Novel ankle orthosis with elastomer-embedded flexible joint.

In this study, we propose a new ankle orthosis with elastomer-embedded flexible joints (EEFJ), composed of C-shaped springs and 3D-printed circular elastomer. This orthosis was designed to reduce burden on the tibialis anterior muscle (TA) and to achieve clearance between the tip of the toe and the ground. Fabrication method, strength testing, and gait analysis were conducted.

Upper limb training/assessment program using passive force controllable rehabilitation system.

Upper limb rehabilitation training for Hemiplegie patients has been conducted mainly by human therapists. Training methods and conditions depend strongly on their experience because of the wide range of individual differences between patients. The force control and sensing functions of rehabilitation robots are expected to be used for the qualitative assessment of next-generation computational rehabilitation.

Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis.

Trt14 from Aspergillus terreus is involved in unusual skeletal reconstruction during the biosynthesis of the fungal meroterpenoid terretonin. Detailed in vitro characterization revealed that this novel multifunctional enzyme catalyzes not only the D-ring expansion via intramolecular methoxy rearrangement, but also the hydrolysis of the expanded D-ring. The X-ray crystal structures of Trt14, in complex with substrate or product, and two Trt14 homologs, AusH and PrhC from Aspergillus nidulans and Penicillium brasilianum, respectively, indicated similar overall structures to those of the NTF2-like superfamily of enzymes, despite lacking sequence and functional similarities.

Naturally occurring Vpr inhibitors from medicinal plants of Myanmar.

Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication.

Five-year Survival Associated with Stage I Gastric Cancer after Resection of Early Recurrence at Nodal Station No. 14v: a Case Report.

The role of nodal station No. 14v (along the superior mesenteric vein) in lymphadenectomy for distal gastric cancer remains elusive. A 73-year-old woman underwent endoscopic submucosal dissection for gastric cancer, and was referred to our division for additional surgery because of pathologically non-curative resection.

Identification and Characterization of Daurichromenic Acid Synthase Active in Anti-HIV Biosynthesis.

Daurichromenic acid (DCA) synthase catalyzes the oxidative cyclization of grifolic acid to produce DCA, an anti-HIV meroterpenoid isolated from We identified a novel cDNA encoding DCA synthase by transcriptome-based screening from young leaves of The gene coded for a 533-amino acid polypeptide with moderate homologies to flavin adenine dinucleotide oxidases from other plants. The primary structure contained an amino-terminal signal peptide and conserved amino acid residues to form bicovalent linkage to the flavin adenine dinucleotide isoalloxazine ring at histidine-112 and cysteine-175. In addition, the recombinant DCA synthase, purified from the culture supernatant of transgenic , exhibited structural and functional properties as a flavoprotein.

Mechanistic Characterization of Two Chimeric Sesterterpene Synthases from Penicillium.

The products of two bifunctional fungal sesterterpene synthases (StTPS), with prenyl transferase (PT) and terpene synthase (TPS) domains from Penicillium, were structurally characterized and their mechanisms studied in detail by labeling experiments. A phylogenetic analysis of the TPS domains of the new and previously characterized enzymes revealed six distinct clades. Enzymes from the same clade catalyze a common initial cyclization step, which suggests the potential for structural predictions from amino acid sequences.

Prognostic Factors and Recurrence Pattern of Far-advanced Gastric Cancer with Pathologically-positive Para-aortic Lymph Nodes.

Background: The role of para-aortic lymph node (PALN) dissection for far-advanced gastric cancer is controversial in patients with clinical PALN positivity who have responded to chemotherapy.

Materials And Methods: We retrospectively analyzed long-term outcomes of patients with pathologically-positive PALNs who underwent radical gastrectomy.

Results: The 3- and 5-year overall survival (OS) rates of 65 pathologically PALN-positive patients who underwent PALN dissection (n=704) were 33.

Combinatorial Biosynthesis of (+)-Daurichromenic Acid and Its Halogenated Analogue.

Daurichromenic acid is a meroterpenoid with various pharmacological activities that is biosynthesized from grifolic acid in Rhododendron dauricum. Heterologous expression of grifolic acid synthases from Stachybotrys bisbyi and a daurichromenic acid synthase from R. dauricum in Aspergillus oryzae mediated three-step combinatorial biosynthesis of (+)-daurichromenic acid through enantioselective 6-endo-trig cyclization.

Spinal anesthesia increases the risk of venous thromboembolism in total arthroplasty: Secondary analysis of a J-PSVT cohort study on anesthesia.

Clinical guidance on the choice of anesthetic modality vis-à-vis the risk of perioperative venous thromboembolism (VTE) is largely lacking because of a paucity of recent evidence. A comparative effect of general anesthesia and neuraxial blockade on the perioperative incidence of VTE has not been well-investigated.We compared the effects of different types of anesthetic modalities on the risk of VTE after total hip arthroplasty (THA) and total knee arthroplasty (TKA).

2-Alkylquinolone alkaloid biosynthesis in the medicinal plant involves collaboration of two novel type III polyketide synthases.

2-Alkylquinolone (2AQ) alkaloids are pharmaceutically and biologically important natural products produced by both bacteria and plants, with a wide range of biological effects, including antibacterial, cytotoxic, anticholinesterase, and quorum-sensing signaling activities. These diverse activities and 2AQ occurrence in vastly different phyla have raised much interest in the biosynthesis pathways leading to their production. Previous studies in plants have suggested that type III polyketide synthases (PKSs) might be involved in 2AQ biosynthesis, but this hypothesis is untested.

Posttranslational isoprenylation of tryptophan in bacteria.

Posttranslational isoprenylation is generally recognized as a universal modification of the cysteine residues in peptides and the thiol groups of proteins in eukaryotes. In contrast, the quorum sensing peptide pheromone, the ComX pheromone, possesses a posttranslationally modified tryptophan residue, and the tryptophan residue is isoprenylated with either a geranyl or farnesyl group at the gamma position to form a tricyclic skeleton that bears a newly formed pyrrolidine, similar to proline. The post-translational dimethylallylation of two tryptophan residues of a cyclic peptide, kawaguchipeptin A, from cyanobacteria has also been reported.

Identification of Pyridinium with Three Indole Moieties as an Antimicrobial Agent.

A novel pyridinium with three indole moieties, tricepyridinium, was obtained from the culture of an Escherichia coli clone incorporating metagenomic libraries from the marine sponge Discodermia calyx. For the important structural elements of tricepyridinium to be investigated for antibacterial activity, tricepyridinium and its analogues were chemically synthesized. Tricepyridinium had antimicrobial activity, but not against E.

Intraoperative blood pressure changes during cemented versus uncemented bipolar hemiarthroplasty for displaced femoral neck fracture: a multi-center cohort study : The effect of bone cement for bipolar hemiarthroplasty in elderly patients.

Introduction: The purpose of this study was to compare the cemented bipolar hemiarthroplasty with uncemented about the change of intraoperative blood pressure and the incidence of major complications in elderly patients with femoral neck fracture.

Materials And Methods: This multiple center prospective cohort study included only patients with acute displaced femoral neck fracture (Garden stage III or IV). All patients were treated with cemented or uncemented bipolar hemiarthroplasty using modified Hardinge or Watson-Jones approach in the lateral decubitus position.

Characterization of Giant Modular PKSs Provides Insight into Genetic Mechanism for Structural Diversification of Aminopolyol Polyketides.

Polyketides form many clinically valuable compounds. However, manipulation of their biosynthesis remains highly challenging. An understanding of gene cluster evolution provides a rationale for reprogramming of the biosynthetic machinery.

Blood pressure control status and relationship between salt intake and lifestyle including diet in hypertensive outpatients treated at a general hospital.

The purpose of the present study was to investigate blood pressure (BP) control and salt intake in hypertensive outpatients treated at a general hospital and to examine the relationship between their lifestyles and amount of salt intake. Subjects comprised 429 hypertensive patients (206 males, 223 females, and average age of 71 ± 11 years). We estimated 24-hour salt excretion using spot urine samples and assessed lifestyle using a self-description questionnaire.

Role of atrial endothelial cells in the development of atrial fibrosis and fibrillation in response to pressure overload.

Background: Monocyte chemoattractant protein-1 (MCP-1)-mediated inflammatory mechanisms have been shown to play a crucial role in atrial fibrosis induced by pressure overload. In the present study, we investigated whether left atrial endothelial cells would quickly respond structurally and functionally to pressure overload to trigger atrial fibrosis and fibrillation.

Methods And Results: Six-week-old male Sprague-Dawley rats underwent suprarenal abdominal aortic constriction (AAC) or a sham operation.

Structural Insight into the Enzymatic Formation of Bacterial Stilbene.

In contrast to stilbene biosynthesis by type III polyketide synthase in plants, in bacteria stilbene is produced by the collaboration of two enzymes in Photorhabdus luminescens: the unusual β-ketosynthase StlD catalyzes the condensation of the β-ketoacyl starter with an α,β-unsaturated-acyl substrate (two C-C bond-forming reactions) to produce isopropylstyrylcyclohexanedione, which is subsequently converted to stilbene by the aromatase StlC. Here we report the in vitro characterizations of StlD and StlC, and the X-ray crystal structures of StlD. Interestingly, structure-based mutagenesis demonstrated that His302, within the conserved Cys-His-Asn triad, is not essential for the enzyme reaction, while Glu154 functions as a base-catalyst to activate the β-ketoacyl intermediate bound to the catalytic Cys126.

Metagenomic Analysis of the Sponge Discodermia Reveals the Production of the Cyanobacterial Natural Product Kasumigamide by 'Entotheonella'.

Sponge metagenomes are a useful platform to mine cryptic biosynthetic gene clusters responsible for production of natural products involved in the sponge-microbe association. Since numerous sponge-derived bioactive metabolites are biosynthesized by the symbiotic bacteria, this strategy may concurrently reveal sponge-symbiont produced compounds. Accordingly, a metagenomic analysis of the Japanese marine sponge Discodermia calyx has resulted in the identification of a hybrid type I polyketide synthase-nonribosomal peptide synthetase gene (kas).

Stereospecific prenylation of tryptophan by a cyanobacterial post-translational modification enzyme.

Prenylation is a key post-translational reaction to increase the structural diversity and bioactivity of peptides and proteins. Until now, only one post-translational modification enzyme, ComQ, has been identified to mediate the prenylation of a tryptophan residue in ribosomally synthesized peptides. Here, we report the in vitro characterization of KgpF, a novel prenyltransferase which transfers dimethylallyl moieties to tryptophan residues during kawaguchipeptin A biosynthesis.

Discovery of Key Dioxygenases that Diverged the Paraherquonin and Acetoxydehydroaustin Pathways in Penicillium brasilianum.

Paraherquonin (1), a fungal meroterpenoid produced by Penicillium brasilianum NBRC 6234, possesses a unique, highly congested hexacyclic molecular architecture. Here we identified the biosynthetic gene cluster of 1 (the prh cluster) and elucidated the pathway up to berkeleydione (2), which serves as the key intermediate for the biosynthesis of 1 as well as many other meroterpenoids. Interestingly, the nonheme iron and α-ketoglutarate-dependent dioxygenase PrhA constructs the cycloheptadiene moiety to afford 2 from preaustinoid A1 (6), probably via the homoallyl-homoallyl radical rearrangement.

Quassinoids: Viral protein R inhibitors from Picrasma javanica bark collected in Myanmar for HIV infection.

Viral protein R (Vpr) is an accessory protein that plays important roles in the viral pathogenesis of Human Immunodeficiency Virus-1 (HIV-1). An assay for anti-Vpr activity, using TREx-HeLa-Vpr cells, is a promising strategy to discover Vpr inhibitors. The anti-Vpr assay revealed that the CHCl3-soluble extract of Picrasma javanica bark possesses potent anti-Vpr activity.

Sulfoureido Lipopeptides from the Marine Sponge Discodermia kiiensis.

New N-sulfoureidylated lipopeptides, sulfolipodiscamides A-C (1-3), were isolated by gel filtration chromatography of the n-butanol fraction of the marine sponge Discodermia kiiensis. By extensive NMR analyses and high-resolution mass spectrometry, the structures of 1-3 were elucidated as having an unprecedented N-sulfoureidyl group on the d-citrulline residue, a distinct feature that was not found in the structurally related lipodiscamides A-C (4-6), derived from the ether fraction of the same sponge. Furthermore, the absolute configurations of 1-3 were confirmed by comparisons of the HPLC retention times of the hydrolytic products and the corresponding authentic lipodiscamides.