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Various individual resources for successful aging have improved during the last decades. However, a limited number of studies have examined historical changes in how older individuals view their own aging. This study examined cohort differences in aging self-perceptions among Japanese older adults. Using nationally representative data obtained 9 years apart in 1987 and 1996, we compared two cohorts born in the 1920s versus the 1930s. To control for relevant correlates, we identified casematched controls based on age, sex, and education (age range = 60-65 years; n = 499 per cohort). Results indicated that the later-born cohort held more positive self-perceptions of aging than the earlier-born cohort, even after adjusting for relevant correlates. The correlates with self-perceptions of aging did not differ across cohorts. Our findings suggest that selfperceptions of aging have improved over the historical time. We discuss the potential role of societal forces on personal views on aging. [ABSTRACT FROM AUTHOR]

Although there is growing clinical interest in problematic pornography use (PPU), few studies focus on differences between men and women. The purpose of this study was to examine gender differences in the effects of pornographic media and personality traits on the PPU. Participants were a community sample of 502 men and 509 women, who completed an online questionnaire. Pornographic video, low self-control, and Fun Seeking affected the PPU for men and women. For women, Reward Responsiveness and Drive are also related to the severity of PPU. Gender differences should be considered when considering treatment and prevention of problematic pornography use. [ABSTRACT FROM AUTHOR]

OBJECTIVE To assess visualization of the intracranial arteries and internal carotid artery (ICA) on 3-D time-of-flight (TOF) magnetic resonance angiography (MRA) images obtained at 1.5 T and to investigate factors that affect the image quality of those arteries in dogs. ANIMALS 39 dogs with idiopathic epilepsy. PROCEDURES Each dog underwent 3-D TOF MRA, and 5 pairs of intracranial arteries, the basilar artery, and both ICAs were evaluated. Each artery was assigned an image-quality score on a scale of 0 to 3, where 0 = poor and 3 = excellent. Multivariable regression analysis was used to assess whether age, body weight (BW), serum total cholesterol concentration, intracranial volume (ICV), and mean arterial pressure were significantly associated with the image quality of each vessel. RESULTS In all dogs, the image-quality score was 2 or 3 for the proximal middle cerebral arteries, basilar artery, and caudal aspect of the caudal communicating arteries. In some dogs, the rostral cerebellar arteries, rostral aspect of the caudal communicating arteries, and middle and rostral aspects of the ICA were poorly visualized. For various arteries, image quality was negatively associated with age and positively associated with BW and ICV. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 3-D TOF MRA images obtained at 1.5 T did not consistently and clearly delineate the ICA and narrow or peripheral intracranial arteries of dogs; therefore, careful attention is required when such images are assessed. Patient age, BW, and ICV can also affect the image quality of some intracranial arteries on 3-D TOF MRA images. [ABSTRACT FROM AUTHOR]

Background: Cognitions associated with Compulsive Sexual Behavior Disorder (CSBD) need to be clarified. ICD-11 diagnostic criteria state that distress related to moral disapproval of sexual urges is not sufficient to meet diagnostic requirements. However, disapproval of pornography and sexual behavior may influence CSB. Previous studies have focused on disapproval related to religiosity. In Japan, religious beliefs are low. This study aims to clarify the relationship between moral disapproval and cognition about sexual behaviors and CSB in Japan. Method: An online survey was conducted with a sample representing Japan (N = 1,094, 49%women, Mage = 39.9, SD = 11.6). Participants were completed CSBD-19, Problematic Pornography Use Scale (PPUS), Negative Sexual Attitude Inventory (NSAI), and Questions about cognition about sexual behaviors. Results: Regression analyses were conducted. Sexual avoidance of the NSAI subscale and one item (I should only have sexual relations with people I really love) was negatively associated with CSBD-19 and PPUS (ps < .001). Sexual anxiety as subfactor of NSAI and one item (Sexual desires must be released) was positively associated with the CSBD-19 and PPUS (ps < .001). One item (It is morally bad to use pornography) was not significantly associated. For men and women, respectively, the results showed different. Conclusions: These results suggested that individuals with higher CSB scores may have an open mind about sexual behavior, be more sexually anxious, and believe that they must release their sexual desires. It was suggested that cognition should be considered in the treatment and assessment of CSB. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of ipragliflozin versus pioglitazone in patients with type 2 diabetes complicated by nonalcoholic fatty liver disease (NAFLD).Research Design and Methods: In this open-label, randomized, active-controlled trial, we randomly assigned 66 patients with type 2 diabetes and NAFLD to receive ipragliflozin 50 mg (n = 32) or pioglitazone 15-30 mg (n = 34) orally once daily. The primary outcome was a change from baseline in the liver-to-spleen attenuation ratio (L/S ratio) on computed tomography at week 24.Results: At week 24, the mean ± SD L/S ratio had increased by 0.22 (from 0.80 ± 0.24 to 1.00 ± 0.18) in the ipragliflozin group and 0.21 (from 0.78 ± 0.26 to 0.98 ± 0.16) in the pioglitazone group (P = 0.90). Serum aspartate and alanine aminotransferase levels, HbA1c, and fasting plasma glucose were similarly reduced in the two treatment groups. Nevertheless, body weight and visceral fat area showed significant reductions only in the ipragliflozin group compared with the pioglitazone group (P < 0.0001 and P = 0.0013, respectively). There were no serious adverse events in either group.Conclusions: Compared with pioglitazone, ipragliflozin exerts equally beneficial effects on NAFLD and glycemic control during the treatment of patients with type 2 diabetes complicated by NAFLD. Furthermore, ipragliflozin significantly reduced body weight and abdominal fat area. [ABSTRACT FROM AUTHOR]

Yellowing symptoms sometimes cause yield losses in green soybean cultivation. The objective of this study was to estimate the yield loss factors in a glasshouse. The parameters evaluated were plant-parasitic nematodes (Heterodera glycines, Pratylenchus penetrans, Meloidogyne spp.) and soil chemical properties. While the density of H. glycines did not show a negative correlation with yield in the February planting date, it showed a strongly negative correlation in the March planting date. Multiple regression analysis showed that yield was significantly correlated with P. penetrans and nitrate in the February planting, and with H. glycines and K in the March planting. The present study revealed that yield loss was caused by P. penetrans and nitrate in seasons with unsuitable temperatures for H. glycines hatch, and by H. glycines and alleviated by K in seasons with optimum temperatures for H. glycines hatching. [ABSTRACT FROM AUTHOR]

Mutations in RNA-binding proteins, including fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43, encoded by TARDBP), are associated with sporadic and familial amyotrophic lateral sclerosis. A major question is whether neuronal loss is caused by toxic gain-of-function cytoplasmic aggregates or loss of nuclear RNA-binding protein function. We generated a transgenic mouse overexpressing exogenous FUS without a nuclear localization signal (ΔNLS-FUS), which developed progressive spastic motor deficits and neuronal loss in the motor cortex. The ΔNLS-FUS protein was restricted to the cytoplasm and formed ubiquitin/p62-positive aggregates. Endogenous FUS expression, nuclear localization, and splicing activity were not altered, indicating that mislocated FUS is sufficient for proteinopathy. Crossing ΔNLS-FUS with wild-type human TDP-43 transgenic mice exacerbated pathological and behavioural phenotypes, suggesting that both proteins are involved in a common cascade. RNA-sequence analysis revealed specific transcriptome alterations, including genes regulating dynein-associated molecules and endoplasmic reticulum stress. ΔNLS-FUS mice are promising tools for understanding amyotrophic lateral sclerosis pathogenesis and testing new therapeutic approaches. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare conventional MRI and nonenhanced 3-D time-of-flight (TOF) magnetic resonance angiography (MRA) findings between dogs with meningioma and dogs with intracranial histiocytic sarcoma (IHS). DESIGN: Retrospective case series. ANIMALS: 14 dogs with meningioma and 5 dogs with IHS. PROCEDURES: Medical records of dogs with meningioma or IHS that were examined at a tertiary veterinary hospital from 2010 through 2014 and underwent 3-D TOF MRA in conjunction with conventional MRI were reviewed. Findings for conventional MRI and 3-D TOF MRA were compared between the 2 groups of dogs to evaluate whether there were any characteristics that could be used to differentiate meningioma from IHS. RESULTS: Tumor type was significantly associated with signal intensity on conventional T2- weighted and fluid-attenuated inversion recovery MRI images; most meningiomas were hyperintense.and most IHSs were isointense or hypointense on those images. Tumor type was not associated with signal uniformity, tumor location, tumor origin, or the presence of edema, midline shift, or brain herniation. On MRA, blood vessels adjacent to the tumor were identified and characterized for 9 of 14 dogs with meningioma and all 5 dogs with IHS.Vessels adjacent to meningiomas were displaced in 8 of 9 dogs, whereas vessels adjacent to IHSs were not displaced. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated nonenhanced 3-DTOF MRA findings provided additional information that can be assessed in conjunction with conventional MRI findings to help differentiate meningiomas from IHSs in dogs. [ABSTRACT FROM AUTHOR]

Background: There were only few case reports in which CTC was performed in patients with colostomy. Case Presentation: A 68-year-old man was admitted with right abdominal pain and bloody stool that had been present for 2 weeks prior to admission. His medical history included abdominoperineal rectal resection with permanent sigmoid stoma (Miles operation). Colonoscopy showed a sub-occlusive tumor in the transverse colon but provided no information about the proximal colon. Thus, computed tomographic colonography (CTC) was planned to assist our examination of the proximal colon under sigmoid colostomy. CTC revealed the apple core sign in the hepatic flexure, without any evident tumor in the proximal colon. Therefore, we performed transverse colectomy and lymph node dissection, preserving a part of the ascending colon and Bauhin valve. Conclusion: CTC examination can be an effective means of preoperatively evaluating the proximal colon in patients with occlusive tumor. Further, CTC examination was technically feasible through a sigmoid stoma. [ABSTRACT FROM AUTHOR]

Although numerous studies have shown that each neuropsychological test is effective for diagnosing mild cognitive impairment (MCI) or Alzheimer's disease (AD), studies comparing diagnostic accuracies of various neuropsychological tests are relatively rare and practical cutoff values are not available. The present study aimed to investigate the validity of neuropsychological tests and develop cutoff values for each in differentiating healthy control (HC), MCI and AD groups. A total of 84 HC, 187 with MCI and 195 with AD were evaluated by the selected seven neuropsychological tests using receiver operating characteristic (ROC) curve analysis. Logical Memory (LM) delayed recall (cutoff, 7) and Rey Auditory Verbal Learning Test (RAVLT) delayed recall (cutoff, 6) were effective for differentiating HC from MCI. To distinguish MCI and AD, Rey Osterrieth Complex Figure Test (ROCFT) 3 mindelayed recall (cutoff, 6) and LM immediate recall (cutoff, 4) were excellent. Delayed recall of verbal materials, as indexed by LM and RAVLT was sensitive for discriminating MCI from HC. Handling visual memory traces, as indexed by ROCFT and immediate verbal information by LM were sensitive for differentiating MCI and AD. [ABSTRACT FROM AUTHOR]

Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4+ T cell responses, the involvement of mTOR in CD8+ T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8+ T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A-/- CD8+ T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8+ T cell responses were significantly impaired in SEMA4A-/- mice. Furthermore, SEMA4A-/- CD8+ T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8+ T cells. IFN-γ production and mTORC1 activity in SEMA4A-/- CD8+ T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8+ T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8+ T cells, but also reveal a novel link between a semaphorin and mTOR signaling. [ABSTRACT FROM AUTHOR]

The soybean cyst nematode (SCN), Heterodera glycines, is a widespread pest in most soybean-producing areas, causing serious damage to soybean crops and resulting in economic losses. We have previously reported that bean sprout residue might function as an environmentally-friendly control agent against SCN. In order to understand the role of water extracted from bean sprout residue as a possible factor in lowering the number of SCN, either water extract of bean sprout residue (WE) or water (W) was applied to pots containing soil infested with SCN, and komatsuna plants, a leafy vegetable, were grown in these pots. After 2 months, the number of SCN, estimated with real-time PCR, was 80% lower in WE than in W and the biomass of komatsuna plants was 100% higher in WE than in W, suggesting that WE has not only an SCN eradication effect but also a fertilisation effect. In field experiments, WE or W was applied ten times during the experimental period from July 2010 to June 2011. The number of SCN decreased by 82% in WE and by 36% in W; however, the marked decrease was observed only between July and September and between April and June. Green soybean plants were grown in the field where WE or W had been applied and the yield was markedly higher in WE (750 g m-2) than in W (200 g m-2). The hatching stimulation of SCN eggs by WE was tested at four different temperatures (10, 20, 25, 30°C) and was observed only at 25°C. These results show that water extract of bean sprout residue decreases the density of SCN and thereby damage to green soybeans, and that the suppressive effect depends on soil temperature. [ABSTRACT FROM AUTHOR]

Background: Circumsporozoite protein (CSP) is essential for sporozoite formation and sporozoite invasion into human hepatocyte. Previously, a recombinant P. vivax CSP based on chimeric repeats (rPvCSP-c) representing two major alleles VK210 and VK247 within central region has been designed. Naturally acquired humoral immune responses study show that antigenicity of rPvCSP-c was much higher than that of native strain. However, the serologic reactivity of rPvCSP-c was still unclear in detail. Methods: In present study, recognition of rPvCSP-c in vivax malaria typed VK210 and VK247 alleles was assessed. VK210 typed and VK247 typed sera from adult residents reacted specifically with rPvCSP-c using protein array and immunoblot assay. Additionally, anti-rPvCSP-c serum recognized the fixed VK210 and VK247 sporozoites by immunofluorescence assay. Furthermore, statistic analysis was performed for correlational detection. Results: The rPvCSP-c reacted with both VK210 typed and VK247 typed P. vivax infected patient sera and antirPvCSP- c immune serum also reacted with VK210 and VK247 sporozoite parasites of P. vivax specifically. There was a positive correlation between increased antibody level, age of patients and also associated with pvcsp repeat number, although the level of responses did vary considerably in their reactivity to the rPvCSP-c from negative to very high level within each age group. Conclusions: These data confirmed the serologic reactivity of the novel rPvCSP-c in exposed both VK210 and VK247 populations. These results strongly suggested that this recombinant CSP was biologically active and potently immunogenic across major strains and raised the prospect that this protein could be used as serologic marker. [ABSTRACT FROM AUTHOR]

The spindle checkpoint delays the onset of anaphase until all of the chromosomes properly achieve bipolar attachment to the spindle. It has been shown that unattached kinetochores are the site that emits a signal for activation of the checkpoint. Although the components of the checkpoint such as Bub1, Mad1 and Mad2 selectively accumulate at unattached kinetochores, the answer to how they recognize unattached kinetochores has remained elusive. Mpsl pombe homolog (Mph1) kinase has been shown to function upstream of most of the components of the checkpoint and thus it is thought to recognize unattached kinetochores by itself and recruit other components. In this study we have expressed a fusion protein of Mph1 and Ndc8O (a kinetochore protein of the outer plate) and shown that the fusion protein arrests cell cycle progression in a spindle-checkpoint-dependent manner in fission yeast. When expression of Mad2 is turned off, the cells grow normally with Mph1 constitutively localized at centromeres/ kinetochores. Under this condition, Bub1 can be found with Mph1 throughout the cell cycle, indicating that localization of Mph1 at centromeres/kinetochores is sufficient to recruit Bub1. In contrast, Mad1 is found to transiently localize at kinetochores, which are presumably unattached to the spindle, but soon it dissociates from kinetochores. We propose that Mph1 is a sufficient marker for recruitment of Bub1. Mad1. in contrast, requires an additional condition/component for stable association with kinetochores. [ABSTRACT FROM AUTHOR]

Reactions of excess H 2SiEt 2and H 2SiHex 2with [Pt(PCy 3) 2] at room temperature form mononuclear cis-hydrido(silyl)platinum complexes, cis-[Pt(H)(SiHR 2)(PCy 3) 2] ( 1: R = Et, 2: R = Hex), which are converted into diplatinum complexes with bridging dialkylsilyl ligands, [{Pt(PCy 3)} 2(µ-η 2-HSiR 2) 2] ( 3: R = Et, 4: R = Hex), upon heating at 80 °C. Complex 3reacts with excess H 2SiPhMe and H 2SiPh 2to afford dinuclear complexes [{Pt(PCy 3)} 2(µ-η 2-HSiPhR) 2] ( 5: R = Me, 6: R = Ph) via exchange of the bridging silyl ligands. An equimolar reaction of H 2SiPh 2with 3yields a mixture of diplatinum complexes [{Pt(PCy 3)} 2(µ-η 2-HSiEt 2)(µ-η 2-HSiPh 2)] ( 7) and [{Pt(PCy 3)} 2(µ-η 2:η 2-H 2SiEt 2)(µ-SiPh 2)] ( 8). Use of D 2SiPh 2in the reaction results in distribution of deuterium in the diethylsilyl and diphenylsilyl ligands of 7, the diethylsilane ligand of 8, and the diphenylsilyl ligand of 6. Complex 6undergoes exchange of the phosphine ligands with dmpe (1,2-bis(dimethylphosphino)ethane) and with dppe (1,2-bis(diphenylphosphino)ethane) to afford diplatinum complexes with bridging silylene ligands and the chelating diphosphine ligands, [{Pt(dmpe)} 2(µ-SiPh 2) 2] ( 9) and [{Pt(dppe)} 2(µ-SiPh 2) 2] ( 10). Short contact between the two Si atoms (2.718(2) and 2.646(2) Å) suggests a weak Si···Si interaction. [ABSTRACT FROM AUTHOR]

Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome. Seipin protein is reportedly a transmembrane protein localized in the endoplasmic reticulum (ER). N88S and S90L mutations of this protein disrupt its glycosylation, resulting in its aggregation, but the mechanism of neurodegeneration remains unclear. To clarify the molecular pathogenesis of seipin‐related motor neuron diseases, we expressed wild‐type and mutant seipin proteins in neuronal and nonneuronal cells.Coexpression of human seipin and ubiquitin showed that seipin is polyubiquitinated and its ubiquitination is enhanced by mutation. Treatment of cells with a proteasome inhibitor increased the amounts of mutant seipin in the cells, suggesting that they are degraded through the ER‐associated degradation pathway. Immunoprecipitation studies showed that mutant seipin stably binds to the ER chaperone calnexin, indicating accumulation of unfolded mutant seipin in the ER. Furthermore, expression of mutant seipin increased the level of ER stress–mediated molecules and induced apoptosis in cultured cells.These findings demonstrate that seipin/BSCL2‐related motor neuron diseases are novel conformational diseases, and we suspect that they are tightly associated with ER stress–mediated cell death. Ann Neurol 2007;61:237–250 [ABSTRACT FROM AUTHOR]

A diplatinum complex with bridging diethylsilyl ligands, Pt(PCy3)2(-2-HSiEt2)2(1), reacted with an excess of H2SiPh2to yield Pt(PCy3)2(-2-HSiPh2)2(2) via exchange of the bridging SiHEt2ligands with SiHPh2groups. An equimolar reaction of H2SiPh2with 1afforded a mixture of the dinuclear complexes Pt(PCy3)2(-2-HSiEt2)(-2-HSiPh2) (3) and Pt(PCy3)2(-2:2-H2SiEt2)(-SiPh2) (4). X-ray crystallographic structure determination of 4showed bridging coordination of the H2SiEt2ligand to two Pt centers via two Pt−H−Si three-center two-electron bonds (Pt−Si 2.375(8) and 2.39(1) Å). [ABSTRACT FROM AUTHOR]

The converse piezoelectric responses of (111) and (001)-epitaxial tetragonal Pb(Zr0.35Ti0.65)O3 [PZT] films were compared to investigate the orientation dependence of the substrate clamping effect. Synchrotron X-ray diffraction (XRD) and piezoelectric force microscopy revealed that the as-grown (111)-PZT film has a polydomain structure with normal twin boundaries that are changed by the poling process to inclined boundaries, as predicted by Romanov et al. [Phys. Status Solidi A 172, 225 (1999)]. Time-resolved synchrotron XRD under bias voltage showed the negligible impact of substrate clamping on the piezoelectric response in the (111)-PZT film, unlike the case for (001)-PZT film. The origin of the negligible clamping effect in the (111)-PZT film is discussed from the viewpoint of the elastic properties and the compensation of lattice distortion between neighboring domains. [ABSTRACT FROM AUTHOR]

We previously reported that incorporation of bean sprout residue into soil stimulated hatching of the soybean cyst nematode (SCN), Heterodera glycines. The objective of this study was to evaluate the effects of short-term growth of mung bean (Vigna radiata), the raw material of bean sprout, and its incorporation into the soil on the density of SCN in soil. When mung bean was grown in pots for 2 and 4 weeks in a SCN-infested andosol, incorporated into the soil and further incubated for 2 weeks, the SCN density decreased markedly. Mung bean was also grown in pots under different moisture conditions. The SCN density decreased in the soils with 48-68 g water, but not with 39 g water (100 g dry soil)-1 in which mung bean grew the poorest. The present study suggests that short-term growth of mung bean may be useful to decrease the density of SCN in soil. [ABSTRACT FROM AUTHOR]

Effective adjuvant therapies have not been established for hepatocellular carcinoma (HCC). The study aimed to determine prognostic influence of statin against HCC recurrence after initial resection. From 2003 to 2013, 734 patients underwent initial HCC resection. Exposure to statins was defined as the use at the recommended daily dosage for > 90 days after surgery. Outcomes were compared between patients who did and did not receive statins. Of 734 patients, 31 (4.2%) received statins for dyslipidemia (statin group) and 703 (95.8%) did not (non-statin group). The proportions of hepatitis B (6.5% vs. 22.8%, P = 0.032), C (19.4% vs. 45.0%, P = 0.005), and a fibrosis score of F3-4 (16.1 % vs. 39.8%, P = 0.008) were significantly lower in the statin than non-statin group. The recurrence-free survival rate was significantly higher in the statin than non-statin group (P < 0.001), without significant difference of the overall survival rate (P = 0.142). A multivariable Cox proportional hazards model revealed that the use of statins (hazard ratio, 0.34; P = 0.005) was associated with a significantly lower risk of HCC recurrence. After one-to-two propensity score matching, the RFS rate was also significantly higher in the statin group (n = 31) than in the non-statin group (n = 62) (P = 0.008). In conclusion: The statins use reduced the risk of HCC recurrence after initial resection. Statins may have protective influences on HCC recurrence in patients who undergo initial liver resection. [ABSTRACT FROM AUTHOR]

The Seipin/BSCL2 gene was originally identified as a loss-of-function gene for congenital generalized lipodystrophy type 2 (CGL2), a condition characterized by severe lipoatrophy, insulin resistance, hypertriglyceridaemia and mental retardation. Recently, gain-of-toxic-function mutations (namely, mutations N88S and S90L) in the seipin gene have been identified in autosomal dominant motor neuron diseases such as Silver syndrome/spastic paraplegia 17 (SPG17) (OMIM #270685) and distal hereditary motor neuropathy type V (dHMN-V) (OMIM #182960). Detailed phenotypic analyses have revealed that upper motor neurons, lower motor neurons and peripheral motor axons are variously affected in patients with these mutations. The clinical spectrum for these mutations is broad, encompassing Silver syndrome, some variants of Charcot-Marie-Tooth disease type 2, dHMNV and spastic paraplegia, even within a common pedigree. Therefore, we propose that seipin-related motor neuron diseases can be collectively referred to as ‘seipinopathies’. Expression of the seipin protein can be detected in motor neurons in the spinal cord and white matter in the frontal lobe. This is consistent with the distribution of seipinopathies in the upper and lower motor neurons. Recent studies have shown that seipin, an endoplasmic reticulum (ER)-resident membrane protein, is an N-glycosylated protein that is proteolytically cleaved into N- and C-terminal fragments and is polyubiquitinated. Interestingly, the N88S and S90L mutations are in the N-glycosylation motif, and these mutations enhance ubiquitination and degradation of seipin by the ubiquitin–proteasome system (UPS). Furthermore, both mutations appear to result in proteins that are improperly folded, which leads to accumulation of the mutant protein in the ER. We have shown that expression of mutant forms of seipin in cultured cells activates the unfolded protein response (UPR) pathway and induces ER stress-mediated cell death. These findings suggest that seipinopathies are novel conformational diseases and that neurodegeneration in these diseases is tightly associated with ER stress, which has recently been reported to be associated with other neurodegenerative diseases. Further study of the pathological mechanisms of the mutant forms of seipin may lead to important new insights into motor neuron diseases, including other spastic paraplegia diseases and amyotrophic lateral sclerosis. [ABSTRACT FROM AUTHOR]

Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX_096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R² = 0.11) or PvRALP1-Tr (R² = 0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites. [ABSTRACT FROM AUTHOR]

Background: Proteins secreted from the rhoptry in Plasmodium merozoites are associated with the formation of tight junctions and parasitophorous vacuoles during invasion of erythrocytes and are sorted within the rhoptry neck or bulb. Very little information has been obtained to date about Plasmodium vivax rhoptry-associated leucine (Leu) zipper-like protein 1 (PvRALP1; PVX_096245), a putative rhoptry protein. PvRALP1 contains a signal peptide, a glycine (Gly)/glutamate (Glu)-rich domain, and a Leu-rich domain, all of which are conserved in other Plasmodium species. Methods: Recombinant PvRALP1s were expressed as full-length protein without the signal peptide (PvRALP1-Ecto) and as truncated protein consisting of the Gly/Glu- and Leu-rich domains (PvRALP1-Tr) using the wheat germ cell-free expression system. The immunoreactivity to these two fragments of recombinant PvRALP1 protein in serum samples from P. vivax-infected patients and immunized mice, including analysis of immunoglobulin G (IgG) subclasses, was evaluated by enzyme-linked immunosorbent assay or protein microarray technology. The subcellular localization of PvRALP1 in blood stage parasites was also determined. Results: Recombinant PvRALP1-Ecto and PvRALP1-Tr proteins were successfully expressed, and in serum samples from P. vivax patients from the Republic of Korea, the observed immunoreactivities to these proteins had 58.9% and 55.4% sensitivity and 95.0% and 92.5% specificity, respectively. The response to PvRALP1 in humans was predominantly cytophilic antibodies (IgG1 and IgG3), but a balanced Th1/Th2 response was observed in mice. Unexpectedly, there was no significant inverse correlation between levels of parasitaemia and levels of antibody against either PvRALP1-Ecto (R2 = 0.11) or PvRALP1-Tr (R2 = 0.14) antigens. PvRALP1 was localized in the rhoptry neck of merozoites, and this was the first demonstration of the localization of this protein in P. vivax. Conclusions: This study analysed the antigenicity and immunogenicity of PvRALP1 and suggested that PvRALP1 may be immunogenic in humans during parasite infection and might play an important role during invasion of P. vivax parasites. [ABSTRACT FROM AUTHOR]

Objective--To investigate age-related and regional differences in estimated metabolite concentrations in the brain of healthy dogs by means of magnetic resonance spectroscopy (MRS). Animals--15 healthy Beagles. Procedures--Dogs were grouped according to age as young (n = 5; all dogs were 2 months old), adult (5; mean age, 4.5 years), or geriatric (5; all dogs were 12 years old). Imaging was performed by use of a 1.5-T MRI system withT1- andT2-weighted spin-echo and fluid-attenuated inversion recovery sequences. Signal intensity measurements for N-acetyl aspartate, creatine, choline, and lactate-alanine (the spectroscopic peaks associated with alanine and lactate could not be reliably differentiated) were determined with MRS, and areas under the spectroscopic peaks (representing concentration estimates) were calculated. Ratios of these metabolite values were compared among age groups and among brain regions with regression analysis. Results--The choline-to-creatine ratio was significantly higher in young dogs, compared with other age groups. The N-acetyl aspartate-to-choline ratio was significantly lower in young dogs and geriatric dogs than in adult dogs. When all age groups were considered, the choline-to-creatine ratio was significantly higher and N-acetyl aspartate-to-choline ratio was significantly lower in the frontal lobe than in all other regions.The N-acetyl aspartate-to-creatine ratio was significantly lower in the cerebellum than in other regions. Conclusions and Clinical Relevance--Metabolite ratios varied significantly among age groups and brain regions in healthy dogs. Future studies should evaluate absolute concentration differences in a larger number of dogs and assess clinical applications in dogs with neurologic diseases. [ABSTRACT FROM AUTHOR]

Background: In previous studies, the association between Compulsive Sexual Behavior Disorder (CSBD) and childhood sexual abuse (CSA) has been discussed (Slavin et al., 2020). However, the mechanism that CSA leads to CSBD has not been clarified in detail. Some studies have described that CSA related to self-objectification (e.g., Talmon & Ginzburg, 2016). Furthermore, it has been suggested that self-objectification increases sexual risk behaviors (e.g., Ingram et al., 2023). In short, self-objectification may mediate the association between CSBD and CSA. This study aimed to examine a model of the effects of CSA, self-objectification, and self-compassion on CSBD. Methods: 935 participants via online were included in the analysis (Korean: n = 329, Japan: n = 377, the UK: n = 229). The scales were the CSBD-19, Self-Compassion scale, Childhood Trauma Questionnaire, and Objectified Body Consciousness scale. Results: Moderated mediation model indicated that the mediation effect of self-objectification measured by body surveillance, and moderation effect of self-compassion were not significant. Additional exploratory analyzes showed that body shame significantly mediated between CSA and CSBD in three countries, and self-compassion mediated in only the UK and Korea. Conclusion: The result indicates that individuals with CSA experiences may develop CSBD through Body shame in three countries. Therefore, it is necessary to focus on body shame when reducing the risk of CSBD. Self-compassion intervention may be applicable to support CSBD with CSA in the UK and Korea. However, in Japan, it was shown that it is necessary to further examine the function of self-compassion. [ABSTRACT FROM AUTHOR]

Amino acid metabolism plays important roles in innate immune cells' including macrophages. Recently' we reported that a lysosomal adaptor protein' Lamtorl' which serves as the scaffold for amino acid-activated mechanistic target of rapamycin complex 1 (mTORCl)' is critical for the polarization of M2 macrophages. However' little is known about how Lamtorl affects the inflammatory responses that are triggered by the stimuli for TLRs. In this article' we show that Lamtorl controls innate immune responses by regulating the phosphorylation and nuclear translocation of transcription factor EB (TFEB)' which has been known as the master regulator for lysosome and autophagosome biogenesis. Furthermore' we show that nuclear translocation of TFEB occurs in alveolar macrophages of myeloid-specific Lamtorl conditional knockout mice and that these mice are hypersensitive to intratracheal administration of LPS and bleomycin. Our observation clarified that the amino acid-sensing pathway consisting of Lamtorl' mTORCl' and TFEB is involved in the regulation of innate immune responses. The Journal of Immunology' 20l8' 200: 3790-3800. [ABSTRACT FROM AUTHOR]

Mechanistic target of rapamycin complex (mTORC)1 integrates intracellular sufficiency of nutrients and regulates various cellular functions. Previous studies using mice with conditional knockout of mTORC1 component proteins (i.e., mTOR, Raptor, and Rheb) gave conflicting results on the roles of mTORC1 in CD4+ T cells. Lamtor1 is the protein that is required for amino acid sensing and activation of mTORC1; however, the roles of Lamtor1 in T cells have not been investigated. In this article, we show that Lamtor1- deficient CD4+ T cells exhibited marked reductions in proliferation, IL-2 production, mTORC1 activity, and expression of purineand lipid-synthesis genes. Polarization of Th17 cells, but not Th1 and Th2 cells, diminished following the loss of Lamtor1. Accordingly, CD4-Cre--driven Lamtor1-knockout mice exhibited reduced numbers of CD4+ and CD8+ T cells at rest, and they were completely resistant to experimental autoimmune encephalomyelitis. In contrast, genetic ablation of Lamtor1 in Foxp3+ T cells resulted in severe autoimmunity and premature death. Lamtor1-deficient regulatory T cells survived ex vivo as long as wild-type regulatory T cells; however, they exhibited a marked loss of suppressive function and expression of signature molecules, such as CTLA-4. These results indicate that Lamtor1 plays essential roles in CD4+ T cells. Our data suggest that Lamtor1 should be considered a novel therapeutic target in immune systems. [ABSTRACT FROM AUTHOR]

Background: Individual drug treatment may select resistant parasites in the human body, a process termed in vivo selection. Some single nucleotide polymorphisms in Plasmodium falciparum chloroquine-resistance transporter (pfcrt) and multidrug resistance gene 1 (pfmdr1) genes have been reportedly selected after artemether-lumefantrine treatment. However, there is a paucity of data regarding in vivo selection of P. falciparum Kelch propeller domain (pfkelch13) polymorphisms, responsible for artemisinin-resistance in Asia, and six putative background mutations for artemisinin resistance; D193Y in ferredoxin, T484I in multiple resistance protein 2, V127M in apicoplast ribosomal protein S10, I356T in pfcrt, V1157L in protein phosphatase and C1484F in phosphoinositide-binding protein. Methods: Artemether-lumefantrine efficacy study with a follow-up period of 28 days was conducted in northern Uganda in 2014. The above-mentioned genotypes were comparatively analysed before drug administration and on days; 3, 7, and 28 days after treatment. Results: In 61 individuals with successful follow-up, artemether-lumefantrine treatment regimen was very effective with PCR adjusted efficacy of 95.2%. Among 146 isolates obtained before treatment, wild-type alleles were observed in 98.6% of isolates in pfkelch13 and in all isolates in the six putative background genes except I356T in pfcrt, which had 2.4% of isolates as mixed infections. In vivo selection study revealed that all isolates detected in the follow-up period harboured wild type alleles in pfkelch13 and the six background genes. Conclusion: Mutations in pfkelch13 and the six background genes may not play an important role in the in vivo selection after artemether-lumefantrine treatment in Uganda. Different mechanisms might rather be associated with the existence of parasites after treatment. [ABSTRACT FROM AUTHOR]

Study Design: Prospective experimental study on humans. Purpose: To determine whether postural differences during a low-speed impact are observed in the sagittal and axial views, particularly in a relaxed state. Overview of Literature: Three-dimensional motion capture systems have been used to analyze posture and head-neck-torso kinematics in humans during a simulated low-speed impact, yet little research has focused on the axial view. Since a seatbelt asymmetrically stabilizes a driver's right shoulder and left lower waist into the seat, it potentially creates movement in the axial view. Methods: Three healthy adult men participated in the experimental series, which used a low-speed sled system. The acceleration pulse created a full sine shape with a maximum acceleration of 8.0 m/s² at 500 ms, during which the kinematics were evaluated in relaxed and tensed states. The three-dimensional motion capture system used eight markers to record and analyze body movement and head-neck-torso kinematics in the sagittal and axial views during the low-speed impact. Head and trunk rotation angles were also calculated. Results: Larger movements were observed in the relaxed than in the tensed state in the sagittal view. The cervical and thoracic spine flexed and extended, respectively, in the relaxed state. In the axial view, larger movements were also observed in the relaxed state than in the tensed state, and the left shoulder rotated. Conclusions: During simulated frontal impact, the rotation angle between the head and trunk was significantly larger in the relaxed state. Therefore, we recommend also observing movement in the axial view during impact tests. [ABSTRACT FROM AUTHOR]

The crucian carp Carassius carassius (Linnaeus, 1758) is a species with restricted and decreasing distribution in Europe. Six males and six females of the species from the Baltic Sea basin in Poland were examined to show sequentially CMA3/AgNO3 staining pattern, DAPI staining, and, for the first time in literature, molecular cytogenetic analysis using double-colour fluorescence in situ hybridisation (FISH) with 28S and 5S rDNA probes. The karyotype consisted of 20 m, 36 sm and 44 sta chromosomes, NF=156. The AgNO3 stained NORs were most frequently located terminally in the short arms of two sm and two sta elements, and CMA3-positive sites were also observed suggesting abundant GC-rich repetitive DNA in the regions. Other CMA3-positive sites in the short arms of six to ten sm and sta chromosomes were detected. The results based on 28S rDNA FISH confirmed the location of rDNA sites. DAPI-negative staining of NORs suggested the scarcity of AT-rich DNA in the regions. FISH with 5S rDNA probe revealed 8-14 loci (ten and 12 in respectively 49 and 29% of metaphases). They were located in two sm and eight to ten sta chromosomes and six of them were larger than others. Simultaneously, mapping of the two rDNA families on the chromosomes of C. carassius revealed that both 28S and 5S rDNA probes were located in different chromosomes. Molecular cytogenetic data of C. carassius presented here for the first time give an important insight into the structure of chromosomes of this polyploid and declining species and may be useful in its systematics. [ABSTRACT FROM AUTHOR]

Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α and estrogen-related receptor (ERR)α also significantly decreased, without changes in the expression of PPAR-α. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1α, or ERRα did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1α, and ERRα in PTECs. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the CNS and a leading cause of lasting neurologic disabilities in young adults. Although the precise mechanism remains incompletely understood, Ag presentation and subsequent myelin-reactive CD4+ T cell activation/differentiation are essential for the pathogenesis of MS. Although semaphorins were initially identified as axon guidance cues during neural development, several semaphorins are crucially involved in various phases of immune responses. Sema4A is one of the membrane-type class IV semaphorins, which we originally identified from the cDNA library of dendritic cell (DC). Sema4A plays critical roles in T cell activation and Thl differentiation during the course of experimental autoimmune encephalomyelitis, an animal model of MS; however, its pathological involvement in human MS has not been determined. In this study, we report that Sema4A is increased in the sera of patients with MS. The expression of Sema4A is increased on DCs in MS patients and shed from these cells in a metalloproteinase-dependent manner. DC-derived Sema4A is not only critical for Thl but also for Th17 cell differentiation, and MS patients with high Sema4A levels exhibit Th17 skewing. Furthermore, patients with high Sema4A levels have more severe disabilities and are unresponsive to IFN-β treatment. Taken together, our results suggest that Sema4A is involved in the pathogenesis of MS by promoting Th17 skewing. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra (SN). The familial form of PD, PARK2, is caused by mutations in the parkin gene. parkin-knockout mouse models show some abnormalities, but they do not fully recapitulate the pathophysiology of human PARK2. Results: Here, we generated induced pluripotent stem cells (iPSCs) from two PARK2 patients. PARK2 iPSC-derived neurons showed increased oxidative stress and enhanced activity of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. iPSC-derived neurons, but not fibroblasts or iPSCs, exhibited abnormal mitochondrial morphology and impaired mitochondrial homeostasis. Although PARK2 patients rarely exhibit Lewy body (LB) formation with an accumulation of α-synuclein, α-synuclein accumulation was observed in the postmortem brain of one of the donor patients. This accumulation was also seen in the iPSC-derived neurons in the same patient. Conclusions: Thus, pathogenic changes in the brain of a PARK2 patient were recapitulated using iPSC technology. These novel findings reveal mechanistic insights into the onset of PARK2 and identify novel targets for drug screening and potential modified therapies for PD. [ABSTRACT FROM AUTHOR]

Micropatterning techniques have become increasingly important in cellular biology. Cell patterning is achieved by various methods. Photolithography is one of the most popular methods, and several light sources (e.g., excimer lasers and mercury lamps) are used for that purpose. Vacuum ultraviolet (VUV) light that can be produced by an excimer lamp is advantageous for fabricating material patterns, since it can decompose organic materials directly and efficiently without photoresist or photosensitive materials. Despite the advantages, applications of VUV light to pattern biological materials are few. We have investigated cell patterning by using a template of a microstructured organosilane layer fabricated by VUV lithography. We first made a template of a microstructured organosilane layer by VUV lithography. Cell adhesive materials (poly(d-lysine) and polyethyleneimine) were chemically immobilized on the organosilane template, producing a cell adhesive material pattern. Primary rat cardiac and neuronal cells were successfully patterned by culturing them on the pattern substrate. Long-term culturing was attained for up to two weeks for cardiac cells and two months for cortex cells. We have discussed the reproducibility of cell patterning and made suggestions to improve it. [ABSTRACT FROM AUTHOR]