Magnetic anisotropy driven by ligand in 4d transition metal oxide SrRuO3

The origin of magnetic anisotropy in magnetic compounds is a longstanding issue in solid state physics and nonmagnetic ligand ions are considered to contribute little to magnetic anisotropy. Here, we introduce the concept of ligand driven magnetic anisotropy in a complex transition-metal oxide. We conducted X ray absorption and X ray magnetic circular dichroism spectroscopies at the Ru and O edges in the 4d ferromagnetic metal SrRuO3. Systematic variation of the sample thickness in the range below 10 nm allowed us to control the localization of Ru 4d t2g states, which affects the magnetic coupling between the Ru and O ions. We found that the orbital magnetization of the ligand induced via hybridization with the Ru 4d orbital determines the magnetic anisotropy in SrRuO3

ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer

Ganglioside GD2 is specifically expressed in small-cell lung cancer (SCLC) cells, leading to enhancement of malignant phenotypes, such as cell proliferation and migration. However, how GD2 promotes malignant phenotypes in SCLC cells is not well known. In this study, to reveal the mechanisms by which GD2 increases malignant phenotypes in SCLC cells, we used enzyme-mediated activation of radical sources combined with mass spectrometry in GD2+ SCLC cells. Consequently, we identified ASC amino acid transporter 2 (ASCT2), a major glutamine transporter, which coordinately works with GD2. We showed that ASCT2 was highly expressed in glycolipid-enriched microdomain/rafts in GD2+ SCLC cells, and colocalized with GD2 in both proximity ligation assay and immunocytostaining, and bound with GD2 in immunoprecipitation/TLC immunostaining. Malignant phenotypes of GD2+ SCLC cells were enhanced by glutamine uptake, and were suppressed by L-γ-glutamyl-p-nitroanilide, a specific inhibitor of ASCT2, through reduced phosphorylation of p70 S6K1 and S6. These results suggested that ASCT2 enhances glutamine uptake in glycolipid-enriched microdomain/rafts in GD2+ SCLC cells, leading to the enhancement of cell proliferation and migration through increased phosphorylation of the mTOR complex 1 signaling axis

Malignant Mesothelioma in the Thoracic Cavity of a Crj:CD(SD) Rat Characterized by Round Hyalinous Stroma

Spontaneous malignant mesothelioma was found in a 104-week-old male Crj:CD(SD) rat. The tumor was scattered on the surface of the lung, heart, mediastinal pleura and thoracic wall and metastasized to the alveolar septa. Histopathologically, small flattened or cuboidal tumor cells proliferated with stroma, formed almost normal papillary structures and reacted positively to colloidal iron stain and immunohistochemical staining for mesothelin. Round hyalinous stromata were pronounced, which is a characteristic feature, and the possible reason for this is as follows; at first, a small amount of collagen fibers was formed in the center of the clusters of several tumor cells, and then the cell clusters expanded like balloons with an increase in the collagen fibers

Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse Hippocampus

Gangliosides are particularly abundant in the central nervous system (CNS) and thought to play important roles in memory formation, neuritogenesis, synaptic transmission, and other neural functions. Although several molecular species of gangliosides have been characterized and their individual functions elucidated, their differential distribution in the CNS are not well understood. In particular, whether the different molecular species show different distribution patterns in the brain remains unclear. We report the distinct and characteristic distributions of ganglioside molecular species, as revealed by imaging mass spectrometry (IMS). This technique can discriminate the molecular species, raised from both oligosaccharide and ceramide structure by determining the difference of the mass-to-charge ratio, and structural analysis by tandem mass spectrometry. Gangliosides in the CNS are characterized by the structure of the long-chain base (LCB) in the ceramide moiety. The LCB of the main ganglioside species has either 18 or 20 carbons (i.e., C18- or C20-sphingosine); we found that these 2 types of gangliosides are differentially distributed in the mouse brain. While the C18-species was widely distributed throughout the frontal brain, the C20-species selectively localized along the entorhinal-hippocampus projections, especially in the molecular layer (ML) of the dentate gyrus (DG). We revealed development- and aging-related accumulation of the C-20 species in the ML-DG. Thus it is possible to consider that this brain-region specific regulation of LCB chain length is particularly important for the distinct function in cells of CNS

Imaging Mass Spectrometry Technology and Application on Ganglioside Study; Visualization of Age-Dependent Accumulation of C20-Ganglioside Molecular Species in the Mouse Hippocampus

Gangliosides are particularly abundant in the central nervous system (CNS) and thought to play important roles in memory formation, neuritogenesis, synaptic transmission, and other neural functions. Although several molecular species of gangliosides have been characterized and their individual functions elucidated, their differential distribution in the CNS are not well understood. In particular, whether the different molecular species show different distribution patterns in the brain remains unclear. We report the distinct and characteristic distributions of ganglioside molecular species, as revealed by imaging mass spectrometry (IMS). This technique can discriminate the molecular species, raised from both oligosaccharide and ceramide structure by determining the difference of the mass-to-charge ratio, and structural analysis by tandem mass spectrometry. Gangliosides in the CNS are characterized by the structure of the long-chain base (LCB) in the ceramide moiety. The LCB of the main ganglioside species has either 18 or 20 carbons (i.e., C18- or C20-sphingosine); we found that these 2 types of gangliosides are differentially distributed in the mouse brain. While the C18-species was widely distributed throughout the frontal brain, the C20-species selectively localized along the entorhinal-hippocampus projections, especially in the molecular layer (ML) of the dentate gyrus (DG). We revealed development- and aging-related accumulation of the C-20 species in the ML-DG. Thus it is possible to consider that this brain-region specific regulation of LCB chain length is particularly important for the distinct function in cells of CNS

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study

IntroductionAdolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated.Material and methodsMendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese.ResultsSignificant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI.ConclusionsOur Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu NishidaGuideline

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.other authors: Yasuhiro Norisue, Satoru Hashimoto, Daisuke Hasegawa, Junji Hatakeyama, Naoki Hara, Naoki Higashibeppu, Nana Furushima, Hirotaka Furusono, Yujiro Matsuishi, Tasuku Matsuyama, Yusuke Minematsu, Ryoichi Miyashita, Yuji Miyatake, Megumi Moriyasu, Toru Yamada, Hiroyuki Yamada, Ryo Yamamoto, Takeshi Yoshida, Yuhei Yoshida, Jumpei Yoshimura, Ryuichi Yotsumoto, Hiroshi Yonekura, Takeshi Wada, Eizo Watanabe, Makoto Aoki, Hideki Asai, Takakuni Abe, Yutaka Igarashi, Naoya Iguchi, Masami Ishikawa, Go Ishimaru, Shutaro Isokawa, Ryuta Itakura, Hisashi Imahase, Haruki Imura, Takashi Irinoda, Kenji Uehara, Noritaka Ushio, Takeshi Umegaki, Yuko Egawa, Yuki Enomoto, Kohei Ota, Yoshifumi Ohchi, Takanori Ohno, Hiroyuki Ohbe, Kazuyuki Oka, Nobunaga Okada, Yohei Okada, Hiromu Okano, Jun Okamoto, Hiroshi Okuda, Takayuki Ogura, Yu Onodera, Yuhta Oyama, Motoshi Kainuma, Eisuke Kako, Masahiro Kashiura, Hiromi Kato, Akihiro Kanaya, Tadashi Kaneko, Keita Kanehata, Ken-ichi Kano, Hiroyuki Kawano, Kazuya Kikutani, Hitoshi Kikuchi, Takahiro Kido, Sho Kimura, Hiroyuki Koami, Daisuke Kobashi, Iwao Saiki, Masahito Sakai, Ayaka Sakamoto, Tetsuya Sato, Yasuhiro Shiga, Manabu Shimoto, Shinya Shimoyama, Tomohisa Shoko, Yoh Sugawara, Atsunori Sugita, Satoshi Suzuki, Yuji Suzuki, Tomohiro Suhara, Kenji Sonota, Shuhei Takauji, Kohei Takashima, Sho Takahashi, Yoko Takahashi, Jun Takeshita, Yuuki Tanaka, Akihito Tampo, Taichiro Tsunoyama, Kenichi Tetsuhara, Kentaro Tokunaga, Yoshihiro Tomioka, Kentaro Tomita, Naoki Tominaga, Mitsunobu Toyosaki, Yukitoshi Toyoda, Hiromichi Naito, Isao Nagata, Tadashi Nagato, Yoshimi Nakamura, Yuki Nakamori, Isao Nahara, Hiromu Naraba, Chihiro Narita, Norihiro Nishioka, Tomoya Nishimura, Kei Nishiyama, Tomohisa Nomura, Taiki Haga, Yoshihiro Hagiwara, Katsuhiko Hashimoto, Takeshi Hatachi, Toshiaki Hamasaki, Takuya Hayashi, Minoru Hayashi, Atsuki Hayamizu, Go Haraguchi, Yohei Hirano, Ryo Fujii, Motoki Fujita, Naoyuki Fujimura, Hiraku Funakoshi, Masahito Horiguchi, Jun Maki, Naohisa Masunaga, Yosuke Matsumura, Takuya Mayumi, Keisuke Minami, Yuya Miyazaki, Kazuyuki Miyamoto, Teppei Murata, Machi Yanai, Takao Yano, Kohei Yamada, Naoki Yamada, Tomonori Yamamoto, Shodai Yoshihiro, Hiroshi Tanaka & Osamu Nishid