susceptibility in an AS mouse model. Our findings suggest that BK channelopathy underlies epilepsy in AS and support the use of human cells to model human developmental diseases., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Bacteriorhodopsin (bR) is a light-driven proton pump and a model membrane transport protein. We used time-resolved serial femtosecond crystallography at an x-ray free electron laser to visualize conformational changes in bR from nanoseconds to milliseconds following photoactivation. An initially twisted retinal chromophore displaces a conserved tryptophan residue of transmembrane helix F on the cytoplasmic side of the protein while dislodging a key water molecule on the extracellular side. The resulting cascade of structural changes throughout the protein shows how motions are choreographed as bR transports protons uphill against a transmembrane concentration gradient., (Copyright © 2016, American Association for the Advancement of Science.)

A 62-year-old diabetic man was admitted to our hospital because of acute myocardial infarction. Emergent coronary angiography showed multiple thromboembolic occlusions in the distal circumflex and anterior descending arteries. For the first 2 weeks of hospitalization, he suffered multiple organ manifestations including the gastrointestinal, central nervous, renal and respiratory systems. The anticardiolipin beta2GP1 complex antibody titer on the 15th day was as high as 27.2 U/l (normal value < 3.5). These clinical manifestations and laboratory findings suggested catastrophic antiphospholipid antibody syndrome. He was discharged on the 83rd day with anticoagulant therapy and regular hemodialysis. Acute myocardial infarction is rare as the initial manifestation of catastrophic antiphospholipid antibody syndrome.

An 81-year-old man with broad cerebral infarction presented with coronary air embolism secondary to bowel infarction and developed cardiogenic shock. Electrocardiography revealed ST elevation in the inferior leads and complete atrioventricular block with atrial fibrillation. Emergent angiography showed total occlusion of the right coronary artery without apparent thrombi. A multifunctional probe catheter was inserted into the right coronary artery for selective angiography. A moderate amount of air was aspirated from the catheter. The diagnosis was coronary air embolism. Coronary flow was restored after aspiration and normal saline flushing. Computed tomography showed massive portal venous gas. Emergent laparotomy disclosed broad bowel necrosis. The coronary air emboli may have originated from the portal vein and passed through the intrahepatic (portal to hepatic) shunt and patent foramen ovale(paradoxical embolization).