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Polarized transport is essential for constructing multiple plasma membrane domains in the cell. Drosophila photoreceptors are an excellent model system to study the mechanisms of polarized transport. Rab11 is the key factor regulating the post-Golgi transport of rhodopsin 1 (Rh1; also known as NinaE), a photoreceptive protein, to the rhabdomere, a photoreceptive plasma membrane. Here, we found that neuronal Synaptobrevin (nSyb) colocalizes with Rab11 on the trans-side of Golgi stacks and post-Golgi vesicles at the rhabdomere base, and nSyb deficiency impairs rhabdomeric transport and induces accumulation of Rh1 and vesicles in the cytoplasm; this is similar to the effects of Rab11 loss. These results indicate that nSyb acts as a post-Golgi SNARE toward rhabdomeres. Surprisingly, in Rab11-, Rip11- and nSyb-deficient photoreceptors, illumination enhances cytoplasmic accumulation of Rh1, which colocalizes with Rab11, Rabenosyn5, nSyb and Arrestin 1 (Arr1). Arr1 loss, but not Rab5 dominant negative (Rab5DN) protein expression, inhibits the light-enhanced cytoplasmic Rh1 accumulation. Rab5DN inhibits the generation of Rh1-containing multivesicular bodies rather than Rh1 internalization. Overall, these results indicate that exocytic Rh1 mingles with endocytosed Rh1 and is then transported together to rhabdomeres.

Stratum is required for polarized transport in Drosophila photoreceptors through the stable expression of Rab10 and Rab35, which regulate basolateral and rhabdomere transport, respectively.

International audience; France (CEA and FRAMATOME) and Japan (JAEA, MFBR, and MHI) teams have carried out collaborative works to have common technical views regarding a sodium-cooled fast reactor (SFR) concept. This paper mainly describes the capabilities of ASTRID 600 to demonstrate SFR technologies of both countries. Japan has studied the feasibility of an enhanced high burnup low-void effect (CFV) core and fuel using oxide dispersion-strengthened steel cladding in ASTRID 600, considering Japan’s target for core performance. The neutronics design of the core has satisfied most required design targets and conditions. Regarding passive shutdown capabilities, Japan team has performed a preliminary numerical analysis for ASTRID 600 using a complementary safety device (CSD), called a self-actuated shutdown system (SASS), one of the safest approaches in Japan. Japan’s team used the SASS in place of the hydraulically suspended absorber rod, called RBH, one of the safest approaches of France, to investigate the potential of the SASS as a design measure common to the countries. The preliminary analysis has shown that the SASS can satisfy the countries’ main requirements. This study has also revealed that the mitigation measures of ASTRID 600 against a severe accident are promising to achieve in-vessel retention for both countries.

In this paper, we study the root distributions of Ehrhart polynomials of free sums of certain reflexive polytopes. We investigate cases where the roots of the Ehrhart polynomials of the free sums of $A_d^\vee$'s or $A_d$'s lie on the canonical line $\mathrm{Re}(z)=-\frac{1}{2}$ on the complex plane $\mathbb{C}$, where $A_d$ denotes the root polytope of type A of dimension $d$ and $A_d^\vee$ denotes its polar dual. For example, it is proved that $A_m^\vee \oplus A_n^\vee$ with $\min\{m,n\} \leq 1$ or $m+n \leq 7$, $A_2^\vee \oplus (A_1^\vee)^{\oplus n}$ and $A_3^\vee \oplus (A_1^\vee)^{\oplus n}$ for any $n$ satisfy this property. We also perform computational experiments for other types of free sums of $A_n^\vee$'s or $A_n$'s., 16 pages, 3 tables

McArdle disease (glycogen storage disease type V) is a rare hereditary metabolic myopathy. It can be overlooked clinically because it often presents as chronic asymptomatic hypercreatine phosphokinasemia (hyperCKemia). However, vigorous exercise or infections can trigger severe rhabdomyolysis. We present the case of a patient with long-term idiopathic hyperCKemia who, after contracting an upper respiratory tract infection, developed severe rhabdomyolysis and acute kidney injury. Upon hemodialysis, his renal function recovered and CK levels fell to below baseline, and maintenance therapy with vitamin B6 was also started. A molecular diagnosis of McArdle disease was subsequently made. Whole-exome sequencing revealed homozygous c1538delG (p.Asp511Thr fs*28) mutations in the PYGM gene, which was a novel mutation. Therefore, when investigating idiopathic hyperCKemia, glycogen storage disorders should also be considered.

Mesenchymal stem cells (MSCs) are a potential therapeutic tool for preventing the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). Herein, we investigated the localization and maintenance of engrafted human bone marrow-derived MSCs in rats subjected to a renal ischemia-reperfusion injury (IRI) and compared the effectiveness of two intravascular injection routes via the renal artery or inferior vena cava. Renal artery injection of MSCs was more effective than intravenous injection at reducing IRI-induced renal fibrosis. Additionally, MSCs injected through the renal artery persisted in injured kidneys for over 21 days, whereas MSCs injected through the inferior vena cava survived for less than 7 days. This difference may be attributed to the antifibrotic effects of MSCs. Interestingly, MSCs injected through the renal artery were localized primarily in glomeruli until day 3 post-IRI, and they decreased in number thereafter. In contrast, the number of MSCs localized in tubular walls, and the interstitium increased gradually until day 21 post-IRI. This localization change may be related to areas of damage caused by IRI because ischemia-induced AKI leads to tubular cell damage. Taken together, these findings suggest renal artery injection of MSCs may be useful for preventing the progression of AKI to CKD.

Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia–reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.

The Standard Language Test of Aphasia (SLTA) is the most frequently used comprehensive aphasia rating scale in Japan. Although the SLTA has been verified for reliability, verification for validity is inadequate. The purpose of this study was to examine criterion-related validity of the SLTA. The SLTA was performed on patients who had passed 3months or more after onset of the aphasia-causing disease such as stroke, and the Japanese version of the Western Aphasia Battery (WAB) was subsequently performed. We investigated age, gender, disease, and calculated Spearman's rank correlation coefficient for total score and each item of the SLTA and the WAB. There were 20participants (14males, 6females), with a mean age of 68.5±12.5years. Correlations of the SLTA and the WAB were as follows: SLTA total index score and WAB aphasia quotient; r=0.870 (P0.001), SLTA Writing factor and WAB (VI) Writing; r=0.852 (P0.001), SLTA writing instructions and WAB writing instructions; r=0.807 (P0.001). Many of the correlations of Z-scores between sub-tests were r≥0.7. The SLTA has criteria-related validity and now the aphasia test that has been tested for reliability and validity. (Received July 22, 2019; Accepted March 4, 2020; Published July 1, 2020).

Background:Mesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes may require a substantial period of time, leading to a delayed onset of MSCs therapeutic effects. Here, we investigatedwhetherpretreatment with IFN-γ potentiates the anti-fibrotic and anti-inflammatory activities of MSCs in an injured kidney. Methods:MSCs with or without IFN-γ treatment were injected into rats after ischemia-reperfusion injury (IRI) or unilateral ureter obstruction (UUO) to evaluate the therapeutic effect of IFN-γ-treated MSCs. In addition, we used conditioned medium obtained from IFN-γ-treated MSCs to investigate fibrotic change in cultured cells induced by transforming growth factor-β1 and phenotypic change of macrophages using THP-1 monocytes.Results:Administration of MSCs treated with IFN-γ strongly ameliorated renal fibrosis and inflammation in rat IRI and UUO models compared with that of untreated MSCs. In vitro experiments demonstrated that IFN-γ treatment enhanced the anti-fibrotic effects of MSCs by inhibiting the transforming growth factor-β1/Smad signaling pathway. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 induced polarization of immunosuppressive CD163-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ.Conclusions:Administration of MSCs treated with IFN-γ may represent a promising therapy to prevent the progression of renal fibrosis.

Design optimization of single emitter broad stripe 900-nm laser diodes was experimentally studied to achieve high power conversion efficiency (PCE) for a use in fiber laser systems. We chose two approaches for PCE improvement. The first is an optical confinement factor Γwell optimization which affects threshold current and internal loss. The second is electric resistance minimization to suppress unwanted power consumption causing heat generation. As a result, the newly designed LD successfully demonstrates the high PCE of 72.5 % at middle power range and 66.7 % at practical high power of 20 W.

Nanoparticles have been cited as a tool to solve many pharmaceutical problems, also in the cosmetic field. Some advantages in using them are to vectorize or retard the release and action of a cosmetic active substance, to increase stability, effectiveness, and safety, etc. However, there are many kinds of nanoparticles that should be chosen accordingly to the need of application. Although there are advantages related to the use of nanoparticles, some difficulties could be cited, such as the scale up of the technology and safety assessment. Considering the above, this chapter aimed to show the main kinds of nanoparticles employed in the cosmetic area, highlighting the advantages obtained with their use. Also, it will discuss the scale-up and the safety assessment, mainly in relation to the pathway followed by the nanoparticle when applied on the skin.

The incidence of metachronous gastric cancer (MGC) in patients whose primary gastric neoplasm is discovered after Helicobacter pylori eradication remains unclear. Here, we evaluated the long-term effect of previous H pylori eradication on development of MGC after endoscopic submucosal dissection (ESD).We analyzed prospectively collected data of consecutive patients with successful H pylori eradication more than 1 year before (eradicated group, 180 patients) or after (control group, 602 patients) initial curative ESD. These patients were also followed by endoscopy for over 2 years. Propensity score matching and inverse probability of treatment weighting (IPTW) were used to adjust for confounding variables during data analysis. The main outcome was the incidence of MGC after initial ESD.In a propensity-matched analysis of 174 pairs, the incidence of MGC was similar in the 2 cohorts (33.9 per 1000 person-years vs 40.8 per 1000 person-years in the control group, P = .454) at a median follow-up of 4.1 years (interquartile range, 3.0-5.6). Incidences were also similar in the 2 groups when data were analyzed using IPTW, even after exclusion of 123 patients with successful H pylori eradication 5 years before initial ESD. Multiple Cox regression analysis revealed age, differentiated-type histology, and initial multiplicity were predictors of MGC in patients after initial curative ESD.The frequency of follow-up surveillance after initial curative ESD should be kept constant, irrespective of whether H pylori eradication is performed before or after initial curative ESD.

Sarcopenic dysphagia is partly characterized by a decline in the strength of the swallowing muscles. However, its associated characteristics and symptoms are unclear. The aim of this study was to clarify the characteristics and symptoms of swallowing ability associated with low tongue muscle strength, which is one of the swallowing muscles in older adults.This was a cross-sectional study of 197 older patients admitted to the hospital for orthopedic conditions. We measured the maximum tongue pressure (MTP) against the palate. Swallowing-related characteristics were assessed with the Mann assessment of swallowing ability. Sarcopenia was diagnosed using the 2019 Asian Working Group for Sarcopenia.The mean age of patients was 81.3 ± 7.6 y, and 80.2% of patients were women. Forty-two patients (21.3%) showed low MTP, defined as20 kPa. Approximately 50% of participants had sarcopenia. Patients in the low MTP group had a significantly higher incidence of sarcopenia compared with the normal MTP group (71.4% vs. 48.4%; P = .008). After adjusting for potential confounders in the multivariate analyses, low MTP was found to be independently associated with abnormalities in tongue coordination (odds ratio [OR]: 5.251; 95% confidence interval [CI], 2.336-11.807; P.001), oral transit (OR: 5.248; 95% CI, 1.424-19.345; P = .013), cough reflex (OR: 2.709; 95% CI, 1.280-5.733; P = .009), and voluntary cough (OR: 7.786; 95% CI, 3.329-18.208; P.001).Patients with low tongue strength are characterized by abnormal oral and cough-related characteristics.

International audience; In the frame of the France-Japan agreement on nuclear collaboration, a bilateral collaboration agreement on nuclear energy was signed on March 21st, 2017, including a topic dedicated to Sodium-cooled Fast Reactor (SFR). This agreement has set the framework to start a bilateral discussion on a joint view of an SFR concept. France (CEA and FRAMATOME) and Japan (JAEA, MHI and MFBR) have carried out these studies from 2017 to 2019. Based on the beginning of the basic design phase of ASTRID project − ASTRID − 600 MWe (ASTRID for Advanced Sodium Technological Reactor for Industrial Demonstration), the two countries performed a common work to examine ways to develop a feasible common design concept, which could be realized both in France and in Japan. The subject was then extended and extrapolated with the ASTRID − 150 MWe data (reduced power reactor and enhanced experimental capabilities) in a second phase of this study. France and Japan first focused on design requirements. Common requirements were identified, as well as differences in the safety approach and the structural design requirements, according to national standards and respective site conditions, in particular considering seismic hazards. The teams developed common Top-Level design Requirements (TLRs) to allow common specification data, then joint design. This collaborative work was carried out through the implementation of twelve France-Japan Working Groups, working jointly. This paper is providing a review of this joint synthesis on Sodium Fast Reactor design concept. It is summarizing the context and objectives, then the definition and approaches of the Top Level Requirements. This paper is then dealing with the major design features: the core design and their related safety aspects, and the nuclear island design. Thus, this paper is providing a comprehensive review of this joint work gathering French and Japan nuclear design teams during two full years.

Respiratory virus-induced wheezing, such as that induced by respiratory syncytial virus (RSV) and human rhinovirus, is an important risk factor for recurrent wheezing and childhood asthma. However, no biomarkers for predicting recurrent wheezing have been identified.We searched for predictors of recurrent wheezing using nasopharyngeal aspirates obtained from patients during the first wheezing episode who were hospitalized with an acute lower respiratory tract illness.We enrolled 82 infants during the first wheezing episode (median age, 5.0 months) who were hospitalized for acute lower respiratory tract illness between August 2009 and June 2012 and followed these patients for 2.5 years. Nasopharyngeal aspirates and blood samples were obtained on the first day of hospitalization. Viral genomes were identified by using RT-PCR and sequencing. Levels of 33 cytokines, tryptase, IgE, anti-RSV IgE, and anti-RSV IgG were measured by using ELISAs or the Bio-Plex multiplex assay. Predictors of recurrent wheezing were examined by using a stepwise logistic regression model with backward elimination.Sixty percent of the patients experienced recurrent wheezing episodes. One or more viruses were detected in the nasopharynxes of 93% of the patients during the first wheezing episode. IFN-γ, IL-2, IL-9, MIP-1α, and MIP-1β levels were significantly higher among patients with recurrent wheezing than among those without recurrent wheezing (P.05 or .01). The stepwise model demonstrated that the MIP-1α level (odds ratio, 7.72; 95% CI, 1.50-39.77; P = .015) was the strongest independent predictor of the occurrence of recurrent wheezing.An increased MIP-1α level in nasopharyngeal aspirates from patients with acute respiratory symptoms during the first wheezing episode caused by viral infections might predict recurrent wheezing.

Japan hosts more than 40% population of Brent Goose Branta bernicla wintering in East Asia. We used satellite-tracking technology to monitor the seasonal movements and habitat usage of Brent Goose wintering in northern Japan. We marked five geese on the Oya sandy beach, Miyagi Prefecture, northeast Honshu, on 21 January 2014. The geese utilized areas along the seacoast, especially concentrating at a small bay, close to the capture site. Most of the geese offshore were found at fishery rafts. No geese were found more than 2 km offshore or more than 6 km from the capture site along the seacoast. In early April, the geese left the southern Sanriku coast and moved up to eastern Hokkaido, crossing the sea directly or via the coastal areas of Iwate and Aomori Prefectures. The geese predominantly remained in the vicinity of the Veslovskiy Peninsula, Kunashiri (Kunashir) Island, while some were distributed along the northern coast of the Nemuro Peninsula. We identified eastern Hokkaido and Kunashiri Isla...

A 42-year-old woman with bronchial asthma was admitted to our hospital due to sensory dominant mononeuritis multiplex lasting for more than 6 months. At that time, her eosinophil count was 761/μl and her sural nerve biopsy showed no findings suggestive of vasculitis. Four months later, she experienced sudden convulsions and right hemiparesis due to left lobular parietal subcortical hemorrhage, when her eosinophil count was elevated to 3,257/μl. Numerous microbleeds and small infarctions were also detected in the intracerebral areas of different regions with MRI. Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis of the small vessels, commonly affecting the peripheral nerves. Subarachnoid hemorrhage in patients with EGPA is extremely rare. Steep elevation of the eosinophil count may release certain cytokines, causing cerebral hemorrhage.

Multicentric Castleman disease (MCD) is a rare systemic lymphoproliferative disorder and is infrequently associated with renal complications that include amyloid A (AA) amyloidosis. Although it has been reported that patients with MCD and amyloidosis usually have a poor prognosis, recently, tocilizumab, a humanized anti-interleukin-6 receptor antibody, has emerged as an effective and specific treatment for AA amyloidosis secondary to chronic inflammatory disorders. Here we report a case of an MCD patient with secondary AA renal amyloidosis who was successfully treated with tocilizumab. The patient was initially referred to nephrology specialists because of a decline in renal function and proteinuria. Percutaneous renal biopsy revealed the presence of Congo red-positive amorphous depositions and AA protein-positive areas in glomeruli, vessel walls, and interstitium, confirming a diagnosis of renal AA amyloidosis secondary to MCD. At 1 year after starting tocilizumab treatment, a second renal biopsy showed the clearance of amyloid deposits in the interstitium. These observations suggest that tocilizumab may be an effective therapy for AA amyloidosis secondary to MCD. .

Polarization characteristics of self-aligned stripe (SAS) laser diodes (LDs) and Ridge-LDs are investigated to realize highly efficient polarization beam combined (PBC) LD modules. Vertical layers of both lasers are designed identically. Near field patterns (NFP) of TM polarization for the Ridge-LD showed peaks at the side edges, as expected by the strain simulation. On the other hand, SAS-LD showed a relatively flat and weak profile. Polarization purity (ITE/ (ITE+ITM)) of SAS-LDs exceeds 99%, while those of the Ridge-LDs are as low as 96%. It is confirmed that our SAS-LDs are suitable sources for PBC with low power loss.

The patient was a 43-year-old Japanese man. At age 41, he underwent carpal tunnel release surgeries for bilateral carpal tunnel syndrome. At age 42, he began experiencing recurrent episodes of naus...

Background: If asthmatic children cannot obtain sufficient control of their disease, not only do they suffer from asthma symptoms, but the daily life activities of their caregivers are also disrupted. We investigated the effectiveness of an inhaled corticosteroid (ICS) for symptom control in previously ICS-untreated school-aged asthmatic children as well as caregiver treatment satisfaction (CTS). Methods: A multicenter, open-label, single-arm study on 12-week ICS (budesonide Turbuhaler®) monotherapy was undertaken in subjects aged 5–15 years with bronchial asthma not treated with ICS during the previous 3 months. At 0, 4, 8, and 12 weeks after start of ICS administration, Japanese Pediatric Asthma Control Program (JPAC) scores, and CTS scores were summated and lung function measured. At weeks 0 and 12, questionnaires on caregiver anxiety were also assessed. Results: Seventy-five patients were enrolled, and 69 assessed. Ninety percent of subjects had been treated with asthma controller medication except ICS before study enrollment. JPAC score and CTS score were improved significantly at weeks 4, 8, and 12 (p

Leukotriene receptor antagonists (LTRAs) are identified as a monotherapy for asthma and allergic rhinitis; however, their use in children for treatment of these diseases has not been examined. Accordingly, the present study investigated the efficacy of pranlukast dry syrup for children with both pollinosis and asthma. The subjects were children receiving treatment for asthma who were also diagnosed with cedar pollen allergy. Patients were divided into a group that received continuous treatment with pranlukast (group A; n=20) and a group that commenced add-on treatment for pollinosis following the onset of symptoms (group B; n=20). Patients in group B were randomly allocated to subgroup B1 (add-on treatment with pranlukast dry syrup) or subgroup B2 (add-on treatment with a second-generation antihistamine). In both groups, nasal and ocular symptoms were evaluated every day and recorded in a diary. Exacerbation of nasal obstruction was demonstrated in group B; however, not in group A. There was a significant difference in symptoms observed between the two groups during the late peak pollen period (P

Design optimization of single emitter broad stripe 9xx-nm laser diodes was studied to achieve ultimate high power and high efficiency operation for a use in fiber laser pumping and other industrial applications. We tuned laser vertical layer design and stripe width in terms of optical confinement as well as electrical resistance. As a result, newly designed LDs with 4mm-long cavity and 220 μm-wide stripe successfully demonstrate maximum CW output power as high as 33 W and high efficiency operation of more than 60 % PCE even at 27 W output power. In pulse measurement, the maximum output of 68 W was obtained.