Peripheral Blood as a Preferable Source of Stem Cells for Salvage Transplantation in Patients with Graft Failure after Cord Blood Transplantation: A Retrospective Analysis of the Registry Data of the Japanese Society for Hematopoietic Cell Transplantation

To compare the different stem cell sources used in salvage transplantation for graft failure (GF) after cord blood transplantation (CBT), we retrospectively analyzed data of 220 patients who developed GF after undergoing CBT between January 2001 and December 2007 and underwent a second hematopoietic stem cell transplantation (HSCT) within 3 months. The donor sources for salvage HSCT were cord blood (n = 180), peripheral blood stem cells (PBSCs; n = 24), and bone marrow (BM; n = 16). The cumulative incidence of neutrophil engraftment on day 30 after the second HSCT was 39% with CB, 71% with PBSCs, and 75% with BM. Multivariate analysis revealed that PBSC and BM grafts were associated with a significantly higher engraftment rate than CB (hazard ratio [HR], 7.77; P < .001 and HR, 2.81; P = .016, respectively). Although the incidence of grade II-IV acute graft-versus-host disease was significantly higher in the PBSC group than in the CB group (HR, 2.83; P = .011), the incidence of 1-year nonrelapse mortality was lower in the PBSC group than in the CB group (HR, 0.43; P = .019), and 1-year overall survival was superior in the PBSC group compared with the CB group (HR, 0.45; P = .036). Our results suggest that PBSC is the preferable source of stem cells in salvage HSCT for GF after CBT

PACAP centrally mediates emotional stress-induced corticosterone responses in mice

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide widely distributed in the nervous system. Recently, PACAP was shown to be involved in restraint stress-induced corticosterone release and concomitant expression of the genes involved in hypothalamic–pituitary–adrenal (HPA) axis activation. Therefore, in this study, we have addressed the types of stressors and the levels of the HPA axis in which PACAP signaling is involved using mice lacking PACAP (PACAP−/−). Among four different types of stressors, open-field exposure, cold exposure, ether inhalation, and restraint, the corticosterone response to open-field exposure and restraint, which are categorized as emotional stressors, but not the other two, was markedly attenuated in PACAP−/− mice. Peripheral administration of corticotropin releasing factor (CRF) or adrenocorticotropic hormone induced corticosterone increase similarly in PACAP and wild-type mice. In addition, the restraint stress-induced c-Fos expression was significantly decreased in the paraventricular nucleus (PVN) and medial amygdala (MeA), but not the medial prefrontal cortex, in PACAP−/− mice. In the PVN of PACAP−/− mice, the stress-induced c-Fos expression was blunted in the CRF neurons. These results suggest that PACAP is critically involved in activation of the MeA and PVN CRF neurons to centrally regulate the HPA axis response to emotional stressors

A new approach? China's approach towards the Philippines over the South China Sea dispute after the arbitral tribunal's ruling 2016

Diese Masterarbeit wird untersuchen, ob China seine Herangehensweise in dem SCS Konflikt mit den Philippinen in folge der Entscheidung\ud des Schiedsgerichts zu Gunsten der Philippinen im Juli 2016 verändert hat. Ein Bericht des Mischief Reef Vorfalles in 1995 und dem ‘Joint Marine Seismic Undertaking’ in dem Vereinbarungsgebiet in der Süd-Chinesischen See-Vereinbarung von 2005, liefert den Hintergrund zu China’s SCS Position. Diese wurde durch die politischen Interaktionen zwischen China, den Philippinen, den ASEAN Staaten, den USA und auch Chinas internen politischen Faktoren beeinflusst. Eine Untersuchung von Chinas’ Position nach der Entscheidung verglichen mit den Handlungen vor der Schiedsentscheidung zeigt, dass China zumindest auf kurze Sicht die Herangehensweise von einem aggressiven zu einem friedlicheren Ansatz verändert hat. Aufgrund von Chinas bekannter Taktik seine Position je nach Ausgangslage von klarem Durchsetzungswillen hin zu diplomatischen Vorgehen zu verändern, kann zu diesem Zeitpunkt nicht bestätigt werden, dass China in Zukunft auf seine Durchsetzungsfähigkeit verzichten wird.This thesis will examine whether China has changed its approach over the SCS dispute with the Philippines, after the arbitral tribunal’s ruling in favor of the Philippines in July 2016. A review of the Mischief Reef incident in 1995 and the Joint Marine Seismic Undertaking in the Agreement Area in the South China Sea agreement in 2005 provides context to China’s SCS position, which was influenced by the dynamics of political interaction between China, the Philippines, ASEAN and the U.S, as well as China’s domestic political factors. An examination of China’s position after the ruling compared with its actions before shows that China has modified its approach from an assertive one to a more peaceful position, at least in the short term. Given China’s previous pattern of shifting between positions of assertiveness and diplomacy, in the long term, we cannot say that China will not take an assertive approach again

Alteration of Leucine Aminopeptidase from Streptomyces septatus TH-2 to Phenylalanine Aminopeptidase by Site-Directed Mutagenesis

To tailor leucine aminopeptidase from Streptomyces septatus TH-2 (SSAP) to become a convenient biocatalyst, we are interested in Phe221 of SSAP, which is thought to interact with the side chain of the N-terminal residue of the substrate. By using saturation mutagenesis, the feasibility of altering the performance of SSAP was evaluated. The hydrolytic activities of 19 mutants were investigated using aminoacyl p-nitroanilide (pNA) derivatives as substrates. Replacement of Phe221 resulted in changes in the activities of all the mutants. Three of these mutants, F221G, F221A, and F221S, specifically hydrolyzed l-Phe-pNA, and F221I SSAP exhibited hydrolytic activity with l-Leu-pNA exceeding that of the wild type. Although the hydrolytic activities with peptide substrates decreased, the hydrolytic activities with amide and methyl ester substrates were proportional to the changes in the hydrolytic activities with pNA derivatives. Furthermore, based on a comparative kinetic study, the mechanism underlying the alteration in the preference of SSAP from leucine to phenylalanine is discussed

Change in Substrate Preference of Streptomyces Aminopeptidase through Modification of the Environment around the Substrate Binding Site

We attempted to alter the substrate preference of aminopeptidase from Streptomyces septatus TH-2 (SSAP). Because Asp198 and Phe221 of SSAP are located in the substrate binding site, we screened 2,000 mutant enzymes with D198X/F221X mutations. By carrying out this examination, we obtained two enzymes; one specifically hydrolyzed an arginyl derivative, and the other specifically hydrolyzed a cystinyl derivative (65- and 12.5-fold higher k(cat) values for hydrolysis of p-nitroanilide derivatives than those of the wild type, respectively)