Multiple-system atrophy and anesthesia

Multiple-system atrophy is an adult-onset progressive neurodegenerative disease affecting the central nervous system, including the spinal cord. There has been no perioperative guideline of the muscle relaxants used in multiple-system atrophy, although a recent article recommends anesthesiologists to use shorter-acting drugs at the lowest possible doses in the patients. Here, we document the first case with multiple-system atrophy undergoing surgery managed with a combination of rocuronium and sugammadex. The recovery time to the train-of-four count 2 after intravenous rocuronium 0.6 mg / kg, or the time from the start of sugammadex 2 mg / kg intravenously to the train-of-four ratio over 0.9 was prolonged in our case more than 20 and 2 minutes compared with those in healthy subjects, respectively. Neuromuscular monitoring, in addition to the careful vigilance in the perioperative period, seems mandatory in the patients

Production and N-glycan engineering of Varlilumab in Nicotiana benthamiana

N-glycan engineering has dramatically evolved for the development and quality control of recombinant antibodies. Fc region of IgG contains two N-glycans whose galactose terminals on Fc-glycan have been shown to increase the stability of CH2 domain and improve effector functions. Nicotiana benthamiana has become one of the most attractive production systems for therapeutic antibodies. In this study, Varlilumab, a CD27-targeting monoclonal antibody, was transiently produced in fresh leaves of soil-grown and hydroponic-grown N. benthamiana, resulted in the yield of 174 and 618 µg/gram, respectively. However, the IgG produced in wild-type N. benthamiana lacked the terminal galactose residues in its N-glycan. Therefore, N-glycan engineering was applied to fine-tune recombinant antibodies produced in plant platforms. We further co-expressed IgG together with murine β1,4-galactosyltransferase (β1,4-GALT) to modify plant N-glycan with β1,4-linked Gal residue(s) and Arabidopsis thaliana β1,3-galactosylatransferase (β1,3-GALT) to improve galactosylation. The co-expression of IgG with each of GALTs successfully resulted in modification of N-glycan structures on the plant-produced IgG. Notably, IgG co-expressed with murine β1,4-GALT in soil-grown N. benthamiana had 42.5% of N-glycans variants having galactose (Gal) residues at the non-reducing terminus and 55.3% of that in hydroponic-grown N. benthamiana plants. Concomitantly, N-glycan profile analysis of IgG co-expressed with β1,3-GALT demonstrated that there was an increased efficiency of galactosylation and an enhancement in the formation of Lewis a structure in plant-derived antibodies. Taken together, our findings show that the first plant-derived Varlilumab was successfully produced with biantennary β1,4-galactosylated N-glycan structures.Nguyen K.D., Kajiura H., Kamiya R., et al. Production and N-glycan engineering of Varlilumab in Nicotiana benthamiana. Frontiers in Plant Science 14, 1215580 (2023); https://doi.org/10.3389/fpls.2023.1215580

Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis

Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants

ハイヨウ セツジョ ニオケル デンドウシキ ジドウ ホウゴウキ ノ シヨウ ケイケン

Objective : It has been accepted to use staplers for open and video-assisted thoracic surgery, however there was a risk in stapling of the pulmonary vasculatures. A newly developed stapler, powered ECHELON FLEX （Ethicon） is an electrically-powered stapler. It may reduce tip movement during cutting and stapling, which results in reduction of the risk of trauma to surrounding tissue. The aim of this study was to evaluate powered ECHELON FLEX for pulmonary lobectomy. Methods : We reviewed 16 patients who underwent pulmonary lobectomy with powered ECHELON FLEX in our institution from December, 2013 to April, 2014. Results : There were 25 stapling for the pulmonary artery, 17 stapling for the pulmonary vein, 16 stapling for the bronchus, and 33 stapling for the pulmonary parenchyma. Though two case of oozing from the stamps of a pulmonary artery and pulmonary parenchyma, there were no serious complications related to use of the staplers. Conclusions : The powered ECHELON FLEX can be used for pulmonary lobectomy safely

Biphasic Aire expression in early embryos and in medullary thymic epithelial cells before end-stage terminal differentiation

The roles of autoimmune regulator (Aire)–expressing medullary thymic epithelial cells (mTECs) in the organization of the thymic microenvironment for establishing self-tolerance are enigmatic. We sought to monitor the production and maintenance of Aire-expressing mTECs by a fate-mapping strategy in which bacterial artificial chromosome transgenic (Tg) mice expressing Cre recombinase under the control of the Aire regulatory element were crossed with a GFP reporter strain. We found that, in addition to its well recognized expression within mature mTECs, Aire was expressed in the early embryo before emergence of the three germ cell layers. This observation may help to explain the development of ectodermal dystrophy often seen in patients with AIRE deficiency. With the use of one Tg line in which Cre recombinase expression was confined to mTECs, we found that Aire+CD80high mTECs further progressed to an Aire−CD80intermediate stage, suggesting that Aire expression is not constitutive from after its induction until cell death but instead is down-regulated at the beginning of terminal differentiation. We also demonstrated that many mTECs of Aire-expressing lineage are in close contact with thymic dendritic cells. This close proximity may contribute to transfer of tissue-restricted self-antigens expressed by mTECs to professional antigen-presenting cells

Alkaline hydrolysis of coconut pith: process optimization, enzymatic saccharification, and nitrobenzene oxidation of Kraft lignin

The accumulation of pith in a coconut husk processing facility leads to disposal problems, fire hazards, and contamination of groundwater. The leachate contains phenolic compounds that percolate through the soil and contaminate groundwater. Monolignols (guaiacyl (G), syringyl (S), and p-hydroxyphenyl (H)) in soil and groundwater pose a threat to the land and water resources. This study focuses on minimizing waste accumulation by treating the accumulated pith with sodium hydroxide to recover lignin and sugar. Pith, which has about with 24% cellulose and 49% lignin, was used as a substrate for recovery of Kraft lignin (KL) and sugar. The operating condition for the recovery of KL was optimized using response surface methodology (RSM). Maximum KL recovery (~ 86%) was achieved with optimal biomass loading of 65 mg/ml, NaOH concentration 5.12% w/w, residence time 31 min, and temperature 121 °C. A glucose yield of 95% was obtained after 48 h of saccharification. The removal of the aromatic layer increased the crystallinity index (CrI) after hydrolysis from 65 to 81.7%. The S/G ratio of 0.49 indicated that the lignin structure of pith is a matrix with many branches, thus making the lignin matrix strong and rigid. [Figure not available: see fulltext.] © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

Evidence for new beta 1-3 galactosyltransferase activity involved in biosynthesis of unusual N-glycan harboring T-antigen in Apis mellifera

In a previous study (Y. Kimura et al., Biosci. Biotechnol Biochem., 70, 2583-2587, 2006), we found that new complex type N-glycans harboring Thomsen-Friedenreich antigen (Ga1 beta 1-3GalNAc) unit occur on royal jelly glycoproteins, suggesting the involvement of a new beta 1-3galactosyltransferase in the synthesis of the unusual complex type N-glycans. So far, such beta 1-3galactosyltransferase activity, which can transfer galactosyl residues with the beta 1-3 linkage to beta 1-4 GalNAc residues in N-glycan, has not been found among any eucaryotic cells. But using GalNAc(2)GlcNAc(2)Man(3)-GlcNAc(2)-PA as acceptor N-glycan, we detected the beta 1-3 galactosyltransferase activity in membrane fraction prepared from honeybee cephalic portions. This result indicates that honeybee expresses a unique beta 1-3 galactosyltransferase involved in biosynthesis of the unusual N-glycan containing a tumor related antigen in the hypopharyngeal gland