Structural characterization of a binuclear center of a Cu-containing NO reductase homologue from Roseobacter denitrificans: EPR and resonance Raman studies

AbstractAerobic phototrophic bacterium Roseobacter denitrificans has a nitric oxide reductase (NOR) homologue with cytochrome c oxidase (CcO) activity. It is composed of two subunits that are homologous with NorC and NorB, and contains heme c, heme b, and copper in a 1:2:1 stoichiometry. This enzyme has virtually no NOR activity. Electron paramagnetic resonance (EPR) spectra of the air-oxidized enzyme showed signals of two low-spin hemes at 15 K. The high-spin heme species having relatively low signal intensity indicated that major part of heme b3 is EPR-silent due to an antiferromagnetic coupling to an adjacent CuB forming a Fe–Cu binuclear center. Resonance Raman (RR) spectrum of the oxidized enzyme suggested that heme b3 is six-coordinate high-spin species and the other hemes are six-coordinate low-spin species. The RR spectrum of the reduced enzyme showed that all the ferrous hemes are six-coordinate low-spin species. ν(Fe–CO) and ν(C–O) stretching modes were observed at 523 and 1969 cm−1, respectively, for CO-bound enzyme. In spite of the similarity to NOR in the primary structure, the frequency of ν(Fe–CO) mode is close to those of aa3- and bo3-type oxidases rather than that of NOR

Correlations of perioperative coagulopathy, fluid infusion and blood transfusions with survival prognosis in endovascular aortic repair for ruptured abdominal aortic aneurysm

Background: Factors associated with survival prognosis among patients who undergo endovascular aortic repair (EVAR) for ruptured abdominal aortic aneurysms (rAAA) have not been sufficiently investigated. In the present study, we examined correlations between perioperative coagulopathy and 24-h and 30-day postoperative survival. Relationships between coagulopathy and the content of blood transfusions, volumes of crystalloid infusion and survival. Methods: This was a retrospective study of the medical records of all patients who underwent EVAR for rAAA at Chiba-Nishi General Hospital during the period from October 2013 to December 2015. Major coagulopathy was defined using the international normalized ratio or activated partial thromboplastin time (APTT) ratio of at least 1.5, or platelet count less than 50 × 10/l. We quantified the amounts of blood transfusions and crystalloid infusions administered from arrival to the hospital to admission to ICU following operations. Results: Coagulopathy among patients with rAAA was found to progress even after they had presented at the hospital. No statistically significant correlation between preoperative coagulopathy and mortality was found, although a significantly greater degree of postoperative coagulopathy was seen among patients who died both within 24-h and 30 days postoperatively. Among patients with postoperative coagulopathy, lesser quantities of fresh frozen plasma (FFP) compared with red cell concentrate (RCC) were used during the period from hospital arrival to postoperative ICU entry. In both groups of patients who did not survive after 24-h and 30 days, FFP was used less than RCC. Large transfusions of crystalloids administered during the periods from hospital arrival to surgery and from hospital arrival to the end of surgery were associated with postoperative incidence of major coagulopathy, death within 24-h, and death within 30 days. Conclusion: Coagulopathy progressed during care in the emergency outpatient clinic and operations. Postoperative coagulopathy was associated with poorer outcomes. Smaller FFP/RCC ratios and larger volumes of crystalloid infusion were associated with development of coagulopathy and poorer prognosis of survival

クリオ上清中の高分子VWFマルチマー非結合型ADAMTS13の存在:血栓性血小板減少性紫斑病の治療に、より効果的な血漿分画製剤の選択

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective. STUDY DESIGN AND METHODS: To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA). RESULTS: IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products. CONCLUSION: Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 in complex with larger VWF multimers.博士（医学）・乙第1322号・平成25年11月27日© 2013 American Association of Blood BanksCopyright © 1999-2018 John Wiley & Sons, Inc. All rights reservedThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1111/trf.12182], which has been published in final form at [http://dx.doi.org/10.1111/trf.12182]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

2d SCFTs from M2-branes

We consider the low-energy limit of the two-dimensional theory on k M2-branes suspended between a straight M5-brane and a curved M5-brane. We argue that it is described by an N=(2,2) supersymmetric gauge theory with no matter fields but with a non-trivial twisted superpotential, and also by an N=(2,2) supersymmetric Landau-Ginzburg model, such that the (twisted) superpotentials are determined by the shape of the M5-branes. We find particular cases realize Kazama-Suzuki models. Evidence is provided by the study of ground states, chiral rings, BPS spectra and S^2 partition functions of the systems

Elliptic genera of 2d N=2 gauge theories

We compute the elliptic genera of general two-dimensional and gauge theories. We find that the elliptic genus is given by the sum of Jeffrey-Kirwan residues of a meromorphic form, representing the one-loop determinant of fields, on the moduli space of flat connections on T (2). We give several examples illustrating our formula, with both Abelian and non-Abelian gauge groups, and discuss some dualities for U(k) and SU(k) theories. This paper is a sequel to the authors' previous paper (Benini et al., Lett Math Phys 104:465-493, 2014)

2.Sediments

小樽商科大学Geological Survey of Hokkaido北海道大学Editor : Tazaki, Kazue, Cover:Scanning electoron microscopic photograph of Gallionella sp. in biomats of Aso caldera, Kyusyu, Japan. Various shapes of Gallonella sp. are shown (image:Moriichi, Shingo).COE, 金沢大学 水・土壌環境領域シンポジウム「地球環境における微生物の役割」, 日時：2002年12月4日（水）13：00～, 場所：金沢大学理学部3階第一実験

Chemogenetic sensory fMRI reveals behaviorally relevant bidirectional changes in primate somatosensory network

手と足の感覚は、実は脳の中でつながっていた --脳障害による活動変化の広がりを見ることで常識を覆す発見、脳機能・疾患機序の理解へ前進--. 京都大学プレスリリース. 2021-10-21.Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates

Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan

Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed