UK PubMed Central (United Kingdom)

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia with a population prevalence of about 1%. Natriuretic peptide level is elevated in patients with AF with...Full Text Available

International Science & Technology Center (ISTC)

Natural Biologically Active HLDF6 Peptide as Potential Preparation for Correction of Different Drugabuse Forms

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Background: Thyroid-stimulating autoantibodies (TSAb) bind to the thyrotropin receptor (TSHR) extracellular domain, or ectodomain (ECD), comprising a leucine-rich repeat domain (LRD) linked by a hinge region to the transmembrane domain (TMD). The LRD (residues 22???260; signal peptide 1???21) contains two disulfide-bonded loops at its N-terminus. In the crystal structure of the isolated LRD complexed with human TSAb monoclonal antibody (mAb) M22, N-terminal disulfide loop 1 (residues 22???30) could not be determined because of crystal disorder. Nevertheless, present crystal structure data are interpreted to exclude a role for the LRD N-terminal disulfide loops in the TSAb epitope(s), contradicting prior functional evidence of a role for these loops in TSAb function. Materials and Methods: ...

UK PubMed Central (United Kingdom)

The p90 ribosomal S6 kinases (RSKs) also known as MAPKAP-Ks are serine/threonine protein kinases that are activated by ERK or PDK1 and act as downstream effectors of mitogen-activated protein kinase...Full Text Available

Science.gov (United States)

A hallmark of congestive heart failure (CHF) is the activation of the cardiac endocrine system, in particular atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). The natriuretic peptides are a group of structurally similar but genetically distinct peptides that have diverse actions in cardiovascular, renal, and endocrine homeostasis. ANP and BNP are of myocardial cell origin and C-type natriuretic peptide (CNP) is of endothelial origin. ANP and BNP bind to the natriuretic peptide-A receptor (NPR-A), which, via 3',5'-cyclic guanosine monophosphate (cGMP), mediates natriuresis, vasodilatation, renin inhibition, antimitogenesis, and lusitropic properties. CNP lacks natriuretic actions but possesses vasodilating and growth inhibiting actions via the guanylyl cyclase-linked natriuretic peptide-B receptor. ...

Science.gov (United States)

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these ...

Science.gov (United States)

In view of the findings that several Kunitz-type protein inhibitors suppress tumor invasion and metastasis, the aim of the present study is to explore whether Bungarus multicinctus protease inhibitor-like protein-2 (PILP-2) and PILP-3 exhibit anti-tumor activity. Although approximately 28% of amino acid substitutions occurred between PILP-2 and PILP-3, molecular modeling suggested that PILP-2 and PILP-3 shared similar folded structures. Unlike PILP-2, PILP-3 showed a notable activity in abolishing migration and invasion of human neuroblastoma SK-N-SH cells. The ability of PILP-3 to inhibit matrix metalloprotease-2 (MMP-2) activity was higher than that of PILP-2. Pull-down assay revealed protein-protein interaction between PILP-3 and MMP-2. In contrast to mutation on N-terminal region, replacement of amino acids at C-terminus attenuated notably the ability of PILP-3 to inhibit cell invasion, cell ...

British Library Electronic Table of Contents (United Kingdom)

Heme peroxidases are a class of multifunctional redox-active proteins found in all organisms. We recently cloned, expressed, and characterized an ascorbate peroxidase from Leishmania major (LmAPX) that was capable of detoxifying hydrogen peroxide. Localization studies using green fluorescent protein fusions revealed that LmAPX was localized within the mitochondria by its N-terminal signal sequence. Subcellular fractionation analysis of the cell homogenate by the Percoll density-gradient method and subsequent Western blot analysis with anti-LmAPX antibody further confirmed the mitochondrial localization of mature LmAPX. Submitochondrial fractionation analysis showed that the mature enzyme (?3.6?kDa shorter than the theoretical value of the whole gene) was present in the intermembrane space ...

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Four extracellular keratinases (designated KI, KII, KIII, and KIV) were produced during submerged aerobic cultivation in a medium containing native human foot skin (NHFS) for enzyme synthesis. The molecular weights, determined by SDS-PAGE, were 25, 50, 34, and 19kDa, respectively. Gel filtration of the four purified enzymes in native conditions indicated that active keratinase KI is a novel homo-octamer, KII a homo-dimer, and KIII and KIV monomers. All four keratinases exhibited high activities at pH 8.0-10.0 with an optimal pH of 9.0. The optimal temperature for keratinolytic activity of KI, KII, and KIII was approximately 50, and 60degreeC for KIV. One millimolar of PMSF completely inhibited the keratinolytic activities of the four enzymes. The N-terminal sequences of KI, KII, and KIII s...

UK PubMed Central (United Kingdom)

Constitutive activation of the transcription factor Stat5 in hematopoietic stem/progenitor cells leads to various hematopoietic malignancies including myeloproliferative neoplasm (MPN). Our recent study...Full Text Available

Science.gov (United States)

CD-NP is a novel chimeric natriuretic peptide (NP) consisting of the 22-amino-acid (AA) human C-type natriuretic peptide (CNP), a venodilating peptide with limited renal actions and minimal effects on blood pressure, and the 15-AA C-terminus of Dendroaspis NP (DNP). The rationale for the design of CD-NP was to enhance the renal actions of CNP, the ligand for natriuretic peptide receptor-B, but without inducing excessive hypotension. Here we report the first-in-human studies for CD-NP, which represent the first successful clinical testing of a chimeric NP demonstrating in normal human volunteers that CD-NP possesses cyclic guanosine monophosphate-activating, natriuretic, and aldosterone-suppressing properties without inducing excessive hypotension, laying the foundation for additional studies on this first-in-class new cardiovascular therapeutic in human heart failure, which are now ...

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PMID:11809176

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This study was conducted to investigate the antibacterial effect of BSAP-254 on Bacillus cereus with the induced stress proteins. The BSAP-254 is an antimicrobial peptide isolated from soybean-fermenting bacteria, Bacillus subtilis SC-8. It had a narrow spectrum of activity against B. cereus group. The growth inhibitory effect of BSAP-254 (50??g/mL) reduced the population of B. cereus from >108 to 104 colony-forming units per milliliter within 30?min. In B. cereus exposed to BSAP-254, 14 intracellular proteins were differentially expressed as determined by 2-DE coupled with MS. Of the differentially expressed proteins identified, the stress protein GroEL, which is heat shock protein, was induced in B. cereus exposed to antibacterial peptide.

Science.gov (United States)

From the dried fruiting bodies of the mushroom Armillaria luteo-virens, a dimeric lectin with a molecular mass of 29.4 kDa has been isolated. The purification procedure involved (NH{sub 4}){sub 2}SO{sub 4} precipitation, ion exchange chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose, and gel filtration by fast protein liquid chromatography on Superdex 75. The hemagglutinating activity of the lectin could not be inhibited by simple sugars but was inhibited by the polysaccharide inulin. The activity was stable up to 70 {sup o}C but was acid- and alkali-labile. Salts including FeCl{sub 3}, AlCl{sub 3}, and ZnCl{sub 2} inhibited the activity whereas MgCl{sub 2}, MnCl{sub 2}, and CaCl{sub 2} did not. The lectin stimulated mitogenic response of mouse splenocytes with the maximal response achieved by 1 {mu}M lectin. Proliferation of tumor cells including MBL2 cells, HeLa cells, and L1210 cells was inhibited by the ...

UK PubMed Central (United Kingdom)

The exocyst is an evolutionarily conserved octameric complex involved in polarized exocytosis from yeast to humans. The Sec3 subunit of the exocyst acts as a spatial landmark for exocytosis through...Full Text Available

UK PubMed Central (United Kingdom)

E-cadherins belong to a family of membrane-bound, cellular adhesion proteins. Their adhesive properties mainly involve the two N-terminal extracellular domains (EC1 and EC2). The junctions between these...Full Text Available

Science.gov (United States)

BackgroundDespite an ever-improving understanding of the molecular biology of cancer, the treatment of most cancers has not changed dramatically in the past three decades and drugs that do not discriminate between tumor cells and normal tissues remain the mainstays of anticancer therapy. Since Hsp90 is typically involved in cell proliferation and survival, this is thought to play a key role in cancer, and Hsp90 has attracted considerable interest in recent years as a potential therapeutic target.MethodsWe focused on the interaction of Hsp90 with its cofactor protein p60/Hop, and engineered a cell-permeable peptidomimetic, termed "hybrid Antp-TPR peptide", modeled on the binding interface between the molecular chaperone Hsp90 and the TPR2A domain of Hop.ResultsIt was demonstrated that this designed hybrid Antp-TPR peptide inhibited the interaction of Hsp90 with the TPR2A domain, inducing cell death of breast, pancreatic, renal, lung, prostate, ...

International Nuclear Information System (INIS)

An improved labeling procedure for peptides attached to organometallic 99mTc(III) '4+1' mixed-ligand complexes in which the radiometal is coordinated by a tripodal tetradentate chelator 2,2',2''-nitrilotriethanethiol (NS3) and a monodentate isocyanide ligand is presented. The labeling procedure was evaluated by the synthesis of [99mTc(NS3)(L2-RGD)]. The containing radiopharmaceutically interesting RGD-peptide cyclo[Arg-Gly-Asp-D-Tyr-Lys] was modified with 4-isocyanobutanoic acid (L2) as linker conjugated to N6-Lys to get the monodentate ligand L2-RGD. The structural identity of the 99mTc-conjugate was confirmed by comparison to a Re reference compound. The Tc- and Re-conjugates had matching retention times under identical HPLC conditions. The 99mTc-labeling was performed in a novel one-step procedure using the eluate of a 99Mo/99mTc generator, NS3, the isocyanide modified peptide, SnCl2, Na2EDTA, mannitol and ascorbic acid ...

UK PubMed Central (United Kingdom)

A cDNA library was constructed from HL60 human promyelocyte poly(A)+ RNA harvested 3 h after induction of macrophage differentiation with 12-O-tetradecanoyl phorbol-13-acetate in the presence of cycloheximide....Full Text Available

International Nuclear Information System (INIS)

Several examples of the 14-membered, para-bridged ring system of the cyclopeptide alkaloids have been synthesized via an active ester cyclization. The yield of monomeric cyclopeptide varied from 1 to 33% and was affected by the amino acid substitution pattern and amide conformation of the linear peptide precursors. Both the synthetic models and a naturally occurring cyclopeptide alkaloid, ceanothine B, bind monovalent (Li"+) and divalent (Ca"2"+, Mg"2"+) cations. 4 figures, 1 table.

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Peptide sequences such as lysine-arginine-serine-arginine (KRSR) selectively bind transmembrane proteoglycans (e.g. heparin sulfate) of osteoblasts (bone-forming cells) and are, therefore, actively being investigated for orthopedic applications. Further, nanophase materials (or materials with grain or particle sizes less than 100 nm) are promising new materials that promote new bone growth more than compared to conventional (that is, micron grain or particle size) materials. To combine the above two promising approaches for improving orthopedic implants, the objective of this in vitro study was to functionalize titanium (Ti) surfaces (both nanophase and conventional) with KRSR peptides and study their osteoblast cell adhesive properties. Materials were characterized by X-ray photoelectron ...

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PMID:18795096

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a-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of a-dystroglycan may be proteolytically processed to generate a small 38kDa protein (a-DG-N). The physiological significance of a-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that a-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of a-DG-N in CSF we examined the levels of a-DG-N and known neurodegenerative markers in CSF from patients di...

Energy Technology Data Exchange (ETDEWEB)

The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in ...

UK PubMed Central (United Kingdom)

Scyl1 is an evolutionarily conserved N-terminal protein kinase-like domain protein that plays a role in COP1-mediated retrograde protein trafficking in mammalian cells. Furthermore, loss of Scyl1 function...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Amyloid precursor protein (APP), a key protein in pathogenesis of Alzheimer's disease (AD), is a type I transmembrane protein which can be cleaved by b- and g-secretase to release the amyloidogenic b-amyloid peptides (Ab) and the APP intracellular domain (AICD). While Ab has been widely believed to initiate pathogenic cascades culminating AD, the physiological functions and regulations of AICD remain elusive. In present study, endogenous AICD was demonstrated to be increased by canonical Wnt signal. Instead of due to g-secretase activity, enhanced AICD expression was found due to the increased protein stability by Wnt/b-catenin. b-Catenin was demonstrated to be an associating partner of AICD, capable of promoting AICD mediated transcriptional activity. Investigation by AICD mutants proved ...

UK PubMed Central (United Kingdom)

BackgroundThe binding of peptide fragments of antigens to class II MHC is a crucial step in initiating a helper T cell immune response. The identification of such peptide epitopes...Full Text Available

UK PubMed Central (United Kingdom)

The sequences of the peptide binding domains of 33 70 kd heat shock proteins (hsp70) have been aligned and a consensus secondary structure has been deduced. Individual members showed no significant...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Endogenous opioid peptides (EOP) are molecules affecting many biological functions influencing productive and reproductive performance. They increase in stress conditions and interact with specific opioidergic receptors (OR): delta, kappa and mu. Several studies in other animal species suggest that they can also affect sperm cell motility. In fish the ionic external environment modulates the increase of intracellular calcium ion that is required to activate sperm motility after spawning. In mammals OR are functionally associated to calcium channels and in fishes calcium is highly required for fish sperm activation. In this study the presence of OR on spermatozoa of two Perciform fish, the sharpsnout seabream (Diplodus puntazzo, family Sparidae) and the European sea bass (Dicentrarchus labr...

International Nuclear Information System (INIS)

The active site of chicken gizzard myosin was labeled by direct photoaffinity labeling with ["3H]UDP. ["3H] UDP was stably trapped at the active site by addition of vanadate (Vi) and Co"2"+. The extraordinary stability of the myosin.Co2+.[3H]UDP.Vi complex (t1/2 greater than 5 days at 0 degrees C) allowed it to be purified free of extraneous ["3H]UDP before irradiation began. Upon UV irradiation, greater than 60% of the trapped ["3H]UDP was photoincorporated into the active site. Only the 200-kDa heavy chain was labeled, confirming earlier results using ["3H]UTP. Extensive tryptic digestion of photolabeled myosin subfragment 1 followed by high performance liquid chromatography separations and removal of nucleotide phosphates by treatment with alkaline phosphatase allowed two labeled peptides to be isolated. Sequencing of the labeled peptides and radioactive counting showed that ...

KoreaScience (Korea)

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Neurodegeneration observed in Alzheimer disease (AD) is believed to be related to the toxicity from reactive oxygen species (ROS) produced in the brain by the amyloid-{beta} (A{beta}) protein bound primarily to copper ions. The evidence for an oxidative stress role of A{beta}-Cu redox chemistry is still incomplete. Details of the copper binding site in A{beta} may be critical to the etiology of AD. Here we present the structure determined by combining x-ray absorption spectroscopy (XAS) and density functional theory analysis of A{beta} peptides complexed with Cu{sup 2+} in solution under a range of buffer conditions. Phosphate-buffered saline buffer salt (NaCl) concentration does not affect the high-affinity copper binding mode but alters the second coordination sphere. The XAS spectra for truncated and full-length A{beta}-Cu{sup 2+} peptides are similar. The novel distorted six-coordinated (3N3O) geometry around copper in the A{beta}-Cu{sup ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Acid-treated cobia (Rachycentron canadum) skin was extracted in a retort (121C) to obtain retorted skin gelatin hydrolysates (RSGHs) containing antioxidant peptides with noticeable antioxidant properties. To improve the antioxidant activity of cobia RSGHs, five processing factors including alkali concentration, alkali pretreatment time, phosphoric acid concentration (PC), water/skin ratio (WS) and retorting time (RT) in RSGH production were screened using a fractional factorial design to identify critical factors. It indicated that PC, WS and RT had significant effects on ,-diphenyl--picrylhydrazyl (DPPH) scavenging by RSGHs. Subsequently, the optimization of PC, WS and RT on the DPPH scavenging of RSGHs was studied using a central composite design to collect data that resulted in...

Science.gov (United States)

Snake envenomation employs three well integrated strategies: prey immobilization via hypotension, prey immobilization via paralysis, and prey digestion. Purines (adenosine, guanosine and inosine) evidently play a central role in the envenomation strategies of most advanced snakes. Purines constitute the perfect multifunctional toxins, participating simultaneously in all three envenomation strategies. Because they are endogenous regulatory compounds in all vertebrates, it is impossible for any prey organism to develop resistance to them. Purine generation from endogenous precursors in the prey explains the presence of many hitherto unexplained enzyme activities in snake venoms: 5'-nucleotidase, endonucleases (including ribonuclease), phosphodiesterase, ATPase, ADPase, phosphomonoesterase, and NADase. Phospholipases A(2), cytotoxins, myotoxins, and heparinase also participate in purine liberation, in addition to their better known functions. Adenosine contributes to ...

International Nuclear Information System (INIS)

The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0"0C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage ...

Energy Technology Data Exchange (ETDEWEB)

The authors have shown previously that the domain recognizing receptors on activated human platelets is located on the human fibrinogen {gamma} chain between residues 400 and 411. To study the correlation between the structure of this segment of the {gamma} chain and its reactivity toward receptors on ADP-activated human platelets, they designed a series of analogues containing replacements at 9 out of 12 positions. A double substitution of the normal His{sup 400}-His{sup 401} sequence by Ala-Ala reduced the inhibitory potency of the dodecapeptide 3-fold. When Lys{sup 406} was replaced by Arg, the inhibitory potency of the dodecapeptide decreased 15 times. On the other hand, substitution of Ala{sup 408} with Arg increased the inhibitory potency of the dodecapeptide 6-fold. A drastic decrease in the reactivity of the dodecapeptide toward platelet receptors was observed when Val{sup 411} was replaced by leucine or cysteine or tyrosine. A 3-fold ...

UK PubMed Central (United Kingdom)

BackgroundCalcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been...Full Text Available

UK PubMed Central (United Kingdom)

A unique antibacterial peptide derivative found in immune honeybee lymph, apidaecin 1b (AP1), was randomly mutagenized and characterized by a newly established system to analyze in vivo its structure-function...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Atrial natriuretic peptide (ANP) causes relaxation in the opossum lower esophageal sphincter. The effects of dendroaspis natriuretic peptide (DNP) and other natriuretic peptides in the lower esophageal sphincter were not known. We measured the relaxation of transverse strips from the guinea pig lower esophageal sphincter caused by DNP, ANP, brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and a natriuretic peptide receptor-C agonist des[Gln^1^8, Ser^1^9, Gly^2^0, Leu^2^1, Gly^2^2]ANP(4-23) amide (cANF(4-23)) in vitro. In resting strips of the guinea pig lower esophageal sphincter DNP and BNP caused marked relaxations. Furthermore, in both sarafotoxin S6c and carbachol-contracted lower esophageal sphincter strips, DNP caused marked and BNP caused moderate, concentration-de...

UK PubMed Central (United Kingdom)

CART peptides are endogenous neurotransmitters that are involved in a variety of physiologic functions. Injection of CART 55-102 into the nucleus accumbens produces no effect, but when co-administered...Full Text Available

UK PubMed Central (United Kingdom)

Background: The causes of elevated B-Type natriuretic peptide (BNP) levels are multifactorial. Renal dysfunction has been shown to affect BNP levels in some studies and...Full Text Available

UK PubMed Central (United Kingdom)

In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard,...Full Text Available

KoreaScience (Korea)

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UK PubMed Central (United Kingdom)

A new proprietary de novo peptide design technique generated ten 15-residue peptides targeting and containing the leading nontransmembrane hydrophobic autocorrelation wavelengths, “modes”,...Full Text Available

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Alzheimer's disease (AD) is a neurodegenerative disorder for which the research of new treatments is highly challenging. Since the fibrillogenesis of amyloid-b peptide 1-42 (Ab1-42) peptide is considered as a major cause of neuronal degeneration, specific interest has been focused on aromatic molecules for targeting this peptide. In this paper, the synthesis of selegiline-functionalized and fluorescent poly(alkyl cyanoacrylate) nanoparticles (NPs) and their evaluation for the targeting of the Ab1-42 peptide are reported. The synthetic strategy relied on the design of amphiphilic copolymers by tandem Knoevenagel-Michael addition of cyanoacetate derivatives, followed by their self-assembly in aqueous solutions to give the corresponding NPs. Different cyanoacetates were used: (i) hexadecyl cy...

International Nuclear Information System (INIS)

Cholera toxin catalyzes transfer of radiolabel from ["3"2P]NAD"+ to several peptides in particulate preparations of human foreskin fibroblasts. Resolution of these peptides by two-dimensional gel electrophoresis allowed identification of two peptides of M/sub r/ = 42,000 and 52,000 as peptide subunits of a regulatory component of adenylate cyclase. The radiolabeling of another group of peptides (M/sub r/ = 50,000 to 65,000) suggested that cholera toxin could catalyze ADP-ribosylation of cytoskeletal proteins. This suggestion was confirmed by showing that incubation with cholera toxin and ["3"2P]NAD"+ caused radiolabeling of purified microtubule and intermediate filament proteins.

Science.gov (United States)

PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the distribution of PAC(1), VPAC(1) and VPAC(2) receptor mRNA's. In the parathyroid gland a large number of nerve fibres displaying PACAP-immunoreactivity were distributed beneath the capsule, around blood vessels and close to glandular cells. Most of the PACAP-nerves were sensory, since they co-stored CGRP (calcitonin-gene-related peptide) and were sensitive to capsaicin-treatment. mRNA's for PAC(1) and VPAC(2) receptors occurred in the parathyroid gland, mainly located in the glandular cells. In the thyroid gland PACAP-immunoreactive nerve fibres were associated with blood vessels, thyroid follicles and parafollicular C-cells. A high degree of ...

British Library Electronic Table of Contents (United Kingdom)

SR proteins are essential splicing factors whose function is controlled by multi-site phosphorylation of a C-terminal domain rich in arginine-serine repeats (RS domain). The protein kinase SRPK1 has been shown to polyphosphorylate the N-terminal portion of the RS domain (RS1) of the SR protein ASF/SF2, a modification that promotes nuclear entry of this splicing factor and engagement in splicing function. Later, dephosphorylation is required for maturation of the spliceosome and other RNA processing steps. While phosphates are attached to RS1 in a sequential manner by SRPK1, little is known about how they are removed. To investigate factors that control dephosphorylation, we monitored region-specific mapping of phosphorylation sites in ASF/SF2 as a function of the protein phosphatase PP1. W...

Science.gov (United States)

The problem of homochirality is of crucial importance for the origins of Life. While most laboratory studies are focused on the search of physical and chemical sources of handedness in the Universe, they reflect only one aspect of the problem: the origin of homochiral biomolecules. At the same time, any space environments where biomolecules are expected to form and where they have to pass through before the first primitive forms of Life emerge, include strong irradiation or/and high temperatures. This automatically implies the possibility of losing the optical activity, i.e. racemization. The simulation experiments performed by our group deal with the following two aspects of amino acid abiotic chemistry: (1) amino acid pyrolysis associated with their extraterrestrial delivery; and (2) peptide formation from amino acids catalyzed by inorganic oxides. According to our observations, the racemization phenomena are very common in the systems ...

Science.gov (United States)

The structural organization of the genes encoding Bungarus multicinctus protease inhibitor-like proteins (PILPs), PILP-1, PILP-2 and PILP-3, are reported in this study. Unlike PILP-2 and PILP-3, recombinant PILP-1 exhibited inhibitory activity on trypsin. PILP genes and B chain genes shared identical organization with three exons interrupted by two introns in similar positions. On the contrary, intron 1 of these genes had a similar size, a notable variation with the size of intron 2 was observed. It was found that two regions at the second intron of B1 chain and B2 chain genes were absent in that of PILP genes. Noticeably, intronic insertion in the second intron of B chain genes appeared in the promoter region of PILP-1 gene, but not in that of PILP-2 and PILP-3 genes. Comparative analyses of PILP genes and B chain genes showed that the protein-coding regions of the exons are more diverse than introns, except for in the signal peptide domain. ...

Energy Technology Data Exchange (ETDEWEB)

The term "homology" or "homologous" means an amino acid similarity measured by the program, BLAST (Altschul et al (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", Nucleic Acids Res. 25:33 89 3402), and expressed as --(% identity n/n). In measuring homology between a peptide and a protein of greater size, homology is measured only in the corresponding region; that is, the protein is regarded as only having the same general length as the peptide, allowing for gaps and insertions.

UK PubMed Central (United Kingdom)

In an effort to develop octahedral metal complexes as chemotherapeutic and diagnostic agents targeted to DNA, it is critical to optimize the properties of their cellular uptake. Appending d-octaarginine...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundGenetic predisposition to scrapie in sheep is associated with several variations in the peptide sequence of the prion protein gene (PRNP). DNA-based tests...Full Text Available

International Nuclear Information System (INIS)

This study aims to investigate the difference in the interaction of antimicrobial peptides with two classes of zwitterionic peptides, phosphatidylethanolamines (PE) and phosphatidylcholines (PC). Further experiments were performed on model membranes prepared from specific bacterial lipids, lipopolysaccharides (LPS) isolated from Salmonella minnesota. The structure of the lipid-peptide aqueous dispersions was studied by small-and wide-angle X-ray diffraction during heating and cooling from 5 to 85 C. The lipids and peptides were mixed at lipid-to-peptide ratios 10-10000 (POPE and POPC) or 2-50 (LPS). All experiments were performed at synchrotron soft condensed matter beamline A2 in Hasylab at Desy in Hamburg, Germany. The phases were identified and the lattice parameters were calculated. Alamethicin and melittin interact in similar ways with the lipids. Pure POPC forms only lamellar ...

UK PubMed Central (United Kingdom)

Insulin-degrading enzyme (IDE) degrades insulin and other peptides, including the Aβ peptide of Alzheimer’s disease. However, the mechanism by which IDE acts on its substrates...Full Text Available

Science.gov (United States)

Cell-penetrating peptides (CPPs) are useful tools for the delivery of hydrophilic bioactive molecules, such as peptides, proteins, and oligonucleotides, across the cell membrane. To realize the delivery of therapeutic macromolecules by CPPs, the CPPs are required to show resistance to protease and no cytotoxicity. In order to produce potent non-toxic and protease-resistant CPPs with high cellular uptake, we designed an amphipathic helix peptide using ?-aminoisobutyric acid (Aib, U) and named it MAP(Aib). In the MAP(Aib) molecule, five Aib residues are aligned on the hydrophobic face of the helix and five lysine (K) residues are aligned on the hydrophilic face. MAP(Aib) showed potent resistance to trypsin and pronase compared with MAP, an amphipathic helix peptide formed by usual amino acids. Fluorescein-labeled MAP(Aib) efficiently traversed the A549 cell membrane, diffusing into the cytoplasm and ...

Science.gov (United States)

Myostatin is a member of the transforming growth factor-{beta} (TGF-{beta}) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF-{beta} class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. Overall, we have identified several ...

Energy Technology Data Exchange (ETDEWEB)

The amino acid residues 114-118 in actin were found to be implicated strongly in the binding of nucleotide, and as would be expected for such an important binding site, they are located in a completely conserved region of the actin sequence. A 19-residue peptide with the actin sequence 106-124 was synthesized in order to span the putative triphosphate binding site. Proton NMR spectra of the actin peptide 114-118 in the presence and absence of ATP indicated that Arg-116 and Lys-118 are particularly involved in binding ATP. A strong binding of ATP to the peptide 106-124 also was measured. Tripolyphosphate bound to the peptide 106-124 somewhat more weakly than ATP. Binding involved residues 115-118 and 121-124, indicating the presence of a reverse turn between these segments. Proton resonances were assigned by using two-dimensional double quantum correlated spectroscopy, one-dimensional spin decoupling ...

British Library Electronic Table of Contents (United Kingdom)

The atmospheric processing by ozone of peptide-containing mixed particles was investigated as proxies for biogenic and sea spray primary organic aerosol. Reactions were performed in a flow reactor and particle composition was monitored by photoelectron resonance capture ionization aerosol mass spectrometry. Mixed particles containing dipeptides in a saturated organic matrix of stearic and palmitic acids showed no reaction under ozonolysis at exposure levels of 2.5???10?4?atm s O3. However reactions of mixed particles of a dipeptide (Leu-Leu) in an unsaturated matrix (oleic acid) under the same conditions resulted in a rapid loss of the peptide ion signal, as well as the carrier matrix, and appearance of a number of ion signals corresponding to secondary products. High molecular weight imid...

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A cytochrome P450 that hydroxylates lauric acid at the 12 position (P450LA omega) was isolated from liver microsomes of clofibrate treated rats. P450LA omega was immunologically distinct from P450s a,b,c,d,e,f,g,h,j,PB1, and PCN1. Polyclonal antibody against P450LA omega was utilized to screen a gt11 cDNA library. A clone (pP450LA omega), was isolated and its sequence determined. The P450LA omega mRNA is a minimum 2387 nts in length and codes for a P450 of Mr.58,222 daltons. This protein shares less than 35% amino acid similarity with P450s b,c,d,e,f,PB1, and PCN1; however, it does contain a hydrophobic amino terminal peptide and a conserved sequence surrounding the Cys residue at position 456, which is similar to other microsomal P450s. P450LA omega is present at high levels in untreated rat kidney and is induced by clofibrate in both kidney and liver. This induction is the result of an accumulation of mRNA through a rapid transcriptional ...

UK PubMed Central (United Kingdom)

The acyl coenzyme A (CoA) binding protein AcbA is secreted unconventionally and processed into spore differentiation factor 2 (SDF-2), a peptide that coordinates sporulation in Dictyostelium...Full Text Available

UK PubMed Central (United Kingdom)

1. Seven unique carboxymethylcysteine-containing peptides have been isolated from tryptic digests of rabbit muscle aldolase carboxymethylated with iodo[2-¹⁴C]acetic acid in 8m-urea....Full Text Available

CERN Document Server

We have performed multicanonical Monte Carlo simulations of C-peptide of ribonuclease A. It is known by CD and NMR experiments that this peptide has high alpha-helix content in aqueous solution and that the side-chain charges of residues Glu-2$^-$ and His-12$^+$ play an important role in the stability of the alpha-helix. In order to confirm these experimental implications, we have used two analogues of the peptide with charged and neutral side chains of Glu-2 and His-12. Two dielectric functions, distance-dependent and constant, are considered to study the effects of solvent contributions. All the simulations were started from random initial conformations. Various thermodynamic quantities such as average helicity as a function of residue number and average distance between two side chains as a function of temperature are calculated. The results are found to be in accord with the implications of CD and NMR experiments. The ...

UK PubMed Central (United Kingdom)

Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated...Full Text Available

UK PubMed Central (United Kingdom)

In this work, we explore the potential of the metalloendopeptidase Lys-N for MALDI-MS/MS proteomics applications. Initially we digested a HEK293 cellular lysate with Lys-N and, for comparison, in parallel...Full Text Available

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BackgroundBaculovirus, which has a width of 40 nm and a length of 250-300 nm, can display functional peptides, receptors and antigens on its surface by their fusion with a baculovirus...Full Text Available

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Secreted human bronchial mucins, directly collected from macroscopically healthy bronchial mucosa, were prepared in the presence of six proteinase inhibitors, and analysed by electron microscopy. These...Full Text Available

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Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction...Full Text Available

UK PubMed Central (United Kingdom)

Gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptor superfamily, has been utilized for receptor-mediated targeting of imaging and therapeutic agents; here we extend...Full Text Available

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In the synthesis of the peptidyl-polymer corresponding to the sequence (57-100) of the ..beta.. chain of human hemoglobin on Teflon with radiationally grafted polystyrene a comparative study was made of different methods of fragment condensation. It was shown that the most effective methods are azide condensation and condensation with the use of complex F.

UK PubMed Central (United Kingdom)

A monensin-sensitive ruminal peptostreptococcus was able to grow rapidly (growth rate of 0.5/h) on an enzymatic hydrolysate of casein, but less than 23% of the amino acid nitrogen was ever utilized....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe successful interaction of bacterial pathogens with host tissues requires the sensing of specific chemical and physical cues. The human gut contains a huge number of...Full Text Available

UK PubMed Central (United Kingdom)

A pentapeptide open reading frame equipped with a canonical ribosome-binding site is present in the Escherichia coli 23S rRNA. Overexpression of 23S rRNA fragments containing the mini-gene renders cells...Full Text Available

Science.gov (United States)

Nine secondary metaboites of cyclic peptide were isolated from three mangrove endophytic fungi Paecilomyces sp. (treel-7), 4557,ZZF65. They were viscumamide(1),cyclo(Pro-Iso)(2),cyclo(Phe-Gly)(3),cyclo(Phe-Ana)(4),cyclo(Gly-Pro) (5),cyclo(Gly-Leu)(6), cyclo(Trp-Ana)(7),neoechinulin A(8),cyclo(Pro-Thr)(9). The compounds 1,7,8,9 were firstly isolated from marine fungus. PMID:18422185

Science.gov (United States)

Eight phospholipases A2 (PLAs) and four three-finger-toxins (3FTx) from the pooled venom of Bungarus fasciatus (Bf) were previously studied and sequenced, but their expression pattern in individual Bf venom and possible geographic variations remained to be investigated. We herein analyze the individual venom of two Bf specimens from Kolkata (designated as KBf) to address this question. Seven PLAs and five 3FTx were purified from the KBf venoms, and respective cDNAs were cloned from venom glands of one of the snakes. Comparison of their mass and N-terminal sequence revealed that all the PLAs were conserved in both KBf venoms, but that two of their 3FTx isoforms were variable. When comparing the sequences of these KBf-PLAs with those published, only one was found to be identical to that of Bf Vb-2, and the other five were 94-98% identical to those of Bf II, III, Va, VI and XI-2, respectively. Notably, the most abundant PLA isoforms of Bf and KBf venoms contain Pro31 ...

Science.gov (United States)

The presence of endothelin (ET)-like immunoreactivity and the cardiovascular effects of mammalian ET-1 in fish have been reported. To identify ET-related peptides in fish, we screened the cDNA library of the salmon (Oncorhynchus keta) stomach by means of rapid amplification of cDNA ends, and we cloned cDNAs encoding an ET-related peptide. The salmon ET-related sequence of 21 amino acids is identical to the trout ET-1 peptide recently purified from kidney specimens of Oncorhynchus mykiss. The deduced amino acid sequence of salmon pre-proET-1 (PPET-1) comprises 244 amino acids, including a putative signal sequence and mature ET-1, as well as big ET-1 and ET-1-like sequences. This precursor, the first reported PPET-1 sequence for Salmoniformes, Teleostei, has low homology with the sequences of human, mouse, frog (Xenopus laevis), and zebrafish (Danio rerio) PPET-1 (26%, 29%, 24%, and 39%, respectively). PMID:16740985

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The recent development of matrix-assisted UV laser desorption (LD) mass spectrometry has made possible the ionization and detection of extremely large molecules (with molecular weights exceeding 100,000 Daltons). This technique has generated enormous interest in the biological community for the direct examination of large peptides and oligonucleotides. Although this matrix-assisted ionization method has been developed and used almost exclusively with time-of-flight (TOF) mass spectrometers, research is currently in progress to demonstrate this technique with trapped ion mass spectrometers, such as Fourier transform ion cyclotron resonance mass spectrometry (FTMS). The potential capabilities of FTMS for wide mass range, high resolution measurement, and ion trapping experiments suggest that this instrumental technique should be useful for the detailed structural characterization of large ions generated by the matrix-assisted technique. We have recently demonstrated ...

British Library Electronic Table of Contents (United Kingdom)

The antimicrobial peptide scygonadin (Scy) was first isolated from the gonad of Scylla serrata and its gene is predominantly expressed in the ejaculatory duct of adult males. Thus, its function was predicted to be associated with reproductive immunity, but this is still unclear and needs further investigation. In our study, the expression pattern of Scy at different developmental stages of both male and female S. paramamosain was investigated, so that the potential function of this peptide could be examined. Using real-time quantitative PCR, Scy mRNA transcripts were demonstrated obviously in the vulnerable embryos and larvae-zoea I but very weakly detected in the larvae-zoea III, megalops and juveniles. The gene expression pattern showed a decreasing trend during the early developmental s...

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Background/Objectives: Cardiotoxic drug poisoning can lead to severe cardiac shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established diagnostic and prognostic marker in heart failure but has never been assessed in patients with cardiotoxic drug poisoning. The aim of the study was to determine whether BNP could be useful for early stratification of patients admitted to intensive care unit. Methods: 30 consecutive patients experiencing shock and cardiotoxic drug exposure were enrolled in a prospective monocentric study and underwent at least two BNP measurements within the first 24 h after admission. Results: While BNP values on admission were poorly informative, subsequent BNP measurements (11 +- 6 h after admission) were significantly increased in patients with CS comp...

British Library Electronic Table of Contents (United Kingdom)

A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4prime-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively. Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. The reduction of the imine is not accompanied by hydroboration of the fullerene cage. The [70]fullerene phenylalanine derivative has also been prepared as have the di-amino acid derivatives. The compounds were characterized by MALDI-TOF mass spectrometry, UV/Vis spectroscopy, and cyclic voltammetry. 1H and 13C NMR spectroscopy allowed the observation of diastereomers. Fullerene-substituted peptides may be synthesized on relatively large scale by solid-pha...

Scientific Electronic Library Online (English)

Abstract in english Functional properties of soy proteins for food are closely related to the composition of their storage protein subunits. Using base excision sequence scanning (BESS), we show that the absence of the A4 peptide in the G4 glycinin subunit of the soybean (Glycine max L.) cultivar Enrei was caused by the same point mutation in the Gy4 gene as previously reported in the soybean cultivar Raiden. Although the genetic relationship between Raiden and Enrei is not known, the same p (more) oint mutation in their Gy4 genes may indicate that they probably share a related origin. The application of BESS to identify single nucleotide polymorphisms (SNPs) as co-dominant markers for marker-assisted selection (MAS) of a recessive null allele is also discussed.

UK PubMed Central (United Kingdom)

BackgroundOur previous studies indicate that either PEP-1-superoxide dismutase 1 (SOD1) or PEP-1-catalase (CAT) fusion proteins protects myocardium from ischemia-reperfusion-induced...Full Text Available

UK PubMed Central (United Kingdom)

The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles...Full Text Available

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There are about fifty SET domain protein methyltransferases (PMTs) in the human genome, that transfer a methyl group from S-adenosyl-L-methionine (SAM) to substrate lysines on histone tails or other peptides. A number of structures in complex with cofactor, substrate, or inhibitors revealed the mechanisms of substrate recognition, methylation state specificity, and chemical inhibition. Based on these structures, we review the structural chemistry of SET domain PMTs, and propose general concepts towards the development of selective inhibitors.

UK PubMed Central (United Kingdom)

Low-level lead exposure during early childhood has long been associated with altered neurocognitive development and diminished cognitive functions. Over nine thousand U.S. industrial facilities...Full Text Available

Environmental Research Database

DescriptionIron deficiency anaemia is a common problem and may be particularly important to certain groups of vegetarians. This project investigates isolating and identifying iron-binding constituents of meat digests using human Caco-2 cell lines. Stable isotope techniques used to test whether one or more of these compounds enhance iron absorpion in vivo and could therefore be added to vegetarian products to imporve iron nutrition.

UK PubMed Central (United Kingdom)

BackgroundThe human endogenous retrovirus HERV-K(HML-2) family is associated with testicular germ cell tumors (GCT). Various HML-2 proviruses encode viral proteins such as Env and...Full Text Available

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During this report period our research efforts have concentrated on studies of the dissociation reactions of model peptides and other biologically important molecules. In addition, a considerable amount of research effort has been directed toward improving the apparatus used for laser-ion beam photodissociation. The instrumental improvements include some changes on the original apparatus, but most of this effort involved designing a second generation laser-ion beam photodissociation instrument.

UK PubMed Central (United Kingdom)

The catecholamine release-inhibitory catestatin [Cts; human chromogranin (Cg) A_352-372, bovine CgA_344-364] is a vasoreactive and anti-hypertensive peptide derived...Full Text Available

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Science.gov (United States)

We cloned and characterized horse preproendothelin-2 (PPET-2) cDNA from intestinal tissue. The cDNA encoded 178 amino acids of the PPET-2 polypeptide, in which a 21-amino-acid mature endothelin-2 peptide and a 16-amino acid endothelin-2-like peptide were found. For the open reading frame the correspondence of horse PPET-2 cDNA with those of the ferret, human, dog, mouse and rat was 85.1%, 84.9%, 82.1%, 77.8% and 77.2%, respectively. Analysis of the organ distribution of PPET-2 mRNA by reverse transcription-polymerase chain reaction demonstrated that the kidney, stomach and small intestine are major sites of expression of the PPET-2 gene. Surprisingly, the mRNA is not detected in the large intestine, where high expression is demonstrated in the mouse and rat. This difference may result from the underlying functional differences of the large intestine between a herbivore (horse) and an omnivore (mouse and rat). PMID:15838341

Science.gov (United States)

A novel single-chain immunotoxin was constructed by combining a CD33-specific single chain Fv (scFv) antibody fragment with an engineered variant of Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum. The purified recombinant fusion protein induced potent apoptosis of the human myeloid cell lines U937, HL-60 and THP-1. Up to 98% of U937 cells were eliminated after treatment for 72 h with a single dose of 500 ng/ml (c. 7 nmol/l). Killing was antigen-specific and occurred by apoptosis. A control protein, consisting of a CD19-specific scFv antibody fragment fused to the ETA-KDEL toxin, failed to induce death of the CD19-negative cell lines U937, HL-60 and THP-1. The CD33-ETA toxin also mediated apoptosis of fresh patient-derived acute myeloid leukaemia cells from bone marrow and peripheral blood. The pronounced ...

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This paper describes the study of kinetically controlled enzymatic coupling of N- and O-glycopeptide fragments using subtilisin BPN' and two of its variants developed for use in high concentrations of dimethylformamide and in aqueous solution, respectively. Glycosyl amino acids were exploited as the P[sub 1], P[sub 2], P[sub 3], P'[sub 1], P'[sub 2], or P'[sub 3] residue in the enzymatic coupling. Glycosyltransferase-mediated glycosylation of the glycopeptide fragments obtained prior to or after enzymatic peptide bond formation is demonstrated. 19 refs., 5 figs., 1 tab.

International Nuclear Information System (INIS)

2-Azido[#alpha#-"3"2P]adenosine diphosphate (2-azido[#alpha#-"3"2P]ADP) has been used to photolabel the ADP/ATP carrier in beef heart mitochondria. In reversible binding assays carried out in the dark, this photoprobe was found to inhibit ADP/ATP transport in beef heart mitochondria and to bind to two types of specific sites of the ADP/ATP carrier characterized by high-affinity binding (K/sub d/ = 20 #mu#M) and low-affinity binding (K/sub d/ = 400 #mu#M). In contrast, it was unable to bind to specific carrier sites in inverted submitochondrial particles. Upon photoirradiation of beef heart mitochondria in the presence of 2-azido[#alpha#-"3"2P]ADP, the ADP/ATP carrier was covalently labeled. After purification, the photolabeled carrier protein was cleaved chemically by acidolysis or cyanogen bromide and enzymatically with the Staphylococcus aureus V8 protease. In the ADP/ATP carrier protein, which is 297 amino acid residues in length, two discrete regions extending from Phe-153 to ...

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PMID:4423540

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The T cell receptor is a fundamental mediator of the adaptive immune responses, since TR ab on T cells recognize foreign structures (peptides derived from processed antigens) bound to the major histocompatibility complex (MHC) on APC cells. In the present study, we report the cloning of six TRB chains cDNA sequences from gilthead sea bream (Sparus aurata), a fish of high economical impact in South Mediterranean aquaculture. The V-BETA domains have the canonical features of known teleost and mammalian TR V-BETA domains and have been divided in four different subgroups. A multiple alignment of the six sea bream TRB chains with other known TRB sequences was assembled and showed the conservation of the four cysteine residues involved in disulphide bonds and of some amino acids with an importan...

British Library Electronic Table of Contents (United Kingdom)

Aberrant amyloid-b peptide (Ab) accumulation along with altered expression and function of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery that Ab is bound to a7 nAChRs under many experimental settings, including post-mortem AD brain, much effort has been expended to understand the implications of this interaction in the disease milieu. This research update will review the current literature on the a7 nAChR-Ab interaction in vitro and in vivo, the functional consequences of this interaction from sub-cellular to cognitive levels, and discuss the implications these relationships might have for AD therapies.

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Abstract Under eons of evolutionary and environmental pressure, biological systems have developed strong and lightweight peptide-based polymeric materials by using the 20 naturally occurring amino acids as principal monomeric units. These materials outperform their man-made counterparts in the following ways: 1)-multifunctionality/tunability, 2)-adaptability/stimuli-responsiveness, 3)-synthesis and processing under ambient and aqueous conditions, and 4)-recyclability and biodegradability. The universal design strategy that affords these advanced properties involves -bottom-up- synthesis and modular, hierarchical organization both within and across multiple length-scales. The field of -biomimicry--elucidating and co-opting nature-s basic material design principles and molecular building blo...

British Library Electronic Table of Contents (United Kingdom)

Successful electron capture dissociation (ECD) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) applications to peptide and protein structural analysis have been enabled by constant progress in implementation of improved electron injection techniques. The rate of ECD product ion formation has been increased to match the liquid chromatography and capillary electrophoresis timescales, and ECD has been combined with infrared multiphoton dissociation in a single experimental configuration to provide simultaneous irradiation, fast switching between the two techniques, and good spatial overlap between ion, photon, and electron beams. Here we begin by describing advantages and disadvantages of the various existing electron injection techniques for ECD in FT-ICR MS. We next ...

British Library Electronic Table of Contents (United Kingdom)

Phage display is effective in screening peptides that mimic venom's neutralizing epitopes. A phage display cyclized heptapeptide library (C7C library) was panned with purified divalent antivenin IgG, which neutralizes Naja naja atra venom (NAV) and Bungarus multicinctus venom (BMV). The selected heptapeptide sequences were aligned with known protein sequences of NAV and BMV in GenBank. One of the four consensus sequences, L/PKSSLL, mimicked the crucial epitope on Loop III of Taiwan cobra cardiotoxin that is associated with the venom's lethal potency. In dot blot analysis, several clones showed varying reactivities for NAV monovalent antivenin and lesser cross-reactions with BMV monovalent antivenin. The KSSLLRN-carrying phage occurred four times in selected clones and showed the strongest ...

British Library Electronic Table of Contents (United Kingdom)

Abstract A 3-month, open-label, single-center study was conducted to determine whether a uniquely formulated and physiologically balanced topical treatment serum containing multiple growth factors, cytokines, peptides, antioxidants and depigmenting agents could improve the visible signs of facial photodamage. Thirty-seven females, aged 32-55 years, with mild to severe, fine and coarse peri-ocular wrinkles were enrolled and completed the study. Subjects applied the treatment serum to the face twice daily for 3 months in conjunction with a basic skincare regimen. Clinical evaluations of photodamage were performed at baseline and months 1, 2 and 3. Cutometer measurements and subject self-assessment questionnaires were also conducted during the study. Clinical evaluations showed statistically ...

British Library Electronic Table of Contents (United Kingdom)

Protein hydrogels were prepared by substituting ovalbumin with different concentrations of ethyl vinyl sulfone (EVS) or acrylic acid (AA) and crosslinking with divinyl sulfone (DVS). Fourier transform-infrared (FT-IR) spectroscopic studies confirmed the addition of EVS, AA, and DVS onto the protein. Swelling was assessed as a function of pH in the range of 2.5 to 9.4 and ionic strength. The elastic modulus of the gels was determined in shear and compression. Stress relaxation was assessed in compression. The substituent highly affected swelling and modulus with both hydrogels displaying non-Gaussian behavior in the range of hydrogel environments studied. Acrylic acid substituted ovalbumin exhibited a decreasing modulus with increasing swelling behaving as a polyelectrolyte with low added s...

British Library Electronic Table of Contents (United Kingdom)

Using the peptide hormone glucagon and Ab(1-40) as model systems, we have sought to elucidate the mechanisms by which fibrils grow and multiply. We here present real-time observations of growing fibrils at a single-fibril level. Growing from preformed seeds, glucagon fibrils were able to generate new fibril ends by continuously branching into new fibrils. To our knowledge, this is the first time amyloid fibril branching has been observed in real-time. Glucagon fibrils formed by branching always grew in the forward direction of the parent fibril with a preferred angle of 35-40degree. Furthermore, branching never occurred at the tip of the parent fibril. In contrast, in a previous study by some of us, Ab(1-40) fibrils grew exclusively by elongation of preformed seeds. Fibrillation kinetics i...

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... activation analysis biological materials bremsstrahlung environment lead lead

International Nuclear Information System (INIS)

... activation analysis bremsstrahlung environment gamma spectroscopy

UK PubMed Central (United Kingdom)

Peripartal serum alkaline phosphatase activity and lactate dehydrogenase activity were measured in 30 dairy cows in order to examine the association between retained fetal membranes and enzyme activity....Full Text Available

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Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as ...

Science.gov (United States)

Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes ...

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Four low activation alloy classes, two austenitic and two ferritic, have been incorporated into the MOTA-1B experiment in the FFTF reactor to provide an early assessment of the suitability of such alloys for reactor service.

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PMID:4462663

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UK PubMed Central (United Kingdom)

In addition to inducing new transcriptional activities that lead within a few hours to the accumulation of heat shock proteins (Hsps), heat shock activates within minutes the major signaling transduction...Full Text Available

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... activation analysis gamma spectra mev range molybdenum molybdenum ores

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Information is presented concerning reactor research activities; isotope geology; NERC radiocarbon laboratory; teaching activities; and reactor operation.

International Nuclear Information System (INIS)

In this paper the structural and functional changes of gamma irradiated bovine hemoglobin are presented. Aqueous solutions/1%/of HbO_2 were irradiated in air with doses ranging from 1 to 4 Mrad. Isoelectric focusing indicated change of the charge of irradiated hemoglobin. The isoelectric point of hemoglobin was displaced towards more acid values with increasing doses, up from 1 Mrad. Fingerprint analysis and peptide column chromatography of irradiated hemoglobin demonstrated disturbances increasing with the dose. These changes were confirmed by amino acid analysis which showed that Cys, Met, Trp, His, Pro and Tyr residues were destroyed or modified following irradiation. At doses exceeding 1 Mrad the irradiated solutions of hemoglobin showed a decrease of heme-heme interaction and an increase of affinity for oxygen. Differences observed in oxygen-dissociation curves seem to be correlated with the radiation induced destruction of amino acid residues which are ...

International Nuclear Information System (INIS)

A radioimmunoassay is described for the molluscan neuropeptide, Phe-Met-Arg-Phe-NH"2(FMRFamide). The antibody used is C-terminal-specific and shows slight but significant (1-2%) cross-reactivity with chicken pancreatic polypeptide (APP). The assay has been used to identify in rat brain extracts a pair of molecules that may represent mammalian counterparts of FMRFamide. Their concentrations were highest in spinal cord and hypothalamus (>10 pmol.g"-_1) and lowest in cerebellum and striatum (<3.5 pmol.g"-_1). The two immunoreactive peptides were separated on CM ion-exchange chromatography where they appeared to be less basic than FMRFamide. On Sephadex G50 gel filtration one eluted in a similar position to FMRFamide and the other slightly earlier suggesting it may be of higher molecular weight. The rat immunoreactive components do not correspond to previously described neuropeptides or hormones, and may be members of a new group of mammalian neuropeptides with ...

Science.gov (United States)

Selecting an appropriate matrix solution is one of the most effective means of increasing the ionization efficiency of phosphopeptides in matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). In this study, we systematically assessed matrix combinations of 2, 6-dihydroxyacetophenone (DHAP) and diammonium hydrogen citrate (DAHC), and demonstrated that the low ratio DHAP/DAHC matrix was more effective in enhancing the ionization of phosphopeptides. Low femtomole level of phosphopeptides from the tryptic digests of ?-casein and ?-casein was readily detected by MALDI-TOF-MS in both positive and negative ion mode without desalination or phosphopeptide enrichment. Compared with the DHB/PA matrix, the optimized DHAP/DAHC matrix yielded superior sample homogeneity and higher phosphopeptide measurement sensitivity, particularly when multiple phosphorylated peptides were assessed. Finally, the DHAP/DAHC matrix was applied to identify ...

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The study of chemoattractant receptors on human monocytes had been limited by the lack of a radioligand suitable for use with the small numbers of cells routinely available from human donors. A new synthetic oligopeptide radioligand f(/sup 35/S)Met-leu-phe, with a higher specific radioactivity than was available with the tritiated compound, was used to characterize a chemoattractant receptor on freshly isolated human blood monocytes. These cells bind f(/sup 35/)met-leu-phe with a dissociation constant (KD) of 30.2 +/- 5.6 nM and contain 84,000 +/- 11,300 receptors per cell. f(/sup 35/)met-leu-phe does not bind specifically to blood lymphocytes. The specificity of the oligopeptide receptor on monocytes is indistinguishable from the oligopeptide chemoattractant receptor on human polymorphonuclear leukocytes. Using f(/sup 35/)met-leu-phe, it will now be feasible to study the chemotactic peptide receptor on small numbers of partially purified peripheral blood monocytes ...

British Library Electronic Table of Contents (United Kingdom)

Summary Background Treatment of localised renal cell carcinoma consists of partial or radical nephrectomy. A substantial proportion of patients are at risk for recurrence because no effective adjuvant therapy exists. We investigated the use of an autologous, tumour-derived heat-shock protein (glycoprotein 96)-peptide complex (HSPPC-96; vitespen) as adjuvant treatment in patients at high risk of recurrence after resection of locally advanced renal cell carcinoma. Methods In this open-label trial, patients were randomly assigned to receive either vitespen (n=409) or observation alone (n=409) after nephrectomy. Randomisation was done in a one to one ratio by a computer-generated pseudo-random number generator, with a block size of four, and was stratified by performance score, lymph node stat...

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Orientational constraints obtained from solid state NMR experiments on anisotropic samples are used here in molecular dynamics (MD) simulations for determining the structure and dynamics of several different membrane-bound molecules. The new MD technique is based on the inclusion of orientation dependent pseudo-forces in the COSMOS-NMR force field. These forces drive molecular rotations and re-orientations in the simulation, such that the motional time-averages of the tensorial NMR properties approach the experimentally measured parameters. The orientational-constraint-driven MD simulations are universally applicable to all NMR interaction tensors, such as chemical shifts, dipolar couplings and quadrupolar interactions. The strategy does not depend on the initial choice of coordinates, and is in principle suitable for any flexible molecule. To test the method on three systems of increasing complexity, we used as constraints some deuterium quadrupolar couplings from the literature on ...

British Library Electronic Table of Contents (United Kingdom)

Glabridin, an active constituent of Glycyrrhiza glabra roots, was found to be active against both yeast and filamentous fungi. Glabridin also showed resistance modifying activity against drug resistant mutants of Candida albicans at a minimum inhibitory concentration of 31.25-250 g/mL. Although the compound was reported earlier to be active against Candida albicans, but this is the first report of its activity against drug resistant mutants. Copyright Copyright 2009 John Wiley & Sons, Ltd.

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As with mammalian enzymes, green crab (Scylla serrata) alkaline phosphatase can be activated by Mg2+ through a time-dependent course. The activation is mainly a Vmax effect. Tsou's method was used to study the kinetic course of activation. The results show that the enzyme was activated by a complexing scheme that had not been previously identified: the enzyme first reversibly and quickly binds Mg2+ and then undergoes a slow reversible course to activation, with a relatively high activation energy (78 +/- 4 kJ/mol) and a slow conformational change. The activation reaction is a single molecule reaction, and the apparent activation rate constant is independent of Mg2+ concentration if the concentration is sufficiently high. The microscopic rate constants of activation and the association constant were ...

UK PubMed Central (United Kingdom)

BackgroundActivation of the signal transducer and activator of transcription 3 (STAT3) within antigen presenting cells (APCs) is linked to abnormal APCs differentiation and function....Full Text Available

UK PubMed Central (United Kingdom)

The patterns of nitrate reductase activity (NRA) in the leaves (in vivo assay) and root nodule nitrogenase activity (C₂H₂ reduction) were investigated throughout...Full Text Available

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Emphasis was put on the comparative quantitative structure-activity approaches to the exploration of action mechanisms of structurally different classes of compounds showing the same type of activity...Full Text Available

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Background and objectives: Chronic kidney disease (CKD) is associated with impaired physical activity. However, it is unclear whether the associations of physical activity with mortality are modified...Full Text Available

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Materials World Network: Cooperative Activity in Materials Research between US Investigators and ... Program Title: Materials World Network: Cooperative Activity in Materials Research between US ...

UK PubMed Central (United Kingdom)

Given the high prevalence of overweight and low levels of physical activity among children, a better understanding of physical activity behaviour is an important step in intervention planning. This...Full Text Available

UK PubMed Central (United Kingdom)

Human apurinic/apyrimidinic endonuclease (hApe1) encodes two important functional activities: an essential base excision repair (BER) activity and a redox activity that regulates expression...Full Text Available

UK PubMed Central (United Kingdom)

Objective:To investigate the combined effect of both pioglitazone and methotrexate on disease activity of rheumatoid arthritis in a biphasic study; experimental and clinical.Methods:Experimentally:...Full Text Available

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BACKGROUND--Interstitial lung diseases are characterised by the recruitment of mononuclear cells to disease sites where maturation occurs and activation products, including lysozyme (LZM), are released....Full Text Available

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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Their discovery in the 1990s provided insights...Full Text Available

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AMP-activated protein kinase (AMPK) was initially viewed as energy sensor and activated by increased intracellular concentrations of AMP following nutrient deprivation. Physiological or pathological...Full Text Available

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This paper obtains the acidity spectra of modernites and SVK-zeolites from the heats of adsorption of NH/sub 3/ at 300 C and compares the catalytic activity of these zeolites with the cracking of n-octane and the isomerization of o-xylene. It is shown that the calculation of the specific catalytic activity of centers of different strengths by the method of regional rates allows one to predict the activity of the zeolites from the acidity spectra. It follows from the calculation that only the centers of Bronsted acidity are active towards cracking but that the centers of Lewis acidity are also active towards isomerization.

International Nuclear Information System (INIS)

... activation analysis aluminium 28 calcium 49 chlorine 38 cotton plants li-drifted

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Rheumatoid Arthritis; Psoriatic Arthritis; Ankylosing Spondylitis; Endothelial Dysfunction; Inflammatory Disease Activity

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A residue in the production of alumina by the Bayer process is red mud. It contains oxides of Fe and Ti, active as hydrogenation catalyst in sulfided form, and whose catalytic activity can be improved by the activation method proposed by Pratt and Christoverson. The paper describes how the development of its activity and selectivity with reaction time was studied for the hydrogenation of a light fraction of an anthracene oil, and compared with untreated sulfided red mud. Catalyst samples were collected at different reaction times, and their texture, morphology and composition characterized by nitrogen adsorption, SEM and SEM-EDX. The loss of catalytic activity of activated sulfided red mud is slower than for untreated sulfided red mud. The main cause of this decrease in catalytic activity is the loss of surface area and superficial Fe.

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BackgroundThe aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative...Full Text Available

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The ability of a number of mycobacteria and some of their components to activate complement was examined. Mycobacterium bovis BCG (Glaxo strain), Mycobacterium leprae, Mycobacterium lepraemurium, and...Full Text Available

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PMID:1455781

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Inhibition of large conductance calcium-activated potassium (BK_Ca) channels mediates, in part, oxygen sensing by carotid body type I cells. However, BK_Ca channels remain active...Full Text Available

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Udgivelsesdato: 2002-May

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Udgivelsesdato: 1988-Jul

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PMID:10354000

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Program activities and achievements in 1982 of the geodynamic program are summarized. The significant results presented are summarized.

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... electric utilities electrochemistry energy storage fuel cells organizational models

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Experiments were carried out to determine the adsorption capability of some commercial activated and non-activated charcoal samples with methanol to select the most favourable pair to be used in a solar adsorption refrigeration system. The results obtained are presented. A simple method has been used to enhance the adsorption capability of the lumpwood charcoal. (Author)

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... science in places outside of schools, with materials and activities initially not developed for ...

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We prepared cathodes with various types of activated carbon and measured the cathodes' electrochemical performance according to the kind of activated carbon. Activated carbon supplies airflow channels and reaction sites in the cathode of zinc air batteries. When we use activated carbon with a high specific surface area as the cathode's catalyst substrate, we expect high electrochemical performance because this type of carbon provides more air flow channels and reaction sites. We focused on investigating the relationship between the cathode's pore structure and its electrochemical characterizations. We also studied the effects of the various activated carbon materials on the zinc air batteries' performance. Increasing the macropores or mesopores in the activated carbon resulted in achieving more power from the battery. (author)

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Red mud has been activated by dissolution in hydrochloric acid and reprecipitation with ammonia. The activated material has been evaluated as a catalyst for the hydrogenation of naphthalene, phenanthrene and pyrene and in the hydroliquefaction of both a high and low rank coal utilizing solvents of high and low hydrogen donating ability. Activation led to a substantial increase in the ability to hydrogenate the model compounds and a significant increase in oil yield was obtained in the hydroliquefaction of a low rank coal in the presence of a poor donor solvent. However, activation did not lead to significant increases in overall yields of liquids in other cases and the activated red mud was significantly less active than a commercial nickel-molybdenum-sulphur catalyst. 27 refs., 1 fig., 5 tabs.

International Nuclear Information System (INIS)

Activation has been used for many kinds of useful applications, such as use of the radioisotopes for diagnosis and treatment of cancer, and wear (or corrosion) investigation for using thin layer activation (TLA) technique, etc. But activation also has severe problems for the post-processing of the samples; such as time-loss, inconvenience of sample handling, personal radiation safety, etc. For in-vitro experiments, we observed death of tumor cells by proton irradiation. The use of large activated container material can cause erroneous results in this case. To solve these problems, we studied why the samples were activated and how the level of the activation could be reduced. In proton beam irradiation experiments, the target materials could be defined as the container and sample itself. We could easily reduce activation of container material ...

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Research activity during the 1991--1992 funding period has been concerned with the following topics relevant to carbon monoxide activation. (1) Exploratory studies of water gas shift catalysts heterogenized on polystyrene based polymers. (2) Mechanistic investigation of the nucleophilic activation of CO in metal carbonyl clusters. (3) Application of fast reaction techniques to prepare and to investigate reactive organometallic intermediates relevant to the activation of hydrocarbons toward carbonylation and to the formation of carbon-carbon bonds via the migratory insertion of CO into metal alkyl bonds.

International Nuclear Information System (INIS)

Tests for the applicability of a CFD (Computational Fluid Dynamics) code for simulating activity transport in PNA (Pulsed Neutron Activation) fluid measurements have been performed. The CFD code was combined with a Monte Carlo code used for the calculation of the initial activity distribution. The results from the calculations show that it is possible to use CFD for calculation of the activity distribution in PNA. The mainly qualitative results in this work are encouraging and suggest further work. In the continuation of this work a response function for the gamma detector will be calculated so that a PNA time spectrum can be simulated. A more accurate comparison with experimental data can then be performed

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Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal alpha7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC(50) approximately 1muM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves the regulation of ...

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A carrier-free radioiodinated phenylazide derivative of forskolin, 3-iodo-4-azidophenethylamido-7-O-succinyl-deacetyl-forskolin (({sup 125}I)IAPS-forskolin), has been shown to be a highly selective photoaffinity probe for the human erythrocyte glucose transported and the glucose transport proteins found in several mammalian tissues and cultured cells where the glucose transport protein is present at a low concentration. The photoincorporation of ({sup 125}I)IAPS-forskolin into these glucose transporters was blocked by D- (but not L-) glucose, cytochalasin B, and forskolin. In addition to labeling the mammalian glucose transport proteins, ({sup 125}I)IAPS-forskolin also labeled the L-arabinose transporter from E. coli. In muscle and adipose tissues, glucose transport is markedly increased in response to insulin. ({sup 125}I)IAPS-forskolin was shown to selectivity tag the glucose transporter in membranes derived from these cells. In addition, the covalent derivatization of the transport ...