Hepatic Branch Vagotomy Can Suppress Liver Regeneration in Partially Hepatectomized Rats

The role of the vagus nerve in liver regeneration after partial hepatectomy was studied by comparing the effects of hepatic branch vagotomy with those of hepatic branch sympathectomy in rats. The liver weight as a percentage of body weight decreased significantly 7 days after vagotomy compared with the controls and this was associated with a reduction in food intake. There was no difference in the liver weights between the control rats and the pair-fed vagotomized rats. Hepatic sympathectomy had no significant effect on the liver weight. The serum scores indicating hepatic function showed no difference between the control and the vagotomized rats except alkaline phosphatase. The concentration of insulin was unchanged. The number of mitotic hepatocytes remained high at 7 days after vagotomy: These observations led us to conclude that the vagus nerve stimulates liver regeneration, and its effect depends on vagal factors directly and specifically

High thermal-stability ceria synthesized via thermal-hydrolysis route and methane-combustion performance

Enhancement of the thermal stability of a catalyst is an efficient way to improve the catalytic activity of a catalytic reaction performed at high temperature. In this study, cerium oxide (ceria, CeO2) with a high thermal stability was synthesized by controlling the agglomeration of the primary particles via the thermal hydrolysis of ceric nitrate, accompanied by testing for the catalytic combustion of methane (CH4). The specific surface area of this material after calcination at 1,173K for 5 h was 50m2/g, which was much higher than that of the two reference materials (ceria made via precipitation of cerous nitrate using aqueous ammonia at 4.1m2/g, and the Japan reference catalyst JRC-CEO-1 at 1.4m2/g). The ceria made via thermal hydrolysis showed high crystallinity and a much higher pore volume, which resulted in excellent thermal resistance. For O2 conversion in ceria, catalyzed CH4 combustion at 923 K, the ceria created in this study demonstrated higher activity than that for either reference. The high CH4 combustion performance was due to the high specific surface area and to a superior oxygen storage capacity (OSC) even after a combustion test

Phosphorus dynamics during growth and maturation periods of a brown alga Sargassum macrocarpum

海藻類の生育に必須な栄養塩は、温帯沿岸域において、冬季に豊富に存在し、夏季に枯渇する季節性を示す。ワカメなどに代表される一年生の海藻類は、栄養塩が豊富な冬季に生長し、栄養塩が枯渇する初夏には枯死する。一方で、ホンダワラ類などの多年生の褐藻類は、栄養塩が枯渇する夏季を通して周年生長を維持し、沿岸生態系の生物多様性や生物生産を支える藻場を構成する。藻場構成種は、冬季に藻体内に蓄えた栄養塩を生長維持のために利用でき、栄養塩制限に対する耐性を有するものと考えられている。しかし、近年、沿岸域のリン枯渇（貧栄養化）の進行が指摘され、藻場の衰退との因果関係を理解することの重要性が高まっている。藻場保全や衰退した藻場の再生手法を検討するためにも、藻場構成種の貧栄養化に対する生理生態学的メカニズムを解明することが不可欠である。本博士研究では、リンが季節的に枯渇する長崎県五島列島北部を調査海域とし、現存する褐藻ノコギリモク (Sargassum macrocarpum) の生長・成熟過程における、リンの利用動態を培養実験により明らかにすることを目的とした。本研究は、本種の生活史を通して、まず研究①で藻体の「リン吸収速度」と生長維持のための「リン要求速度」の周年変動を実験的に明らかにし、両速度の関係から本種のリン制限の期間を推定した。研究②では、リン制限下で貯留したリンのみを利用して生長を維持できる期間と定義される「リン貯留能」を試算した。本論文は英文で書かれ、4 章から構成されている。第1 章の総合序論では、先進国の沿岸域における富栄養化から貧栄養化への変遷と、それに伴う沿岸生態系のレジームシフトついて論じ、栄養塩環境の変化に対する海藻類の生理生態学的応答をまとめた。第2 章では、リン吸収速度とリン要求速度の周年変動を推定するため、幼体期から成熟期にあたる藻体を毎月採集し、現場環境を再現した実験系で培養した（研究①）。リン吸収速度は、各月で採集された藻体の単位重量・単位時間あたりのリン吸収能に、現場環境のリン濃度を代入して推定した。リン要求速度は、各時期の藻体の日間生長速度と藻体内リン含量を乗じて推定した。その結果、幼体期（冬季）ではリン吸収速度がリン要求速度を上回り、藻体内にリンを貯留することが考えられた。一方で、幼体期後半から成熟期の藻体（春季から夏季）ではリン要求速度がリン吸収速度を上回ったことから、本種は約26 週間の長期間にわたるリン制限にさらされていることが明らかとなった。リン制限期間における、リン要求速度に対するリン吸収速度の割合は、約30%と算出されたことから、本種は要求するリンの約30%を現場環境から吸収し、約70%を幼体期に貯留したリンを利用することにより、周年の生存が可能となると考えられた。そこで、第3 章では、リン制限時に貯留したリンを生長に利用できる期間を示す「リン貯留能」（研究②）を調べるため、本種の幼体期と成熟期にあたる藻体を採集し、栄養塩添加条件下で9 日間培養した。その後、栄養塩枯渇条件にさらして生長速度を推定し、藻体内に貯留しうるリン含量を生長速度で除してリン貯留能を定量した。その結果、リン貯留能は幼体期で約19 週間、成熟期で約16 週間とされ、本種は藻体内のリンを利用して生長を長期間維持できることが明らかとなった。加えて、夏季に発達する梅雨前線や台風などにより、本種の生息域に突発的なリンの増加が観測され、夏季のリン制限下で成熟する本種にとっては、それらの気象条件がリンのパルス的な供給源となる可能性を指摘した。総合考察となる第4 章では、約26 週間のリン制限期間で、本種は枯死することなく生長を維持できることを定量的に明らかにした。本種はリン制限期間で藻体内に貯留したリンだけでなく、現場環境のリンも利用していることから、研究②で推定された伸長期のリン貯留能（約19 週間）にリン吸収を考慮すると、約27 週間と見積もられた。しかし、将来的に、調査海域においてリン枯渇が進行すると、リン制限期間が現在よりも長期化するため、本種は生存が困難となることが予測される。創価大

Hydrothermally Synthesized Ceria with a High Specific Surface Area for Catalytic Conversion of Ethanol to Ethylene

Morphological control can be used to improve the catalytic activity of cerium oxide (ceria, CeO2). In this study, ceria with a high specific surface area was synthesized via the hydrothermal reaction of ceric nitrate and was tested for the catalytic conversion of ethanol to ethylene. As a reference, ceria was also synthesized via a precipitation reaction of cerous nitrate using aqueous ammonia. The Japan reference catalyst JRC-CEO-1 also served as a reference. The specific surface area of the hydrothermally synthesized ceria was as high as that of JRC-CEO-1, but was much higher than that of either reference after calcination at 873 K. Thermogravimetric analysis and IR spectroscopy revealed that the cerias made by hydrothermal and precipitation reactions consisted of high-purity CeO2, whereas JRC-CEO-1 contained 1.5% decomposable functional groups (OH-, CO3 2-). For both ethanol conversion and ethylene selectivity in a catalytic dehydration reaction of ethanol, the activity of the hydrothermally developed ceria was higher than that for either reference. The reaction pathway for the dehydration reaction of ethanol over ceria showed that the specific surface area and the basicity of the Lewis basic sites of the ceria were influential properties. The high catalytic activity of the hydrothermally synthesized ceria was derived from its high specific surface area and high-purity CeO2

Genetic Encoding of 3-Iodo-l-Tyrosine in Escherichia coli for Single-Wavelength Anomalous Dispersion Phasing in Protein Crystallography

SummaryWe developed an Escherichia coli cell-based system to generate proteins containing 3-iodo-l-tyrosine at desired sites, and we used this system for structure determination by single-wavelength anomalous dispersion (SAD) phasing with the strong iodine signal. Tyrosyl-tRNA synthetase from Methanocaldococcus jannaschii was engineered to specifically recognize 3-iodo-l-tyrosine. The 1.7 Å crystal structure of the engineered variant, iodoTyrRS-mj, bound with 3-iodo-l-tyrosine revealed the structural basis underlying the strict specificity for this nonnatural substrate; the iodine moiety makes van der Waals contacts with 5 residues at the binding pocket. E. coli cells expressing iodoTyrRS-mj and the suppressor tRNA were used to incorporate 3-iodo-l-tyrosine site specifically into the ribosomal protein N-acetyltransferase from Thermus thermophilus. The crystal structure of this enzyme with iodotyrosine was determined at 1.8 and 2.2 Å resolutions by SAD phasing at CuKα and CrKα wavelengths, respectively. The native structure, determined by molecular replacement, revealed no significant structural distortion caused by iodotyrosine incorporation

A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome

稀少遺伝性自己炎症性疾患: OTULIN関連自己炎症症候群の新たな病態を解明～既報の疾患に新たな視点を追加し、未診断患者の診断や炎症・細胞死研究の進展に期待～. 京都大学プレスリリース. 2024-04-25.OTULIN-related autoinflammatory syndrome (ORAS), a severe autoinflammatory disease, is caused by biallelic pathogenic variants of OTULIN, a linear ubiquitin-specific deubiquitinating enzyme. Loss of OTULIN attenuates linear ubiquitination by inhibiting the linear ubiquitin chain assembly complex (LUBAC). Here, we report a patient who harbors two rare heterozygous variants of OTULIN (p.P152L and p.R306Q). We demonstrated accumulation of linear ubiquitin chains upon TNF stimulation and augmented TNF-induced cell death in mesenchymal stem cells differentiated from patient-derived iPS cells, which confirms that the patient has ORAS. However, although the de novo p.R306Q variant exhibits attenuated deubiquitination activity without reducing the amount of OTULIN, the deubiquitination activity of the p.P152L variant inherited from the mother was equivalent to that of the wild-type. Patient-derived MSCs in which the p.P152L variant was replaced with wild-type also exhibited augmented TNF-induced cell death and accumulation of linear chains. The finding that ORAS can be caused by a dominant-negative p.R306Q variant of OTULIN furthers our understanding of disease pathogenesis

間欠的な曝気撹拌が海産珪藻Chaetoceros gracilis の生産性に与える影響

The demand for global fisheries protein source continues to increase with the increase of the worldʼs population, causing decrease of natural fishery resources due to the overfishing and the degradation of habitats. Under these circumstances, the fisheries industry for marine products has rapidly grown in recent decades to promote the stable production and utilization of fishery resources while managing and conserving them. Mass cultivation of microalgae is essential for efficient production of artificial seedlings of bivalves whose resources are rapidly decreasing. Diatoms can provide high utility as a primary feed because they contain a high content of fucoxanthin, a carotenoid pigment. The marine diatom, Chaetoceros gracilis which can accumulate fucoxanthin, is a promising feed for fishery products. However, marine diatoms are known as a taxonomic group in which stable cultivation is difficult, and it is necessary to establish a cultivation method that enables high-density cultivation. In previous studies, the factors involved in the growth of marine diatoms have been investigated by controlling the external environment such as light intensity, water temperature and nutrient concentration. However, the establishment of high-density cultivation for marine diatoms under each optimal environmental condition has still not been achieved. A problematic point in the high-density cultivation involves the heterogeneity of the light intensity, water temperature, and nutrient concentration in the culture tank, which limits the growth of algae. Previous studies have reported that “agitation” of the culture solution has the effect of promoting the supply of CO2, as a carbon source, and the removal of dissolved oxygen by equalizing the internal environment of the culture tank, and is essential to improve the productivity of microalgae. However, the performance of using the agitation method remain to be solved in mass culture operation. Intermittent agitation frequency is one of the solutions for low-energy cost operation. There is no previous research comparing biomass productivity per unit of agitation energy input between the same species using both continuous and intermittent agitation methods. The objective of this study was to evaluate the productivity per aeration energy under different agitation frequencies toward high-density cultivation of marine diatom C. gracilis. C. gracilis (UPMC-A0010-2) isolated from Malaysian coastal waters was semi-continuously cultured using modified Conway medium in 1.2-L bubble column reactors (n=2). The culture was conducted under stable light intensity 300 μmol m-2 s-1 (12 hours cycle of light and dark) and temperature (25oC). The dilution rates were adjusted at 0.3 d-1. The aeration rate in each reactor was set to 0.2 L min-1 (2% CO2), and aeration frequency was set to the following three conditions: (1) continuous agitation condition, (2) intermittent agitation condition once 9 every minutes, and (3) intermittent agitation condition once 18 every minutes. The cultivation period was a stationary phase of the biomass for up to 5 days, and the absorbance (750 nm) and pH of the culture, and the dry weight were measured. The biomass productivity per algal volume was equivalent to that under continuous agitation conditions even with relatively high frequency of intermittent agitation once 9 every minutes. This may be caused by the high light utilization efficiency of the cells because the cells in the culture are distributed on an average without sedimentation even after the aeration pause period without agitation. The biomass productivity per unit of agitation energy input in the intermittent agitation conditions showed a higher value than the continuous agitation condition by several times. Intermittent agitation performance can be evaluated as an environmental control technology that can maintain biomass productivity equivalent to continuous agitation conditions. The reduction of energy consumption by intermittent agitation is expected to significantly contribute to the reduction of operating costs for outdoor closed-system reactors

Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms

Azacitidine is a mainstay of therapy for MDS-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their post-treatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pre- (n=449) and post- (n=289) treatment bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their post-treatment clone size on treatment outcomes. In Cox proportional hazard modeling, multi-hit TP53 mutation (HR, 2.03; 95% CI, 1.42-2.91; P<.001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P=.009), and DDX41 mutations (HR, 0.33; 95% CI, 0.17-0.62; P<.001), together with age, high-risk karyotypes, low platelet, and high blast counts, independently predicted OS. Post-treatment clone size accounting for all drivers significantly correlated with International Working Group (IWG)-response (P<.001, trend test), except for that of DDX41-mutated clones, which did not predict IWG-response. Combined, IWG-response and post-treatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, IPSS-M (c-index, 0.653 vs 0.688; P<.001, likelihood ratio test). In conclusion, evaluation of post-treatment clone size, together with pre-treatment mutational profile as well as IWG-response have a role in better prognostication of azacitidine-treated myelodysplasia patients

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour and Sporadic Chromophobe Renal Cell Carcinoma

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated. METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated renal tumours and sporadic renal tumours. FINDINGS: RNA-seq analysis revealed that BHD-associated renal tumours and sporadic renal tumours have totally different expression profiles. Sporadic ChRCCs were clustered into two distinct clusters characterized by L1CAM and FOXI1 expressions, molecular markers for renal tubule subclasses. Increased mitochondrial DNA (mtDNA) copy number with fewer variants was observed in BHD-associated renal tumours compared to sporadic ChRCCs. Cell-of-origin analysis using WGS data demonstrated that BHD-associated renal tumours and sporadic ChRCCs may arise from different cells of origin and second hit FLCN alterations may occur in early third decade of life in BHD patients. INTERPRETATION: These data further our understanding of renal tumourigenesis of these two different types of renal tumours with similar histology. FUNDING: This study was supported by JSPS KAKENHI Grants, RIKEN internal grant, and the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute (NCI), Center for Cancer Research