Microbial platform to synthesize chorismate derivatives via metabolic engineering approach

A synthetic metabolic pathway suitable for the production of chorismate derivatives was designed in Escherichia coli. An L-phenylalanine-overproducing E. coli strain was engineered to enhance the availability of phosphoenolpyruvate (PEP), which is a key precursor in the biosynthesis of aromatic compounds in microbes. Two major reactions converting PEP to pyruvate were inactivated. Using this modified E.coli as a base strain, we tested our system by carrying out the production of salicylate, a high-demand aromatic chemical. The titer of salicylate reached 11.5 g/L in batch culture after 48 h cultivation in a 1-liter jar fermentor, and the yield from glucose as the sole carbon source exceeded 40% (mol/mol). In this test case, we found that pyruvate was synthesized primarily via salicylate formation and the reaction converting oxaloacetate to pyruvate. In order to demonstrate the generality of our designed strain, we employed this platform for the production of each of 7 different chorismate derivatives. Each of these industrially important chemicals was successfully produced to levels of 1-3 g/L in test tube-scale culture. In addition, by extending chorismate pathway, we successfully achieved maleate production, which is one of significant dicarboxylic acid as well as succinate and malate. A novel synthetic pathway of maleate was constructed in our base strain, and the productivity reached 7.1 g/L. This is the first report about maleate production using genetically engineered micro-organisms

Metabolic design of Escherichia coli for muconic acid production

Adipic acid(AA) is a versatile bulk chemical to be used for raw materials such as nylon 6,6. Currently, AA biosynthesis from bio-resources have received a lot of attention in recent years as environment-friendly and renewable AA production process. Muconic acid(MA), also known as 2,4-hexadienedioic acid, is expected as a biosynthesis precursor of AA. There are Several studies on MA biosynthesis using Escherichia coli introduced foreign genes. In those studies, MA is synthesized from intermediate products of shikimate pathway. However, the production volume is not sufficient and it is a hindrance to industrialization. In this study, we aimed to the high efficiency biosynthesis of MA using metabolic designed Escherichia coli. First, we designed the metabolism to increase the accumulation of phosphoenolpyruvic acid (PEP), which is one of the starting materials of the shikimate pathway. Next, we determined the optimal MA synthetic pathway branched from the shikimate pathway. Specifically, we examined three types of MA production pathway with PEP accumulation strain as parent and selected the pathway with the highest MA production. Finally, we examined efficient production of MA using fusion proteins. Shikimate pathway protein and MA production pathway protein were combined to direct carbon flux into MA production

Leveraging Image-Text Similarity and Caption Modification for the DataComp Challenge: Filtering Track and BYOD Track

Large web crawl datasets have already played an important role in learning multimodal features with high generalization capabilities. However, there are still very limited studies investigating the details or improvements of data design. Recently, a DataComp challenge has been designed to propose the best training data with the fixed models. This paper presents our solution to both filtering track and BYOD track of the DataComp challenge. Our solution adopts large multimodal models CLIP and BLIP-2 to filter and modify web crawl data, and utilize external datasets along with a bag of tricks to improve the data quality. Experiments show our solution significantly outperforms DataComp baselines (filtering track: 6.6% improvement, BYOD track: 48.5% improvement).Comment: Accepted at the ICCV 2023 Workshop on Towards the Next Generation of Computer Vision Datasets: DataComp Trac

Establishment of Neurospora crassa as a model organism for fungal virology

The filamentous fungus Neurospora crassa is used as a model organism for genetics, developmental biology and molecular biology. Remarkably, it is not known to host or to be susceptible to infection with any viruses. Here, we identify diverse RNA viruses in N. crassa and other Neurospora species, and show that N. crassa supports the replication of these viruses as well as some viruses from other fungi. Several encapsidated double-stranded RNA viruses and capsid-less positive-sense single-stranded RNA viruses can be experimentally introduced into N. crassa protoplasts or spheroplasts. This allowed us to examine viral replication and RNAi-mediated antiviral responses in this organism. We show that viral infection upregulates the transcription of RNAi components, and that Dicer proteins (DCL-1, DCL-2) and an Argonaute (QDE-2) participate in suppression of viral replication. Our study thus establishes N. crassa as a model system for the study of host-virus interactions. The fungus Neurospora crassa is a model organism for the study of various biological processes, but it is not known to be infected by any viruses. Here, Honda et al. identify RNA viruses that infect N. crassa and examine viral replication and RNAi-mediated antiviral responses, thus establishing this fungus as a model for the study of host-virus interactions

POEMS Syndrome in a 20-year-old Patient Diagnosed Following a Complaint of Reduced Visual Acuity

We report a case of POEMS syndrome in a 20-year-old patient diagnosed after visiting an eye clinic with a chief complaint of reduced visual acuity. A male university student aged 20 years was referred to our department complaining of blurred vision in both eyes that had persisted for 1 month. He also noted headache, nausea, and paresthesia in the lower extremities around the same time. The visual acuity of his right and left eye was 20/40 and 20/20, respectively. Optic disc edema and serous retinal detachment were present. Brain magnetic resonance imaging showed no intracranial abnormalities, while elevated cerebrospinal fluid pressure, reduced nerve conduction velocity in both lower extremities, hepatosplenomegaly, M proteinemia, high blood VEGF levels, osteoblastic and osteolytic changes in the spine, and atypical plasma cells in bone lesions were noted. From the above findings, the patient was diagnosed with POEMS syndrome. He received high-dose dexamethasone, thalidomide, and radiotherapy on the sacral mass, followed by high-dose melphalan with autologous stem-cell support, and showed subsequent systemic and ophthalmologic improvement. Here, we report the youngest case ever of POEMS syndrome with ocular manifestation. If patients have optic disc edema in both eyes with no intracranial space-occupying lesion, POEMS syndrome should be considered in differential diagnosis, regardless of age

The Effect of Dual-Hemisphere Transcranial Direct Current Stimulation Over the Parietal Operculum on Tactile Orientation Discrimination

The parietal operculum (PO) often shows ipsilateral activation during tactile object perception in neuroimaging experiments. However, the relative contribution of the PO to tactile judgment remains unclear. Here, we examined the effect of transcranial direct current stimulation (tDCS) over bilateral PO to test the relative contributions of the ipsilateral PO to tactile object processing. Ten healthy adults participated in this study, which had a double-blind, sham-controlled, cross-over design. Participants discriminated grating orientation during three tDCS and sham conditions. In the dual-hemisphere tDCS conditions, anodal and cathodal electrodes were placed over the left and right PO. In the uni-hemisphere tDCS condition, anodal and cathodal electrodes were applied over the left PO and contralateral orbit, respectively. In the tDCS and sham conditions, we applied 2 mA for 15 min and for 15 s, respectively. Computational models of electric fields (EFs) during tDCS indicated that the strongest electric fields were located in regions in and around the PO. Compared with the sham condition, dual-hemisphere tDCS improved the discrimination threshold of the index finger contralateral to the anodal electrode. Importantly, dual-hemisphere tDCS with the anodal electrode over the left PO yielded a decreased threshold in the right finger compared with the uni-hemisphere tDCS condition. These results suggest that the ipsilateral PO inhibits tactile processing of grating orientation, indicating interhemispheric inhibition (IHI) of the PO

Relation between Prolonged Sedentary Bouts and Health-Related Quality of Life in Patients on Chronic Hemodialysis

This study aimed to investigate the link between prolonged sedentary bouts and health-related quality of life (QOL) in patients on chronic hemodialysis (CHD). A total of 84 outpatients on CHD, aged 71.6±11.8 years, were enrolled in this cross-sectional study. Parameters for prolonged sedentary bouts [i.e., ≧ 30 min (% and bout) and ≧ 60 min (% and bout)] were measured using a triaxial accelerometer. Health-related QOL (HRQOL) was evaluated by the Euro-QOL (EQ-5D). Clinical parameters were obtained from medical records. Relatively prolonged sedentary bouts (%) were 44.0±18.2 (≧ 30 min) and 29.8±16.5 (≧ 60 min) for total days. Prolonged sedentary bouts (bouts) were 6.2±2.7 (≧ 30 min) and 2.7±1.6 (≧ 60 min) for total days. EQ-5D scores were 0.728±0.220. All prolonged sedentary bout parameters were negatively correlated with EQ-5D scores, except for prolonged sedentary bouts (≧ 60 min) (min) and relatively prolonged sedentary bouts (%) on hemodialysis days. Multiple regression analysis showed that prolonged sedentary bout parameters were an important factor in EQ-5D scores even after adjusting for confounding factors for total and non-hemodialysis days. Our results suggested that prolonged sedentary bouts were closely associated with HRQOL in patients on CHD, especially on non-hemodialysis days

Possible westward extension of submerged Oyashio waters to off Tanagashima Island, Kyushu, western Japan: based on the occurrence of the subarctic copepod Neocalanus cristatus

大型浮遊性カイアシ類Neocalanus cristatus は北太平洋亜寒帯に分布し，日本列島の太平洋側に沿って南進する親潮潜流に無効分散する。親潮潜流において本種の最も西側における過去の出現記録は北緯28°，東経134° であった。2015年5月に実施した調査で，種子島約300 km 東方（北緯30°50′，東経131°30′）において本種のコペポディドV 期幼体が出現したため，親潮潜流がこの地点の水深600～950 m まで達している可能性が示唆された。The large-sized planktonic copepod Neocalanus cristatus is distributed in the subarctic Pacific Ocean, and also occurs in the submerged Oyashio Current flowing southward along the Pacific side of Japan as pseudopopulations. These have been recorded from 28˚N, 134˚E, suggesting this may be the westernmost and southernmost boundary of the submergence. The present survey implies that the submergence reaches further westwards to off Tanegashima Island, Kyushu (30˚50′N, 131˚30′E) (ca. 300km), based on the occurrence of the fifth copepodid stage of N. cristatus at presumed depths of 600 to 950m.本研究の一部は日本学術振興会科学研究費（基盤研究C, No.16K07825，代表 大塚　攻）によって行われた

An observation of the walking behavior of Podosphaeraster toyoshiomaruae collected from the bank Oshima-shinsone, Kagoshima Prefecture, Japan

トヨシオマリヒトデPodosphaeraster toyoshiomaruae Fujita and Rowe, 2002は体がほぼ球形で，腕が発達しないという特殊な形態を持つ小型ヒトデ類である。鹿児島県奄美大島北西部に位置する大島新曽根水深100-200 m 程度の堆に生息している。この堆はROV で観察するとカイメン類，八放サンゴ類などで覆われている。2017年5月21日に本種の生きた個体が大島新曽根で採集され，管足を伸ばした状態や歩行が観察されたのでその行動を記載した。管足を体内にしまった状態とは異なり，体がやや口・肛門軸方向に扁平になり，約1.65 cm/min の速度で歩行した。通常の腕の発達したヒトデ類の歩行速度と比較すると相対的に著しく遅い。管足には少なくとも2種類が認められ，歩行用と感覚用と考えられる。The podosphaerastrid asteroid Podosphaeraster toyoshiomaruae Fujita and Rowe, 2002 is small-sized, nearly spherical in shape. The species exclusively inhabits on the bank Oshima-shinsone at depths of 100 to 200 m, northwest of Amami-Oshima Island, Kagoshima Prefecture, Japan, where the bottom is entirely covered with sponges, octocorals, and hyrozoan polyps with patches of sandy bottom. The bottom conditions were clearly observed with a ROV on September 29, 2009. A living specimen was collected from this locality on May 21, 2017. During locomotion by tube feet, the body was depressed dorso-ventrally in contrast with the spherical body shape with tube feet unexpanded. The locomotion rate of the specimen was about 1.65 cm/min. Two types of tube feet were identified. Presumably one is for locomotion with a sucker terminally, while the other for sensing.本研究の一部は日本学術振興会科学研究費（基盤研究C，No.16K07825，代表 大塚攻），国立科学博物館総合研究「黒潮に注目した地史・生物史・人類史」によって行われた