Synthesis of Saxitoxin Biosynthetic Intermediates: Reveal the Mechanism for Formation of its Tricyclic Skeleton in Biosynthesis.

The synthesis and biosynthesis of the complex saxitoxin (STX) structure have garnered significant interest. Previously, we hypothesized that the tricyclic skeleton of STX originates from the monocyclic precursor 11-hydroxy-IntC'2 during biosynthesis, although direct evidence has been lacking. In this study, we identified conditions to synthesize a proposed tricyclic biosynthetic intermediate, 12,12-dideoxy-decarbamoyloxySTX (dd-doSTX), along with its 6-epimer (6-epi-dd-doSTX) and a bicyclic compound, in a single step from di-Boc protected 11-hydroxy-IntC'2.

Novel and highly reliable leak check tests for drop- and external pressure-type cell-free and concentrated ascites reinfusion therapy.

Introduction: For safe management of cell-free and concentrated ascites reinfusion therapy (CART), a highly reliable leak test for detecting ascites filter damage is essential. However, such a test has not been established for drop-type CART.

Methods: We devised two novel leak tests for drop- and external pressure-type CART, manual or pump pressurization methods, using high-pressure loading and pressure monitoring, and investigated their reliability.

Disease-related protein co-expression networks are associated with the prognosis of resectable node-positive pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a multifactorial disease, the molecular profile of which remains unclear. This study aimed at unveiling the disease-related protein networks associated with different outcomes of resectable, node-positive PDAC cases. We assessed laser-microdissected cancerous cells from PDAC tissues of a poor outcome group (POG; n = 4) and a better outcome group (BOG; n = 4).

Visualized procollagen Iα1 demonstrates the intracellular processing of propeptides.

The processing of type I procollagen is essential for fibril formation; however, the steps involved remain controversial. We constructed a live cell imaging system by inserting fluorescent proteins into type I pre-procollagen α1. Based on live imaging and immunostaining, the C-propeptide is intracellularly cleaved at the perinuclear region, including the endoplasmic reticulum, and subsequently accumulates at the upside of the cell.

Non-metal sensory electrode design and protocol of DNA-nucleobases in living cells exposed to oxidative stresses.

Sensory protocols for evaluation of DNA distortion due to exposure to various harmful chemicals and environments in living cells are needed for research and clinical investigations. Here, a design of non-metal sensory (NMS) electrode was built by using boron-doped carbon spherules for detection of DNA nucleobases, namely, guanine (Gu), adenine (Ad), and thymine (Th) in living cells. The key-electrode based nanoscale NMS structures lead to voids with a facile diffusion, and strong binding events of the DNA nucleobases.

Identification of a Novel Saxitoxin Analogue, 12β-Deoxygonyautoxin 3, in the Cyanobacterium, (TA04).

Saxitoxin (STX) and its analogues, the potent voltage-gated sodium channel blockers, are biosynthesized by freshwater cyanobacteria and marine dinoflagellates. We previously identified several biosynthetic intermediates in the extract of the cyanobacterium, (TA04), that are primarily produced during the early and middle stages in the biosynthetic pathway to produce STX. These findings allowed us to propose a putative biosynthetic pathway responsible for STX production based on the structures of these intermediates.

PDZK1-interacting protein 1 (PDZK1IP1) traps Smad4 protein and suppresses transforming growth factor-β (TGF-β) signaling.

Transforming growth factor (TGF)-β signaling in humans is stringently regulated to prevent excessive TGF-β signaling. In tumors, TGF-β signaling can both negatively and positively regulate tumorigenesis dependent on tumor type, but the reason for these opposite effects is unclear. TGF-β signaling is mainly mediated via the Smad-dependent pathway, and herein we found that PDZK1-interacting protein 1 (PDZK1IP1) interacts with Smad4.

A Glutathione-Responsive Short Sequence of Metal-Organic Complex Array.

A short metal-organic complex array (MOCA) containing a sequence of RPtRRu (1 ) was found to exhibit unique responses to a major biothiol, glutathione (GSH). Upon binding of GSH to 1 , the resultant 1:1 complex (1 ) formed nanofibrous assemblies that suggested supramolecular polymerization through the double-salt-bridge structure formation. The binding behavior of this MOCA sequence to calf thymus DNA was also dependent on GSH; a larger conformational change of DNA was observed upon binding with 1 , relative to that with 1 .

Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration.

Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated.

Slender transradial iliac artery stenting using a 4.5Â French guiding sheath.

We previously reported safety and usefulness of transradial iliac artery stenting using 6 Fr guiding sheath. However, radial artery occlusion was a major limitation of this procedure. We analyzed the safety and utility of slender transradial iliac artery stenting using a 4.

Technical Performance and Clinical Effectiveness of Drop Type With Adjustable Concentrator-Cell Free and Concentrated Ascites Reinfusion Therapy.

Cell-free and concentrated ascites reinfusion therapy (CART) is a very useful treatment method for refractory ascites but is difficult for many hospitals to employ due to its need for specialized equipment. We have therefore developed drop-type with adjustable concentrator CART (DC-CART) that uses a drop-type filtration mechanism and requires only a simple pump and pressure monitor for its concentration process. Easy adjustment of ascites concentration is possible through a recirculation loop, and filter membrane washing is aided by DC-CART's external pressure-type filtration to enable the processing of any quality or quantity of ascites.

Transradial intervention for chronic total occlusion at the external iliac artery using a bidirectional approach through a single guiding catheter.

A 64-year-old male with intermittent claudication due to long chronic total occlusion of external iliac artery was successfully treated with a bi-directional approach. The retrograde guidewire was inserted into the ipsilateral internal iliac artery to the distal femoral artery through a collateral channel. The procedure was performed with a single guiding catheter through a single puncture of the left radial artery.

Mass spectrometry-based proteomic analysis of formalin-fixed paraffin-embedded extrahepatic cholangiocarcinoma.

Background: Extrahepatic cholangiocarcinoma is very difficult to diagnose at an early stage, and has a poor prognosis. Novel markers for diagnosis and optimal treatment selection are needed. However, there has been very limited data on the proteome profile of extrahepatic cholangiocarcinoma.

The co-transplantation of bone marrow derived mesenchymal stem cells reduced inflammation in intramuscular islet transplantation.

Aims/hypothesis: Although the muscle is one of the preferable transplant sites in islet transplantation, its transplant efficacy is poor. Here we attempted to determine whether an intramuscular co-transplantation of mesenchymal stem cells (MSCs) could improve the outcome.

Methods: We co-cultured murine islets with MSCs and then analyzed the morphological changes, viability, insulin-releasing function (represented by the stimulation index), and gene expression of the islets.

Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis.

Study Design: A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum.

Objective: To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology.

Summary Of Background Data: Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS).

Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters.

T cell receptor (TCR) phosphorylation requires the kinase Lck and phosphatase CD45. CD45 activates Lck by dephosphorylating an inhibitory tyrosine of Lck to relieve autoinhibition. However, CD45 also dephosphorylates the TCR, and the spatial exclusion of CD45 from TCR clustering in the plasma membrane appears to attenuate this negative effect of CD45.

Comprehensive genetic analysis of early host body reactions to the bioactive and bio-inert porous scaffolds.

To design scaffolds for tissue regeneration, details of the host body reaction to the scaffolds must be studied. Host body reactions have been investigated mainly by immunohistological observations for a long time. Despite of recent dramatic development in genetic analysis technologies, genetically comprehensive changes in host body reactions are hardly studied.

Role of S-palmitoylation on IFITM5 for the interaction with FKBP11 in osteoblast cells.

Recently, one of the interferon-induced transmembrane (IFITM) family proteins, IFITM3, has become an important target for the activity against influenza A (H1N1) virus infection. In this protein, a post-translational modification by fatty acids covalently attached to cysteine, termed S-palmitoylation, plays a crucial role for the antiviral activity. IFITM3 possesses three cysteine residues for the S-palmitoylation in the first transmembrane (TM1) domain and in the cytoplasmic (CP) loop.

Lectin-like oxidized LDL receptor-1 is palmitoylated and internalizes ligands via caveolae/raft-dependent endocytosis.

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial scavenger receptor that is important for oxidized low-density lipoprotein uptake. LOX-1 functions as an oligomer; however, little is known about the oligomeric complex and ligand processing after recognition by LOX-1. Here, we found that LOX-1 recognized and internalized ligands through the caveolae/raft-dependent endocytosis pathway in human coronary artery endothelial cells.

Novel prognostic protein markers of resectable pancreatic cancer identified by coupled shotgun and targeted proteomics using formalin-fixed paraffin-embedded tissues.

Pancreatic cancer is among the most lethal malignancies worldwide. We aimed to identify novel prognostic markers by applying mass spectrometry (MS)-based proteomic analysis to formalin-fixed paraffin-embedded (FFPE) tissues. Resectable, node positive pancreatic ductal adenocarcinoma (PDAC) with poor (n = 4) and better (n = 4) outcomes, based on survival duration, with essentially the same clinicopathological backgrounds, and noncancerous pancreatic ducts (n = 5) were analyzed.

Nm23/nucleoside diphosphate kinase-A as a potent prognostic marker in invasive pancreatic ductal carcinoma identified by proteomic analysis of laser micro-dissected formalin-fixed paraffin-embedded tissue.

Background: Pancreatic cancer is among the most lethal malignancies worldwide. This study aimed to identify a novel prognostic biomarker, facilitating treatment selection, using mass spectrometry (MS)-based proteomic analysis with formalin-fixed paraffin-embedded (FFPE) tissue.

Results: The two groups with poor prognosis (n = 4) and with better prognosis (n = 4) had been carefully chosen among 96 resected cases of pancreatic cancer during 1998 to 2007 in Tohoku University Hospital.

Evaluation of mutagenicity and co-mutagenicity of strong static magnetic fields up to 13 Tesla in Escherichia coli deficient in superoxide dismutase.

Purpose: To evaluate the biological effects of static magnetic fields (SMFs) up to 13 Tesla (T), with respect to superoxide behavior, by determining the effect on mutagenicity in superoxide dismutase (SOD)-deficient Escherichia coli strain QC774, and its parental strain GC4468.

Materials And Methods: Experimental strains were exposed to a 5, 10, or 13T SMF for 24 h at 37°C in Luria-Bertani medium. To evaluate mutagenicity after SMF exposure, the mutation frequency in thymine synthesis genes was determined.