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Abstract Background Cepharanthin® alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin®. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions. Methods Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4+CD25+Foxp3+ regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot. Results CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4+ cells, CD8+ cells, and lymphocytes (P

ABSTRACT Prokaryotes contribute to the global sulfur cycle by using diverse sulfur compounds as sulfur sources or electron acceptors. In this study, we report that a nitrogenase-like enzyme (NFL) and a radical SAM enzyme (RSE) are involved in the novel anaerobic assimilation pathway of a sulfonate, isethionate, in the photosynthetic bacterium Rhodobacter capsulatus. The nflHDK genes for NFL are localized at a locus containing genes for known sulfonate metabolism in the genome. A gene nflB encoding an RSE is present just upstream of nflH, forming a small gene cluster nflBHDK. Mutants lacking any nflBHDK genes are incapable of growing with isethionate as the sole sulfur source under anaerobic photosynthetic conditions, indicating that all four NflBHDK proteins are essential for the isethionate assimilation pathway. Heterologous expression of the islAB genes encoding a known isethionate lyase that degrades isethionate to sulfite and acetaldehyde restored the isethionate-dependent growth of a mutant lacking nflDK, indicating that the enzyme encoding nflBHDK is involved in an isethionate assimilation reaction to release sulfite. Furthermore, the heterologous expression of nflBHDK and ssuCAB encoding an isethionate transporter in the closely related species R. sphaeroides, which does not have nflBHDK and cannot grow with isethionate as the sole sulfur source, conferred isethionate-dependent growth ability to this species. We propose to rename nflBHDK as isrBHDK (isethionate reductase). The isrBHDK genes are widely distributed among various prokaryote phyla. Discovery of the isethionate assimilation pathway by IsrBHDK provides a missing piece for the anaerobic sulfur cycle and for understanding the evolution of ancient sulfur metabolism.IMPORTANCENitrogenase is an important enzyme found in prokaryotes that reduces atmospheric nitrogen to ammonia and plays a fundamental role in the global nitrogen cycle. It has been noted that nitrogenase-like enzymes (NFLs), which share an evolutionary origin with nitrogenase, have evolved to catalyze diverse reactions such as chlorophyll biosynthesis (photosynthesis), coenzyme F430 biosynthesis (methanogenesis), and methionine biosynthesis. In this study, we discovered that an NFL with unknown function in the photosynthetic bacterium Rhodobacter capsulatus is a novel isethionate reductase (Isr), which catalyzes the assimilatory degradation of isethionate, a sulfonate, releasing sulfite used as the sulfur source under anaerobic conditions. Isr is widely distributed among various bacterial phyla, including intestinal bacteria, and is presumed to play an important role in sulfur metabolism in anaerobic environments such as animal guts and microbial mats. This finding provides a clue for understanding ancient metabolism that evolved under anaerobic environments at the dawn of life.

Abstract When exposed to oxidative and electrophilic stress, a protective antioxidant response is initiated by nuclear factor erythroid 2-related factor 2 (Nrf2). However, the extent of its importance in the forensic diagnosis of acute ischemic heart diseases (AIHD), such as myocardial infarction (MI), remains uncertain. On the other hand, immunohistochemical analyses of fibronectin (FN) and the terminal complement complex (C5b-9) prove valuable in identifying myocardial ischemia that precedes necrosis during the postmortem diagnosis of sudden cardiac death (SCD). In this study, we investigated the immunohistochemical levels of Nrf2, FN, and C5b-9 in human cardiac samples to explore their forensic relevance for the identification of acute cardiac ischemia. Heart samples were obtained from 25 AIHD cases and 39 non-AIHD cases as controls. Nrf2 was localized in the nuclei of cardiomyocytes, while FN and C5b-9 were detected in the myocardial cytoplasm. The number of intranuclear Nrf2 positive signals in cardiomyocytes increased in AIHD cases compared to control cases. Additionally, the grading of positive portions of cardiac FN and C5b-9 in the myocardium was also significantly enhanced in AIHD, compared to controls. Collectively, these results indicate that the immunohistochemical investigation of Nrf2 combined with FN, and/or C5b-9 holds the potential for identifying early-stage myocardial ischemic lesions in cases of SCD.

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agβ1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agβ1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control.

We designed and fabricated our original laminated materials that simultaneously exhibited different properties: magneto-optical (MO), i.e., the transverse MO Kerr effects (T-MOKE) and surface-plasmon resonance (SPR). The material design was composed of dielectric, magnetic, and noble-metal layers. We selected the soft-magnetic FeSi thin film as a T-MOKE magnetic layer, while an Au thin film was chosen as a SPR-source layer, creating an FeSi-/Au-based “MO-SPR material.” Strong interactions between T-MOKE and SPR were demonstrated. When the material is irradiated with a laser beam of wavelength 660 nm, at the SPR angle to the material, θR, the highest T-MOKE value was attained. The T-MOKE was markedly enhanced at θR: ∼32 to ∼84 times higher compared with the FeSi single layer (reference). The T-MOKE was amplified by a strong interaction between MO activities and electromagnetic field distributions. The FeSi (5.0 nm)/Au (14.8 nm) specimen achieved the best signal-to-noise ratio (SNR). The sample was then tested for its sensing efficiency by measuring the T-MOKE using distilled water and a glucose solution, respectively: It was possible to distinguish between two different solutions. Our MO-SPR materials utilizing both magnetism and near-field light are thus sufficiently sensitive to be applicable as sensing materials. Furthermore, the polarity of the T-MOKE signal is flipped under the application of a small, external magnetic field owing to the soft magnetism of the FeSi T-MOKE layer. This is highly advantageous to create high-frequency AC-magnetic synchronized T-MOKE sensing systems with low-power consumption.

Although end-to-end (E2E) text-to-speech (TTS) models with HiFi-GAN-based neural vocoder (e.g. VITS and JETS) can achieve human-like speech quality with fast inference speed, these models still have room to further improve the inference speed with a CPU for practical implementations because HiFi-GAN-based neural vocoder unit is a bottleneck. Additionally, HiFi-GAN is widely used not only for TTS but also for many speech and audio applications. To accelerate HiFi-GAN while maintaining the synthesis quality, Multi-stream (MS)-HiFi-GAN, iSTFTNet and MS-iSTFT-HiFi-GAN have been proposed. Although inverse short-term Fourier transform (iSTFT)-based fast upsampling is introduced in iSTFTNet and MS-iSTFT-HiFi-GAN, we first find that the predicted intermediate features input to the iSTFT layer are completely different from the original STFT spectra due to the redundancy of the overlap-add operation in iSTFT. To further improve the synthesis quality and inference speed, we propose FC-HiFi-GAN and MS-FC-HiFi-GAN by introducing trainable fully-connected (FC) layer-based fast upsampling without overlap-add operation instead of the iSTFT layer. The experimental results for unseen speaker synthesis and E2E TTS conditions show that the proposed methods can slightly accelerate the inference speed and significantly improve the synthesis quality in JETS-based E2E TTS than iSTFTNet and MS-iSTFT-HiFi-GAN. Therefore, the iSTFT layer can be replaced by the proposed trainable FC layer-based upsampling without overlap-add operation in HiFi-GAN-based neural vocoders.

Aim: The deep squat test (DST) is a screening test to assess the function of the lower extremity and the flexibility of ankle dorsiflexion. Previous study reported that approximately 70% of players with disabled throwing shoulder and/or elbows were unable to perform DST. The aim of this study was to reveal the relationship between performance of DST and history of disabled throwing shoulder/elbow. Methods: A total of 1,439 youth baseball players (10.9 years; range 6–16 years), who participated in pre-season medical examination were included in the study. Players who experienced shoulder or elbow pain of the throwing side during or after playing baseball in the past were defined as players with a history of disabled throwing shoulder/elbow. The DST was evaluated by having the players perform a full squat with while having their arms crossed in front of their chest and their feet apart without lifting the heel off the floor or falling backwards. The relationship between a history of disabled throwing shoulder/elbow and the ability to perform DST was analyzed. Results: Among the study participants, 499 (34.7%) had a history of disabled throwing shoulder/elbow, and 532 players (37.0%) were unable to perform DST. Of the players with disabled throwing shoulder/elbow history, 227 players (45.5%) were unable to perform DST, as were 305 players out of 940 players (32.5%) without a disability; this difference was statistically significant (P

Abstract Estimating the age and vitality of human skin wounds is essential in forensic practice, and the use of immunohistochemical parameters in this regard remains a challenge. Heat shock proteins (HSPs) are evolutionarily conserved universal proteins that protect biological systems from various types of stress. However, its importance in forensic pathology for determining wound activation in neck compression skin remains unclear. The expression of HSP27 and HSP70 in neck skin samples was immunohistochemically examined to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 45 cases of neck compression (hanging, 32 cases; strangulation, 10 cases; manual strangulation, 2 cases; other, 1 case) during forensic autopsies; intact skin from the same individual was used as a control. HSP27 expression was detected in 17.4% of keratinocytes in the intact skin samples. In the compressed region, the frequency of HSP27 expression in keratinocytes was 75.8%, which was significantly higher than that in intact skin. Similarly, HSP70 expression was 24.8% in intact skin samples and 81.9% in compressed skin samples, significantly higher in compressed skin than in intact skin samples. This increase in case compression cases may be due to the cell defence role of HSPs. From a forensic pathology perspective, the immunohistochemical examination of HSP27 and HSP70 expression in neck skin could be considered a valuable marker for diagnosing traces of antemortem compression.

Background: Stair climbing is a part of the basic activities of daily living. Previous biomechanical analyses of stairs have been conducted in the laboratory, resulting in only a few steps. Therefore, the biomechanical characteristics of long stair climbing in the real world remain unclear. The purpose of this study was to identify differences in kinematic and kinetic in the lower limb between the beginning and end phases of long stair climbing in an outdoor environment using a wearable motion analysis system. Eight subjects (four males and four females) were included in the data analysis (age: 23.6 ± 0.5 years). The long stair was 66 consecutive steps out of 202 stone steps. A wearable motion analysis system comprised six inertial measurement units and foot pressure sensors. The maximum ankle joint flexion angle in the end phase was significantly increased more than in the beginning phase (p < 0.001). On the other hand, the other kinematic, kinetic, and stair climbing speeds showed no significant difference between the phases. The findings indicated that fatigue during long stair climbing might increase ankle dorsiflexion to compensate for forwarding propulsion.

Abstract We investigated the dynamics of the gene expression of M1 and M2 macrophage markers during skin wound healing in mice. Expression of M1-macrophage markers, such as Il12a, Tnf, Il6, Il1b, and Nos2 was upregulated after wounding and peaked at 1 or 3 days after injury, and that of M2-macrophage markers such as Mrc1, Cd163, Ccl17, Arg, and Tgfb1, peaked at 6 days after injury. Consistent with these findings, using triple-color immunofluorescence analysis revealed that F4/80+CD80+ M1 macrophages were more abundant than F4/80+CD206+ M2 macrophages on day 3 in mouse wound specimens, and that M2 macrophages were prominently detected in day 6 wounds. For application in forensic practice, we examined macrophage polarization using human wound specimens. The average ratios of CD68+iNOS+ M1 macrophages to CD68+CD163+ M2 macrophages (M1/M2 ratios) were greater than 2.5 for the wounds aged 2–5 days. Out of 11 wounds aged 1–5 days, five samples had the M1/M2 ratios of > 3.0. These observations propose that the M1/M2 ratios of 3.0 would indicate a wound age of 1–5 days as the forensic opinion. This study showed that M1 and M2 macrophages in human skin wound might be a promising marker for wound age determination.

Abstract We demonstrate magneto-optical (MO) polarization transformation due to surface plasmons in CoPt perpendicular magnetic films in the polar Kerr geometry. An extraordinary Kerr rotation angle (θ K = ± 88.9°) that almost reaches the upper limit of polarization is produced in the attenuated total reflection (Kretschmann) configuration. P-polarized incident radiation is almost transformed upon reflection to s-polarized radiation, which may be out of phase depending on whether the magnetization of CoPt is up or down. Moreover, the reflected intensity may be drastically modulated by applying an external magnetic field. The reflectivity goes almost to zero in the demagnetized state and increases with increasing external magnetic field. This drastic optical response is attributed to the MO destructive interference produced by the subwavelength magnetic domain structure.

We aimed to evaluate the effect of dietary calcium (Ca)-octanoate supplementation on concentrations of ghrelin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin in plasma and milk of beef cattle during late gestation and early postpartum. Twelve Japanese Black cattle were offered concentrate without (CON, n = 6) or with Ca-octanoate supplementation at 1.5% of dietary dry matter (OCT, n = 6). Blood samples were collected at −60, −30, and −7 d relative to the expected parturition date and daily from d 0 to 3 after parturition. Milk samples were collected daily postpartum. Compared to the CON group, concentrations of acylated ghrelin increased in plasma as parturition approached in the OCT group (P = 0.02). However, concentrations of GH, IGF-1, and insulin in plasma and milk were not affected by treatment groups throughout the study. Additionally, we showed for the first time that bovine colostrum and transition milk contain acylated ghrelin at a significantly higher concentration than plasma (P = 0.01). Interestingly, concentrations of acylated ghrelin in milk were negatively correlated with those in plasma postpartum (r = −0.50, P

Class A G protein-coupled receptors (GPCRs) represent the largest class of GPCRs. They are essential targets of drug discovery and thus various computational approaches have been applied to predict their ligands. However, there are a large number of orphan receptors in class A GPCRs and it is difficult to use a general protein-specific supervised prediction scheme. Therefore, the compound-protein interaction (CPI) prediction approach has been considered one of the most suitable for class A GPCRs. However, the accuracy of CPI prediction is still insufficient. The current CPI prediction model generally employs the whole protein sequence as the input because it is difficult to identify the important regions in general proteins. In contrast, it is well-known that only a few transmembrane helices of class A GPCRs play a critical role in ligand binding. Therefore, using such domain knowledge, the CPI prediction performance could be improved by developing an encoding method that is specifically designed for this family. In this study, we developed a protein sequence encoder called the Helix encoder, which takes only a protein sequence of transmembrane regions of class A GPCRs as input. The performance evaluation showed that the proposed model achieved a higher prediction accuracy compared to a prediction model using the entire protein sequence. Additionally, our analysis indicated that several extracellular loops are also important for the prediction as mentioned in several biological researches.

Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, can progress to hepatic steatosis, inflammation, and advanced fibrosis, increasing the risk of cirrhosis. Resveratrol, a natural polyphenol with antioxidant and anti-inflammatory properties, is beneficial in treating multiple metabolic diseases. Gnetin C, a resveratrol derivative obtained from Melinjo seed extract (MSE), shares similar health-promoting properties. We investigated the role of gnetin C in preventing NAFLD in a mouse model and compared it with resveratrol. Male C57BL/6J mice were fed a control diet (10% calories from fat), a high-fat choline-deficient (HFCD) diet (46% calories from fat) and HFCD diet supplemented with gnetin C (150 mg/kg BW·day−1) or resveratrol (150 mg/kg BW·day−1) for 12 weeks. Gnetin C supplementation reduced body and liver weight, and improved blood glucose levels and insulin sensitivity. Both gnetin C- and resveratrol reduced hepatic steatosis, with gnetin C also decreasing liver lipid content. Gnetin C and resveratrol ameliorated HFCD diet-induced hepatic fibrosis. The mRNA expression results, and western blot analyses showed that gnetin C and, to some extent, resveratrol downregulated fibrosis markers in the TGF-β1 signaling pathway, indicating a possible safeguarding mechanism against NAFLD. These results suggest that gnetin C supplementation may protect against lipid deposition and hepatic fibrosis.

PtxRh1−x (x = 0.76, 0.54, and 0.27) solid solutions were prepared by arc-melting. For these solid solutions, the lattice constant was linearly related to the Pt content. The surface compositions of the solid solutions determined by X-ray photoelectron spectroscopy were quite similar to their bulk compositions estimated by energy dispersive X-ray spectroscopy. The CO-stripping voltammograms demonstrated that the onset potential of CO oxidation current density (Eonset) shifted negatively as the surface Pt content decreased, suggesting an increased CO-poisoning resistance. Linear sweep voltammograms of the solid solution electrodes in an Ar-saturated (1 M ethanol + 0.1 M HClO4) solution exhibited that the onset potentials of ethanol oxidation reaction (EOR) current for all solid solution electrodes were lower than of a Pt electrode, and Pt0.54Rh0.46 gave the highest specific activity (SA) of 312 μA·cm−2, which was about 1.8 and 2.5 times higher than the SAs of Pt and Rh, respectively. In situ infrared reflection-absorption spectra exhibited that the Pt0.54Rh0.46 electrode had the bands due to the linear-bonded CO on Pt and bridge-bonded CO on Rh as EOR intermediates around 0.2 V vs. the reversible hydrogen electrode, but the band due to the linear-bonded CO on Rh was not observed even at 0.6 V, suggesting that the existence of the adjacent Pt-Rh sites and the preferential formation of bridge-bonded CO on Rh accelerated the C-C bond cleavage and improved the EOR activity.

A study on separation control mechanisms of tandemly arranged wing with linear leading edge (LLE) and leading edge protuberance (LEP) in low Reynolds number was conducted. In this study, to investigate the separation control mechanism, we carried out the visualization experiment using smoke-wire method, the streamwise and spanwise velocity measurements above the upper surface of the backward wing by using hotwire anemometer, and the numerical simulation. From the results of flow visualization experiment, it was found that the high lift coefficient obtained by tandemly arranged wing with LLE and singly and tandemly arranged wing with LEP were caused by reducing the flow separation region. From the results of velocity measurements and numerical simulation, it was found that in the case of wing with LLE, the turbulence generated by forward wing, which had mainly streamwise component with peak frequency of 230Hz and broadband frequency over than 30Hz, controled the flow separation. Whereas in the case of wing with LEP, regardless of the wing arrangement, separation control was brought by the separation bubble that caused by the longitudinal vortices generated by the LEP. It was also found that the turbulence from forward wing affected the position of the valley part where the separation bubble and the strong negative pressure were formed.

Abstract Type 2 diabetes mellitus patients are immunocompromised, particularly under poorly controlled conditions, and thereby they could develop rare inflammatory diseases, such as spontaneous discitis, pyogenic psoas abscess, spinal epidural abscess and bacterial meningitis. Herein we report a pyogenic psoas abscess on the dorsal side, and bacterial meningitis and spinal epidural abscess on the ventral side, both of which were induced by spontaneous discitis in a patient with poorly controlled type 2 diabetes mellitus. This case was very rare and interesting, because we successfully treated various infections with antibiotics over a long period of time, complicated by hyperglycemic crises, although the patient suffered severe bone destruction and required rehabilitation for a long time.

Abstract Background Hospital volume is known to be associated with outcomes of patients requiring complicated medical care. However, the relationship between hospital volume and prognosis of hospitalized patients with heart failure (HF) remains not fully understood. We aimed to clarify the impact of hospital volume on clinical outcomes of hospitalized HF patients using a nationwide inpatient database. Methods and results We studied 447,818 hospitalized HF patients who were admitted from January 2010 and discharged until March 2018 included in the Japanese Diagnosis Procedure Combination database. According to the number of patients, patients were categorized into three groups; those treated in low-, medium-, and high-volume centers. The median age was 81 years and 238,192 patients (53%) were men. Patients who had New York Heart Association class IV symptom and requiring inotropic agent within two days were more common in high volume centers than in low volume centers. Respiratory support, hemodialysis, and intra-aortic balloon pumping were more frequently performed in high volume centers. As a result, length of hospital stay was shorter, and in-hospital mortality was lower in high volume centers. Lower in-hospital mortality was associated with higher hospital volume. Multivariable logistic regression analysis fitted with generalized estimating equation indicated that medium-volume group (Odds ratio 0.91, p = 0.035) and high-volume group (Odds ratio 0.86, p = 0.004) had lower in-hospital mortality compared to the low-volume group. Subgroup analysis showed that this association between hospital volume and in-hospital mortality among overall population was seen in all subgroups according to age, presence of chronic renal failure, and New York Heart Association class. Conclusion Hospital volume was independently associated with ameliorated clinical outcomes of hospitalized patients with HF.

Ubiquitin is a member of the heat shock protein family and is rapidly induced by various types of stimuli, including ischemic and mechanical stress. However, its significance in determining wound vitality of neck compression skin in forensic pathology remains unclear. We immunohistochemically examined the expression of ubiquitin in the neck skin samples to understand its forensic applicability in determining wound vitality. Skin samples were obtained from 53 cases of neck compression (hanging, 42 cases; strangulation, 11 cases) during forensic autopsies. Intact skin from the same individual was used as the control. Ubiquitin expression was detected in 73.9% of keratinocytes in intact skin samples, but only in 21.2% of keratinocytes in the compression regions, with statistical differences between the control and compression groups. This depletion in the case of neck compression may be caused by the impaired conversion of conjugated to free ubiquitin and failure of de novo ubiquitin synthesis. From a forensic pathological perspective, immunohistochemical examination of ubiquitin expression in the skin of the neck can be regarded as a valuable marker for diagnosing traces of antemortem compression.

We previously identified Alcaligenes spp. as a commensal bacterium that resides in lymphoid tissues, including Peyer’s patches. We found that Alcaligenes-derived lipopolysaccharide acted as a weak agonist of Toll-like receptor four due to the unique structure of lipid A, which lies in the core of lipopolysaccharide. This feature allowed the use of chemically synthesized Alcaligenes lipid A as a safe synthetic vaccine adjuvant that induces Th17 polarization to enhance systemic IgG and respiratory IgA responses to T-cell–dependent antigens (e.g., ovalbumin and pneumococcal surface protein A) without excessive inflammation. Here, we examined the adjuvant activity of Alcaligenes lipid A on a Haemophilus influenzae B conjugate vaccine that contains capsular polysaccharide polyribosyl ribitol phosphate (PRP), a T-cell–independent antigen, conjugated with the T-cell–dependent tetanus toxoid (TT) antigen (i.e., PRP-TT). When mice were subcutaneously immunized with PRP alone or mixed with TT, Alcaligenes lipid A did not affect PRP-specific IgG production. In contrast, PRP-specific serum IgG responses were enhanced when mice were immunized with PRP-TT, but these responses were impaired in similarly immunized T-cell—deficient nude mice. Furthermore, TT-specific—but not PRP-specific—T-cell activation occurred in mice immunized with PRP-TT together with Alcaligenes lipid A. In addition, coculture with Alcaligenes lipid A promoted significant proliferation of and enhanced antibody production by B cells. Together, these findings suggest that Alcaligenes lipid A exerts an adjuvant activity on thymus-independent Hib polysaccharide antigen in the presence of a T-cell–dependent conjugate carrier antigen.

Bovine colostrum contains growth factors, cytokines, hormones, and enzymes, which have important roles in stimulating gastrointestinal development of neonatal calves. In the present study, we measured the concentration of glucagon-like peptide 2 (GLP-2), one of the gut-derived peptides secreted from intestinal L-cells, in colostrum and transition milk of Japanese black cattle. All colostrum samples were collected within 24 h after calving (d 0) and transition milk was collected at 24, 48 and 72 h relative to the time at colostrum sampling (d 1, d 2 and d 3, respectively). Concentrations of GLP-2 in colostrum were 5.53 ± 1.07 ng/mL on average (range = 0.94–9.60 ng/mL) and decreased from d 0 to 3 (P < 0.01). Furthermore, concentrations of GLP-2 in colostrum and transition milk were quadratically decreased with the elapsed time from parturition until colostrum sampling (R2 = 0.48, P < 0.01). Our results show for the first time that GLP-2 is present in bovine colostrum and transition milk and that concentrations decreased with elapsed time from parturition.

Acaryochloris is a marine cyanobacterium that synthesizes chlorophyll d, a unique chlorophyll that absorbs far-red lights. Acaryochloris is also characterized by the loss of phycobiliprotein (PBP), a photosynthetic antenna specific to cyanobacteria; however, only the type-strain A. marina MBIC11017 retains PBP, suggesting that PBP-related genes were reacquired through horizontal gene transfer (HGT). Acaryochloris is thought to have adapted to various environments through its huge genome size and the genes acquired through HGT; however, genomic information on Acaryochloris is limited. In this study, we report the complete genome sequence of A. marina MBIC10699, which was isolated from the same area of ocean as A. marina MBIC11017 as a PBP-less strain. The genome of A.marina MBIC10699 consists of a 6.4 Mb chromosome and four large plasmids totaling about 7.6 Mb, and the phylogenic analysis shows that A.marina MBIC10699 is the most closely related to A. marina MBIC11017 among the Acaryochloris species reported so far. Compared with A. marina MBIC11017, the chromosomal genes are highly conserved between them, while the genes encoded in the plasmids are significantly diverse. Comparing these genomes provides clues as to how the genes for PBPs were reacquired and what changes occurred in the genes for photosystems during evolution.

Protochlorophyllide (Pchlide) reduction in the late stage of chlorophyll a (Chl) biosynthesis is catalyzed by two enzymes: light-dependent Pchlide oxidoreductase (LPOR) and dark-operative Pchlide oxidoreductase (DPOR). The differential operation of LPOR and DPOR enables a stable supply of Chl in response to changes in light conditions and environmental oxygen levels. When a DPOR-deficient mutant (YFC2) of the cyanobacterium Leptolyngbya boryana is grown heterotrophically in the dark, Pchlide accumulates in the cells and is secreted into the culture medium. In this study, we demonstrated the extracellular vesicle-mediated secretion of Pchlide. Pchlide fractions were isolated from the culture medium using sucrose density gradient centrifugation. Mass spectrometry analysis revealed that the Pchlide fractions contained porin isoforms, TolC, and FG-GAP repeat-containing protein, which are localized in the outer membrane. Transmission electron microscopy revealed extracellular vesicle-like structures in the vicinity of YFC2 cells and the Pchlide fractions. These findings suggested that the Pchlide secretion is mediated by extracellular vesicles in dark-grown YFC2 cells.

A marine cyanobacterium Acaryochloris marina synthesizes chlorophyll (Chl) d as a major Chl. Chl d has a formyl group at its C3 position instead of a vinyl group in Chl a. This modification allows Chl d to absorb far-red light addition to visible light, yet the enzyme catalyzing the formation of the C3-formyl group has not been identified. In this study, we focused on light and oxygen, the most important external factors in Chl biosynthesis, to investigate their effects on Chl d biosynthesis in A. marina. The amount of Chl d in heterotrophic dark-grown cells was comparable to that in light-grown cells, indicating that A. marina has a light-independent pathway for Chl d biosynthesis. Under anoxic conditions, the amount of Chl d increased with growth in light conditions; however, no growth was observed in dark conditions, indicating that A. marina synthesizes Chl d normally even under such “micro-oxic” conditions caused by endogenous oxygen production. Although the oxygen requirement for Chl d biosynthesis could not be confirmed, interestingly, accumulation of pheophorbide d was observed in anoxic and dark conditions, suggesting that Chl d degradation is induced by anaerobicity and darkness.

If the octet truss core, which is a space filling structure of half regular octahedrons and regular tetrahedrons, has excellent sound insulation characteristics, the possibility of using the octet truss core is sufficiently widened. From this fact, we have studied to obtain sound insulation characteristics of the flat plate and the plate with single core using acoustic tube by the finite element method (FEM) with high accuracy. The calculation of sound insulation performance by FEM was limited to the qualitative study so far. For example, the correction is required due to the difference from the theoretical value, and the magnitudes of the correction values differ depending on the test pieces. In this study, we considered the incident wave and compared the sound insulation calculation result by the FEM calculation using the non-reflective boundary at the rear end of the sound receiving room with the theoretical calculation. As a result, both calculation values were almost the same. Therefore, it can be said that when the magnitudes of the incident wave and the reflective wave are almost equal, a quantitative study is possible. Taking advantage of this fact, in this paper the sound insulation characteristics of the plate with single core are compared with that of flat plate, and the effects of the sound insulation characteristics by the aspect ratio of the core are examined.

Background The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain. Methods and Results We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged

We experienced a case of meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) with symptomatic intratumoral hemorrhage in a 67-year-old Japanese woman. Her chief complaints were sudden onset of motor aphasia and right hemiparesis. Brain computed tomography showed the hemorrhagic mass adjacent to the superior sagittal sinus. The mass was resected and pathological examination of the specimen revealed a tumor that is rich in vessels and accompanied with intratumoral hemorrhage. Short spindle tumor cells were proliferating with myxoid stroma. Tumor cells appeared to be arranged around the vessels and sometimes attached to the vessel wall directly. Although hyalinization of the vessel wall was observed, neither patternless pattern nor staghorn vessels were seen. Immunohistochemistry revealed that the tumor cells were positive for both CD34 and nuclear STAT6. Moreover, gene analyses revealed unique NAB2-STAT6 fusion. Immunohistochemical findings and fusion-gene analyses enabled us to make the definite diagnosis of meningeal myxoid SFT/HPC. The present case showed the three unique features such as clinically symptomatic intratumoral hemorrhage at the onset, rare variant of myxoid SFT/HPC, and unique NAB2-STAT6 fusion. Keyword: Meninx, Myxoid solitary fibrous tumor/hemangiopericytoma, Cerebral hemorrhage, NAB2-STAT6 fusion

Abstract Dark-operative protochlorophyllide oxidoreductase (DPOR) is a key enzyme to produce chlorophyll in the dark. Among photosynthetic eukaryotes, all three subunits chlL, chlN, and chlB are encoded by plastid genomes. In some gymnosperms, two codons of chlB mRNA are changed by RNA editing to codons encoding evolutionarily conserved amino acid residues. However, the effect of these substitutions on DPOR activity remains unknown. We first prepared cyanobacterial ChlB variants with amino acid substitution(s) to mimic ChlB translated from pre-edited mRNA. Their activities were evaluated by measuring chlorophyll content of dark-grown transformants of a chlB-lacking mutant of the cyanobacterium Leptolyngbya boryana that was complemented with pre-edited mimic chlB variants. The chlorophyll content of the transformant cells expressing the ChlB variant from the fully pre-edited mRNA was only one-fourth of the control cells. Co-purification experiments of ChlB with Strep-ChlN suggested that a stable complex with ChlN is greatly impaired in the substituted ChlB variant. We then confirmed that RNA editing efficiency was markedly greater in the dark than in the light in cotyledons of the black pine Pinus thunbergii. These results indicate that RNA editing on chlB mRNA is important to maintain appropriate DPOR activity in black pine chloroplasts.

Since nitrogenase is extremely vulnerable to oxygen, aerobic or micro-aerobic nitrogen-fixing organisms need to create anaerobic microenvironments in the cells for diazotrophic growth, which would be one of the major barriers to express active nitrogenase in plants in efforts to create nitrogen-fixing plants. Numerous cyanobacteria are able to fix nitrogen with nitrogenase by coping with the endogenous oxygen production by photosynthesis. Understanding of the molecular mechanisms enabling to the coexistence of nitrogen fixation and photosynthesis in nonheterocystous cyanobacteria could offer valuable insights for the transfer of nitrogen fixation capacity into plants. We previously identified the cnfR gene encoding the master regulator for the nitrogen fixation (nif) gene cluster in the genome of a nonheterocystous cyanobacterium Leptolyngbya boryana, in addition to initial characterization of the nif gene cluster. Here we isolated nine mutants, in which the nif and nif-related genes were individually knocked out in L. boryana to investigate the individual functions of (1) accessory proteins (NifW, NifX/NafY, and NifZ) in the biosynthesis of nitrogenase metallocenters, (2) serine acetyltransferase (NifP) in cysteine supply for iron-sulfur clusters, (3) pyruvate formate lyase in anaerobic metabolism, and (4) NifT and HesAB proteins. ΔnifW, ΔnifXnafY, and ΔnifZ exhibited the most severe phenotype characterized by low nitrogenase activity (

A shallow draft cylindrical barge type floater with footing close to the water surface was experimentally evaluated in waves to investigate non-linear motion characteristics. The floater was designed to be used as an option for FOWT—floating offshore wind turbines. The non-linear mechanism can be promoted due to the viscous force that acts on the footing edges and the footing interaction with the free surface. In general, the observed non-linear viscous damping is modeled as a force proportional to the square of the relative velocity between the floater and the water. Therefore, the viscous damping levels is expected to increase, and the response in waves, to decrease. However, an increase in motion responses was observed for a broad range of wave periods. An attempt was made to clarify the hydrodynamic mechanism by comparing wave tank experiments, numerical calculations by CFD—computational fluid dynamics codes, and linear potential theory codes. Regular wave tests for three different wave height conditions were carried out, including free decay tests in still waters. For CFD simulations, the OpenFOAM code was selected. For potential theory simulations, the WAMIT code was chosen. As a result of the research, three points could be highlighted and discussed: first, the hydrodynamic phenomenon that contributed to the non-linear motion of the floater was identified; second, the increase and coupling of the motions response of heave and pitch motions; and finally, the phenomenon that the footing held water mass and lifted it to the water surface. The CFD calculations were able to get good qualitative results compared with the experiments and confirmed the use of CFD as a useful tool to capture the non-linear hydrodynamic phenomenon. The linear potential theory was not able to capture the phenomenon discussed herein.

Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer’s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against Streptococcus pneumoniae infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific CD4+ Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.

Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized Alcaligenes lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus Alcaligenes lipid A relative to those that were immunized with OVA alone. In addition, Alcaligenes lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with Alcaligenes lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, Alcaligenes lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that Alcaligenes lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination.

Effects of new types of reinforcement, alien type and alien combined with external type (double reinforcement), were examined in comparison with a conventional external one. One hundred and twenty children, 6th grade boys and girls, worked on learning discrimination tasks. Under alien reinforcement, upon correct responses of the child the experimenter received reinforcers from him- (or her-) self thus reinforcing the child responses. Under each condition, alien, external or double, children learned the tasks and their learning efficacy increased. Personality characteristics of children, in terms of extraversion and emotionality, differentiated effects of three reinforcement conditions on learning behavior and efficacy. The effect of alien reinforcement was influenced by the personality factors most, and that of double reinforcement least. In addition, personality factors influenced differently between alien and external conditions. Learning occurred differently under three different conditions of reinforcement, depending on the personality type of learners. Underlying mechanisms of alien reinforcement were different from, and its functions were independent of, those of external reinforcement. None of the effects of alien reinforcement on learning and motivation were contaminated by the intellectual faculties of learners. [ABSTRACT FROM AUTHOR]

Polarized Raman spectra of a β-FeSi2(100)//Si(001) epitaxial film grown by molecular beam epitaxy were measured to identify the Raman mode of the observed Raman active lines. Twelve of the observed 18 Raman lines showed a clear dependence of the Raman intensity on the crystal rotation angle. By factor group analysis using the orthorhombic symmetry D2h18 of β-FeSi2, five Raman lines (193, 200, 249, 401, 494 cm-1) and seven lines (175, 277, 284, 298, 327, 410, 442 cm-1) were completely assigned to the Ag and B3g modes, respectively. The depolarization ratio of Raman scattering intensities was obtained from polarized Raman spectra measured in two polarization configurations. The values of the depolarization ratio also support the assignment of the Ag and B3g modes in β-FeSi2.

Phototrophic microorganisms adjust photosystem synthesis in response to changes in light intensity and wavelength. A variety of different photoreceptors regulate this process. Purple photosynthetic bacteria synthesize a novel photoreceptor AerR that uses cobalamin (B12) as a blue-light absorbing chromophore to control photosystem synthesis. AerR directly interacts with the redox responding transcription factor CrtJ, affecting CrtJ’s interaction with photosystem promoters. In this study, we show that AerR is translated as two isoforms that differ by 41 amino acids at the amino terminus. The ratio of these isoforms was affected by light and cell growth phase with the long variant predominating during photosynthetic exponential growth and the short variant predominating in dark conditions and/or stationary phase. Pigmentation and transcriptomic analyses show that the short AerR variant represses, while long variant activates, photosynthesis genes. The long form of AerR also activates many genes involved in cellular metabolism and motility.

In an actively driven rotary tool, the principal cutting force and tool tangential force are measured based on the power consumption of the main spindle and the tool spindle, respectively. In rotary turning, the principal cutting force, extent of chip flow angle change, and chip thickness are typically independent of tool rotation direction either clockwise or counterclockwise. The high-efficiency reciprocating turning can be regulated such that the tool tangential force acts in direct opposition to that of the feed force. In addition, cutting scenarios where the continuous chip is broken by the chip breaker are investigated using high-speed cameras.

Objective(s): This study was designed to assess defect detectability in positron emission tomography (PET) imaging of abdominal lesions. Methods: A National Electrical Manufactures Association International Electrotechnical Commission phantom was used. The simulated abdominal lesion was scanned for 10 min using dynamic list-mode acquisition method. Images, acquired with scan duration of 1-10 min, were reconstructed using VUE point HD and a 4.7 mm full-width at half-maximum (FWHM) Gaussian filter. Iteration-subset combinations of 2-16 and 2-32 were used. Visual and physical analyses were performed using the acquired images. To sequentially evaluate defect detectability in clinical settings, we examined two middle-aged male subjects. One had a liver cyst (approximately 10 mm in diameter) and the other suffered from pancreatic cancer with an inner defect region (approximately 9 mm in diameter). Results: In the phantom study, at least 6 and 3 min acquisition durations were required to visualize 10 and 13 mm defect spheres, respectively. On the other hand, spheres with diameters ≥17 mm could be detected even if the acquisition duration was only 1 min. The visual scores were significantly correlated with background (BG) variability. In clinical settings, the liver cyst could be slightly visualized with an acquisition duration of 6 min, although image quality was suboptimal. For pancreatic cancer, the acquisition duration of 3 min was insufficient to clearly describe the defect region. Conclusion: The improvement of BG variability is the most important factor for enhancing lesion detection. Our clinical scan duration (3 min/bed) may not be suitable for the detection of small lesions or accurate tumor delineation since an acquisition duration of at least 6 min is required to visualize 10 mm lesions, regardless of reconstruction parameters. Improvements in defect detectability are important for radiation treatment planning and accurate PET-based diagnosis.