A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evidence at molecular, cellular and whole heart levels to implicate a sarcolemma membrane targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β -adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis

Medical Curriculum to Motivate Students

Despite advancements in the pedagogy of medical education in various fields, Japan has no standardized medical English education. The U.S. Medical Licensing Examination (USMLE) Study Group of Tokushima is an extracurricular activity in which medical students and recent graduates meet every 1–2 months. The aim is to stimulate students’ curiosity ; cultivate their initiative, self-efficacy, and English learning goals ; and motivate them to be self-regulated learners. Accordingly, we conducted near-peer teaching style lectures that focused on sharing medical English-related experiences, so students could have regular opportunities to visualize the benefits of learning medical English. Following the activities, we observed increased motivation and self-study among students, resulting in a high USMLE passing rate. Furthermore, five members started their training at American hospitals and pursued careers in English-speaking environments. Thus, near-peer teaching style leads to shared medical English-related experiences that help students to visualize English-related opportunities. This education style taught by similar generations aids in setting a specific goal by providing access to role models, cultivating their initiative and self-efficacy, motivating them to learn English, and producing positive outcomes. Modifying the curriculum to actively create opportunities for students to visualize themselves in an international environment can motivate them to continue learning English

Distribution of Polysulfide in Human Biological Fluids and Their Association with Amylase and Sperm Activities

Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confirmed the presence of polysulfide in other biological fluids, such as semen and nasal discharge. The levels of polysulfide in these biological fluids from healthy volunteers (n = 9) with identical characteristics were compared. Additionally, the circadian rhythm of plasma polysulfide was also investigated. The polysulfide levels detected from nasal discharge and seminal fluid were approximately 400 and 600 μM, respectively. No correlation could be found between plasma polysulfide and the polysulfide levels of tear, saliva, and nasal discharge. On the other hand, seminal polysulfide was positively correlated with plasma polysulfide, and almost all polysulfide contained in semen was found in seminal fluid. Intriguingly, saliva and seminal polysulfide strongly correlated with salivary amylase and sperm activities, respectively. These results provide a foundation for scientific breakthroughs in various research areas like infertility and the digestive system process

Multiple transcripts of Ca 2ϩ channel ␣ 1 -subunits and a novel spliced variant of the ␣ 1C -subunit in rat ductus arteriosus

3 H]thymidine incorporation, suggesting that L-and T-type Ca 2ϩ channels are involved in smooth muscle cell proliferation in the DA. Third, we found that a novel alternatively spliced variant of the ␣ 1C-isoform was highly expressed in the neointimal cushion of the DA, where proliferating and migrating smooth muscle cells are abundant. The basic channel properties of the spliced variant did not differ from those of the conventional ␣1C-subunit. We conclude that multiple VDCC subunits were identified in the DA, and, in particular, ␣ 1C-and ␣1G-subunits were predominant in the DA. A novel spliced variant of the ␣1C-subunit gene may play a distinct role in neointimal cushion formation in the DA. alternative spliced; development; gene expression; fetal circulation THE DUCTUS ARTERIOSUS (DA) is a fetal arterial connection between the pulmonary artery and the descending aorta. After birth, the DA closes immediately, in accordance with its smooth muscle contraction. An increase in oxygen tension and a dramatic decline in circulating prostaglandins are the most important triggers of DA contraction (5). Generally, vascular smooth muscle contraction is induced by Ca 2ϩ / calmodulin-dependent phosphorylation of the regulatory myosin light chain, which is mediated by an increase in intracellular Ca 2ϩ . Ca 2ϩ influx through voltage-dependent Ca 2ϩ channels (VDCCs) and Ca 2ϩ release from intracellular stores are major sources of this increase (8, 26). Thus VDCCs must play an important role in vascular myogenic reactivity and tone of the DA. VDCCs are classified, according to their distinct electrophysiological and pharmacological properties, into low (Ttype) and high (L-, N-, P-, Q-, and R-type) VDCCs (20, In addition to their role in determining contractile state, a growing body of evidence has demonstrated that VDCCs play an important role in regulating differentiation and remodeling of vascular smooth muscle cells (SMCs) (14, In the present study, we identified multiple VDCC subunits in the DA by semiquantitative and quantitative RT-PCR and immunodetection. In particular, ␣ 1C -and ␣ 1G -subunits were predominant in the DA. Furthermore, we will demonstrate the identification of a novel spliced variant of the ␣ 1C -subunit gene that may play a role in neointimal cushion formation of the DA

Plasma Free Amino Acid Profiling of Five Types of Cancer Patients and Its Application for Early Detection

BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods

Pleiotropic effects of levofloxacin, fluoroquinolone antibiotics, against influenza virus-induced lung injury

© 2015 Enoki 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. Reactive oxygen species (ROS) and nitric oxide (NO) are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX), one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1) influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress) and nitrotyrosine (a nitrative marker) in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites) and IFN-? in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs

A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart.

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evidence at molecular, cellular and whole heart levels to implicate a sarcolemma membrane targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β -adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis

Transcriptional profiles in the chicken ductus arteriosus during hatching.

The ductus arteriosus, an essential embryonic blood vessel between the pulmonary artery and the descending aorta, constricts after birth or hatching and eventually closes to terminate embryonic circulation. Chicken embryos have two long ductus arteriosi, which anatomically differ from mammal ductus arteriosus. Each long ductus arteriosus is divided into two parts: the pulmonary artery-sided and descending aorta-sided ductus arteriosi. Although the pulmonary artery-sided and descending aorta-sided ductus arteriosi have distinct functional characteristics, such as oxygen responsiveness, the difference in their transcriptional profiles has not been investigated. We performed a DNA microarray analysis (GSE 120116 at NCBI GEO) with pooled tissues from the chicken pulmonary artery-sided ductus arteriosus, descending aorta-sided ductus arteriosus, and aorta at the internal pipping stage. Although several known ductus arteriosus-dominant genes such as tfap2b were highly expressed in the pulmonary artery-sided ductus arteriosus, we newly found genes that were dominantly expressed in the chicken pulmonary artery-sided ductus arteriosus. Interestingly, cluster analysis showed that the expression pattern of the pulmonary artery-sided ductus arteriosus was closer to that of the descending aorta-sided ductus arteriosus than that of the aorta, whereas the morphology of the descending aorta-sided ductus arteriosus was closer to that of the aorta than that of the pulmonary artery-sided ductus arteriosus. Subsequent pathway analysis with DAVID bioinformatics resources revealed that the pulmonary artery-sided ductus arteriosus showed enhanced expression of the genes involved in melanogenesis and tyrosine metabolism compared with the descending aorta-sided ductus arteriosus, suggesting that tyrosinase and the related genes play an important role in the proper differentiation of neural crest-derived cells during vascular remodeling in the ductus arteriosus. In conclusion, the transcription profiles of the chicken ductus arteriosus provide new insights for investigating the mechanism of ductus arteriosus closure