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Lipophosphoglycans (LPGs) are found on the surface of Leishmania, a protozoan parasite, and are immunologically important. Herein, disaccharide 1‐phosphate repeating units of LPGs were successfully synthesized on a solid support with high anomeric purity using a disaccharide α‐1‐phosphoramidite building block. To enhance solubility in the reaction solvent, hydroxy‐protecting groups in the form of para‐t‐butylbenzoyl were introduced to the building block. The saccharide chain was elongated via stable glycosyl boranophosphate linkages, followed by the conversion of inter‐sugar linkages to phosphodiester counterparts using an oxaziridine derivative. The addition of a silylating reagent post‐reaction with the oxaziridine derivative efficiently facilitated the conversion of boranophosohodiesters to phosphodiesters. This method enabled the α‐selective synthesis of up to 15 repeating units, marking the longest homogeneous repeating units of LPGs synthesized chemically. Given the chain length equivalence to native LPGs, the method developed herein holds promise for advancing anti‐Leishmanial pharmaceuticals and vaccines. [ABSTRACT FROM AUTHOR]

Since assessing aerobic capacity is key to enhancing swimming performance, a simple and widely applicable technology should be developed. Therefore, we aimed to noninvasively visualize real‐time changes in sweat lactate (sLA) levels during swimming and investigate the relationship between lactate thresholds in sweat (sLT) and blood (bLT). This prospective study included 24 university swimmers (age: 20.7 s ± 1.8 years, 58% male) who underwent exercise tests at incremental speeds with or without breaks in a swimming flume to measure heart rate (HR), bLT, and sLT based on sLA levels using a waterproof wearable lactate sensor attached to the dorsal upper arm on two different days. The correlation coefficient and Bland–Altman methods were used to verify the similarities of the sLT with bLT and personal performance. In all tests, dynamic changes in sLA levels were continuously measured and projected onto the wearable device without delay, artifacts, or contamination. Following an initial minimal current response, with increasing speed the sLA levels increased substantially, coinciding with a continuous rise in HR. The speed at sLT strongly correlated with that at bLT (p < 0.01 and r = 0.824). The Bland–Altman plot showed a strong agreement (mean difference: 0.08 ± 0.1 m/s). This prospective study achieved real‐time sLA monitoring during swimming, even with vigorous movement. The sLT closely approximated bLT; both were subsequently validated for their relevance to performance. Highlights: A new technique using a wearable device can measure sweat lactate (sLA) levels during swimming without artifacts or contamination.Lactate threshold assessed using sLA dynamics is consistent with that calculated from blood samples.The current novel measurement method is expected to promote a personalized training regimen and simultaneous multi‐person measurements. [ABSTRACT FROM AUTHOR]

α‐Synuclein (αS) is a key molecule in the pathomechanism of Parkinson's disease. Most studies on αS to date have focused on its function in the neuronal cytosol, but its action in the nucleus has also been postulated. Indeed, several lines of evidence indicate that overexpressed αS leads to epigenomic alterations. To clarify the functional role of αS in the nucleus and its pathological significance, HEK293 cells constitutively expressing αS were used to screen for nuclear proteins that interact with αS by nanoscale liquid chromatography/tandem mass spectrometry. Interactome analysis of the 229 identified nuclear proteins revealed that αS interacts with the BRG1‐associated factor (BAF) complex, a family of multi‐subunit chromatin remodelers important for neurodevelopment, and protein arginine methyltransferase 5 (PRMT5). Subsequent transcriptomic analysis also suggested a functional link between αS and the BAF complex. Based on these results, we analyzed the effect of αS overexpression on the BAF complex in neuronally differentiated SH‐SY5Y cells and found that induction of αS disturbed the BAF maturation process, leading to a global increase in symmetric demethylation of histone H4 on arginine 3 (H4R3me2s) via enhanced BAF–PRMT5 interaction. Chromatin immunoprecipitation sequencing confirmed accumulated H4R3me2s methylation near the transcription start site of the neuronal cell adhesion molecule (NRCAM) gene, which has roles during neuronal differentiation. Transcriptional analyses confirmed the negative regulation of NRCAM by αS and PRMT5, which was reconfirmed by multiple datasets in the Gene Expression Omnibus (GEO) database. Taken together, these findings suggest that the enhanced binding of αS to the BAF complex and PRMT5 may cooperatively affect the neuronal differentiation process. [ABSTRACT FROM AUTHOR]

Recent developments in sequencing and bioinformatics have advanced our understanding of adenosine‐to‐inosine (A‐to‐I) RNA editing. Surprisingly, recent analyses have revealed the capability of adenosine deaminase acting on RNA (ADAR) to edit DNA:RNA hybrid strands. However, edited inosines in DNA remain largely unexplored. A precise biochemical method could help uncover these potentially rare DNA editing sites. We explore maleimide as a scaffold for inosine labeling. With fluorophore‐conjugated maleimide, we were able to label inosine in RNA or DNA. Moreover, with biotin‐conjugated maleimide, we purified RNA and DNA containing inosine. Our novel technique of inosine chemical labeling and affinity molecular purification offers substantial advantages and provides a versatile platform for further discovery of A‐to‐I editing sites in RNA and DNA. [ABSTRACT FROM AUTHOR]

Immunomodulators (tocilizumab/baricitinib) improve outcomes of coronavirus disease 2019 (COVID‐19) patients, but the synergistic effect of remdesivir is unknown. The effect of combination therapy with remdesivir, immunomodulators, and standard treatment in COVID‐19 patients was investigated. This retrospective, single‐center study included COVID‐19 patients who were treated with tocilizumab or baricitinib. The severity of respiratory status in the two groups on Days 14 and 28 and the duration to respiratory recovery in both groups were compared, and the effect of remdesivir use on respiratory status was examined in a multivariate analysis. Ninety‐eight patients received tocilizumab or baricitinib; among them, 72 used remdesivir (remdesivir group) and 26 did not (control group). The remdesivir group achieved faster respiratory recovery than the control group (median 11 vs. 21 days, p = 0.033), faster weaning from supplemental oxygen (hazard ratio [HR]: 2.54, 95% confidence interval [CI]: 1.14–5.66, p = 0.021). Age, body mass index, diabetes mellitus, and time from onset to oxygen administration were independent prognostic factors. The remdesivir group achieved better severity level at Days 14 and 28 (p = 0.033 and 0.003, respectively) and greater improvement from baseline severity (p = 0.047 and 0.018, respectively). Remdesivir combination therapy did not prolong survival (HR: 0.31, 95% CI: 0.04–2.16, p = 0.23). Among severely ill COVID‐19 patients who received immunomodulator, remdesivir contributed to a shorter respiratory recovery time and better respiratory status at Days 14 and 28. Concomitant remdesivir with immunomodulators and standard treatment may provide additional benefit in improving respiratory status of COVID‐19 patients. [ABSTRACT FROM AUTHOR]

This article, titled "Front Cover: α-Selective Solid-Phase Synthesis of Glycosyl Phosphate Repeating Structure Via the Phosphoramidite Method," discusses the synthesis of glycosyl phosphate repeating units found in lipophosphoglycans (LPGs) and capsular polysaccharides. The authors, K. Kawato, K. Sato, and T. Wada, describe their research on the α-selective solid-phase synthesis of these structures using glycosyl boranophosphates as stable intermediates. The cover art of the article depicts the structure of a synthesized disaccharide 1-phosphate repeating unit found in LPGs of Leishmania donovani. [Extracted from the article]

Extracorporeal photochemotherapy (ECP) is one of the more effective cell therapies for graft‐versus‐host disease (GvHD). ECP is a widely recommended therapeutic approach for the treatment of chronic GvHD, particularly steroid‐refractory GVHD. In recent years, the use of a light emitting diode (LED) in the clinic has attracted considerable interest. In this study, we examined the issue of whether an ultraviolet A1‐light emitting diode (UVA1‐LED) can be used as a light source in ECP. To compare the efficacy of ECP with conventional UVA lamp and a UVA1‐LED, we established an in vitro ECP model. Treatment efficacy was evaluated by measuring the % apoptosis and the inhibition of T‐cell proliferation. To investigate the effect of ECP on the innate immune reaction, THP‐1 cells with a luciferase reporter gene driven by a NF‐kB response element (THP‐1 luc NF‐kB) were treated with ECP. The LED‐ECP induced apoptosis and inhibition of T‐cell proliferation as efficiently as a conventional ECP. However, LED‐ECP induced less innate immunity in THP‐1. Since LED devices are more compact compared with conventional UVA irradiation devices, the use of a UVA1‐LED in the treatment of ECP may be a better alternative to conventional ECP therapy. [ABSTRACT FROM AUTHOR]

Leiomyosarcoma arising from the ovarian vein has rarely been reported. Herein, we report two cases from a single institute. Given their direct connections to ovarian vessels, both leiomyosarcomas were initially suspected to be gynecological malignancies. In one case, leiomyosarcoma was discovered incidentally without any clinical symptoms; it had a close connection with the ovarian vein, was removed surgically, and the patient has survived for over 12 years. In another case, bowel obstruction caused by the tumor helped to identify metastatic leiomyosarcoma. Blood flow was supplied by the ovarian artery and grew into the lumen of the ovarian vein without invading adjacent organs. After surgical resection, the patient underwent 18 months of chemotherapy prior to palliative care. We propose that leiomyosarcoma arising from the ovarian vein should be treated as a gynecologic malignancy, especially if it develops in the lower abdomen. [ABSTRACT FROM AUTHOR]

Objectives: The minimum body mass index (BMI) required to menarche and the relationship between the training onset age of sports and menarche is not fully understood. The aim of this study is to elucidate the minimum BMI required to attain menarche in female adolescent athletes competing at a national level, and to determine how the occurrence of menarche is associated with training onset age in track‐and‐field athletes. Methods: Overall, 134 sprinters and 44 long‐distance (LD) runners of ninth‐grade females at a national level were enrolled and an anonymous questionnaire was administered. Results: As BMI increased, the proportion of athletes who had attained menarche increased. The BMI cutoff values for menarche were 17.3 and 17.1 kg/m2 for sprinters and LD runners, respectively. Menarche had not occurred in almost 50% of the LD runners who began training at elementary school, and among LD runners, those who began training at elementary school had 18.4 higher odds of not attaining menarche until the age of 15 years as opposed to those who started training after elementary school. Conclusions: The BMI cutoff values could be an indicator for menarche in sprinters and LD runners. For LD runners, starting to compete at elementary school could be a risk factor for delayed menarche. [ABSTRACT FROM AUTHOR]

N‐terminal thiourea‐modified l‐Leu‐based peptide {(3,5‐diCF3Ph)NHC(=S)‐(l‐Leu‐l‐Leu‐Ac5c)2‐OMe} with five‐membered ring α,α‐disubstituted α‐amino acids (Ac5c) catalyzed a highly enantioselective 1,4‐addition reaction between β‐nitrostyrene and dimethyl malonate. The enantioselective reaction required only 0.5 mol % chiral peptide‐catalyst in the presence of iPr2EtN (2.5 equiv.), and gave a 1,4‐adduct with 93 % ee of an 85 % yield. As Michael acceptors, various β‐nitrostyrene derivatives such as methyl, p‐fluoro, p‐bromo, and p‐methoxy substituents on the phenyl group, 2‐furyl, 2‐thiophenyl, and naphthyl β‐nitroethylenes could be applied. Furthermore, various alkyl malonates and cyclic β‐keto‐esters could be used as Michael donors. It became clear that the length of the peptide chain, a right‐handed helical structure, amide N−Hs, and the N‐terminal thiourea moiety play crucial roles in asymmetric induction. [ABSTRACT FROM AUTHOR]

Intracellular signaling pathways that promote axon regeneration are closely linked to the mechanism of neurite outgrowth. TC10, a signaling molecule that acts on neurite outgrowth through membrane transport, is a member of the Rho family G proteins. Axon injury increases the TC10 levels in motor neurons, suggesting that TC10 may be involved in axon regeneration. In this study, we tried to understand the roles of TC10 in the nervous system using TC10 knock‐out mice. In cultured hippocampal neurons, TC10 ablation significantly reduced axon elongation without affecting ordinary polarization. We determined a role of TC10 in microtubule stabilization at the growth cone neck; therefore, we assume that TC10 limits axon retraction and promotes in vitro axon outgrowth. In addition, there were no notable differences in the size and structure of brains during prenatal and postnatal development between wild‐type and TC10 knock‐out mice. In motor neurons, axon regeneration after injury was strongly suppressed in mice lacking TC10 (both in conventional and injured nerve specific deletion). In retinal ganglion cells, TC10 ablation suppressed the axon regeneration stimulated by intraocular inflammation and cAMP after optic nerve crush. These results show that TC10 plays an important role in axon regeneration in both the peripheral and central nervous systems, and the role of TC10 in peripheral axon regeneration is neuron‐intrinsic. [ABSTRACT FROM AUTHOR]

Aim: End‐of‐life care for people with dementia is becoming increasingly important as the global population ages. However, there is no agreed definition of a good death for people with dementia. The current review examined previous literature to establish the current state of knowledge on this issue. Methods: We conducted a scoping review using a standard methodological framework. Relevant studies were identified from four databases. Studies were included if they were in English, discussed palliative or end‐of‐life care for dementia, and defined or explained a good death. The definitions or explanations of a good death were categorized into subthemes, and grouped into broader themes. Results: We identified 11 articles discussing or explaining a good death in dementia, which were published between 2009 and 2017. Most of these studies drew on the views of healthcare professionals and/or family members of people with dementia, and only one considered the views of people with dementia themselves. Ten themes were identified, including pain‐free status, peaceful/comfort, dignity, family presence, surrounded by familiar things and people, person‐centered communication, spirituality, life completion, treatment preferences, and other. Conclusions: The characteristics of a good death in dementia showed similarities with those identified more generally. However, there were some themes that were specific to end‐of‐life care in dementia, notably "surrounded by familiar things and people" and "person‐centered communication". To obtain a fuller picture of the nature of a good death in dementia, researchers need to examine the views of people living with dementia. [ABSTRACT FROM AUTHOR]

From these findings, we speculate that LP0132 may have an immunological effect, other than inducing the expansion of Treg cells, which may contribute to the alleviation of JCPsis symptoms in the early phase. In this trial, the specific subtypes of Treg cells induced by LP0132 to alleviate JCPsis symptoms were not examined. In summary, citrus juice fermented with LP0132 alleviated JCPsis symptoms in the early season and suppressed reduction in circulating Treg cells in the peak season. [Extracted from the article]

The vacuolar (H+)‐ATPases (V‐ATPases) are ATP‐driven proton pumps with multiple functions in many organisms. In this study, we performed structural and functional analysis of vha55 gene that encodes V‐ATPase subunit B in the smokybrown cockroach Periplaneta fuliginosa (Blattodea). We observed a high homology score of the deduced amino acid sequences between 10 species in seven orders. RNAi of the vha55 gene in P. fuliginosa caused nymphal/nymphal molting defects with incomplete shedding of old cuticles, growth inhibition, as well as bent and wrinkled cuticles of thoraxes and abdominal segments. Since growth inhibition caused by vha55 RNAi did not interfere in the commencement of cockroach molting, molting timing and body growth might be controlled by independent mechanism. Our study suggested V‐ATPases might be a good candidate molecule for evolutionary and developmental studies of insect molting. [ABSTRACT FROM AUTHOR]

Abstract: Bacterial and protozoan sugar chains contain glycosyl 1‐phosphate repeating structures; these repeating structures have been studied for vaccine development. The fluorinated analogues of [β‐Gal‐(1→4)‐α‐Man‐(1→6)‐P‐]n, which are glycosyl 1‐phosphate repeating structures found in Leishmania, were synthesised using the solid‐phase phosphoramidite method. This method has been less extensively studied for the synthesis of glycosyl 1‐phosphate units than H‐phosphonate chemistry. A stepwise synthesis of a compound containing five such repeating units has been conducted using the phosphoramidite method herein, which is the longest glycosyl 1‐phosphate structures to be chemically constructed in a stepwise manner. [ABSTRACT FROM AUTHOR]

We have found that Suzuki-Miyaura-type reactions of o-allyloxy(bromoethynyl)benzenes with arylboronic acids using a hydrazone/Cu catalyst system proceeded smoothly in iPrOH under mild conditions to afford the corresponding o-allyloxy(arylethynyl)benzene derivatives in good yields without decomposition of the allyloxy group. We have further demonstrated that annulation and enyne metathesis of the o-allyloxy(arylethynyl)benzene derivatives using transition-metal catalysts led to various heterocyclic compounds. [ABSTRACT FROM AUTHOR]

Background Several patient-/caregiver-completed questionnaires have been utilized for the assessment of asthma control. However, due to the diversity in medical/social circumstances, they may not be optimal for use in all countries. The Japanese pediatric asthma guideline ( JPGL) aims at higher levels of control compared with other international guidelines, based on a strong social demand for best care. We developed a new control test to help meet that demand. Methods A 34-item working questionnaire was developed based on input from pediatric asthma specialists and the caregivers of preschool children with asthma. The questionnaire was administered to caregivers of 565 patients aged <6 years who had physician-diagnosed asthma or β2-agonist-responsive recurrent wheeze. Then, 6 questions for assessing JPGL-defined control levels were selected from the 34 questions by stepwise logistic regression methods using randomly selected questionnaires completed by two-thirds of the caregivers. We named that set of questions the Best Asthma Control Test for Preschoolers (Best ACT-P). Validation of Best ACT-P was performed using the remaining completed questionnaires. Results The 6 questions asked about the frequency/severity of cold-induced wheeze, nighttime awakening, exercise-induced symptoms, and disruption of family life due to asthma in the past 4 weeks and hospitalization in the past 12 months. The 6-item logistic model showed good statistical fit, and the scores for the physicians' ratings of the asthma control differed significantly in the hypothetical direction. Conclusions Best ACT-P is a valid caregiver-completed questionnaire of asthma control in preschoolers in whom total control needs to be achieved. [ABSTRACT FROM AUTHOR]

Vaccine modified measles (VMM) affects individuals with attenuated vaccine induced immunity. An outbreak of measles occurred in a junior high school, starting from an unvaccinated eighth-grade student who developed natural measles and affected a majority of students who were immunized with a low potent strain of measles vaccine (TD97). To determine whether environmental tobacco smoke (ETS) exposure was associated with the development of VMM in this population, a questionnaire was used asking whether students had VMM symptoms during the outbreak and the smoking status of family members. VMM was defined in the study population as occurrence of fever and/or erythema, along with documented history of measles vaccination. A total of 513 students (85.9%) responded. Overall, the presence of in-house smokers did not differ between VMM students (49.3%) and non-VMM students (50.2%). However, in the ninth grade, presence of an in-house smoker was significantly higher in the family of VMM students (54.0%) than in non-VMM students (36.6%) ( P = 0.044). Urinary cotinine levels were also measured in selected students (n = 37). Among families with at least one smoker, urinary cotinine levels were significantly higher in VMM students than in non-VMM students ( P = 0.032). Furthermore, a multivariable logistic regression analysis showed that a high urinary cotinine level (>10 ng/mg creatinine; 13.5 percentile) was associated with the development of VMM. Our findings suggest that a high level of ETS exposure may be associated with an increased risk of VMM in a population with attenuated vaccine induced immunity against measles. J. Med. Virol. 87:1853-1859, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to compare the effects of pre-surgical medication with dienogest or leuprorelin on post-surgical ovarian function. Material and Methods We conducted an exploratory study in two centers in Japan that comprised 30 patients with ovarian endometrial cysts for whom surgical excision was planned. Patients were enrolled and divided into pre-surgical medication groups with dienogest or leuprorelin for 12 weeks. Thereafter, patients were treated by laparoscopic cystectomy. The primary outcome was ovarian function post-surgery, as assessed by serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC) and resumption of menses. Secondary outcome was the effect of pre-surgical medication, as assessed by the size of endometrial cysts and visual analog scale (VAS) score. Serum AMH, AFC, size of endometrial cysts, and VAS scores were measured at baseline (before medication), after medication (1 day before surgery), and at 4 and 12 weeks post-surgery. Results Serum AMH levels did not change after pre-surgical medication with either dienogest or leuprorelin. Although AMH decreased after surgery, it recovered by 12 weeks post-surgery in both groups with no statistically significant difference. Mean AFC did not change after surgery in either group. Menses returned by 12 weeks post-surgery in all patients except for those who were pregnant. The rate of reduction of endometrial cyst volume did not differ between the groups. Both dienogest and leuprorelin were associated with substantial reductions in VAS scores. Conclusion There were no statistically significant differences between pre-surgical medication with dienogest and leuprorelin in post-surgical ovarian function. Both medications were effective in reducing endometrial cyst volume and VAS score. [ABSTRACT FROM AUTHOR]

To study in detail the roles of basic amino acid residues in the activity of μ-conotoxin GIIIA ( μ- GIIIA) and GIIIB ( μ- GIIIB), specific blockers of muscle sodium channels, seven analogs of μ- GIIIA, and two analogs of μ- GIIIB were synthesized. μ- GIIIA analogs were synthesized by replacing systematically the three Arg residues (Arg1, Arg13, and Arg19) with one, two, and three Lys residues. μ- GIIIB analogs were synthesized by replacing simultaneously all four Lys residues (Lys9, Lys11, Lys16, and Lys19) with Arg residues and further replacement of acidic Asp residues with neutral Ala residues. Circular dichroism spectra of the synthesized analogs suggested that the replacement did not affect the three dimensional structure. The inhibitory effects on the twitch contractions of the rat diaphragm showed that the side chain guanidino group of Arg13 of μ- GIIIA was important for the activity, whereas that of Arg19 had little role for biological activity. Although [Arg9,11,16,19] μ- GIIIB showed higher activity than native μ- GIIIB, highly basic [Ala2,12, Arg9,11,16,19] μ- GIIIB showed lower activity, suggesting that there was an appropriate molecular basicity for the maximum activity. [ABSTRACT FROM AUTHOR]

ABSTRACT Toxoplasma gondii is an obligate intracellular protozoan pathogen that can cross the placenta, resulting in congenital toxoplasmosis with severe fetal brain abnormalities. The molecular mechanisms of immune responses against T. gondii infection in the placenta have largely remained unclear. An analytical method for characterizing phenotypes of immune cells in the placenta by flow cytometry was established and it was found that numbers of CD11b+ Gr-1+ cells in the placenta increased significantly after T. gondii infection. These results suggest that innate immune responses play an important role in immunity against T. gondii infection via the feto-maternal interface. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to validate the potential association between cigarette smoking and cubital tunnel syndrome (CubTS).Methods: One hundred patients with CubTS were compared with 100 controls with ulnar abutment syndrome matched for age, gender, and body mass index. The smoking status was compared between patients and controls using the sign test and the Wilcoxon signed rank test. Conditional logistic regression was used to calculate the association between CubTS and pack-years smoked.Results: A significant association was found between increased pack-years smoked and CubTS. A significant difference in the number of never smokers and ever smokers was observed between the patients with CubTS and controls. The difference in mean pack-years in the patients and controls was highly significant. A dose-dependent association with pack-years was found between patients and controls.Conclusions: High cumulative cigarette smoking is associated with CubTS. Muscle Nerve 54: 1136-1138, 2016. [ABSTRACT FROM AUTHOR]

Infants' ability to recognize uncanny human faces increases during the first year of life. In turn, their ability to recognize faces of other species declines at almost the same period (perceptual narrowing). In the current study, we aimed to clarify the relationship between the perception of uncanniness of faces and perceptual narrowing in infants and adults. We used the "uncanny valley task," in which the participants were required to discriminate the faces of humans and monkeys by different eye size. Results showed that 3- to 5-month-old infants could not discriminate either monkey or human faces by eye size, whereas 6- to 8-month olds could. Adults showed higher discrimination performance for human than monkey faces and perceived the human faces with extremely large or small eyes as exceedingly eerie. Our results suggest that perception of uncanniness of faces is formed after perceptual narrowing. [ABSTRACT FROM AUTHOR]

To realize an ultra-flat diamond surface with a three-dimensional (3D) structure, we performed dressed-photon-phonon (DPP) etching. A DPP is generated on nano-scale protrusions. Hence, the generation of DPPs results in selective removal of nano-scale protrusions, thereby achieving an ultra-flat surface even on the sidewall of a diamond mesa structure. By controlling the polarization of the incident light, a smooth diamond mesa structure sidewall was obtained, and a higher etching rate was obtained with a perpendicular polarization on the corrugations. In addition, by selective deposition of n-layer diamond on the p-layer diamond mesa structure, smooth n-layer diamond was confirmed on the DPP etched sidewall. Schematic of dressed-photon-phonon (DPP) etching on the sidewall: (a) before and (b) after etching, in which DPP selectively generates on the corrugations and etching automatically stops when the surface was smooth. Scanning electron microscopy image of the selective deposition of the n-layer (c) without and (d) with the DPP etched sidewall. [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to validate an instrument for measuring bereaved family members' perceptions of caregiving consequences and to examine the association between caregiving consequences and psychological distress. Methods: Cross-sectional questionnaires were administered to family members of patients who had died in regional cancer centers. We measured the Caregiving Consequences Inventory (CCI), respondent's optimism, overall reward scale, and psychological distress and collected background data. A retest was conducted. Results: Bereaved families from two regional cancer centers were surveyed (N=189 and 109; effective response rate, 57 and 80%). By exploratory and confirmatory factor analyses, we identified four perceived reward domains: ‘mastery’, ‘appreciation for others’, ‘meaning in life’, and ‘reprioritization’, and one perceived burden domain. Although the four reward domains were highly correlated with each other (0.47

Background: Although it is important to achieve a good death in Japan, there have been no studies to explore factors associated with a good death. The aim of this study was to explore factors contributing to a good death from the bereaved family members' perspectives, including patient and family demographics and medical variables. Methods: A cross-sectional anonymous questionnaire survey for bereaved family members of cancer patients who had died in a regional cancer center and a medical chart review were conducted. We measured the results from the Good Death Inventory and family demographics. In addition, we extracted patient demographics, medical variables, and medical interventions in the last 48 h before death from a medical chart review. Results: Of the 344 questionnaires sent to bereaved family members, 165 responses were analyzed (48%). We found, first, that death in the palliative care unit was more likely to be described as a good death compared with death on a general ward. Some significant characteristics were ‘environmental comfort,’ ‘physical and psychological comfort,’ ‘being respected as an individual,’ and ‘natural death.’ Second, we found that a patient's and family member's age and other demographic factors significantly correlated with an evaluation of a good death. In addition, life prolongation treatment and aggressive treatment such as chemotherapy in the last 2 weeks of life were barriers to attainment of a good death. Moreover, appropriate opioid medication contributed to a good death. Conclusion: Withholding aggressive treatment and life-prolonging treatment for dying patients and appropriate opioid use may be associated with achievement of a good death in Japan. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The in vitro culture of porcine bone marrow-derived mesenchymal stem cells (MSCs) was used for the investigation of adult stem cell biology. Isolated porcine MSCs possessed the ability to proliferate extensively in an antioxidants-rich medium containing 5% fetal bovine serum (FBS). Greater than 40 serial MSC passages and 100 cell population doublings have been recorded for some MSC batches. Early and late passage MSCs were defined here as those cultures receiving less than 5 trypsin passages and more than 15 trypsin passages, respectively. Consistent with their robust ability to proliferate, both the early and late passage MSCs expressed the cell-cycle promoting enzyme p34cdc2 kinase. Late MSCs, however, exhibited certain features reminiscent of cellular aging such as actin accumulation, reduced substrate adherence, and increased activity of lysosomal acid β-galactosidase. Early MSCs retained the multipotentiality capable of chondrogenic, osteogenic, and adipogenic differentiation upon induction in vitro. In contrast, late MSCs were only capable of adipogenic differentiation, which was greatly enhanced at the expense of the osteochondrogenic potential. Along with these changes in multipotentiality, late MSCs expressed decreased levels of the bone morphogenic protein (BMP-7) and reduced activity of alkaline phosphatase. Late MSCs also exhibited attenuated synthesis of the hematopoietic cytokines granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), and stem cell factor (SCF). The long-term porcine MSC culture, thus, provides a model system to study the molecular interplay between multiple MSC differentiation cascades in the context of cellular aging. © 2005 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Activation of the superoxide-producing phagocyte NADPH oxidase, crucial in host defense, requires the cytosolic proteins p67phox and p47phox. They translocate to the membrane upon cell stimulation and activate flavocytochrome b558, the membrane-integrated catalytic core of this enzyme system. The activators p67phox and p47phox form a ternary complex together with p40phox, an adaptor protein with unknown function, comprising the PX/PB2, SH3 and PC motif-containing domains: p40phox associates with p67phox via binding of the p40phox PC motif to the p67phox PB1 domain, while p47phox directly interacts with p67phox but not with p40phox. Here we show that p40phox enhances membrane translocation of p67phox and p47phox in stimulated cells, which leads to facilitated production of superoxide. The enhancement cannot be elicited by a mutant p40phox carrying the D289A substitution in PC or a p67phox with the K355A substitution in PB1, each being defective in binding to its respective partner. Thus p40phox participates in activation of the phagocyte oxidase by regulating membrane recruitment of p67phox and p47phox via the PB1-PC interaction with p67phox. [ABSTRACT FROM AUTHOR]

Neurotransmitter release involves the assembly of a heterotrimeric SNARE complex composed of the vesicle protein synaptobrevin (VAMP 2) and two plasma membrane partners, syntaxin 1 and SNAP-25. Calcium influx is thought to control this process via Ca2+-binding proteins that associate with components of the SNARE complex. Ca2+/calmodulin or phospho- lipids bind in a mutually exclusive fashion to a C-terminal domain of VAMP (VAMP77-90), and residues involved were identified by plasmon resonance spectroscopy. Microinjection of wild-type VAMP77-90, but not mutant peptides, inhibited catecholamine release from chromaffin cells monitored by carbon fibre amperometry. Pre-incubation of PC12 pheochromocytoma cells with the irreversible calmodutin antagonist ophiobolin A inhibited Ca2+-dependent human growth hormone release in a permeabilized cell assay. Treatment of permeabilized cells with tetanus toxin tight chain (TeNT) also suppressed secretion. In the presence of TeNT, exocytosis was restored by transfection of TeNT-resistant (Q76V, F77W) VAMP, but additional targeted mutations in VAMP77-90 abolished its ability to rescue release. The calmodulin- and phospholipid-binding domain of VAMP 2 is thus required for Ca2+-dependent exocytosis, possibly to regulate SNARE complex assembly. [ABSTRACT FROM AUTHOR]

μ-Conotoxin (μ-CTX) inhibits Na+ flux by obstructing the Na+ channel pore. Previous studies of μ-CTX have focused only on charged toxin residues, ignoring the neutral sites. Here we investigated the proximity between the C-terminal neutral alanine (A22) of μ-CTX and the Na+ channel pore by replacing it with the negatively charged glutamate. The analog A22E and wild-type (WT) μ-CTX exhibited identical nuclear magnetic resonance spectra except at the site of replacement, verifying that they have identical backbone structures. A22E significantly reduced μ-CTX affinity for WT μ1 Na+ channels (90-fold↓), as if the inserted glutamate repels the anionic pore receptor. We then looked for the interacting partner(s) of residue 22 by determining the potency of block of Y401K, Y401A, E758Q, D762K, D762A, E765K, E765A and D1241K channels by WT μ-CTX and A22E, followed by mutant cycle analysis to assess their individual couplings. Our results show that A22E interacts strongly with E765K from domain II (DII) (ΔΔG=2.2±0.1 vs. <1 kcal/mol for others). We conclude that μ-CTX residue 22 closely associates with the DII pore in the toxin-bound channel complex. The approach taken may be further exploited to study the proximity of other neutral toxin residues with the Na+ channel pore. [Copyright &y& Elsevier]

Abstract: Presenilin 1 (PS1) has been identified as a causativegene for most early-onset familial Alzheimer's disease. Biochemical studiesrevealed that PS1 exists predominantly as two processed fragments in cells andbrain tissues. We prepared stably transfected cells expressing the wild-typeand familial Alzheimer's disease-associated mutants of PS1 and investigatedthe enzyme that participates in the metabolism of PS1. After treatment of thecells with proteasome inhibitors, the full-length PS1 was significantlyaccumulated. The levels of N- and C-terminal fragments were also increased.The accumulation of PS1 with a deletion of exon 10, which is unable to beprocessed, on treatment of the transfected cells with lactacystin indicatedthat proteasome can degrade full-length PS1. A synthetic peptide that includesthe processing region of PS1 was cleaved by 20S proteasome at the putativeprocessing sites after Met[sup 288] and Glu[sup 299]. Metaboliclabeling experiments showed that the appearance of the N-terminal fragment wasattenuated by the inhibitor. Finally, 28-kDa N- and 20-kDa C-terminalfragments were generated by purified PS1 in vitro. These data indicated thatthe proteasome pathway is involved in PS1 processing. These resultsdemonstrate that the proteasome pathway plays dual roles in processing anddegradation of PS1. [ABSTRACT FROM AUTHOR]

Review: 74 refs. [ABSTRACT FROM AUTHOR]