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1

Autoradiography of phosphatidyl choline  

SciTech Connect

Saturated choline phosphatides are extracted during conventional tissue processing for electron microscopy. To facilitate autoradiographic subcellular localization of arrhythmogenic myocardial phospholipids, we evaluated tissue processing procedures for preservation of saturated phosphatidyl choline (PC). Suspensions, of a murine plasmacytoma were incubated with negative, unilamellar liposomes containing 14C-choline-labeled PC or 14C-1-palmitate dipalmitoyl PC. Extraction of radioactivity was monitored at each processing step by liquid scintillation spectrometry. Conventional fixation with glutaraldehyde and osmium tetroxide followed by acetone dehydration and Spurr's plastic embedding led to extraction of nearly all radioactivity. However, treatment of cells with 1.5% tannic acid after glutaraldehyde but before osmium tetroxide fixation preserved 93.1 +/- .6% of 14C-choline-labeled PC. Virtually identical results were obtained with dipalmitoyl PC. Autoradiography demonstrated no significant translocation of labeled PC from plasmacytoma cells to unlabeled avian erythrocytes, mixed in equal proportions after fixation but before dehydration and embedding.

Saffitz, J.E.; Gross, R.W.; Williamson, J.R.; Sobel, B.E.

1981-03-01

2

Preparation of Phosphatidylated Terpenes via Phospholipase D-Mediated Transphosphatidylation  

Microsoft Academic Search

Terpenes such as geraniol, geranylgeraniol, farnesol, and phytol are known as functional compounds which exhibit anticancer\\u000a effects and activate nuclear receptors. For the application of functional terpenes in various fields, including the cosmetic\\u000a and food industries, we attempted to synthesize phosphatidylated terpenes (terpene-PLs) by using phospholipase D (PLD). Transphosphatidylation\\u000a of phosphatidylcholine with terpenes was carried out using PLD in a

Yukihiro Yamamoto; Masashi Hosokawa; Hideyuki Kurihara; Kazuo Miyashita

2008-01-01

3

INTERACTION OF GENTAMICIN WITH PHOSPHATIDYL SERINE IN HOMOGENOUS AND PHASE SEPARATED MONO AND BILAYER FILMS  

Microsoft Academic Search

Aminoglycoside are antibiotics used to treat serious infections caused by aerobic gram-negative bacilli. These antibiotics and especially Gentamicin possess aggressive nephro- and ototoxicity. Gentamicin accumulates in the renal cortex before renal failure. Furthermore calcium reduces Gentamicin binding to cell membranes and dietary calcium reduces Gentamicin nephrotoxicity. Possible molecular mechanism underlying nephro- and ototoxicity is kidney cell membrane fusion, this event

Georgi D. Georgiev; Georgi A. Georgiev; Z. Lalchev

4

Mercury Induces the Externalization of Phosphatidyl-Serine in Human Renal Proximal Tubule (HK-2) Cells  

PubMed Central

The underlying mechanism for the biological activity of inorganic mercury is believed to be the high affinity binding of divalent mercuric cations to thiols of sulfhydryl groups of proteins. A comprehensive analysis of published data indicates that inorganic mercury is one of the most environmentally abundant toxic metals, is a potent and selective nephrotoxicant that preferentially accumulates in the kidneys, and is known to produce cellular injury in the kidneys. Binding sites are present in the proximal tubules, and it is in the epithelial cells of these tubules that toxicants such as inorganic mercury are reabsorbed. This can affect the enzymatic activity and the structure of various proteins. Mercury may alter protein and membrane structure and function in the epithelial cells and this alteration may result in long term residual effects. This research was therefore designed to evaluate the dose-response relationship in human renal proximal tubule (HK-2) cells following exposure to inorganic mercury. Cytotoxicity was evaluated using the MTT assay for cell viability. The Annexin-V assay was performed by flow cytometry to determine the extent of phosphatidylserine externalization. Cells were exposed to mercury for 24 hours at doses of 0, 1, 2, 3, 4, 5, and 6 ?g/mL. Cytotoxicity experiments yielded a LD50 value of 4.65 ± 0.6 ?g/mL indicating that mercury is highly toxic. The percentages of cells undergoing early apoptosis were 0.70 ± 0.03%, 10.0 ± 0.02%, 11.70 ± 0.03%, 15.20 ± 0.02%, 16.70 ± 0.03%, 24.20 ±0.02%, and 25.60 ± 0.04% at treatments of 0, 1, 2, 3, 4, 5, and 6 ?g/mL of mercury respectively. This indicates a dose-response relationship with regard to mercury-induced cytotoxicity and the externalization of phosphatidylserine in HK-2 cells. PMID:17617677

Sutton, Dwayne J.; Tchounwou, Paul B.

2007-01-01

5

COBRA, an Arabidopsis Extracellular Glycosyl-Phosphatidyl Inositol-Anchored Protein, Specifically Controls Highly  

E-print Network

COBRA, an Arabidopsis Extracellular Glycosyl-Phosphatidyl Inositol-Anchored Protein, Specifically of the orientation of cell expansion. COBRA (COB) has been identified previously as a potential regulator

Baskin, Tobias

6

Facile Synthesis of Phosphatidyl Saccharides for Preparation of Anionic Nanoliposomes with Enhanced Stability  

PubMed Central

Physical stability during storage and against processing such as dehyration/rehydration are the cornerstone in designing delivery vehicles. In this work, mono-, di- and tri-saccharides were enzymatically conjugated to phosphatidyl group through a facile approach namely phospholipase D (PLD) mediated transphosphatidylation in a biphasic reaction system. The purified products were structurally identified and the connectivities of carbohydrate to phosphatidyl moiety precisely mapped by 1H, 31P, 13C NMR pulse sequences and LC-ESI-FTMS. The synthetic phosphatidyl saccharides were employed as the sole biomimetic component for preparation of nanoliposomes. It was found that the critical micelle concentration (CMC) of phosphatidyl saccharides increases as more bulky sugar moiety (mono- to tri-) is introduced. Phosphatidyl di-saccharide had the largest membrane curvature. In comparison to the zwitterionic phosphatidylcholine liposome, all phosphatidyl saccharides liposomes are anionic and demonstrated significantly enhanced stability during storage. According to the confocal laser scan microscopy (CLSM) and atom force microscopy (AFM) analyses, the nanoliposomes formed by the synthetic phosphatidyl saccharides also show excellent stability against dehydration/rehydration process in which most of the liposomal structures remained intact. The abundance hydroxyl groups in the saccharide moieties might provide sufficient H-bondings for stabilization. This work demonstrated the synthesized phosphatidyl saccharides are capable of functioning as enzymatically liable materials which can form stable nanoliposomes without addition of stabilizing excipients. PMID:24069243

Song, Shuang; Cheong, Ling-Zhi; Falkeborg, Mia; Liu, Lei; Dong, Mingdong; Jensen, Henrik Max; Bertelsen, Kresten; Thorsen, Michael; Tan, Tianwei; Xu, Xuebing; Guo, Zheng

2013-01-01

7

Nuclear magnetic resonance and thermal studies of drug doped dipalmitoyl phosphatidyl choline-H 2 O systems  

Microsoft Academic Search

The influence of the sulfone drugs, diamino diphenyl sulfone and diamino monophenyl sulfone on the phase transitions and dynamics\\u000a of dipalmitoyl phosphatidyl choline-H2O\\/D2O vesicles have been investigated using differential scanning calorimetry and nuclear magnetic resonance. Our results show\\u000a that diamino diphenyl sulfone interacts quite strongly with the headgroups of dipalmitoyl phosphatidyl choline whereas the\\u000a diamino monophenyl sulfone-dipalmitoyl phosphatidyl choline interaction

K. Usha Deniz; P. S. Parvathanathan; Geeta Datta; C. L. Khetrapal; K. V. Ramanathan; N. Suryaprakash; S. Raghotama

1990-01-01

8

Phosphatidyl derivative of hydroxytyrosol. In vitro intestinal digestion, bioaccessibility, and its effect on antioxidant activity.  

PubMed

Intestinal digestion of phosphatidyl derivatives of HT (PHT) and its bioaccessibility under in vitro conditions was performed. First, an in vitro intestinal digestion model for phospholipids was developed. The impact of digestion in the antioxidant ability of PHT was also assayed. PHT was progressively hydrolyzed to lyso-PHT. However, digestion was slower than the phospholipid control. Nevertheless, most hydrolysis products were found at the micellar phase fraction, meaning a high bioaccessibility. Either PHT or digested PHT showed lower antioxidant activity than HT. However, PHT improved its antioxidant ability after digestion, likely related to lyso-PHT. As a summary, the synthetic phosphatidyl derivative of HT as PHT is recognized by phospholipases during simulation of intestinal digestion, although less efficiently than analogous phospholipids. Nevertheless, taking into account the bioaccessibility and the antioxidant activity of digested PHT, the potential of carriers of HT under the form of phospholipids might be of interest. PMID:25255083

Martin, Diana; Moran-Valero, Maria I; Casado, Víctor; Reglero, Guillermo; Torres, Carlos F

2014-10-01

9

Bilobalide regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway  

Microsoft Academic Search

Bilobalide (BB) is a sesquiterpenoid extracted from Ginkgo biloba leaves. An increasing number of studies have demonstrated its neuroprotective effects. The neuroprotective mechanisms may be associated with modulation of intracellular signaling cascades such as the phosphatidyl inositol 3-kinase (PI3K) pathway. Using differentiated SH-SY5Y cells, this study investigated whether BB modulation of intracellular signaling pathways, such as the protein kinase C

Chun Shi; Fengming Wu; Jie Xu; Juntao Zou

2011-01-01

10

The relation of carnitine to the formation of phosphatidyl-?-methylcholine by Tenebrio molitor L. Larvae  

Microsoft Academic Search

Results demonstrate thatTenebrio molitor larvae can incorporate ?-methylcholine into their phospholipids and that ?-methylcholine spares larval choline. Phosphatidyl-?-methylcholine\\u000a is detected when larvae are reared on a diet in which choline is replaced by ?-methylcholine. Results indicate that, in contrast\\u000a to housefly and blowfly larvae,Tenebrio larvae do not metabolize carnitine to ?-methylcholine. The same phospholipids were found with all rearing conditions.

L. L. Bieber; R. E. Monroe

1969-01-01

11

Molecular Structure of Serine  

NSDL National Science Digital Library

Serine is required for the metabolism of fat, tissue growth, and a healthy immune system. It assists in the production of immunoglobulins and antibodies. Some of its derivatives such as ethanolamine are important components of the phospholipids found in biological membranes. Serine is found in meat and dairy products, wheat gluten, peanuts, and soy products. It is not clear how toxic this substance can be, although it is known that high levels of serine may cause immune suppression and psychological symptoms such as cerebral allergies.

2002-08-21

12

Serine metabolism in Lactobacillus plantarum.  

PubMed

This study investigated the metabolism of (L-) serine by Lactobacillus plantarum B3089 isolated from cheese. Serine was deaminated by growing cells to ammonia with the corresponding formation of acetate and formate. Serine was also deaminated by non-growing cells to ammonia but with the formation of acetate only (no production of formate). Phosphoserine and threonine were not catabolised. It is proposed that serine was deaminated by serine dehydratase (deaminase) to ammonia and pyruvate. Pyruvate was further catabolised predominantly to acetate, carbon dioxide and formate in growing cells, catalysed by pyruvate-formate lyase and pyruvate oxidase; some of the pyruvate was converted to acetoin. In non-growing cells, however, pyruvate-formate lyase was inactive and pyruvate oxidase degraded the pyruvate to acetate and carbon dioxide. Serine dehydratase activity could not be detected in cell-free extracts, presumably because of enzyme instability. The growth of L. plantarum was neither enhanced nor stimulated by serine under the current conditions. Whereas there was little difference in serine utilisation between pH 7.0 and pH 5.8, serine utilisation was decreased by 30% at pH 5.0. NaCl of up to 4% (w/v) concentration had little effect on serine utilisation. Serine had no impact on lactose metabolism. Lactose was fermented mainly to lactate (73%) with the remainder converted to an unidentified polysaccharide (27%). PMID:14623392

Liu, S-Q; Holland, R; McJarrow, P; Crow, V L

2003-12-31

13

Synthesis and Structural Characterization of Three Unique Helicobacter pylori ?-Cholesteryl Phosphatidyl Glucosides.  

PubMed

Steryl glycosides produced by bacteria play important biological roles in the evasion and modulation of host immunity. Step-economical syntheses of three cholesteryl-6-O-phosphatidyl-?-D-glucopyranosides (?CPG) unique to Helicobacter pylori have been achieved. The approach relies upon regioselective deprotection of per-O-trimethylsilyl-?-D-cholesterylglucoside at C6 followed by phosphoramidite coupling. Global TMS ether deprotection in the presence of oxygen and subsequent deprotection of the cyano ethyl phosphoester afforded the target compounds in 16-21?% overall yield starting from D-glucose. The structures of these natural products were determined using a combination of 2D NMR methods and mass spectrometry. These robust synthesis and characterization protocols provide analogues to facilitate glycolipidomic profiling and biological studies. PMID:25195783

Nguyen, Huy Q; Davis, Ryan A; Gervay-Hague, Jacquelyn

2014-12-01

14

SHORT COMMUNICATION Chiral Enrichment of Serine  

E-print Network

by means of electrospray and sonic spray ionization of aqueous solutions of d3-L-serine (108 Da) and D-serine-serine and D-serine after APCI-MS analysis. Both of these experiments showed comparable results, suggesting

Clemmer, David E.

15

The ps in therapeutics.  

PubMed

The decline of ps (pharmaceutical sciences) content and emphasis, especially pharmaceutics in pharmacy education, has been followed by pharmacy practice journals since the final BS to PharmD degree transition of 1990-2000. The particular deficit of drug compatibility, compounding, packaging, reactivity, solubility, stability and storage instruction, and information was a major impetus for the 1996 premier of the International journal of pharmaceutical compounding and the 2011 introduction of the Science and technology for the hospital pharmacist electronic newsletter. The four ps examples provided in this article to corroborate the introduction to Vol. 1, No. 2 of the Science and technology for the hospital pharmacist, which featured Dr. Richard Penna's prudent reflection that biological, chemical, and physical ps facts and knowledge are vital to patient care. PMID:23050313

Newton, David W

2012-01-01

16

Serine proteinase inhibitors in arthropod immunity  

Microsoft Academic Search

Arthropod hemolymph contains proteins with serine proteinase inhibitory activity. These inhibitors may exist in plasma or in hemocyte granules. Serine proteinase inhibitors from the Kazal, Kunitz, ?-macroglobulin, and serpin families have been identified in arthropod hemolymph and have been characterized biochemically. Two new families of low molecular weight serine proteinase inhibitors have recently been discovered: one in silkworms (the Bombyx

Michael R. Kanost

1999-01-01

17

p73 regulates serine biosynthesis in cancer.  

PubMed

Activation of serine biosynthesis supports growth and proliferation of cancer cells. Human cancers often exhibit overexpression of phosphoglycerate dehydrogenase (PHGDH), the metabolic enzyme that catalyses the reaction that diverts serine biosynthesis from the glycolytic pathway. By refueling serine biosynthetic pathways, cancer cells sustain their metabolic requirements, promoting macromolecule synthesis, anaplerotic flux and ATP. Serine biosynthesis intersects glutaminolysis and together with this pathway provides substrates for production of antioxidant GSH. In human lung adenocarcinomas we identified a correlation between serine biosynthetic pathway and p73 expression. Metabolic profiling of human cancer cell line revealed that TAp73 activates serine biosynthesis, resulting in increased intracellular levels of serine and glycine, associated to accumulation of glutamate, tricarboxylic acid (TCA) anaplerotic intermediates and GSH. However, at molecular level p73 does not directly regulate serine metabolic enzymes, but transcriptionally controls a key enzyme of glutaminolysis, glutaminase-2 (GLS-2). p73, through GLS-2, favors conversion of glutamine in glutamate, which in turn drives the serine biosynthetic pathway. Serine and glutamate can be then employed for GSH synthesis, thus the p73-dependent metabolic switch enables potential response against oxidative stress. In knockdown experiment, indeed, TAp73 depletion completely abrogates cancer cell proliferation capacity in serine/glycine-deprivation, supporting the role of p73 to help cancer cells under metabolic stress. These findings implicate p73 in regulation of cancer metabolism and suggest that TAp73 influences glutamine and serine metabolism, affecting GSH synthesis and determining cancer pathogenesis. PMID:24186203

Amelio, I; Markert, E K; Rufini, A; Antonov, A V; Sayan, B S; Tucci, P; Agostini, M; Mineo, T C; Levine, A J; Melino, G

2014-10-16

18

Metabolism of the neuromodulator d -serine  

Microsoft Academic Search

Over the past years, accumulating evidence has indicated that d-serine is the endogenous ligand for the glycine-modulatory binding site on the NR1 subunit of N-methyl-d-aspartate receptors in various brain areas. d-Serine is synthesized in glial cells and neurons by the pyridoxal-5? phosphate-dependent enzyme serine racemase, and it is\\u000a released upon activation of glutamate receptors. The cellular concentration of this novel

Loredano Pollegioni; Silvia Sacchi

2010-01-01

19

Levels of d-serine in the brain and peripheral organs of serine racemase ( Srr) knock-out mice  

Microsoft Academic Search

d-Serine, an endogenous co-agonist of the N-methyl-d-aspartate (NMDA) receptor, plays an important role in mammalian brain neurotransmission, via the NMDA receptor. d-Serine is synthesized from l-serine by the pyridoxal-5? phosphate-dependent enzyme serine racemase (SRR), and d-serine is metabolized by d-amino acid oxidase (DAAO). In this study, we measured levels of the neurotransmission related amino acids, d-serine, l-serine, glycine, glutamine and

Mao Horio; Mami Kohno; Yuko Fujita; Tamaki Ishima; Ran Inoue; Hisashi Mori; Kenji Hashimoto

2011-01-01

20

An update on serine deficiency disorders.  

PubMed

Serine deficiency disorders are caused by a defect in one of the three synthesising enzymes of the L-serine biosynthesis pathway. Serine deficiency disorders give rise to a neurological phenotype with psychomotor retardation, microcephaly and seizures in newborns and children or progressive polyneuropathy in adult patients. There are three defects that cause serine deficiency of which 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, the defect affecting the first step in the pathway, has been reported most frequently. The other two disorders in L-serine biosynthesis phosphoserine aminotransferase (PSAT) deficiency and phosphoserine phosphatase (PSP) deficiency have been reported only in a limited number of patients. The biochemical hallmarks of all three disorders are low concentrations of serine in cerebrospinal fluid and plasma. Prompt recognition of affected patients is important, since serine deficiency disorders are treatable causes of neurometabolic disorders. The use of age-related reference values for serine in CSF and plasma can be of great help in establishing a correct diagnosis of serine deficiency, in particular in newborns and young children. PMID:23463425

van der Crabben, S N; Verhoeven-Duif, N M; Brilstra, E H; Van Maldergem, L; Coskun, T; Rubio-Gozalbo, E; Berger, R; de Koning, T J

2013-07-01

21

G/sub o/ protein of fat cells: role in hormonal regulation of agonist-stimulated phosphatidyl inositol breakdown  

SciTech Connect

Incubating rat fat cell membranes in the presence of (/sup 32/P)NAD/sup +/ and pertussis toxin (PT) results in the ADP-ribosylation of two peptides (M/sub r/ = 41,000 and 40,000). The 41,000-M/sub r/ peptide is the inhibitory G-protein of adenylate cyclase (G/sub i/). The 40,000-M/sub r/ peptide radiolabeled in the presence of (/sup 32/P)NAD/sup +/ and PT has been purified from rabbit heart and bovine brain, but has not been identified uniformly in membranes of fat cells. Two rabbit polyclonal antisera raised against the alpha-subunit of bovine brain G/sub o/ were used to probe the nature of the 40,000-M/sub r/ peptide in rat fat cell membranes that had been separated by gel electrophoresis in the presence of sodium dodecyl sulfate and transferred electrophoretically to nitrocellulose. Both antisera specific for the alpha-subunit of G/sub o/ recognized the M/sub r/ = 40,000 peptide of fat cells that is ADP-ribosylated in the presence of PT. PT treatment of rat fat cells blocks epinephrine-stimulated inositol 1,4,5 trisphosphate (IP/sub 3/) generation. The inhibition of IP/sub 3/ generation by PT suggests a role for either G/sub i/ or G/sub o/ in receptor-mediated phosphatidyl inositol breakdown in the rat fat cell.

Rapiejko, P.J.; Northup, J.K.; Malbon, C.C.

1986-05-01

22

D-serine and serine racemase are present in the vertebrate retina and contribute to the physiological  

E-print Network

D-serine and serine racemase are present in the vertebrate retina and contribute for Biological Studies, La Jolla, CA, and approved April 11, 2003 (received for review November 19, 2002) D-serine detected D-serine and its synthesizing enzyme, serine racemase, in the retinas of several vertebrate

Newman, Eric A.

23

L-serine synthesis in the central nervous system: a review on serine deficiency disorders.  

PubMed

The de novo synthesis of the amino acid L-serine plays an essential role in the development and functioning of the central nervous system (CNS). L-serine displays many metabolic functions during different developmental stages; among its functions providing precursors for amino acids, protein synthesis, nucleotide synthesis, neurotransmitter synthesis and L-serine derived lipids. Patients with congenital defects in the L-serine synthesizing enzymes present with severe neurological abnormalities and underscore the importance of this synthetic pathway. In this review, we will discuss the cellular functions of the L-serine pathway, structure and enzymatic properties of the enzymes involved and genetic defects associated with this pathway. PMID:19963421

Tabatabaie, L; Klomp, L W; Berger, R; de Koning, T J

2010-03-01

24

Metabolism of the neuromodulator D-serine.  

PubMed

Over the past years, accumulating evidence has indicated that D-serine is the endogenous ligand for the glycine-modulatory binding site on the NR1 subunit of N-methyl-D-aspartate receptors in various brain areas. D-Serine is synthesized in glial cells and neurons by the pyridoxal-5' phosphate-dependent enzyme serine racemase, and it is released upon activation of glutamate receptors. The cellular concentration of this novel messenger is regulated by both serine racemase isomerization and elimination reactions, as well as by its selective degradation catalyzed by the flavin adenine dinucleotide-containing flavoenzyme D-amino acid oxidase. Here, we present an overview of the current knowledge of the metabolism of D-serine in human brain at the molecular and cellular levels, with a specific emphasis on the brain localization and regulatory pathways of D-serine, serine racemase, and D-amino acid oxidase. Furthermore, we discuss how D-serine is involved with specific pathological conditions related to N-methyl-D-aspartate receptors over- or down-regulation. PMID:20195697

Pollegioni, Loredano; Sacchi, Silvia

2010-07-01

25

Glial transport of the neuromodulator d-serine  

Microsoft Academic Search

d-Serine is an endogenous agonist of NMDA receptors that occurs in astrocytes in gray matter areas of the brain. d-Serine is synthesized from l-serine by the activity of a glial enriched serine racemase, but little is known on the properties of d-serine transport and factors regulating its synaptic concentration. In the present report we characterize the transport of d-serine in

Cátia S. Ribeiro; Marcelo Reis; Rogério Panizzutti; Joari de Miranda; Herman Wolosker

2002-01-01

26

Studies on dodecyl betainate in combination with its degradation products or with phosphatidyl choline-phase behavior and hemolytic activity.  

PubMed

Surface active betaine esters contain a hydrolysable bond and give naturally occurring products (fatty alcohol and the amino acid betaine) on degradation. They are therefore interesting candidates for use as cationic surfactants in pharmaceutical applications. In this work the phase behavior of two systems of relevance for the utilization of dodecyl betainate as a pharmaceutical excipient is studied, namely dodecyl betainate/dodecanol/betaine hydrochloride/D2O and dodecyl betainate/phosphatidyl choline (PC)/ethanol/D2O. The techniques used for phase characterisation were 2H NMR measured on the solvent, small angle X-ray spectroscopy and optical microscopy. Dilute dodecyl betainate/PC dispersions were characterized using laser diffraction. It is shown that introduction of relatively small amounts of the hydrolysis products of dodecyl betainate, i.e., dodecanol and betaine (used in the form of betaine hydrochloride), has a strong effect on the phase behavior of the binary dodecyl betainate/D2O system. The degradation products change the average curvature of the surfactant film so that, instead of a hexagonal phase at concentrations above the micellar phase, a probably defective, lamellar phase seems to form. The dodecyl betainate/PC/ethanol/D2O system shows a large region of a highly swelling lamellar phase. Dispersions of dodecyl betainate/PC/ethanol in water can be prepared with low energy input; i.e., the preconcentrate can be regarded as a self-dispersing solution. Introduction of dodecyl betainate and its degradation products does not impair the ability of PC to form vesicles. Experiments for evaluating the toxicity of surface active betaine esters to erythrocytes were also performed. There are indications that the hemolytic activity of dodecyl betainate is lower than that of the stable surfactant tetradecyltrimethylammonium chloride, which has similar critical micelle concentration. A combination of dodecyl betainate and PC gives very low hemolytic activity. PMID:15450470

Lundberg, D; Ljusberg-Wahren, H; Norlin, A; Holmberg, K

2004-10-15

27

Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer's disease and tauopathies.  

PubMed

Neuronal insulin signaling abnormalities have been associated with Alzheimer's disease (AD). However, the specificity of this association and its underlying mechanisms have been unclear. This study investigated the expression of abnormal serine phosphorylation of insulin receptor substrate 1 (IRS1) in 157 human brain autopsy cases that included AD, tauopathies, ?-synucleinopathies, TDP-43 proteinopathies, and normal aging. IRS1-pS(616), IRS1-pS(312) and downstream target Akt-pS(473) measures were most elevated in AD but were also significantly increased in the tauopathies: Pick's disease, corticobasal degeneration and progressive supranuclear palsy. Double immunofluorescence labeling showed frequent co-expression of IRS1-pS(616) with pathologic tau in neurons and dystrophic neurites. To further investigate an association between tau and abnormal serine phosphorylation of IRS1, we examined the presence of abnormal IRS1-pS(616) expression in pathological tau-expressing transgenic mice and demonstrated that abnormal IRS1-pS(616) frequently co-localizes in tangle-bearing neurons. Conversely, we observed increased levels of hyperphosphorylated tau in the high-fat diet-fed mouse, a model of insulin resistance. These results provide confirmation and specificity that abnormal phosphorylation of IRS1 is a pathological feature of AD and other tauopathies, and provide support for an association between insulin resistance and abnormal tau as well as amyloid-?. PMID:25107476

Yarchoan, Mark; Toledo, Jon B; Lee, Edward B; Arvanitakis, Zoe; Kazi, Hala; Han, Li-Ying; Louneva, Natalia; Lee, Virginia M-Y; Kim, Sangwon F; Trojanowski, John Q; Arnold, Steven E

2014-11-01

28

Purification of Serine Racemase: Biosynthesis of the Neuromodulator D-Serine  

Microsoft Academic Search

High levels of D-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate receptors. In glial cultures of rat cerebral cortex, D-serine is enriched in type II astrocytes and is released upon stimulation with agonists of non-N-methyl-D-aspartate glutamate receptors. The high levels of D-serine in discrete areas of rat brain imply

Herman Wolosker; Kevin N. Sheth; Masaaki Takahashi; Jean-Pierre Mothet; Roscoe O. Brady Jr.; Christopher D. Ferris; Solomon H. Snyder

1999-01-01

29

STAT3 Phosphorylation at Tyrosine 705 and Serine 727 Differentially Regulates Mouse ESC Fates  

PubMed Central

STAT3 can be transcriptionally activated by phosphorylation of its tyrosine 705 or serine 727 residue. In mouse embryonic stem cells (mESCs), leukemia inhibitory factor (LIF) signaling maintains pluripotency by inducing JAK-mediated phosphorylation of STAT3 Y705 (pY705). However, the function of phosphorylated S727 (pS727) in mESCs remains unclear. In this study, we examined the roles of STAT3 pY705 and pS727 in regulating mESC identities, using a small molecule-based system to post-translationally modulate the quantity of transgenic STAT3 in STAT3?/? mESCs. We demonstrated that pY705 is absolutely required for STAT3-mediated mESC self-renewal, while pS727 is dispensable, serving only to promote proliferation and optimal pluripotency. S727 phosphorylation is regulated directly by fibroblast growth factor/Erk signaling and crucial in the transition of mESCs from pluripotency to neuronal commitment. Loss of S727 phosphorylation resulted in significantly reduced neuronal differentiation potential, which could be recovered by a S727 phosphorylation mimic. Moreover, loss of pS727 sufficed LIF to reprogram epiblast stem cells to naïve pluripotency, suggesting a dynamic equilibrium of STAT3 pY705 and pS727 in the control of mESC fate. PMID:24302476

Huang, Guanyi; Yan, Hexin; Ye, Shoudong; Tong, Chang; Ying, Qi-Long

2014-01-01

30

Serine racemase: Activation by glutamate neurotransmission via glutamate receptor interacting  

E-print Network

racemase (SR), localized to astrocytic glia that ensheathe synapses, converts L-serine to D-serine physiologically binds SR, augmenting SR activity and D-serine release. GRIP infection of neonatal mouse cerebellum in vivo enhances granule cell migration. Selective deg- radation of D-serine by D-amino acid oxidase

Newman, Eric A.

31

D-serine increases adult hippocampal neurogenesis  

PubMed Central

Adult hippocampal neurogenesis results in the continuous formation of new neurons and is a process of brain plasticity involved in learning and memory. The neurogenic niche regulates the stem cell proliferation and the differentiation and survival of new neurons and a major contributor to the neurogenic niche are astrocytes. Among the molecules secreted by astrocytes, D-serine is an important gliotransmitter and is a co-agonist of the glutamate, N-methyl-D-aspartate (NMDA) receptor. D-serine has been shown to enhance the proliferation of neural stem cells in vitro, but its effect on adult neurogenesis in vivo is unknown. Here, we tested the effect of exogenous administration of D-serine on adult neurogenesis in the mouse dentate gyrus. We found that 1 week of treatment with D-serine increased cell proliferation in vivo and in vitro and increased the density of neural stem cells and transit amplifying progenitors. Furthermore, D-serine increased the survival of newborn neurons. Together, these results indicate that D-serine treatment resulted in the improvement of several steps of adult neurogenesis in vivo. PMID:24009551

Sultan, Sebastien; Gebara, Elias G.; Moullec, Kristell; Toni, Nicolas

2013-01-01

32

The Origin and Turnover of D-Serine in Brain  

Microsoft Academic Search

The origin of D-serine was investigated using microdialysis probes to administer radiolabeled glucose, glycine, and L-serine directly into rat brain. In these experiments the labeling of D-serine was found to be determined only by the radioactivity present in the L-serine pool, regardless of the precursor employed, indicating that L-serine is the direct precursor of the D-isomer. Its rate of synthesis

David S. Dunlop; Amos Neidle

1997-01-01

33

Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model .  

E-print Network

??N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence ofD-serine, synthesized from L-serine by a pyridoxal 5 -phosphate-dependent serine racemase (SR). D-serine levels can be lowered… (more)

Laurido, Claudio

2012-01-01

34

Reduced d-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients  

Microsoft Academic Search

Several lines of evidence suggest that d-serine, an endogenous agonist of the glycine site on the NMDA receptors, might play a role in the pathophysiology of schizophrenia. The purpose of this study was to determine whether levels of d- and l-serine or d-serine ratio (d-serine\\/total serine) in cerebrospinal fluid (CSF) were altered in first episode and drug-naive schizophrenic patients. The

Kenji Hashimoto; Göran Engberg; Eiji Shimizu; Conny Nordin; Leif H. Lindström; Masaomi Iyo

2005-01-01

35

Induction of serine racemase expression and D-serine release from microglia by amyloid ?-peptide  

Microsoft Academic Search

BACKGROUND: Roles for excitotoxicity and inflammation in Alzheimer's disease have been hypothesized. Proinflammatory stimuli, including amyloid ?-peptide (A?), elicit a release of glutamate from microglia. We tested the possibility that a coagonist at the NMDA class of glutamate receptors, D-serine, could respond similarly. METHODS: Cultured microglial cells were exposed to A?. The culture medium was assayed for levels of D-serine

Sheng-Zhou Wu; Angela M Bodles; Mandy M Porter; W Sue T Griffin; Anthony S Basile; Steven W Barger

2004-01-01

36

BAP1 is phosphorylated at serine 592 in S-phase following DNA damage.  

PubMed

The human BAP1 deubiquitinating enzyme is a chromatin-bound transcriptional regulator and tumor suppressor. BAP1 functions in suppressing cell proliferation, yet its role in the DNA damage response pathway is less understood. In this study we characterized DNA damage-induced phosphorylation of BAP1 at serine 592 (pS592) and the cellular outcomes of this modification. In contrast to the majority of BAP1, pS592-BAP1 is predominantly dissociated from chromatin. Our findings support a model whereby stress induced phosphorylation functions to displace BAP1 from specific promoters. We hypothesize that this regulates the transcription of a subset of genes involved in the response to DNA damage. PMID:24211834

Eletr, Ziad M; Yin, Luming; Wilkinson, Keith D

2013-12-11

37

D-serine in the developing human central nervous system.  

PubMed

To elucidate the role of D-serine in human central nervous system, we analyzed D-serine, L-serine, and glycine concentrations in cerebrospinal fluid of healthy children and children with a defective L-serine biosynthesis (3-phosphoglycerate dehydrogenase deficiency). Healthy children showed high D-serine concentrations immediately after birth, both absolutely and relative to glycine and L-serine, declining to low values at infancy. D-Serine concentrations were almost undetectable in untreated 3-phosphoglycerate dehydrogenase-deficient patients. In one patient treated prenatally, D-serine concentration was nearly normal at birth and the clinical phenotype was normal. These observations suggest a pivotal role for D-serine in normal and aberrant human brain development. PMID:17068790

Fuchs, Sabine A; Dorland, Lambertus; de Sain-van der Velden, Monique G; Hendriks, Margriet; Klomp, Leo W J; Berger, Ruud; de Koning, Tom J

2006-10-01

38

ps  

E-print Network

non-zero complex number has infinitely many arguments: w does not change. if we add .... powers of all N-th roots of unity is N when m is divisible by N and zero .... possibility of detecting Soviet underground nuclear tests by seismic observa-.

39

ps  

E-print Network

Cartan's theory deals ... gives a new characterization of T(r) for n = 1: T(r) = 1 .... proving the SMT can be also extended to holomorphic curves (Ahlfors, 1939); this proof is much more ... morphes données, Mathematica (Clij) 7 (1933) 5–31.

40

ps  

E-print Network

Apr 15, 2003 ... Given a parameterized space of square matrices, the associated set of ... This work was stimulated by the Gibbs Lecture of Sir Michael Berry given at ..... we again get a spectral line bundle over B , but this time the bundle is ...

2003-04-15

41

ps  

E-print Network

Sep 7, 2014 ... In this case, the line element of the metric has the global representa- ... to single out geodesic quadrilaterals in the construction of Schönflies and .... standard Young tableau (SSYT) is a filling of such a diagram with positive.

2014-09-07

42

The expanding diversity of serine hydrolases  

PubMed Central

Summary Serine hydrolases use a hydroxyl of a serine, assisted by one or more other residues, to cleave peptide bonds. They belong to several different families whose general mechanism is well known. However, the subtle structural differences that have recently been observed across a variety of families shed light on their functional diversity, including variations in mechanism of action, differences in the modes of substrate binding, and substrate-assisted orientation of catalytic residues. Of particular interest are the rhomboid family serine proteinases that are active within the plasma membrane, for which several new structures have been reported. Because these enzymes are involved in biological and pathological processes, many are becoming important targets of drug design. PMID:17890078

Botos, Istvan

2007-01-01

43

Significance of the D-serine-deaminase and D-serine metabolism of Staphylococcus saprophyticus for virulence.  

PubMed

Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a D-serine-deaminase (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the D-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that D-serine-deaminase or the ability to respond to or to metabolize D-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular D-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high D-serine concentrations; however, its D-serine metabolism has not been described. The activity of the D-serine-deaminase was verified by analyzing the formation of pyruvate from D-serine in different strains with and without D-serine-deaminase. Cocultivation experiments were performed to show that D-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ?dsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of D-serine. In addition, we show that S. saprophyticus is able to use D-serine as the sole carbon source, but interestingly, D-serine had a negative effect on growth when glucose was also present. Taken together, D-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of D-serine and a ?dsdA mutant was attenuated in virulence murine model of urinary tract infection. PMID:24082071

Korte-Berwanger, Miriam; Sakinc, Türkan; Kline, Kimberly; Nielsen, Hailyn V; Hultgren, Scott; Gatermann, Sören G

2013-12-01

44

Significance of the d-Serine-Deaminase and d-Serine Metabolism of Staphylococcus saprophyticus for Virulence  

PubMed Central

Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a d-serine-deaminase (DsdA). As d-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the d-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that d-serine-deaminase or the ability to respond to or to metabolize d-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular d-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high d-serine concentrations; however, its d-serine metabolism has not been described. The activity of the d-serine-deaminase was verified by analyzing the formation of pyruvate from d-serine in different strains with and without d-serine-deaminase. Cocultivation experiments were performed to show that d-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of d-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ?dsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of d-serine. In addition, we show that S. saprophyticus is able to use d-serine as the sole carbon source, but interestingly, d-serine had a negative effect on growth when glucose was also present. Taken together, d-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of d-serine and a ?dsdA mutant was attenuated in virulence murine model of urinary tract infection. PMID:24082071

Sakinc, Turkan; Kline, Kimberly; Nielsen, Hailyn V.; Hultgren, Scott; Gatermann, Soren G.

2013-01-01

45

Console Hacking 2010 PS3 Epic Fail  

E-print Network

Console Hacking 2010 PS3 Epic Fail bushing, marcan, segher, sven 27th Chaos Communication Congress Wii Xbox 360 PS3 2006 2011 2010 2009 2008 2007 Mittwoch, 29. Dezember 2010 #12;Twiizer Attack Twilight Xbox 360 PS3 2006 2011 2010 2009 2008 2007 Mittwoch, 29. Dezember 2010 #12;Twiizer Attack Twilight Hack

Touretzky, David S.

46

Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: comparison of bovine cortex PS with egg PS and soybean PS.  

PubMed

There are various clinical and non-clinical studies that have indicated that phosphatidylserine (PS) treatment can improve cognitive functions in humans and other animals. However, treatment with PS derived from bovine cortex is not desirable because of possible transfer of infectious diseases. The present study investigated the cognition-enhancing properties of different types of PS in rats. Seventeen-month-old male Fischer 344 rats were treated daily with a dose of 15 mg/kg of PS derived from bovine cortex (BC-PS), soybean (S-PS), egg (E-PS), or vehicle (n = 9 for each group). The effects of treatment were evaluated in three different behavioral tests. An open field test was conducted to examine the effects of treatment on psychomotor behavior. Two other tests (Morris water escape task and two-way active avoidance) assessed treatment effects on the cognitive performance of rats. Treatment with the different forms of PS did not affect the psychomotor or spatial discrimination performance of the rats. In accordance with previous studies, the cognition-enhancing effects of BC-PS were observed in the two-way active avoidance task. It appeared that the cognition-enhancing effects of S-PS were not different from those of BC-PS. The performance of rats treated with E-PS did not deviate from that of vehicle-treated rats. On the basis of the present study, it was concluded that S-PS, but not E-PS, may have comparable effects on cognition when compared with BC-PS. PMID:10501292

Blokland, A; Honig, W; Brouns, F; Jolles, J

1999-10-01

47

Name: Hanife Serin Subject: MA Childhood  

E-print Network

In the Spotlight Name: Hanife Serin Subject: MA Childhood Studies Home Town: Cyprus MA Childhood chance of securing employment. Can you tell us about your course? MA Childhood Studies is an amazing to childhood memories, but also it was quite enjoyable to listen about the research con- ducted in different

Martin, Ralph R.

48

Human serine racemase: moleular cloning, genomic organization and functional analysis  

Microsoft Academic Search

High levels of d-serine are found in mammalian brain, where it is an endogenous agonist of the strichinine-insensitive site of N-methyl d-aspartate type of glutamate receptors. d-serine is enriched in protoplasmic astrocytes that occur in gray matter areas of the brain and was shown to be synthesized from l-serine . We now report cloning and expression of human serine racemase,

Joari De Miranda; Ana Santoro; Simone Engelender; Herman Wolosker

2000-01-01

49

Nitric Oxide S-Nitrosylates Serine Racemase, Mediating Feedback Inhibition of D-Serine Formation  

Microsoft Academic Search

Serine racemase (SR) generates D-serine, a coagonist with glutamate at NMDA receptors. We show that SR is physiologically S-nitrosylated leading to marked inhibition of enzyme activity. Inhibition involves interactions with the cofactor ATP reflecting juxtaposition of the ATP-binding site and cysteine-113 (C113), the site for physiological S-nitrosylation. NMDA receptor physiologically enhances SR S-nitrosylation by activating neuronal nitric-oxide synthase (nNOS). These

Asif K. Mustafa; Manish Kumar; Balakrishnan Selvakumar; Gary P. H. Ho; Jeffrey T. Ehmsen; Roxanne K. Barrow; L. Mario Amzel; Solomon H. Snyder

2007-01-01

50

Spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase during mouse postnatal development1  

Microsoft Academic Search

AIM: To elucidate the spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase (EC 1.4.3.3; DAO) in mouse cortex, striatum, cerebellum, heart, lung, liver, spleen, kidney, and skeletal muscle during mouse postnatal development. METHODS: The transcription levels of serine racemase and DAO were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of serine racemase were examined by

WANG Li-Zhen; ZHU Xing-Zu

2003-01-01

51

In Vivo d-Serine Hetero-Exchange through Alanine-Serine-Cysteine (ASC) Transporters Detected by Microelectrode Biosensors  

PubMed Central

d-Serine, a co-agonist of N-methyl d-aspartate (NMDA) receptors, has been implicated in neurological and psychiatric disorders such as cerebral ischemia, lateral amyotrophic sclerosis, or schizophrenia. d-Serine signaling represents an important pharmacological target for treating these diseases; however, the biochemical mechanisms controlling extracellular d-serine levels in vivo are still unclear. d-Serine heteroexchange through small neutral amino acid transporters has been shown in cell cultures and brain slices and could provide a biochemical mechanism for the control of d-serine extracellular concentration in vivo. Alternatively, exocytotic d-serine release has also been proposed. In this study, the dynamics of d-serine release and clearance were explored in vivo on a second-by-second time scale using microelectrode biosensors. The rate of d-serine clearance in the rat frontal cortex after a microionophoretic injection revealed a transporter-mediated uptake mechanism. d-Serine uptake was blocked by small neutral l-amino acids, implicating alanine-serine-cysteine (ASC) transporters, in particular high affinity Asc-1 and low affinity ASCT2 transporters. Interestingly, changes in alanine, serine, or threonine levels resulted in d-serine release through ASC transporters. Asc-1, but not ASCT2, appeared to release d-serine in response to changes in amino acid concentrations. Finally, neuronal silencing by tetrodotoxin increased d-serine extracellular concentration by an ASC-transporter-dependent mechanism. Together, these results indicate that d-serine heteroexchange through ASC transporters is present in vivo and may constitute a key component in the regulation of d-serine extracellular concentration. PMID:23581544

2013-01-01

52

Treatment with amino acids in serine deficiency disorders.  

PubMed

Serine deficiency disorders are rare defects in the biosynthesis of the amino acid L-serine. At present two disorders have been reported: 3-phosphoglycerate dehydrogenase deficiency and 3-phosphoserine phosphatase deficiency. These enzyme defects lead to severe neurological symptoms such as congenital microcephaly and severe psychomotor retardation and in addition in patients with 3-phosphoglycerate dehydrogenase deficiency to intractable seizures. These symptoms respond to a variable degree to treatment with L-serine, sometimes combined with glycine. In this paper the current practice of amino acid treatment with L-serine and glycine in serine deficiency is reviewed. PMID:16763900

de Koning, T J

2006-01-01

53

Effect of Egg Yolk and Phosphatides on Anthrax Infection of Rats and Guinea Pigs.  

National Technical Information Service (NTIS)

Suspension of anthrax spores or vegetative cells in phosphatidyl ethanolamine, or the related phosphatides, phosphatidyl serine and phosphatidyl inositol, markedly reduced the intraperitoneal median lethal dose for guinea pigs and Sprague-Dawley rats, thu...

W. D. Sawyer, R. W. Kuehne, W. Gochenour

1964-01-01

54

-Standard -PS 3.18-2008  

E-print Network

.18-2008 Page 3 - Standard - FOREWORD This part of the DICOM standard was developed jointly with ISO TC 215- Standard - PS 3.18-2008 Digital Imaging and Communications in Medicine (DICOM) Part 18: Web and Pan American Copyright Conventions. #12;PS 3.18-2008 Page 2 - Standard - NOTICE AND DISCLAIMER

Rumolo, Giovanni

55

Franklin PS-2 (XPS-2) Glider  

NASA Technical Reports Server (NTRS)

This Franklin PS-2 training glider is about to be towed aloft by the specially modified car in front. NACA researchers used the PS-2 in a study of ground effect on a towed glider. Langley flew two of the Franklin gliders in the late 1930s, but the Navy never really found a good use for training gliders.

1938-01-01

56

Franklin PS-2 (XPS-2) Glider  

NASA Technical Reports Server (NTRS)

Franklin PS-2 (XPS-2) Glider: This Franklin PS-2 training glider is about to be towed aloft by the specially modified car in front. NACA researchers used the PS-2 in a study of ground effect on a towed glider. Langley flew two of the Franklin gliders in the late 1930s, but the Navy never really found a good use for training gliders.: This Franklin PS-2 training glider is about to be towed aloft by the specially modified car in front. NACA researchers used the PS-2 in a study of ground effect on a towed glider. Langley flew two of the Franklin gliders in the late 1930s, but the Navy never really found a good use for training gliders.

1938-01-01

57

PP/PS anisotropic stereotomography  

NASA Astrophysics Data System (ADS)

Stereotomography is a slope tomographic method which gives good results for background velocity model estimation in 2-D isotropic media. We develop here the extension of the method to 3-D general anisotropic media for PP and PS events. We do not take into account the issue of shear wave degeneracy. As in isotropic media, the sensitivity matrix of the inversion can be computed by paraxial ray tracing. We introduce a `constant Z stereotomography' approach, which can reduce the size of the sensitivity matrix. Based on ray perturbation theory, we give all the derivatives of stereotomography data parameters with respect to model parameters in a 3-D general anisotropic medium. These general formulas for the derivatives can also be used in other applications that rely on anisotropic ray perturbation theory. In particular, we obtain derivatives of the phase velocity with respect to position, phase angle and elastic medium parameters, all for general anisotropic media. The derivatives are expressed using the Voigt notation for the elastic medium parameters. We include a Jacobian that allows to change the model parametrization from Voigt to Thomsen parameters. Explicit expressions for the derivatives of the data are given for the case of 2-D tilted transversely isotropic (TTI) media. We validate the method by single-parameter estimation of each Thomsen parameter field of a 2-D TTI synthetic model, where data are modelled by ray tracing. For each Thomsen parameter, the estimated velocity field fits well with the true velocity field.

Nag, Steinar; Alerini, Mathias; Ursin, Bjørn

2010-04-01

58

Levels of D-serine in the brain and peripheral organs of serine racemase (Srr) knock-out mice.  

PubMed

D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, plays an important role in mammalian brain neurotransmission, via the NMDA receptor. D-Serine is synthesized from L-serine by the pyridoxal-5' phosphate-dependent enzyme serine racemase (SRR), and D-serine is metabolized by D-amino acid oxidase (DAAO). In this study, we measured levels of the neurotransmission related amino acids, d-serine, L-serine, glycine, glutamine and glutamate in the frontal cortex, hippocampus, striatum and cerebellum as well as in peripheral tissues of blood, heart, pancreas, spleen, liver, kidney, testis, epididymis, heart, lung, muscle and eyeball, in wild-type (WT) and Srr-knockout (Srr-KO) mice. Levels of D-serine in the frontal cortex, hippocampus, and striatum of Srr-KO mice were significantly lower than in WT mice, while levels in the cerebellum stayed the same. In contrast, levels of L-serine, glycine, glutamine and glutamate remained the same in all tested brain regions. In vivo microdialysis using free-moving mice showed that extracellular levels of D-serine in the hippocampus of Srr-KO mice were significantly lower than in WT mice while the other amino acid levels remained the same between mice. In peripheral organs, levels of D-serine in the kidney, testis, and muscle of Srr-KO mice were significantly lower than in WT mice. Tissue levels of the other tested amino acids in peripheral organs were not altered. These results suggest that SRR is the major enzyme responsible for D-serine production in the mouse forebrain, and that other pathways of d-serine production may exist in the brain and peripheral organs. PMID:21906644

Horio, Mao; Kohno, Mami; Fujita, Yuko; Ishima, Tamaki; Inoue, Ran; Mori, Hisashi; Hashimoto, Kenji

2011-11-01

59

Fatal cerebral edema associated with serine deficiency in CSF.  

PubMed

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy. PMID:20300853

Keularts, Irene M L W; Leroy, Piet L J M; Rubio-Gozalbo, Estela M; Spaapen, Leo J M; Weber, Biene; Dorland, Bert; de Koning, Tom J; Verhoeven-Duif, Nanda M

2010-12-01

60

D-Serine is reabsorbed in rat renal pars recta.  

PubMed

D-Serine normally contributes up to 3% to total plasma serine and up to 23% in chronic renal failure. D-Serine is metabolized by tubular D-amino acid oxidase (D-AAO), and high D-serine plasma levels are nephrotoxic; both events are localized in the straight part of the proximal tubule. We therefore investigated if and how D-serine is reabsorbed there. We microinfused 14C-labeled D- or -L-serine + [3H]inulin into early proximal (EP), late proximal (LP), or early distal (ED) tubule sections of superficial nephrons and into long loops of Henle (LLH) of rats in vivo and in situ. The fractional reabsorption (FR) of the 14C label was determined from the 14C:3H ratio in the final urine. At 0.36 mM, FR of D-[14C]serine was 86% (EP), 90% (LP), and approximately 0 (ED, LLH). FR of D-serine could be saturated and inhibited by L-serine (and vice versa). D-methionine, but not D-glutamate or D-arginine, blocked FR of D-serine (LP). We conlude that filtered D-serine is able to enter the pars recta cells, thereby getting access to D-AAO. The uptake carrier has a very low stereospecificity and is, therefore, different from that in the proximal convolution. The colocalization of exclusive reabsorption and metabolism makes the pars recta the tubule site for the recycling of the carbon structure of D-amino acids and, at the same time, the target of D-serine nephrotoxicity. PMID:10362774

Silbernagl, S; Völker, K; Dantzler, W H

1999-06-01

61

Serine racemase binds to PICK1: potential relevance to schizophrenia  

Microsoft Academic Search

Accumulating evidence from both genetic and clinico-pharmacological studies suggests that D-serine, an endogenous coagonist to the NMDA subtype glutamate receptor, may be implicated in schizophrenia (SZ). Although an association of genes for D-serine degradation, such as D-amino acid oxidase and G72, has been reported, a role for D-serine in SZ has been unclear. In this study, we identify and characterize

K Fujii; K Maeda; T Hikida; A K Mustafa; R Balkissoon; J Xia; T Yamada; Y Ozeki; R Kawahara; M Okawa; R L Huganir; H Ujike; S H Snyder; A Sawa

2006-01-01

62

Metal ion dependency of serine racemase from Dictyostelium discoideum.  

PubMed

D-Serine is known to act as an endogenous co-agonist of the N-methyl-D-aspartate receptor in the mammalian brain and is endogenously synthesized from L-serine by a pyridoxal 5'-phosphate-dependent enzyme, serine racemase. Though the soil-living mycetozoa Dictyostelium discoideum possesses no genes homologous to that of NMDA receptor, it contains genes encoding putative proteins relating to the D-serine metabolism, such as serine racemase, D-amino acid oxidase, and D-serine dehydratase. D. discoideum is an attractive target for the elucidation of the unknown functions of D-serine such as a role in cell development. As part of the elucidation of the role of D-serine in D. discoideum, we cloned, overexpressed, and examined the properties of the putative serine racemase exhibiting 46% amino acid sequence similarity with the human enzyme. The enzyme is unique in its stimulation by monovalent cations such as Na(+) in addition to Mg(2+) and Ca(2+), which are well-known activators for the mammalian serine racemase. Mg(2+) or Na(+) binding caused two- to ninefold enhancement of the rates of both racemization and dehydration. The half-maximal activation concentrations of Mg(2+) and Na(+) were determined to be 1.2 ?M and 2.2 mM, respectively. In the L-serine dehydrase reaction, Mg(2+) and Na(+) enhanced the k (cat) value without changing the K (m) value. Alanine mutation of the residues E207 and D213, which correspond to the Mg(2+)-binding site of Schizosaccharomyces pombe serine racemase, abolished the Mg(2+)- and Na(+)-dependent stimulation. These results suggest that Mg(2+) and Na(+) share the common metal ion-binding site. PMID:22311068

Ito, Tomokazu; Murase, Hirotaka; Maekawa, Motoki; Goto, Masaru; Hayashi, Shuhei; Saito, Hajime; Maki, Masatoshi; Hemmi, Hisashi; Yoshimura, Tohru

2012-10-01

63

A serine hydroxymethyltransferase from marine bacterium Shewanella algae: Isolation, purification, characterization and l-serine production.  

PubMed

Currently, l-serine is mainly produced by enzymatic conversion, in which serine hydroxymethyltransferase (SHMT) is the key enzyme, suggesting the importance of searching for a SHMT with high activity. Shewanella algae, a methanol-utilizing marine bacterium showing high SHMT activity, was selected based on screening bacterial strains and comparison of the activities of SHMTs. A glyA was isolated from the S. algae through thermal asymmetric interlaced PCR (TAIL-PCR) and it encoded a 417 amino acid polypeptide. The SaSHMT, encoded by the glyA, showed the optimal activity at 50°C and pH 7.0, and retained over 45% of its maximal activity after incubation at 40°C for 3h. The enzyme showed better stability under alkaline environment (pH 6.5-9.0) than Hyphomicrobium methylovorum GM2's SHMT (pH 6.0-7.5). The SaSHMT can produce 77.76mM of l-serine by enzymatic conversion, with the molecular conversion rate in catalyzing glycine to l-serine being 1.41-fold higher than that of Escherichia coli. Therefore, the SaSHMT has the potential for industrial applications due to its tolerance of alkaline environment and a relatively high enzymatic conversion rate. PMID:23632047

Jiang, Wei; Xia, Bingzhao; Liu, Ziduo

2013-10-01

64

Evolutionary genomics of Glossina morsitans immune-related CLIP domain serine proteases and serine protease inhibitors.  

PubMed

Several species of haematophagous tsetse flies (genus Glossina) are vectors for trypanosomes, the parasitic protozoans that cause Human African Trypanosomiasis (HAT). Although there was a reduced incidence of HAT in the mid 1960s, decreased disease surveillance has led to a resurgence of HAT in sub-Saharan Africa. Despite being efficient vectors for HAT transmission, the prevalence of G. morsitans infection by trypanosomes in the wild is surprisingly minimal. The precise mechanisms by which G. morsitans remain refractory to trypanosome infection are largely unknown although it has been demonstrated that G. morsitans mounts a strong immune response to invading pathogens. This study identifies G. morsitans immune-related CLIP domain serine proteases and their inhibitors, serine protease inhibitors (serpin) genes. It further establishes their evolutionary relationships with counterparts in Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Manduca sexta and Culex quinquefasciatus. Multiple sequence alignments show conservation of most secondary structure elements for both CLIPs and serpins. Amino acid composition of the serpin reactive site loop (RSL) indicates that the G. morsitans serpins act through an inhibitory mechanism to the target serine protease. Similar to D. melanogaster and unlike A. gambiae, the transcriptome data suggest that G. morsitans does not contain gene expansions in their CLIP-domain serine protease and serpin families. The presence of alternatively spliced variants in the G. morsitans serpins transcriptome data mirrors that of the D. melanogaster transcriptome. PMID:21055483

Mwangi, Sarah; Murungi, Edwin; Jonas, Mario; Christoffels, Alan

2011-06-01

65

A bumblebee (Bombus ignitus) venom serine protease inhibitor that acts as a microbial serine protease inhibitor.  

PubMed

Serine protease inhibitors from bumblebee venom have been shown to block plasmin activity. In this study, we identified the protein BiVSPI from the venom of Bombus ignitus to be a serine protease inhibitor and an antimicrobial factor. BiVSPI is a 55-amino acid mature peptide with ten conserved cysteine residues and a P1 methionine residue. BiVSPI is expressed in the venom gland and also found in the venom as an 8-kDa peptide. Recombinant BiVSPI that was expressed in baculovirus-infected insect cells exhibited inhibitory activity against chymotrypsin but not trypsin. BiVSPI also inhibited microbial serine proteases, such as subtilisin A (Ki=6.57nM) and proteinase K (Ki=7.11nM). In addition, BiVSPI was shown to bind directly to Bacillus subtilis, Bacillus thuringiensis, and Beauveria bassiana but not to Escherichia coli. Consistent with these results, BiVSPI exhibited antimicrobial activity against Gram-positive bacteria and fungi. These findings provide evidence for a novel serine protease inhibitor in bumblebee venom that has antimicrobial functions. PMID:24158004

Wan, Hu; Kim, Bo Yeon; Lee, Kwang Sik; Yoon, Hyung Joo; Lee, Kyung Yong; Jin, Byung Rae

2014-01-01

66

Neonatal Disruption of Serine Racemase Causes Schizophrenia-Like Behavioral Abnormalities in Adulthood: Clinical Rescue by D-Serine  

PubMed Central

Background D-Serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, is synthesized from L-serine by serine racemase (SRR). Given the role of D-serine in both neurodevelopment and the pathophysiology of schizophrenia, we examined whether neonatal disruption of D-serine synthesis by SRR inhibition could induce behavioral abnormalities relevant to schizophrenia, in later life. Methodology/Principal Findings Neonatal mice (7–9 days) were injected with vehicle or phenazine methosulfate (Met-Phen: 3 mg/kg/day), an SRR inhibitor. Behavioral evaluations, such as spontaneous locomotion, novel object recognition test (NORT), and prepulse inhibition (PPI) were performed at juvenile (5–6 weeks old) and adult (10–12 weeks old) stages. In addition, we tested the effects of D-serine on PPI deficits in adult mice after neonatal Met-Phen exposure. Finally, we assessed whether D-serine could prevent the onset of schizophrenia-like behavior in these mice. Neonatal Met-Phen treatment reduced D-serine levels in the brain, 24 hours after the final dose. Additionally, this treatment caused behavioral abnormalities relevant to prodromal symptoms in juveniles and to schizophrenia in adults. A single dose of D-serine improved PPI deficits in adult mice. Interestingly, chronic administration of D-serine (900 mg/kg/day from P35 to P70) significantly prevented the onset of PPI deficits after neonatal Met-Phen exposure. Conclusions/Significance This study shows that disruption of D-serine synthesis during developmental stages leads to behavioral abnormalities relevant to prodromal symptoms and schizophrenia, in later life. Furthermore, early pharmacological intervention with D-serine may prevent the onset of psychosis in adult. PMID:23630632

Hagiwara, Hiroko; Iyo, Masaomi; Hashimoto, Kenji

2013-01-01

67

D-serine and serine racemase are localized to neurons in the adult mouse and human forebrain.  

PubMed

D-Serine, a co-agonist at the NMDA receptor (NMDAR), is synthesized from L-serine by the enzyme serine racemase (SR), which is heavily expressed in the forebrain. Although SR was originally reported to be localized exclusively to astrocytes, recent conditional knock out results demonstrate that little SR is expressed in forebrain astrocytes. As a consequence, the cellular location of its product, D-serine, in the brain is also uncertain. Immunocytochemistry now indicates that SR is expressed primarily in forebrain glutamatergic neurons with the remainder in GABAergic interneurons. We utilized SR deficient (SR-/-) mice, which have <15 % of normal D-serine levels, to validate and optimize a D-serine immunohistochemical method. Nearly all of the D-serine in neocortex and hippocampus (HP) is found in neurons, with virtually no D-serine co-localizing with two astrocyte markers. Interestingly, only a subset of the D-serine positive neurons contained SR in the neocortex and HP. Greater than half of the D-serine positive neurons were GABAergic interneurons, with a majority of these neurons containing parvalbumin and/or somatostatin. Only ~25-40 % of interneurons expressed SR in the neocortex and HP. Finally, we demonstrate in human post-mortem neocortex that SR is found in both excitatory and inhibitory neurons, but not in S100?-containing astrocytes. In sum, these findings conclusively demonstrate that the majority of D-serine is both synthesized and stored in neurons. It will be important to determine the functional significance for the separation of synthesis and storage of D-serine in neurons, as well as the presence of this NMDAR co-agonist in GABAergic interneurons. PMID:24436034

Balu, Darrick T; Takagi, Shunsuke; Puhl, Matthew D; Benneyworth, Michael A; Coyle, Joseph T

2014-04-01

68

Cellular distribution of d-serine, serine racemase and d-amino acid oxidase in the rat vestibular sensory epithelia  

Microsoft Academic Search

Glutamate is the main neurotransmitter at the synapses between sensory cells and primary afferents in the peripheral vestibular system. Evidence has recently been obtained demonstrating that the atypical amino acid d-serine is the main endogenous co-agonist of the N-methyl-d-aspartate receptors in the CNS. We studied the distribution of d-serine and its synthesizing and degrading enzymes, serine racemase and d-amino acid

D. Dememes; J.-P. Mothet; M.-T. Nicolas

2006-01-01

69

Franklin PS-2 (XPS-2) Glider  

NASA Technical Reports Server (NTRS)

Franklin PS-2 (XPS-2) Glider: This beefy-looking glider is a Franklin PS-2, a pair of which were operated by the NACA at Langley beginning in April 1936. The Navy only ordered half a dozen of these training gliders, which had a glide ratio of 15 feet forward for every foot down. The devices above the pilot's seat are venturi tubes, which gathered data for the instruments. Airfield lights are seen above the wing.

1936-01-01

70

Effectiveness of intranasal vaccination against Angiostrongylus costaricensis using a serine/threonine phosphatase 2 A synthetic peptide and recombinant antigens.  

PubMed

Intranasal immunization was assayed in C57BL/6 mice against Angiostrongylus costaricensis using a synthetic and a recombinant peptide belonging to the catalytic region of the serine/threonine phosphatase 2 A (PP2A) of the parasite. Immunization was carried out with the synthetic peptide (SP) polymerized either with itself or with the beta fraction of the cholera toxin (CTB) and then enclosed in nanocapsules of phosphatidyl choline, cholesterol and Quil A (ISCOM). Another group of mice was immunized with recombinant peptide. Immunization consisted of two intranasal inoculations at two-week intervals, and the challenge with L3 larvae was made one month after the last vaccination. The effectiveness of immunization was evaluated 30 days after infection by analysis of the number of parasites in the arteries of the immunized mice, as well as by measuring spleen sizes in the experimental groups. The response induced was determined by identifying the isotypes of IgG as well as the IgE and IgA specific antigen response. The interleukins produced by the splenocyte culture of the different groups were assessed after exposing them to the peptide used in the immunization. From our results, 60%, 80%, and 100% protection against the A. costaricensis challenge was achieved in mice immunized with polymerized synthetic peptide in ISCOM, synthetic peptide polymerized with the CTB in ISCOM and inclusion bodies respectively. Splenomegaly was found to be less evident in the immunized mice than in the controls. A significant increase in IFN gamma and IL-17 levels was observed in the group with 100% protection. The results showed that vaccination through the nasal mucosa may constitute a useful method of immunization and result in a protective immune response against A. costaricensis. PMID:20558243

Solano-Parada, J; Gonzalez-Gonzalez, G; Torró, L M de Pablos; dos Santos, M F Brazil; Espino, A M; Burgos, M; Osuna, A

2010-07-19

71

The pharmacological landscape and therapeutic potential of serine hydrolases  

Microsoft Academic Search

Serine hydrolases perform crucial roles in many biological processes, and several of these enzymes are targets of approved drugs for indications such as type 2 diabetes, Alzheimer's disease and infectious diseases. Despite this, most of the human serine hydrolases (of which there are more than 200) remain poorly characterized with respect to their physiological substrates and functions, and the vast

Daniel A. Bachovchin; Benjamin F. Cravatt

2012-01-01

72

D-Serine: A key to synaptic plasticity?  

PubMed Central

Two discoveries have put D-serine in the spotlight of neuroscience. First, D-serine was detected in brain tissue at high levels. Second, it was found to act on the N-methyl-D-aspartate receptor (NMDAR). This receptor is central to use-dependent synaptic plasticity, the cellular process which is widely believed to underlie learning. The ensuing quest for the mechanisms of D-serine synthesis, release and clearance, as well as for its physiological significance has provided a wealth of experimental evidence implicating D-serine in synaptic plasticity. However some key questions remain unanswered. Which cells release D-serine and upon what stimuli? Is D-serine supply dynamically regulated? What is the fate of released D-serine? Answering these questions appears to be an essential step in our understanding of how NMDARs trigger synaptic plasticity and learning. This review will highlight some recent advances and avenues of enquiry in dynamic D-serine signaling in the mammalian brain with emphasis on neurophysiology. PMID:22266400

Henneberger, Christian; Bard, Lucie; Rusakov, Dmitri A.

2012-01-01

73

Contributions of the D-serine pathway to schizophrenia.  

PubMed

The glutamate neurotransmitter system is one of the major candidate pathways for the pathophysiology of schizophrenia, and increased understanding of the pharmacology, molecular biology and biochemistry of this system may lead to novel treatments. Glutamatergic hypofunction, particularly at the NMDA receptor, has been hypothesized to underlie many of the symptoms of schizophrenia, including psychosis, negative symptoms and cognitive impairment. This review will focus on D-serine, a co-agonist at the NMDA receptor that in combination with glutamate, is required for full activation of this ion channel receptor. Evidence implicating D-serine, NMDA receptors and related molecules, such as D-amino acid oxidase (DAO), G72 and serine racemase (SRR), in the etiology or pathophysiology of schizophrenia is discussed, including knowledge gained from mouse models with altered D-serine pathway genes and from preliminary clinical trials with D-serine itself or compounds modulating the D-serine pathway. Abnormalities in D-serine availability may underlie glutamatergic dysfunction in schizophrenia, and the development of new treatments acting through the D-serine pathway may significantly improve outcomes for many schizophrenia patients. PMID:21295046

Labrie, Viviane; Wong, Albert H C; Roder, John C

2012-03-01

74

Continuing education in neurometabolic disorders--serine deficiency disorders.  

PubMed

Serine deficiency disorders comprise a new group of inborn errors of serine metabolism. Patients affected with these disorders present with major neurological symptoms including congenital microcephaly, seizures, psychomotor retardation or polyneuropathy. The diagnosis of serine deficiency is based on the detection of low concentrations of the amino acids serine and glycine in fasted plasma and cerebrospinal fluid (CSF). Amino acid analysis of cerebrospinal fluid is preferable over plasma analysis, because the deficiencies are more pronounced in CSF. Because of the interference of amino acids absorbed from the diet, diagnostic procedures have to be performed in the fasted state. Although the disorders are probably rare and not many cases have been reported, recognition of serine deficiency is important, given the fact that the disorders are potentially treatable. The clinical symptoms respond well to amino acid replacement therapy. So far, three serine deficiency disorders have been reported; 3-phosphoglycerate dehydrogenase deficiency, 3-phosphoserine phosphatase deficiency and a still unexplained serine deficiency disorder. In this paper, we will discuss the various serine deficiency disorders, their biochemical abnormalities and the results of amino acid replacement therapy. PMID:10222452

de Koning, T J; Poll-The, B T; Jaeken, J

1999-02-01

75

D-Serine Regulation of NMDA Receptor Activity  

NSDL National Science Digital Library

The N-Methyl-D-aspartate–type glutamate receptor (NMDAR) plays a key role in several important processes involving the nervous system, including brain development, synaptic plasticity, and learning. Unlike other neurotransmitter receptors, which are activated by individual neurotransmitters, activation of NMDARs requires the binding of a coagonist (D-serine or glycine) in addition to glutamate. Although previously considered an "unnatural" amino acid, D-serine is a key regulator of NMDAR activity and may be the main physiological ligand at the coagonist site. D-Serine is synthesized in the mammalian brain and is enriched in astrocytes, a class of glial cells that ensheath synapses in the brain. Astrocytes physiologically affect NMDAR neurotransmission by releasing D-serine, suggesting that D-serine acts as a gliotransmitter. However, recent findings indicate that D-serine signaling does not depend solely on glia, because D-serine and its biosynthetic enzyme are also present in substantial amounts in neurons. Here, we discuss these new findings, which begin to shed light on the relative roles of glia and neurons in D-serine signaling.

Herman Wolosker (Technion-Israel Institute of Technology;Department of Biochemistry REV)

2006-10-10

76

Chemotaxis of Escherichia coli to L-serine  

Microsoft Academic Search

A novel experimental technique was used to quantify the motion of E. coli to varying serine concentrations and gradients so as to capture the spatial and temporal variation of the chemotactic response. The average run speed and the cell diffusivity are found to be dependent on the serine concentration. The measured diffusivities were in the range of 1.2-2.5 × 10

Rajitha R. Vuppula; Mahesh S. Tirumkudulu; K. V. Venkatesh

2010-01-01

77

d-serine prevents cognitive deficits induced by acute stress.  

PubMed

Increasing evidence indicates that acute stress disrupts cognitive functions mediated by glutamate-NMDA receptors, although the mechanisms are not fully understood. Here we investigated whether d-serine and glycine, the endogenous co-agonists of the NMDA receptor, are regulated by acute stress. We studied the biochemical and behavioral effects of acute restraint stress in C57BL/6 mice. Acute restraint stress decreased d-serine levels in the prefrontal cortex and glycine levels in the hippocampus. Behaviorally, acute stress impaired memory consolidation in the object recognition task and prepulse inhibition of the startle response. Importantly, d-serine administration (1 g/kg, i.p.) prevented both stress-induced impairments. Taken together, our results show for the first time an interplay between stress and d-serine and warrant further research on the role of d-serine in stress-related disorders. PMID:24978104

Guercio, G D; Bevictori, L; Vargas-Lopes, C; Madeira, C; Oliveira, A; Carvalho, V F; d'Avila, J C; Panizzutti, R

2014-11-01

78

Production of L-serine by Sarcina albida.  

PubMed Central

Conditions for the production of microbial L-serine hydroxymethyltransferase and for the conversion of glycine to L-serine were studied. A number of microorganisms were screened for their abilities to form and accululate L-serine from glycine, and Sarcina albida was selected as the best organism. Enzyme activity in this organism as high as 0.12 U/ml could be produced in shaken cultures at 30 degrees C in a medium containing glucose, ammonium sulfate, glycine, yeast extract, and inorganic salts. L-Serine was produced most efficiently by shaking cells at 30 degrees C in a reaction mixture containing 20% glycine, 5 X 10(-3) M formaldehyde, and 3 X 10(-4) M pyridoxal phosphate in yields of 22 mg of broth in 5 days. L-Serine was easily isolated in 84% yields by ion-exchange resin. PMID:39497

Ema, M; Kakimoto, T; Chibata, I

1979-01-01

79

3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis.  

PubMed

Serine concentrations were markedly decreased in the cerebrospinal fluid of two brothers with congenital microcephaly, profound psychomotor retardation, hypertonia, epilepsy, growth retardation, and hypogonadism. The youngest boy also had congenital bilateral cataract. Magnetic resonance imaging of the brain showed evidence of dysmyelination. Plasma serine as well as plasma and cerebrospinal fluid glycine concentrations were also decreased but to a lesser extent. Treatment with oral serine in the youngest patient significantly increased cerebrospinal fluid serine and abolished the convulsions. In fibroblasts of both patients, a decreased activity was demonstrated of 3-phosphoglycerate dehydrogenase, the first step of serine biosynthesis (22% and 13% of the mean control value). This is an unusual disorder as the great majority of aminoacidopathies are catabolic defects. It is a severe but potentially treatable inborn error of metabolism that has not been previously reported in man. PMID:8758134

Jaeken, J; Detheux, M; Van Maldergem, L; Foulon, M; Carchon, H; Van Schaftingen, E

1996-06-01

80

Separation of PS-PMMA block copolymers from PS precursors via selective adsorption on nanoprous silica  

NASA Astrophysics Data System (ADS)

We report a simple adsorption-based separation method using nanoporous silica in solution via controlling solvent quality to remove polystyrene (PS) homopolymers from polystyrene-poly(methyl methacrylate) (PS-PMMA) diblock copolymers. In particular, the solvent quality is controlled by employing binary mixed solvents of THF (good solvent) and isooctane (nonsolvent for both PS and PMMA). The aim of this work is to qualitatively study the competitive adsorption between PS and PS-PMMA and to provide a correlative understanding of polymer adsorption in nanopores with interaction chromatography techniques. In addition, the quantitative understanding of polymer adsorption is further employed to develop a simple polymer separation scheme for manipulating polymer adsorption via solvent quality. In particular, concentration changes of PS and PS-PMMA in the supernatant solution have been quantitatively measured for the adsorption studies using solvent gradient interaction chromatography techniques. We found that the PS-PMMA (43k-32k) selectively adsorb over PS (43k) precursors at the THF composition window between 42 % and 55% in THF/IO (v/v) mixed solvents. For THF/IO solvents with composition higher than 60 % THF, polymers did not adsorb to the nanoporous silica due to the good solvent quality.

Ryu, Chang Yeol

2005-03-01

81

Effect of the intracerebroventricular and systemic administration of l-serine on the concentrations of d- and l-serine in several brain areas and periphery of rat  

Microsoft Academic Search

To gain further insight into the metabolic mechanism of endogenous d-serine, the effect of the intracerebroventricular and intraperitoneal administration of l-serine on the concentrations of d- and l-serine in several brain areas and periphery was investigated. The intracerebroventricular injection of l-serine caused a rapid and marked increase in the l-serine levels in almost all brain regions of adult rats. This

Atsushi Hashimoto

2002-01-01

82

d-Serine in Glia and Neurons Derives from 3-Phosphoglycerate Dehydrogenase  

PubMed Central

d-Serine is an endogenous ligand for NMDARs generated from l-serine by the enzyme serine racemase (Srr). Both neuronal and glial localizations have been reported for d-serine and Srr. 3-Phosphoglycerate dehydrogenase is an exclusively astrocytic enzyme that catalyzes the first committed step of l-serine biosynthesis. Using transgenic mice expressing enhanced green fluorescent protein under the Srr promoter and mice with targeted deletion of Srr or 3-Phosphoglycerate dehydrogenase, we demonstrate predominantly neuronal sources of d-serine dependent on astrocytic supply of l-serine. These findings clarify the cellular basis for the regulation of NMDAR neurotransmission by d-serine. PMID:23884950

Ehmsen, Jeffrey T.; Ma, Ting Martin; Sason, Hagit; Rosenberg, Dina; Ogo, Tadashi; Furuya, Shigeki

2013-01-01

83

Effects of Halothane on Phosphatidylcholine, -ethanolamine, -glycerol, and -serine Monolayer Order at a  

E-print Network

Effects of Halothane on Phosphatidylcholine, -ethanolamine, -glycerol, and -serine Monolayer Order headgroups (choline, ethanolamine, glycerol, and serine) were studied. Each monolayer exhibits significant

Richmond, Geraldine L.

84

Phospholipid Composition and Metabolism of Micrococcus denitrificans  

PubMed Central

The phospholipid composition of Micrococcus denitrificans was unusual in that phosphatidyl choline (PC) was a major phospholipid (30.9%). Other phospholipids were phosphatidyl glycerol (PG, 52.4%), phosphatidyl ethanolamine (PE, 5.8%), an unknown phospholipid (5.3%), cardiolipin (CL, 3.2%), phosphatidyl dimethylethanolamine (PDME, 0.9%), phosphatidyl monomethylethanolamine (PMME, 0.6%), phosphatidyl serine (PS, 0.5%), and phosphatidic acid (0.4%). Kinetics of 32P incorporation suggested that PC was formed by the successive methylations of PE. Pulse-chase experiments with pulses of 32P or acetate-1-14C to exponentially growing cells showed loss of isotopes from PMME, PDME, PS, and CL with biphasic kinetics suggesting the same type of multiple pools of these lipids as proposed in other bacteria. The major phospholipids, PC, PG, and PE, were metabolically stable under these conditions. The fatty acids isolated from the complex lipids were also unusual in being a simple mixture of seven fatty acids with oleic acid representing 86% of the total. Few free fatty acids and no non-extractable fatty acids associated with the cell wall or membrane were found. Images PMID:4640503

Wilkinson, Brian J.; Morman, Manuel R.; White, David C.

1972-01-01

85

Immunohistochemical localization of D-serine dehydratase in chicken tissues.  

PubMed

Chicken D-serine dehydratase (DSD) degrades d-serine to pyruvate and ammonia. The enzyme requires both pyridoxal 5'-phosphate and Zn(2+) for its activity. d-Serine is a physiological coagonist that regulates the activity of the N-methyl-d-aspartate receptor (NMDAR) for l-glutamate. We have recently found in chickens that d-serine is degraded only by DSD in the brain, whereas it is also degraded to 3-hydroxypyruvate by d-amino acid oxidase (DAO) in the kidney and liver. In mammalian brains, d-serine is degraded only by DAO. It has not been clarified why chickens selectively use DSD for the control of d-serine concentrations in the brain. In the present study, we measured DSD activity in chicken tissues, and examined the cellular localization of DSD using a specific anti-chicken DSD antibody. The highest activity was found in kidney. Skeletal muscles and heart showed no activity. In chicken brain, cerebellum showed about 6-fold-higher activity (1.1 ± 0.3 U/g protein) than cerebrum (0.19 ± 0.03 U/g protein). At the cellular level DSD was demonstrated in proximal tubule cells of the kidney, in hepatocytes, in Bergmann-glia cells of the cerebellum and in astrocytes. The finding of DSD in glial cells seems to be important because d-serine is involved in NMDAR-dependent brain functions. PMID:24529545

Nishimura, Yoshihiro; Tanaka, Hiroyuki; Ishida, Tetsuo; Imai, Shinji; Matsusue, Yoshitaka; Agata, Yasutoshi; Horiike, Kihachiro

2014-06-01

86

Fibrin(ogen)olytic activity of bumblebee venom serine protease  

SciTech Connect

Bee venom is a rich source of pharmacologically active components; it has been used as an immunotherapy to treat bee venom hypersensitivity, and venom therapy has been applied as an alternative medicine. Here, we present evidence that the serine protease found in bumblebee venom exhibits fibrin(ogen)olytic activity. Compared to honeybee venom, bumblebee venom contains a higher content of serine protease, which is one of its major components. Venom serine proteases from bumblebees did not cross-react with antibodies against the honeybee venom serine protease. We provide functional evidence indicating that bumblebee (Bombus terrestris) venom serine protease (Bt-VSP) acts as a fibrin(ogen)olytic enzyme. Bt-VSP activates prothrombin and directly degrades fibrinogen into fibrin degradation products. However, Bt-VSP is not a plasminogen activator, and its fibrinolytic activity is less than that of plasmin. Taken together, our results define roles for Bt-VSP as a prothrombin activator, a thrombin-like protease, and a plasmin-like protease. These findings offer significant insight into the allergic reaction sequence that is initiated by bee venom serine protease and its potential usefulness as a clinical agent in the field of hemostasis and thrombosis. - Graphical abstract: Display Omitted Highlights: > Bumblebee venom serine protease (Bt-VSP) is a fibrin(ogen)olytic enzyme. > Bt-VSP activates prothrombin. > Bt-VSP directly degrades fibrinogen into fibrin degradation products. > Bt-VSP is a hemostatically active protein that is a potent clinical agent.

Qiu Yuling [College of Natural Resources and Life Science, Dong-A University, Busan 604-714 (Korea, Republic of); Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang (China); Choo, Young Moo [College of Natural Resources and Life Science, Dong-A University, Busan 604-714 (Korea, Republic of); Yoon, Hyung Joo [Department of Agricultural Biology, National Academy of Agricultural Science, Suwon (Korea, Republic of); Jia Jingming; Cui Zheng; Wang Dong [Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang (China); Kim, Doh Hoon [College of Natural Resources and Life Science, Dong-A University, Busan 604-714 (Korea, Republic of); Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang (China); Sohn, Hung Dae [College of Natural Resources and Life Science, Dong-A University, Busan 604-714 (Korea, Republic of); Jin, Byung Rae, E-mail: brjin@dau.ac.kr [College of Natural Resources and Life Science, Dong-A University, Busan 604-714 (Korea, Republic of); Joint Laboratory between Dong-A University and Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Shenyang (China)

2011-09-01

87

Transmission Line Theory 51 MOTOROLAECLinPS and ECLinPS Lite  

E-print Network

Transmission Line Theory 5­1 MOTOROLAECLinPS and ECLinPS Lite DL140 -- Rev 3 SECTION 2 Transmission interconnects to determine if transmission line phenomena will occur. A handy rule of thumb to determine if an interconnect trace should be considered a transmission line is if the interconnect delay is greater than 1/8th

McNeill, John A.

88

Final results for ?± production in the HARP/PS214 experiment at CERN PS  

NASA Astrophysics Data System (ADS)

The final results on ?± production in proton nucleus or ?± nucleus interactions for incident particle momenta between 1.5 GeV/c and 15 GeV/c as measured in the HARP/PS214 experiment at CERN PS are presented.

Bonesini, M.; HARP/PS214 Collaboration

2012-08-01

89

Nanocomposites Consisting of Nanoparticles with Multidentate PS Brushes Mixed with PS Matrices  

NASA Astrophysics Data System (ADS)

In order to prevent massive phase separation of nanoparticles (NP) in a polymer matrix, the relevant hybridization of NPs with polymer matrices has proven to be an effective method for the high performance of nanocomposites in applications. The surface of inorganic (gold or QD) NPs of various size was modified with polystyrene (PS) polymer brushes, poly(styrene)-block-poly(cysteamine methyl disulfide), by the ligand exchange procedure. The disulfide groups in the PS brushes act as anchoring blocks for NPs. Different PS brushes were prepared with different total molecular weights and mole fractions of disulfide moieties. Compared with NPs dispersed in PS without disulfide anchoring groups, NPs anchored with PS brushes through disulfide groups were uniformly distributed within PS matrices. The dispersion of NPs within a polymer matrix was found to be influenced by the total molecular weight of PS brushes as well as the number of anchoring disulfide groups. Furthermore, the effect of the ratio between relative size of NP and the radius of gyration of a polymer brush as well as the grafting density of PS brushes anchored onto NPs on the NP distribution within a polymer matrix is discussed.

Lee, Hyemin; Wooh, Sanghyuk; Lim, Jaehoon; Zorn, Matthias; Zentel, Rudolf; Char, Kookheon

2011-03-01

90

The Binding Energy of PsH  

NASA Astrophysics Data System (ADS)

In response to proposed measurements of Ps scattering by the St. Olaf's positron experimental group [1], we have begun a theoretical investigation of Ps scattering from simple atoms. For our first step of this investigation, we have computed the binding energy of the fundamental four-body Coulomb system, PsH. We have used a very flexible trial function of Hylleraas form which includes all inter-particle distances. Our most accurate value of the binding energy compares favorably with a previous calculation that also used Hylleraas functions [2] and with the most accurate calculation to-date which used explicitly correlated Gaussians [3]. [4pt] [1] Jason Engbrecht, Private communication, (2008).[0pt] [2] Zong-Chao Yan and Y. K. Ho, Phys. Rev. A 59, 2697 (1999).[0pt] [3] Sergiy Bubin and Ludwik Adamowicz, Phys. Rev. A 74, 052502 (2006).

Woods, D.; Ward, S. J.; van Reeth, P.

2010-03-01

91

100-ps framing-camera tube.  

PubMed

The optoelectronic framing-camera tube described is capable of recording two-dimensional image frames with high spatial resolution in the <100-ps range. Framing is performed by streaking a two-dimensional electron image across narrow slits. The resulting dissected electron line images from the slits are restored into framed images by a restorer deflector operating synchronously with the dissector deflector. The number of framed images on the tube's viewing screen equals the number of dissecting slits in the tube. Performance has been demonstrated in a prototype tube by recording 135-ps-duration framed images of 2.5-mm patterns at the cathode. The limitation in the framing speed is in the external drivers for the deflectors and not in the tube design characteristics. Faster frame speeds in the <100-ps range can be obtained by use of faster deflection drivers. PMID:18699219

Kalibjian, R

1978-07-01

92

D-Serine metabolism in C6 glioma cells: Involvement of alanine-serine-cysteine transporter (ASCT2) and serine racemase (SRR) but not D-amino acid oxidase (DAO).  

PubMed

D-serine is an endogenous N-methyl-D-aspartate (NMDA) receptor coagonist. It is synthesized from L-serine by serine racemase (SRR), but many aspects of its metabolism remain unclear, especially in the forebrain, which lacks active D-amino acid oxidase (DAO), the major D-serine degradative enzyme. Candidate mechanisms include SRR operating in alpha,beta-eliminase mode (converting D-serine to pyruvate) and regulation by serine transport, in which the alanine-serine-cysteine transporter ASCT2 is implicated. Here we report studies in C6 glioma cells, which "simulate" the forebrain, in that the cells express SRR and ASCT2 but lack DAO activity. We measured D-serine, ASCT2, SRR, and DAO expression and DAO activity in two situations: after incubation of cells for 48 hr with serine isomers and after increased or decreased SRR expression by transfection and RNA interference, respectively. Incubation with serine enantiomers decreased [(3)H]D-serine uptake and ASCT2 mRNA and increased SRR immunoreactivity but did not alter DAO immunoreactivity, and DAO activity remained undetectable. SRR overexpression increased D-serine and pyruvate and decreased [(3)H]D-serine uptake and ASCT2 mRNA but did not affect DAO. SRR knockdown did not alter any of the parameters. Our data suggest that D-serine transport mediated by ASCT2 contributes prominently to D-serine homeostasis when DAO activity is absent. The factors regulating D-serine are important for understanding normal NMDA receptor function and because D-serine, along with DAO and SRR, is implicated in the pathogenesis and treatment of schizophrenia. PMID:20091774

Sikka, Pilleriin; Walker, Rosie; Cockayne, Rebecca; Wood, Matthew J A; Harrison, Paul J; Burnet, Philip W J

2010-06-01

93

Accelerators for the PS neutrino beam  

NASA Astrophysics Data System (ADS)

A recent memorandum for an experimental proposal [1] was discussed during the CERN PS and SPS experimental committee (SPSC) of April 2011 and at the Research Board of June 2011. The proposed experiment, with objective to investigate the anomalous ?? ? ?e oscillations, aims at re-using the discontinued CERN PS Neutrino Facility (PSNF) and experimental zones to install a 150 ton liquid argon time projection chamber (LArTPC) as near detector and a 600 ton LArTPC as far detector. This article will summarize the experimental needs, the proposed facility layout, a primary beam production scheme and the requirements for the reconstruction of the PSNF.

Steerenberg, R.; Calviani, M.; Gschwendtner, E.; Pardons, A.; Vincke, H.

2013-02-01

94

Mycobacterium tuberculosis Serine/Threonine Protein Kinases  

PubMed Central

The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs). A similar number of two-component systems are also present, indicating that these two signal transduction mechanisms are both important in the adaptation of this bacterial pathogen to its environment. The M. tuberculosis phosphoproteome includes hundreds of Ser- and Thr-phosphorylated proteins that participate in all aspects of M. tuberculosis biology, supporting a critical role for the STPKs in regulating M. tuberculosis physiology. Nine of the STPKs are receptor type kinases, with an extracytoplasmic sensor domain and an intracellular kinase domain, indicating that these kinases transduce external signals. Two other STPKs are cytoplasmic and have regulatory domains that sense changes within the cell. Structural analysis of some of the STPKs has led to advances in our understanding of the mechanisms by which these STPKs are activated and regulated. Functional analysis has provided insights into the effects of phosphorylation on the activity of several proteins, but for most phosphoproteins the role of phosphorylation in regulating function is unknown. Major future challenges include characterizing the functional effects of phosphorylation for this large number of phosphoproteins, identifying the cognate STPKs for these phosphoproteins, and determining the signals that the STPKs sense. Ultimately, combining these STPK-regulated processes into larger, integrated regulatory networks will provide deeper insight into M. tuberculosis adaptive mechanisms that contribute to tuberculosis pathogenesis. Finally, the STPKs offer attractive targets for inhibitor development that may lead to new therapies for drug-susceptible and drug-resistant tuberculosis.

PRISIC, SLADJANA; HUSSON, ROBERT N.

2014-01-01

95

Proteolytic processing of presenilin-1 (PS1) is not associated with Alzheimer's disease with or without PS1 mutations  

Microsoft Academic Search

Cerebral presenilin-1 protein (PS-1) is normally composed of the amino-terminal fragment (NTF) with Mr 28 kDa and the carboxy-terminal fragment (CTF) with 18 kDa. We analyzed human PS-1 in brains with early-onset familial Alzheimer's disease (FAD) with and without PS-1 mutations to study whether mutated PS-1 was abnormally metabolized. Cerebral PS-1 were found to be cleaved into two fragments of

Masayasu Okochi; Kazuhiko Ishii; Mihoko Usami; Naruhiko Sahara; Fuyuki Kametani; Kikuko Tanaka; Peter E Fraser; Masaki Ikeda; Ann M Saunders; Lydia Hendriks; Shin-Ichi Shoji; Linda E Nee; Jean-Jacques Martin; Christine Van Broeckhoven; Peter H St. George-Hyslop; Allen D Roses; Hiroshi Mori

1997-01-01

96

The Pharmacological Landscape and Therapeutic Potential of Serine Hydrolases  

PubMed Central

Serine hydrolases play critical roles in many biological processes, and several are targets of approved drugs for indications such as type 2 diabetes, Alzheimer’s disease, and infectious disease. Despite this, most of the 200+ human serine hydrolases remain poorly characterized with respect to their physiological substrates and functions, and the vast majority lack selective, in vivo-active inhibitors. Here, we review the current state of pharmacology for mammalian serine hydrolases, including marketed drugs, compounds under clinical investigation, and selective inhibitors emerging from academic probe development efforts. We also highlight recent methodological advances that have accelerated the rate of inhibitor discovery and optimization for serine hydrolases, which we anticipate will aid in their biological characterization and, in some cases, therapeutic validation. PMID:22212679

Bachovchin, Daniel A.; Cravatt, Benjamin F.

2013-01-01

97

A randomized, double-blind, crossover study on the pharmacokinetics of a novel formulation of CoQ?? with pyridoxal 5'-phosphate and phosphatidyl choline.  

PubMed

The pharmacokinetics of a single 30-mg dose of a novel enteric-coated coenzyme Q10 (CoQ(10)) formulation with pyridoxal 5'-phosphate and phosphatidyl choline (CoQ(10)-P5P-PC) was investigated against two comparators CoQ(10) (NPN 02176955) and CoQ(10) (DIN 02231736) in 21 healthy volunteers, with screening CoQ(10) levels of 0.8 ± 0.2 mg/L. A randomized, double-blind, crossover study was designed with a washout period of 2 weeks between each formulation and blood sampled at 2, 4, 5, 6, 8, 12, 24, 48 and 72 hr postdose. Significantly, higher plasma concentrations were demonstrated for the CoQ(10) (NPN 02176955) formulation at 6 and 8 hr postdose (p = .010 and p = .042, respectively). There were no significant differences between formulations with respect to the area under the curve, AUC((0-72 hr)), or the maximum plasma concentration (C(max)). Total CoQ(10) (T(max)) reached maximum plasma concentrations at 6.4 ± 2.5 hr after supplementation with CoQ(10) (NPN 02176955), 8.0 ± 9.8 hr with CoQ(10)-P5P-PC, and 9.5 ± 9.3 hr with CoQ(10) (DIN 02231736). The estimated elimination half-life (t(1/2)) was 92.3 hr after a single oral dose of CoQ(10)-P5P-PC, 38.2 hr with CoQ(10) (NPN 02176955), and 80.7 hr with CoQ(10) (DIN 02231736). The results suggest that CoQ(10) is available for a longer time in subjects' administered with CoQ(10)-P5P-PC in comparison with the other two formulations studied. There were no significant differences in adverse events, by severity, causality, or organ system. The CoQ(10)-P5P-PC formulation was found to be superior in the t(1/2), and it may be suggested that fewer doses are required to maintain healthy circulatory CoQ(10) levels. PMID:22432561

Evans, Malkanthi; Sharma, Prachi; Guthrie, Najla

2010-12-01

98

Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine  

E-print Network

Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine Yunlei medium. Sup- plement of D-serine, an agonist for the glycine-binding site of N- methyl-D-aspartate (NMDA endogenous D-serine. By providing extracellular D-serine that facili- tates activation of NMDA receptors

Newman, Eric A.

99

ACTIVATION OF A CRYPTIC D-SERINE DEAMINASE (DSD) GENE FROM PSEUDOMONAS CEPACIA 17616  

EPA Science Inventory

D-serine inhibits growth of P. cepacia 17616; however, resistant mutants able to express an ordinarily cryptic D-serine deaminase (dsd) gene were isolated readily. The resistant strains formed high levels of a D-serine deaminase active on D-threonine as well as D-serine. IS eleme...

100

Amino Acids in Schizophrenia – Glycine, Serine and Arginine  

Microsoft Academic Search

\\u000a In recent years, there has been increased interest in the possible role of amino acids in the etiology and pharmacotherapy\\u000a of schizophrenia. Much of this research has focused on glutamate and ?-aminobutyric acid (GABA), and these are the subjects\\u000a of other chapters in this book. However, there have also been interesting findings reported with glycine, serine (particularly\\u000a D-serine) and arginine,

Glen B. Baker; Jaime E. C. Hallak; Alexandria F. Dilullo; Lisa Burback; Serdar M. Dursun

101

d-Serine-induced nephrotoxicity: possible interaction with tyrosine metabolism  

Microsoft Academic Search

d-Serine selectively damages renal proximal tubule cells in rats by a mechanism that is not fully understood. Recent proteomic analysis identified that d-serine elevated plasma fumarylacetoacetate hydrolase (FAH). FAH is involved in tyrosine catabolism; hence, this pathway may be involved in mediating the toxicity. This work examines whether 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC), a potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) located

R. E Williams; E. A Lock

2004-01-01

102

D-serine-induced nephrotoxicity: possible interaction with tyrosine metabolism.  

PubMed

D-serine selectively damages renal proximal tubule cells in rats by a mechanism that is not fully understood. Recent proteomic analysis identified that D-serine elevated plasma fumarylacetoacetate hydrolase (FAH). FAH is involved in tyrosine catabolism; hence, this pathway may be involved in mediating the toxicity. This work examines whether 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione (NTBC), a potent inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) located upstream of FAH, modulates D-serine-induced nephrotoxicity. Rats were pretreated with NTBC (0.5 mg/kg p.o.) or corn oil and then 30 min later given either D-serine (250 mg/kg i.p.) or water. Urine was collected every 12 h until termination (48 h) and analysed by 1H NMR spectroscopy and principal component analysis (PCA). Markers of proximal tubule injury were evident in urine following treatment with D-serine and NTBC + D-serine. PCA could not distinguish between these urine samples suggesting that NTBC does not effect the development of nephrotoxicity. Clinical chemistry analysis of urine and terminal plasma samples and histopathological examination of the kidneys confirmed this. NTBC alone caused a marked increase in the excretion of 4-hydroxyphenylpyruvate (HPPA) and 4-hydroxyphenyllactate (HPLA); however, HPPA and HPLA excretion was minimal following NTBC + D-serine. Instead marked tyrosinuria was observed suggesting that D-serine-induced renal damage markedly affects the handling of increased levels of HPPA and HPLA resulting from the inhibition of HPPD. PMID:15297036

Williams, R E; Lock, E A

2004-09-01

103

Astrocytes release D-serine by a large vesicle.  

PubMed

Long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus depends on the activation of N-methyl-D-aspartate receptors (NMDARs), which can be regulated by Ca²?-dependent release of D-serine from astrocytes. The detailed mechanism underlying astrocytic d-serine release is still unknown. In hippocampal slices prepared from Sprague-Dawley rats, we found that clamping astrocytic [Ca²?] at 100-150 nM or puffing artificial cerebrospinal fluid (ACSF) into the extracellular space (weak mechanical stimulation) enhanced the synaptic activation of NMDARs. The enhancement was blocked by the NMDAR glycine site antagonist 5,7-dichlorokynurenic acid, glycine saturation, and infusion of astrocytes with D-amino acid oxidase and the serine racemase inhibitor L-erythro-3-hydroxyaspartate, suggesting the involvement of astrocytic D-serine release. Intracellular 100-150 nM [Ca²?] or puffing ACSF stimulated astrocytes to generate D-serine-containing large vesicles (1-3 ?m), exocytotic fusion of which released D-serine. The formation of astrocytic large vesicles involved the intracellular fusion of small vesicles and/or other organelles. Spontaneous fusion of large vesicles occurred occasionally in astrocytes at rest, contributing to baseline D-serine levels, which increased the rising slope of NMDAR post-burst potentiation (PBP) without altering the PBP peak amplitude. Thus, under physiological conditions, astrocytic D-serine release by large vesicles facilitated weak theta-burst (TBS consisting of five bursts), but not strong TBS (TBS consisting of 10 bursts) stimulation-induced LTP. PMID:23485803

Kang, N; Peng, H; Yu, Y; Stanton, P K; Guilarte, T R; Kang, J

2013-06-14

104

Structural and functional diversities in lepidopteran serine proteases  

Microsoft Academic Search

Primary protein-digestion in Lepidopteran larvae relies on serine proteases like trypsin and chymotrypsin. Efforts toward\\u000a the classification and characterization of digestive proteases have unraveled a considerable diversity in the specificity\\u000a and mechanistic classes of gut proteases. Though the evolutionary significance of mutations that lead to structural diversity\\u000a in serine proteases has been well characterized, detailing the resultant functional diversity has

Ajay Srinivasan; Ashok P. Giri; Vidya S. Gupta

2006-01-01

105

Chromosome 14 familial Alzheimer’s disease: the clinical and neuropathological characteristics of a family with a leucine?serine (L250S) substitution at codon 250 of the presenilin 1 gene  

Microsoft Academic Search

BACKGROUNDSeven affected members are described from a kindred with autosomal dominant familial Alzheimer’s disease associated with a novel mutation in the presenilin 1 (PS1) gene on chromosome 14 that results in a leucine to serine substitution at codon 250 (L250S).METHODClinical information on the pedigree was collected directly from family members including affected members and their carers and also from hospital

Richard J Harvey; David Ellison; John Hardy; Mike Hutton; Penelope K Roques; John Collinge; Nick C Fox; Martin N Rossor

1998-01-01

106

Beyond metric gravity: Progress on PS-200  

SciTech Connect

The reconciliation of quantum mechanics and gravity on varying distance scales requires changes to General Relativity that may be testable implications. We briefly review the status of tests with matter of the inverse square law and the principle of equivalence, then report on progress on the drift-tube measurement section of PS- 200, the experiment to measure the gravitational acceleration of antiprotons.

Goldman, T.; Brown, R.E.; Camp, J.B.; Darling, T.; Dyer, P.; Holzscheiter, M.H.; Hughes, R.J.; Jarmie, N.; King, N.S.P.; Lizon, D.C.; Nieto, M.M.; Schauer, M.M.M.; Schecker, J.A. (Los Alamos National Lab., NM (United States)); Cornford, S.; Hosea, K.; Kenefick, R.A. (Texas A and M Univ., College Station, TX (United States)); Hoibraaten, S.; Midzor, M.M.; Parry, S.P.; Ristenen, R.A. (Colorado Univ., Boulder, CO (U

1993-01-01

107

Beyond metric gravity: Progress on PS-200  

SciTech Connect

The reconciliation of quantum mechanics and gravity on varying distance scales requires changes to General Relativity that may be testable implications. We briefly review the status of tests with matter of the inverse square law and the principle of equivalence, then report on progress on the drift-tube measurement section of PS- 200, the experiment to measure the gravitational acceleration of antiprotons.

Goldman, T.; Brown, R.E.; Camp, J.B.; Darling, T.; Dyer, P.; Holzscheiter, M.H.; Hughes, R.J.; Jarmie, N.; King, N.S.P.; Lizon, D.C.; Nieto, M.M.; Schauer, M.M.M.; Schecker, J.A. [Los Alamos National Lab., NM (United States); Cornford, S.; Hosea, K.; Kenefick, R.A. [Texas A and M Univ., College Station, TX (United States); Hoibraaten, S.; Midzor, M.M.; Parry, S.P.; Ristenen, R.A. [Colorado Univ., Boulder, CO (United States); Witteborn, F.C. [National Aeronautics and Space Administration, Moffett Field, CA (United States). Ames Research Center; Rochet, J. [European Organization for Nuclear Research, Geneva (Switzerland)

1993-03-01

108

Sequence and phylogenetic analysis of viper venom serine proteases  

PubMed Central

Snakebites are a major neglected tropical disease responsible for as many as 95000 deaths every year worldwide. Viper venom serine proteases disrupt haemostasis of prey and victims by affecting various stages of the blood coagulation system. A better understanding of their sequence, structure, function and phylogenetic relationships will improve the knowledge on the pathological conditions and aid in the development of novel therapeutics for treating snakebites. A large dataset for all available viper venom serine proteases was developed and analysed to study various features of these enzymes. Despite the large number of venom serine protease sequences available, only a small proportion of these have been functionally characterised. Although, they share some of the common features such as a C-terminal extension, GWG motif and disulphide linkages, they vary widely between each other in features such as isoelectric points, potential N-glycosylation sites and functional characteristics. Some of the serine proteases contain substitutions for one or more of the critical residues in catalytic triad or primary specificity pockets. Phylogenetic analysis clustered all the sequences in three major groups. The sequences with substitutions in catalytic triad or specificity pocket clustered together in separate groups. Our study provides the most complete information on viper venom serine proteases to date and improves the current knowledge on the sequence, structure, function and phylogenetic relationships of these enzymes. This collective analysis of venom serine proteases will help in understanding the complexity of envenomation and potential therapeutic avenues. PMID:23055627

Vaiyapuri, Sakthivel; Thiyagarajan, Nethaji; Hutchinson, E Gail; Gibbins, Jonathan M

2012-01-01

109

Serine protease activities in Leishmania (Leishmania) chagasi promastigotes.  

PubMed

The present work reports the isolation, biochemical characterization, and subcellular location of serine proteases from aqueous, detergent soluble, and culture supernatant of Leishmania chagasi promastigote extracts, respectively, LCSII, LCSI, and LCSIII. The active enzyme molecular masses of LCSII were about 105, 66, and 60 kDa; of LCSI, 60 and 58 kDa; and of LCSIII, approximately 76 and 68 kDa. Optimal pH for the enzymes was 7.0 for LCSI and LCSIII and 8.5 for LCSII, and the optimal temperature for all enzymes was 37°C, using ?-N-?-tosyl-L: -arginine methyl ester as substrate. Assay of thermal stability indicated that LCSIII is the more stable enzyme. Hemoglobin, bovine serum albumin, and ovalbumin were hydrolyzed by LCSII and LCSI but not by LCSIII. Inhibition studies suggested that enzymes belong to the serine protease class modulated by divalent cations. Rabbit antiserum against 56-kDa serine protease of Leishmania amazonensis identified proteins in all extracts of L. chagasi. Furthermore, immunocytochemistry demonstrated that serine proteases are located in flagellar pocket region and cytoplasmic vesicles of L. chagasi promastigotes. These findings indicate that L. chagasi serine proteases differ from L. amazonensis proteases and all known flagellate proteases, but display some similarities with serine proteases from other Leishmania species, suggesting a conservation of this enzymatic activity in the genus. PMID:20668879

da Silva-López, Raquel Elisa; dos Santos, Tatiana Resende; Morgado-Díaz, José Andrés; Tanaka, Marcelo Neves; de Simone, Salvatore Giovanni

2010-10-01

110

D-Serine, an Endogenous Synaptic Modulator: Localization to Astrocytes and Glutamate-Stimulated Release  

Microsoft Academic Search

Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-serine immunoreactivity correlate closely with those of D-serine binding to the glycine modulatory site of the N-methyl-D-aspartate (NMDA)

Michael J. Schell; Mark E. Molliver; Solomon H. Snyder

1995-01-01

111

D-Serine Production, Degradation, and Transport in ALS: Critical Role of Methodology  

PubMed Central

In mammalian systems, D-serine is perhaps the most biologically active D-amino acid described to date. D-serine is a coagonist at the NMDA-receptor, and receptor activation is dependent on D-serine binding. Because D-serine binding dramatically increases receptor affinity for glutamate, it can produce excitotoxicity without any change in glutamate per se. D-serine is twofold higher in the spinal cords of mSOD1 (G93A) ALS mice, and the deletion of serine racemase (SR), the enzyme that produces D-serine, results in an earlier onset of symptoms, but with a much slower rate of disease progression. Localization studies within the brain suggest that mSOD1 and subsequent glial activation could contribute to the alterations in SR and D-serine seen in ALS. By also degrading both D-serine and L-serine, SR appears to be a prime bidirectional regulator of free serine levels in vivo. Therefore, accurate and reproducible measurements of D-serine are critical to understanding its regulation by SR. Several methods for measuring D-serine have been employed, and significant issues related to validation and standardization remain unresolved. Further insights into the intracellular transport and tissue-specific compartmentalization of D-serine within the CNS will aid in the understanding of the role of D-serine in the pathogenesis of ALS. PMID:23029613

Crow, John P.; Marecki, John C.; Thompson, Misty

2012-01-01

112

A new strategy to decrease N-methyl-D-aspartate (NMDA) receptor coactivation: Inhibition of D-serine synthesis by converting serine racemase into an eliminase  

Microsoft Academic Search

Serine racemase is a brain-enriched enzyme that synthesizes D- serine, an endogenous modulator of the glycine site of N-methyl- D-aspartate (NMDA) receptors. We now report that serine race- mase catalyzes an elimination reaction toward a nonphysiological substrate that provides a powerful tool to study its neurobiological role and will be useful to develop selective enzyme inhibitors. Serine racemase catalyzes robust

Rogério Panizzutti; Joari de Miranda; Cátia S. Ribeiro; Simone Engelender; Herman Wolosker

2001-01-01

113

Paradoxical roles of serine racemase and D-serine in the G93A mSOD1 mouse model of amyotrophic lateral sclerosis.  

PubMed

D-serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of D-serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of D-serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by D-amino acid oxidase (DAO). However, SR itself possesses a well-characterized eliminase activity, which effectively degrades D-serine as well. D-serine is increased two-fold in spinal cords of G93A Cu,Zn-superoxide dismutase (SOD1) mice--the standard model of amyotrophic lateral sclerosis (ALS). ALS mice with SR disruption show earlier symptom onset, but survive longer (progression phase is slowed), in an SR-dependent manner. Paradoxically, administration of D-serine to ALS mice dramatically lowers cord levels of D-serine, leading to changes in the onset and survival very similar to SR deletion. D-serine treatment also increases cord levels of the alanine-serine-cysteine transporter 1 (Asc-1). Although the mechanism by which SOD1 mutations increases D-serine is not known, these results strongly suggest that SR and D-serine are fundamentally involved in both the pre-symptomatic and progression phases of disease, and offer a direct link between mutant SOD1 and a glial-derived toxic mediator. PMID:22117694

Thompson, Misty; Marecki, John C; Marinesco, Stephane; Labrie, Viviane; Roder, John C; Barger, Steven W; Crow, John P

2012-02-01

114

Intrinsic Viscosity Characterization of PS and PMMA  

NSDL National Science Digital Library

In this experiment, you will use intrinsic viscosity measurements to determine the molecular weight of polystyrene, PS, or poly(methyl methacrylate), PMMA. After in-class presentation, completion of hands-on laboratory experiment and review of the information provided, you should be able to: ⢠Identify several laboratory methods for molecular weight analysis of polymers. ⢠Confidently discuss the differences between the methods of analysis for polymer molecular weight. ⢠Discuss how polymer solution behavior affects molecular weight measurements.

Derosa, Rebecca L.

2008-09-26

115

Small-angle AVO response of PS-waves in tilted transversely isotropic media  

E-print Network

the small-angle reflection coefficients of the split converted PS1- and PS2-waves RPS1 and RPS2 of energy between the PS1 and PS2 modes. Because of their substantial amplitude, small-angle PS reflec into two modes traveling with different velocities -- PS1 and PS2. The main focus of the paper

Tsvankin, Ilya

116

Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy  

PubMed Central

Background Recent data indicate that inflammatory mechanisms contribute to diabetic retinopathy (DR). We have determined that serine racemase (SR) expression is increased by inflammatory stimuli including liposaccharide (LPS), amyloid ?-peptide (A-beta), and secreted amyloid precursor protein (sAPP); expression is decreased by the anti-inflammatory drug, dexamethasone. We tested possibility that SR and its product, D-serine, were altered in a rat model of DR. Methods Intraperitoneal injection of streptozotocin (STZ; 70 mg/kg body weight) to Sprague-Dawley rats produced type-I diabetic mellitus (fasting blood sugar higher than 300 mg/dL). At 3 and 5 months after STZ or saline injection, retinas from some rats were subjected to cryosectioning for immunofluorescent analysis of SR and TUNEL assay of apoptosis. Retinal homogenates were used to detect SR levels and Jun N-terminal kinase (JNK) activation by immunoblotting. Aqueous humor and retina were also collected to assay for neurotransmitters, including glutamate and D-serine, by reverse-phase HPLC. Results Compared to saline-injected rats, STZ-injected (diabetic) rats showed elevation of SR protein levels in retinal homogenates, attributed to the inner nuclear layer (INL) by immunofluorescence. Aqueous humor fluid from STZ-injected rats contained significantly higher levels of glutamate and D-serine compared to controls; by contrast, D-serine levels in retinas did not differ. Levels of activated JNK were elevated in diabetic retinas compared to controls. Conclusions Increased expression of SR in retina and higher levels of glutamate and D-serine in aqueous humor of STZ-treated rats may result from activation of the JNK pathway in diabetic sequelae. Our data suggest that the inflammatory conditions that prevail during DR result in elevation of D-serine, a neurotransmitter contributing to glutamate toxicity, potentially exacerbating the death of retinal ganglion cells in this condition. PMID:21939517

2011-01-01

117

D-serine in neurobiology: CNS neurotransmission and neuromodulation.  

PubMed

Homochirality is fundamental for life. L-Amino acids are exclusively used as substrates for the polymerization and formation of peptides and proteins in living systems. However, D- amino acids were recently detected in various living organisms, including mammals. Of these D-amino acids, D-serine has been most extensively studied. D-Serine was found to play an important role as a neurotransmitter in the human central nervous system (CNS) by binding to the N-methyl- D-aspartate receptor (NMDAr). D-Serine binds with high affinity to a co-agonist site at the NMDAr and, along with glutamate, mediates several vital physiological and pathological processes, including NMDAr transmission, synaptic plasticity and neurotoxicity. Therefore, a key role for D-serine as a determinant of NMDAr mediated neurotransmission in mammalian CNS has been suggested. In this context, we review the known functions of D-serine in human physiology, such as CNS development, and pathology, such as neuro-psychiatric and neurodegenerative diseases related to NMDAr dysfunction. PMID:24534026

Bardaweel, Sanaa K; Alzweiri, Muhammed; Ishaqat, Aman A

2014-03-01

118

Effects of L-serine ingestion on human sleep.  

PubMed

To investigate the effects of L-serine intake on human sleep, we conducted two randomized double-blinded crossover studies. In Study 1, healthy subjects who were dissatisfied with their sleep were given L-serine or a placebo 30 min before going to bed. After waking the next morning, subjective sleep quality was rated using the Ogri-Shirakawa-Azumi subjective sleep rating scale. In Study 2, subjective sleep quality was rated using the St. Mary's Hospital sleep questionnaire, and objective parameters, including sleep initiation time, number of nighttime awakenings, and hours of sleep, were evaluated using actigraphy. In Study 1, factors related to "sleep initiation" and "sleep maintenance" during the L-serine intake period were significantly improved compared to the placebo intake period (p?=?0.02 and p?=?0.008, respectively). In Study 2, scores for "How well did you sleep last night?" and "How satisfied were you with last night's sleep?" were significantly better during L-serine intake compared to placebo (p?=?0.04 and p?=?0.03, respectively). Subjective evaluation of sleep quality on waking was thus improved. In addition, objective evaluation using actigraphy showed that the "number of nighttime awakenings" tended to be decreased (p?=?0.08). These findings suggest that intake of L-serine before going to bed may improve human sleep. PMID:25197619

Ito, Yukihiko; Takahashi, Satomi; Shen, Manzhen; Yamaguchi, Kohji; Satoh, Makoto

2014-01-01

119

The serine shuttle between glia and neurons: implications for neurotransmission and neurodegeneration.  

PubMed

D-Serine is a physiological co-agonist of NMDARs (N-methyl-D-aspartate receptors) required for neurotransmission, synaptic plasticity and neurotoxicity. There is no consensus, however, on the relative roles of neurons and astrocytes in D-serine signalling. The effects of D-serine had been attributed to its role as a gliotransmitter specifically produced and released by astrocytes. In contrast, recent studies indicate that neurons regulate their own NMDARs by releasing D-serine via plasma membrane transporters and depolarization-sensitive pathways. Only a minority of astrocytes contain authentic D-serine, whereas neuronal D-serine accounts for up to 90% of the total D-serine pool. Neuronal and glial D-serine production requires astrocytic L-serine generated by a 3-phosphoglycerate dehydrogenase-dependent pathway. These findings support a model whereby astrocyte-derived L-serine shuttles to neurons to fuel the synthesis of D-serine by serine racemase. We incorporate these new findings in a revised model of serine dynamics, called the glia-neuron serine shuttle, which highlights the role of glia-neuron cross-talk for optimal NMDAR activity and brain development. PMID:24256252

Wolosker, Herman; Radzishevsky, Inna

2013-12-01

120

Memantine improves spatial learning and memory impairments by regulating NGF signaling in APP/PS1 transgenic mice.  

PubMed

Memantine (MEM) is used for improving the cognitive impairments of the patients suffering from Alzheimer's disease (AD) by multiple neuroprotective mechanisms. However, it is still not clear whether nerve growth factor (NGF) signaling is involved in the mechanisms of MEM. The present study investigated the neuroprotective effects of MEM treatment on the cognitive performance and amyloidosis in APP/PS1 transgenic mice, and disclosed the NGF-related mechanism of MEM. We found that MEM treatment improved the cognitive performance by decreasing the escape latency and path length in the navigation test, by shortening the duration in target quadrant and reducing the frequency to pass through the target in probe trial, and by prolonging the latency and decreasing the frequencies of entering the dark compartment in passive avoidance test. The over-expressions of A?(1-42) and amyloid precursor protein (APP) were also decreased in the brains of APP/PS1 mice. Interestingly, MEM treatment improved the decreased NGF levels in APP/PS1 mice. Furthermore, NGF/TrkA signaling was activated by increasing the phosphorylation levels of tyrosine kinase (TrkA), proto-oncogene serine/threonine-protein kinase, Raf1 (c-Raf), extracellular regulated protein kinases (ERK)1/2 and cAMP-response element binding protein (CREB) after MEM treatment. Simultaneously, MEM also inhibited NGF/p75(NTR) signaling via decreasing the cleavage substrate of p75(NTR), increasing the JNK2 phosphorylation and decreasing the levels of p53 and cleaved-caspase 3. Therefore, the dual-regulation on NGF signaling was attributed to the improvements of cognitive deficits and A? depositions in APP/PS1 mice. In conclusion, MEM treatment activated the NGF/TrkA signaling, and inhibited the p75(NTR) signaling in APP/PS1 mice to ameliorate the behavioral deficits and amyloidosis, indicating that NGF signaling was a new potential target of MEM treatment for AD therapy. PMID:24846616

Liu, M Y; Wang, S; Yao, W F; Zhang, Z J; Zhong, X; Sha, L; He, M; Zheng, Z H; Wei, M J

2014-07-25

121

Paradoxical roles of serine racemase and D-serine in the G93A mSOD1 mouse model of ALS  

PubMed Central

D-serine is an endogenous neurotransmitter that binds to the NMDA receptor, thereby increasing the affinity for glutamate, and the potential for excitotoxicity. The primary source of D-serine in vivo is enzymatic racemization by serine racemase (SR). Regulation of D-serine in vivo is poorly understood, but is thought to involve a combination of controlled production, synaptic reuptake by transporters, and intracellular degradation by D-amino acid oxidase (DAO). However, SR itself possesses a well-characterized eliminase activity which effectively degrades D-serine as well. D-serine is increased two-fold in spinal cords of G93A SOD1 mice – the standard model of amyotrophic lateral sclerosis (ALS). ALS mice with SR disruption show earlier symptom onset, but survive longer (progression phase is slowed), in an SR-dependent manner. Paradoxically, administration of D-serine to ALS mice dramatically lowers cord levels of D-serine, leading to changes in onset and survival very similar to SR deletion. D-serine treatment also increases cord levels of the transporter Asc-1. Although the mechanism by which SOD1 mutations increases D-serine is not known, these results strongly suggest that SR and D-serine are fundamentally involved in both the presymptomatic and progression phases of disease, and offer a direct link between mutant SOD1 and a glial-derived toxic mediator. PMID:22117694

Thompson, Misty; Marecki, John C.; Marinesco, Stephane; Labrie, Viviane; Roder, John C.; Barger, Steven W.; Crow, John P.

2012-01-01

122

Singly differential cross sections with exchange for Ps-fragmentation  

E-print Network

Ps ionization in Ps-atom scattering is of fundamental importance. The singly differential cross sections (SDCS) provides more accurate information to test a theory than integrated or total ionization cross section since the averaging over one parameter is not required. We evaluate the SDCS for Ps-ionization with respect to the longitudinal energy distribution of the break-up positron and electron in Ps-H and Ps-He scattering and compare them with the recently available experimental and theoretical data.

Hasi Ray

2008-08-28

123

PAN/PS elctrospun fibers for oil spill cleanup  

NASA Astrophysics Data System (ADS)

A high-capacity oil sorbent was fabricated by electrospinning using PS/PAN blend. Morphology, contact angle and oil adsorption of PAN/PS fiber and PP nonwoven fabric were studied. It was found that the PAN/PS fiber had a smaller diameter than PP, and the maximum sorption capacities of the PAN/PS sorbent for pump oil, peanut oil, diesel, and gasoline were 194.85, 131.7, 66.75, and 43.38 g/g, which were far higher than those of PP. The sorbent PS/PAN fiber showed a contact angle of water144.32° and diesel oil 0°. The sorption kinetics of PAN/PS and PP sorbent were also investigated. Compared with the commercial PP fabric, the PAN/PS fiber seems to have the ability to be used in oil-spill cleanup application.

Ying, Qiao; Lili, Zhao; Haixiang, Sun; Peng, Li

2014-08-01

124

Phospholipid Metabolism in Ferrobacillus ferrooxidans  

PubMed Central

The lipid composition of the chemoautotroph Ferrobacillus ferrooxidans has been examined. Fatty acids represent 2% of the dry weight of the cells and 86% of the total are extractable with organic solvents. About 25% of the total fatty acids are associated with diacyl phospholipids. Polar carotenoids, the benzoquinone coenzyme Q-8, and most of the fatty acids are present in the neutral lipids. The phospholipids have been identified as phosphatidyl monomethylethanolamine (42%), phosphatidyl glycerol (23%), phosphatidyl ethanolamine (20%), cardiolipin (13%), phosphatidyl choline (1.5%), and phosphatidyl dimethylethanolamine (1%) by chromatography of the diacyl lipids, by chromatography in four systems of the glycerol phosphate esters derived from the lipids by mild alkaline methanolysis, and by chromatographic identification of the products of acid hydrolysis of the esters. No trace of phosphatidylserine (PS), glycerolphosphorylserine, or serine could be detected in the lipid extract or in derivatives of that extract. This casts some doubt on the postulated involvement of PS in iron metabolism. After growth in the presence of 14C and 32P, there was essentially no difference in the turnover of either isotope in the glycerolphosphate ester derived from each lipid in cells grown at pH 1.5 or 3.5. Images PMID:5802599

Short, Steven A.; White, David C.; Aleem, M. I. H.

1969-01-01

125

Changes in plasma d-serine, l-serine, and glycine levels in treatment-resistant schizophrenia before and after clozapine treatment.  

PubMed

Hypofunction of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptors may be involved in the pathophysiology of schizophrenia. Many studies have investigated peripheral NMDA receptor-related glutamatergic amino acid levels because of their potential as biological markers. Peripheral d-serine levels and the ratio of d-serine to total serine have been reported to be significantly lower in patients with schizophrenia than in controls. Peripheral d-serine levels and the d-/l-serine ratio have also been reported to significantly increase in patients with schizophrenia as their clinical symptoms improve from the time of admission to the time of discharge. In this study, we examined whether peripheral NMDA receptor-related glutamatergic amino acids levels were altered in patients with treatment-resistant schizophrenia compared to controls and whether these peripheral amino acids levels were altered by clozapine treatment. Twenty-two patients with treatment-resistant schizophrenia and 22 age- and gender-matched healthy controls were enrolled. The plasma levels of d-serine, l-serine, glycine, glutamate, and glutamine were measured before and after clozapine treatment. We found that the plasma levels of d-serine and the d-/l-serine ratio were significantly lower in the patients before clozapine treatment than in the controls. The d-/l-serine ratio was significantly increased by clozapine treatment in patients, and no significant difference was observed in the plasma levels of d-serine and the d-/l-serine ratio between the patients after clozapine treatment and the controls. We also found that plasma glycine levels and the glycine/l-serine ratio were significantly increased following clozapine treatment in the patients, and the glycine/l-serine ratio was significantly higher in the patients after clozapine treatment than in the controls. There was no significant difference in the plasma levels of glutamate and glutamine both between the controls and patients and between before and after clozapine treatment. This study firstly demonstrated changes of d-/l-serine and glycine/l-serine ratio between before and after clozapine treatment, suggesting that the plasma d-/l-serine ratio and glycine/l-serine ratio could be markers of therapeutic efficacy or clinical state in treatment-resistant schizophrenia. PMID:25218715

Yamamori, Hidenaga; Hashimoto, Ryota; Fujita, Yuko; Numata, Shusuke; Yasuda, Yuka; Fujimoto, Michiko; Ohi, Kazutaka; Umeda-Yano, Satomi; Ito, Akira; Ohmori, Tetsuro; Hashimoto, Kenji; Takeda, Masatoshi

2014-10-17

126

A r t i c l e SERINE PROTEASE FROM MIDGUT  

E-print Network

was isolated from midguts of the bumblebee male Bombus terrestris by a combination of precipitation procedures and Physiology, March 2013 Keywords: Bombus terrestris; midgut; serine protease; bumblebee INTRODUCTION Serine

Miksik, Ivan

127

Localization of serine racemase and its role in the skin.  

PubMed

D-serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase (SR). Recently, the NMDA receptor has been found to be expressed in keratinocytes (KCs) of the skin and involved in the regulation of KC growth and differentiation. However, the localization and role of SR in the skin remain unknown. Here, using SR-knockout (SR-KO) mice as the control, we demonstrated the localization of the SR protein in the granular and cornified layer of the epidermis of wild-type (WT) mice and its appearance in confluent WT KCs. We also demonstrated the existence of a mechanism for conversion of L-serine to D-serine in epidermal KCs. Furthermore, we found increased expression levels of genes involved in the differentiation of epidermal KCs in adult SR-KO mice, and alterations in the barrier function and ultrastructure of the epidermis in postnatal day 5 SR-KO mice. Our findings suggest that SR in the skin epidermis is involved in the differentiation of epidermal KCs and the formation of the skin barrier. PMID:24441099

Inoue, Ran; Yoshihisa, Yoko; Tojo, Yosuke; Okamura, Chieko; Yoshida, Yuzo; Kishimoto, Jiro; Luan, Xinghua; Watanabe, Masahiko; Mizuguchi, Mineyuki; Nabeshima, Yuko; Hamase, Kenji; Matsunaga, Kenji; Shimizu, Tadamichi; Mori, Hisashi

2014-06-01

128

Localization of Serine Racemase and Its Role in the Skin  

PubMed Central

D-Serine is an endogenous coagonist of the N-methyl-D-aspartate (NMDA)–type glutamate receptor in the central nervous system and its synthesis is catalyzed by serine racemase (SR). Recently, the NMDA receptor has been found to be expressed in keratinocytes (KCs) of the skin and involved in the regulation of KC growth and differentiation. However, the localization and role of SR in the skin remain unknown. Here, using SR-knockout (SR-KO) mice as the control, we demonstrated the localization of the SR protein in the granular and cornified layer of the epidermis of wild-type (WT) mice and its appearance in confluent WT KCs. We also demonstrated the existence of a mechanism for conversion of L-serine to D-serine in epidermal KCs. Furthermore, we found increased expression levels of genes involved in the differentiation of epidermal KCs in adult SR-KO mice, and alterations in the barrier function and ultrastructure of the epidermis in postnatal day 5 SR-KO mice. Our findings suggest that SR in the skin epidermis is involved in the differentiation of epidermal KCs and the formation of the skin barrier. PMID:24441099

Inoue, Ran; Yoshihisa, Yoko; Tojo, Yosuke; Okamura, Chieko; Yoshida, Yuzo; Kishimoto, Jiro; Luan, Xinghua; Watanabe, Masahiko; Mizuguchi, Mineyuki; Nabeshima, Yuko; Hamase, Kenji; Matsunaga, Kenji; Shimizu, Tadamichi; Mori, Hisashi

2014-01-01

129

A serine sensor for multicellularity in a bacterium  

PubMed Central

We report the discovery of a simple environmental sensing mechanism for biofilm formation in the bacterium Bacillus subtilis that operates without the involvement of a dedicated RNA or protein. Certain serine codons, the four TCN codons, in the gene for the biofilm repressor SinR caused a lowering of SinR levels under biofilm-inducing conditions. Synonymous substitutions of these TCN codons with AGC or AGT impaired biofilm formation and gene expression. Conversely, switching AGC or AGT to TCN codons upregulated biofilm formation. Genome-wide ribosome profiling showed that ribosome density was higher at UCN codons than at AGC or AGU during biofilm formation. Serine starvation recapitulated the effect of biofilm-inducing conditions on ribosome occupancy and SinR production. As serine is one of the first amino acids to be exhausted at the end of exponential phase growth, reduced translation speed at serine codons may be exploited by other microbes in adapting to stationary phase. DOI: http://dx.doi.org/10.7554/eLife.01501.001 PMID:24347549

Subramaniam, Arvind R; DeLoughery, Aaron; Bradshaw, Niels; Chen, Yun; O'Shea, Erin; Losick, Richard; Chai, Yunrong

2013-01-01

130

Potentiation of NMDA Receptor Function by the Serine Protease Thrombin  

E-print Network

Potentiation of NMDA Receptor Function by the Serine Protease Thrombin Melissa B. Gingrich, Candice protease sig- naling system including the protease-activated receptor-1 (PAR1), for which thrombin- ceptor responses by thrombin can be blocked by thrombin and a protein kinase inhibitor, and the effects

Traynelis, Stephen F.

131

Food availability and immune capacity in serin ( Serinus serinus ) nestlings  

Microsoft Academic Search

Parental feeding effort is an important determinant of chick development in birds. Quality and amount of food provided to each nestling, however, might affect the development of the immune system. Food availability around the nest site may account for part of the difference in body condition and immune capacity of nestlings. We tested this idea in the socially monogamous serin

Maria Hoi-Leitner; Marilo Romero-Pujante; Herbert Hoi; A. Pavlova

2001-01-01

132

Serine protease from midgut of Bombus terrestris males.  

PubMed

A serine protease was isolated from midguts of the bumblebee male Bombus terrestris by a combination of precipitation procedures with column chromatography. The purified enzyme exhibited two bands with molecular masses of 25 and 26 kDa as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. These bands showed a proteolytic activity in zymography assay. Midgut enzymes showed optimum proteolytic activity at pH 9 and 35°C using N-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenyl-alanine 4-nitroanilide as a substrate. The Michaelis constant (Km) and maximum reaction rate (Vmax) were 0.55±0.042 mM and 0.714±0.056 ?mol p-nitroalanine produced min(-1) mg protein(-1) , respectively. Inhibition was affected by trypsin inhibitor, but not by phenylmethylsulfonyl fluoride and N-tosyl-L-phenylalanine chloromethyl ketone, which indicated the trypsin-like but not chymotrypsin-like specificity. The identity of the serine protease was confirmed by nanoliquid-tandem mass spectrometry. Eleven unique peptides of the B. terrestris serine protease were found. It shows high homology to a previously reported B. ignitus serine protease covering more than 65% of the protein amino acid sequence. PMID:23303700

Brabcová, Jana; Kindl, Ji?í; Valterová, Irena; Pichová, Iva; Zarevúcka, Marie; Brabcová, Jana; Jágr, Michal; Mikšík, Ivan

2013-03-01

133

Subcellular Discharge of a Serine Protease Mediates Release of Invasive  

E-print Network

, Medical Research Council Technology, Mill Hill, London NW7 1AA, UK 3Guy's, King's and St. Thomas of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates al., 2003). Particular interest has focused on members of the serine-rich anti- gen (SERA) family

Arnold, Jonathan

134

Dynamics simulation of the interaction between serine and water  

NASA Astrophysics Data System (ADS)

Using the first principles density functional theory (DFT), we simulated the neutron scattering spectra of the hydration dynamics of serine. Experimental data analyses have shown that dissociative H2O molecules were more likely to form hydrogen bonds (H-bonds) with an -OH group in monohydrated serine and easily shift to a -NH_3 ^ + group at a higher hydration level [P. Zhang, Y. Zhang, S. H. Han, Q. W. Yan, R. C. Ford, and J. C. Li, J. Phys. Chem. A 110, 5000 (2006), 10.1021/jp0569741]. We set the 1:1 ratio hydrated compounds at the two positions and found that the H2O could be optimized to form H-bonds with -OH and -NH3+ separately. When the simulated phonon signals of the -OH…H2O and -NH3+…H2O combinations were summed on a 3:1 scale, the calculating spectra were in good agreement with the experimental results, especially for the peak at 423 cm-1 of the -OH…H2O combination and the peak at 367 cm-1 of the -NH3+…H2O combination, which mutually complemented the real spectrum. We confirm that H2O may break the intermolecular H-bonds of the interlaced binding -OH to form a new structure, and that with the skeleton deformation of serine, H2O forms stronger H-bonds more often with the -NH3+ side indicating the flexible dynamic mechanism of the serine hydration process.

Liu, Yang; Zhang, Peng; Lu, Ying-Bo; Han, Sheng-Hao; Yu, Hui

2013-05-01

135

Dynamics simulation of the interaction between serine and water.  

PubMed

Using the first principles density functional theory (DFT), we simulated the neutron scattering spectra of the hydration dynamics of serine. Experimental data analyses have shown that dissociative H2O molecules were more likely to form hydrogen bonds (H-bonds) with an -OH group in monohydrated serine and easily shift to a -NH3 (+) group at a higher hydration level [P. Zhang, Y. Zhang, S. H. Han, Q. W. Yan, R. C. Ford, and J. C. Li, J. Phys. Chem. A 110, 5000 (2006)]. We set the 1:1 ratio hydrated compounds at the two positions and found that the H2O could be optimized to form H-bonds with -OH and -NH3 (+) separately. When the simulated phonon signals of the -OH···H2O and -NH3(+)···H2O combinations were summed on a 3:1 scale, the calculating spectra were in good agreement with the experimental results, especially for the peak at 423 cm(-1) of the -OH···H2O combination and the peak at 367 cm(-1) of the -NH3(+)···H2O combination, which mutually complemented the real spectrum. We confirm that H2O may break the intermolecular H-bonds of the interlaced binding -OH to form a new structure, and that with the skeleton deformation of serine, H2O forms stronger H-bonds more often with the -NH3 (+) side indicating the flexible dynamic mechanism of the serine hydration process. PMID:23742519

Liu, Yang; Zhang, Peng; Lu, Ying-Bo; Han, Sheng-Hao; Yu, Hui

2013-05-28

136

Glial uptake of intracerebroventricularly injected d-serine in the rat brain: an immunocytochemical study  

Microsoft Academic Search

Recent studies have shown that free d-serine, an agonist for the N-methyl-d-aspartate receptor, is present in the forebrain of rats. In the present study, we raised antibodies against d-serine and examined the distribution of both endogenous and intracerebroventricularly administered d-serine in the rat forebrain by an immunocytochemical method. d-Serine-like immunoreactive cells were found in glial cells in the brains of

Kazuhisa Wako; Ning Ma; Takashi Shiroyama; Reiji Semba

1995-01-01

137

Uptake of d- and l-serine in C6 glioma cells  

Microsoft Academic Search

Cultured C6 glioma cells were able to accumulate [3H]d- and [3H]l-serine in a temperature- and Na+-dependent and saturable manner. The kinetic analysis of these accumulation phenomena indicates that the d- or l-serine uptake into the glioma cells might occur by a single-component system with an apparent Km value around 2480 ?M (for d-serine) or 110 ?M (for l-serine) and a

Fumihiko Hayashi; Katsunobu Takahashi; Toru Nishikawa

1997-01-01

138

High dose D-serine in the treatment of schizophrenia  

PubMed Central

Background D-serine is an allosteric modulator of the brain N-methyl-D-aspartate (NMDA) receptor and a potential novel treatment of schizophrenia. Double-blind studies have been performed at 30 mg/kg/day (~2 g/day) with encouraging results, but no formal dose escalation studies have been performed. We describe the first evaluation of the efficacy and safety of D-serine at doses >30 mg/kg/day; a 4-week, open-label trial of adjunctive D-serine (30, 60 or 120 mg/kg/day). Methods 42 antipsychotic-stabilized patients with schizophrenia or schizoaffective disorder participated. PANSS was obtained bi-weekly and neuropsychological (MATRICS) was obtained pre- and post medication phase. The pharmacokinetics/pharmacodynamics (PK/PD), and safety of doses ?30 mg/kg was also evaluated. Results Significant improvement in symptoms and neuropsychological measures was noted across doses. On the PANSS, improvement was observed for positive (p=0.006;d=0.46), negative (p<0.001;d=0.68), general (p=0.001;d=0.53), and total (p<0.0001;d=0.74) symptoms. On MATRICS, while only non-significant improvement was noted at 30 mg/kg, highly significant, large effect size improvement was noted on the composite score (p<0.01;d=1.0) for doses ?60 mg/kg, leading to a significant dose-by-time interaction (p<0.01). In PK analyses, significant dose-dependent increases in plasma D-serine levels were seen during the study, predictive of significantly increased brain levels. Furthermore, increases in plasma levels correlated with improved symptomatic and neuropsychological function. Discussion These findings support double-blind investigation of D-serine at doses ?60 mg/kg/d, and suggest effectiveness in treatment of both persistent symptoms and neurocognitive dysfunction. PMID:20541910

Kantrowitz, Joshua T.; Malhotra, Anil K.; Cornblatt, Barbara; Silipo, Gail; Balla, Andrea; Suckow, Raymond F.; D'Souza, Cyril; Saksa, John; Woods, Scott W.; Javitt, Daniel C.

2011-01-01

139

Calcium-induced inactivation of alamethicin in asymmetric lipid bilayers  

PubMed Central

This paper discusses a calcium-dependent inactivation of alamethicin- induced conductance in asymmetric lipid bilayers. The bilayers used were formed with one leaflet of phosphatidyl ethanolamine (PE) and one of phosphatidyl serine (PS). Calcium, initially confined to the neutral lipid (PE) side, can pass through the open alamethicin channel to the negative lipid (PS) side, where it can bind to the negative lipid and reduce the surface potential. Under appropriate circumstances, the voltage-dependent alamethicin conductance is thereby inactivated. We have formulated a model for this process based on the diffusion of calcium in the aqueous phases and we show that the model describes the kinetic properties of the alamethicin conductance under various circumstances. EGTA on the PS side of the membrane reduces the effects of calcium dramatically as predicted by the model. PMID:7077290

1982-01-01

140

Separate mechanisms for age-related truncation and racemisation of peptide-bound serine.  

PubMed

Some amino acids are particularly susceptible to degradation in long-lived proteins. Foremost among these are asparagine, aspartic acid and serine. In the case of serine residues, cleavage of the peptide bond on the N-terminal side, as well as racemisation, has been observed. To investigate the role of the hydroxyl group, and whether cleavage and racemisation are linked by a common mechanism, serine peptides with a free hydroxyl group were compared to analogous peptides where the serine hydroxyl group was methylated. Peptide bond cleavage adjacent to serine was increased when the hydroxyl group was present, and this was particularly noticeable when it was present as the hydroxide ion. Adjacent amino acid residues also had a pronounced affect on cleavage at basic pH, with the SerPro motif being especially susceptible to scission. Methylation of the serine hydroxyl group abolished truncation, as did insertion of a bulky amino acid on the N-terminal side of serine. By contrast, racemisation of serine occurred to a similar extent in both O-methylated and unmodified peptides. On the basis of these data, it appears that racemisation of Ser, and cleavage adjacent to serine, occur via separate mechanisms. Addition of water across the double bond of dehydroalanine was not detected, suggesting that this mechanism was unlikely to be responsible for conversion of L-serine to D-serine. Abstraction of the alpha proton may account for the majority of racemisation of serine in proteins. PMID:24306455

Lyons, Brian; Jamie, Joanne F; Truscott, Roger J W

2014-01-01

141

Brief Communications D-Serine in Glia and Neurons Derives from  

E-print Network

Brief Communications D-Serine in Glia and Neurons Derives from 3-Phosphoglycerate Dehydrogenase and Bioenvironmental Sciences, Kyushu University, Fukuokashi, Fukuoka 812-8581, Japan D-Serine is an endogenous ligand have been reported for D-serine and Srr. 3-Phosphoglycerate dehydrogenase is an exclusively astrocytic

Newman, Eric A.

142

Long-term potentiation depends on release of D-serine from astrocytes  

E-print Network

LETTERS Long-term potentiation depends on release of D-serine from astrocytes Christian Henneberger regulate their activation through Ca21 -dependent release of the NMDAR co- agonist D-serine2­4 . Release of D-serine from glia enables LTP in cultures5 and explains a correlation between glial coverage

Newman, Eric A.

143

Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase  

E-print Network

Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice of penetrating arterioles in a man- ner attenuated by scavenging D-serine with D-amino acid oxidase, deleting

Newman, Eric A.

144

Inhibition of Growth of Mycobacterium smegmatis and of Cell Wall Synthesis by d-Serine  

PubMed Central

d-Serine inhibited the growth of Mycobacterium smegmatis and induced the morphological alteration of the bacilli. The growth inhibitory action of d-serine was partially reduced by an equimolecular concentration of d-alanine. The combination of glycine with d-alanine reversed the growth inhibition produced by d-serine more than did d-alanine alone. In cells cultured in the presence of d-serine, the amounts of alanine, diaminopimelic acid, and glycine inserted into the cell wall mucopeptide were reduced, and serine was increased. The intracellular accumulation of a precursor of cell wall mucopeptide was increased by d-serine, and this accumulation was reduced by d-alanine. d-Serine competed with glycine for incorporation into the cell wall mucopeptide. The incorporation of l-aspartic acid into diaminopimelic acid residues in the cell wall mucopeptide was markedly inhibited by d-serine. Three mutants resistant to d-serine were isolated by nitrosoguanidine treatment. In these mutants the effects of d-serine on the sites of cell wall mucopeptide synthesis were all reduced. Thus, d-serine inhibition of the growth is due to replacement of glycine residues of the cell wall mucopeptide with d-serine and inhibition of the cell wall synthesis by blocking the formation of d-alanine and diaminopimelic acid. PMID:15828163

Yabu, Kunihiko; Huempfner, Herman R.

1974-01-01

145

Identification and structural analysis of four serine proteases in a monotreme, the platypus, Ornithorhynchus anatinus  

Microsoft Academic Search

To study the emergence of the major subfamilies of serine proteases during vertebrate evolution, we present here the primary structure of four serine proteases expressed in the spleen of a monotreme, the platypus, Ornithorhynchus anatinus. Partial cDNA clones for four serine proteases were isolated by a PCR-based strategy. This strategy is based on the high level of sequence identity between

Maryam Poorafshar; Maria Aveskogh; Barry Munday; Lars Hellman

2000-01-01

146

Serine Racemase: A Glial Enzyme Synthesizing D-Serine to Regulate Glutamate-N-Methyl-D-Aspartate Neurotransmission  

Microsoft Academic Search

Although D amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate\\/N-methyl-D-aspartate receptors by interacting with the \\

Herman Wolosker; Seth Blackshaw; Solomon H. Snyder

1999-01-01

147

photocredit PlayStation3'SabilitytoblaStdatabetweenchiPS  

E-print Network

that is going to change the way we experience games. This past May, gamers got a taste of some much-awaited PS3 as a backdrop. Sony Corp., in Tokyo, has a lot staked on the success of the PS3--hundreds of millions of dollars a great deal from the PS3, because Sony has promised a lot," says Brian O'Rourke, an analyst at market

Davis, Brian T.

148

Plasma Motion during the Formation Phase of the PS-3 and PS-3.5 Spheromaks  

NASA Astrophysics Data System (ADS)

Spectroscopic Doppler shift measurements of a CIII impurity ion in the ultraviolet are reported from the University of Maryland spheromak experiments PS-3 and PS-3.5. A new time and space resolved Doppler shift diagnostic with absolute wavelength calibration to +/- 0.02 A is described. The spheromak is a member of the compact toroid class of magnetic confinement devices. Spheromak formation is thought to proceed through a magnetic reconnection or relaxation process characterized by evolution to a minimum energy equilibrium subject to the constraint that the magnetic helicity is invariant. Large velocity fields (on the order of the Alfven speed) observed in both the PS-3 and PS-3.5 experiments during the formation phase, but not during the equilibrium, suggest that flow fields may play an important role in the reconnection and relaxation process. The standard theory of Taylor relaxation may need to be modified in order to include the effects of bulk plasma motion. Doppler shift measurements of the CIII 2296.87 A impurity emission line in the PS-3.5 spheromak were made side-on above and below the machine axis. During the formation phase, blue shifts are observed below and red shifts observed above the axis suggesting a toroidal rotation in the direction of the confined plasma diamagnetic drift. The plasma emissivity near the CIII wavelength was obtained from Abel inversion of the line-integrated intensities. Computer modelling of velocity fields, emissivity profiles and line shapes is used to interpret the experimental data. Variation of the flow fields as a function of the static fill pressure indicated the possible significance of the density profile to bulk motion of the plasma. A quadarature interferometer was used to obtain the time history of the line-integrated density through two chords of the plasma. Double-floating probe measurements gave the radial component of the electric field. The University of Maryland PS experiments utilize a combined theta and z discharge to produce the spheromak magnetic field configuration. The theory of rotation in theta pinch devices is briefly reviewed and a comparison is made with the results of the present experiment. The theoretical implications of including velocity terms in the energy minimization problem are also discussed. The decay rate of an ideal MHD invariant, the cross helicity, is considered in view of viscous and resistive effects in the experiments.

Peyser, Thomas Arnold

149

Photoinactivation of PS2 secondary donors by PS2 cation radicals and superoxide radicals  

SciTech Connect

Illumination of Mn- and Cl-depleted PS2 causes rapid irreversible inactivation of specific redox-active components on the donor side of the PS2 Reaction Center (RC). Under aerobic conditions, weak light preillumination of NH{sub 2}OH-PS2 causes rapid loss of Y{sub Z}{sup {plus_minus}} formation, Y{sub Z} {yields} P{sub 680}{sup +}, the A{sub T}-band thermoluminescence emission, the Y{sub Z}{sup +}-dependent (Site 1) photooxidation of exogenous e{sup {minus}} donors, and the capability to photoligate Mn{sup 2+} into the water oxidizing enzyme (photoactivation), all without significantly affecting P{sub 680}{sup +}/Q{sub A}{sup {minus}} charge separation. In contrast, aerobic high light preillumination of Mn-depleted PS2 promotes very rapid and parallel loss of photoactivation and A{sub T}-band emission capabilities significantly than loss of either Y{sub Z}{sup +}-formation or P{sub 680}{sup +}/Q{sub A}{sup {minus}} charge separation capabilities. These photodamages and those to Cl-depleted thylakoids (4,5) generally are believed to be caused by reactions between the highly oxidizing cation radicals (P{sub 680}{sup +}/Chl{sup +}) and nearby amino acid residues of D{sub 1}>D{sub 2}. The reported promotion of the photodamages by e{sup {minus}} acceptors of Q{sub A}{sup {minus}}/Q{sub B}{sup {minus}} their inhibition by e{sup {minus}} donors to Y{sub Z}{sup +} and their occurrence under strict anaerobic conditions all tend to support the idea of direct damage by P{sub 680}{sup +}/Chl{sup +}. Our studies lead us to conclude that the photodamages to the donor side components are caused minimally by a rapid mechanism requiring both superoxide and PS2 cation radicals; and by a slower mechanism driven by the PS2 cation radicals only.

Chen, G.X.; Cheniae, G.M. [Kentucky Univ., Lexington, KY (United States); Blubaugh, D.J. [Utah State Univ., Logan, UT (United States); Golbeck, J.H. [Nebraska Univ., Lincoln, NE (United States)

1991-12-31

150

Distinct iPS Cells Show Different Cardiac Differentiation Efficiency  

PubMed Central

Patient-specific induced pluripotent stem (iPS) cells can be generated by introducing transcription factors that are highly expressed in embryonic stem (ES) cells into somatic cells. This opens up new possibilities for cell transplantation-based regenerative medicine by overcoming the ethical issues and immunological problems associated with ES cells. Despite the development of various methods for the generation of iPS cells that have resulted in increased efficiency, safety, and general versatility, it remains unknown which types of iPS cells are suitable for clinical use. Therefore, the aims of the present study were to assess (1) the differentiation potential, time course, and efficiency of different types of iPS cell lines to differentiate into cardiomyocytes in vitro and (2) the properties of the iPS cell-derived cardiomyocytes. We found that high-quality iPS cells exhibited better cardiomyocyte differentiation in terms of the time course and efficiency of differentiation than low-quality iPS cells, which hardly ever differentiated into cardiomyocytes. Because of the different properties of the various iPS cell lines such as cardiac differentiation efficiency and potential safety hazards, newly established iPS cell lines must be characterized prior to their use in cardiac regenerative medicine. PMID:24367382

Yuasa, Shinsuke; Egashira, Toru; Seki, Tomohisa; Hashimoto, Hisayuki; Shimoji, Kenichiro; Kageyama, Toshimi; Tanaka, Tomofumi; Hattori, Fumiyuki; Murata, Mitsushige; Kimura, Kensuke; Fukuda, Keiichi

2013-01-01

151

PS: A nonprocedural language with data types and modules  

NASA Technical Reports Server (NTRS)

The Problem Specification (PS) nonprocedural language is a very high level language for algorithm specification. PS is suitable for nonprogrammers, who can specify a problem using mathematically-oriented equations; for expert programmers, who can prototype different versions of a software system for evaluation; and for those who wish to use specifications for portions (if not all) of a program. PS has data types and modules similar to Modula-2. The compiler generates C code. PS is first shown by example, and then efficiency issues in scheduling and code generation are discussed.

Gokhale, M. B.

1986-01-01

152

Ischemic acute kidney injury perturbs homeostasis of serine enantiomers in the body fluid in mice: early detection of renal dysfunction using the ratio of serine enantiomers.  

PubMed

The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little D-serine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D-/L-serine from 2.82 ± 0.18 to 1.10 ± 0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D-/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D-/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury. PMID:24489731

Sasabe, Jumpei; Suzuki, Masataka; Miyoshi, Yurika; Tojo, Yosuke; Okamura, Chieko; Ito, Sonomi; Konno, Ryuichi; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

2014-01-01

153

Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model  

PubMed Central

N-methyl-D-aspartic acid receptor (NMDAr) activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5?-phosphate-dependent serine racemase (SR). D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS) and L-erythro-3-hydroxyaspartate (LEHA), among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100??g/10??L) and LEHA (100??g/10??L) in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300??g/10??L of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain. PMID:22536130

Laurido, Claudio; Hernandez, Alejandro; Pelissier, Teresa; Constandil, Luis

2012-01-01

154

Ischemic Acute Kidney Injury Perturbs Homeostasis of Serine Enantiomers in the Body Fluid in Mice: Early Detection of Renal Dysfunction Using the Ratio of Serine Enantiomers  

PubMed Central

The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little D-serine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D?/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D?/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D?/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury. PMID:24489731

Sasabe, Jumpei; Suzuki, Masataka; Miyoshi, Yurika; Tojo, Yosuke; Okamura, Chieko; Ito, Sonomi; Konno, Ryuichi; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

2014-01-01

155

D-Serine metabolism: new insights into the modulation of D-amino acid oxidase activity.  

PubMed

Over the years, accumulating evidence has indicated that D-serine represents the main endogenous ligand of NMDA (N-methyl-D-aspartate) receptors. In the brain, the concentration of D-serine stored in cells is defined by the activity of two enzymes: serine racemase (responsible for both the synthesis and degradation) and D-amino acid oxidase (which catalyses D-serine degradation). The present review is focused on human D-amino acid oxidase, discussing the mechanisms involved in modulating enzyme activity and stability, with the aim to substantiate the pivotal role of D-amino acid oxidase in brain D-serine metabolism. PMID:24256253

Sacchi, Silvia

2013-12-01

156

An Alzheimer's Disease-Linked PS1 Variant Rescues the Developmental Abnormalities of PS1Deficient Embryos  

Microsoft Academic Search

Mutations in presenilin 1 (PS1) cosegregate with ?25% of early onset familial Alzheimer's disease (FAD) pedigrees. A variety of in vitro and in vivo paradigms have established that one mechanism by which PS1 variants cause AD is by elevating the production of highly amyloidogenic A?1–42\\/43 peptides. PS1 is homologous to sel-12, a C. elegans protein that facilitates signaling mediated by

Janine A Davis; Satoshi Naruse; Hua Chen; Chris Eckman; Steven Younkin; Donald L Price; David R Borchelt; Sangram S Sisodia; Philip C Wong

1998-01-01

157

Design Differences between the Pan-STARRS PS1 and PS2 Telescopes  

E-print Network

The PS2 telescope is the second in an array of wide-field telescopes that is being built for the Panoramic-Survey Telescope and Rapid Response System (Pan-STARRS) on Haleakala. The PS2 design has evolved incrementally based on lessons learned from PS1, but these changes should result in significant improvements in image quality, tracking performance in windy conditions, and reductions in scattered light. The optics for this telescope are finished save for their coatings and the fabrication for the telescope structure itself is well on the way towards completion and installation on-site late this year (2012). The most significant differences between the two telescopes include the following: secondary mirror support changes, improvements in the optical polishing, changes in the optical coatings to improve throughput and decrease ghosting, removal of heat sources inside the mirror cell, expansion of the primary mirror figure control system, changes in the baffle designs, and an improved cable wrap design. This p...

Morgan, Jeffrey S; Moreau, Vincent; Anderson, David; Burgett, William

2012-01-01

158

In silico and pharmacological screenings identify novel serine racemase inhibitors.  

PubMed

D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation. PMID:25066953

Mori, Hisashi; Wada, Ryogo; Li, Jie; Ishimoto, Tetsuya; Mizuguchi, Mineyuki; Obita, Takayuki; Gouda, Hiroaki; Hirono, Shuichi; Toyooka, Naoki

2014-08-15

159

Architecture of a Serine Recombinase-DNA Regulatory Complex  

SciTech Connect

An essential feature of many site-specific recombination systems is their ability to regulate the direction and topology of recombination. Resolvases from the serine recombinase family assemble an interwound synaptic complex that harnesses negative supercoiling to drive the forward reaction and promote recombination between properly oriented sites. To better understand the interplay of catalytic and regulatory functions within these synaptic complexes, we have solved the structure of the regulatory site synapse in the Sin resolvase system. It reveals an unexpected synaptic interface between helix-turn-helix DNA-binding domains that is also highlighted in a screen for synapsis mutants. The tetramer defined by this interface provides the foundation for a robust model of the synaptic complex, assembled entirely from available crystal structures, that gives insight into how the catalytic activity of Sin and other serine recombinases may be regulated.

Mouw, Kent W.; Rowland, Sally-J.; Gajjar, Mark M.; Boocock, Martin R.; Stark, W. Marshall; Rice, Phoebe A. (Glasgow); (UC)

2008-04-29

160

Chemical basis for brain-specific serine transfer RNAs.  

PubMed Central

Serine tRNA from rat brain can be resolved into six isoaccepting species. Three of these species show the same chromatographic behavior as the seryl tRNAs from other rat organs, whereas the remaining species appear to be specific for brain. The isoacceptor tRNAs were purified to homogeneity by chromatography on benzoylated DEAE-cellulose followed by reversed-phase chromatography. We found that the additional species of serine tRNA in brain differ from their counterparts derived from other rat organs by a lack of a specific guanosine ribose-methylation in the dihydrouridine loop. In addition, when total liver tRNA was compared with total brain tRNA, the same degree of undermethylation with respect to 2'-O-methylguanosine was found as a general phenomenon. Images PMID:270667

Rogg, H; Müller, P; Keith, G; Staehelin, M

1977-01-01

161

Serine\\/Threonine Protein Phosphatase Inhibitors with Antitumor Activity  

Microsoft Academic Search

Recent studies with fostriecin and derivatives of cantharidin suggest that the development of specific, or highly selective,\\u000a inhibitors of serine\\/threonine protein phosphatases, notably PP2A, PP4, and PP5, may prove useful for the medical management\\u000a of human cancer. This chapter will review the discovery and development of natural compounds that were originally shown to\\u000a have marked antitumor activity and subsequently found

R. E. Honkanen

162

Granules of cytolytic T-lymphocytes contain two serine esterases.  

PubMed Central

Cytoplasmic granules from cytolytic T-lymphocytes (CTL) contain two proteins which react with the serine esterase-specific affinity label diisopropylfluorophosphate (DFP). One of these is a trypsin-like esterase which consists of two disulfide-linked 35-kd subunits. The other consists of a single 29-kd chain. Both molecules are induced concomitantly with cytolytic activity and perforin activity in a CTL-derived T-cell hybrid. Images Fig. 1. Fig. 2. Fig. 3. Fig. 5. PMID:3488903

Masson, D; Nabholz, M; Estrade, C; Tschopp, J

1986-01-01

163

Serine protease activities in Leishmania ( Leishmania ) chagasi promastigotes  

Microsoft Academic Search

The present work reports the isolation, biochemical characterization, and subcellular location of serine proteases from aqueous,\\u000a detergent soluble, and culture supernatant of Leishmania chagasi promastigote extracts, respectively, LCSII, LCSI, and LCSIII. The active enzyme molecular masses of LCSII were about 105,\\u000a 66, and 60 kDa; of LCSI, 60 and 58 kDa; and of LCSIII, approximately 76 and 68 kDa. Optimal pH for the

Raquel Elisa da Silva-López; Tatiana Resende dos Santos; José Andrés Morgado-Díaz; Marcelo Neves Tanaka; Salvatore Giovanni de Simone

2010-01-01

164

A novel serine protease inhibitor from Bungarus fasciatus venom  

Microsoft Academic Search

By Sephadex G-50 gel filtration, cation-exchange CM-Sephadex C-25 chromatography and reversed phase high-performance liquid chromatography (HPLC), a novel serine protease inhibitor named bungaruskunin was purified and characterized from venom of Bungarus fasciatus. Its cDNA was also cloned from the cDNA library of B. fasciatus venomous glands. The predicted precursor is composed of 83 amino acid (aa) residues including a 24-aa

Jia Lu; Hailong Yang; Haining Yu; Weikai Gao; Ren Lai; Jingze Liu; Xingcai Liang

2008-01-01

165

Protein chemical synthesis by serine and threonine ligation  

PubMed Central

An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides––ovine-corticoliberin and Forteo––and the human erythrocyte acylphosphatase protein (?11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc–solid-phase peptide synthesis. PMID:23569249

Zhang, Yinfeng; Lam, Hiu Yung; Lee, Chi Lung; Li, Xuechen

2013-01-01

166

VZV ORF47 Serine Protein Kinase and Its Viral Substrates  

Microsoft Academic Search

\\u000a ORF47, a serine protein kinase of varicella-zoster virus (VZV) and homolog of herpes simplex virus UL13, is an interesting\\u000a modulator of VZV pathogenesis. This chapter summarizes research showing that ORF47 protein kinase activity, by virtue of phosphorylation\\u000a of or binding to various viral substrates, regulates VZV proteins during all phases of viral infection and has a pronounced\\u000a effect on the

Teri K. Kenyon; Charles Grose

167

Serine racemase: a key player in apoptosis and necrosis.  

PubMed

A fine balance between cell survival and cell death is required to sculpt the nervous system during development. However, an excess of cell death can occur following trauma, exposure to neurotoxins or alcohol, and some developmental and neurodegenerative diseases, such as Alzheimer's disease (AD). N-Methyl-D-aspartate receptors (NMDARs) support synaptic plasticity and survival of many neuronal populations whereas inappropriate activation may promote various forms of cell death, apoptosis, and necrosis representing the two extremes of a continuum of cell death processes both "in vitro" and "in vivo." Hence, by identifying the switches controlling pro-survival vs. apoptosis and apoptosis vs. pro-excitotoxic outcome of NMDAR stimulation, NMDAR modulators could be developed that selectively block the cell death enhancing pro-survival signaling or synaptic plasticity mediated by NMDAR. Among these modulators, a role is emerging for the enzyme serine racemase (SR) that synthesizes D-serine, a key co-agonist with glutamate at NMDAR. This review summarizes the experimental evidence from "in vitro" neuronal cultures-with special emphasis on cerebellar granule neurons (CGNs)-and "in vivo" models of neurodegeneration, where the dual role of the SR/D-serine pathway as a master regulator of apoptosis and the apoptosis-necrosis shift will be discussed. PMID:24795622

Canu, Nadia; Ciotti, Maria Teresa; Pollegioni, Loredano

2014-01-01

168

PS3 CELL Development for Scientific Computation and Research  

Microsoft Academic Search

The Cell processor is one of the most powerful processors on the market, and researchers in the earth sciences may find its parallel architecture to be very useful. A cell processor, with 7 cores, can easily be obtained for experimentation by purchasing a PlayStation 3 (PS3) and installing linux and the IBM SDK. Each core of the PS3 is capable

M. Christiansen; E. Sevre; S. M. Wang; D. A. Yuen; S. Liu; M. D. Lyness; M. Broten

2007-01-01

169

The proteasome inhibitor PS-341 in cancer therapy.  

PubMed

The anticancer activity of the boronic acid dipeptide proteasome inhibitor PS-341 was examined in vitro and in vivo. PS-341 was a potent cytotoxic agent toward MCF-7 human breast carcinoma cells in culture, producing an IC90 of 0.05 microM on 24 h of exposure to the drug. In the EMT-6 tumor cell survival assay, PS-341 was equally cytotoxic administered p.o. or by i.p. injection up to a dose of 2 mg/kg. PS-341 was also toxic to the bone marrow colony-forming unit-granulocyte macrophage. PS-341 increased the tumor cell killing of radiation therapy, cyclophosphamide, and cisplatin in the EMT-6/Parent tumor, but was not able to overcome the in vivo resistance of the EMT-6/CTX and EMT-6/CDDP tumors. In the tumor growth delay assay, PS-341 administered p.o. had antitumor activity against the Lewis lung carcinoma, both primary and metastatic disease. In combination, regimens with 5-fluorouracil, cisplatin, Taxol and adriamycin, PS-341 seemed to produce primarily additive tumor growth delays against the s.c. tumor and was highly effective against disease metastatic to the lungs. The proteasome is an interesting new target for cancer therapy, and the proteasome inhibitor PS-341 warrants continued investigation in cancer therapy. PMID:10499643

Teicher, B A; Ara, G; Herbst, R; Palombella, V J; Adams, J

1999-09-01

170

L-Serine Catabolism via an Oxygen-Labile L-Serine Dehydratase Is Essential for Colonization of the Avian Gut by Campylobacter jejuni  

Microsoft Academic Search

Campylobacter jejuni is a microaerophilic, asaccharolytic bacterium. The identity of the carbon and energy sources used by C. jejuni in vivo is unknown, but the genome sequence of strain NCTC11168 indicates the presence of genes for catabolism of a limited range of amino acids, including serine. Specific omission of L-serine from a defined medium containing a mixture of amino acids

Jyoti Velayudhan; Michael A. Jones; Paul A. Barrow; David J. Kelly

2004-01-01

171

A wavelength tunable 2-ps pulse VECSEL  

NASA Astrophysics Data System (ADS)

We report a mode-locked Vertical-External-Cavity Surface-Emitting Laser (VECSEL) that exhibits 13.7 nm of tuning around a centre wavelength of 1042 nm. The wavelength tuning is achieved by incorporating an uncoated, 25 ?m thick, fused silica etalon into the cavity of the laser at Brewster's angle. The etalon is then tilted with respect to the cavity axis. The etalon has a calculated free spectral range of 14 nm at normal incidence. The repetition rate of the laser is measured to be 1.88 GHz. The pulse duration, averaged over the tuning range, is 1.9 ps corresponding to a mean time bandwidth product of 0.46. For a sech2 pulse this is 1.46 times larger than the transform limit. The average power of the laser does not fall below 2.6 mW and, over the tuning range, averages 3.5 mW. With appropriate amplification, such a laser would be highly suited to the generation of heralded single photons in photonic crystal fibre.

Morris, Oliver J.; Wilcox, Keith G.; Head, C. Robin; Turnbull, Andrew P.; Mosley, Peter J.; Quarterman, Adrian H.; Kbashi, Hani J.; Farrer, Ian; Beere, Harvey E.; Ritchie, David A.; Tropper, Anne C.

2012-03-01

172

Telomere Reprogramming and Maintenance in Porcine iPS Cells  

PubMed Central

Telomere reprogramming and silencing of exogenous genes have been demonstrated in mouse and human induced pluripotent stem cells (iPS cells). Pigs have the potential to provide xenotransplant for humans, and to model and test human diseases. We investigated the telomere length and maintenance in porcine iPS cells generated and cultured under various conditions. Telomere lengths vary among different porcine iPS cell lines, some with telomere elongation and maintenance, and others telomere shortening. Porcine iPS cells with sufficient telomere length maintenance show the ability to differentiate in vivo by teratoma formation test. IPS cells with short or dysfunctional telomeres exhibit reduced ability to form teratomas. Moreover, insufficient telomerase and incomplete telomere reprogramming and/or maintenance link to sustained activation of exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced expression of exogenous genes or partial exogene silencing exhibit insufficient activation of endogenous pluripotent genes and telomerase genes, accompanied by telomere shortening with increasing passages. Moreover, telomere doublets, telomere sister chromatid exchanges and t-circles that presumably are involved in telomere lengthening by recombination also are found in porcine iPS cells. These data suggest that both telomerase-dependent and telomerase-independent mechanisms are involved in telomere reprogramming during induction and passages of porcine iPS cells, but these are insufficient, resulting in increased telomere damage and shortening, and chromosomal instability. Active exogenes might compensate for insufficient activation of endogenous genes and incomplete telomere reprogramming and maintenance of porcine iPS cells. Further understanding of telomere reprogramming and maintenance may help improve the quality of porcine iPS cells. PMID:24098638

Ji, Guangzhen; Ruan, Weimin; Liu, Kai; Wang, Fang; Sakellariou, Despoina; Chen, Jijun; Yang, Yang; Okuka, Maja; Han, Jianyong; Liu, Zhonghua; Lai, Liangxue; Gagos, Sarantis; Xiao, Lei; Deng, Hongkui; Li, Ning; Liu, Lin

2013-01-01

173

Evaluation of oxidative stress in D-serine induced nephrotoxicity.  

PubMed

It has been suggested that oxidative stress is involved in d-serine-induced nephrotoxicity. The purpose of this study was to assess if oxidative stress is involved in this experimental model using several approaches including (a) the determination of several markers of oxidative stress and the activity of some antioxidant enzymes in kidney and (b) the use of compounds with antioxidant or prooxidant effects. Rats were sacrificed at several periods of time (from 3 to 24h) after a single i.p. injection of d-serine (400mg/kg). Control rats were injected with l-serine (400mg/kg) and sacrificed 24h after. The following markers were used to assess the temporal aspects of renal damage: (a) urea nitrogen (BUN) and creatinine in blood serum, (b) kidney injury molecule (KIM-1) mRNA levels, and (c) tubular necrotic damage. In addition, creatinine clearance, proteinuria, and urinary excretion of N-acetyl-beta-d-glucosaminidase (NAG) were measured 24h after d-serine injection. Protein carbonyl content, malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), fluorescent products of lipid peroxidation, reactive oxygen species (ROS), glutathione (GSH) content, and heme oxygenase-1 (HO-1) expression were measured as markers of oxidative stress in the kidney. Additional experiments were performed using the following compounds with antioxidant or pro-oxidant effects before d-serine injection: (a) alpha-phenyl-tert-butyl-nitrone (PBN), a spin trapping agent; (b) 5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron(III) (FeTPPS), a soluble complex able to metabolize peroxynitrite; (c) aminotriazole (ATZ), a catalase (CAT) inhibitor; (d) stannous chloride (SnCl(2)), an HO-1 inductor; (e) tin mesoporphyrin (SnMP), an HO inhibitor. In the time-course study, serum creatinine and BUN increased significantly on 15-24 and 20-24h, respectively, and KIM-1 mRNA levels increased significantly on 6-24h. Histological analyses revealed tubular necrosis at 12h. The activity of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase remained unchanged at all times studied. Protein carbonyl content, MDA, 4-HNE, and ROS remained unchanged at all time-points studied. GSH content decreased transiently on 9 and 12h. Interestingly, fluorescent products of lipid peroxidation decreased significantly on 3-24h. HO-1 expression was undetectable by Western blot and the immunohistochemistry studies revealed that the intensity of HO-1 staining was weak. The administration of PBN, FeTPPS, ATZ, SnCl(2), and SnMP did not prevent or enhance renal damage induced by d-serine. Our data taken as a whole suggest that oxidative stress is not involved in the early phase of the nephrotoxicity induced by d-serine. PMID:17110013

Orozco-Ibarra, Marisol; Medina-Campos, Omar Noel; Sánchez-González, Dolores Javier; Martínez-Martínez, Claudia María; Floriano-Sánchez, Esaú; Santamaría, Abel; Ramirez, Victoria; Bobadilla, Norma A; Pedraza-Chaverri, José

2007-01-01

174

¹³C magnetic resonance spectroscopy detection of changes in serine isotopomers reflects changes in mitochondrial redox status.  

PubMed

The glycine cleavage system (GCS), the major pathway of glycine catabolism in liver, is found only in the mitochondria matrix and is regulated by the oxidized nicotinamide adenine dinucleotide (NAD(+) )/reduced nicotinamide adenine dinucleotide (NADH) ratio. In conjunction with serine hydroxymethyltransferase, glycine forms the 1 and 2 positions of serine, while the 3 position is formed exclusively by GCS. Therefore, we sought to exploit this pathway to show that quantitative measurements of serine isotopomers in liver can be used to monitor the NAD(+) /NADH ratio using (13) C NMR spectroscopy. Rat hepatocytes were treated with modulators of GCS activity followed by addition of 2-(13) C-glycine, and the changes in the proportions of newly synthesized serine isotopomers were compared to controls. Cysteamine, a competitive inhibitor of GCS, prevented formation of mitochondrial 3-(13) C-serine and 2,3-(13) C-serine isotopomers while reducing 2-(13) C-serine by 55%, demonstrating that ca. 20% of glycine-derived serine is produced in the cytosol. Glucagon, which activates GCS activity, and the mitochondrial uncoupler carbonyl cyanide-3-chlorophenylhydrazone both increased serine isotopomers, whereas rotenone, an inhibitor of complex I, had the opposite effect. These results demonstrate that (13) C magnetic resonance spectroscopy monitoring of the formation of serine isotopomers in isolated rat hepatocytes given 2-(13) C-glycine reflects the changes of mitochondrial redox status. PMID:22190282

Johnson, C Bryce; Tikunov, Andrey P; Lee, Haakil; Wolak, Justyna E; Pediaditakis, Peter; Romney, Doug A; Holmuhamedov, Ekhson; Gamcsik, Michael P; Macdonald, Jeffrey M

2012-09-01

175

Storage and uptake of d-serine into astrocytic synaptic-like vesicles specify gliotransmission  

PubMed Central

Glial cells are increasingly recognized as active players that profoundly influence neuronal synaptic transmission by specialized signalling pathways. In particular, astrocytes have recently been shown to release small molecules such as the amino acids l-glutamate and d-serine as “gliotransmitters”, which directly control the efficacy of adjacent synapses. However, it is still controversial whether gliotransmitters are released from a cytosolic pool or by Ca2+-dependent exocytosis from secretory vesicles, i.e., by a mechanism similar to the release of synaptic vesicles in synapses. Here we report that rat cortical astrocytes contain storage vesicles that display morphological and biochemical features similar to neuronal synaptic vesicles. These vesicles share some, but not all, membrane proteins with synaptic vesicles including the SNARE synaptobrevin 2 and contain both l-glutamate and d-serine. Furthermore, they show uptake of l-glutamate and d-serine that is driven by a proton electrochemical gradient. d-Serine uptake is associated with vesicle acidification and is dependent on chloride. While l-serine is not transported, serine racemase, the synthesizing enzyme for d-serine, is anchored to the membrane of the vesicles allowing local generation of d-serine. Finally, we reveal a previously unexpected mutual vesicular synergy between d-serine and l-glutamate filling in glia vesicles. We conclude that astrocytes contain vesicles capable of storing and releasing d-serine, l-glutamate, and most likely other neuromodulators in an activity-dependent manner. PMID:23426669

Martineau, Magalie; Shi, Ting; Puyal, Julien; Knolhoff, Ann M.; Dulong, Jerome; Gasnier, Bruno; Klingauf, Jurgen; Sweedler, Jonathan V.; Jahn, Reinhard; Mothet, Jean-Pierre

2013-01-01

176

d-Serine enhancement of NMDA receptor-mediated calcium increases in rat retinal ganglion cells.  

PubMed

NMDA receptor (NMDAR) activation is enhanced by d-serine or glycine acting at a specific binding site. Previous work has shown d-serine enhancement of NMDAR currents in retinal ganglion cells. One of the major functions of most NMDA channels is to permit calcium influx into cells. We show that d-serine enhances glutamate-induced calcium responses in immunopanned retinal ganglion cells. This effect was specific to NMDA receptors as similar results were found with NMDA, but not kainate, and was reduced or blocked by modulators of the NMDAR coagonist binding site. d-Serine and glycine enhanced glutamate-induced calcium responses in a dose-dependent manner and at equimolar concentrations there was no difference in the efficacy of the coagonists. In isolated retinas NMDA-induced calcium responses were enhanced by d-serine coapplication in 46% of ganglion cells. Endogenous d-serine degradation by treatment with d-amino acid oxidase caused a approximately 45% decrease in the NMDA-induced response that could be reversed by coapplication with d-serine. d-Serine and glycine were equally effective in enhancing glutamatergic calcium responses. Endogenous d-serine contributes to NMDAR activation in retinal wholemounts and some but not all retinal ganglion cells may experience saturating levels of d-serine or glycine. PMID:19968757

Daniels, Bryan A; Baldridge, William H

2010-03-01

177

Winter 2014 ESAM 448 PS1 1. The standard forms for the estimators of mean and variance,  

E-print Network

is iiii dggh == -1 , just as desired. 2:1 MUX 50ps 25ps 1-bit differentially encoded gi at 40Gbit/s 4 data streams di with 10Gbit/s each 2:1 MUX 100ps 100ps 2:1 MUX 100ps 100ps 50ps 1-bit differentially encoded fi

178

Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes  

PubMed Central

We have found that, in the peritoneums of normal adult mice, 5-15% of lymphocytes bind a fluorescent liposome probe. In ontogeny, cells with this specificity were shown to appear by 8 d after birth, and increase to the adult frequency by 2-3 wk. Some older mice contain an expanded population of these cells. We have shown that liposome binding occurs by cell surface IgM recognizing the common membrane phospholipid, phosphatidyl choline (PtC). Virtually all of these PtC-specific cells bear the cell surface marker Ly-1. Our results indicate that roughly 1 in 10 peritoneal Ly-1+ B cells has this single specificity. We have found that the precursors to all the cells that form plaques on protease-treated autologous erythrocytes (BrMRBC) are included in the PtC-specific population and can be isolated by FACS. We believe this is the first report of sorting large numbers of B cells with a single antigen specificity from normal, unimmunized animals. This method will allow for in vitro and in vivo studies of differentiative and proliferative properties of Ly-1+ B cells, which may help define their role in development and disease. PMID:3045250

1988-01-01

179

Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma.  

PubMed

Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive lymphoma, with a great demand for novel treatments for relapsing and refractory disease. Constitutive activation of the phosphatidyl-inositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is often detected in this lymphoma. Inhibition of this signaling cascade with the pan-class I PI3K inhibitor NVP-BKM120 decreased cell proliferation and increased apoptotic cell death. DLBCL proliferation was further decreased if NVP-BKM120-induced autophagy was blocked. Treatment with NVP-BKM120 was associated with an increase of the pro-apoptotic BH3-only proteins Puma and Bim and down-regulation of the anti-apoptotic Bcl-xL and Mcl-1. Translation of Bcl-xL and Mcl-1 is facilitated by cap-dependent mRNA translation, a process that was partially inhibited by NVP-BKM120. Overall, we demonstrated here the potential of NVP-BKM120 for the treatment of DLBCL. PMID:23721513

Zang, Chuanbing; Eucker, Jan; Liu, Hongyu; Coordes, Annekatrin; Lenarz, Minoo; Possinger, Kurt; Scholz, Christian Wilfried

2014-02-01

180

A novel serine protease predominately expressed in macrophages.  

PubMed Central

We have identified a novel serine protease designated EOS by sequence identity searches. The deduced protein contains 284 amino acids with an active form containing 248 amino acids starting from an Ile-Val-Gly-Gly motif. The active form comprises a catalytic triad of conserved amino acids: His77, Asp126 and Ser231. It shares 44% identity with beta-tryptase and belongs to the S1 trypsin-like serine-protease family. Interestingly, this gene also maps to human chromosome 16p13.3. The purified protease showed amidolytic activity, cleaving its substrates before arginine residues. Tissue distribution by immunohistochemistry analysis demonstrated that EOS is highly expressed in spleen and moderately expressed in intestine, colon, lung and brain. We confirmed this expression pattern at the mRNA level by performing in situ hybridization. The results from both immunohistochemistry and in situ hybridization indicate that EOS is associated with macrophages. We corroborated this observation by double immunofluorescence using the anti-EOS antibody and an anti-CD68 antibody, a macrophage specific marker. Furthermore, we have detected a dramatic increase in immune staining of EOS in cultured U937 cells treated with PMA, which represent activated macrophages. This up-regulation is also reflected by elevated EOS mRNA in the PMA-treated U937 cells detected by Northern blotting. Since macrophages have important roles in various pathological conditions, such as wound healing, atherosclerosis and numerous inflammatory diseases, the localization of this novel serine protease to active macrophages may help to further the elucidation of the roles of this gene product in modulating these disorders. PMID:12795636

Chen, Cailin; Darrow, Andrew L; Qi, Jian-Shen; D'Andrea, Michael R; Andrade-Gordon, Patricia

2003-01-01

181

Role of insulin receptor and insulin signaling on ?PS2C?PS integrins' lateral diffusion.  

PubMed

Integrins are ubiquitous transmembrane receptors with adhesion and signaling properties. The influence of insulin receptor and insulin signaling on ?PS2C?PS integrins' lateral diffusion was studied using single particle tracking in S2 cells before and after reducing the insulin receptor expression or insulin stimulation. Insulin signaling was monitored by Western blotting for phospho-Akt expression. The expression of the insulin receptor was reduced using RNA interference (RNAi). After insulin receptor RNAi, four significant changes were measured in integrin diffusion properties: (1) there was a 24 % increase in the mobile integrin population, (2) 14 % of the increase was represented by integrins with Brownian diffusion, (3) for integrins that reside in confined zones of diffusion, there was a 45 % increase in the diameter of the confined zone, and (4) there was a 29 % increase in the duration integrins spend in confined zones of diffusion. In contrast to reduced expression of the insulin receptor, which alters integrin diffusion properties, insulin stimulation alone or insulin stimulation under conditions of reduced insulin receptor expression have minimal effects on altering the measured integrin diffusion properties. The differences in integrin diffusion measured after insulin receptor RNAi in the presence or absence of insulin stimulation may be the result of other insulin signaling pathways that are activated at reduced insulin receptor conditions. No change in the average integrin diffusion coefficient was measured for any conditions included in this study. PMID:25331198

Mainali, Dipak; Syed, Aleem; Arora, Neha; Smith, Emily A

2014-12-01

182

Click-generated triazole ureas as ultrapotent in vivo–active serine hydrolase inhibitors  

Microsoft Academic Search

Serine hydrolases are a diverse enzyme class representing ?1% of all human proteins. The biological functions of most serine hydrolases remain poorly characterized owing to a lack of selective inhibitors to probe their activity in living systems. Here we show that a substantial number of serine hydrolases can be irreversibly inactivated by 1,2,3-triazole ureas, which show negligible cross-reactivity with other

Alexander Adibekian; Brent R Martin; Chu Wang; Ku-Lung Hsu; Daniel A Bachovchin; Sherry Niessen; Heather Hoover; Benjamin F Cravatt

2011-01-01

183

A CSF and postmortem brain study of d-serine metabolic parameters in schizophrenia  

Microsoft Academic Search

Clinical trials demonstrated that d-serine administration improves schizophrenia symptoms, raising the possibility that altered levels of endogenous d-serine may contribute to the N-methyl d-aspartate receptor hypofunction thought to play a role in the disease. We hypothesized that cerebro-spinal fluid (CSF) d-serine levels are decreased in the patients due to reduced synthesis and\\/or increased degradation in brain. We now monitored amino

Inna Bendikov; Carmit Nadri; Shirly Amar; Rogerio Panizzutti; Joari De Miranda; Herman Wolosker; Galila Agam

2007-01-01

184

D-Amino Acids as Putative Neurotransmitters: Focus on D-Serine  

Microsoft Academic Search

Of the twenty amino acids in the mammalian body, only serine and aspartate occur in D-configuration as well as L-configuration in significant amount. D-serine is selectively concentrated in the brain, localized to protoplasmic astrocytes that ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. D-serine has been found to function as an endogenous ligand for the “glycine”

Solomon H. Snyder; Paul M. Kim

2000-01-01

185

Ionotropic glutamate-like receptor 2 binds D-serine and glycine  

E-print Network

Ionotropic glutamate-like receptor 2 binds D-serine and glycine Peter Naur*, Kasper B. Hansen-binding core of GluR 2 (GluR 2­S1S2) was found to bind neutral amino acids such as D-serine and glycine, as demonstrated by isothermal titration calorimetry. Direct evidence for binding of D-serine and structural

Traynelis, Stephen F.

186

Transport of d-Serine via the Amino Acid Transporter ATB 0,+ Expressed in the Colon  

Microsoft Academic Search

d-Serine, synthesized endogenously in the brain, is an important modulator of glutamatergic neurotransmission. Since colonic bacteria produce d-serine, we asked the question whether there are transport mechanisms in the colon that might make this exogenously produced d-serine available to the host. Here we identify for the first time an amino acid transporter in the intestine for high-affinity active transport of

Takahiro Hatanaka; Wei Huang; Takeo Nakanishi; Christy C. Bridges; Sylvia B. Smith; Puttur D. Prasad; Malliga E. Ganapathy; Vadivel Ganapathy

2002-01-01

187

New L-Serine Derivative Ligands as Cocatalysts for Diels-Alder Reaction  

PubMed Central

New L-serine derivative ligands were prepared and tested as cocatalyst in the Diels-Alder reactions between cyclopentadiene (CPD) and methyl acrylate, in the presence of several Lewis acids. The catalytic potential of the in situ formed complexes was evaluated based on the reaction yield. Bidentate serine ligands showed good ability to coordinate medium strength Lewis acids, thus boosting their catalytic activity. The synthesis of the L-serine ligands proved to be highly efficient and straightforward. PMID:24383009

Sousa, Carlos A. D.; Rodriguez-Borges, Jose E.; Freire, Cristina

2013-01-01

188

The long road of research on snake venom serine proteinases.  

PubMed

It has long been recognized that snake venom serine proteinases (SVSPs) affect various physiological functions including blood coagulation, fibrinolysis, blood pressure and platelet aggregation. Therefore, SVSPs have been used as refined tools to study molecular mechanisms involved in the activation of key factors that control hemostasis and as therapeutic agents in various thrombotic and hemostatic conditions. The aim of this review is to highlight the state of our knowledge on the advances made in SVSP research since the 18th century. It includes the personal accounts of some distinguished scientists that addressed specific problems and contributed to advance the field. PMID:23010164

Serrano, Solange M T

2013-02-01

189

Quantitative analysis of 77K fluorescence emission spectra in Synechocystis sp. PCC 6714 and Chlamydomonas reinhardtii with variable PS I\\/PS II stoichiometries  

Microsoft Academic Search

Low-temperature (77 K) fluorescence emission spectra of intact cells of a cyanobacterium, Synechocystis sp. PCC 6714, and a green alga, Chlamydomonas reinhardtii, were quantitatively analyzed to examine differences in PS I\\/PS II stoichiometries. Cells cultured under different spectral conditions had various PS I\\/PS II molar ratios when estimated by oxidation-reduction difference absorption spectra of P700 (for PS I) and Cyt

Akio Murakami

1997-01-01

190

Pharmacokinetics of Oral d-Serine in d-Amino Acid Oxidase Knockout Mice  

PubMed Central

d-Amino acid oxidase (DAAO) catalyzes the oxidative deamination of d-amino acids including d-serine, a full agonist at the glycine modulatory site of the N-methyl-d-aspartate (NMDA) receptor. To evaluate the significance of DAAO-mediated metabolism in the pharmacokinetics of oral d-serine, plasma d-serine levels were measured in both wild-type mice and transgenic mice lacking DAAO. Although d-serine levels were rapidly diminished in wild-type mice (t½ = 1.2 h), sustained drug levels over the course of 4 h (t½ > 10 h) were observed in mice lacking DAAO. Coadministration of d-serine with 6-chlorobenzo[d]isoxazol-3-ol (CBIO), a small-molecule DAAO inhibitor, in wild-type mice resulted in the enhancement of plasma d-serine levels, although CBIO seems to have only temporary effects on the plasma d-serine levels due to glucuronidation of the key hydroxyl group. These findings highlight the predominant role of DAAO in the clearance of d-serine from the systemic circulation. Thus, a potent DAAO inhibitor with a longer half-life should be capable of maintaining high plasma d-serine levels over a sustained period of time and might have therapeutic implications for the treatment of schizophrenia. PMID:22837388

Rais, Rana; Thomas, Ajit G.; Wozniak, Krystyna; Wu, Ying; Jaaro-Peled, Hanna; Sawa, Akira; Strick, Christine A.; Engle, Sandra J.; Brandon, Nicholas J.; Rojas, Camilo; Slusher, Barbara S.

2012-01-01

191

Pharmacokinetics of oral D-serine in D-amino acid oxidase knockout mice.  

PubMed

D-Amino acid oxidase (DAAO) catalyzes the oxidative deamination of D-amino acids including D-serine, a full agonist at the glycine modulatory site of the N-methyl-d-aspartate (NMDA) receptor. To evaluate the significance of DAAO-mediated metabolism in the pharmacokinetics of oral D-serine, plasma D-serine levels were measured in both wild-type mice and transgenic mice lacking DAAO. Although D-serine levels were rapidly diminished in wild-type mice (t(½) = 1.2 h), sustained drug levels over the course of 4 h (t(½) > 10 h) were observed in mice lacking DAAO. Coadministration of D-serine with 6-chlorobenzo[d]isoxazol-3-ol (CBIO), a small-molecule DAAO inhibitor, in wild-type mice resulted in the enhancement of plasma D-serine levels, although CBIO seems to have only temporary effects on the plasma D-serine levels due to glucuronidation of the key hydroxyl group. These findings highlight the predominant role of DAAO in the clearance of D-serine from the systemic circulation. Thus, a potent DAAO inhibitor with a longer half-life should be capable of maintaining high plasma D-serine levels over a sustained period of time and might have therapeutic implications for the treatment of schizophrenia. PMID:22837388

Rais, Rana; Thomas, Ajit G; Wozniak, Krystyna; Wu, Ying; Jaaro-Peled, Hanna; Sawa, Akira; Strick, Christine A; Engle, Sandra J; Brandon, Nicholas J; Rojas, Camilo; Slusher, Barbara S; Tsukamoto, Takashi

2012-11-01

192

Phylogenetic analysis of serine proteases from Russell's viper (Daboia russelli siamensis) and Agkistrodon piscivorus leucostoma venom  

PubMed Central

Serine proteases are widely found in snake venoms. They have variety of functions including contributions to hemostasis. In this study, five serine proteases were cloned and characterized from two different cDNA libraries: factor V activator (RVV-V), alpha fibrinogenase (RVAF) and beta fibrinogenase (RVBF) from Russell's viper (Daboia russelli siamensis), and plasminogen activator (APL-PA) and protein C activator (APL-C) from Agkistrodon piscivorus leucostoma. The snake venom serine proteases were clustered in phylogenetic tree according to their functions. KA/KS values suggested that accelerated evolution has occurred in the mature protein coding regions in cDNAs of snake venom serine proteases. PMID:21640745

Sukkapan, Pattadon; Jia, Ying; Nuchprayoon, Issarang; Perez, John C.

2012-01-01

193

Phylogenetic analysis of serine proteases from Russell's viper (Daboia russelli siamensis) and Agkistrodon piscivorus leucostoma venom.  

PubMed

Serine proteases are widely found in snake venoms. They have variety of functions including contributions to hemostasis. In this study, five serine proteases were cloned and characterized from two different cDNA libraries: factor V activator (RVV-V), alpha fibrinogenase (RVAF) and beta fibrinogenase (RVBF) from Russell's viper (Daboia russelli siamensis), and plasminogen activator (APL-PA) and protein C activator (APL-C) from Agkistrodon piscivorus leucostoma. The snake venom serine proteases were clustered in phylogenetic tree according to their functions. K(A)/K(S) values suggested that accelerated evolution has occurred in the mature protein coding regions in cDNAs of snake venom serine proteases. PMID:21640745

Sukkapan, Pattadon; Jia, Ying; Nuchprayoon, Issarang; Pérez, John C

2011-08-01

194

Adaptational modification of serine and threonine metabolism in the liver to essential amino acid deficiency in rats.  

PubMed

It is known that plasma serine and threonine concentrations are elevated in rats chronically fed an essential amino acid deficient diet, but the underlying mechanisms including related gene expressions or serine and threonine concentrations in liver remained to be elucidated. We fed rats lysine or valine deficient diet for 4 weeks and examined the mRNA expressions of serine synthesising (3-phosphoglycerate dehydrogenase, PHGDH) and serine/threonine degrading enzymes (serine dehydratase, SDS) in the liver. Dietary deficiency induced marked elevation of hepatic serine and threonine levels associated with enhancement of PHGDH mRNA expression and repression of SDS mRNA expression. Increases in plasma serine and threonine levels due to essential amino acid deficiency in diet were caused by marked increases in hepatic serine and threonine levels. Proteolytic responses to the amino acid deficiency may be lessened by storing amino radicals as serine and inducing anorexia through elevation of threonine. PMID:18584286

Nagao, Kenji; Bannai, Makoto; Seki, Shinobu; Mori, Masato; Takahashi, Michio

2009-03-01

195

T-PS-P Task Force Minutes April 25, 2012  

E-print Network

the peer review guidelines developed by Kirby Barrick and obtain feedback from the Faculty Assembly with an NSF grant proposal summary. · A summary would assist the T-PS-P Committee's and Dean's evaluations

Jawitz, James W.

196

Sub20 ps silicon bipolar technology using selective epitaxial growth  

Microsoft Academic Search

A sub-20 ps silicon bipolar technology has been developed using selective epitaxial growth (SEG) for the active base and collector regions. This transistor concept allows the simultaneous reduction of base width and base\\/collector capacitance while maintaining low extrinsic base resistance. At a current of 0.8 mA a record CML gate delay time of 18 ps is achieved with devices showing

T. F. Meister; R. Stengl; H. W. Meul; R. Weyl; P. Packan; A. Felder; H. Klose; R. Schreiter; J. Popp; H. M. Rein; L. Treitinger

1992-01-01

197

The PS1 Science Mission - Status and Results  

NASA Astrophysics Data System (ADS)

PS1, the Pan-STARRS1 Telescope is in its last year of the PS1 Science Mission. Operations of the PS1 System include the Observatory, Telescope, 1.4 Gigapixel Camera, Image Processing Pipeline , PSPS relational database and reduced science product software servers. The PS1 Surveys include: (1) A 3pi Steradian Survey, (2) A Medium Deep survey of 10 PS1 footprints spaced around the sky; (3) A solar system survey optimized for Near Earth Objects, (4) a Stellar Transit Survey; and (5) a Deep Survey of M31. The PS1 3pi Survey has now covered the sky north of dec=-30 with 8 to 12 visits in five bands: g,r,i,z and y or over ~45 epochs per point on sky. The performance of the PS1 system, sky coverage, cadence, and data quality of the surveys will be presented as well as progress in reprocessing of the data taken to date and plans for serving the data to the public. A summary of science highlights will be included. The PS1 Science Consortium consists of The Institute for Astronomy at the University of Hawai'i in Manoa, the Max Planck Institute for Astronomy, Heidelberg and the Max Planck Institute for Extraterrestrial Physics, Garching, The Johns Hopkins University, the University of Durham, the University of Edinburgh, the Queen's University Belfast, the Harvard-Smithsonian Center for Astrophysics, the Los Cumbres Observatory Global Telescope Network Incorporated, and the National Central University of Taiwan, NASA, and NSF.

Chambers, Kenneth C.

2013-06-01

198

Part (a) of Hunter's Proof of Henkin's Completeness Theorem for PS Branden Fitelson  

E-print Network

on the right) required to generate each MP step. PS1 A (B A) PS2 A (B C)) ((A B) (A C)) PS3 (A B) (B. A ((B C) (C B)) [MP, PS3, PS1] 4. (A ((B A) C)) (A C) [MP, 2, 1] 5. (A (B C)) (A (C B)) [MP, 3, PS2] 6. A (A B) [MP, 5, PS1] 7. A (B A) [MP, 6, 5] 8. A A [MP, 7, 4] 9. A A [MP, 8, PS3] 10

Fitelson, Branden

199

Electrical and thermal behavior of PS/ferrite composite  

NASA Astrophysics Data System (ADS)

This work aims to study the effect of gamma radiation on the structure, thermal and electrical properties of PS/ferrite composite. The Ni0.6Cd0.4Fe2-xSmxO4 was prepared using a conventional sintering ceramic process. Ferrite powder and Styrene was mixed and achieve polymerization process by gamma irradiation at 50 kGy. The composite samples have single spinel phase structure. Stability of the crystalline structure and no phase transition due to irradiation are found. The bulk density decreases whereas X-ray density increases with increasing Sm contents for both ferrite and PS/ferrite. The tetrahedral radii rA remains constant with Sm content but octahedral radii rB increases for both ferrite and PS/ferrite composite. The grain size shows increasing trend for PS/ferrite composite. The PS nearly coat the grains and so their boundaries become faint and not sharp. The gamma radiation transfer Fe3+ to Fe2+ due to its ionizing effect.The Fe2+ occupy octahedral site and the stretching vibration of its bond with oxygen (Fe2+-O2-) gives absorption at about 392 cm-1, near octahedral absorption at 462 cm-1.The PS/Ni0.6Cd0.4SmxFe2-xO4 composite becomes thermally more stable than pure polystyrene. The activation energy of conduction E? has a small values and in the range of hopping conduction mechanism.

Ashour, A. H.; Hemeda, O. M.; Heiba, Z. K.; Al-Zahrani, S. M.

2014-11-01

200

Spectroscopic and thermal studies of PS/PVAc blends  

NASA Astrophysics Data System (ADS)

Polystyrene and polyvinyl acetate (PS/PVAc) films were blended with different contents using casting method. The effect of PS content on PVAc blends was investigated by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), Ultra violet and visible studies (UV/VIS), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Significant changes in FT-IR, XRD and DSC analysis are observed which reveals an interactions between the two polymers and PS/PVAc blends had good or certain miscibility. XRD scans show some changes in the intensity and the height of the amorphous halos with increased PS. UV/VIS analysis revealed that the optical band gap decreases with increasing content of PS from 5 to 4.11 eV. A single glass transition temperature for each blend was observed, this DSC results supported that the miscibility existed in the blend. The apparent activation energy (E) of the blends was evaluated using TGA analysis. The value of E was increased with the increase of PS content.

Elashmawi, I. S.; Hakeem, N. A.; Abdelrazek, E. M.

2008-10-01

201

Reduced serine racemase expression contributes to age-related deficits in hippocampal cognitive function.  

PubMed

To gain insight into the contribution of d-serine to impaired cognitive aging, we compared the metabolic pathway and content of the amino acid as well as d-serine-dependent synaptic transmission and plasticity in the hippocampus of young and old rats of the Wistar and Lou/C/Jall strains. Wistar rats display cognitive impairments with aging that are not found in the latter strain, which is therefore considered a model of healthy aging. Both mRNA and protein levels of serine racemase, the d-serine synthesizing enzyme, were decreased in the hippocampus but not in the cerebral cortex or cerebellum of aged Wistar rats, whereas the expression of d-amino acid oxidase, which degrades the amino acid, was not affected. Consequently, hippocampal levels of endogenous d-serine were significantly lower. In contrast, serine racemase expression and d-serine levels were not altered in the hippocampus of aged Lou/C/Jall rats. Ex vivo electrophysiological recordings in hippocampal slices showed a marked reduction in N-methyl-d-aspartate-receptor (NMDA-R)-mediated synaptic potentials and theta-burst-induced long-term potentiation (LTP) in the CA1 area of aged Wistar rats, which were restored by exogenous d-serine. In contrast, NMDA-R activation, LTP induction and responses to d-serine were not altered in aged Lou/C/Jall rats. These results further strengthen the notion that the serine racemase-dependent pathway is a prime target of hippocampus-dependent cognitive deficits with aging. Understanding the processes that specifically affect serine racemase during aging could thus provide key insights into the treatment of memory deficits in the elderly. PMID:19800712

Turpin, F R; Potier, B; Dulong, J R; Sinet, P-M; Alliot, J; Oliet, S H R; Dutar, P; Epelbaum, J; Mothet, J-P; Billard, J-M

2011-08-01

202

Crystal structure of a zinc-dependent D-serine dehydratase from chicken kidney.  

PubMed

D-serine is a physiological co-agonist of the N-methyl-D-aspartate receptor. It regulates excitatory neurotransmission, which is important for higher brain functions in vertebrates. In mammalian brains, D-amino acid oxidase degrades D-serine. However, we have found recently that in chicken brains the oxidase is not expressed and instead a D-serine dehydratase degrades D-serine. The primary structure of the enzyme shows significant similarities to those of metal-activated D-threonine aldolases, which are fold-type III pyridoxal 5'-phosphate (PLP)-dependent enzymes, suggesting that it is a novel class of D-serine dehydratase. In the present study, we characterized the chicken enzyme biochemically and also by x-ray crystallography. The enzyme activity on D-serine decreased 20-fold by EDTA treatment and recovered nearly completely by the addition of Zn(2+). None of the reaction products that would be expected from side reactions of the PLP-D-serine Schiff base were detected during the >6000 catalytic cycles of dehydration, indicating high reaction specificity. We have determined the first crystal structure of the D-serine dehydratase at 1.9 Å resolution. In the active site pocket, a zinc ion that coordinates His(347) and Cys(349) is located near the PLP-Lys(45) Schiff base. A theoretical model of the enzyme-D-serine complex suggested that the hydroxyl group of D-serine directly coordinates the zinc ion, and that the ?-NH(2) group of Lys(45) is a short distance from the substrate C? atom. The ?-proton abstraction from D-serine by Lys(45) and the elimination of the hydroxyl group seem to occur with the assistance of the zinc ion, resulting in the strict reaction specificity. PMID:21676877

Tanaka, Hiroyuki; Senda, Miki; Venugopalan, Nagarajan; Yamamoto, Atsushi; Senda, Toshiya; Ishida, Tetsuo; Horiike, Kihachiro

2011-08-01

203

Crystal Structure of a Zinc-dependent d-Serine Dehydratase from Chicken Kidney*  

PubMed Central

d-Serine is a physiological co-agonist of the N-methyl-d-aspartate receptor. It regulates excitatory neurotransmission, which is important for higher brain functions in vertebrates. In mammalian brains, d-amino acid oxidase degrades d-serine. However, we have found recently that in chicken brains the oxidase is not expressed and instead a d-serine dehydratase degrades d-serine. The primary structure of the enzyme shows significant similarities to those of metal-activated d-threonine aldolases, which are fold-type III pyridoxal 5?-phosphate (PLP)-dependent enzymes, suggesting that it is a novel class of d-serine dehydratase. In the present study, we characterized the chicken enzyme biochemically and also by x-ray crystallography. The enzyme activity on d-serine decreased 20-fold by EDTA treatment and recovered nearly completely by the addition of Zn2+. None of the reaction products that would be expected from side reactions of the PLP-d-serine Schiff base were detected during the >6000 catalytic cycles of dehydration, indicating high reaction specificity. We have determined the first crystal structure of the d-serine dehydratase at 1.9 Å resolution. In the active site pocket, a zinc ion that coordinates His347 and Cys349 is located near the PLP-Lys45 Schiff base. A theoretical model of the enzyme-d-serine complex suggested that the hydroxyl group of d-serine directly coordinates the zinc ion, and that the ?-NH2 group of Lys45 is a short distance from the substrate C? atom. The ?-proton abstraction from d-serine by Lys45 and the elimination of the hydroxyl group seem to occur with the assistance of the zinc ion, resulting in the strict reaction specificity. PMID:21676877

Tanaka, Hiroyuki; Senda, Miki; Venugopalan, Nagarajan; Yamamoto, Atsushi; Senda, Toshiya; Ishida, Tetsuo; Horiike, Kihachiro

2011-01-01

204

An essential role for de novo biosynthesis of L-serine in CNS development.  

PubMed

L-serine plays a versatile role in intermediary metabolism in eukaryotic cells. The physiological significance of its de novo biosynthesis, however, remains largely unexplored. We demonstrated previously that neurons lose the ability to synthesize L-serine after their final differentiation and thus depend on astrocytes to supply this amino acid. This is due to a lack of neuronal expression of 3-phosphoglycerate dehydrogenase (Phgdh), which initiates de novo L-serine synthesis via the phosphorylated pathway from the glycolytic intermediate 3-phosphoglycerate. In rodent brain, Phgdh is expressed exclusively by the neuroepithelium/radial glia/astrocyte lineage. In humans, serine deficiency disorders can result from a deficiency of Phgdh or other enzymes involved in serine biosynthesis in the phosphorylated pathway. Patients with such disorders have lower serine levels in plasma and cerebrospinal fluid; they exhibit severe neurological symptoms including congenital microcephaly, feeding disabilities, and psychomotor retardation. L-serine supplementation can attenuate developmental defects in these patients. To define the physiological importance of de novo L-serine production, we generated Phgdh knockout mice using targeted gene disruption technique. Phgdh deletion drastically reduced serine and glycine levels in the body. Phgdh knockout mice exhibited overall growth retardation with severe brain malformation, culminating in embryonic lethality. These observations highlight the vital role of de novo L-serine synthesis in the formation and function of the mammalian central nervous system. Furthermore, the embryonic lethal phenotype of Phgdh knockouts indicates that L-serine must be synthesized endogenously in mouse (and probably humans) during embryonic development. PMID:18296366

Furuya, Shigeki

2008-01-01

205

Brain-specific Phgdh deletion reveals a pivotal role for L-serine biosynthesis in controlling the level of D-serine, an N-methyl-D-aspartate receptor co-agonist, in adult brain.  

PubMed

In mammalian brain, D-serine is synthesized from L-serine by serine racemase, and it functions as an obligatory co-agonist at the glycine modulatory site of N-methyl-D-aspartate (NMDA)-selective glutamate receptors. Although diminution in D-serine level has been implicated in NMDA receptor hypofunction, which is thought to occur in schizophrenia, the source of the precursor L-serine and its role in D-serine metabolism in adult brain have yet to be determined. We investigated whether L-serine synthesized in brain via the phosphorylated pathway is essential for D-serine synthesis by generating mice with a conditional deletion of D-3-phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95). This enzyme catalyzes the first step in L-serine synthesis via the phosphorylated pathway. HPLC analysis of serine enantiomers demonstrated that both L- and D-serine levels were markedly decreased in the cerebral cortex and hippocampus of conditional knock-out mice, whereas the serine deficiency did not alter protein expression levels of serine racemase and NMDA receptor subunits in these regions. The present study provides definitive proof that L-serine-synthesized endogenously via the phosphorylated pathway is a key rate-limiting factor for maintaining steady-state levels of D-serine in adult brain. Furthermore, NMDA-evoked transcription of Arc, an immediate early gene, was diminished in the hippocampus of conditional knock-out mice. Thus, this study demonstrates that in mature neuronal circuits L-serine availability determines the rate of D-serine synthesis in the forebrain and controls NMDA receptor function at least in the hippocampus. PMID:20966073

Yang, Jung Hoon; Wada, Akira; Yoshida, Kazuyuki; Miyoshi, Yurika; Sayano, Tomoko; Esaki, Kayoko; Kinoshita, Masami O; Tomonaga, Shozo; Azuma, Norihiro; Watanabe, Masahiko; Hamase, Kenji; Zaitsu, Kiyoshi; Machida, Takeo; Messing, Albee; Itohara, Shigeyoshi; Hirabayashi, Yoshio; Furuya, Shigeki

2010-12-31

206

Brain-specific Phgdh Deletion Reveals a Pivotal Role for l-Serine Biosynthesis in Controlling the Level of d-Serine, an N-methyl-d-aspartate Receptor Co-agonist, in Adult Brain*  

PubMed Central

In mammalian brain, d-serine is synthesized from l-serine by serine racemase, and it functions as an obligatory co-agonist at the glycine modulatory site of N-methyl-d-aspartate (NMDA)-selective glutamate receptors. Although diminution in d-serine level has been implicated in NMDA receptor hypofunction, which is thought to occur in schizophrenia, the source of the precursor l-serine and its role in d-serine metabolism in adult brain have yet to be determined. We investigated whether l-serine synthesized in brain via the phosphorylated pathway is essential for d-serine synthesis by generating mice with a conditional deletion of d-3-phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95). This enzyme catalyzes the first step in l-serine synthesis via the phosphorylated pathway. HPLC analysis of serine enantiomers demonstrated that both l- and d-serine levels were markedly decreased in the cerebral cortex and hippocampus of conditional knock-out mice, whereas the serine deficiency did not alter protein expression levels of serine racemase and NMDA receptor subunits in these regions. The present study provides definitive proof that l-serine-synthesized endogenously via the phosphorylated pathway is a key rate-limiting factor for maintaining steady-state levels of d-serine in adult brain. Furthermore, NMDA-evoked transcription of Arc, an immediate early gene, was diminished in the hippocampus of conditional knock-out mice. Thus, this study demonstrates that in mature neuronal circuits l-serine availability determines the rate of d-serine synthesis in the forebrain and controls NMDA receptor function at least in the hippocampus. PMID:20966073

Yang, Jung Hoon; Wada, Akira; Yoshida, Kazuyuki; Miyoshi, Yurika; Sayano, Tomoko; Esaki, Kayoko; Kinoshita, Masami O.; Tomonaga, Shozo; Azuma, Norihiro; Watanabe, Masahiko; Hamase, Kenji; Zaitsu, Kiyoshi; Machida, Takeo; Messing, Albee; Itohara, Shigeyoshi; Hirabayashi, Yoshio; Furuya, Shigeki

2010-01-01

207

Profiling the microRNA Expression in Human iPS and iPS-derived Retinal Pigment Epithelium  

PubMed Central

The purpose of this study is to characterize the microRNA (miRNA) expression profiles of induced pluripotent stem (iPS) cells and retinal pigment epithelium (RPE) derived from induced pluripotent stem cells (iPS-RPE). MiRNAs have been demonstrated to play critical roles in both maintaining pluripotency and facilitating differentiation. Gene expression networks accountable for maintenance and induction of pluripotency are linked and share components with those networks implicated in oncogenesis. Therefore, we hypothesize that miRNA expression profiling will distinguish iPS cells from their iPS-RPE progeny. To identify and analyze differentially expressed miRNAs, RPE was derived from iPS using a spontaneous differentiation method. MiRNA microarray analysis identified 155 probes that were statistically differentially expressed between iPS and iPS-RPE cells. Up-regulated miRNAs including miR-181c and miR-129–5p may play a role in promoting differentiation, while down-regulated miRNAs such as miR-367, miR-18b, and miR-20b are implicated in cell proliferation. Subsequent miRNA–target and network analysis revealed that these miRNAs are involved in cellular development, cell cycle progression, cell death, and survival. A systematic interrogation of temporal and spatial expression of iPS-RPE miRNAs and their associated target mRNAs will provide new insights into the molecular mechanisms of carcinogenesis, eye differentiation and development.

Wang, Heuy-Ching; Greene, Whitney A; Kaini, Ramesh R; Shen-Gunther, Jane; Chen, Hung-I H; Cai, Hong; Wang, Yufeng

2014-01-01

208

Quantum chemical study of simple positronic systems using explicitly correlated Gaussian functions - PsH and PsLi+  

NASA Astrophysics Data System (ADS)

The electronic structure of positronium hydride has been studied using explicitly correlated Gaussian functions. The resulting energy constitutes new upper bound to the exact nonrelativistic energy of PsH within the Born-Oppenheimer approximation. The two photon annihilation rate was computed using the optimized wave function. Preliminary results for the positron bonded with the lithium atom indicate the stability of this system against the dissociation into Li+ cation and Ps atom.

Strasburger, K.; Chojnacki, H.

1998-02-01

209

Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine.  

PubMed

Trigeminal neuropathic pain affects millions of people worldwide. Despite decades of study on the neuronal processing of pain, mechanisms underlying enhanced pain states after injury remain unclear. N-methyl-D-aspartate (NMDA) receptor-dependent changes play a critical role in triggering central sensitization in neuropathic pain. These receptors are regulated at the glycine site through a mandatory endogenous co-agonist D-serine, which is synthesized by astrocytes. Therefore, the present study was carried out to determine whether astrocytes are involved, through D-serine secretion, in dynamic mechanical allodynia (DMA) obtained after chronic constriction of the infraorbital nerve (CCI-IoN) in rats. Two weeks after CCI-IoN, an important reaction of astrocytes was present in the medullary dorsal horn (MDH), as revealed by an up-regulation of glial fibrillary acidic protein (GFAP) in allodynic rats. In parallel, an increase in D-serine synthesis, which co-localized with its synthesis enzyme serine racemase, was strictly observed in astrocytes. Blocking astrocyte metabolism by intracisternal delivery of fluorocitrate alleviated DMA. Furthermore, the administration of D-amino-acid oxidase (DAAO), a D-serine-degrading enzyme, or that of L-serine O-sulfate (LSOS), a serine racemase inhibitor, significantly decreased pain behavior in allodynic rats. These results demonstrate that astrocytes are involved in the modulation of orofacial post-traumatic neuropathic pain via the release of the gliotransmitter D-serine. PMID:23881719

Dieb, W; Hafidi, A

2013-09-01

210

Construction of an L-serine producing Escherichia coli via metabolic engineering.  

PubMed

L-Serine is a nonessential amino acid, but plays a crucial role as a building block for cell growth. Currently, L-serine production is mainly dependent on enzymatic or cellular conversion. In this study, we constructed a recombinant Escherichia coli that can fermentatively produce L-serine from glucose. To accumulate L-serine, sdaA encoding the L-serine dehydratase, iclR encoding the isocitrate lyase regulator, and arcA encoding the aerobic respiration control protein were deleted in turn. In batch fermentation, the engineered E. coli strain YF-5 exhibited obvious L-serine accumulation but poor cell growth. To restore cell growth, aceB encoding the malate synthase was knocked out, and the engineered strain was then transformed with plasmid that overexpressed serA (FR) , serB, and serC genes. The resulting strain YF-7 produced 4.5 g/L L-serine in batch cultivation and 8.34 g/L L-serine in fed-batch cultivation. PMID:24997624

Gu, Pengfei; Yang, Fan; Su, Tianyuan; Li, Fangfang; Li, Yikui; Qi, Qingsheng

2014-09-01

211

A novel serine protease inhibitor acts as an immunomodulatory switch while maintaining homeostasis.  

PubMed

Serine protease cascades boost immune responses while maintaining homeostasis. These crucial actions are intricately regulated by cognate serine protease inhibitors. However, the mechanism underlying such a dynamic immunomodulation during acute phase infection remains obscure, particularly where the pathogen's serine protease adds a new challenge to the host. Here, we found that infection of horseshoe crab, Carcinoscorpius rotundicauda, induced reciprocal profiles of CrSPI (serine protease inhibitor) and CrFurin (serine protease) with respect to their transcription and protein activities. Using recombinant rCrSPI, we explored its inhibitory activity against various microbial proteases and found it most efficacious against a model serine protease, subtilisin A. rCrSPI inhibited subtilisin at Ki 10(-9)M with a molar ratio of 1 rCrSPI:2 subtilisin. The rCrSPI also inhibited plasma CrFurin, suppressed subtilisin-mediated activation of prophenoloxidase (PPO) and interacted with complement C3. Taken together, CrSPI acts as a key immunomodulatory 'on-off' switch in a 2-way regulation of serine protease microbial subtilisin and host serine proteases (CrFurin and CrC3), thereby controlling immune responses involving the complements and the PPO-mediated antimicrobial activities, while maintaining homeostasis. PMID:20375604

Jiang, N; Thangamani, S; Chor, C F; Wang, S Y; Winarsih, I; Du, R J; Sivaraman, J; Ho, B; Ding, J L

2009-01-01

212

Drosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease  

E-print Network

, to generate two distinct inhibitor of apoptosis (IAP) binding motifs. Depending upon the proapoptotic stimulusDrosophila Omi, a mitochondrial-localized IAP antagonist and proapoptotic serine protease Madhavi. Herein, we demon- strate that Drosophila Omi (dOmi), a fly homologue of the serine protease Omi/HtrA2

Yin, Y. Whitney

213

14-3-3 Inhibits Bad-Induced Cell Death through Interaction with Serine-136  

E-print Network

14-3-3 Inhibits Bad-Induced Cell Death through Interaction with Serine-136 SHANE C. MASTERS-3-3 is the proapoptotic Bcl-2 family member Bad. Serine phosphorylation of Bad is associated with 14-3-3 binding and inhibition of Bad-induced cell death, but the rela- tive contributions of the three known phosphorylation

Datta, Sandeep Robert

214

Amperometric microbiosensor as an alternative tool for investigation of D-serine in brain.  

PubMed

This paper discusses the application of a reagentless, selective microbiosensor as a useful alternative tool for monitoring D-serine in neural samples. The main components of the 125-?m-diameter disk biosensor were D-amino acid oxidase for D-serine sensitivity (linear region slope, 61 ± 7 ?A cm(-2) mM(-1); limit of detection, 20 nM), and poly-phenylenediamine for rejection of electroactive interference. The response time of the biosensor was of the order of 1 s, ideal for 'real-time' monitoring, and detection of systemically administered D-serine in brain extracellular fluid is demonstrated. Exploitation of this probe might resolve queries involving regulation of D-serine in excitotoxicity, and modulation of N-methyl-D-aspartate receptor function by D-serine and glycine in the central nervous system. PMID:22865247

Mohd Zain, Zainiharyati; Ab Ghani, Sulaiman; O'Neill, Robert D

2012-11-01

215

Serine is a natural ligand and allosteric activator of pyruvate kinase M2  

PubMed Central

Cancer cells exhibit several unique metabolic phenotypes that are critical for cell growth and proliferation. Specifically, they over-express the M2 isoform of the tightly regulated enzyme pyruvate kinase (PKM2), which controls glycolytic flux, and they are highly dependent on de novo biosynthesis of serine and glycine. Here we describe a novel rheostat-like mechanistic relationship between PKM2 activity and serine biosynthesis. We show that serine can bind to and activate human PKM2 and that following serine deprivation, PKM2 activity in cells is reduced. This reduction in PKM2 activity shifts cells to a fuel-efficient mode where more pyruvate is diverted to the mitochondria and more glucose derived carbon is channelled into serine biosynthesis to support cell proliferation. PMID:23064226

Zheng, Liang; Martin, Agnes C.L.; Maddocks, Oliver D.K.; Chokkathukalam, Achuthanunni; Coyle, Joseph E; Jankevics, Andris; Holding, Finn P.; Vousden, Karen H.; Frezza, Christian; O'Reilly, Marc; Gottlieb, Eyal

2013-01-01

216

Activity based protein profiling to detect serine hydrolase alterations in virus infected cells  

PubMed Central

Activity-based protein profiling (ABPP) is a newly emerging technique that uses active site-directed probes to monitor the functional status of enzymes. Serine hydrolases are one of the largest families of enzymes in mammals. More than 200 serine hydrolases have been identified, but little is known about their specific roles. Serine hydrolases are involved in a variety of physiological functions, including digestion, immune response, blood coagulation, and reproduction. ABPP has been used recently to investigate host–virus interactions and to understand the molecular pathogenesis of virus infections. Monitoring the altered serine hydrolases during viral infection gives insight into the catalytic activity of these enzymes that will help to identify novel targets for diagnostic and therapeutic application. This review presents the usefulness of ABPP in detecting and analyzing functional annotation of host cell serine hydrolases as a result of host–virus interaction. PMID:23024641

Shahiduzzaman, Md.; Coombs, Kevin M.

2012-01-01

217

Rapid purification of serine proteinases from Bothrops alternatus and Bothrops moojeni venoms.  

PubMed

Envenomation by Bothrops species results, among other symptoms, in hemostatic disturbances. These changes can be ascribed to the presence of enzymes, primarily serine proteinases some of which are structurally similar to thrombin and specifically cleave fibrinogen releasing fibrinopeptides. A rapid, three-step, chromatographic procedure was developed to routinely purify serine proteinases from the venoms of Bothrops alternatus and Bothrops moojeni. The serine proteinase from B. alternatus displays an apparent molecular mass of ~32 kDa whereas the two closely related serine proteinases from B. moojeni display apparent molecular masses of ~32 kDa and ~35 kDa in SDS-PAGE gels. The partial sequences indicated that these enzymes share high identity with serine proteinases from the venoms of other Bothrops species. These proteins coagulate plasma and possess fibrinogenolytic activity but lack fibrinolytic activity. PMID:24140922

Fernandes de Oliveira, Liliane Maria; Ullah, Anwar; Masood, Rehana; Zelanis, André; Spencer, Patrick J; Serrano, Solange M T; Arni, Raghuvir K

2013-12-15

218

Cloning and Expression of the Two Genes Coding for L-Serine Dehydratase from Peptostreptococcus asaccharolyticus: Relationship of the Iron-Sulfur Protein to Both L-Serine Dehydratases from Escherichia coli  

Microsoft Academic Search

L-Serine dehydratases and L-threonine dehydratases catalyze the irreversible overall deaminations of L-serine to pyruvate and L-threonine to 2-oxobutyrate. Most L-threonine dehydrata- ses have been shown to contain pyridoxal-59-phosphate as the prosthetic group. In contrast to L-threonine dehydratases, none of the bacterial L-serine dehydratases investigated to date has been conclusively proven to be dependent on pyridoxal-59- phosphate (6). An L-serine dehydratase

ANTJE E. M. HOFMEISTER; SUSANNE TEXTOR; WOLFGANG BUCKEL

219

The nature of D-serine--induced nephrotoxicity.  

PubMed

Renal structural changes were studied sequentially between 1 hour and 6 days in rats treated with D-serine. Extensive necrosis of proximal straight tubules was rapid in onset and was followed by complete tubular regeneration 6 days post-treatment. The apparent progression of cellular changes was initial shrinkage, followed either by swelling and loss of apical cytoplasm or immediate lysis of cytoplasmic and nuclear contents. Tubular damage left only the basement membrane as a barrier between interstitial and luminal fluids. In similarly treated rats, proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by epithelium suggesting that they are due to diffusion of protein and glucose from interstitium into tubular fluid across the denuded basement membranes and that epithelial cells, under normal conditions, act as a barrier to diffusion of certain substances between the interstitium and tubular fluid. PMID:4447130

Ganote, C E; Peterson, D R; Carone, F A

1974-11-01

220

Arabidopsis PPP family of serine/threonine phosphatases.  

PubMed

Serine/threonine-specific phosphoprotein phosphatases (PPPs) are ubiquitous enzymes in all eukaryotes, but their regulatory functions are largely unknown in higher plants. The Arabidopsis genome encodes 26 PPP catalytic subunits related to type 1, type 2A and so-called novel phosphatases, including four plant-specific enzymes carrying large N-terminal kelch-domains, but no apparent homologue of the PP2B family. The catalytic subunits of PPPs associate with regulatory protein partners that target them to well defined cellular locations and modulate their activity. Recent studies of phosphatase partners and their interactions have directed attention again to functional dissection of plant PPP families, and highlight their intriguing roles in the regulation of metabolism, cell cycle and development, as well as their roles in light, stress and hormonal signalling. PMID:17368080

Farkas, Ilona; Dombrádi, Viktor; Miskei, Márton; Szabados, László; Koncz, Csaba

2007-04-01

221

A Self-compartmentalizing Hexamer Serine Protease from Pyrococcus Horikoshii  

PubMed Central

Oligopeptidases impose a size limitation on their substrates, the mechanism of which has long been under debate. Here we present the structure of a hexameric serine protease, an oligopeptidase from Pyrococcus horikoshii (PhAAP), revealing a complex, self-compartmentalized inner space, where substrates may access the monomer active sites passing through a double-gated “check-in” system, first passing through a pore on the hexamer surface and then turning to enter through an even smaller opening at the monomers' domain interface. This substrate screening strategy is unique within the family. We found that among oligopeptidases, a residue of the catalytic apparatus is positioned near an amylogenic ?-edge, which needs to be protected to prevent aggregation, and we found that different oligopeptidases use different strategies to achieve such an end. We propose that self-assembly within the family results in characteristically different substrate selection mechanisms coupled to different multimerization states. PMID:23632025

Menyhard, Dora K.; Kiss-Szeman, Anna; Tichy-Racs, Eva; Hornung, Balazs; Radi, Krisztina; Szeltner, Zoltan; Domokos, Klarissza; Szamosi, Ilona; Naray-Szabo, Gabor; Polgar, Laszlo; Harmat, Veronika

2013-01-01

222

Competitive Activity-Based Protein Profiling Identifies Aza-?-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition  

E-print Network

Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered ...

Zuhl, Andrea M.

223

ATP binding to human serine racemase is cooperative and modulated by glycine.  

PubMed

The N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, and control learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists d-serine and glycine. In the human brain, d-serine is synthesized from l-serine by the dimeric pyridoxal 5'-phosphate-dependent enzyme serine racemase, which also degrades l- and d-serine to pyruvate and ammonia. The dependence of l- and d-serine ?-elimination and l-serine racemization activities on ATP concentration was characterized, and was found to be strongly cooperative, with Hill coefficients close to 2 and apparent ATP dissociation constants ranging from 0.22 to 0.41 mm. ATP binding to the holo-enzyme, monitored by the fluorescence changes of the coenzyme, was also determined to be cooperative, with an apparent dissociation constant of 0.24 mm. Glycine, an active-site ligand, increased the serine racemase affinity for ATP by ~ 22-fold, abolishing cooperativity. Conversely, ATP increased the non-cooperative glycine binding 15-fold. These results indicate cross-talk between allosteric and active sites, leading to the stabilization of two alternative protein conformations with ATP affinities of ~ 10 ?M and 1.8 mm, as evaluated within the Monod, Wyman and Changeux model. Therefore, intracellular ATP and glycine control d-serine homeostasis, and, indirectly, NMDA receptor activity. Because hyper- and hypo-activation of NMDA receptors are associated with neuropathologies, the development of allosteric drugs modulating serine racemase activity is a promising therapeutic strategy. PMID:23992455

Marchetti, Marialaura; Bruno, Stefano; Campanini, Barbara; Peracchi, Alessio; Mai, Nicole; Mozzarelli, Andrea

2013-11-01

224

Characterization of crosslinked polystyrene(PS) beads in SBR matrix  

SciTech Connect

Monodisperse sized crosslinked polystyrene(PS) beads were prepared by a reaction of semibatch emulsion polymerization with styrene monomer, divinylbenzene(DVB) crosslinking agent and potassium persulfate(K{sub 2}S{sub 2}O{sub 9}) initiator in the absence of emulsifier. The glass transition temperature(T{sub g}) and the mean diameter of the beads were increased from 100{degrees}C to 135{degrees}C and from 402 nm to 532 nm, respectively, for an incorporation of 2 to 10 mol% DVB. Crosslinking density was also linearly increased with DVB content. SEM microphotographs of SBR composite filled with various contents of PS beads revealed that PS beads are relatively well dispersed without changing the spherical shape of the beads in all range of compositions. In stress-strain analysis, elongation at break and tensile strength of SBR composite were increased with the bead content. Applicability of the PS beads as a filler in SBR matrix is tested by plotting Mooney-Rivlin or Guth-Smallwood equations. However, mechanical properties of the composite with the beads were not so excellent as those of the composite with carbon black. Crosslinked PS beads are still tentative as a white color reinforcing filler on SBR matrix.

Cha, Yoon-Jong; Choe, Soonja [Inha Univ. (Korea, Republic of)

1995-12-01

225

RAF protein-serine/threonine kinases: Structure and regulation  

SciTech Connect

Research highlights: {yields} The formation of unique side-to-side RAF dimers is required for full kinase activity. {yields} RAF kinase inhibitors block MEK activation in cells containing oncogenic B-RAF. {yields} RAF kinase inhibitors can lead to the paradoxical increase in RAF kinase activity. -- Abstract: A-RAF, B-RAF, and C-RAF are a family of three protein-serine/threonine kinases that participate in the RAS-RAF-MEK-ERK signal transduction cascade. This cascade participates in the regulation of a large variety of processes including apoptosis, cell cycle progression, differentiation, proliferation, and transformation to the cancerous state. RAS mutations occur in 15-30% of all human cancers, and B-RAF mutations occur in 30-60% of melanomas, 30-50% of thyroid cancers, and 5-20% of colorectal cancers. Activation of the RAF kinases requires their interaction with RAS-GTP along with dephosphorylation and also phosphorylation by SRC family protein-tyrosine kinases and other protein-serine/threonine kinases. The formation of unique side-to-side RAF dimers is required for full kinase activity. RAF kinase inhibitors are effective in blocking MEK1/2 and ERK1/2 activation in cells containing the oncogenic B-RAF Val600Glu activating mutation. RAF kinase inhibitors lead to the paradoxical increase in RAF kinase activity in cells containing wild-type B-RAF and wild-type or activated mutant RAS. C-RAF plays a key role in this paradoxical increase in downstream MEK-ERK activation.

Roskoski, Robert, E-mail: rrj@brimr.org [Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742 (United States)] [Blue Ridge Institute for Medical Research, 3754 Brevard Road, Suite 116, Box 19, Horse Shoe, NC 28742 (United States)

2010-08-27

226

D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor  

Microsoft Academic Search

Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of D-serine with D-amino

Jean-Pierre Mothet; Angèle T. Parent; Herman Wolosker; Roscoe O. Brady Jr.; David J. Linden; Christopher D. Ferris; Michael A. Rogawski; Solomon H. Snyder

2000-01-01

227

D-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors  

Microsoft Academic Search

D-Serine is localized in mammalian brain to a discrete popula- tion of glial cells near NMDA receptors, suggesting that D-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immu- nohistochemical localizations of D-serine, glycine, and NMDA receptors in rat brain. In the telencephalon, D-serine is concen- trated in protoplasmic astrocytes, which

Michael J. Schell; Roscoe O. Brady Jr; Mark E. Molliver; Solomon H. Snyder

1997-01-01

228

Development of a high-throughput method for the determination of pharmacological levels of plasma d-serine  

Microsoft Academic Search

d-Serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, d-serine must be administered at high doses to observe clinical effects. This is due in large part to d-serine undergoing oxidation by d-amino acid oxidase (DAAO) before it reaches the brain. Consequently, coadministration of d-serine with a DAAO inhibitor has been suggested as a way

Jesse Alt; Camilo Rojas; Krystyna Wozniak; Ying Wu; Dana Ferraris; Takashi Tsukamoto; Barbara Slusher

2011-01-01

229

New insights into the evolution of subtilisin-like serine protease genes in Pezizomycotina  

PubMed Central

Background Subtilisin-like serine proteases play an important role in pathogenic fungi during the penetration and colonization of their hosts. In this study, we perform an evolutionary analysis of the subtilisin-like serine protease genes of subphylum Pezizomycotina to find if there are similar pathogenic mechanisms among the pathogenic fungi with different life styles, which utilize subtilisin-like serine proteases as virulence factors. Within Pezizomycotina, nematode-trapping fungi are unique because they capture soil nematodes using specialized trapping devices. Increasing evidence suggests subtilisin-like serine proteases from nematode-trapping fungi are involved in the penetration and digestion of nematode cuticles. Here we also conduct positive selection analysis on the subtilisin-like serine protease genes from nematode-trapping fungi. Results Phylogenetic analysis of 189 subtilisin-like serine protease genes from Pezizomycotina suggests five strongly-supported monophyletic clades. The subtilisin-like serine protease genes previously identified or presumed as endocellular proteases were clustered into one clade and diverged the earliest in the phylogeny. In addition, the cuticle-degrading protease genes from entomopathogenic and nematode-parasitic fungi were clustered together, indicating that they might have overlapping pathogenic mechanisms against insects and nematodes. Our experimental bioassays supported this conclusion. Interestingly, although they both function as cuticle-degrading proteases, the subtilisin-like serine protease genes from nematode-trapping fungi and nematode-parasitic fungi were not grouped together in the phylogenetic tree. Our evolutionary analysis revealed evidence for positive selection on the subtilisin-like serine protease genes of the nematode-trapping fungi. Conclusions Our study provides new insights into the evolution of subtilisin-like serine protease genes in Pezizomycotina. Pezizomycotina subtilisins most likely evolved from endocellular to extracellular proteases. The entomopathogenic and nematode-parasitic fungi likely share similar properties in parasitism. In addition, our data provided better understanding about the duplications and subsequent functional divergence of subtilisin-like serine protease genes in Pezizomycotina. The evidence of positive selection detected in the subtilisin-like serine protease genes of nematode-trapping fungi in the present study suggests that the subtilisin-like serine proteases may have played important roles during the evolution of pathogenicity of nematode-trapping fungi against nematodes. PMID:20211028

2010-01-01

230

Development of a high-throughput method for the determination of pharmacological levels of plasma D-serine.  

PubMed

D-Serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, D-Serine must be administered at high doses to observe clinical effects. This is due in large part to D-Serine undergoing oxidation by D-Serine acid oxidase (DAAO) before it reaches the brain. Consequently, coadministration of D-Serine with a DAAO inhibitor has been suggested as a way to lower the dose of D-serine required to treat schizophrenia. During the characterization of DAAO inhibitors as potential drugs, inhibitors are evaluated in rodents for their ability to increase plasma D-Serine levels after oral coadministration. Current high-performance liquid chromatography (HPLC)-based methodologies to measure D-Serine in plasma are time-consuming and are not amenable to concomitant analysis of multiple samples. We report the characterization of a 96-well format assay to monitor D-Serine in plasma that greatly expedites analysis time. The assay involves the use of strong cation exchange solid phase extraction (SPE) to isolate D-Serine from plasma followed by quantitation of D-Serine using the DAAO-catalyzed reaction. Plasma D-Serine determination using this assay could also be used as pharmacodynamic marker and as biomarker. PMID:21889486

Alt, Jesse; Rojas, Camilo; Wozniak, Krystyna; Wu, Ying; Ferraris, Dana; Tsukamoto, Takashi; Slusher, Barbara

2011-12-15

231

Local order in layered NiPS3 and Ni0.7Mg0.3PS3  

NASA Astrophysics Data System (ADS)

The family of two-dimensional magnetic materials MIIPS3 where M = Mn, Fe, Ni, Mg, Zn, etc shows a wide range of fascinating magnetic behaviour. It also shows potentially useful chemical properties including intercalation of nonlinear optical molecules and lithium ions. These properties are due to a crystal structure in which the ab planes are well-ordered in the plane but poorly correlated along c. Here, the short-range ordering is modelled in NiPS3 and Ni1 - xMgxPS3 (x = 0.3). X-ray diffuse scattering from NiPS3 shows pronounced streaking along c*, indicative of stacking faulting in these layered compounds. Electron diffraction from Ni1 - xMgxPS3 (x = 0.3) shows substantial diffuse scattering due to short-range order within the ab plane, and this can be modelled by allowing the metal species to cluster. The possibility of clustering has implications for interpretation of the magnetic behaviour of the family, including the glassiness observed in Fe1 - xMnxPS3.

Goossens, D. J.; James, D.; Dong, J.; Whitfield, R. E.; Norén, L.; Withers, R. L.

2011-02-01

232

Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase.  

PubMed

For elucidation of the regulation mechanisms of intrinsic amounts of D-serine (D-Ser) which modulates the neuro-transmission of N-methyl-D-aspartate receptors in the brain, mutant animals lacking serine racemase (SRR) and D-amino acid oxidase (DAO) were established, and the amounts of D-Ser in the tissues and physiological fluids were determined. D-Ser amounts in the frontal brain areas were drastically decreased followed by reduced SRR activity. On the other hand, a moderate but significant decrease in D-Ser amounts was observed in the cerebellum and spinal cord of SRR knock-out (SRR(-/-)) mice compared with those of control mice, although the amounts of D-Ser in these tissues were low. The amounts of D-Ser in the brain and serum were not altered with aging. To clarify the uptake of exogenous D-Ser into the brain tissues, we have determined the D-Ser of SRR(-/-) mice after oral administration of D-Ser for the first time, and a drastic increase in D-Ser amounts in all the tested tissues was observed. Because both DAO and SRR are present in some brain areas, we have established the double mutant mice lacking SRR and DAO for the first time, and the contribution of both enzymes to the intrinsic D-Ser amounts was investigated. In the frontal brain, most of the intrinsic D-Ser was biosynthesized by SRR. On the other hand, half of the D-Ser present in the hindbrain was derived from the biosynthesis by SRR. These results indicate that the regulation of intrinsic D-Ser amounts is different depending on the tissues and provide useful information for the development of treatments for neuronal diseases. PMID:22990841

Miyoshi, Yurika; Konno, Ryuichi; Sasabe, Jumpei; Ueno, Kyoko; Tojo, Yosuke; Mita, Masashi; Aiso, Sadakazu; Hamase, Kenji

2012-11-01

233

Effects of Serine Protease Inhibitors on Growth and Development and Digestive Serine Proteinases of the Sunn Pest, Eurygaster integriceps  

PubMed Central

In the current study the effects of serine proteinase inhibitors (TLCK, TPCK, SBTI, and a combination of SBTI and TPCK) with concentrations of 1% and 4% of dietary protein in artificial diets were tested against growth of the Sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), development, and its gut serine proteinase targets. Analysis of variance indicated that protease inhibitors affected nymphal development time, adult weight, and survival. Mean development time of third instar nymphs in control, SBTI (1%), TLCK (1%), and TPCK was 7.18, 9.74, 9.97, and 8.52 days, respectively. The highest mortality (100 % mortality) was observed when a combination of TPCK and SBTI, both at 4% of dietary protein, was used followed by TPCK (4%) that produced 95% mortality. There were significant differences in proteinase activity between treatments and controls when BApNA and SAAPFpNA were used as substrates for trypsin and chymotrypsin, respectively. Reduction of trypsin activity in insects fed with low doses of SBTI (1%), TLCK (1%), and both doses of TPCK (1% and 4%) was 40, 26, 23, and 17%, respectively. Inhibition of chymotrypsin activity was seen in the insects fed on SBTI (1%), TLCK (1%), and TPCK (4%) where inhibition was 14, 9, and 36%, respectively. Maximum inhibition of chymotrypsin activity was observed in the insects fed on diets containing high doses of TPCK (4%). In gel assays, the greatest effects were observed when E. integriceps were fed on high doses of SBTI and TPCK. Therefore, TPCK followed by SBTI proved to be the most effective proteinase inhibitors of E. integriceps. PMID:21867440

Saadati, Fatemeh; Bandani, Ali R.

2011-01-01

234

Effects of serine protease inhibitors on growth and development and digestive serine proteinases of the Sunn pest, Eurygaster integriceps.  

PubMed

In the current study the effects of serine proteinase inhibitors (TLCK, TPCK, SBTI, and a combination of SBTI and TPCK) with concentrations of 1% and 4% of dietary protein in artificial diets were tested against growth of the Sunn pest, Eurygaster integriceps Puton (Hemiptera: Scutelleridae), development, and its gut serine proteinase targets. Analysis of variance indicated that protease inhibitors affected nymphal development time, adult weight, and survival. Mean development time of third instar nymphs in control, SBTI (1%), TLCK (1%), and TPCK was 7.18, 9.74, 9.97, and 8.52 days, respectively. The highest mortality (100 % mortality) was observed when a combination of TPCK and SBTI, both at 4% of dietary protein, was used followed by TPCK (4%) that produced 95% mortality. There were significant differences in proteinase activity between treatments and controls when BApNA and SAAPFpNA were used as substrates for trypsin and chymotrypsin, respectively. Reduction of trypsin activity in insects fed with low doses of SBTI (1%), TLCK (1%), and both doses of TPCK (1% and 4%) was 40, 26, 23, and 17%, respectively. Inhibition of chymotrypsin activity was seen in the insects fed on SBTI (1%), TLCK (1%), and TPCK (4%) where inhibition was 14, 9, and 36%, respectively. Maximum inhibition of chymotrypsin activity was observed in the insects fed on diets containing high doses of TPCK (4%). In gel assays, the greatest effects were observed when E. integriceps were fed on high doses of SBTI and TPCK. Therefore, TPCK followed by SBTI proved to be the most effective proteinase inhibitors of E. integriceps. PMID:21867440

Saadati, Fatemeh; Bandani, Ali R

2011-01-01

235

Breast Cancer-Associated pS2 Protein: Synthesis and Secretion by Normal Stomach Mucosa  

Microsoft Academic Search

The human pS2 gene is specifically expressed under estrogen transcriptional control in a subclass of estrogen receptor-containing human breast cancer cells. The pS2 gene encodes an 84-amino acid protein that is secreted after signal peptide cleavage. The distribution of pS2 protein in normal human tissues was studied with antibodies to pS2; pS2 was specifically expressed and secreted by mucosa cells

M. C. Rio; J. P. Bellocq; J. Y. Daniel; C. Tomasetto; R. Lathe; M. P. Chenard; A. Batzenschlager; P. Chambon

1988-01-01

236

My Rendition of Hunter's Strong Inductive Proof of The Deduction Theorem for PS Branden Fitelson  

E-print Network

[Axiom, by assumption of Case 1] [2] B (A B) [Axiom, by PS1] [3] A B [MP, 1, 2] Note: D is a proof-line derivation D showing PS A B: [1] B [Given as a member of the set ] [2] B (A B) [Axiom, by PS1 A A: [1] A ((A A) A) [Axiom, by PS1] [2] (A ((A A) A)) ((A (A A)) (A A)) [Axiom, by PS2] [3

Fitelson, Branden

237

iPS Cell Modeling of Cardiometabolic Diseases  

PubMed Central

Cardiometabolic diseases encompass simple monogenic enzyme deficiencies with well-established pathogenesis and clinical outcomes to complex polygenic diseases such as the cardiometabolic syndrome. The limited availability of relevant human cell types such as cardiomyocytes has hampered our ability to adequately model and study pathway or drugs relevant to these diseases in the heart. The recent discovery of induced pluripotent stem (iPS) cell technology now offers a powerful opportunity to establish translational platforms for cardiac disease modeling, drug discovery and pre-clinical testing. In this article, we discuss the excitement and challenges of modeling cardiometabolic diseases using iPS cell and their potential to revolutionize translational research. PMID:23070616

Nakamura, Kenta; Hirano, Ken-ichi; Wu, Sean M.

2012-01-01

238

[Induced pluripotent stem cells (iPS) in medical research].  

PubMed

Pluripotent stem cells are capable of differentiating into cells of any tissue. The fact that iPS cell lines can be produced from skin cells or blood cells and directed to differentiate into a desired direction makes it possible to investigate e.g. myocardial or nerve cells having a disease-associated genotype. This will enable the development of experimental models of disease mechanisms and also apply them to drug screening, which may allow the development of novel types of treatment. In the future it may become possible to replace injured cells of a patient with autologous iPS cell derived transplants. PMID:24822328

Weltner, Jere; Trokovic, Ras; Otonkoski, Timo

2014-01-01

239

Overdose of D-serine Induces Movement Disorder and Neuromuscular Changes of Zebrafish Larvae.  

PubMed

D-serine is a well-known activator of N-methyl-D-aspartate receptors; however, little is known about the teratogenic effects of D-serine overdose during early embryonic development. Here, we used zebrafish as a model to test toxicity and teratogenicity, since they have transparent eggs, making the organogenesis of zebrafish embryos easier to be observed. After D-serine injection (100-1000 ppm), the most evident defective phenotypes were bent trunk phenotypes, including malformed somite boundary, twisted body axis and shorter body length. As the injection dosages increased, the rates of embryos with bent trunk phenotypes decreased (0% for 0 ppm, n=573; 59.9~84.3% for 100-1000 ppm of D-serine, n=383-451). In addition, D-serine-injected embryos exhibited significantly reduced the frequencies of spontaneous in-chorion contraction (21.7 for 0 ppm vs. 18.3-0.9 for 100-1000 ppm D-serine, n=30) in comparison with mock-treated controls (0 ppm). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1, Zn5 and ?-bungarotoxin to detect morphological changes in muscle fibers, primary motor axons, secondary motor axon projections and neuromuscular junctions, respectively. Our data show that overdose of D-serine leads to misalignment of muscle fibers and motor neuron defects, especially secondary motor neuron axonal growth defects. PMID:24791063

Chen, Xing-Guang; Wang, Yun-Hsin; Wen, Chi-Chung; Chen, Yau-Hung

2014-04-01

240

Overdose of D-serine Induces Movement Disorder and Neuromuscular Changes of Zebrafish Larvae  

PubMed Central

D-serine is a well-known activator of N-methyl-D-aspartate receptors; however, little is known about the teratogenic effects of D-serine overdose during early embryonic development. Here, we used zebrafish as a model to test toxicity and teratogenicity, since they have transparent eggs, making the organogenesis of zebrafish embryos easier to be observed. After D-serine injection (100–1000 ppm), the most evident defective phenotypes were bent trunk phenotypes, including malformed somite boundary, twisted body axis and shorter body length. As the injection dosages increased, the rates of embryos with bent trunk phenotypes decreased (0% for 0 ppm, n=573; 59.9~84.3% for 100–1000 ppm of D-serine, n=383–451). In addition, D-serine-injected embryos exhibited significantly reduced the frequencies of spontaneous in-chorion contraction (21.7 for 0 ppm vs. 18.3–0.9 for 100–1000 ppm D-serine, n=30) in comparison with mock-treated controls (0 ppm). Subtle changes are easily observed by staining with specific monoclonal antibodies F59, Znp1, Zn5 and ?-bungarotoxin to detect morphological changes in muscle fibers, primary motor axons, secondary motor axon projections and neuromuscular junctions, respectively. Our data show that overdose of D-serine leads to misalignment of muscle fibers and motor neuron defects, especially secondary motor neuron axonal growth defects. PMID:24791063

Chen, Xing-Guang; Wang, Yun-Hsin; Wen, Chi-Chung; Chen, Yau-Hung

2014-01-01

241

Proteome-wide reactivity profiling identifies diverse carbamate chemotypes tuned for serine hydrolase inhibition  

PubMed Central

Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Inhibitors of serine hydrolases are used to treat many diseases, including obesity, diabetes, cognitive dementia, and bacterial and viral infections. Nonetheless, the majority of the 200+ serine hydrolases in mammals still lack selective inhibitors for their functional characterization. We and others have shown that activated carbamates, through covalent reaction with the conserved serine nucleophile of serine hydrolases, can serve as useful inhibitors for members of this enzyme family. The extent to which carbamates, however, cross-react with other protein classes remains mostly unexplored. Here, we address this problem by investigating the proteome-wide reactivity of a diverse set of activated carbamates in vitro and in vivo using a combination of competitive and click chemistry (CC)-activity-based protein profiling (ABPP). We identify multiple classes of carbamates, including O-aryl, O-hexafluoroisopropyl (HFIP), and O-N-hydroxysuccinimidyl (NHS) carbamates that react selectively with serine hydrolases across entire mouse tissue proteomes in vivo. We exploit the proteome-wide specificity of HFIP carbamates to create in situ imaging probes for the endocannabinoid hydrolases monoacylglycerol lipase (MAGL) and alpha-beta hydrolase-6 (ABHD6). These findings, taken together, designate the carbamate as a privileged reactive group for serine hydrolases that can accommodate diverse structural modifications to produce inhibitors that display exceptional potency and selectivity across the mammalian proteome. PMID:23701408

Chang, Jae Won; Cognetta, Armand B.; Niphakis, Micah J.; Cravatt, Benjamin F.

2013-01-01

242

Serine integrase chimeras with activity in E. coli and HeLa cells  

PubMed Central

ABSTRACT In recent years, application of serine integrases for genomic engineering has increased in popularity. The factor-independence and unidirectionality of these large serine recombinases makes them well suited for reactions such as site-directed vector integration and cassette exchange in a wide variety of organisms. In order to generate information that might be useful for altering the specificity of serine integrases and to improve their efficiency, we tested a hybridization strategy that has been successful with several small serine recombinases. We created chimeras derived from three characterized members of the serine integrase family, phiC31, phiBT1, and TG1 integrases, by joining their amino- and carboxy-terminal portions. We found that several phiBT1-phiC31 (BC) and phiC31-TG1 (CT) hybrid integrases are active in E. coli. BC chimeras function on native att-sites and on att-sites that are hybrids between those of the two donor enzymes, while CT chimeras only act on the latter att-sites. A BC hybrid, BC{?1}, was also active in human HeLa cells. Our work is the first to demonstrate chimeric serine integrase activity. This analysis sheds light on integrase structure and function, and establishes a potentially tractable means to probe the specificity of the thousands of putative large serine recombinases that have been revealed by bioinformatics studies. PMID:25217617

Farruggio, Alfonso P.; Calos, Michele P.

2014-01-01

243

D-serine modulates non-adrenergic non-cholinergic contraction of lower esophageal sphincter in rats.  

PubMed

Endogenous D-serine is known to modulate glutamatergic transmission via interaction with the glycine site of N-methyl-D-aspartate (NMDA) receptors. D-serine is synthesized by racemization of L-serine using an enzymatic reaction catalyzed by serine racemase. Although much attention has been focused on the role of D-serine within the central nervous system, the physiological role of D-serine in enteric nervous system has not been investigated. Lower esophageal sphincter (LES) function is known to be modulated by NMDA-dependent mechanisms. The present study was aimed to study the expression of enzymes involved in D-serine metabolism and the function of D-serine in lower esophageal sphincter in rats. Reverse transcription polymerase chain reaction (RT-PCR) and western blotting showed the expression of serine racemase in isolated rat LES. Electrical field stimulation was used to induce non-adrenergic non-cholinergic (NANC) contraction/relaxation of isolated rat LES in an organ bath using an isometric force transducer. The organ bath studies on isolated rat LES showed that incubation with D-serine (100 ?M) is associated with a significant increase in the NANC contraction of isolated LES. This effect of exogenous D-serine was inhibited by NMDA receptor antagonists (MK-801), suggesting that NMDA receptors are involved in the effects of D-serine on NANC contraction of LES. Incubation with D-serine did not show a significant effect on NANC relaxation within our experimental setting. The results of this study suggest that serine racemase is expressed in LES and D-serine modulates contraction of the lower esophageal sphincter in rats. PMID:23022330

Ghasemi-Kasman, Maryam; Dehpour, Ahmad R; Mani, Ali R

2012-12-01

244

Proteomic characterization of serine hydrolase activity and composition in normal urine  

PubMed Central

Background Serine hydrolases constitute a large enzyme family involved in a diversity of proteolytic and metabolic processes which are essential for many aspects of normal physiology. The roles of serine hydrolases in renal function are largely unknown and monitoring their activity may provide important insights into renal physiology. The goal of this study was to profile urinary serine hydrolases with activity-based protein profiling (ABPP) and to perform an in-depth compositional analysis. Methods Eighteen healthy individuals provided random, mid-stream urine samples. ABPP was performed by reacting urines (n =?18) with a rhodamine-tagged fluorophosphonate probe and visualizing on SDS-PAGE. Active serine hydrolases were isolated with affinity purification and identified on MS-MS. Enzyme activity was confirmed with substrate specific assays. A complementary 2D LC/MS-MS analysis was performed to evaluate the composition of serine hydrolases in urine. Results Enzyme activity was closely, but not exclusively, correlated with protein quantity. Affinity purification and MS/MS identified 13 active serine hydrolases. The epithelial sodium channel (ENaC) and calcium channel (TRPV5) regulators, tissue kallikrein and plasmin were identified in active forms, suggesting a potential role in regulating sodium and calcium reabsorption in a healthy human model. Complement C1r subcomponent-like protein, mannan binding lectin serine protease 2 and myeloblastin (proteinase 3) were also identified in active forms. The in-depth compositional analysis identified 62 serine hydrolases in urine independent of activity state. Conclusions This study identified luminal regulators of electrolyte homeostasis in an active state in the urine, which suggests tissue kallikrein and plasmin may be functionally relevant in healthy individuals. Additional serine hydrolases were identified in an active form that may contribute to regulating innate immunity of the urinary tract. Finally, the optimized ABPP technique in urine demonstrates its feasibility, reproducibility and potential applicability to profiling urinary enzyme activity in different renal physiological and pathophysiological conditions. PMID:24237849

2013-01-01

245

Acute D-serine treatment produces antidepressant-like effects in rodents.  

PubMed

Research suggests that dysfunctional glutamatergic signalling may contribute to depression, a debilitating mood disorder affecting millions of individuals worldwide. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts rapid antidepressant effects in approximately 70% of patients. Glutamate evokes the release of D-serine from astrocytes and neurons, which then acts as a co-agonist and binds at the glycine site on the NR1 subunit of NMDA receptors. Several studies have implicated glial deficits as one of the underlying facets of the neurobiology of depression. The present study tested the hypothesis that D-serine modulates behaviours related to depression. The behavioural effects of a single, acute D-serine administration were examined in several rodent tests of antidepressant-like effects, including the forced swim test (FST), the female urine sniffing test (FUST) following serotonin depletion, and the learned helplessness (LH) paradigm. D-serine significantly reduced immobility in the FST without affecting general motor function. Both D-serine and ketamine significantly rescued sexual reward-seeking deficits caused by serotonin depletion in the FUST. Finally, D-serine reversed LH behaviour, as measured by escape latency, number of escapes, and percentage of mice developing LH. Mice lacking NR1 expression in forebrain excitatory neurons exhibited a depression-like phenotype in the same behavioural tests, and did not respond to D-serine treatment. These findings suggest that D-serine produces antidepressant-like effects and support the notion of complex glutamatergic dysfunction in depression. It is unclear whether D-serine has a convergent influence on downstream synaptic plasticity cascades that may yield a similar therapeutic profile to NMDA antagonists like ketamine. PMID:21906419

Malkesman, Oz; Austin, Daniel R; Tragon, Tyson; Wang, Gang; Rompala, Gregory; Hamidi, Anahita B; Cui, Zhenzhong; Young, W Scott; Nakazawa, Kazu; Zarate, Carlos A; Manji, Husseini K; Chen, Guang

2012-09-01

246

Crystal Structure of Serine Racemase that Produces Neurotransmitter d-Serine for Stimulation of the NMDA Receptor  

NASA Astrophysics Data System (ADS)

d-Serine is an endogenous coagonist for the N-methyl-d-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5’-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of l-serine to yield d-serine and vice versa. We have determined the structures of three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe. Lys57 and Ser82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique lysino-d-alanyl residue at the active site, also binds the substrate serine in the active site, suggesting that the lysino-d-alanyl residue acts as a catalytic base in the same manner as Lys57 of the wild type enzyme.

Goto, Masaru

247

d-Serine-induced nephrotoxicity: a HPLC–TOF\\/MS-based metabonomics approach  

Microsoft Academic Search

HPLC–MS-based metabonomic analysis was used to investigate urinary metabolic perturbations associated with d-serine-induced nephrotoxicity. d-Serine causes selective necrosis of the proximal straight tubules in the rat kidney accompanied by aminoaciduria, proteinuria and glucosuria. Alderely Park (Wistar-derived) rats were dosed with either d-serine (250mg\\/kg ip) or vehicle (deionised water) and urine was collected at 0–12, 12–24, 24–36 and 36–48h post-dosing. Samples

R. E. Williams; H. Major; E. A. Lock; E. M. Lenz; I. D. Wilson

2005-01-01

248

Intramolecular Modulation of Serine Protease Inhibitor Activity in a Marine Cyanobacterium with Antifeedant Properties  

PubMed Central

Extracts of the Floridian marine cyanobacterium Lyngbya cf. confervoides were found to deter feeding by reef fish and sea urchins (Diadema antillarum). This antifeedant activity may be a reflection of the secondary metabolite content, known to be comprised of many serine protease inhibitors. Further chemical and NMR spectroscopic investigation led us to isolate and structurally characterize a new serine protease inhibitor 1 that is formally derived from an intramolecular condensation of largamide D (2). The cyclization resulted in diminished activity, but to different extents against two serine proteases tested. This finding suggests that cyanobacteria can endogenously modulate the activity of their protease inhibitors. PMID:20631871

Matthew, Susan; Ratnayake, Ranjala; Becerro, Mikel A.; Ritson-Williams, Raphael; Paul, Valerie J.; Luesch, Hendrik

2010-01-01

249

Quantum-chemical approach to serine formation in the interstellar medium: A possible reaction pathway  

NASA Astrophysics Data System (ADS)

Radical-radical and radical-neutral interaction schemes are very important for the formation of comparatively complex molecules in low-temperature chemistry. The formation of amino acids, such as serine, in the interstellar medium is quite difficult. We explored the possibility of serine formation in the interstellar medium through detected interstellar molecules such as CH, CO, and OH by radical-radical and radical-neutral interactions in the gaseous phase using rigorous quantum-chemical calculations. The reaction energies, the low potential barrier and the structures of all the geometries involved in the reaction path show that serine formation is possible in interstellar space via the reaction paths.

Shivani; Singh, Amresh; Gupta, Vineet; Misra, Alka; Tandon, Poonam

2014-03-01

250

Origin of d -serine present in urine of mutant mice lacking d -amino-acid oxidase activity  

Microsoft Academic Search

Summary  Urine of ddY\\/DAO mice lackingd-amino-acid oxidase contained 5.7 times more serine than that of normal ddY\\/DAO+ mice. Most of the serine wasd-isomer. The origin of thisd-serine was examined. Oral administration of 0.02% amoxicillin and 0.004% minocycline to the ddY\\/ DAO- mice for 7 days did not reduce the urinaryd-serine, indicating that thed-serine was not of intestinal bacterial origin. When the

S. Asakura; R. Konno

1997-01-01

251

PS145A Making Democracy Work: Lessons from India  

E-print Network

PS145A Making Democracy Work: Lessons from India Course Information Course Instructor Dr. Pradeep fragmentation. When India gained independence from British Rule in 1947, observers noted that the likelihood of the new country remaining democratic was limited. Yet, India proved such observers wrong and remained one

Jacobs, Lucia

252

Beam Loss Studies for the CERN PS Booster Using FLUKA  

E-print Network

In view of future upgrade plans, the beam loss monitor (BLM) coverage of the four PS Booster (PSB) rings was reviewed. FLUKA studies at Linac4 injection and PSB extraction energies were performed to simulate the loss patterns. The results of these studies, presented in this paper, have led to the proposal to double the number of beam loss monitors in the PSB.

Damjanovic, S; Mikulec, B; Sapinski, M

2013-01-01

253

Further Comments on the Nature of iPS Cells  

Microsoft Academic Search

A criticism that induced pluripotent stem (iPS) cells may well be pre-existing stem cells was first accepted by the corresponding author of the original Nature publication but that confession was totally changed to a strong defiance after being guided by the Nature for a new response. The three reviews given by Nature actually contained an apparent duplication or \\

Shi V. Liu

2007-01-01

254

Petroleum Technology (AS) Curriculum Guide Student Name: PS#  

E-print Network

Petroleum Technology (AS) ­ Curriculum Guide Student Name: PS# GENERAL EDUCATION REQUIREMENTS ENG Introduction to Petroleum Industry PET 0102 Environment and Safety PET 0103 Introduction to Petroleum Geology PET 0201 Petroleum & Natural Gas Chemistry PET 0203 Oil & Gas Gathering & Transportation PET 0204 Well

Jiang, Huiqiang

255

PS: A Policy Simulator Issam Aib and Raouf Boutaba  

E-print Network

1 PS: A Policy Simulator Issam Aib and Raouf Boutaba David R.Cheriton School of Computer Science, a Policy Simulator tool intended to serve in the validation and performance evaluation of policy of all major components required for a policy-based manage- ment solution. These include the ability

Boutaba, Raouf

256

3Ps, Task-Based Learning, and the Japanese Learner.  

ERIC Educational Resources Information Center

Summarizes the findings of a work in progress that attempted to investigate to what extent task-based learning was more effective than the 3Ps approach in the teaching of Japanese as a foreign language in Thailand. (Author/VWL)

Tanasarnsanee, Mika

2002-01-01

257

PC PE PS PI SPM GangChol  

E-print Network

PC PE PS PI SPM GangChol TM1 TM2GPI Acyl Raft 1 Raft 2 Lipid rafts are localized regions invaginations that are coated with the cholesterol-binding protein caveolin, are a subset of lipid rafts. The acyl groups of the phospholipids present in lipid rafts and caveolae are more highly saturated than

Pike, Linda J.

258

BioMaPS: A Roadmap for Success  

ERIC Educational Resources Information Center

The manuscript outlines the impact that our National Science Foundation Interdisciplinary Training for Undergraduates in Biological and Mathematical Sciences program, BioMaPS, has had on the students and faculty at Murray State University. This interdisciplinary program teams mathematics and biology undergraduate students with mathematics and…

McCarthy, Maeve L.; Fister, K. Renee

2010-01-01

259

PS10 Solar Power Tower Xi Jing, Fang  

E-print Network

area equivalent of 17 American Football Tower Solar receiver 4 vertical panels 18ft*39ft Steam turbinePS10 Solar Power Tower Xi Jing, Fang #12;Overview Magnitudes , Cost & TechnologiesMagnitudes , Cost Government . #12;Further ExplanationFurther Explanation Plataforma Solar de Sanlúcar la Mayor,PSSM Megawatts

Prevedouros, Panos D.

260

DEVELOPMENT OF A HIGH THROUGHPUT METHOD FOR THE DETERMINATION OF PHARMACOLOGICAL LEVELS OF PLASMA D-SERINE  

PubMed Central

D-serine administration has been shown to be effective for the treatment of schizophrenia symptoms. However, D-serine has to be administered at high doses in order to observe clinical effects. This is in large part due to D-serine undergoing oxidation by D-amino acid oxidase (DAAO) before it reaches the brain. Consequently, co-administration of D-serine with a DAAO inhibitor has been suggested as a way to lower the dose of D-serine required to treat schizophrenia. During the characterization of DAAO inhibitors as potential drugs, inhibitors are evaluated in rodents for their ability to increase plasma D-serine levels after oral co-administration. Current HPLC-based methodologies to measure D-serine in plasma are time consuming and are not amenable to concomitant analysis of multiple samples. We report the characterization of a 96-well-format assay to monitor D-serine in plasma that greatly expedites analysis time. The assay involves the use of strong cation exchange solid phase extraction (SPE) to isolate D-serine from plasma followed by quantitation of D-serine using the DAAO catalyzed reaction. Plasma D-serine determination using this assay could also be used as pharmacodynamic marker and as biomarker. PMID:21889486

Alt, Jesse; Rojas, Camilo; Wozniak, Krystyna; Wu, Ying; Ferraris, Dana; Tsukamoto, Takashi; Slusher, Barbara

2011-01-01

261

Improvement in Regional CBF by L-Serine Contributes to Its Neuroprotective Effect in Rats after Focal Cerebral Ischemia  

PubMed Central

To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF). Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1) reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2) improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3) increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca2+-activated K+ channels on the cerebral blood vessel endothelium. PMID:23825613

Jiang, Zheng-Lin; Wang, Guo-Hua; Sun, Li; Jiang, Rui; Zhao, Guang-Wei; Han, Le-Yang

2013-01-01

262

Stromal serine protein kinase activity in spinach chloroplasts  

SciTech Connect

At least twelve /sup 32/P-labeled stromal proteins were detected by electrophoresis under denaturing conditions when intact chloroplasts were incubated with /sup 32/Pi, in the light but only three were detected in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) or in the dark. Incubation of isolated stroma with (gamma-/sup 32/P)ATP resulted in the preferential phosphorylation of one of them, a 70-kDa polypeptide, in serine residues. Thylakoid membranes in the dark promoted the phosphorylation of two additional stromal polypeptides of 55 and 40 kDa. Illumination during the phosphorylation of stroma in the presence of thylakoids stimulated severalfold the labeling of the 40-kDa polypeptide but not when DCMU was added. The protein kinase activity present in isolated stroma phosphorylated exogenous substrates like histone III, phosvitin, histone II, and casein with specific activities of 3, 1.8, 0.7, and 0.2 pmol X mg-1 X min-1. Histone III polypeptides were phosphorylated differently by stroma and by thylakoids in the dark. Moreover, histone III phosphorylated by thylakoids in the dark yielded a pattern of phosphopeptides after V8 protease treatment that was different from the pattern obtained when histone III was phosphorylated by stroma.

Cortez, N.; Lucero, H.A.; Vallejos, R.H.

1987-05-01

263

Homologous inhibitors from potato tubers of serine endopeptidases and metallocarboxypeptidases.  

PubMed Central

A potent polypeptide inhibitor of chymotrypsin has been purified from Russett Burbank potatoes. The inhibitor has no effect on bovine carboxypeptidases A or B but exhibits homology with a carboxypeptidase inhibitor that is also present in potato tubers. The chymotrypsin inhibitor has a molecular weight of approximately 5400 as estimated by gel filtration, amino acid analysis, and titration with chymotrypsin. The polypeptide chain consists of 49 amino acid residues, of which six are half-cystine, forming three disulfide bonds. Its size is similar to that of the carboxypeptidase inhibitor, which contains 39 amino acid residues and also has three disulfide bridges. In immunological double diffusion assays, the chymotrypsin inhibitor and the carboxypeptidase inhibitor do not crossreact; however, automatic Edman degradation of reduced and alkylated derivatives of the chymotrypsin inhibitor, yielding a partial sequence of 18 amino acid residues at the NH2-terminus, reveals a similarity in sequence to that of the carboxypeptidase inhibitor. Thus, inhibitors directed toward two distinct classes of proteases, the serine endopeptidases and the metallocarboxypeptidases, appear to have evolved from a common ancestor. Images PMID:1064864

Hass, C M; Venkatakrishnan, R; Ryan, C A

1976-01-01

264

The Nature of D-Serine-Induced Nephrotoxicity  

PubMed Central

Renal structural changes were studied sequentially between 1 hour and 6 days in rats treated with D-serine. Extensive necrosis of proximal straight tubules was rapid in onset and was followed by complete tubular regeneration 6 days post-treatment. The apparent progression of cellular changes was initial shrinkage, followed either by swelling and loss of apical cytoplasm or immediate lysis of cytoplasmic and nuclear contents. Tubular damage left only the basement membrane as a barrier between interstitial and luminal fluids. In similarly treated rats, proteinuria and glucosuria developed at the onset of tubular necrosis and disappeared when the tubules were completely relined by epithelium suggesting that they are due to diffusion of protein and glucose from interstitium into tubular fluid across the denuded basement membranes and that epithelial cells, under normal conditions, act as a barrier to diffusion of certain substances between the interstitium and tubular fluid. ImagesFig 10Fig 11Fig 1Fig 2Fig 3Fig 12Fig 13Fig 14Fig 15Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9 PMID:4447130

Ganote, Charles E.; Peterson, Darryl R.; Carone, Frank A.

1974-01-01

265

Conformation effects on the molecular orbitals of serine  

NASA Astrophysics Data System (ADS)

This paper calculates the five most stable conformers of serine with Hartree—Fock theory, density functional theory (B3LYP), Møller—Plesset perturbation theory (MP4(SDQ)) and electron propagation theory with the 6-311++G(2d,2p) basis set. The calculated vertical ionization energies for the valence molecular orbitals of each conformer are in agreement with the experimental data, indicating that a range of molecular conformations would coexist in an equilibrium sample. Information of the five outer valence molecular orbitals for each conformer is explored in coordinate and momentum spaces using dual space analysis to investigate the conformational processes, which are generated from the global minimum conformer Ser1 by rotation of C2-C3 (Ser4), C1-C2 (Ser5) and C1-O2 (Ser2 and Ser3). Orbitals 28a, 27a and 26a are identified as the fingerprint orbitals for all the conformational processes. Project supported by the Doctoral Research Fund of Henan Normal University, China (Grant No. 525449).

Wang, Ke-Dong; Ma, Peng-Fei; Shan, Xu

2011-03-01

266

Action of Bauhinia bauhinioides synthetic peptides on serine proteinases.  

PubMed

The kallikrein inhibitor found in Bauhinia bauhinioides seeds (BbKI) differs from classical Kunitz plant inhibitors in the lack of disulfide bridges in its structure [Biochim. Biophys. Acta 1477 (2000) 64-74]. In this study, we examined whether structural properties may be involved in inhibitory specificity and, if so, whether those properties might be useful tools in designing compounds that interfere with enzyme activity. Peptides structurally related to the BbKI (RPGLPVRFESPLRINIIKE-NH(2)) reactive site were synthesized by solid-phase method and assayed for serine proteinase activity. The peptides RPGLPVRFESPLRINIIKE-NH(2), RPGLPVRFESPL-NH(2), and GLPVRFES-NH(2) were efficient tissue kallikrein inhibitors, with I(50) values of 0.54 microM, 0.87 microM, and 0.5mM, respectively. The lasting inhibitory effect was observed in incubation periods of up to 120 min. None of the studied peptides interfere with the activity of thrombin, factor Xa or trypsin, although the native protein BbKI is a potent trypsin inhibitor. PMID:14575720

Cagliari, Cristina I; De Caroli, Fernanda P; Nakahata, Adriana M; Araújo, Mariana S; Nakaie, Clovis R; Sampaio, Misako U; Sampaio, Claudio A M; Oliva, Maria Luiza V

2003-11-01

267

Bacterial serine proteases secreted by the autotransporter pathway: classification, specificity, and role in virulence.  

PubMed

Serine proteases exist in eukaryotic and prokaryotic organisms and have emerged during evolution as the most abundant and functionally diverse group. In Gram-negative bacteria, there is a growing family of high molecular weight serine proteases secreted to the external milieu by a fascinating and widely employed bacterial secretion mechanism, known as the autotransporter pathway. They were initially found in Neisseria, Shigella, and pathogenic Escherichia coli, but have now also been identified in Citrobacter rodentium, Salmonella, and Edwardsiella species. Here, we focus on proteins belonging to the serine protease autotransporter of Enterobacteriaceae (SPATEs) family. Recent findings regarding the predilection of serine proteases to host intracellular or extracellular protein-substrates involved in numerous biological functions, such as those implicated in cytoskeleton stability, autophagy or innate and adaptive immunity, have helped provide a better understanding of SPATEs' contributions in pathogenesis. Here, we discuss their classification, substrate specificity, and potential roles in pathogenesis. PMID:23689588

Ruiz-Perez, Fernando; Nataro, James P

2014-03-01

268

Sodium benzoate attenuates d-serine induced nephrotoxicity in the rat  

Microsoft Academic Search

d-Serine causes selective necrosis to the straight portion of the rat renal proximal tubules. The onset is rapid, occurring within 3–4h and accompanied by proteinuria, glucosuria and aminoaciduria. The metabolism of d-serine by d-amino acid oxidase (d-AAO) may be involved in the mechanism of toxicity. d-AAO is localized within the peroxisomes of renal tubular epithelial cells, which is also the

R. E. Williams; E. A. Lock

2005-01-01

269

Development and application of serine/threonine ligation for synthetic protein chemistry.  

PubMed

Chemical synthesis of proteins, especially those with post-translational modifications, has offered new opportunities to study the protein structure-function relationship. In the past four years, we have developed the serine/threonine ligation (STL), which involves the chemoselective reaction between peptide salicylaldehyde esters and peptides with N-terminal serine or threonine. The method has been successfully applied to the synthesis of both linear and cyclic peptides/proteins. PMID:24788202

Liu, Han; Li, Xuechen

2014-06-21

270

D-serine added to antipsychotics for the treatment of schizophrenia  

Microsoft Academic Search

Background: Hypofunction of N-methyl-D-aspartate (NMDA) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia. D-serine is a full agonist of the glycine site of NMDA receptor, an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor. Supplementation of D-serine may improve the symptoms of schizophrenia.Methods: Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind,

Guochuan Tsai; Pinchen Yang; Li-Chen Chung; Nicholas Lange; Joseph T. Coyle

1998-01-01

271

Free d-serine concentration in normal and Alzheimer human brain  

Microsoft Academic Search

We have analyzed both free l- and d-serine in frontal cortex of normal and Alzheimer human brain by high-performance liquid chromatography (HPLC). There was no significant difference between the two brains. In normal brain, l- and d-serine concentrations were 666 ± 222 and 66 ± 41 nmol\\/g of wet tissue, respectively, and the ratio of d-isomer to l-isomer (dl) was

Yoko Nagata; Mauro Borghi; George H. Fisher; Antimo D'Aniello

1995-01-01

272

Free d-aspartate and d-serine in the mammalian brain and periphery  

Microsoft Academic Search

It has long been assumed that l-forms of amino acids exclusively constitute free amino acid pools in mammals. However, a variety of studies in the last decade has demonstrated that free d-aspartate and d-serine occur in mammals and may have important physiological function in mammals. Free d-serine is confined predominantly to the forebrain structure, and the distribution and development of

Atsushi Hashimoto; Tetsuo Oka

1997-01-01

273

Glia-Derived d-Serine Controls NMDA Receptor Activity and Synaptic Memory  

Microsoft Academic Search

SUMMARY The NMDA receptor is a key player in excitatory transmission and synaptic plasticity in the cen- tral nervous system. Its activation requires the binding of both glutamate and a coagonist like D-serine to its glycine site. As D-serine is re- leased exclusively by astrocytes, we studied the physiological impact of the glial environ- ment on NMDA receptor-dependent activity and

Aude Panatier; Dionysia T. Theodosis; Jean-Pierre Mothet; Bastien Touquet; Loredano Pollegioni; Dominique A. Poulain; Stéphane H. R. Oliet

2006-01-01

274

Role for D-Serine within the Ventral Tegmental Area in the Development of Cocaine's Sensitization  

Microsoft Academic Search

Repeated exposure to cocaine results in motor sensitization that, in the ventral tegmental area (VTA), is associated to enhanced glutamate release, which in turn leads to enhanced calcium levels in dopaminergic neurons. Calcium influx activates calcium–calmodulin-dependent protein kinases such as CaMKII. D-Serine could participate on these effects, and the objective was to discern the role of VTA D-serine after a

Emilio Fernandez-Espejo; Susana Ramiro-Fuentes; Manuel Portavella; Rocio Moreno-Paublete

2008-01-01

275

Glycine inhibitory dysfunction turns touch into pain through astrocyte-derived D-serine.  

PubMed

Glycine inhibitory dysfunction provides a useful experimental model for studying the mechanism of dynamic mechanical allodynia, a widespread and intractable symptom of neuropathic pain. In this model, allodynia expression relies on N-methyl-d-aspartate receptors (NMDARs), and it has been shown that astrocytes can regulate their activation through the release of the NMDAR coagonist d-serine. Recent studies also suggest that astrocytes potentially contribute to neuropathic pain. However, the involvement of astrocytes in dynamic mechanical allodynia remains unknown. Here, we show that after blockade of glycine inhibition, orofacial tactile stimuli activated medullary dorsal horn (MDH) astrocytes, but not microglia. Accordingly, the glia inhibitor fluorocitrate, but not the microglia inhibitor minocycline, prevented allodynia. Fluorocitrate also impeded activation of astrocytes and blocked activation of the superficial MDH neural circuit underlying allodynia, as revealed by study of Fos expression. MDH astrocytes are thus required for allodynia. They may also produce d-serine because astrocytic processes were selectively immunolabeled for serine racemase, the d-serine synthesizing enzyme. Accordingly, selective degradation of d-serine with d-amino acid oxidase applied in vivo prevented allodynia and activation of the underlying neural circuit. Conversely, allodynia blockade by fluorocitrate was reversed by exogenous d-serine. These results suggest the following scenario: removal of glycine inhibition makes tactile stimuli able to activate astrocytes; activated astrocytes may provide d-serine to enable NMDAR activation and thus allodynia. Such a contribution of astrocytes to pathological pain fuels the emerging concept that astrocytes are critical players in pain signaling. Glycine disinhibition makes tactile stimuli able to activate astrocytes, which may provide d-serine to enable NMDA receptor activation and thus allodynia. PMID:21392888

Miraucourt, Loïs S; Peirs, Cédric; Dallel, Radhouane; Voisin, Daniel L

2011-06-01

276

Copper(II)-mediated O-arylation of protected serines and threonines.  

PubMed

An effective protocol toward the O-arylation of ?-hydroxy-?-amino acid substrates serine and threonine has been developed via Chan-Lam cross-coupling. This Cu(II)-catalyzed transformation involves benign open-flask conditions that are well-tolerated with a variety of protected (Boc-, Cbz-, Tr-, and Fmoc-) serine and threonine derivatives and various potassium organotrifluoroborates and boronic acids. PMID:25208062

El Khatib, Mirna; Molander, Gary A

2014-09-19

277

High level of endogenous l-serine initiates senescence in Spirodela polyrrhiza  

Microsoft Academic Search

Half-fronds of Spirodela polyrrhiza accumulated high level of endogenous serine when they had been cultivated under long-day conditions and on a cytokinin-free medium for 4 days, after which the irreversible senescence process was triggered. When 1?M 6-benzyl adenine (6-BA) was included in the medium, the accumulation of endogenous serine was significantly inhibited, and at the same time the biological activity

Ye-Rong Zhu; Han-Lin Tao; Xian-Yu Lv; Shu-Fang Wang; Ning-Ning Wang; Yong Wang

2004-01-01

278

A CUB-serine protease in the olfactory organ of the spiny lobsterPanulirus argus  

Microsoft Academic Search

csp, a gene encoding a protein with high sequence identity to trypsinlike serine protease and CUB domains, was identified from a cDNA library from the olfactory organ (antennular lateral flagellum) of the spiny lobster Panulirus argus. The full-length cDNA sequence of csp is 1801 bp, encoding a protein of 50.25 kD, with three domains: signal peptide, trypsinlike serine protease, and

Min Z. Levine; Paul J. H. Harrison; W. William Walthall; Phang C. Tai; Charles D. Derby

2001-01-01

279

Glycine consumption and mitochondrial serine hydroxymethyltransferase in cancer cells: the heme connection.  

PubMed

It was recently discovered that glycine consumption is strongly related to the rate of proliferation across cancer cells. This is very intriguing and raises the question of what is the actual role of this amino acid in cancer metabolism. Cancer cells are greedy for glycine. In particular, the mitochondrial production of glycine seems to be utterly important. Overexpression of mitochondrial serine hydroxymethyltransferase, the enzyme converting l-serine to glycine, assures an adequate supply of glycine to rapidly proliferating cancer cells. In fact, silencing of mitochondrial serine hydroxymethyltransferase was shown to halt cancer cell proliferation. Direct incorporation of glycine carbon atoms into the purine ring has been proposed to be one main reason for the importance of glycine in cancer cell metabolism. We believe that, as far as the importance of glycine in cancer is concerned, a central role of this amino acid, namely its participation to heme biosynthesis, has been neglected. In mitochondria, glycine condenses with succinyl-CoA to form 5-aminolevulinate, the universal precursor of the different forms of heme contained in cytochromes and oxidative phosphorylation complexes. Our hypothesis is that mitochondrial serine hydroxymethyltransferase is fundamental to sustain cancer metabolism since production of glycine fuels heme biosynthesis and therefore oxidative phosphorylation. Respiration of cancer cells may then ultimately rely on endogenous glycine synthesis by mitochondrial serine hydroxymethyltransferase. The link between mitochondrial serine hydroxymethyltransferase activity and heme biosynthesis represents an important and still unexplored aspect of the whole picture of cancer cell metabolism. Our hypothesis might be tested using a combination of metabolic tracing and gene silencing on different cancer cell lines. The experiments should be devised so as to assess the importance of mitochondrial serine hydroxymethyltransferase and the glycine deriving from its reaction as a precursor of heme. If the observed increase of glycine consumption in rapidly proliferating cancer cells has its basis in the need for heme biosynthesis, then mitochondrial serine hydroxymethyltransferase should be considered as a key target for the development of new chemotherapeutic agents. PMID:23474074

di Salvo, Martino L; Contestabile, Roberto; Paiardini, Alessandro; Maras, Bruno

2013-05-01

280

Purification and characterisation of a serine peptidase from the marine psychrophile strain PA43  

Microsoft Academic Search

An extracellular serine peptidase, purified from the culture supernatant of the sub-Arctic psychrophilic bacterium strain PA-43, is monomeric, with a relative molecular mass of 76?000, and an unusually low pI of 3.8. The peptidase is active towards N-succinyl AAPF p-nitroanilide and N-succinyl AAPL p-nitroanilide, indicating a chymotrypsin-like substrate specificity. It is inhibited by the serine peptidase inactivator phenylmethylsulfonyl fluoride, but

Jane A Irwin; Gudni A Alfredsson; Anthony J Lanzetti; Haflidi M Gudmundsson; Paul C Engel

2001-01-01

281

In-cell Selectivity Profiling of Serine Protease Inhibitors by Activity-based Proteomics  

Microsoft Academic Search

Activity-based proteomics is a methodology that is used to quantify the catalytically active subfraction of enzymes present in complex mixtures such as lysates or living cells. To apply this approach for in-cell selectivity profiling of inhibitors of serine proteases, we designed a novel activity-based probe (ABP). This ABP consists of (i) a fluorophosphonate-reactive group, directing the probe toward serine hydrolases

Ludovic C. J. Gillet; Kenji Namoto; Alexandra Ruchti; Sjouke Hoving; Danielle Boesch; Bruno Inverardi; Dieter Mueller; Michele Coulot; Patrick Schindler; Patrick Schweigler; Anna Bernardi; Shirley Gil-Parrado

2008-01-01

282

Interaction between Two Putative Glycosyltransferases Is Required for Glycosylation of a Serine-Rich Streptococcal Adhesin  

Microsoft Academic Search

Fap1, a serine-rich glycoprotein, is essential for fimbrial biogenesis and biofilm formation of Streptococcus parasanguinis (formerly S. parasanguis). Fap1-like proteins are conserved in many streptococci and staphylo- cocci and have been implicated in bacterial virulence. Fap1 contains two serine-rich repeat regions that are modified by O-linked glycosylation. A seven-gene cluster has been identified, and this cluster is implicated in Fap1

Su Bu; Yirong Li; Meixian Zhou; Parastoo Azadin; Meiqin Zeng; Paula Fives-Taylor; Hui Wu

2008-01-01

283

L-Serine Potentiates the Mitogenic Effects of Growth Factors on Cultured Human Keratinocytes  

Microsoft Academic Search

L-Serine increased the growth of passaged human foreskin keratinocytes in terms of DNA and protein per dish of cells, and potentiated the mitogenic effects of serum and epidermal growth factor and also insulin, keratinocyte growth factor, and a bovine pituitary extract. The effects of serine were apparent with as little as 0.05 mM. The stimulatory effects of these various growth

David I. Wilkinson

1987-01-01

284

Spk1, a new kinase from Saccharomyces cerevisiae, phosphorylates proteins on serine, threonine, and tyrosine.  

PubMed Central

A Saccharomyces cerevisiae lambda gt11 library was screened with antiphosphotyrosine antibodies in an attempt to identify a gene encoding a tyrosine kinase. A subclone derived from one positive phage was sequenced and found to contain an 821-amino-acid open reading frame that encodes a protein with homology to protein kinases. We tested the activity of the putative kinase by constructing a vector encoding a glutathione-S-transferase fusion protein containing most of the predicted polypeptide. The fusion protein phosphorylated endogenous substrates and enolase primarily on serine and threonine. The gene was designated SPK1 for serine-protein kinase. Expression of the Spk1 fusion protein in bacteria stimulated serine, threonine, and tyrosine phosphorylation of bacterial proteins. These results, combined with the antiphosphotyrosine immunoreactivity induced by the kinase, indicate that Spk1 is capable of phosphorylating tyrosine as well as phosphorylating serine and threonine. In in vitro assays, the fusion protein kinase phosphorylated the synthetic substrate poly(Glu/Tyr) on tyrosine, but the activity was weak compared with serine and threonine phosphorylation of other substrates. To determine if other serine/threonine kinases would phosphorylate poly(Glu/Tyr), we tested calcium/calmodulin-dependent protein kinase II and the catalytic subunit of cyclic AMP-dependent protein kinase. The two kinases had similar tyrosine-phosphorylating activities. These results establish that the functional difference between serine/threonine- and tyrosine-protein kinases is not absolute and suggest that there may be physiological circumstances in which tyrosine phosphorylation is mediated by serine/threonine kinases. Images PMID:1899289

Stern, D F; Zheng, P; Beidler, D R; Zerillo, C

1991-01-01

285

Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major  

PubMed Central

Ecotin is a potent inhibitor of family S1A serine peptidases, enzymes lacking in the protozoan parasite Leishmania major. Nevertheless, L. major has three ecotin-like genes, termed inhibitor of serine peptidase (ISP). ISP1 is expressed in vector-borne procyclic and metacyclic promastigotes, whereas ISP2 is also expressed in the mammalian amastigote stage. Recombinant ISP2 inhibited neutrophil elastase, trypsin and chymotrypsin with Kis between 7.7 and 83 nM. L. major ISP2–ISP3 double null mutants (?isp2/3) were created. These grew normally as promastigotes, but were internalized by macrophages more efficiently than wild-type parasites due to the upregulation of phagocytosis by a mechanism dependent on serine peptidase activity. ?isp2/3 promastigotes transformed to amastigotes, but failed to divide for 48 h. Intracellular multiplication of ?isp2/3 was similar to wild-type parasites when serine peptidase inhibitors were present, suggesting that defective intracellular growth results from the lack of serine peptidase inhibition during promastigote uptake. ?isp2/3 mutants were more infective than wild-type parasites to BALB/c mice at the early stages of infection, but became equivalent as the infection progressed. These data support the hypothesis that ISPs of L. major target host serine peptidases and influence the early stages of infection of the mammalian host. PMID:19016791

Eschenlauer, Sylvain C P; Faria, Marilia S; Morrison, Lesley S; Bland, Nicolas; Ribeiro-Gomes, Flavia L; DosReis, George A; Coombs, Graham H; Lima, Ana Paula C A; Mottram, Jeremy C

2009-01-01

286

Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging  

PubMed Central

An association between age-related memory impairments and changes in functional plasticity in the aging brain has been under intense study within the last decade. In this article, we show that an impaired activation of the strychnine-insensitive glycine site of N-methyl-d-aspartate receptors (NMDA-R) by its agonist d-serine contributes to deficits of synaptic plasticity in the hippocampus of memory-impaired aged rats. Supplementation with exogenous d-serine prevents the age-related deficits of isolated NMDA-R-dependent synaptic potentials as well as those of theta-burst-induced long-term potentiation and synaptic depotentiation. Endogenous levels of d-serine are reduced in the hippocampus with aging, that correlates with a weaker expression of serine racemase synthesizing the amino acid. On the contrary, the affinity of d-serine binding to NMDA-R is not affected by aging. These results point to a critical role for the d-serine-dependent pathway in the functional alterations of the brain underlying memory impairment and provide key information in the search for new therapeutic strategies for the treatment of memory deficits in the elderly. PMID:20552041

Potier, B.; Turpin, F. R.; Sinet, P.-M.; Rouaud, E.; Mothet, J.-P.; Videau, C.; Epelbaum, J.; Dutar, P.; Billard, J.-M.

2009-01-01

287

Impaired D-serine-mediated cotransmission mediates cognitive dysfunction in epilepsy.  

PubMed

The modulation of synaptic plasticity by NMDA receptor (NMDAR)-mediated processes is essential for many forms of learning and memory. Activation of NMDARs by glutamate requires the binding of a coagonist to a regulatory site of the receptor. In many forebrain regions, this coagonist is d-serine. Here, we show that experimental epilepsy in rats is associated with a reduction in the CNS levels of d-serine, which leads to a desaturation of the coagonist binding site of synaptic and extrasynaptic NMDARs. In addition, the subunit composition of synaptic NMDARs changes in chronic epilepsy. The desaturation of NMDARs causes a deficit in hippocampal long-term potentiation, which can be rescued with exogenously supplied d-serine. Importantly, exogenous d-serine improves spatial learning in epileptic animals. These results strongly suggest that d-serine deficiency is important in the amnestic symptoms of temporal lobe epilepsy. Our results point to a possible clinical utility of d-serine to alleviate these disease manifestations. PMID:23926260

Klatte, Katharina; Kirschstein, Timo; Otte, David; Pothmann, Leonie; Müller, Lorenz; Tokay, Tursonjan; Kober, Maria; Uebachs, Mischa; Zimmer, Andreas; Beck, Heinz

2013-08-01

288

Thermodynamic characteristics of protolytic equilibria of L-serine in aqueous solutions  

NASA Astrophysics Data System (ADS)

The heat effects of the reaction of aqueous solution of L-serine with aqueous solutions of HNO3 and KOH were determined by calorimetry at temperatures of 288.15, 298.15, and 308.15 K, and ionic strength values of 0.2, 0.5, and 1.0 (background electrolyte, KNO3). Standard thermodynamic characteristics (?r H o, ?r G o, ?r S o, ? C {/p o}) of the acid-base reactions in aqueous solutions of L-serine were calculated. The effect of the concentration of background electrolyte and temperature on the heats of dissociation of amino acid was considered. The combustion energy of L-serine by bomb calorimetry in the medium of oxygen was determined. The standard combustion and formation enthalpies of crystalline L-serine were calculated. The heats of dissolution of crystalline L-serine in water and solutions of potassium hydroxide at 298.15 K were measured by direct calorimetry. The standard enthalpies of formation of L-serine and products of its dissociation in aqueous solution were calculated.

Kochergina, L. A.; Volkov, A. V.; Khokhlova, E. A.; Krutova, O. N.

2011-05-01

289

Mechanistic, inhibitory and stereochemical studies on cytoplasmic and mitochondrial serine transhydorxymethylases.  

PubMed Central

By using cytoplasmic and mitochondrial serine transhydroxymethylase isoenzymes from rabbit liver, it was shown that both enzymes exhibited similar ratios of serine transhydroxymethylase/threonine aldolase activities. Both enzymes catalysed the removal of the pro-S hydrogen atom of glycine, which was greatly enhanced by the presence of tetrahydrofolate. The cytoplasmic as well as the mitochondrial enzyme catalysed the synthesis of serine from glycine and [3H2]formaldehyde in the absence of tetrahydrofolate. The results are consistent with our previous suggestion that a role of tetrahydrofolate in the serine transhydroxymethylase reaction is to transport formaldehyde in and out of the active site (Jordan & Akhtar, 1970). The isoenzymes, however, showed remarkable differences in their inactivation by inhibitors. The serine transhydroxymethylase as well as the threonine aldolase activities of the cytoplasmic enzyme were inactivated in a similar fashion by chloroacetaldehyde, iodoacetamide, bromopyruvate and glycidaldehyde (2,3-epoxypropionaldehyde). These inhibitors had no effect on the two activities of the mitochondrial enzyme. The rate of inactivation of the cytoplasmic enzyme by glycidaldehyde was enhanced by the presence of glycine but decreased by the presence of serine. The implications of these results to the mechanism of catalysis and the nature of the active site of the enzymes are discussed. PMID:1156355

Akhtar, M; El-Obeid, H A; Jordan, P M

1975-01-01

290

A novel serine protease with caspase- and legumain-like activities from edible basidiomycete Flammulina velutipes.  

PubMed

A serine protease with caspase- and legumain-like activities from basidiocarps of the edible basidiomycete Flammulina velutipes was characterized. The protease was purified to near homogeneity by three steps of chromatography using acetyl-Tyr-Val-Ala-Asp-4-methylcoumaryl-7-amide (Ac-YVAD-MCA) as a substrate. The enzyme was termed FvSerP (F. velutipes serine protease). This enzyme activity was completely inhibited by the caspase-specific inhibitor, Ac-YVAD-CHO, as well as moderately inhibited by serine protease inhibitors. Based on the N-terminal sequence, the cDNA of FvSerP was identified. The deduced protease sequence was a peptide composed of 325 amino acids with a molecular mass of 34.5 kDa. The amino acid sequence of FvSerP showed similarity to neither caspases nor to the plant subtilisin-like serine protease with caspase-like activity called saspase. FvSerP shared identity to the functionally unknown genes from class of Agaricomycetes, with similarity to the peptidase S41 domain of a serine protease. It was thus concluded that this enzyme is likely a novel serine protease with caspase- and legumain-like activities belonging to the peptidase S41 family and distributed in the class Agaricomycetes. This enzyme possibly functions in autolysis, a type of programmed cell death that occurs in the later stages of development of basidiocarps with reference to their enzymatic functions. PMID:23537874

Iketani, Aya; Nakamura, Mayumi; Suzuki, Yuya; Awai, Koichiro; Shioi, Yuzo

2013-03-01

291

Detection of serine proteases in extracts of the domestic mite Blomia tropicalis.  

PubMed

Previous studies have shown that the domestic mites Dennatophagoides pteronyssinus and D. farinae contain allergens with serine protease activity. These proteolytic allergens include trypsin, chymotrypsin, elastase, kallikrein, and C3/C5 convertase. However, it is not known whether the domestic mite Blomia tropicalis shares with other mite species the serine protease activities. The enzymatic activity present in extracts obtained from food-free B. tropicalis was investigated using specific substrates and inhibitors. Based upon the concentration response and inhibition profiles, and the digestion of specific substrates our data demonstrate that extracts from B. tropicalis exhibit several serine-protease-like activities. The enzyme activities detected in the B. tropicalis extracts are trypsin, elastase, chymotrypsin, kallikrein, C3/C5 convertase, and mast cell protease. Our results also demonstrate that kallikrein and C3/C5 convertase-like activities were not significantly affected by the alpha1-antiprotease, a naturally occurring serine protease inhibitor which protects lung mucosa from the enzymatic action. These data strongly suggest that the Echymyopodidae mite B. tropicalis shares at least five serine proteases with members of other mite families, the Glycyphagidae and Pyroglyphidae. In addition, our data demonstrate the potential use of biochemical methods to detect serine proteases for evaluation of mite growth in viitro, or to detect environmental exposures to these enzymes. PMID:12475079

Montealegre, Federico; Quiñones, Carmen; Torres, Nanette; Goth, Kirsteen

2002-01-01

292

Mapping the APP\\/Presenilin (PS) Binding Domains: The Hydrophilic N-Terminus of PS2 Is Sufficient for Interaction with APP and Can Displace APP\\/PS1 Interaction  

Microsoft Academic Search

Mutations in presenilin 1 and presenilin 2 (PS1 and PS2, respectively) genes cause the large majority of familial forms of early-onset Alzheimer's disease. The physical interaction between presenilins and APP has been recently described using coimmunoprecipitation. With a similar technique, we confirmed this interaction and have mapped the interaction domains on both PS2 and APP. Using several carboxy-terminal truncated forms

Laurent Pradier; Nathalie Carpentier; Laurence Delalonde; Nicole Clavel; Marie-Dominique Bock; Luc Buée; Luc Mercken; Bruno Tocqué; Christian Czech

1999-01-01

293

Characterization of polystyrene-binding peptides (PS-tags) for site-specific immobilization of proteins.  

PubMed

In this study, we characterized polystyrene-binding peptides (PS-tags) that possess a specific binding affinity for hydrophilic polystyrene (phi-PS) plates. Both the FITC-labeled PS19-1 (RAFIASRRIKRP) and PS19-6 (RIIIRRIRR) peptides showed strong binding affinity for commercially available hydrophilic, but not hydrophobic, PS plates in the presence of the non-ionic surfactant Tween 20. The dissociation constants (K(d)) of the PS19-1 and PS19-6 peptides for the hydrophilic PS-A plate were 169 and 86 nM, respectively, and the K(d) of both peptides increased with the concentration of NaCl or urea. Based on adsorption yield and residual activity of glutathione S-transferase (GST) after fusion with the PS19-6 peptide or its variants, it was found that the basic amino acid in the PS-tags, i.e., Arg was essential for the strong binding affinity of PS-tags in both the peptide and peptide-fused protein forms The aliphatic amino acids in PS19-6 and PS19-6L, such as Ile or Leu, were also effective. Thus, a series of PS-tags that possess this unusual feature, especially the peptides PS19-6 (RIIIRRIRR) and PS19-6L (RLLLRRLRR), are potential candidate affinity peptide tags for site-specific immobilization of proteins onto hydrophilic PS plates, which show potential as solid supports for protein-based biochips. PMID:20471598

Kumada, Yoichi; Kuroki, Daisuke; Yasui, Hidefumi; Ohse, Takuhito; Kishimoto, Michimasa

2010-06-01

294

Integrin-linked kinase regulates phosphorylation of serine 473 of protein kinase B by an indirect mechanism.  

PubMed

The serine threonine kinase protein kinase B regulates cellular activities as diverse as glycogen metabolism and apoptosis. Full activation of protein kinase B requires 3-phosphoinositides and dual phosphorylation on threonine-308 and serine-473. CaM-K kinase and 3-phosphoinositide dependent-kinase-1 phosphorylate threonine-308. Integrin-linked kinase reportedly phophorylates serine-473. Consistent with this, in a model COS cell system we show that expression of wild-type integrin-linked kinase promotes the wortmannin sensitive phosphorylation of serine-473 of protein kinase B and its downstream substrates, and inhibits C2-ceramide induced apoptosis. In contrast, integrin-linked kinase mutated in a lysine residue critical for function in protein kinases is inactive in these experiments, and furthermore, acts dominantly to block serine-473 phosphorylation induced by ErbB4. However, alignment of analogous sequences from different species demonstrates that integrin-linked kinase is not a typical protein kinase and identifies a conserved serine residue which potentially regulates kinase activity in a phosphorylation dependent manner. Mutation of this serine to aspartate or glutamate, but not alanine, in combination with the inactivating lysine mutation restores integrin-linked kinase dependent phosphorylation of serine-473 of protein kinase B. These data strongly suggest that integrin-linked kinase does not possess serine-473 kinase activity but functions as an adaptor to recruit a serine-473 kinase or phosphatase. PMID:10637513

Lynch, D K; Ellis, C A; Edwards, P A; Hiles, I D

1999-12-23

295

Cellular responses to L-serine in Saccharomyces cerevisiae: roles of general amino acid control, compartmentalization, and aspartate synthesis.  

PubMed

In addition to its other roles, L-serine functions in one-carbon metabolism and is interconvertable with glycine via serine hydroxymethyltransferases. However, the transcriptional response by Saccharomyces cerevisiae to L-serine addition is markedly different from that to glycine, with L-serine acting as a nutrient source rather than one-carbon units. Following addition of excess L-serine, 743 genes showed significant expression changes. Induced functions included amino acid synthesis, some stress responses, and FeS metabolism, while ribosomal RNA processing, ribosome biogenesis and hexose transport were repressed. A co-regulated network of ten transcription factors could together control more than 90% of the induced and repressed genes forming a general response to changes induced by other amino acids or stresses and including the general amino acid control system usually activated in response to starvation for amino acids. A specific response to L-serine was induction of CHA1 encoding serine (threonine) dehydratase. L-serine addition resulted in a substantial transient increase in L-aspartate, which is, rather than L-glutamate, the major metabolite for short-term storage of ammonia derived from degradation of L-serine. L-aspartate synthesis was exclusively through mitochondrial metabolism of L-serine to pyruvate and ammonia, involving Cha1p, cytoplasmic pyruvate carboxylases Pyc1p and Pyc2p, and the cytoplasmic aspartate aminotransferase Aat2p. PMID:23837815

Lee, Johnny C-Y; Tsoi, Abraham; Kornfeld, Geoffrey D; Dawes, Ian W

2013-11-01

296

STAT3 serine 727 phosphorylation influences clinical outcome in glioblastoma  

PubMed Central

Besides STAT3 tyrosine 705 phosphorylation (pTyr705-STAT3), phosphorylation of STAT3 at serine 727 (pSer727-STAT3) is shown to contribute to tumorigenesis and be closely related with resistance to radiotherapy and chemotherapy in glioma, but there is currently no study regarding its relevance to prognosis in glioblastoma (GBM). Here, the expression of phosphorylated STAT3 was detected in tumor specimens from 88 patients with newly diagnosed GBM by immunohistochemistry, the Kaplan-Meier survival curve and COX proportional hazards regression model were applied to estimate its influences on progression-free survival (PFS) and overall survival (OS). Immunohistochemical assay showed elevated expression of pSer727-STAT3 in GBM compared with normal brain tissue. Univariate analysis indicated significant correlations of high percentage of pSer727-STAT3 positive tumor cells with shorter PFS (P = 0.006) and OS (P = 0.002). In multivariate analysis, high pSer727-STAT3 expression was demonstrated as an independent unfavorable prognostic indicator for PFS (HR 1.830, P = 0.022) and OS (HR 1.797, P = 0.040). And patients with high expression of both pTyr705-STAT3 and pSer727-STAT3 had a poorer prognosis compared with the remainder (P < 0.005). In conclusion, the high proportion of pSer727-STAT3 positive neoplastic cells in GBM is an independent unfavorable prognostic factor, and increased expression of both pTyr705-STAT3 and pSer727-STAT3 is predictive of poorer clinical outcome, thereby adding to the growing evidence that STAT3 inhibition may be a potential therapeutic strategy in glioblastoma. PMID:25031733

Lin, Guo-Shi; Chen, Yu-Peng; Lin, Zhi-Xiong; Wang, Xing-Fu; Zheng, Zong-Qing; Chen, Long

2014-01-01

297

Structural mechanisms of inactivation in scabies mite serine protease paralogues.  

PubMed

The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 A and 2.0 A resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical "canonical" fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite. PMID:19427318

Fischer, Katja; Langendorf, Christopher G; Irving, James A; Reynolds, Simone; Willis, Charlene; Beckham, Simone; Law, Ruby H P; Yang, Sundy; Bashtannyk-Puhalovich, Tanya A; McGowan, Sheena; Whisstock, James C; Pike, Robert N; Kemp, David J; Buckle, Ashley M

2009-07-24

298

Synchronization between Linac4 and the PS Booster  

E-print Network

Linac4 will be equipped with a low energy chopper and an energy modulation system to tailor the beam structure to the needs of the PS Booster. This allows optimizing the PS Booster machine performance and reducing beam losses around the injection. In particular, an active longitudinal painting scheme becomes possible for the most demanding high brightness and high intensity beams. This implies that an interface between the low level RF systems of the two machines has to be designed carefully to make sure that the beam generated by Linac4 suits the challenging timing requirements. This reports summarizes the requirements from the Booster side to make full use of the possibilities provided by the chopper and the energy ramping system. Functional descriptions of possible interfaces between the two machines involved are sketched and the arguments to choose one of the schemes as baseline for implementation are given.

Angoletta, M E; Butterworth, A; Carli, A; Chanel, M; Findlay, A; Kozsar, I; Mikulec, B; Molendijk, J; Paoluzzi, M; Pedersen, F; Sanchez, J

2010-01-01

299

The CERN PS/SL Controls Java Application Programming Interface  

SciTech Connect

The PS/SL Convergence Project was launched in March 1998. Its objective is to deliver a common control as infrastructure for the CERN accelerators by year 2001. In the framework of this convergence activity, a project was launched to develop a Java Application Programming Interface (API) between programs written in the Java language and the PS and SL accelerator equipment. This Java API was specified and developed in collaboration with TJNAF. It is based on the Java CDEV [1] package that has been extended in order to end up with a CERN/TJNAF common product. It implements a detailed model composed of devices organized in named classes that provide a property-based interface. It supports data subscription and introspection facilities. The device model is presented and the capabilities of the API are described with syntax examples. The software architecture is also described.

I. Deloose; J. Cuperus; P. Charrue; F. DiMaio; K. Kostro; M. Vanden Eynden (CERN); W. Watson (TJNAF)

1999-10-01

300

A stable Na + \\/H + antiporter of thermophilic bacterium PS3  

Microsoft Academic Search

As a first step in the isolation of a stable Na+\\/H+ antiporter, its reaction in sonicated membrane vesicles of thermophilic bacterium PS3 has been characterized. The sonicated vesicles showed quenching of quinacrine fluorescence in either NADH oxidation or ATP hydrolysis. The quenching was reversed by the addition of Na+, Li+, Mn2+, Cd2+, and Co2+, but not of choline+ or Ca2+,

Kimihiko Goto I; Hajime Hirata; Yasuo Kagawa

1980-01-01

301

PS3 CELL Development for Scientific Computation and Research  

NASA Astrophysics Data System (ADS)

The Cell processor is one of the most powerful processors on the market, and researchers in the earth sciences may find its parallel architecture to be very useful. A cell processor, with 7 cores, can easily be obtained for experimentation by purchasing a PlayStation 3 (PS3) and installing linux and the IBM SDK. Each core of the PS3 is capable of 25 GFLOPS giving a potential limit of 150 GFLOPS when using all 6 SPUs (synergistic processing units) by using vectorized algorithms. We have used the Cell's computational power to create a program which takes simulated tsunami datasets, parses them, and returns a colorized height field image using ray casting techniques. As expected, the time required to create an image is inversely proportional to the number of SPUs used. We believe that this trend will continue when multiple PS3s are chained using OpenMP functionality and are in the process of researching this. By using the Cell to visualize tsunami data, we have found that its greatest feature is its power. This fact entwines well with the needs of the scientific community where the limiting factor is time. Any algorithm, such as the heat equation, that can be subdivided into multiple parts can take advantage of the PS3 Cell's ability to split the computations across the 6 SPUs reducing required run time by one sixth. Further vectorization of the code can allow for 4 simultanious floating point operations by using the SIMD (single instruction multiple data) capabilities of the SPU increasing efficiency 24 times.

Christiansen, M.; Sevre, E.; Wang, S. M.; Yuen, D. A.; Liu, S.; Lyness, M. D.; Broten, M.

2007-12-01

302

Dipole Excitation of the Positronium Molecule Ps2  

Microsoft Academic Search

The energy interval between the ground and the P-wave excited states of the recently discovered positronium molecule Ps2 is evaluated, including the relativistic and the leading logarithmic radiative corrections, EP-ES=0.1815867(8)a.u.. The P state, decaying usually via annihilation, is found to decay into the ground state by an electric dipole transition 19% of the time. Anticipated observation of this transition will

Mariusz Puchalski; Andrzej Czarnecki

2008-01-01

303

Sodium benzoate attenuates D-serine induced nephrotoxicity in the rat.  

PubMed

D-Serine causes selective necrosis to the straight portion of the rat renal proximal tubules. The onset is rapid, occurring within 3-4 h and accompanied by proteinuria, glucosuria and aminoaciduria. The metabolism of D-serine by D-amino acid oxidase (D-AAO) may be involved in the mechanism of toxicity. D-AAO is localized within the peroxisomes of renal tubular epithelial cells, which is also the location of D-serine reabsorption. To address the role of D-AAO in D-serine-induced nephrotoxicity, we have examined the effect of sodium benzoate (SB) on the renal injury. SB has been shown to be a potent, competitive inhibitor of kidney D-AAO in vitro. Male Alderley Park rats were exposed to D-serine (500 mg/kg i.p.) 1 h after exposure to SB (125, 250, 500 or 750 mg/kg i.p.). Urine was collected for 0-6 h, then terminal plasma samples and kidneys were taken at 6.5 h. A second group of animals was given SB (500 mg/kg) followed by D-serine (500 mg/kg i.p.; 1 h later) and urine was collected after 0-6, 6-24 and 24-48 h. Terminal plasma samples and kidneys were taken at 48 h. 1H NMR spectroscopic analysis of urine, combined with principal component analysis, demonstrated that SB was able to prevent D-serine-induced perturbations to the urinary profile in a dose dependent manner. This was confirmed by measurement of plasma creatinine and urinary glucose and protein and histopathological examination of the kidneys. Assessment 48 h after D-serine administration revealed that nephrotoxicity was observed in animals pre-treated with SB (500 mg/kg) although the extent of injury was less pronounced than following D-serine alone. These results demonstrate that whilst prior exposure to SB prevents the initial onset of D-serine-induced nephrotoxicity, renal injury is still apparent at later time points. D-AAO activity in the kidney was decreased by 50% 1 h after dosing with SB suggesting that inhibition of this enzyme may be responsible for the observed protection. PMID:15590120

Williams, R E; Lock, E A

2005-02-01

304

Anomalous high ionic conductivity of nanoporous -Li3PS4  

SciTech Connect

Lithium-ion conducting solid electrolytes hold the promise for enabling high-energy battery chemistries and circumventing safety issues of conventional lithium batteries1-3. Achieving the combination of high ionic conductivity and broad electrochemical window in solid electrolytes is a grand challenge for the synthesis of battery materials. Herein we show an enhancement of room-temperature lithium-ion conductivity of 3 orders of magnitude by creating nanostructured Li3PS4. This material has a wide (5V) electrochemical window and superior chemical stability against lithium metal. The nanoporous structure of Li3PS4 reconciles two vital effects that enhance ionic conductivity: (1) The reduced dimension to nanometer-sized framework stabilizes the high conduction beta phase that occurs at elevated temperatures1,4; and (2) The high surface-to-bulk ratio of nanoporous -Li3PS4 promotes surface conduction5,6. Manipulating the ionic conductivity of solid electrolytes has far-reaching implications for materials design and synthesis in a broad range of applications such as batteries, fuel-cells, sensors, photovoltaic systems, and so forth3,7.

Liu, Zengcai [ORNL] [ORNL; Fu, Wujun [ORNL] [ORNL; Payzant, E Andrew [ORNL] [ORNL; Yu, Xiang [ORNL] [ORNL; Wu, Zili [ORNL] [ORNL; Dudney, Nancy J [ORNL] [ORNL; Kiggans, Jim [ORNL] [ORNL; Hong, Kunlun [ORNL] [ORNL; Rondinone, Adam Justin [ORNL; Liang, Chengdu [ORNL] [ORNL

2013-01-01

305

Anomalous high ionic conductivity of nanoporous ?-Li3PS4.  

PubMed

Lithium-ion-conducting solid electrolytes hold promise for enabling high-energy battery chemistries and circumventing safety issues of conventional lithium batteries. Achieving the combination of high ionic conductivity and a broad electrochemical window in solid electrolytes is a grand challenge for the synthesis of battery materials. Herein we show an enhancement of the room-temperature lithium-ion conductivity by 3 orders of magnitude through the creation of nanostructured Li(3)PS(4). This material has a wide electrochemical window (5 V) and superior chemical stability against lithium metal. The nanoporous structure of Li(3)PS(4) reconciles two vital effects that enhance the ionic conductivity: (1) the reduction of the dimensions to a nanometer-sized framework stabilizes the high-conduction ? phase that occurs at elevated temperatures, and (2) the high surface-to-bulk ratio of nanoporous ?-Li(3)PS(4) promotes surface conduction. Manipulating the ionic conductivity of solid electrolytes has far-reaching implications for materials design and synthesis in a broad range of applications, including batteries, fuel cells, sensors, photovoltaic systems, and so forth. PMID:23305294

Liu, Zengcai; Fu, Wujun; Payzant, E Andrew; Yu, Xiang; Wu, Zili; Dudney, Nancy J; Kiggans, Jim; Hong, Kunlun; Rondinone, Adam J; Liang, Chengdu

2013-01-23

306

Genomic imprinting is variably lost during reprogramming of mouse iPS cells  

PubMed Central

Derivation of induced pluripotent stem (iPS) cells is mainly an epigenetic reprogramming process. It is still quite controversial how genomic imprinting is reprogrammed in iPS cells. Thus, we derived multiple iPS clones from genetically identical mouse somatic cells. We found that parentally inherited imprint was variably lost among these iPS clones. Concurrent with the loss of DNA methylation imprint at the corresponding Snrpn and Peg3 imprinted regions, parental origin-specific expression of the Snrpn and Zim1 imprinted genes was also lost in these iPS clones. This loss of parental genomic imprinting in iPS cells was likely caused by the reprogramming process during iPS cell derivation because extended culture of iPS cells did not lead to significant increase in the loss of genomic imprinting. Intriguingly, one to several paternal chromosomes appeared to have acquired de novo methylation at the Snrpn and Zac1 imprinted regions in a high percentage of iPS clones. These results might have some implications for future therapeutic applications of iPS cells. Since DNA methylation imprint can be completely erased in some iPS clones at multiple imprinted regions, iPS cell reprogramming may also be employed to dissect the underlying mechanisms of erasure, reacquisition and maintenance of genomic imprinting in mammals. PMID:23832110

Shamis, Yulia; Wu, Tien-Yuan; Li, Xiajun

2013-01-01

307

PS integrins and laminins: key regulators of cell migration during Drosophila embryogenesis.  

PubMed

During embryonic development, there are numerous cases where organ or tissue formation depends upon the migration of primordial cells. In the Drosophila embryo, the visceral mesoderm (vm) acts as a substrate for the migration of several cell populations of epithelial origin, including the endoderm, the trachea and the salivary glands. These migratory processes require both integrins and laminins. The current model is that ?PS1?PS (PS1) and/or ?PS3?PS (PS3) integrins are required in migrating cells, whereas ?PS2?PS (PS2) integrin is required in the vm, where it performs an as yet unidentified function. Here, we show that PS1 integrins are also required for the migration over the vm of cells of mesodermal origin, the caudal visceral mesoderm (CVM). These results support a model in which PS1 might have evolved to acquire the migratory function of integrins, irrespective of the origin of the tissue. This integrin function is highly specific and its specificity resides mainly in the extracellular domain. In addition, we have identified the Laminin ?1,2 trimer, as the key extracellular matrix (ECM) component regulating CVM migration. Furthermore, we show that, as it is the case in vertebrates, integrins, and specifically PS2, contributes to CVM movement by participating in the correct assembly of the ECM that serves as tracks for migration. PMID:21949686

Urbano, Jose M; Domínguez-Giménez, Paloma; Estrada, Beatriz; Martín-Bermudo, María D

2011-01-01

308

Enhanced Ryanodine-Mediated Calcium Release in Mutant PS1-Expressing  

E-print Network

Enhanced Ryanodine-Mediated Calcium Release in Mutant PS1-Expressing Alzheimer's Mouse Models GRACE non-Tg mice. In contrast, the exag- gerated signals in 3Ã?Tg-AD and PS1KI mice resulted primarily from; endoplasmic reticulum; 2-photon; electrophysiology; calcium; Alzheimer; PS1; 3Ã?Tg-AD; transgenic; ryanodine

Parker, Ian

309

Identification and Characterization of Fusolisin, the Fusobacterium nucleatum Autotransporter Serine Protease  

PubMed Central

Fusobacterium nucleatum is an oral anaerobe associated with periodontal disease, adverse pregnancy outcomes and colorectal carcinoma. A serine endopeptidase of 61–65 kDa capable of damaging host tissue and of inactivating immune effectors was detected previously in F. nucleatum. Here we describe the identification of this serine protease, named fusolisin, in three oral F. nucleatum sub-species. Gel zymogram revealed fusobacterial proteolytic activity with molecular masses ranging from 55–101 kDa. All of the detected proteases were inhibited by the serine protease inhibitor PMSF. analysis revealed that all of the detected proteases are encoded by genes encoding an open reading frame (ORF) with a calculated mass of approximately 115 kDa. Bioinformatics analysis of the identified ORFs demonstrated that they consist of three domains characteristic of autotransporters of the type Va secretion system. Our results suggest that the F. nucleatum fusolisins are derived from a precursor of approximately 115 kDa. After crossing the cytoplasmic membrane and cleavage of the leader sequence, the C-terminal autotransporter domain of the remaining 96–113 kDa protein is embedded in the outer membrane and delivers the N-terminal S8 serine protease passenger domain to the outer cell surface. In most strains the N-terminal catalytic 55–65 kDa domain self cleaves and liberates itself from the autotransporter domain after its transfer across the outer cell membrane. In F. nucleatum ATCC 25586 this autocatalytic activity is less efficient resulting in a full length membrane-anchored serine protease. The mature serine protease was found to cleave after Thr, Gly, Ala and Leu residues at the P1 position. Growth of F. nucleatum in complex medium was inhibited when serine protease inhibitors were used. Additional experiments are needed to determine whether fusolisin might be used as a target for controlling fusobacterial infections. PMID:25357190

Ibrahim, Yara; Eini, Amir; Naor, Ronit; Rosen, Graciela; Bachrach, Gilad

2014-01-01

310

D-Serine-induced nephrotoxicity: a HPLC-TOF/MS-based metabonomics approach.  

PubMed

HPLC-MS-based metabonomic analysis was used to investigate urinary metabolic perturbations associated with D-serine-induced nephrotoxicity. D-Serine causes selective necrosis of the proximal straight tubules in the rat kidney accompanied by aminoaciduria, proteinuria and glucosuria. Alderely Park (Wistar-derived) rats were dosed with either D-serine (250 mg/kg ip) or vehicle (deionised water) and urine was collected at 0-12, 12-24, 24-36 and 36-48 h post-dosing. Samples were analysed using a Waters Alliance HT 2795 HPLC system coupled to a Waters Micromass Q-ToF-micro equipped with an electrospray source operating in either positive or negative ion mode. Changes to the urinary profile were detected at all time points compared to control. In negative ion mode, increases were observed in serine (m/z=103.0077), m/z=104.0376 (proposed to be hydroxypyruvate) and glycerate (m/z=105.0215), the latter being metabolites of D-serine. Furthermore, an increase in tryptophan, phenylalanine and lactate and decreases in methylsuccinic acid and sebacic acid were observed. Positive ion analysis revealed a decrease in xanthurenic acid, which has previously been assigned and reported using HPLC-MS following exposure to mercuric chloride and cyclosporine A. A general aminoaciduria, including proline, methionine, leucine, tyrosine and valine was also observed as well as an increase in acetyl carnitine. Investigation of additional metabolites altered as a result of exposure to D-serine is on-going. Thus, HPLC-MS-based metabonomic analysis has provided information concerning the mechanism of D-serine-induced renal injury. PMID:15596249

Williams, R E; Major, H; Lock, E A; Lenz, E M; Wilson, I D

2005-02-14

311

Antimicrobial activity of a honeybee (Apis cerana) venom Kazal-type serine protease inhibitor.  

PubMed

Insect-derived Kazal-type serine protease inhibitors exhibit thrombin, elastase, plasmin, proteinase K, or subtilisin A inhibition activity, but so far, no functional roles for bee-derived Kazal-type serine protease inhibitors have been identified. In this study, a bee (Apis cerana) venom Kazal-type serine protease inhibitor (AcKTSPI) that acts as a microbial serine protease inhibitor was identified. AcKTSPI contained a single Kazal domain that displayed six conserved cysteine residues and a P1 threonine residue. AcKTSPI was expressed in the venom gland and was present as a 10-kDa peptide in bee venom. Recombinant AcKTSPI Kazal domain (AcKTSPI-Kd) expressed in baculovirus-infected insect cells demonstrated inhibitory activity against subtilisin A (Ki 67.03 nM) and proteinase K (Ki 91.53 nM), but not against ?-chymotrypsin or trypsin, which implies a role for AcKTSPI as a microbial serine protease inhibitor. However, AcKTSPI-Kd exhibited no detectable inhibitory effects on factor Xa, thrombin, tissue plasminogen activator, or elastase. Additionally, AcKTSPI-Kd bound directly to Bacillus subtilis, Bacillus thuringiensis, Beauveria bassiana, and Fusarium graminearum but not to Escherichia coli. Consistent with these findings, AcKTSPI-Kd showed antibacterial activity against Gram-positive bacteria and antifungal activity against both plant-pathogenic and entomopathogenic fungi. These findings constitute molecular evidence that AcKTSPI acts as an inhibitor of microbial serine proteases. This paper provides a novel view of the antimicrobial functions of a bee venom Kazal-type serine protease inhibitor. PMID:24076031

Kim, Bo Yeon; Lee, Kwang Sik; Zou, Feng Ming; Wan, Hu; Choi, Yong Soo; Yoon, Hyung Joo; Kwon, Hyung Wook; Je, Yeon Ho; Jin, Byung Rae

2013-12-15

312

Allosteric activation and contrasting properties of L-serine dehydratase types 1 and 2.  

PubMed

Bacterial L-serine dehydratases differ from mammalian L- and D-serine dehydratases and bacterial D-serine dehydratases by the presence of an iron-sulfur center rather than a pyridoxyl phosphate prosthetic group. They exist in two forms, types 1 and 2, distinguished by their sequence and oligomeric configuration. Both types contain an ASB domain, and the type 1 enzymes also contain an ACT domain in a tandem arrangement with the ASB domain like that in type 1 D-3-phosphoglycerate dehydrogenases (PGDHs). This investigation reveals striking kinetic differences between L-serine dehydratases from Bacillus subtilis (bsLSD, type 1) and Legionella pneumophila (lpLSD, type 2). lpLSD is activated by monovalent cations and inhibited by monovalent anions. bsLSD is strongly activated by cations, particularly potassium, and shows a mixed response to anions. Flouride is a competitive inhibitor for lpLSD but an apparent activator for bsLSD at low concentrations and an inhibitor at high concentrations. The reaction products, pyruvate and ammonia, also act as activators but to different extents for each type. Pyruvate activation is competitive with L-serine, but activation of the enzyme is not compatible with it simply competing for binding at the active site and suggests the presence of a second, allosteric site. Because activation can be eliminated by higher levels of L-serine, it may be that this second site is actually a second serine binding site. This is consistent with type 1 PGDH in which the ASB domain functions as a second site for substrate binding and activation. PMID:22686449

Chen, Shawei; Xu, Xiao Lan; Grant, Gregory A

2012-07-01

313

Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine  

Microsoft Academic Search

The gliotransmitter D-serine is released upon (S)--amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid\\/kainate and metabotropic glutamate receptor stimulation, but the mechanisms involved are unknown. Here, by using a highly sensitive bioassay to continuously monitor extracellular D-serine levels, we have investigated the pathways used in its release. We reveal that D-serine release is inhibited by removal of extracellular calcium and augmented by increasing extracellular calcium or

Jean-Pierre Mothet; Loredano Pollegioni; Gilles Ouanounou; Magalie Martineau; Philippe Fossier; Gérard Baux

2005-01-01

314

Immunohistochemical evidences for localization and production of d-serine in some neurons in the rat brain  

Microsoft Academic Search

d-Amino acids are thought not to occur in mammalian tissues. However, previous studies reported d-serine was present only in astrocytes in the rat brain. In the present study, it was indicated by a highly sensitive immunocytochemical method with a d-serine specific antibody that d-serine was contained not only in astrocytes but also in some neurons, such as pyramidal neurons in

Etsuko Yasuda; Ning Ma; Reiji Semba

2001-01-01

315

Extracellular concentration of endogenous free d-serine in the rat brain as revealed by in vivo microdialysis  

Microsoft Academic Search

Using an in vivo microdialysis technique, we have measured the extracellular concentration of endogenous free d-serine in comparison with that of l-serine, glycine and l-glutamate in the discrete brain areas of the freely moving rat. A high concentration of d-serine was observed in the dialysate obtained from the medial prefrontal cortex and striatum, whereas the cerebellar dialysate contained only a

A. Hashimoto; T. Oka; T. Nishikawa

1995-01-01

316

The presence of free D-serine, D-alanine and D-proline in human plasma  

Microsoft Academic Search

Twelve neutral free amino acids, i. e., serine, threonine, glutamine, asparagine, alanine, proline, methionine, tyrosine, valine, leucine, isoleucine and phenylalanine, were surveyed for the presence of D-enantiomers in plasma samples from patients with renal diseases and from normal subjects. D-serine, D-alanine and D-proline were found in the patient's plasma. The highest concentrations (D\\/L ratio) of D-serine, D-alanine and D-proline were

Y. Nagata; R. Masui; T. Akino

1992-01-01

317

Characterization of a D-Amino Acid Oxidase Microbiosensor for D-Serine Detection in the Central Nervous System  

Microsoft Academic Search

D-serine is a glial neuromodulator that is linked to several brain disorders such as schizophrenia, epilepsy, or stroke. We have developed an in situ D-serine microbiosensor that consists in a cylindrical platinum microelectrode covered with a layer of D-amino acid oxidase from the yeast R. gracilis. This enzyme converts D-serine into hydroxypyruvate, while producing hydrogen peroxide that, in turn, is

Pierre PERNOT; J.-P. Mothet; O. Schuvailo; A. Soldatkin; L. Pollegioni; M. Pilone; R. Cespuglio; S. Marinesco

2007-01-01

318

Application of Infrared Multiphoton Dissociation Spectroscopy for the Study of Chiral Recognition in the Protonated Serine Clusters: Part II  

NASA Astrophysics Data System (ADS)

Serine is an amino acid which has long been known to form the magic-number serine octamer [Ser_8 + H]^+. It has been shown that the serine octamer exhibits strong preference for homochirality. Although a few possible structures for the homochiral serine octamer have been proposed, no definite conclusion has so far been drawn. Last year at this conference, we reported on the study of the protonated serine octamer and dimer as well as the chiral recognition in these clusters using infrared multiphoton dissociation (IRMPD) spectroscopic technique coupled with a Fourier transform ion cyclotron (FTICR) mass spectrometer. Here we present our latest results on the search for the infrared signatures of chiral recognition in the serine octamer and the dimer using a mixture of the deuterated 2,3,3-d_3-L-serine and normal D-serine solution. Using the isotopic labeled species, we could isolate the heterochiral species and obtain their IRMPD spectra which can be directly compared with those of the homochiral species. As an aid to interpret the observed spectra, molecular structures and vibrational frequencies of both homochiral and heterochiral octamer and dimer have been predicted by ab initio calculations. New insights into the hitherto undetermined structure of the serine octamer will be discussed. S. C. Nanita and R. G. Cooks Angew. Chem. Int. Ed. 45, (554), 2006.

Sunahori, Fumie X.; Kitova, Elena N.; Klassen, John S.; Xu, Yunjie; Yang, Guochun

2011-06-01

319

The N-methyl D-aspartate receptor glycine site and D-serine metabolism: an evolutionary perspective.  

PubMed Central

The N-methyl D-aspartate (NMDA) type of glutamate receptor requires two distinct agonists to operate. Glycine is assumed to be the endogenous ligand for the NMDA receptor glycine site, but this notion has been challenged by the discovery of high levels of endogenous d-serine in the mammalian forebrain. I have outlined an evolutionary framework for the appearance of a glycine site in animals and the metabolic events leading to high levels of D-serine in brain. Sequence alignments of the glycine-binding regions, along with the scant experimental data available, suggest that the properties of invertebrate NMDA receptor glycine sites are probably different from those in vertebrates. The synthesis of D-serine in brain is due to a pyridoxal-5'-phosphate (B(6))-requiring serine racemase in glia. Although it remains unknown when serine racemase first evolved, data concerning the evolution of B(6) enzymes, along with the known occurrences of serine racemases in animals, point to D-serine synthesis arising around the divergence time of arthropods. D-Serine catabolism occurs via the ancient peroxisomal enzyme d-amino acid oxidase (DAO), whose ontogenetic expression in the hindbrain of mammals is delayed until the postnatal period and absent from the forebrain. The phylogeny of D-serine metabolism has relevance to our understanding of brain ontogeny, schizophrenia and neurotransmitter dynamics. PMID:15306409

Schell, Michael J

2004-01-01

320

Inhibition of serine and proline racemases by substrate-product analogues.  

PubMed

d-Amino acids can play important roles as specific biosynthetic building blocks required by organisms or act as regulatory molecules. Consequently, amino acid racemases that catalyze the formation of d-amino acids are potential therapeutic targets. Serine racemase catalyzes the reversible formation of d-serine (a modulator of neurotransmission) from l-serine, while proline racemase (an essential enzymatic and mitogenic protein in trypanosomes) catalyzes the reversible conversion of l-proline to d-proline. We show the substrate-product analogue ?-(hydroxymethyl)serine is a modest, linear mixed-type inhibitor of serine racemase from Schizosaccharomyces pombe (Ki=167±21mM, Ki'=661±81mM, cf. Km=19±2mM). The bicyclic substrate-product analogue of proline, 7-azabicyclo[2.2.1]heptan-7-ium-1-carboxylate is a weak inhibitor of proline racemase from Clostridium sticklandii, giving only 29% inhibition at 142.5mM. However, the more flexible bicyclic substrate-product analogue tetrahydro-1H-pyrrolizine-7a(5H)-carboxylate is a noncompetitive inhibitor of proline racemase from C. sticklandii (Ki=111±15mM, cf. Km=5.7±0.5mM). These results suggest that substrate-product analogue inhibitors of racemases may only be effective when the active site is capacious and/or plastic, or when the inhibitor is sufficiently flexible. PMID:24314397

Harty, Matthew; Nagar, Mitesh; Atkinson, Logan; Legay, Christina M; Derksen, Darren J; Bearne, Stephen L

2014-01-01

321

Cell-type specific mechanisms of D-serine uptake and release in the brain  

PubMed Central

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine. PMID:24910611

Martineau, Magalie; Parpura, Vladimir; Mothet, Jean-Pierre

2014-01-01

322

Disk-shaped amperometric enzymatic biosensor for in vivo detection of D-serine.  

PubMed

At the synapse, D-serine is an endogenous co-agonist for the N-methyl-D-aspartate receptor (NMDAR). It plays an important role in synaptic transmission and plasticity and has also been linked to several pathological diseases such as schizophrenia and Huntington's. The quantification of local changes in D-serine concentration is essential to further understanding these processes. We report herein the development of a disk-shaped amperometric enzymatic biosensor for detection of D-serine based on a 25 ?m diameter platinum disk microelectrode with an electrodeposited poly-m-phenylenediamine (PPD) layer and an R. gracilis D-amino acid oxidase (RgDAAO) layer. The disk-shaped D-serine biosensor is 1-5 orders of magnitude smaller than previously reported probes and exhibits a sensitivity of 276 ?A cm(-2) mM(-1) with an in vitro detection limit of 0.6 ?M. We demonstrate its usefulness for in vivo applications by measuring the release of endogenous D-serine in the brain of Xenopus laevis tadpoles. PMID:24650010

Polcari, David; Kwan, Annie; Van Horn, Marion R; Danis, Laurence; Pollegioni, Loredano; Ruthazer, Edward S; Mauzeroll, Janine

2014-04-01

323

Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase.  

PubMed

Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca(2+) produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling. PMID:23386721

Stobart, Jillian L LeMaistre; Lu, Lingling; Anderson, Hope D I; Mori, Hisashi; Anderson, Christopher M

2013-02-19

324

d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum.  

PubMed

The present work investigated the effects of intrastriatal administration of d-serine on relevant parameters of oxidative stress in striatum of young rats. d-Serine significantly induced lipid peroxidation, reflected by the significant increase of thiobarbituric acid-reactive substances, and significantly diminished the striatum antioxidant defenses, as verified by a decrease of the levels of reduced glutathione and total antioxidant status. Finally, d-serine inhibited superoxide dismutase activity, without altering the activities of glutathione peroxidase and catalase. In contrast, this d-amino acid did not alter sulfhydryl oxidation, a measure of protein oxidative damage. The present data indicate that d-serine in vivo administration induces lipid oxidative damage and decreases the antioxidant defenses in the striatum of young rats. Therefore, it is presumed that this oxidative stress may be a pathomechanism involved at least in part in the neurological damage found in patients affected by disorders in which d-serine metabolism is compromised, leading to altered concentrations of this d-amino acid. PMID:20307643

Leipnitz, Guilhian; da Silva, Lucila de Bortoli; Fernandes, Carolina Gonçalves; Seminotti, Bianca; Amaral, Alexandre Umpierrez; Dutra-Filho, Carlos Severo; Wajner, Moacir

2010-06-01

325

Astrocyte-induced cortical vasodilation is mediated by D-serine and endothelial nitric oxide synthase  

PubMed Central

Astrocytes play a critical role in neurovascular coupling by providing a physical linkage from synapses to arterioles and releasing vaso-active gliotransmitters. We identified a gliotransmitter pathway by which astrocytes influence arteriole lumen diameter. Astrocytes synthesize and release NMDA receptor coagonist, D-serine, in response to neurotransmitter input. Mouse cortical slice astrocyte activation by metabotropic glutamate receptors or photolysis of caged Ca2+ produced dilation of penetrating arterioles in a manner attenuated by scavenging D-serine with D-amino acid oxidase, deleting the enzyme responsible for D-serine synthesis (serine racemase) or blocking NMDA receptor glycine coagonist sites with 5,7-dichlorokynurenic acid. We also found that dilatory responses were dramatically reduced by inhibition or elimination of endothelial nitric oxide synthase and that the vasodilatory effect of endothelial nitric oxide synthase is likely mediated by suppressing levels of the vasoconstrictor arachidonic acid metabolite, 20-hydroxy arachidonic acid. Our results provide evidence that D-serine coactivation of NMDA receptors and endothelial nitric oxide synthase is involved in astrocyte-mediated neurovascular coupling. PMID:23386721

Stobart, Jillian L. LeMaistre; Lu, Lingling; Mori, Hisashi; Anderson, Christopher M.

2013-01-01

326

Antibody-dependent tumour cytolysis by human neutrophils: effect of synthetic serine esterase inhibitors and substrates.  

PubMed Central

The requirement for serine esterase activity in antibody-dependent cellular cytotoxicity (ADCC) in human neutrophils against Raji target cells has been investigated. The lysis was prevented when the serine esterase inhibitors TPCK and TLCK (chloromethyl-ketone derivatives of tosylamino acids) were introduced into the system. Moreover, neutrophils pretreated with TPCK or TLCK and washed were inhibited as well, via a process unaffected by the presence of adequate amounts of enzymatic substrates. This suggests that the inhibition mediated by TPCK and TLCK is independent of serine esterase blockade, therefore implying the inactivation of some other step crucial to the lysis. The addition of synthetic chymotrypsin substrates (tyrosine and phenylalanine esters) impaired the Raji cell lysis in a dose-related manner without altering the constitution of neutrophil-target conjugates. Trypsin ester substrates were ineffective. These results are in agreement with the involvement of a serine esterase activity with chymotrypsin-like specificity, which should participate in the lysis at a post-binding step. We conclude that neutrophil-mediated ADCC, as developed in our model system, needs the intervention of a serine esterase or esterases, like other systems of cell-mediated cytotoxicity. PMID:3666787

Dallegri, F; Frumento, G; Ballestrero, A; Goretti, R; Torresin, A; Patrone, F

1987-01-01

327

The Cutting Edge: Membrane Anchored Serine Protease Activities in the Pericellular Microenvironment  

PubMed Central

Synopsis The serine proteases of the trypsin-like (S1) family play critical roles in many key biological processes including digestion, blood coagulation, and immunity. Recent studies have identified members of this family which contain amino- or carboxy-terminal domains that serve to tether the serine protease catalytic domain directly at the plasma membrane. These membrane anchored serine proteases are proving to be key components of the cell machinery for activation of precursor molecules in the pericellular microenvironment, playing vital functions in the maintenance of homeostasis. Substrates activated by membrane anchored serine proteases include peptide hormones, growth and differentiation factors, receptors, enzymes, adhesion molecules and viral coat proteins. In addition, new insights into our understanding of the physiological functions of these proteases and their involvement in human pathology have come from animal models and patient studies. This review discusses emerging evidence for the diversity of this fascinating group of membrane serine proteases as potent modifiers of the pericellular microenvironment through proteolytic processing of diverse substrates. We also discuss the functional consequences of the activities of these proteases on mammalian physiology and disease. PMID:20507279

Antalis, Toni M.; Buzza, Marguerite S.; Hodge, Kathryn M.; Hooper, John D.; Netzel-Arnett, Sarah

2013-01-01

328

Impaired neurogenesis in embryonic spinal cord of Phgdh knockout mice, a serine deficiency disorder model.  

PubMed

Mutations in the d-3-phosphoglycerate dehydrogenase (PHGDH; EC 1.1.1.95) gene, which encodes an enzyme involved in de novol-serine biosynthesis, are shown to cause human serine deficiency disorder. This disorder has been characterized by severe neurological symptoms including congenital microcephaly and psychomotor retardation. Our previous work demonstrated that targeted disruption of mouse Phgdh leads to a marked decrease in serine and glycine, severe growth retardation of the central nervous system, and lethality after embryonic day 13.5. To clarify how a serine deficiency causes neurodevelopmental defects, we characterized changes in metabolites, gene expression and morphological alterations in the spinal cord of Phgdh knockout mice. BeadChip microarray analysis revealed significant dysregulation of genes involved in the cell cycle. Ingenuity Pathway Analysis also revealed a significant perturbation of regulatory networks that operate in the cell cycle progression. Moreover, morphological examinations of the knockout spinal cord demonstrated a marked deficit in dorsal horn neurons. Radial glia cells, native neural stem/progenitor cells, accumulated in the dorsal ventricular zone, but they did not proceed to a G(0)-like quiescent state. The present integrative study provides in vivo evidence that normal cell cycle progression and subsequent neurogenesis of radial glia cells are severely impaired by serine deficiency. PMID:19114063

Kawakami, Yuriko; Yoshida, Kazuyuki; Yang, Jung Hoon; Suzuki, Takeshi; Azuma, Norihiro; Sakai, Kazuhisa; Hashikawa, Tsutomu; Watanabe, Masahiko; Yasuda, Kaori; Kuhara, Satoru; Hirabayashi, Yoshio; Furuya, Shigeki

2009-03-01

329

Cell-type specific mechanisms of D-serine uptake and release in the brain.  

PubMed

Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine. PMID:24910611

Martineau, Magalie; Parpura, Vladimir; Mothet, Jean-Pierre

2014-01-01

330

Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible involvement of D-serine  

PubMed Central

A unique feature of N-methyl-D-aspartate receptors (NMDARs) that distinguishes them from other ionic receptors is that their activation requires more than one agonist to bind simultaneously to distinct binding sites on the receptor. D-serine, a co-agonist binding to the glycine site of NMDARs, has been implicated in several NMDAR-dependent physiological processes, and altered D-serine levels under certain pathophysiological conditions contribute to neural dysfunction via NMDARs in the central nervous system. Entry of HIV-1 in the brain causes neuronal injury leading to cognitive, behavioral and motor impairments known as HIV-associated neurocognitive disorders (HAND). As HIV-1 does not infect neurons, neuronal injury is believed to be primarily mediated by an indirect mechanism,that is, HIV-1-infected and/or immune-activated macrophages and microglial cells release soluble molecules leading to neuronal injury or death. Among the soluble factors is D-serine. In this article we try to address recent progresses on the role D-serine might play in the pathogenesis of neurodegenerative disorders with a particular emphasis of the involvement of D-serine in HIV-1-associated neurotoxicity. PMID:24044033

Xia, Jianxun; Xiong, Huangui

2013-01-01

331

The evidence of quasi-free positronium state in GiPS-AMOC spectra of glycerol  

E-print Network

We present the results of processing of Age-Momentum Correlation (AMOC) spectra that were measured for glycerol by the Gamma-induced positron spectroscopy (GiPS) facility. Our research has shown that the shape of experimental s(t) curve cannot be explained without introduction of the intermediate state of positronium (Ps), called quasi-free Ps. This state yields the wide Doppler line near zero lifetimes. We discuss the possible properties of this intermediate Ps state from the viewpoint of developed model. The amount of annihilation events produced by quasi-free Ps is estimated to be less than 5% of total annihilations. In the proposed model, quasi-free Ps serves as a precursor for trapped Ps of para- and ortho-states.

Zvezhinskiy, D; Wagner, A; Krause-Rehberg, R; Stepanov, S V

2013-01-01

332

Create and Publish a Hierarchical Progressive Survey (HiPS)  

NASA Astrophysics Data System (ADS)

Since 2009, the CDS promotes a method for visualizing based on the HEALPix sky tessellation. This method, called “Hierarchical Progressive Survey" or HiPS, allows one to display a survey progressively. It is particularly suited for all-sky surveys or deep fields. This visualization method is now integrated in several applications, notably Aladin, the SiTools/MIZAR CNES framework, and the recent HTML5 “Aladin Lite". Also, more than one hundred surveys are already available in this view mode. In this article, we will present the progress concerning this method and its recent adaptation to the astronomical catalogs such as the GAIA simulation.

Fernique, P.; Boch, T.; Pineau, F.; Oberto, A.

2014-05-01

333

Genetic transformation in the methanogen Methanococcus voltae PS  

NASA Technical Reports Server (NTRS)

Mutations causing requirements for histidine, purine, and vitamin B12 were obtained in strain PS of Methanococcus voltae (archaebacteria) upon irradiation with UV or gamma rays. The first two mutations were shown to revert at low frequencies and were used to demonstrate the occurrence of transformation with homologous, wild-type DNA. The transformation rates obtained for these presumably chromosomal markers were in the range of 2 to 100 transformants per microgram of DNA. Mutants resistant to 2-bromoethanesulfonate and to 5-methyl-DL-tryptophan were also isolated.

Bertani, G.; Baresi, L.

1987-01-01

334

KSR-based medium improves the generation of high-quality mouse iPS cells.  

PubMed

Induced pluripotent stem (iPS) cells from somatic cells have great potential for regenerative medicine. The efficiency in generation of iPS cells has been significantly improved in recent years. However, the generation of high-quality iPS cells remains of high interest. Consistently, we demonstrate that knockout serum replacement (KSR)-based medium accelerates iPS cell induction and improves the quality of iPS cells, as confirmed by generation of chimeras and all iPS cell-derived offspring with germline transmission competency. Both alkaline phosphatase (AP) activity assay and expression of Nanog have been used to evaluate the efficiency of iPS cell induction and formation of ES/iPS cell colonies; however, appropriate expression of Nanog frequently indicates the quality of ES/iPS cells. Interestingly, whereas foetal bovine serum (FBS)-based media increase iPS cell colony formation, as revealed by AP activity, KSR-based media increase the frequency of iPS cell colony formation with Nanog expression. Furthermore, inhibition of MAPK/ERK by a specific inhibitor, PD0325901, in KSR- but not in FBS-based media significantly increases Nanog-GFP+ iPS cells. In contrast, addition of bFGF in KSR-based media decreases proportion of Nanog-GFP+ iPS cells. Remarkably, PD can rescue Nanog-GFP+ deficiency caused by bFGF. These data suggest that MAPK/ERK pathway influences high quality mouse iPS cells and that KSR- and PD-based media could enrich homogeneous authentic pluripotent stem cells. PMID:25171101

Liu, Kai; Wang, Fang; Ye, Xiaoying; Wang, Lingling; Yang, Jiao; Zhang, Jingzhuo; Liu, Lin

2014-01-01

335

Mosquito Saliva Serine Protease Enhances Dissemination of Dengue Virus into the Mammalian Host  

PubMed Central

Dengue virus (DENV), a flavivirus of global importance, is transmitted to humans by mosquitoes. In this study, we developed in vitro and in vivo models of saliva-mediated enhancement of DENV infectivity. Serine protease activity in Aedes aegypti saliva augmented virus infectivity in vitro by proteolyzing extracellular matrix proteins, thereby increasing viral attachment to heparan sulfate proteoglycans and inducing cell migration. A serine protease inhibitor reduced saliva-mediated enhancement of DENV in vitro and in vivo, marked by a 100-fold reduction in DENV load in murine lymph nodes. A saliva-mediated infectivity enhancement screen of fractionated salivary gland extracts identified serine protease CLIPA3 as a putative cofactor, and short interfering RNA knockdown of CLIPA3 in mosquitoes demonstrated its role in influencing DENV infectivity. Molecules in mosquito saliva that facilitate viral infectivity in the vertebrate host provide novel targets that may aid in the prevention of disease. PMID:24131723

Conway, Michael J.; Watson, Alan M.; Colpitts, Tonya M.; Dragovic, Srdjan M.; Li, Zhiyong; Wang, Penghua; Feitosa, Fabiana; Shepherd, Denueve T.; Ryman, Kate D.; Klimstra, William B.; Anderson, John F.

2014-01-01

336

Studies on 2-benzyloxy-4H-3,1-benzoxazin-4-ones as serine protease inhibitors.  

PubMed

The class of 3,1-benzoxazin-4-ones includes potent inhibitors of various serine proteases. Structural investigation on three 2-benzyloxy-4H-3,1-benzoxazin-4-ones (1-3) are described with respect to their reactivity to alkaline hydrolysis. The 13C NMR data of 2-benzyloxy-5-methyl-4H-3,1-benzoxazin-4-one 3 are discussed. This peri substituted compound was subjected to a crystal structure analysis. The heterocyclic skeleton together with the carbonyl oxygen and the methyl carbon is planar, and only small angle distortions occurred. The inhibition of neutrophil serine proteases by 1-3 is reported. The different reactivity of the 5-methyl derivative 3 towards serine proteases is mainly influenced by specific interactions within the active sites. Thus, 3 was found to rapidly acylate human leukocyte proteinase 3 and exhibited a Ki value of 1.8 nM. PMID:9700938

Gütschow, M; Neumann, U; Sieler, J; Eger, K

1998-07-01

337

Purification and characterization of alkaline serine proteinase from photosynthetic bacterium, Rubrivivax gelatinosus KDDS1.  

PubMed

In order to reduce the protein content of wastewater, photosynthetic bacteria producing proteinases were screened from wastewater of various sources and stocked in culture. An isolated strain, KDDS1, was identified as Rubrivivax gelatinosus, a purple nonsulfur bacterium that secretes proteinase under micro-aerobic conditions under light at 35 degrees C. Molecular weight of the purified enzyme was estimated to be 32.5 kDa. The enzyme showed the highest activity at 45 degrees C and pH 9.6, and the activity was completely inhibited by phenylmethyl sulfonyl fluoride (PMSF), but not by EDTA. The amino-terminal 24 amino acid sequence of the enzyme showed about 50% identity to those of serine proteinases from Pseudoalteromonas piscicida strain O-7 and Burkholderia pseudomallei. Thus, the enzyme from Rvi. gelatinosus KDDS1 was thought to be a serine-type proteinase. This was the first serine proteinase characterized from photosynthetic bacteria. PMID:15056899

Oda, Kohei; Tanskul, Somporn; Oyama, Hiroshi; Noparatnaraporn, Napavarn

2004-03-01

338

Molecular cloning and antifibrinolytic activity of a serine protease inhibitor from bumblebee (Bombus terrestris) venom.  

PubMed

Bumblebee (Bombus spp.) venom contains a variety of components, including bombolitin, phospholipase A(2) (PLA(2)), serine proteases, and serine protease inhibitors. In this study, we identified a bumblebee (Bombus terrestris) venom serine protease inhibitor (Bt-KTI) that acts as a plasmin inhibitor. Bt-KTI consists of a 58-amino acid mature peptide that displays features consistent with snake venom Kunitz-type inhibitors, including six conserved cysteine residues and a P1 site. Recombinant Bt-KTI was expressed as a 6.5-kDa peptide in baculovirus-infected insect cells. The recombinant peptide demonstrated properties similar to Kunitz-type trypsin inhibitors. Bt-KTI showed no detectable inhibitory effects on factor Xa, thrombin, or tissue plasminogen activator; however, Bt-KTI strongly inhibited plasmin, indicating that it acts as an antifibrinolytic agent. These findings demonstrate the antifibrinolytic role of Bt-KTI as a plasmin inhibitor. PMID:23164714

Qiu, Yuling; Lee, Kwang Sik; Choo, Young Moo; Kong, Dexin; Yoon, Hyung Joo; Jin, Byung Rae

2013-03-01

339

Conservation of sequence and function in fertilization of the cortical granule serine protease in echinoderms.  

PubMed

Conservation of the cortical granule serine protease during fertilization in echinoderms was tested both functionally in sea stars, and computationally throughout the echinoderm phylum. We find that the inhibitor of serine protease (soybean trypsin inhibitor) effectively blocks proper transition of the sea star fertilization envelope into a protective sperm repellent, whereas inhibitors of the other main types of proteases had no effect. Scanning the transcriptomes of 15 different echinoderm ovaries revealed sequences of high conservation to the originally identified sea urchin cortical serine protease, CGSP1. These conserved sequences contained the catalytic triad necessary for enzymatic activity, and the tandemly repeated LDLr-like repeats. We conclude that the protease involved in the slow block to polyspermy is an essential and conserved element of fertilization in echinoderms, and may provide an important reagent for identification and testing of the cell surface proteins in eggs necessary for sperm binding. PMID:24878526

Oulhen, Nathalie; Xu, Dongdong; Wessel, Gary M

2014-08-01

340

Microfluidic Analysis of Serine Levels Using Seryl-tRNA Synthetase Coupled with Spectrophotometric Detection.  

PubMed

The measurement of amino acid content is useful for the diagnosis of several types of diseases, including cancer and diabetes. In this study, a microfluidic method for the analysis of serine using enzymatic reactions coupled with spectrophotometric detection was developed. The assay system has some advantages in the analytical field, such as the ability to detect small amounts of analyte and reaction solution and a rapid and efficient reaction. For the specific detection of serine, seryl-tRNA synthetase was coupled with the generation of hydrogen peroxide, which was then detected by the Trinder reagent spectrophotometric method. Seryl- and other aminoacyl-tRNA synthetases are involved in the biosynthesis of peptides and proteins in the human body and should allow precise recognition of the corresponding amino acids. This approach provided selective quantitation of up to 250 ?M serine in 100 mM Tris-HCl buffer (pH 8.0) in a semiautomatic system. PMID:25190303

Kugimiya, Akimitsu; Matsuzaki, Emi

2014-12-01

341

School-Community Interaction Umbrella: English as a Second Language (PS152) & Early Identification Program (PS139); February 13, 1975- June 26, 1975. Final Report.  

ERIC Educational Resources Information Center

This report provides a description and evaluation of two school programs in New York City. The programs are English as a Second language at P.S. 152, and the Early Identification Program at P.S. 139. Both were planned with the participation of the principal, the parents, and the school district staff. The first program was designed to supplement…

Brown, Eric R.

342

Interactome Analyses of Mature ?-Secretase Complexes Reveal Distinct Molecular Environments of Presenilin (PS) Paralogs and Preferential Binding of Signal Peptide Peptidase to PS2*  

PubMed Central

?-Secretase plays a pivotal role in the production of neurotoxic amyloid ?-peptides (A?) in Alzheimer disease (AD) and consists of a heterotetrameric core complex that includes the aspartyl intramembrane protease presenilin (PS). The human genome codes for two presenilin paralogs. To understand the causes for distinct phenotypes of PS paralog-deficient mice and elucidate whether PS mutations associated with early-onset AD affect the molecular environment of mature ?-secretase complexes, quantitative interactome comparisons were undertaken. Brains of mice engineered to express wild-type or mutant PS1, or HEK293 cells stably expressing PS paralogs with N-terminal tandem-affinity purification tags served as biological source materials. The analyses revealed novel interactions of the ?-secretase core complex with a molecular machinery that targets and fuses synaptic vesicles to cellular membranes and with the H+-transporting lysosomal ATPase macrocomplex but uncovered no differences in the interactomes of wild-type and mutant PS1. The catenin/cadherin network was almost exclusively found associated with PS1. Another intramembrane protease, signal peptide peptidase, predominantly co-purified with PS2-containing ?-secretase complexes and was observed to influence A? production. PMID:23589300

Jeon, Amy Hye Won; Bohm, Christopher; Chen, Fusheng; Huo, Hairu; Ruan, Xueying; Ren, Carl He; Ho, Keith; Qamar, Seema; Mathews, Paul M.; Fraser, Paul E.; Mount, Howard T. J.; St George-Hyslop, Peter; Schmitt-Ulms, Gerold

2013-01-01

343

D-amino acid oxidase controls motoneuron degeneration through D-serine.  

PubMed

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving an extensive loss of motoneurons. Aberrant excitability of motoneurons has been implicated in the pathogenesis of selective motoneuronal death in ALS. D-serine, an endogenous coagonist of N-methyl-D-aspartate receptors, exacerbates motoneuronal death and is increased both in patients with sporadic/familial ALS and in a G93A-SOD1 mouse model of ALS (mSOD1 mouse). More recently, a unique mutation in the D-amino acid oxidase (DAO) gene, encoding a D-serine degrading enzyme, was reported to be associated with classical familial ALS. However, whether DAO affects the motoneuronal phenotype and D-serine increase in ALS remains uncertain. Here, we show that genetic inactivation of DAO in mice reduces the number and size of lower motoneurons with axonal degeneration, and that suppressed DAO activity in reactive astrocytes in the reticulospinal tract, one of the major inputs to the lower motoneurons, predominantly contributes to the D-serine increase in the mSOD1 mouse. The DAO inactivity resulted from expressional down-regulation, which was reversed by inhibitors of a glutamate receptor and MEK, but not by those of inflammatory stimuli. Our findings provide evidence that DAO has a pivotal role in motoneuron degeneration through D-serine regulation and that inactivity of DAO is a common feature between the mSOD1 ALS mouse model and the mutant DAO-associated familial ALS. The therapeutic benefit of reducing D-serine or controlling DAO activity in ALS should be tested in future studies. PMID:22203986

Sasabe, Jumpei; Miyoshi, Yurika; Suzuki, Masataka; Mita, Masashi; Konno, Ryuichi; Matsuoka, Masaaki; Hamase, Kenji; Aiso, Sadakazu

2012-01-10

344

d-Amino acid oxidase controls motoneuron degeneration through d-serine  

PubMed Central

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving an extensive loss of motoneurons. Aberrant excitability of motoneurons has been implicated in the pathogenesis of selective motoneuronal death in ALS. d-Serine, an endogenous coagonist of N-methyl-d-aspartate receptors, exacerbates motoneuronal death and is increased both in patients with sporadic/familial ALS and in a G93A-SOD1 mouse model of ALS (mSOD1 mouse). More recently, a unique mutation in the d-amino acid oxidase (DAO) gene, encoding a d-serine degrading enzyme, was reported to be associated with classical familial ALS. However, whether DAO affects the motoneuronal phenotype and d-serine increase in ALS remains uncertain. Here, we show that genetic inactivation of DAO in mice reduces the number and size of lower motoneurons with axonal degeneration, and that suppressed DAO activity in reactive astrocytes in the reticulospinal tract, one of the major inputs to the lower motoneurons, predominantly contributes to the d-serine increase in the mSOD1 mouse. The DAO inactivity resulted from expressional down-regulation, which was reversed by inhibitors of a glutamate receptor and MEK, but not by those of inflammatory stimuli. Our findings provide evidence that DAO has a pivotal role in motoneuron degeneration through d-serine regulation and that inactivity of DAO is a common feature between the mSOD1 ALS mouse model and the mutant DAO-associated familial ALS. The therapeutic benefit of reducing d-serine or controlling DAO activity in ALS should be tested in future studies. PMID:22203986

Sasabe, Jumpei; Miyoshi, Yurika; Suzuki, Masataka; Mita, Masashi; Konno, Ryuichi; Matsuoka, Masaaki; Hamase, Kenji; Aiso, Sadakazu

2012-01-01

345

The serine protease inhibitor TLCK attenuates intrinsic death pathways in neurons upstream of mitochondrial demise.  

PubMed

It is well-established that activation of proteases, such as caspases, calpains and cathepsins are essential components in signaling pathways of programmed cell death (PCD). Although these proteases have also been linked to mechanisms of neuronal cell death, they are dispensable in paradigms of intrinsic death pathways, e.g. induced by oxidative stress. However, emerging evidence implicated a particular role for serine proteases in mechanisms of PCD in neurons. Here, we investigated the role of trypsin-like serine proteases in a model of glutamate toxicity in HT-22 cells. In these cells glutamate induces oxytosis, a form of caspase-independent cell death that involves activation of the pro-apoptotic protein BH3 interacting-domain death agonist (Bid), leading to mitochondrial demise and ensuing cell death. In this model system, the trypsin-like serine protease inhibitor N?-tosyl-l-lysine chloromethyl ketone hydrochloride (TLCK) inhibited mitochondrial damage and cell death. Mitochondrial morphology alterations, the impairment of the mitochondrial membrane potential and ATP depletion were prevented and, moreover, lipid peroxidation induced by glutamate was completely abolished. Strikingly, truncated Bid-induced cell death was not affected by TLCK, suggesting a detrimental activity of serine proteases upstream of Bid activation and mitochondrial demise. In summary, this study demonstrates the protective effect of serine protease inhibition by TLCK against oxytosis-induced mitochondrial damage and cell death. These findings indicate that TLCK-sensitive serine proteases play a crucial role in cell death mechanisms upstream of mitochondrial demise and thus, may serve as therapeutic targets in diseases, where oxidative stress and intrinsic pathways of PCD mediate neuronal cell death. PMID:25146045

Reuther, C; Ganjam, G K; Dolga, A M; Culmsee, C

2014-11-01

346

Dual cross-talk between nitric oxide and D-serine in astrocytes and neurons in the brain.  

PubMed

The present review describes the role of the putative cross-talk between two neurotransmitters, nitric oxide (NO) and D-serine, in the brain. Under physiological conditions NO homeostasis guarantees the correct function of NO in a number of events in the brain such as neurotransmission and vascular tone regulation. D-serine, produced in astrocytes, acts synergistically with glutamate at NMDA receptors on postsynaptic neurons. Neuronal and endothelial NO synthase (nNOS and eNOS) in astrocytes cross-talk with serine racemase (SR) and D-amino acid oxydase (DAAO), catalyzing the synthesis and degradation of D-serine, respectively. SR is inhibited by NO which activates DAAO. D-serine inhibits nNOS but not eNOS and activates SR. Astrocytes and neurons also cross-talk through NO/D-serine system. D-serine released from astrocytes induces a rapid increase in NO contents in postsynaptic neurons. Overall, D-serine production in astrocytes is negatively regulated by NO. Under inflammatory conditions, pro-inflammatory cytokines or Abeta induce, first, a drop in NO contents and an increase in the amounts of D-serine in astrocytes. Together with enhanced glutamate release from presynaptic neurons, D-serine induces an increase in Ca(2+) up-take into presynaptic neurons. In astrocytes an initial drop in NO contents triggers NF-kappaB activation followed by inducible NOS (iNOS) expression. iNOS-derived massive amounts of NO may potentially be toxic. Under schizophrenic conditions, D-serine production is down-regulated. Together with reduced glutamate release, this situation leads to the decreased NO production in postsynaptic neurons. In astrocytes induction of iNOS expression becomes predominant. Initial drop in nNOS-derived NO is potentially toxic in this scenario. PMID:20021361

Darra, Elena; Ebner, Florian Heinrich; Shoji, Kazuo; Suzuki, Hisanori; Mariotto, Sofia

2009-12-01

347

MicroRNA expression profiles of human iPS cells, retinal pigment epithelium derived from iPS, and fetal retinal pigment epithelium.  

PubMed

The objective of this report is to describe the protocols for comparing the microRNA (miRNA) profiles of human induced-pluripotent stem (iPS) cells, retinal pigment epithelium (RPE) derived from human iPS cells (iPS-RPE), and fetal RPE. The protocols include collection of RNA for analysis by microarray, and the analysis of microarray data to identify miRNAs that are differentially expressed among three cell types. The methods for culture of iPS cells and fetal RPE are explained. The protocol used for differentiation of RPE from human iPS is also described. The RNA extraction technique we describe was selected to allow maximal recovery of very small RNA for use in a miRNA microarray. Finally, cellular pathway and network analysis of microarray data is explained. These techniques will facilitate the comparison of the miRNA profiles of three different cell types. PMID:24999033

Greene, Whitney A; Muñiz, Alberto; Plamper, Mark L; Kaini, Ramesh R; Wang, Heuy-Ching

2014-01-01

348

A novel serine protease with clip domain from scallop Chlamys farreri  

Microsoft Academic Search

The serine proteases with clip domain are involved in various innate immune functions in invertebrate such as antimicrobial\\u000a activity, cell adhesion, pattern recognition and regulation of the prophenoloxidase system. A serine protease with clip-domain\\u000a cDNA (Cf SP) was obtained by Expressed sequence taggings (ESTs) method and rapid amplification of cDNA ends (RACE). The Cf\\u000a SP full-length cDNA was of 1,152 bp,

Ling Zhu; Linsheng Song; Yuze Mao; Jiangmin Zhao; Chenghua Li; Wei Xu

2008-01-01

349

Depletion of Cerebral D-Serine in Non-Ketotic Hyperglycinemia: Possible Involvement of Glycine Cleavage System in Control of Endogenous D-Serine  

Microsoft Academic Search

Tissue concentrations of D-serine and other chiral and non-chiral amino acids were measured post-mortem in the cerebral cortex of the neonatal or infantile individuals with (three cases) or without (seven cases) non-ketotic hyperglycinemia (NKH) using high performance liquid chromatography with fluorometric detection. In the cortical tissues of the NKH patients lacking activity of glycine cleavage system, there was a marked

Hisayuki Iwama; Katsunobu Takahashi; Shigeo Kure; Fumihiko Hayashi; Kuniaki Narisawa; Keiya Tada; Masashi Mizoguchi; Sachio Takashima; Urara Tomita; Toru Nishikawa

1997-01-01

350

Unidirectional sub-100-ps magnetic vortex core reversal  

NASA Astrophysics Data System (ADS)

We experimentally demonstrate that unidirectional reversal of the magnetic vortex core polarity is possible by excitation with sub-100-ps-long orthogonal monopolar magnetic pulse sequences in a wide range of pulse lengths and amplitudes. The application of such short digital pulses is a favorable excitation scheme for technological applications. Measured phase diagrams of this unidirectional, spin-wave mediated vortex core reversal are in good qualitative agreement with phase diagrams obtained from micromagnetic simulations. The time dependence of the reversal process, observed by time-resolved scanning transmission x-ray microscopy indicates a switching time of 100 ps and fits well with our simulations. The origin of the asymmetric response to clockwise and counterclockwise excitation which is a prerequisite for reliable unidirectional switching is discussed, based on the gyromode-spin-wave coupling. Situations are found in which a three-dimensional dynamics is important, because a vortex-antivortex pair starts to form close to the core of the original vortex in the lower part of the disk without completing the formation across the whole thickness so that it dissolves later on and does not lead to switching of the original vortex core.

Noske, Matthias; Gangwar, Ajay; Stoll, Hermann; Kammerer, Matthias; Sproll, Markus; Dieterle, Georg; Weigand, Markus; Fähnle, Manfred; Woltersdorf, Georg; Back, Christian H.; Schütz, Gisela

2014-09-01

351

Study on GASTOF - A 10 ps resolution timing detector  

NASA Astrophysics Data System (ADS)

GASTOF (Gas Time Of Flight) is a type of fast-time detector affiliated to the HPS (High Precision Spectrometer) project which is a forward physics collaborator within CMS. It is a picosecond time resolution Cherenkov gas detector using very fast single anode micro-channel plate photomultiplier (Hamamatsu R3809U-50 or Photek 210) as a photon detector. We firstly measured characteristics of these two types of MCP-PMTs by a fast laser pulse in lab. Then two GASTOF detectors both equipped with a Hamamatsu R3809U-50 tube were studied in a beam test at CERN. According to the analysis of beam test data, the average number of photoelectrons (phe) was 2.0 for both phototubes. By making a cut on the number of photoelectrons such that the mean phe was 3.6 in one phototube and 3.2 in another, we obtained a time resolution of ?~11.7 picosecond (ps) and ?~8.2 ps.

Bonnet, Luc; Liao, Junhui; Piotrzkowski, Krzysztof

2014-10-01

352

Properties of Extruded PS-212 Type Self-Lubricating Materials  

NASA Technical Reports Server (NTRS)

Research has been underway at the NASA Lewis Research Center since the 1960's to develop high temperature, self-lubricating materials. The bulk of the research has been done in-house by a team of researchers from the Materials Division. A series of self-lubricating solid material systems has been developed over the years. One of the most promising is the composite material system referred to as PS-212 or PM-212. This material is a powder metallurgy product composed of metal bonded chromium carbide and two solid lubricating materials known to be self-lubricating over a wide temperature range. NASA feels this material has a wide potential in industrial applications. Simplified processing of this material would enhance its commercial potential. Processing changes have the potential to reduce processing costs, but tribological and physical properties must not be adversely affected. Extrusion processing has been employed in this investigation as a consolidation process for PM-212/PS-212. It has been successful in that high density bars of EX-212 (extruded PM-212) can readily be fabricated. Friction and strength data indicate these properties have been maintained or improved over the P.M. version. A range of extrusion temperatures have been investigated and tensile, friction, wear, and microstructural data have been obtained. Results indicate extrusion temperatures are not critical from a densification standpoint, but other properties are temperature dependent.

Waters, W. J.; Sliney, H. E.; Soltis, R. F.

1993-01-01

353

Controlling PS-b-PEO Morphologies by Solution Conditions  

NASA Astrophysics Data System (ADS)

We have investigated the self-assembly behavior of amphiphilic diblock copolymer polystyrene-b-poly(ethylene oxide) (PS-b-PEO) in DMF/water and DMF/acetonitirile mixtures .The morphology of the block copolymer can be controlled in both these systems by varying copolymer concentration and solvent composition The morphologies were visualized directly by transmission electron microscopy. Increasing the water content in the DMF/water mixture or acetonitrile in the DMF/acetonitrile mixture changes the morphology from spheres to worm-like/rods and then to vesicles. Increasing the copolymer concentration shows a similar effect on the morphology. The block copolymer exhibits distinct phases of both exclusive and mixed morphologies. The morphological transitions were also captured by static light scattering and turbidity measurements. Although the trend in morphological changes is similar, there are remarkable differences in the morphological phase behavior of PS-b-PEO in the two solvent systems and thus the role of the `selective solvent' in such systems is also evidenced.

Bhargava, Prachur; Zheng, Xiaoliang; Tu, Yingfeng; Cheng, Stephen Z. D.

2006-03-01

354

Characterization of the biochemical and biophysical properties of the phosphatidylserine receptor (PS-R) gene product.  

PubMed

The PS-R gene product was originally described as a cell surface receptor that interacts with externalized phosphatidylserine (PS) on apoptotic cells, but more recent studies have shown that it plays a critical role in organ development and terminal differentiation of many cell types during embryogenesis. Despite these important developmental functions, the biochemical and molecular properties of PS-R are poorly understood. Here we have used several approaches to show that PS-R undergoes processive post-translational protein cross-linking to form covalent multimers within the nuclear compartment. Although PS-R has a potential Glu-Glu (QQ) duet that is often targeted by transglutaminase TG-2, the oligomerization of PS-R was not effected by QQ-->AA mutation, or when PS-R gene product was expressed in TG-2 (-/-) fibroblasts. Pulse-chase experiments with (35) S-methionine indicates that the PS-R undergoes an initial proteolytic cleavage, followed by progressive multimerization of the monomeric subunits over time. In summary, we report here that PS-R is modified by an unusual post-translational modification, and we speculate that homomultimer of PS-R might be playing an important function as a scaffolding protein in the nucleus. PMID:17534701

Tibrewal, Nitu; Liu, Tong; Li, Hong; Birge, Raymond B

2007-10-01

355

Screening Tests of Reproductive Immunology in Systemic Lupus Erythematosus  

PubMed Central

Female patients in reproductive age with systemic lupus erythematosus and fertility complications together are observed by rheumatologists, gynecologists, and reproductive immunologists. The paper notes the presence of autoantibodies to zona pellucida, to phospholipids (phosphatidyl serine, phosphatidyl ethanolamine, phosphatidyl inositol, phosphatidyl glycerol, phosphatidic acid, annexin V, beta-2 glycoprotein I, and cardiolipin) and of isoantibodies to sperm cells. Isoantibodies to sperm cells are not significantly predominant, but autoimmunity is well expressed in IgG positivity against phosphatidyl inositol, phosphatidyl ethanolamine, phosphatidyl serine, cardiolipin, and beta-2 glycoprotein I, as well as antizona pellucida antibodies in IgG isotype. According to the levels of autoantibodies we have to choose preventive treatment to protect mother and her foetus. PMID:23150811

Ulcova-Gallova, Zdenka; Mockova, Alice; Cedikova, Miroslava

2012-01-01

356

!"! #$%$#&'&()*+,-#-.*&/&012$034#$&56!!756!5& Sep 19 PVC 1 COG 1 PVC 2 PS1 --HD 1  

E-print Network

12-1 Fri 12-1 Sep 19 PVC 1 COG 1 PVC 2 PS1 - - HD 1 Sep 26 PVC 3 COG 2 PVC 4 HD 2 MINI 1 STAT 1 Careers Talk Oct 3 PVC 5 COG 3 PS 2 PS 3 MINI 2 STAT 2 HD 3 Oct 10 PVC 6 COG 4 HD 4 HD 5 - STAT 3 HD 6 Oct 17 PVC 7 COG 5 PS 4 PS 5 - STAT 4 HD 7 Oct 24 PVC 8 COG 6 PS 6 PS 7 - STAT 5 HD 8 Oct 31 PVC 9 COG 7

Williamson, John

357

Coexistence of WiFi and WiMAX systems based on PS-request protocols.  

PubMed

We introduce both the coexistence zone within the WiMAX frame structure and a PS-Request protocol for the coexistence of WiFi and WiMAX systems sharing a frequency band. Because we know that the PS-Request protocol has drawbacks, we propose a revised PS-Request protocol to improve the performance. Two PS-Request protocols are based on the time division operation (TDO) of WiFi system and WiMAX system to avoid the mutual interference, and use the vestigial power management (PwrMgt) bit within the Frame Control field of the frames transmitted by a WiFi AP. The performance of the revised PS-Request protocol is evaluated by computer simulation, and compared to those of the cases without a coexistence protocol and to the original PS-Request protocol. PMID:22163721

Kim, Jongwoo; Park, Suwon; Rhee, Seung Hyong; Choi, Yong-Hoon; Chung, Young-uk; Hwang, Ho Young

2011-01-01

358

Internal structure and positron annihilation in the four-body MuPs system  

E-print Network

A large number of bound state properties of the four-body muonium-positronium system MuPs (or $\\mu^{+} e^{-}_2 e^{+}$) are determined to high accuracy. Based on these expectation values we predict that the weakly-bound four-body MuPs system has the `two-body' cluster structure Mu + Ps. The two neutral clusters Mu ($\\mu^{+} e^{-}$) and Ps ($e^{+} e^{-}$) interact with each other by the attractive van der Waals forces. By using our expectation values of the electron-positron delta-functions we evaluated the half-life $\\tau_a$ of the MuPs system against annihilation of the electron-positron pair: $\\tau_a = \\frac{1}{\\Gamma} \\approx 4.076453 \\cdot 10^{-10}$ $sec$. The hyperfine structure splitting of the ground state in the MuPs system evaluated with our expectation values is $\\Delta \\approx$ 23.064(5) $MHz$.

Frolov, Alexei M

2014-01-01

359

A novel serine protease from the snake venom of Agkistrodon blomhoffii ussurensis  

PubMed Central

A novel serine protease, ABUSV-SPase, was isolated to homogeneity for the first time from Chinese Agkistrodon blomhoffii ussurensis snake venom, and its enzymatic and structural properties were characterized by multiple techniques. ABUSV-SPase is a stable monomeric protein with a molecular mass of 26,752.6 a.m.u. It reacts optimally with its substrate N?-tosyl-L-arginine methyl ester (TAME) at pH 7.0 and 41 °C. ESI-MS/MS analysis indicates that ABUSV-SPase is a new serine protease, sharing peptide homologies with various snake venom serine proteases, especially the snake venom thrombin-like enzymes of this group, and serine protease precursors. It is a zinc-containing protein, and although zinc is not essential for activity, its replacement by various divalent metal ions, including Mg2+, Mn2+, and Ca2+, increases the TAME hydrolysis activity of the enzyme. The intrinsic fluorescences of Tyr and Trp residues of ABUSV-SPase have emission wavelengths red-shifted by 12.8 nm and 3.6 nm from those of free Tyr and Trp, respectively. The zinc ion increases the hydrophobicity of the environment of the Trp residues, increases the thermostability of the protein, and affects the protein secondary structure to stabilize the enzyme, but appears to have no direct role in its esterase hydrolysis activity. PMID:18817802

Liu, Shuqing; Sun, Ming-Zhong; Sun, Changkai; Zhao, Baochang; Greenaway, Frederick T.; Zheng, Qingyin

2010-01-01

360

D-amino-acid oxidase is involved in D-serine-induced nephrotoxicity.  

PubMed

D-serine is nephrotoxic in rats. Based on circumstantial evidence, it has been suspected that D-amino-acid oxidase is involved in this nephrotoxicity. Since we found that LEA/SENDAI rats lacked D-amino-acid oxidase, we examined whether this enzyme was associated with D-serine-induced nephrotoxicity using the LEA/SENDAI rats and control F344 rats. When d-propargylglycine, which is known to have a nephrotoxic effect through its metabolism by D-amino-acid oxidase, was injected intraperitoneally into the F344 rats, it caused glucosuria and polyuria. However, injection of d-propargylglycine into LEA/SENDAI rats did not cause any glucosuria or polyuria, indicating that D-amino-acid oxidase is definitely not functional in these rats. D-serine was then injected into the F344 and LEA/SENDAI rats. It caused glucosuria and polyuria in the F344 rats but not in the LEA/SENDAI rats. These results indicate clearly that D-amino-acid oxidase is responsible for the D-serine-induced nephrotoxicity. PMID:16300376

Maekawa, Masao; Okamura, Tadashi; Kasai, Noriyuki; Hori, Yuuichi; Summer, Karl H; Konno, Ryuichi

2005-11-01

361

Cross-Linking of Serine Racemase Dimer by Reactive Oxygen Species and Reactive Nitrogen Species  

PubMed Central

Serine racemase (SR) is the only identified enzyme in mammals responsible for isomerization of L-serine to D-serine, a co-agonist at NMDA receptors in the forebrain. Our previous data reported that an apparent SR dimer resistant to SDS and ?-mercaptoethanol was elevated in microglial cells after proinflammatory activation. Because the activation of microglia is typically associated with an oxidative burst, oxidative cross-linking between SR subunits was speculated. In this study, an siRNA technique was employed to confirm the identity of this SR dimer band. The oxidative species potentially responsible for the cross-linking was investigated with recombinant SR protein. The data indicate that nitric oxide, peroxynitrite, and hydroxyl radical were the likely candidates, while superoxide and hydrogen peroxide per se failed to contribute. Furthermore, the mechanism of formation of SR dimer by peroxynitrite oxidation was studied by mass spectrometry. A disulfide bond between Cys6 and Cys113 was identified in both SIN-1 treated SR monomer and dimer. Activity assays indicated that SIN-1 treatment decreased SR activity, confirming our previous conclusion that noncovalent dimer is the most active form of SR. These findings suggest a compensatory feedback whereby the consequences of neuroinflammation might dampen D-serine production to limit excitotoxic stimulation of NMDA receptors. PMID:22354542

Wang, Wei; Barger, Steven W.

2011-01-01

362

Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated With the  

E-print Network

Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated--We observed association between rs17880135 in the 3 region of superoxide dismutase 1 (SOD1) and the incidence activity, serum SOD1 mass, or SOD1 mRNA expres- sion in lymphoblastoid cell lines. CONCLUSIONS

Kidd, Kenneth

363

Design of activated serine-containing catalytic triads with atomic level accuracy  

PubMed Central

A challenge in the computational design of enzymes is that multiple properties must be simultaneously optimized -- substrate-binding, transition state stabilization, and product release -- and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads, and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate-reactivity. Following optimization by yeast-display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest the designs could provide the basis for a new class of organophosphate captures agents. PMID:24705591

Rajagopalan, Sridharan; Wang, Chu; Yu, Kai; Kuzin, Alexandre P.; Richter, Florian; Lew, Scott; Miklos, Aleksandr E.; Matthews, Megan L.; Seetharaman, Jayaraman; Su, Min; Hunt, John. F.; Cravatt, Benjamin F.; Baker, David

2014-01-01

364

Cadmium-tolerance of transgenic Ipomoea aquatica expressing serine acetyltransferase and cysteine synthase  

Microsoft Academic Search

Ipomoea aquatica (water spinach) is a common aquatic plant growing in lakes and wetlands in Southeast Asia. Due to its vigorous growth, they were considered to be potentially useful for remediation of polluted water with, for example, high sulfate and heavy metals. In previous studies, we successfully constructed transgenic I. aquatica plants, which simultaneously expressed two genes encoding serine acetyltransferase

Parichart Moontongchoon; Supachitra Chadchawan; Natchanun Leepipatpiboon; Ancharida Akaracharanya; Atsuhiko Shinmyo; Hiroshi Sano

2008-01-01

365

Kazal-type serine proteinase inhibitors in the midgut of Phlebotomus papatasi  

PubMed Central

Sandflies (Diptera: Psychodidae) are important disease vectors of parasites of the genus Leishmania, as well as bacteria and viruses. Following studies of the midgut transcriptome of Phlebotomus papatasi, the principal vector of Leishmania major, two non-classical Kazal-type serine proteinase inhibitors were identified (PpKzl1 and PpKzl2). Analyses of expression profiles indicated that PpKzl1 and PpKzl2 transcripts are both regulated by blood-feeding in the midgut of P. papatasi and are also expressed in males, larva and pupa. We expressed a recombinant PpKzl2 in a mammalian expression system (CHO-S free style cells) that was applied to in vitro studies to assess serine proteinase inhibition. Recombinant PpKzl2 inhibited ?-chymotrypsin to 9.4% residual activity and also inhibited ?-thrombin and trypsin to 33.5% and 63.9% residual activity, suggesting that native PpKzl2 is an active serine proteinase inhibitor and likely involved in regulating digestive enzymes in the midgut. Early stages of Leishmania are susceptible to killing by digestive proteinases in the sandfly midgut. Thus, characterising serine proteinase inhibitors may provide new targets and strategies to prevent transmission of Leishmania. PMID:24037187

Sigle, Leah Theresa; Ramalho-Ortigao, Marcelo

2013-01-01

366

Lysine-156 and serine-119 are required for LexA repressor cleavage: a possible mechanism.  

PubMed Central

LexA repressor of Escherichia coli is inactivated in vivo by a specific cleavage reaction requiring activated RecA protein. In vitro, cleavage requires activated RecA at neutral pH and proceeds spontaneously at alkaline pH. These two cleavage reactions have similar specificities, suggesting that RecA acts indirectly to stimulate self-cleavage, rather than directly as a protease. We have studied the chemical mechanism of cleavage by using site-directed mutagenesis to change selected amino acid residues in LexA, chosen on the basis of kinetic data, homology to other cleavable repressors, and potential similarity of the mechanism to that of proteases. Serine-119 and lysine-156 were changed to alanine, a residue with an unreactive side chain, resulting in two mutant proteins that had normal repressor function and apparently normal structure, but were completely deficient in both types of cleavage reaction. Serine-119 was also changed to cysteine, another residue with a nucleophilic side chain, resulting in a protein that was cleaved at a significant rate. These and other observations suggest that hydrolysis of the scissile peptide bond proceeds by a mechanism similar to that of serine proteases, with serine-119 being a nucleophile and lysine-156 being an activator. Possible roles for RecA are discussed. Images PMID:3108885

Slilaty, S N; Little, J W

1987-01-01

367

Ectopic expression of the serine protease inhibitor PI9 modulates death receptor -mediated apoptosis.  

E-print Network

to the article. Running title: Inhibition of TNF-ligand-mediated apoptosis by PI9. *) Corresponding author; FADD, Fas-associated death domain; FLIP, FLICE-inhibitory protein; serpin, serine protease inhibitor; TNF, tumor necrosis factor; TRAIL, TNF-related apoptosis-inducing ligand. HALauthormanuscriptinserm

Boyer, Edmond

368

Serine Proteinase Inhibitors from Eggs and Larvae of Tick Boophilus microplus: Purification and Biochemical Characterization  

Microsoft Academic Search

The present study describes the purification, characterization, and comparison of serine proteinase inhibitors during the development of egg and larva phases of the tick Boophilus microplus. Samples were collected of eggs between the first day of hatching and the beginning of eclosion (defined as E1, E2, and E3) and of larvae between the first day of eclosion and the infectant

R. Andreotti; K. C. Malavazi-Piza; S. D. Sasaki; R. J. S. Torquato; A. Gomes; A. S. Tanaka

2001-01-01

369

Multiple active forms of a novel serine protease from Bacillus subtilis  

Microsoft Academic Search

We have cloned and sequenced a gene (epr) encoding a novel serine protease from Bacillus subtilis. Several active forms of the enzyme with molecular masses between 40 and 34 kDa were found in the medium of B. subtilis cultures containing the epr gene cloned on a plasmid. Deletions at the 3' end of the gene, removing up to 240 amino

Reinhold Briickner; Oded Shoseyov; Roy H. Doi

1990-01-01

370

Establishment of a sandwich ELISA for human megsin, a kidney-specific serine protease inhibitor  

Microsoft Academic Search

Background. We previously identified a novel serine protease inhibitor (serpin), megsin, which is predomi- nantly expressed in the kidney. Megsin expression is up-regulated in human and experimental renal diseases associated with mesangial proliferation and expansion, suggesting that urinary megsin may be a novel diagnostic marker for some renal diseases. Methods. We established a specific and sensitive sandwich enzyme-linked immunosorbent assay

Reiko Inagi; Yuko Izuhara; Naoto Tominaga; Masaomi Nangaku; Kiyoshi Kurokawa; Toshio Miyata

371

Gelatinases and serine proteinase inhibitors of seminal plasma and the reproductive tract of turkey ( Meleagris gallopavo)  

Microsoft Academic Search

This study examined proteolytic enzymes and serine proteinase inhibitors in turkey seminal plasma with relation to their distribution within the reproductive tract and to yellow semen syndrome (YSS). Proteases of blood plasma, extracts from the reproductive tract, and seminal plasma were analyzed by gelatin zymography. We found a clear regional distribution of proteolytic enzymes in the turkey reproductive tract. Each

M. Kot?owska; R. Kowalski; J. Glogowski; J. Jankowski; A. Ciereszko

2005-01-01

372

Identification of high molecular weight serine-proteases in Loxosceles intermedia (brown spider) venom  

Microsoft Academic Search

High molecular weight serine-proteases have been identified in Loxosceles intermedia (brown spider) venom. The mechanism by which Loxosceles spp venoms cause dermonecrotic injury (a hallmark of loxoscelism) is currently under investigation, but it seems to be molecularly complex and in some instance proteases might be expected to play a role in this skin lesion. In the present investigation, when we

Silvio S. Veiga; Rafael B. da Silveira; Juliana L. Dreyfuss; Juliana Haoach; Aline M. Pereira; Oldemir C. Mangili; Waldemiro Gremski

2000-01-01

373

Substrate specificity of alkaline serine proteinase isolated from photosynthetic bacterium, Rubrivivax gelatinosus KDDS1.  

PubMed

A novel type of fluorescence resonance energy transfer (FRET) combinatorial libraries were used for the characterization of alkaline serine proteinase produced from Rubrivivax gelatinosus KDDS1. This enzyme was the first serine proteinase characterized from photosynthetic bacteria. The proteinase was found to prefer Met and Phe at the P1 position, Ile and Lys at the P2 position, and Arg and Phe at the P3 position. To date, no serine proteinase has exhibited a preference for Met at the P1 position. Thus, the alkaline serine proteinase from R. gelatinosus KDDS1 is very unique in terms of substrate specificity. A highly sensitive substrate, Boc-Arg-Ile-Met-MCA, was synthesized for kinetic study based on the results reported here. The optimum pH of the enzyme for this substrate was pH 10.7, and the values of kcat, Km, and kcat/Km were 23.7 s(-1), 15.4 microM, and 1.54 microM(-1) s(-1), respectively. PMID:12963024

Tanskul, Somporn; Oda, Kohei; Oyama, Hiroshi; Noparatnaraporn, Napavarn; Tsunemi, Masahiko; Takada, Katsumi

2003-09-26

374

Design of activated serine-containing catalytic triads with atomic-level accuracy.  

PubMed

A challenge in the computational design of enzymes is that multiple properties, including substrate binding, transition state stabilization and product release, must be simultaneously optimized, and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate reactivity. Following optimization by yeast display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest that the designs could provide the basis for a new class of organophosphate capture agents. PMID:24705591

Rajagopalan, Sridharan; Wang, Chu; Yu, Kai; Kuzin, Alexandre P; Richter, Florian; Lew, Scott; Miklos, Aleksandr E; Matthews, Megan L; Seetharaman, Jayaraman; Su, Min; Hunt, John F; Cravatt, Benjamin F; Baker, David

2014-05-01

375

Characterization of aL-serine dehydratase activity from Streptococcus faecalis  

E-print Network

by dilution, dialysis and temperature. Pyridoxal phosphate is not required for maximum activity. L-serine dehydratase is strongly inhibited by Cu2 +, Zn2 +, Hg2 +, p-chloromercuriben- zoate, Tris, borate and acetate; elle est inactivée par dilution, dialyse et par la température. Le pyridoxal phosphate n'est pas exigé

Paris-Sud XI, Université de

376

Characterization of an Extracellular Serine Protease of Fusarium eumartii and its Action on Pathogenesis Related Proteins  

Microsoft Academic Search

Proteases have been proposed as part of the invasion strategies of some pathogenic fungi. In this work, a serine protease produced by the phytopathogenic fungus Fusarium solani f.sp. eumartii was purified and characterized. Purification of the enzyme was accomplished by gel filtration through a Superose 12 column, followed by hydrophobic interaction chromatography in Phenyl Superose and gel filtration chromatography through

Florencia Olivieri; María Eugenia Zanetti; Claudia R. Oliva; Alejandra A. Covarrubias; Claudia A. Casalongué

2002-01-01

377

Interhelical Hydrogen Bonds and Spatial Motifs in Membrane Proteins: Polar Clamps and Serine Zippers  

E-print Network

Interhelical Hydrogen Bonds and Spatial Motifs in Membrane Proteins: Polar Clamps and Serine hydrogen bond connections between TM helices. We find that almost all TM helices have interhelical hydrogen there are interhelical hydrogen bonds between them. We further describe several spatial motifs in the TM regions

Dai, Yang

378

Increases in estrogen receptor-concentration in breast cancer cells promote serine 118/104/106-  

E-print Network

Increases in estrogen receptor- concentration in breast cancer cells promote serine 118 of Wisconsin-Madison, Madison, Wisconsin, USA; and *The Breast Center and Department of Medicine, Baylor College of Medicine, Houston, Texas, USA ABSTRACT A common phenotype in breast cancer is the expansion

Alarid, Elaine T.

379

Amelioration of antigen induced arthritis in rabbits treated with a secreted viral serine proteinase inhibitor  

Microsoft Academic Search

OBJECTIVE: To evaluate the effects of intraarticular administration of SERP-1 protein, a myxoma virus derived antiinflammatory serine protease inhibitor, in an antigen induced arthritis (AIA) model of chronic inflammation. METHODS: AIA was induced in a single joint of 15 rabbits after intraarticular (i.a.) injection of ovalbumin in animals previously immunized to the same agent administered in complete Freund's adjuvant. A

W. P. Maksymowych; N. Nation; P. Nash; J. Macen; A. Lucas; G. McFadden; A. S. Russell

1996-01-01

380

Engineering Escherichia coli for Increased Productivity of Serine-Rich Proteins Based on Proteome Profiling  

PubMed Central

Variations in proteome profiles of Escherichia coli in response to the overproduction of human leptin, a serine-rich (11.6% of total amino acids) protein, were examined by two-dimensional gel electrophoresis. The levels of heat shock proteins increased, while those of protein elongation factors, 30S ribosomal protein, and some enzymes involved in amino acid biosynthesis decreased, after leptin overproduction. Most notably, the levels of enzymes involved in the biosynthesis of serine family amino acids significantly decreased. Based on this information, we designed a strategy to enhance the leptin productivity by manipulating the cysK gene, encoding cysteine synthase A. By coexpression of the cysK gene, we were able to increase the cell growth rate by approximately twofold. Also, the specific leptin productivity could be increased by fourfold. In addition, we found that cysK coexpression can improve the production of another serine-rich protein, interleukin-12 ? chain, suggesting that this strategy may be useful for the production of other serine-rich proteins as well. The approach taken in this study should be useful in designing a strategy for improving recombinant protein production. PMID:14532024

Han, Mee-Jung; Jeong, Ki Jun; Yoo, Jong-Shin; Lee, Sang Yup

2003-01-01

381

Cloning, expression and activity analysis of a novel fibrinolytic serine protease from Arenicola cristata  

NASA Astrophysics Data System (ADS)

The full-length cDNA of a protease gene from a marine annelid Arenicola cristata was amplified through rapid amplification of cDNA ends technique and sequenced. The size of the cDNA was 936 bp in length, including an open reading frame encoding a polypeptide of 270 amino acid residues. The deduced amino acid sequnce consisted of pro- and mature sequences. The protease belonged to the serine protease family because it contained the highly conserved sequence GDSGGP. This protease was novel as it showed a low amino acid sequence similarity (< 40%) to other serine proteases. The gene encoding the active form of A. cristata serine protease was cloned and expressed in E. coli. Purified recombinant protease in a supernatant could dissolve an artificial fibrin plate with plasminogen-rich fibrin, whereas the plasminogen-free fibrin showed no clear zone caused by hydrolysis. This result suggested that the recombinant protease showed an indirect fibrinolytic activity of dissolving fibrin, and was probably a plasminogen activator. A rat model with venous thrombosis was established to demonstrate that the recombinant protease could also hydrolyze blood clot in vivo. Therefore, this recombinant protease may be used as a thrombolytic agent for thrombosis treatment. To our knowledge, this study is the first of reporting the fibrinolytic serine protease gene in A. cristata.

Zhao, Chunling; Ju, Jiyu

2014-10-01

382

Calibration of PS09, PS10, and PS11 trans-Alaska pipeline system strong-motion instruments, with acceleration, velocity, and displacement records of the Denali fault earthquake, 03 November 2002  

USGS Publications Warehouse

In September, 2003, the Alyeska Pipeline Service Company (APSC) and the U.S. Geological Survey (USGS) embarked on a joint effort to extract, test, and calibrate the accelerometers, amplifiers, and bandpass filters from the earthquake monitoring systems (EMS) at Pump Stations 09, 10, and 11 of the Trans-Alaska Pipeline System (TAPS). These were the three closest strong-motion seismographs to the Denali fault when it ruptured in the MW 7.9 earthquake of 03 November 2002 (22:12:41 UTC). The surface rupture is only 3.0 km from PS10 and 55.5 km from PS09 but PS11 is 124.2 km away from a small rupture splay and 126.9 km from the main trace. Here we briefly describe precision calibration results for all three instruments. Included with this report is a link to the seismograms reprocessed using these new calibrations: http://nsmp.wr.usgs.gov/data_sets/20021103_2212_taps.html Calibration information in this paper applies at the time of the Denali fault earthquake (03 November 2002), but not necessarily at other times because equipment at these stations is changed by APSC personnel at irregular intervals. In particular, the equipment at PS09, PS10, and PS11 was changed by our joint crew in September, 2003, so that we could perform these calibrations. The equipment stayed the same from at least the time of the earthquake until that retrieval, and these calibrations apply for that interval.

Evans, John R.; Jensen, E. Gray; Sell, Russell; Stephens, Christopher D.; Nyman, Douglas J.; Hamilton, Robert C.; Hager, William C.

2006-01-01

383

Viable Fertile Mice Generated from Fully Pluripotent iPS Cells Derived from Adult Somatic Cells  

Microsoft Academic Search

Previous studies demonstrated that induced pluripotent stem (iPS) cells could produce viable mice through tetraploid complementation,\\u000a which was thought to be the most stringent test for pluripotency. However, these highly pluripotent iPS cells were previously\\u000a reported to be generated from fibroblasts of embryonic origin. Achieving fully pluripotent iPS cells from multiple cell types,\\u000a especially easily accessible adult tissues, will lead

Xiao-yang Zhao; Wei Li; Zhuo Lv; Lei Liu; Man Tong; Tang Hai; Jie Hao; Xiang Wang; Liu Wang; Fanyi Zeng; Qi Zhou

2010-01-01

384

iPS Cells and Pseudoscience: a Huge Detour in Stem Cell Research  

Microsoft Academic Search

A point-by-point comparison of conventional definition on pseudoscience with the claims made in the iPS cell publications is made here. The conclusion of this comparison is that most claims made for the iPS cells are of nature of pseudoscience . The diversion of stem cell research by the mistakes and deceptions contained in the iPS cell publications represents a great

Shi V. Liu

2008-01-01

385

Continuous production of monoacylglycerols from palm olein in packed-bed reactor with immobilized lipase PS  

Microsoft Academic Search

A packed-bed reactor (PBR) system using immobilized lipase PS as biocatalyst was developed for continuous monoacylglycerols (MAG) production. The condition for continuous MAG production using immobilized lipase PS (IM-PS) of 1.5g (550U) in PBR (0.68cm i.d., 25cm long) was optimized. The effect of molar ratio of glycerol to palm olein, water content in glycerol and residence time on MAG production

Aran H-Kittikun; Wiphum Kaewthong; Benjamas Cheirsilp

2008-01-01

386

Medicare program: conditions of participation (CoPs) for community mental health centers. Final rule.  

PubMed

This final rule establishes, for the first time, conditions of participation (CoPs) that community mental health centers (CMHCs) must meet in order to participate in the Medicare program. These CoPs focus on the care provided to the client, establish requirements for staff and provider operations, and encourage clients to participate in their care plan and treatment. The new CoPs enable CMS to survey CMHCs for compliance with health and safety requirements. PMID:24175363

2013-10-29

387

Lattice-Boltzmann (LB) Fluid Simulation on a Playstation3 (PS3) Cluster  

E-print Network

Lattice-Boltzmann (LB) Fluid Simulation on a Playstation3 (PS3) Cluster Ken-ichi Nomura, Liu Peng, & P. Vashishta, Int'l J. Comput. Sci. 2, 437 ('08) #12;CACS Playstation3 (PS3) Cluster 64bit PowerPC 8 synergistic processing elements · 9 PS3's connected via a Gigabit Ethernet switch · 3.2�2�2�2�9 = 230 sp

Southern California, University of

388

Additive Effects of PS1 and APP Mutations on Secretion of the 42Residue Amyloid ?-Protein  

Microsoft Academic Search

Humans harboring missense mutations in the presenilin 1 (PS1) gene undergo progressive cerebral deposition of the 42-residue amyloid ?-protein (A?42) at an early age and develop severe Alzheimer's disease. A?42is selectively elevated in the conditioned media of cells expressing mutant but not wild-type PS1, indicating that presenilin mutations alter APP processing. Here we analyze the effects of various PS1 mutant

Martin Citron; Christopher B. Eckman; Thekla S. Diehl; Chris Corcoran; Beth L. Ostaszewski; Weiming Xia; Georges Levesque; Peter St. George Hyslop; Steven G. Younkin; Dennis J. Selkoe

1998-01-01

389

Modulation of autoimmune diseases by iPS cells.  

PubMed

Autoimmune disease is typically caused by the activated self-reacted immune cells. The mainstream treatment to autoimmune disorders is composed of different mechanisms of immunosuppression. In recent years, a new subtype of T cells called regulatory T (Treg) cells have been identified to maintain the immune homeostasis in terms of suppressing the activated immune components. According to this discovery, it is suggested that treating autoimmune patients by supplementing Treg cells would be a good choice. However, due to their natural scarcity, it is difficult to isolate a desired number of Treg for this therapeutical approach. Here, we report that by using stem cells, especially the induced pluripotent stem (iPS) cells, we are able to generate a significant amount of Treg cells for the autoimmune prevention and treatment. PMID:25173398

Lei, Fengyang; Haque, Rizwanul; Xiong, Xiaofang; Song, Jianxun

2014-01-01

390

Development and characterization of sub-100 ps photomultiplier tubesa)  

NASA Astrophysics Data System (ADS)

We describe the evaluation of a microchannel plate (MCP) photomultiplier tube (PMT), incorporating a 3 ?m pore MCP and constant voltage anode and cathode gaps. The use of the small pore size results in PMTs with response functions of the order of 85 ps full-width-half-maximum, while the constant electric field across the anode and cathode gaps produces a uniform response function over the entire operating range of the device. The PMT was characterized on a number of facilities and employed on gas Cherenkov detectors fielded on various deuterium tritium fuel (DT) implosions on the Omega Laser Facility at the University of Rochester. The Cherenkov detectors are part of diagnostic development to measure Gamma ray reaction history for DT implosions on the National Ignition Facility.

Horsfield, C. J.; Rubery, M. S.; Mack, J. M.; Young, C. S.; Herrmann, H. W.; Caldwell, S. E.; Evans, S. C.; Sedilleo, T. J.; Kim, Y. H.; McEvoy, A.; Milnes, J. S.; Howorth, J.; Davis, B.; O'Gara, P. M.; Garza, I.; Miller, E. K.; Stoeffl, W.; Ali, Z.

2010-10-01

391

Synthesis of PS colloidal crystal templates and ordered ZnO porous thin films by dip-drawing method  

Microsoft Academic Search

Polystyrene spheres (PS) were synthesized by an emulsifier-free emulsion polymerization technique and the PS colloidal crystal templates were assembled orderly on clean glass substrates by dip-drawing method from emulsion of PS. Porous ZnO thin films were prepared by filling the ZnO sol into the spaces among the close-packed PS templates and then annealing to remove the PS templates. The effects

Zhifeng Liu; Zhengguo Jin; Wei Li; Jijun Qiu; Juan Zhao; Xiaoxin Liu

2006-01-01

392

Application of iPS Cells in Dental Bioengineering and Beyond.  

PubMed

The stem-cell-based tissue-engineering approaches are widely applied in establishing functional organs and tissues for regenerative medicine. Successful generation of induced pluripotent stem cells (iPS cells) and rapid progress of related technical platform provide great promise in the development of regenerative medicine, including organ regeneration. We have previously reported that iPS cells could be an appealing stem cells source contributing to tooth regeneration. In the present paper, we mainly review the application of iPS technology in dental bioengineering and discuss the challenges for iPS cells in the whole tooth regeneration. PMID:24917330

Liu, Pengfei; Zhang, Yanmei; Chen, Shubin; Cai, Jinglei; Pei, Duanqing

2014-10-01

393

PS2 protein in breast carcinomas: cut-off value of estrogen-regulated expression.  

PubMed

This study includes 152 patients with histologically confirmed breast carcinoma. Steroid hormone receptors (SR), estrogen (ER) and progesteron (PR) receptors, and pS2 protein were assayed on the same cytosolic extract in accordance with the recommendation of EORTC. Our results showed menopausal- and histologic grade-related expression of pS2 protein. Unfavorable carcinoma subgroups, in relation to expression of pS2 protein were defined: postmenopausal carcinomas with histologic grade II, and pre-, as well as postmenopausal carcinomas with histologic grade III. There were overlappings of individual pS2 protein values between favorable and unfavorable carcinoma subgroups in relation to the expression of pS2 protein. Otherwise, no overlapping of pS2 protein values was obtained between ER-positive and ER-negative carcinomas within defined unfavorable menopausal - and histologic grade-related expression of pS2 protein subgroups. The highest pS2 protein level observed in ER-negative unfavorable subgroups (15 ng/mg) was considered as the cut-off value which defined estrogen-regulated expression of pS2 protein. PMID:11327531

Nikoli?-Vukosavljevi?, D; Gruji?-Adanja, G; Jankovi?, R; Neskovi?-Konstantinovi?, Z; Brankovi?-Magi?, M

2001-01-01

394

Dual Function of a Bee Venom Serine Protease: Prophenoloxidase-Activating Factor in Arthropods and Fibrin(ogen)olytic Enzyme in Mammals  

Microsoft Academic Search

Bee venom contains a variety of peptides and enzymes, including serine proteases. While the presence of serine proteases in bee venom has been demonstrated, the role of these proteins in bee venom has not been elucidated. Furthermore, there is currently no information available regarding the melanization response or the fibrin(ogen)olytic activity of bee venom serine protease, and the molecular mechanism

Young Moo Choo; Kwang Sik Lee; Hyung Joo Yoon; Bo Yeon Kim; Mi Ri Sohn; Jong Yul Roh; Yeon Ho Je; Nam Jung Kim; Iksoo Kim; Soo Dong Woo; Hung Dae Sohn; Byung Rae Jin; François Leulier

2010-01-01

395

Purification and characterization of a group of five novel peptide serine protease inhibitors from ovaries of the desert locust, Schistocerca gregaria  

Microsoft Academic Search

The ovary of the desert locust, Schistocerca gregaria, contains multiple inhibitors of serine proteases. Five serine protease inhibitors, designated SGPI-1–5 (Schistocerca gregaria protease inhibitors) were purified from methanolic extracts of mature ovaries and analyzed by mass spectrometry and amino acid sequencing. The revealed primary structures display amino acid similarities and are related to the serine protease inhibitors identified in the

Ahmed Hamdaoui; Said Wataleb; Bart Devreese; Shean-Jaw Chiou; Jozef Vanden Broeck; Jozef Van Beeumen; Arnold De Loof; Liliane Schoofs

1998-01-01

396

The Postnatal Development of d-Serine in the Retinas of Two Mouse Strains, Including a Mutant Mouse with a Deficiency in d-Amino Acid Oxidase and a Serine Racemase Knockout Mouse.  

PubMed

d-Serine, an N-methyl d-aspartate receptor coagonist, and its regulatory enzymes, d-amino acid oxidase (DAO; degradation) and serine racemase (SR; synthesis), have been implicated in crucial roles of the developing central nervous system, yet the functional position that they play in regulating the availability of d-serine throughout development of the mammalian retina is not well-known. Using capillary electrophoresis and a sensitive method of enantiomeric amino acid separation, we were able to determine total levels of d-serine at specific ages during postnatal development of the mouse retina in two different strains of mice, one of which contained a loss-of-function point mutation for DAO while the other was a SR knockout line. Each mouse line was tested against conspecific wild type (WT) mice for each genetic strain. The universal trend in all WT and transgenic mice was a large amount of total retinal d-serine at postnatal age 2 (P2), followed by a dramatic decrease as the mice matured into adulthood (P70-80). SR knockout mice retinas had 41% less d-serine than WT retinas at P2, and 10 times less as an adult. DAO mutant mice retinas had significantly elevated levels of d-serine when compared to WT retinas at P2 (217%), P4 (223%), P8 (194%), and adulthood (227%). PMID:25083578

Romero, Gabriel E; Lockridge, Amber D; Morgans, Catherine W; Bandyopadhyay, Dipankar; Miller, Robert F

2014-09-17

397

Effect of nano CdS dispersion on thermal conductivity of PS/PVC and PS/PMMA polymeric blend nanocomposites  

NASA Astrophysics Data System (ADS)

The effect of dispersion of CdS nano-filler particles in respective PS/PVC and PS/PMMA polymer blend matrices on the effective thermal conductivity has been studied through Hot Disk Thermal Constant Analyzer based on transient plane source (TPS) technique. The thick film samples have been prepared by dispersing nano-filler particles of CdS (6 wt%) in respective PS/PVC and PS/PMMA binary blend matrices. The nanocomposite nature of prepared samples ascertained through small angle X-ray scattering (SAXS) as well as transmission electron microscopy (TEM) measurements. It is observed that at room temperature nano CdS dispersed polymeric blend samples offer higher effective thermal conductivity.

Mathur, Vishal; Patidar, Dinesh; Sharma, Kananbala

2014-09-01

398

Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation  

PubMed Central

Despite the fact that most cancer cells display high glycolytic activity, cancer cells selectively express the less active M2 isoform of pyruvate kinase (PKM2). Here we demonstrate that PKM2 expression makes a critical regulatory contribution to the serine synthetic pathway. In the absence of serine, an allosteric activator of PKM2, glycolytic efflux to lactate is significantly reduced in PKM2-expressing cells. This inhibition of PKM2 results in the accumulation of glycolytic intermediates that feed into serine synthesis. As a consequence, PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot. Cellular detection of serine depletion depends on general control nonderepressible 2 kinase-activating transcription factor 4 (GCN2-ATF4) pathway activation and results in increased expression of enzymes required for serine synthesis from the accumulating glycolytic precursors. These findings suggest that tumor cells use serine-dependent regulation of PKM2 and GCN2 to modulate the flux of glycolytic intermediates in support of cell proliferation. PMID:22509023

Ye, Jiangbin; Mancuso, Anthony; Tong, Xuemei; Ward, Patrick S.; Fan, Jing; Rabinowitz, Joshua D.; Thompson, Craig B.

2012-01-01

399

Chronic D-serine reverses arc expression and partially rescues dendritic abnormalities in a mouse model of NMDA receptor hypofunction.  

PubMed

Activity-regulated cytoskeleton-associated protein (Arc) is an immediate early gene that is expressed almost exclusively in glutamatergic neurons. Arc protein is enriched in the postsynaptic density (PSD) and colocalizes with the N-methyl-D-aspartate receptor (NMDAR) complex. Arc transcription is positively modulated by NMDAR activity and is important for dendritic spine plasticity. Genetic ablation of serine racemase (SR-/-), the enzyme that converts L-serine to D-serine, a coagonist at the NMDAR, reduces dendritic spine density in the hippocampus. Here we demonstrate that SR deficient (SR-/-) mice also have reduced Arc protein expression in the hippocampus that can be reversed with chronic D-serine administration in adulthood. Furthermore, D-serine treatment partially rescues the hippocampal spine deficit in SR-/- mice. These results demonstrate the importance of D-serine in regulating the hippocampal expression of Arc in vivo. In addition, our findings underscore the potential utility of using the glycine modulatory site agonist D-serine to treat disorders that exhibit Arc and dendritic spine dysregulation as a consequence of NMDAR hypofunction, such as schizophrenia. PMID:24915645

Balu, Darrick T; Coyle, Joseph T

2014-09-01

400

In vitro Characterization of a small molecule inhibitor of the alanine serine cysteine transporter -1 (SLC7A10).  

PubMed

NMDA receptor hypofunction is hypothesized to contribute to cognitive deficits associated with schizophrenia. Since direct activation of NMDA receptors is associated with serious adverse effects, modulation of the NMDA co-agonists, glycine or D-serine, represents a viable alternative therapeutic approach. Indeed, clinical trials with glycine and D-serine have shown positive results, although concerns over toxicity related to the high-doses required for efficacy remain. Synaptic concentrations of D-serine and glycine are regulated by the amino acid transporter alanine serine cysteine transporter-1 (asc-1). Inhibition of asc-1 would increase synaptic D-serine and possibly glycine, eliminating the need for high-dose systemic D-serine or glycine treatment. In this manuscript, we characterize Compound 1 (BMS-466442), the first known small molecule inhibitor of asc-1. Compound 1 selectively inhibited asc-1 mediated D-serine uptake with nanomolar potency in multiple cellular systems. Moreover, Compound 1 inhibited asc-1 but was not a competitive substrate for this transporter. Compound 1 is the first reported selective inhibitor of the asc-1 transporter and may provide a new path for the development of asc-1 inhibitors for the treatment of schizophrenia. PMID:24266811

Brown, Jeffrey M; Hunihan, Lisa; Prack, Margaret M; Harden, David G; Bronson, Joanne; Dzierba, Carolyn D; Gentles, Robert G; Hendricson, Adam; Krause, Rudy; Macor, John E; Westphal, Ryan S

2014-04-01

401

A CBP Binding Transcriptional Repressor Produced by the PS1\\/?-Cleavage of N-Cadherin Is Inhibited by PS1 FAD Mutations  

Microsoft Academic Search

Presenilin1 (PS1), a protein implicated in Alzheimer's disease (AD), forms complexes with N-cadherin, a transmembrane protein with important neuronal and synaptic functions. Here, we show that a PS1-dependent ?-secretase protease activity promotes an ?-like cleavage of N-cadherin to produce its intracellular domain peptide, N-Cad\\/CTF2. NMDA receptor agonists stimulate N-Cad\\/CTF2 production suggesting that this receptor regulates the ?-cleavage of N-cadherin. N-Cad\\/CTF2

Philippe Marambaud; Paul H Wen; Anindita Dutt; Junichi Shioi; Akihiko Takashima; Robert Siman; Nikolaos K Robakis

2003-01-01

402

Neural Stem Cells Differentiated From iPS Cells Spontaneously Regain Pluripotency.  

PubMed

Differentiated somatic cells can be reprogrammed into pluripotent stem cells by transduction of exogenous reprogramming factors. After induced pluripotent stem (iPS) cells are established, exogenous genes are silenced. In the pluripotent state, retroviral genes integrated in the host genome are kept inactive through epigenetic transcriptional regulation. In this study, we tried to determine whether exogenous genes remain silenced or are reactivated upon loss of pluripotency or on differentiation using an in vitro system. We induced differentiation of iPS cells into neural stem cells (NSCs) in vitro; the NSCs appeared morphologically indistinguishable from brain-derived NSCs and stained positive for the NSC markers Nestin and Sox2. These iPS cell-derived NSCs (iPS-NSCs) were also capable of differentiating into all three neural subtypes. Interestingly, iPS-NSCs spontaneously formed aggregates on long-term culture and showed reactivation of the Oct4-GFP marker, which was followed by the formation of embryonic stem cell-like colonies. The spontaneously reverted green fluorescent protein (GFP)-positive (iPS-NSC-GFP(+) ) cells expressed high levels of pluripotency markers (Oct4 and Nanog) and formed germline chimeras, indicating that iPS-NSC-GFP(+) cells had the same pluripotency as the original iPS cells. The reactivation of silenced exogenous genes was tightly correlated with the downregulation of DNA methyltransferases (Dnmts) during differentiation of iPS cells. This phenomenon was not observed in doxycycline-inducible iPS cells, where the reactivation of exogenous genes could be induced only by doxycycline treatment. These results indicate that pluripotency can be regained through reactivation of exogenous genes, which is associated with dynamic change of Dnmt levels during differentiation of iPS cells. Stem Cells 2014;32:2596-2604. PMID:24898298

Choi, Hyun Woo; Kim, Jong Soo; Choi, Sol; Hong, Yean Ju; Kim, Min Jung; Seo, Han Geuk; Do, Jeong Tae

2014-10-01

403

Generation of Endoderm derived Human iPS cells from Primary Hepatocytes  

PubMed Central

Recent advances in induced pluripotent stem (iPS) cell research significantly changed our perspective on regenerative medicine. Patient specific iPS cells have been derived not only for disease modeling but also as sources for cell replacement therapy. However, there have been insufficient data to prove that iPS cells are functionally equivalent to hES cells or safer than hES cells. There are several important issues which need to be addressed and foremost are the safety and efficacy of human iPS cells from different origins. Human iPS cells have been derived mostly from cells originated from mesoderm, with a few cases from ectoderm. So far there has been no report of endoderm derived human iPS cells, preventing comprehensive comparative investigations on the quality of human iPS cells from different origins. Here we show for the first time reprogramming of human endoderm derived cells (i.e. primary hepatocytes) to pluripotency. Hepatocyte-derived iPS cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, and differentiation potential in embryoid body formation and teratoma assays. In addition, these cells were able to directly differentiate into definitive endoderm, hepatic progenitors, and mature hepatocytes. The technology to develop endoderm derived human iPS cell lines, together with other established cell lines, will provide a foundation to elucidate the mechanisms of cellular reprogramming and to study the safety and efficacy of differentially originated human iPS cells for cell therapy. For studying liver disease pathogenesis, this technology also provides a potentially more amenable system to generate liver disease specific iPS cells. PMID:20432258

Liu, Hua; Ye, Zhaohui; Kim, Yong-Hak; Sharkis, Saul; Jang, Yoon-Young

2010-01-01

404

Serine Hydroxymethyltransferase from Mung Bean (Vigna radiata) Is Not a Pyridoxal-5?-Phosphate-Dependent Enzyme 1  

PubMed Central

Serine hydroxymethyltransferase from mammalian and bacterial sources is a pyridoxal-5?-phosphate-containing enzyme, but the requirement of pyridoxal-5?-phosphate for the activity of the enzyme from plant sources is not clear. The specific activity of serine hydroxymethyltransferase isolated from mung bean (Vigna radiata) seedlings in the presence and absence of pyridoxal-5?-phosphate was comparable at every step of the purification procedure. The mung bean enzyme did not show the characteristic visible absorbance spectrum of a pyridoxal-5?-phosphate protein. Unlike the enzymes from sheep, monkey, and human liver, which were converted to the apoenzyme upon treatment with l-cysteine and dialysis, the mung bean enzyme similarly treated was fully active. Additional evidence in support of the suggestion that pyridoxal-5?-phosphate may not be required for the mung bean enzyme was the observation that pencillamine, a well-known inhibitor of pyridoxal-5?-phosphate enzymes, did not perturb the enzyme spectrum or inhibit the activity of mung bean serine hydroxymethyltransferase. The sheep liver enzyme upon interaction with O-amino-d-serine gave a fluorescence spectrum with an emission maximum at 455 nm when excited at 360 nm. A 100-fold higher concentration of mung bean enzyme-O-amino-d-serine complex did not yield a fluorescence spectrum. The following observations suggest that pyridoxal-5?-phosphate normally present as a coenzyme in serine hydroxymethyltransferase was probably replaced in mung bean serine hydroxymethyltransferase by a covalently bound carbonyl group: (a) inhibition by phenylhydrazine and hydroxylamine, which could not be reversed by dialysis and or addition of pyridoxal-5? phosphate; (b) irreversible inactivation by sodium borohydride; (c) a spectrum characteristic of a phenylhydrazone upon interaction with phenylhydrazine; and (d) the covalent labeling of the enzyme with substrate/product serine and glycine upon reduction with sodium borohydride. These results indicate that in mung bean serine hydroxymethyltransferase, a covalently bound carbonyl group has probably replaced the pyridoxal-5?-phosphate that is present in the mammalian and bacterial enzymes. PMID:16667990

Sukanya, Narasimhan; Vijaya, M.; Savithri, H. S.; Radhakrishnan, A. N.; Rao, N. Appaji

1991-01-01

405

Functional evidence for D-serine inhibition of non-N-methyl-D-aspartate ionotropic glutamate receptors in retinal neurons.  

PubMed

D-Serine is an important signaling molecule throughout the central nervous system, acting as an N-methyl-D-aspartate (NMDA) receptor coagonist. This study investigated the D-serine modulation of non-NMDA ionotropic glutamate receptors expressed by inner retinal neurons. We first identified that the degradation of endogenous retinal D-serine, by application of D-amino acid oxidase, caused an enhancement of kainate- and ?-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor-mediated calcium responses from the ganglion cell layer of the isolated rat retina and light-evoked responses obtained by multi-electrode array recordings from the guinea pig retina. Approximately 30-45% of cells were endogenously inhibited by D-serine, as suggested by the effect of D-amino acid oxidase. Conversely, bath application of D-serine caused a reduction in multi-electrode array recorded responses and decreased kainate, but not potassium-induced calcium responses, in a concentration-dependent manner (IC(50), 280 ?m). Using cultured retinal ganglion cells to reduce network influences, D-serine reduced kainate-induced calcium responses and AMPA induced whole-cell currents. Finally, the inhibitory effect of D-serine on the kainate-induced calcium response was abolished by IEM 1460, thereby identifying calcium-permeable AMPA receptors as a potential target for D-serine. To our knowledge, this is the first study to address specifically the effect of D-serine on AMPA/kainate receptors in intact central nervous system tissue, to identify its effect on calcium permeable AMPA receptors and to report the endogenous inhibition of AMPA/kainate receptors. PMID:22128843

Daniels, Bryan A; Wood, Leah; Tremblay, François; Baldridge, William H

2012-01-01

406

Preliminary Evaluation of PS300: A New Self-Lubricating High Temperature Composite Coating for Use to 800 C  

NASA Technical Reports Server (NTRS)

This paper introduces PS300, a plasma sprayed, self-lubricating composite coating for use in sliding contacts at temperatures to 800 C. PS300 is a metal bonded chrome oxide coating with silver and BaF2/CaF2 eutectic solid lubricant additives. PS300 is similar to PS200, a chromium carbide based coating, which is currently being investigated for a variety of tribological applications. In pin-on-disk testing up to 650 C, PS300 exhibited comparable friction and wear properties to PS200. The PS300 matrix, which is predominantly chromium oxide rather than chromium carbide, does not require diamond grinding and polishes readily with silicon carbide abrasives greatly reducing manufacturing costs compared to PS200. It is anticipated that PS300 has potential for sliding bearing and seal applications in both aerospace and general industry.

Dellacorte, C.; Edmonds, B. J.

1995-01-01

407

The midgut of Aedes albopictus females expresses active trypsin-like serine peptidases  

PubMed Central

Background Aedes albopictus is widely distributed across tropical and sub-tropical regions and is associated with the transmission of several arboviruses. Although this species is increasingly relevant to public health due its ability to successfully colonize both urban and rural habitats, favoring the dispersion of viral infections, little is known about its biochemical traits, with all assumptions made based on studies of A. aegypti. In previous studies we characterized the peptidase profile of pre-imaginal stages of A. albopictus and we reported the first proteomic analysis of the midgut from sugar-fed females of this insect species. Methods In the present work, we further analyzed the peptidase expression in the midgut of sugar-fed females using 1DE-substrate gel zymography, two-dimensional electrophoresis (2DE), mass spectrometry (MS), and protein identification based on similarity. Results The combination of zymography, in solution assays using fluorescent substrates and 2DE-MS/MS allowed us to identify the active serine peptidase “fingerprint” in the midgut of A. albopictus females. Zymographic analysis revealed a proteolytic profile composed of at least 13 bands ranging from ~25 to 250 kDa, which were identified as trypsin-like serine peptidases by using specific inhibitors of this class of enzymes. Concomitant use of the fluorogenic substrate Z-Phe-Arg-AMC and trypsin-like serine protease inhibitors corroborated the zymographic findings. Our proteomic approach allowed the identification of two different trypsin-like serine peptidases and one chymotrypsin in protein spots of the alkaline region in 2DE map of the A. albopictus female midgut. Identification of these protein coding genes was achieved by similarity to the A. aegypti genome sequences using Mascot and OMSSA search engines. Conclusion These results allowed us to detect, identify and characterize the expression of active trypsin-like serine peptidases in the midgut of sugar-fed A. albopictus females. In addition, proteomic analysis allowed us to confidently assign the expression of two trypsin genes and one chymotrypsin gene to the midgut of this mosquito. These results contribute to the gene annotation in this species of unknown genome and represent a small but important step toward the protein-level functional and localization assignment of trypsin-like serine peptidase genes in the Aedes genus. PMID:24886160

2014-01-01

408

Rapid loss of perforin and serine protease RNA in cytotoxic lymphocytes exposed to sensitive targets.  

PubMed Central

We have previously reported that cytotoxic lymphocytes, when exposed to sensitive target cells, temporarily lose their lytic potential. The mechanism leading to this loss of lytic activity is still unknown but it is reversible and the lytic potency can be recovered when the effector cells are incubated with interleukin-2 (IL-2) for 12-14 hr. In this study, we have investigated the regulation of RNA coding for perforin and for two serine proteases, HSP1 and HSP2, in cytotoxic lymphocytes exposed to sensitive targets. Perforin and the two serine proteases are contained in granules of major histocompatibility complex (MHC)-restricted and non-MHC-restricted cytotoxic lymphocytes, but their exact role in the lytic mechanism is still debated. Here we used four different human cytotoxic lymphocytes (CTL) as effector cells: an MHC-restricted CTL (SG-CTL), a non-MHC-restricted CTL (IE6), a natural killer (NK)-like cell line (3.3) and lymphokine-activated killer (LAK) cells. In all effector cells we observed a rapid loss of perforin and of serine protease RNAs within 5 min following the addition of sensitive targets. The effector cells recovered the RNA messages as early as 30 min, although the kinetics of recovery was faster with CTL than with NK-like or LAK effector cells. When we exposed the effector cells to resistant targets we did not detect any loss of perforin or serine protease RNAs. Incubation of the effector cells with cycloheximide, prior to the addition of sensitive targets, did not block message loss, indicating that de novo protein synthesis was not required in this process. Cycloheximide treatment, however, inhibited the recovery of perforin and serine protease RNAs. Taken together, our results indicate that the target-mediated loss of lytic activity in cytotoxic lymphocytes may be a consequence of the down-regulation of perforin or of serine protease transcripts, or both. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1721042

Bajpai, A; Kwon, B S; Brahmi, Z

1991-01-01

409

Biochemical characterization and comparative analysis of two distinct serine proteases from Bothrops pirajai snake venom.  

PubMed

This study reports the isolation and biochemical characterization of two different serine proteases from Bothrops pirajai snake venom, thus providing a comparative analysis of the enzymes. The isolation process consisted of three consecutive chromatographic steps (Sephacryl S-200, Benzamidine Sepharose and C2/C18), resulting in two serine proteases, named BpirSP27 and BpirSP41 after their molecular masses by mass spectrometry (27,121 and 40,639 Da, respectively). Estimation by SDS-PAGE under denaturing conditions showed that, when deglycosylated with PNGase F, BpirSP27 and BpirSP41 had their molecular masses reduced by approximately 15 and 42%, respectively. Both are acidic enzymes, with pI of approximately 4.7 for BpirSP27 and 3.7 for BpirSP41, and their N-terminal amino acid sequences showed 57% identity to each other, with high similarity to the sequences of other snake venom serine proteases (SVSPs). The enzymes showed different actions on bovine fibrinogen, with BpirSP27 acting preferentially on the B? chain and BpirSP41 on both A? and B? chains. The two serine proteases were also able to degrade fibrin and blood clots in vitro depending on the doses and incubation periods, with higher results for BpirSP41. Both enzymes coagulated the human plasma in a dose-dependent manner, and BpirSP41 showed a higher coagulant potential, with minimum coagulant dose (MCD) of ?3.5 ?g versus 20 ?g for BpirSP27. The enzymes were capable of hydrolyzing different chromogenic substrates, including S-2238 for thrombin-like enzymes, but only BpirSP27 acted on the substrate S-2251 for plasmin. They also showed high stability against variations of temperature and pH, but their activities were significantly reduced after preincubation with Cu(2+) ion and specific serine protease inhibitors. In addition, BpirSP27 induced aggregation of washed platelets to a greater extent than BpirSP41. The results showed significant structural and functional differences between B. pirajai serine proteases, providing interesting insights into the structure-function relationship of SVSPs. PMID:22819993

Menaldo, Danilo Luccas; Bernardes, Carolina Petri; Santos-Filho, Norival Alves; Moura, Laura de Andrade; Fuly, André Lopes; Arantes, Eliane Candiani; Sampaio, Suely Vilela

2012-12-01

410

Deficiency in the Inhibitory Serine-Phosphorylation of Glycogen Synthase Kinase3 Increases Sensitivity to Mood Disturbances  

Microsoft Academic Search

Bipolar disorder, characterized by extreme manic and depressive moods, is a prevalent debilitating disease of unknown etiology. Because mood stabilizers, antipsychotics, antidepressants, and mood-regulating neuromodulators increase the inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3), we hypothesized that deficient GSK3 serine-phosphorylation may increase vulnerability to mood-related behavioral disturbances. This was tested by measuring behavioral characteristics of GSK3?\\/?21A\\/21A\\/9A\\/9A knockin mice with serine-to-alanine

Abigail Polter; Eléonore Beurel; Sufen Yang; Rakesha Garner; Ling Song; Courtney A Miller; J David Sweatt; Lori McMahon; Alfred A Bartolucci; Xiaohua Li; Richard S Jope; X Li

2010-01-01

411

Beneficial effects of L-serine and glycine in the management of seizures in 3-phosphoglycerate dehydrogenase deficiency.  

PubMed

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is an inborn error of serine biosynthesis. Patients are affected with congenital microcephaly, psychomotor retardation, and intractable seizures. The effects of oral treatment with amino acids were investigated in 2 siblings. L-Serine up to 500 mg/kg/day was not sufficient for seizure control. Addition of glycine 200 mg/kg/day resulted in complete disappearance of seizures. Electroencephalographic abnormalities gradually resolved after 6 months. We conclude that 3-PGDH can be treated effectively by a combination of L-serine and glycine. PMID:9708551

de Koning, T J; Duran, M; Dorland, L; Gooskens, R; Van Schaftingen, E; Jaeken, J; Blau, N; Berger, R; Poll-The, B T

1998-08-01

412

Inhibition of PS II photochemistry by PAR and UV radiation in natural phytoplankton communities  

Microsoft Academic Search

The effects of PAR and UV radiation on PS II photochemistry were examined in natural phytoplankton communities from coastal waters off Rhode Island (USA) and the subtropical Pacific. The photochemical energy conversion efficiency, the functional absorption cross section and the kinetics of electron transfer on the acceptor side of PS II were derived from variable fluorescence parameters using both pump

Ilya R. Vassiliev; Ondrej Prasil; Kevin D. Wyman; Zbigniew Kolber; Alfred K. Hanson; Jennifer E. Prentice; Paul G. Falkowski

1994-01-01

413

The Directed Differentiation of Human iPS Cells into Kidney Podocytes  

PubMed Central

The loss of glomerular podocytes is a key event in the progression of chronic kidney disease resulting in proteinuria and declining function. Podocytes are slow cycling cells that are considered terminally differentiated. Here we provide the first report of the directed differentiation of induced pluripotent stem (iPS) cells to generate kidney cells with podocyte features. The iPS-derived podocytes share a morphological phenotype analogous with cultured human podocytes. Following 10 days of directed differentiation, iPS podocytes had an up-regulated expression of mRNA and protein localization for podocyte markers including synaptopodin, nephrin and Wilm’s tumour protein (WT1), combined with a down-regulation of the stem cell marker OCT3/4. In contrast to human podocytes that become quiescent in culture, iPS-derived cells maintain a proliferative capacity suggestive of a more immature phenotype. The transduction of iPS podocytes with fluorescent labeled-talin that were immunostained with podocin showed a cytoplasmic contractile response to angiotensin II (AII). A permeability assay provided functional evidence of albumin uptake in the cytoplasm of iPS podocytes comparable to human podocytes. Moreover, labeled iPS-derived podocytes were found to integrate into reaggregated metanephric kidney explants where they incorporated into developing glomeruli and co-expressed WT1. This study establishes the differentiation of iPS cells to kidney podocytes that will be useful for screening new treatments, understanding podocyte pathogenesis, and offering possibilities for regenerative medicine. PMID:23029522

Song, Bi; Smink, Alexandra M.; Jones, Christina V.; Callaghan, Judy M.; Firth, Stephen D.; Bernard, Claude A.; Laslett, Andrew L.; Kerr, Peter G.; Ricardo, Sharon D.

2012-01-01

414

NASA PS400: A New Temperature Solid Lubricant Coating for High Temperature Wear Applications  

NASA Technical Reports Server (NTRS)

A new solid lubricant coating, NASA PS400, has been developed for high temperature tribological applications. This plasma sprayed coating is a variant of the patented PS304 coating and has been formulated to provide higher density, smoother surface finish and better dimensional stability than PS304. PS400 is comprised of a nickel-molybdenum binder that provides strength, creep resistance and extreme oxidative and dimensional stability. Chromium oxide, silver and barium-calcium fluoride eutectic are added to the binder to form PS400.Tribological properties were evaluated with a pin-on-disk test rig in sliding contact to 650 C. Coating material samples were exposed to air, argon and vacuum at 760 C followed by cross section microscopic analysis to assess microstructure stability. Oil-Free microturbine engine hot section foil bearing tests were undertaken to assess PS400 s suitability for hot foil gas bearing applications. The preliminary results indicate that PS400 exhibits tribological characteristics comparable to the PS304 coating but with enhanced creep resistance and dimensional stability suitable for demanding, dynamic applications.

DellaCorte, C.; Edmonds, B. J.

2009-01-01

415

Role of propagating ionisation fronts in semiconductor generation of sub-ps THz radiation  

E-print Network

Role of propagating ionisation fronts in semiconductor generation of sub-ps THz radiation S, United Kingdom Abstract Observations of a directional asymmetry in the sub-ps THz radiation generated standing and widely accepted surface-layer current-surge description of the THz emission process. A model

Strathclyde, University of

416

Multi-frame x ray imaging with a large area 40ps camera  

Microsoft Academic Search

The authors have developed a large area short pulse framing camera that is capable of sixteen frames and shutter times of 40ps per frame. This is accomplished with a high fidelity electrical circuit and a L\\/D = 20 microchannel plate, driven by a short pulse (80ps) high amplitude electrical driver. They show results of this work they have done to

P. M. Bell; J. D. Kilkenny; O. L. Landen; R. L. Hanks; J. D. Wiedwald; D. K. Bradley

1992-01-01

417

Multiframe x-ray imaging with a large-area 40ps camera  

Microsoft Academic Search

We have developed a large area short pulse framing camera that is capable of sixteen frames and shutter times of 40 ps per frame. This is accomplished with a high fidelity electrical circuit and a L\\/D equals 20 microchannel plate, driven by a short pulse (80 ps) high amplitude electrical driver. We show results of this work we have done

Perry M. Bell; Joseph D. Kilkenny; Otto L. Landen; Roy L. Hanks; Jay D. Wiedwald; David K. Bradley

1993-01-01

418

Le modle WS-PS et le chmage d'quilibre Antoine d'Autume  

E-print Network

'Hôpital, 75013 Paris halshs-00452567,version1-2Feb2010 #12;Résumé : Le modèle WS-PS (wage-setting, price travailleurs. Abstract : The now standard WS- PS (wage-setting, price-setting) introduced by Layard- Nickell utility and production functions, on one hand, and the indexation of unemployment subsidies, on the other

Boyer, Edmond

419

Complete Nucleotide Sequence of Canine Distemper Virus CDV-PS, Isolated from Dogs in China  

PubMed Central

A new strain of canine distemper virus, CDV-PS, has been isolated from dogs in China, and its complete genome has been sequenced and analyzed. The phylogenetic analysis suggests that CDV-PS belongs to the Asia-1 cluster and has low identity to the vaccine strain. PMID:23682141

Yi, Li; Xu, Hongli; Wang, Jianke; Cheng, Yuening; Zhang, Hailing; Yan, Xijun

2013-01-01

420

30/01/2014 PS1061 Sensation & Perception #3 JMZ 1 Illusions as Key to Reality  

E-print Network

1 30/01/2014 PS1061 Sensation & Perception #3 JMZ 1 Illusions as Key to Reality Johannes M. Zanker Sensation & Perception #1 JMZ 2 Learning Outcomes at the end of this lecture, you should be able in science 30/01/2014 PS1061 Sensation & Perception #3 JMZ 3 · is the internal representation a veridical

Zanker, Johannes M.

421

Leaching of styrene and other aromatic compounds in drinking water from PS bottles  

Microsoft Academic Search

Bottled water may not be safer, or healthier, than tap water. The present studies have proved that styrene and some other aromatic compounds leach continuously from polystyrene (PS) bottles used locally for packaging. Water sapmles in contact with PS were extracted by a preconcentration technique called as “purge and trap” and analysed by gas chromatograph-mass spectrometer (GC\\/MS). Eleven aromatic compounds

Maqbool Ahmad; Ahmad S. Bajahlan

2007-01-01

422

Genome Sequence of Non-O1 Vibrio cholerae PS15  

PubMed Central

The draft genome sequence of a non-O1 Vibrio cholerae strain, PS15, organized into 3,512 open reading frames within a 3.9-Mb genome, was determined. The PS15 genome sequence will allow for the study of the evolution of virulence and environmental adaptation in V. cholerae. PMID:23409261

Kumar, Sanath; Lindquist, Ingrid E.; Sundararajan, Anitha; Rajanna, Chythanya; Floyd, Jared T.; Smith, Kenneth P.; Andersen, Jody L.; He, Guixin; Ayers, Ryan M.; Johnson, Judith A.; Werdann, James J.; Sandoval, Ava A.; Mojica, Nadia M.; Schilkey, Faye D.; Mudge, Joann

2013-01-01

423

Proposed Policy Statement Number: PS-67 Title/Topic: Misuse of Drugs or Alcohol  

E-print Network

603094.2 Proposed Policy Statement Number: PS-67 Title/Topic: Misuse of Drugs or Alcohol Effective Date: 01/07/2013 Revision Number: PS0067.R05 MISUSE OF DRUGS OR ALCOHOL Louisiana State University of the University. Although the University respects an employee's right to privacy, the misuse of drugs or alcohol

Harms, Kyle E.

424

Elastomeric Capture Microparticles (ECmuPs) and Their use with Acoustophoresis to Perform Affinity Capture Assays  

NASA Astrophysics Data System (ADS)

This dissertation describes the development of elastomeric capture microparticles (ECmicroPs) and their use with acoustophoresis to perform affinity capture assays. EC?Ps that function as negative acoustic contrast particles were developed by crosslinking emulsion-based droplets composed of commercially available silicone precursors followed by functionalization with avidin/biotin reagents. The size distribution of the EC?Ps was very broad or narrow depending on the emulsion system that was used during the synthesis process. Elastomeric particles exhibited a very broad size distribution when a bulk-emulsion process was used; however, when microfluidic systems were utilized, their size distribution became comparatively narrow. The functionalization of elastomeric particles was accomplished by the non-specific adsorption of avidin protein followed by bovine serum albumin (BSA) blocking and bio-specific adsorption of a biotinylated-capture antibody. Polydisperse EC?Ps were functionalized to bind prostate specific antigen (PSA) or IgG-phycoerythrin (PE) in aqueous media (buffer, plasma, blood); whereas monodisperse EC?Ps were functionalized to bind a high density lipoprotein in the aqueous media. Polydisperse EC?Ps functionalized to bind PSA in a physiological buffer (PBS pH 7.4) demonstrated nanomolar detection using flow cytometry analysis; whereas EC?Ps functionalized to bind IgG-PE demonstrated picomolar detection in 10% porcine plasma. EC?Ps have a specific density of ~1.03 and are more compressible than their surrounding aqueous media; which allowed the EC?Ps to exhibit negative acoustic contrast properties under an ultrasonic acoustic standing wave field. The negative acoustic contrast property of EC?Ps was advantageously utilized in an IgG-PE assay conducted in 0.1% whole porcine blood. The ligand-bound EC?Ps suspended in the diluted blood sample were flowed through an acoustofluidic device where the application of an ultrasonic acoustic standing wave field focused the ligand-bound EC?Ps to pressure antinodes and the positive acoustic contrast blood cells to the central pressure node of the microchannel. As a result of laminar flow, focused ligand-bound EC?Ps and blood cells were flowed into properly aligned outlet channels at the downstream trifurcation, where they where collected separately off-chip. The cell-free fraction containing ligand-bound EC?Ps was analyzed using flow cytometry; where the detection of IgG-PE was in the picomolar range. This approach has potential applications in the development of rapid assays that detect the presence of low concentrations of biomarkers in a number of biological sample types.

Cushing, Kevin Wallace

425

iPS cell technologies: significance and applications to CNS regeneration and disease.  

PubMed

In 2006, we demonstrated that mature somatic cells can be reprogrammed to a pluripotent state by gene transfer, generating induced pluripotent stem (iPS) cells. Since that time, there has been an enorm