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The AKARI IRC all-sky survey provided more than twenty thousand thermal infrared observations of over five thousand asteroids. Diameters and albedos were obtained by fitting an empirically calibrated version of the standard thermal model to these data. After the publication of the flux catalogue in October 2016, our aim here is to present the AKARI IRC all-sky survey data and discuss valuable scientific applications in the field of small body physical properties studies. As an example, we update the catalogue of asteroid diameters and albedos based on AKARI using the near-Earth asteroid thermal model (NEATM). We fit the NEATM to derive asteroid diameters and, whenever possible, infrared beaming parameters. We fit groups of observations taken for the same object at different epochs of the survey separately, so we compute more than one diameter for approximately half of the catalogue. We obtained a total of 8097 diameters and albedos for 5170 asteroids, and we fitted the beaming parameter for almost two thousand of them. When it was not possible to fit the beaming parameter, we used a straight line fit to our sample’s beaming parameter-versus-phase angle plot to set the default value for each fit individually instead of using a single average value. Our diameters agree with stellar-occultation-based diameters well within the accuracy expected for the model. They also match the previous AKARI-based catalogue at phase angles lower than 50° , but we find a systematic deviation at higher phase angles, at which near-Earth and Mars-crossing asteroids were observed. The AKARI IRC All-sky survey is an essential source of information about asteroids, especially the large ones, since, it provides observations at different observation geometries, rotational coverages and aspect angles. For example, by comparing in more detail a few asteroids for which dimensions were derived from occultations, we discuss how the multiple observations per object may already provide three-dimensional information about elongated objects even based on an idealised model like the NEATM. Finally, we enumerate additional expected applications for more complex models, especially in combination with other catalogues. [ABSTRACT FROM AUTHOR]

The near-Earth asteroid 308635 (2005 YU55) is a potentially hazardous asteroid which was discovered in 2005 and passed Earth on Nov. 8, 2011 at 0.85 lunar distances. This was the closest known approach by an asteroid of several hundred metres in diameter since 1976 when an object of similar size passed at 0.5 lunar distances. We observed 2005 YU55 from the ground with a recently developed mid-IR camera (miniTAO/MAX38) in N and Q bands and with the Submillimeter Array (SMA) at 1.3 mm. In addition, we obtained space observations with Herschel/PACS at 70, 100, and 160 μm. Our thermal measurements cover a wide range of wavelengths from 8.9 μm to 1.3 mm and were taken after opposition at phase angles between -97° and -18°. We performed a radiometric analysis via a thermophysical model and combined our derived properties with results from radar, adaptive optics, lightcurve observations, speckle, and auxiliary thermal data. We find that 308635 (2005 YU55) has an almost spherical shape with an effective diameter of 300 to 312 m and a geometric albedo pV of 0.055 to 0.075. Its spin axis is oriented towards celestial directions (λecl, βecl) = (60° ± 30°, -60° ± 15°), which means it has a retrograde sense of rotation. The analysis of all available data combined revealed a discrepancy with the radar-derived size. Our radiometric analysis of the thermal data together with the problem to find a unique rotation period might be connected to a non-principal axis rotation. A low to intermediate level of surface roughness (rms mean slope in the range 0.1-0.3) is required to explain the available thermal measurements. We found a thermal inertia in the range 350-800 Jm-2 s-0.5 K-1, very similar to the rubble-pile asteroid 25 143 Itokawa and indicating a surface with a mixture of low conductivity fine regolith with larger rocks and boulders of high thermal inertia. [ABSTRACT FROM AUTHOR]

The AKARI (formerly known as ASTRO-F) mission is the first Japanese satellite dedicated for large area surveys in the infrared (Murakami et al. 2004). AKARI was launched successfully on February 22nd 2006 (JST) from JAXA's Uchinoura Space Centre, Japan. AKARI is now orbiting around the Earth in a Sun-synchronous polar orbit at the altitude of 700 km. The 68.5 cm aperture telescope and scientific instruments are cooled to 6K by liquid Helium and mechanical coolers. The expected liquid Helium holding time is now found to be at least one year after the successful aperture lid-opening on 2006 April 13th (JST). AKARI will perform the most advanced all-sky survey in 6 mid- to far-infrared wavebands since the preceding IRAS mission over 2 decades ago. Deep imaging and spectroscopic surveys near the ecliptic poles with pointed observations are also on-going in 13 wavelength bands at 2-160 μm (see Table 1, details are given in Matsuhara et al. 2006). AKARI is a perfect complement to Spitzer in respect of its wide sky area and wavelength coverage. Two unique aspects of the pointing deep surveys with AKARI are: many imaging bands including the wavelength gap of Spitzer (8-24 μm), and the slitless spectroscopic capability (Ohyama et al. in this proceeding). Not only the All-Sky Survey but also the deep pointing surveys near the ecliptic poles over ~15 deg2 in total will be particularly well suited to construct the luminosity functions of the infrared galaxies, to evaluate their clustering nature, and also to discover rare, exotic objects at various redshifts out to z ~ 3. AKARI is also capable of detecting and measuring the spectrum and the fluctuations of the cosmic infrared background. The in-orbit sensitivity and spatial resolution of the surveys are found to be sufficient to achive the scientific goals listed above. [ABSTRACT FROM PUBLISHER]

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Akazawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As a fundamental motor pattern, the ability to run at a range of constant speeds is a prerequisite for participating in competitive games and recreational sports. However, it remains unclear how unilateral transfemoral amputees modulate anterior and posterior ground reaction force impulses (GRFIs) in order to maintain constant running speeds. The purpose of this study was to investigate anterior and posterior GRFIs across a wide range of constant running speeds in unilateral transfemoral amputees wearing a running-specific prosthesis. Eleven runners with unilateral transfemoral amputation ran on an instrumented treadmill at 5 different speeds (30%, 40%, 50%, 60%, and 70% of the average velocity of their 100-m personal records). Anterior-posterior ground reaction forces (GRFs) were measured at 1000 Hz over 14 consecutive steps. Impulse, magnitude, and duration of anterior and posterior GRFs were compared between the affected and unaffected limbs at each speed. The net anterior-posterior GRFI, reflecting the changes in horizontal running velocity, was consistently positive (propulsion) in the affected limb and negative (braking) in the unaffected limb at all speeds. Regardless of running speed, unilateral transfemoral amputees maintain constant running speeds not over each step, but over 2 consecutive steps (i.e., one stride).

Sarcopenia is an age-related condition characterized by progressive loss of muscle mass and strength. Age-related decline in the secretion of growth hormone (GH), a condition called somatopause, is thought to play a role in sarcopenia. As pharmacological GH has adverse effects, we attempted to increase physiological GH. While the relationship between chewing and ghrelin levels has been studied, there are no reports on the relationship between chewing and GH. The aim of this study was to clarify the effects of chewing on the muscle anabolic hormones serum GH and plasma ghrelin. Thirteen healthy adults ingested a chewy nutrition bar containing 5.56 g of protein, 12.71 g of carbohydrate, and 0.09 g of fat on two different days, chewing before swallowing in one trial and swallowing without chewing in the other. Blood samples were taken before and after ingestion (0, 15, 30, and 60 min); GH, acylated ghrelin, glucose, insulin, amino acids, and lactate were measured. Two-way repeated ANOVA revealed a significant difference in the GH concentrations between the "Chew trial" and "Swallow trial" in females ( p = 0.0054). However, post-hoc analyses found no statistically significant difference at each time point. The area under the curve of the percentage increase in GH was significantly increased in the "Chew trial" compared with the "Swallow trial" in females (12,203 ± 15,402% min vs. 3735 ± 988% min, p = 0.0488). Chewing had no effect on glucose, insulin, amino acids, or lactate concentrations. Thus, we found that chewing a protein supplement rather than swallowing it without chewing elevates the blood GH concentration. These results serve as a rationale for larger research and longitudinal studies to confirm the impacts of chewing on GH secretion.

There is limited information available about the physiological content of glyceraldehyde, a precursor of toxic advanced glycation end products. The conventional derivatization method for aldoses using 1-phenyl-3-methyl-5-pyrazolone did not allow reproducible quantification of glyceraldehyde due to the instability of glyceraldehyde compared to other aldoses. We optimized the derivatization condition to achieve high and reproducible recovery of derivatives for liquid chromatography tandem mass spectrometry quantification. Based on the stability of glyceraldehyde during sample preparation and high recovery of spiked standard, the present method provides reproducible quantification of glyceraldehyde in the body. The glyceraldehyde contents in fasting conditions in the rodent liver (mice: 50.0 ± 3.9 nmol/g; rats: 35.5 ± 4.9 nmol/g) were higher than those in plasma (9.4 ± 1.7 and 7.2 ± 1.2 nmol/mL). The liver glyceraldehyde levels significantly increased after food consumption ( p < 0.05) but remained constant in the plasma. High fat diet feeding significantly increased plasma glyceraldehyde levels in mice ( p < 0.005). In healthy human volunteers, the plasma glyceraldehyde levels remained unchanged after the consumption of steamed rice. In patients with type 2 diabetes, the plasma glyceraldehyde level was positively correlated with the plasma glucose level ( r = 0.84; p < 0.0001).

Background: Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated., Methods: A total of 433 healthy subjects aged 40-69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed., Results: The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm 2 vs. 64.9 cm 2 , respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm 2 ) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis., Conclusions: Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40-69 years., (© 2021. The Author(s).)

Background: Understanding the potential risks of running-related injuries in unilateral transfemoral amputees contributes to the development and implementation of the injury prevention programme in running gait rehabilitation. We investigated the vertical ground reaction force loading in unilateral transfemoral amputees who used running-specific prostheses across a range of running speeds., Methods: Ten unilateral transfemoral amputees and ten non-amputees performed running trials on an instrumented treadmill at the incremental speeds of 30, 40, 50, and 60% of their maximum acquired speeds. Per-step and cumulative vertical instantaneous loading rates were calculated from the vertical ground reaction force in the affected, unaffected, and non-amputated control limbs., Findings: Both the per-step and cumulative vertical instantaneous loading rates of the unaffected limbs in runners with unilateral transfemoral amputation were significantly greater than the affected and non-amputated control limbs at all speeds., Interpretation: The results of the present study suggest that runners with unilateral transfemoral amputation may be exposed to a greater risk of running-related injuries in their unaffected limbs compared to the affected and non-amputated control limbs., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Spring-like leg behavior is a general feature of mammalian bouncing gaits, such as running and hopping. Although increases in step frequency at a given running speed are known to increase the stiffness of the leg spring (k leg ) in non-amputees, little is known about stiffness regulation in unilateral transfemoral amputees. In this study, we investigated stiffness regulation at different step frequencies at a given running speed in unilateral transfemoral amputees. We recruited nine unilateral transfemoral amputees wearing running-specific prostheses. They were asked to perform the action of running across a range of step frequencies (±20, ±15, ±10, ±5, and 0% of their preferred step frequency) at a given speed on an instrumented treadmill. The k leg values were calculated using ground reaction force data in both the affected and unaffected limbs. It was found that k leg increased with increasing step frequency for the unaffected limb, but not for the affected limb. Consequently, the unilateral transfemoral amputees attained the desired step frequency in the unaffected limb, but were unable to match the three highest step frequencies using their affected limbs. These results suggest that the stiffness regulation strategy during running differs between the affected and unaffected limbs.

Background: Anorectal malignant melanoma (AMM) is a rare disorder with an extremely poor prognosis. Although there is currently no consensus on the treatment methods for AMM, surgical procedures have been the most common treatment methods used until now. We recently encountered a case of AMM that we diagnosed using endoscopic submucosal dissection (ESD). To our knowledge, this is the first case of ESD for AMM, suggesting that ESD can potentially be a diagnostic and treatment method for AMM., Case Summary: A 77-year-old woman visited our hospital with a chief complaint of anal bleeding and a palpable rectal mass. Colonoscopy revealed a 20-mm protruded lesion in the lower rectum. After obtaining biopsy specimens from the lesion, although a malignant rectal tumor was suspected, a definitive diagnosis was not made. Endoscopic ultrasonography revealed tumor invasion into the submucosal layer but not the muscular layer. Therefore, we performed an excisional biopsy using ESD. Immunohistochemical examination of the ESD-resected specimen revealed tumor cells positive for Human Melanin Black-45, Melan-A, and S-100. Moreover, the tumor cells lacked melanin pigment; thus, a diagnosis of amelanotic AMM was made. Although the AMM had massively invaded the submucosal layer and both lymphatic and venous invasion were present, we closely monitored the patient without any additional therapy on the basis of her request. Six months after ESD, local recurrence was detected, and the patient consented to wide local excision., Conclusion: It is suggested that ESD is a potential diagnostic and treatment method for AMM., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest.

The upper fragment of spirolides A and B, which are marine phycotoxins that exhibit strong antagonistic activities on nicotinic acetylcholine receptors, was constructed. The functionalized cyclohexene in spirolides was stereoselectively synthesized from the bicyclic lactone, which could be readily accessed by the Lewis acid template-catalyzed asymmetric Diels-Alder reaction of the pentadienol and methyl acrylate., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, we present a case of gastric adenocarcinoma of fundic gland type (GA-FG) spreading to heterotopic gastric glands (HGG) in the submucosa. A 58-year-old man with epigastric pain was referred to our hospital and underwent an esophagogastroduodenoscopy. A Borrmann type II gastric cancer at the antrum and a 10 mm submucosal tumor-like lesion in the lesser curvature of the upper third of the stomach were detected. Histological examination of the biopsy specimens obtained from the submucosal tumor-like lesion suggested a GA-FG. Therefore, endoscopic submucosal dissection was performed as excisional biopsy, and histopathological examination of the resected specimen confirmed a GA-FG and HGG proximal to the GA-FG. Although the GA-FG invaded the submucosal layer slightly, the submucosal lesion of the GA-FG had a poor stromal reaction and was located just above the HGG in the submucosa. Therefore, we finally diagnosed the lesion as a GA-FG invading the submucosal layer by spreading to HGG., Competing Interests: Conflict-of-interest statement: We declare that there is no conflict of interest.

Accumulating evidence suggests that dysbiosis plays a role in the pathogenesis of intestinal diseases including inflammatory bowel disease (IBD) as well as extra-intestinal disorders. As a modulator of the intestinal microbiota, we isolated a mouse monoclonal IgA antibody (clone W27) with high affinities for multiple commensal bacteria, but not for beneficial bacteria such as Lactobacillus casei (L. casei). Via specific recognition of an epitope in serine hydroxymethyltransferase (SHMT), a bacterial metabolic enzyme, W27 IgA selectively inhibited the in vitro growth of bound bacteria, including Escherichia coli (E. coli), while having no effect on unbound beneficial bacteria such as L. casei. By modulating the gut microbiota in vivo, oral administration of W27 IgA effectively prevented development of colitis in several mouse models. Here we discuss how intestinal IgA modulates the gut microbiota through recognition of SHMT.

Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity., (Copyright © 2016 the American Physiological Society.)

Herein it is shown that a combination of direct analysis in real time (DART) with a corona discharge system consisting of only a needle electrode easily improves DART ionization efficiency. Positive and negative DC corona discharges led to a formation of abundant excited helium atoms as well as the reactant ions H3O(+)(H2O)n and O2˙(-) in the DART analyte ionization area. These phenomena resulted in an increase in the absolute intensities of (de)protonated analytes by a factor of 2-20 over conventional DART. The other analyte ions detected in this corona-DART system (i.e., molecular ions, fragment ions, oxygenated (de)protonated analytes, dehydrogenated deprotonated analytes, and negative ion adducts) were quite similar to those obtained from DART alone. This indicates a lack of side reactions due to the corona discharge. The change in the relative intensities of individual analyte-related ions due to the combination of a corona discharge system with DART suggests that there is no effect of the abundant excited helium in the analyte ionization area on the fragmentation processes or enhancement of oxidation due to hydroxyl radicals HO˙. Furthermore, it was found that the corona-DART combination can be applied to the highly sensitive analysis of n-alkanes, in which the alkanes are ionized as positive ions via hydride abstraction and oxidation, independent of the type of alkane or the mass spectrometer used.

Immunoglobulin A (IgA) is the main antibody isotype secreted into the intestinal lumen. IgA plays a critical role in the defence against pathogens and in the maintenance of intestinal homeostasis. However, how secreted IgA regulates gut microbiota is not completely understood. In this study, we isolated monoclonal IgA antibodies from the small intestine of healthy mouse. As a candidate for an efficient gut microbiota modulator, we selected a W27 IgA, which binds to multiple bacteria, but not beneficial ones such as Lactobacillus casei. W27 could suppress the cell growth of Escherichia coli but not L. casei in vitro, indicating an ability to improve the intestinal environment. Indeed W27 oral treatment could modulate gut microbiota composition and have a therapeutic effect on both lymphoproliferative disease and colitis models in mice. Thus, W27 IgA oral treatment is a potential remedy for inflammatory bowel disease, acting through restoration of host-microbial symbiosis.

NLRP3 inflammasomes recognize non-microbial danger signals and induce release of proinflammatory cytokine interleukin (IL)-1β, leading to sterile inflammation in cardiovascular disease. Because sterile inflammation is involved in doxorubicin (Dox)-induced cardiotoxicity, we investigated the role of NLRP3 inflammasomes in Dox-induced cardiotoxicity. Cardiac dysfunction and injury were induced by low-dose Dox (15 mg/kg) administration in NLRP3-deficient (NLRP3(-/-)) mice but not in wild-type (WT) and IL-1β(-/-) mice, indicating that NLRP3 deficiency enhanced the susceptibility to Dox-induced cardiotoxicity independent of IL-1β. Although the hearts of WT and NLRP3(-/-) mice showed no significant difference in inflammatory cell infiltration, macrophages were the predominant inflammatory cells in the hearts, and cardiac IL-10 production was decreased in Dox-treated NLRP3(-/-) mice. Bone marrow transplantation experiments showed that bone marrow-derived cells contributed to the exacerbation of Dox-induced cardiotoxicity in NLRP3(-/-) mice. In vitro experiments revealed that NLRP3 deficiency decreased IL-10 production in macrophages. Furthermore, adeno-associated virus-mediated IL-10 overexpression restored the exacerbation of cardiotoxicity in the NLRP3(-/-) mice. These results demonstrated that NLRP3 regulates macrophage IL-10 production and contributes to the pathophysiology of Dox-induced cardiotoxicity, which is independent of IL-1β. Our findings identify a novel role of NLRP3 and provided new insights into the mechanisms underlying Dox-induced cardiotoxicity.

Preeclampsia is a pregnancy-specific syndrome characterized by elevated blood pressure, proteinuria, and intrauterine growth restriction (IUGR). Although sterile inflammation appears to be involved, its pathogenesis remains unclear. Recent evidence indicates that sterile inflammation is mediated through the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes, composed of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1. Here we investigated the role of the NLRP3 inflammasomes in the pathogenesis of preeclampsia using Nlrp3(-/-) and Asc(-/-) (Nlrp3 and Asc deficient) pregnant mice. During pregnancy in mice, continuous infusion of high-dose angiotensin II (AngII) induced hypertension, proteinuria, and IUGR, whereas infusion of low-dose AngII caused hypertension alone. AngII-induced hypertension was prevented in Nlrp3(-/-) mice but not in Asc(-/-), indicating that NLRP3 contributes to gestational hypertension independently of ASC-mediated inflammasomes. Although NLRP3 deficiency had no effect on IUGR, it restored the IL-6 up-regulation in the placenta and kidney of AngII-infused mice. Furthermore, treatment with hydralazine prevented the development of gestational hypertension but not IUGR or IL-6 expression in the placenta and kidney. These findings demonstrate that NLRP3 contributes to the development of gestational hypertension independently of the inflammasomes and that IUGR and kidney injury can occur independent of blood pressure elevation during pregnancy.

Inflammation plays an important role in the development of obesity and metabolic disorders; however, it has not been fully understood how inflammation occurs and is regulated in their pathogenesis. Low-molecular mass protein-7 (LMP7) is a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides on major histocompatibility complex class I molecule. In this study, we investigated the role of LMP7 in the development of obesity and metabolic disorders using LMP7-deficient mice. LMP7 deficiency conveyed resistant to obesity, and improved glucose intolerance and insulin sensitivity in mice fed with high-fat diet (HFD). LMP7 deficiency decreased pancreatic lipase expression, increased fecal lipid contents, and inhibited the increase of plasma triglyceride levels upon oral oil administration or HFD feeding. Using bone marrow-transferred chimeric mice, we found that LMP7 in both bone marrow- and non-bone marrow-derived cells contributes to the development of HFD-induced obesity. LMP7 deficiency decreased inflammatory responses such as macrophage infiltration and chemokine expression while it increased serum adiponection levels. These findings demonstrate a novel role for LMP7 and provide new insights into the mechanisms underlying inflammation in the pathophysiology of obesity and metabolic disorders.

Highly protonated histone-derived peptides impede a sufficient mass spectrometry (MS)-based epigenetic analysis because their relatively low m/z, due to a high degree of proton addition to peptides, would make it difficult to analyze the resulting complex MS/MS spectra. To reduce the degree of protonations, we have developed a new interface, the Ionization Variable Unit (IVU), in which peptides are ionized under a vaporized organic solvent. It is demonstrated that the doubly charged histone tail H2B peptide, PEPAKSAPAPKKGSKKAVTKAQKK (m/z 1238.243, +2), which was not detectable before, can be detected by using the IVU interface and sequenced., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Rhabdomyolysis is one of the main causes of community-acquired acute kidney injury (AKI). Although inflammation is involved in the pathogenesis of rhabdomyolysis-induced AKI (RIAKI), little is known about the mechanism that triggers inflammation during RIAKI. Recent evidence has indicated that sterile inflammation triggered by tissue injury can be mediated through multiprotein complexes called the inflammasomes. Therefore, we investigated the role of NLRP3 inflammasomes in the pathogenesis of RIAKI using a glycerol-induced murine rhabdomyolysis model. Inflammasome-related molecules were upregulated in the kidney of RIAKI. Renal tubular injury and dysfunction preceded leukocyte infiltration into the kidney during the early phase of RIAKI, and they were markedly attenuated in mice deficient in NLRP3, ASC, caspase-1, and interleukin (IL)-1β compared with those in wild-type mice. No difference in leukocyte infiltration was observed between wild-type and NLRP3-deficient mice. Furthermore, NLRP3 deficiency strikingly suppressed the expression of renal injury markers and inflammatory cytokines and apoptosis of renal tubular cells. These results demonstrated that NLRP3 inflammasomes contribute to inflammation, apoptosis, and tissue injury during the early phase of RIAKI and provide new insights into the mechanism underlying the pathogenesis of RIAKI.

[Purpose] To verify the effects of sagittal plane alignment changes in running-specific transtibial prostheses on ground reaction forces (GRFs). [Subjects and Methods] Eight transtibial amputees who used running-specific prostheses during sprinting participated. The sprint movements were recorded using a Vicon-MX system and GRF measuring devices. The experiment levels were set as regularly recommended alignment (REG; the normal alignment for the subjects) and dorsiflexion or plantar flexion from the REG. [Results] The subjects were classified into fast (100-m personal best < 12.50 s) and slow (100-m personal best ≥ 12.50 s) groups. In both groups, there were no significant differences in the center of gravity speed; further, the difference in the stance time was significant in the slow group but not in the fast group. Significant differences were observed in the step length for the fast group, whereas the stance time and step rate significantly differed in the slow group. The GRF impulse showed significant differences in the vertical and braking directions in both groups. [Conclusion] The GRFs are affected by sagittal plane alignment changes in running-specific prostheses. Moreover, our results suggest that the change in GRFs along with the altered sagittal plane alignment influenced the step length and step rate.

Increasing evidence indicates that caspase recruitment domain (CARD)-mediated caspase-1 (CASP1) assembly is an essential process for its activation and subsequent interleukin (IL)-1β release, leading to the initiation of inflammation. Both CARD16 and CARD17 were previously reported as inhibitory homologs of CASP1; however, their molecular function remains unclear. Here, we identified that oligomerization activity allows CARD16 to function as a CASP1 activator. We investigated the molecular characteristics of CARD16 and CARD17 in transiently transfected HeLa cells. Although both CARD16 and CARD17 interacted with CASP1CARD, only CARD16 formed a homo-oligomer. Oligomerized CARD16 formed a filament-like structure with CASP1CARD and a speck with apoptosis-associated speck-like protein containing a CARD. A filament-like structure formed by CARD16 promoted CASP1 filament assembly and IL-1β release. In contrast, CARD17 did not form a homo-oligomer or filaments and inhibited CASP1-dependent IL-1β release. Mutated CARD16D27G, mimicking the CARD17 amino acid sequence, formed a homo-oligomer but failed to form a filament-like structure. Consequently, CARD16D27G weakly promoted CASP1 filament assembly and subsequent IL-1β release. These results suggest that oligomerized CARD16 promotes CARD-mediated molecular assembly and CASP1 activation.

Supplemental oxygen inhalation is frequently used to treat severe respiratory failure; however, prolonged exposure to hyperoxia causes hyperoxic acute lung injury (HALI), which induces acute respiratory distress syndrome and leads to high mortality rates. Recent investigations suggest the possible role of NLRP3 inflammasomes, which regulate IL-1β production and lead to inflammatory responses, in the pathophysiology of HALI; however, their role is not fully understood. In this study, we investigated the role of NLRP3 inflammasomes in mice with HALI. Under hyperoxic conditions, NLRP3(-/-) mice died at a higher rate compared with wild-type and IL-1β(-/-) mice, and there was no difference in IL-1β production in their lungs. Under hyperoxic conditions, the lungs of NLRP3(-/-) mice exhibited reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, as well as increased and decreased expression of MMP-9 and Bcl-2, respectively. NLRP3(-/-) mice exhibited diminished expression and activation of Stat3, which regulates MMP-9 and Bcl-2, in addition to increased numbers of apoptotic alveolar epithelial cells. In vitro experiments revealed that alveolar macrophages and neutrophils promoted Stat3 activation in alveolar epithelial cells. Furthermore, NLRP3 deficiency impaired the migration of neutrophils and chemokine expression by macrophages. These findings demonstrate that NLRP3 regulates Stat3 signaling in alveolar epithelial cells by affecting macrophage and neutrophil function independent of IL-1β production and contributes to the pathophysiology of HALI., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Objective: Abdominal aortic aneurysm (AAA) is considered a chronic inflammatory disease; however, the molecular basis underlying the sterile inflammatory response involved in the process of AAA remains unclear. We previously showed that the inflammasome, which regulates the caspase-1-dependent interleukin-1β production, mediates the sterile cardiovascular inflammatory responses. Therefore, we hypothesized that the inflammasome is a key mediator of initial inflammation in AAA formation., Approach and Results: Apoptosis-associated speck-like protein containing a caspase recruitment domain is highly expressed in adventitial macrophages in human and murine AAA tissues. Using an established mouse model of AAA induced by continuous infusion of angiotensin II in Apoe(-/-) mice, NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in Apoe(-/-) mice were shown to decrease the incidence, maximal diameter, and severity of AAA along with adventitial fibrosis and inflammatory responses significantly, such as inflammatory cell infiltration and cytokine expression in the vessel wall. NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency in Apoe(-/-) mice also reduced elastic lamina degradation and metalloproteinase activation in the early phase of AAA formation. Furthermore, angiotensin II stimulated generation of mitochondria-derived reactive oxygen species in the adventitial macrophages, and this mitochondria-derived reactive oxygen species generation was inhibited by NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, and caspase-1 deficiency. In vitro experiments revealed that angiotensin II stimulated the NLRP3 inflammasome activation and subsequent interleukin-1β release in macrophages, and this activation was mediated through an angiotensin type I receptor/mitochondria-derived reactive oxygen species-dependent pathway., Conclusions: Our results demonstrate the importance of the NLRP3 inflammasome in the initial inflammatory responses in AAA formation, indicating its potential as a novel therapeutic target for preventing AAA progression., (© 2014 American Heart Association, Inc.)

Despite the increasing commercial use of nanoparticles, little is known about their effects on placental inflammation and pregnancy complications. In this study, nanosilica (NS) particles upregulated the inflammasome component nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) and induced placental inflammation and reactive oxygen species (ROS) generation, resulting in pregnancy complications. Furthermore, NS-induced pregnancy complications were markedly improved in Nlrp3(-/-) mice but not in component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-deficient (Asc(-/-)) mice, indicating the independence of NLRP3 inflammasomes. Pregnancy complications in Nlrp3(-/-) and Asc(-/-) mice phenotypes were dependent on the balance between interleukin (IL)-1α and IL-10. NS-induced pregnancy complications were completely prevented by either inhibition of ROS generation or forced expression of IL-10. Our findings provide important information about NS-induced placental inflammation and pregnancy complications and the novel pathophysiological roles of NLRP3 and ASC in pregnancy.

Background: Type I interferons (IFNs), including IFN-alpha (IFNA) and IFN-beta (IFNB), have anti-inflammatory properties and are used to treat patients with autoimmune and inflammatory disorders. However, little is known of the role of IFN-tau (IFNT), a type I IFN produced by ruminant animals for inflammation. Because IFNB has recently been shown to inhibit nucleotide-binding oligomerization domain-like receptor, pyrin domain-containing 3 (NLRP3) inflammasome activation and subsequent secretion of the potent inflammatory cytokine interleukin (IL)-1β, we examined the effects of ruminant IFNT on NLRP3 inflammasome-mediated IL-1β secretion in human THP-1 macrophages., Methods and Results: IFNT dose-dependently inhibited IL-1β secretion induced by nano-silica, a well-known activators of NLRP3 inflammasomes, in human macrophages primed with lipopolysaccharide (LPS, TLR4 agonist) and Pam3CSK4 (TLR1/2 agonist). IFNT also suppressed phagocytosis of nano-silica and reactive oxygen species (ROS) generation. Western blot analysis showed that IFNT inhibited both pro-IL-1β and mature IL-1β. In addition, real-time RT-PCR analysis showed that IFNT suppressed IL-1β mRNA expression induced by LPS and Pam3CSK4. Although nano-silica particles did not induce IL-10 secretion, IFNT induced IL-10 secretion in a dose-dependent manner. Furthermore, IFNT-suppressed IL-1β secretion was restored by anti-IL-10 neutralizing antibody., Conclusions: Ruminant IFNT inhibits NLRP3 inflammasome-driven IL-1β secretion in human macrophages via multiple pathways, including the uptake of nano-silica particles, generation of ROS, and IL-10-mediated inhibition of pro-IL-1β induction. It may be a therapeutic alternative to IFNA and IFNB.

Smoking is a risk factor for lung diseases, including chronic obstructive pulmonary disease and lung cancer. However, the molecular mechanisms mediating the progression of these diseases remain unclear. Therefore, we sought to identify signaling pathways activated by tobacco-smoke exposure, by analyzing nuclear phosphoprotein expression using phosphoproteomic analysis of lung tissue from mice exposed to tobacco smoke. Sixteen mice were exposed to tobacco smoke for 1 or 7 days, and the expression of phosphorylated peptides was analyzed by mass spectrometry. A total of 253 phosphoproteins were identified, including FACT complex subunit SPT16 in the 1-day exposure group, keratin type 1 cytoskeletal 18 (K18), and adipocyte fatty acid-binding protein, in the 7-day exposure group, and peroxiredoxin-1 (OSF3) and spectrin β chain brain 1 (SPTBN1), in both groups. Semi-quantitative analysis of the identified phosphoproteins revealed that 33 proteins were significantly differentially expressed between the control and exposed groups. The identified phosphoproteins were classified according to their biological functions. We found that the identified proteins were related to inflammation, regeneration, repair, proliferation, differentiation, morphogenesis, and response to stress and nicotine. In conclusion, we identified proteins, including OSF3 and SPTBN1, as candidate tobacco smoke-exposure markers; our results provide insights into the mechanisms of tobacco smoke-induced diseases.

The positive and negative ionization characteristics of 20 different α-amino acids were investigated using Direct Analysis in Real Time (DART) mass spectrometry. Almost all of the amino acids M were ionized to generate the (de)protonated analytes [M ± H](±)via proton transfer reactions with the typical background ions H3O(+)(H2O)n and O2˙(-) and resonant electron capture by M. The application of DART to amino acids also resulted in molecular ion formation, fragmentation, oxidations involving oxygen attachment and hydrogen loss, and formation of adducts [M + R](-) with negative background ions R(-) (O2˙(-), HCO2(-), NO2(-) and COO(-)(COOH)), depending on the physicochemical and/or structural properties of individual amino acids. The relationship between each amino acid and the ionization reactions observed suggested that fragmentation can be attributed to pyrolysis during analyte desorption as well as excess energy obtained via (de)protonation. Oxidation and [M + R](-) adduct formation, in contrast, most likely originate from reactions with active oxygen such as hydroxyl radicals HO˙, indicating that the typical background neutral species involved in analyte ionization in DART mass spectrometry contain HO˙.

Inflammation plays a key role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury. However, the mechanism by which hepatic I/R induces inflammatory responses remains unclear. Recent evidence indicates that a sterile inflammatory response triggered by I/R is mediated through a multiple-protein complex called the inflammasome. Therefore, we investigated the role of the inflammasome in hepatic I/R injury and found that hepatic I/R stimuli upregulated the inflammasome-component molecule, nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), but not apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). NLRP3(-/-) mice, but not ASC(-/-) and caspase-1(-/-) mice, had significantly less liver injury after hepatic I/R. NLRP3(-/-) mice showed reduced inflammatory responses, reactive oxygen species production, and apoptosis in I/R liver. Notably, infiltration of neutrophils, but not macrophages, was markedly inhibited in the I/R liver of NLRP3(-/-) mice. Bone marrow transplantation experiments showed that NLRP3 not only in bone marrow-derived cells, but also in non-bone marrow-derived cells contributed to liver injury after I/R. In vitro experiments revealed that keratinocyte-derived chemokine-induced activation of heterotrimeric G proteins was markedly diminished. Furthermore, NLRP3(-/-) neutrophils decreased keratinocyte-derived chemokine-induced concentrations of intracellular calcium elevation, Rac activation, and actin assembly formation, thereby resulting in impaired migration activity. Taken together, NLRP3 regulates chemokine-mediated functions and recruitment of neutrophils, and thereby contributes to hepatic I/R injury independently of inflammasomes. These findings identify a novel role of NLRP3 in the pathophysiology of hepatic I/R injury.