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BackgroundAmino-terminal signal peptides (SPs) are short regions that guide the targeting of secretory proteins to the correct subcellular compartments in the cell. They are cleaved...Full Text Available

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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

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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...

UK PubMed Central (United Kingdom)

Effector proteins expressed in the esophageal gland cells of cyst nematodes are delivered into plant cells through a hollow, protrusible stylet. Although evidence indicates that effector proteins function...Full Text Available

International Nuclear Information System (INIS)

Nop25 is a putative RNA binding nucleolar protein associated with rRNA transcription. The present study was undertaken to determine the mechanism of Nop25 localization in the nucleolus. Deletion experiments of Nop25 amino acid sequence showed Nop25 to contain a nuclear targeting sequence in the N-terminal and a nucleolar targeting sequence in the C-terminal. By expressing derivative peptides from the C-terminal as GFP-fusion proteins in the cells, a lysine and arginine residue-enriched peptide (KRKHPRRAQDSTKKPPSATRTSKTQRRRR) allowed a GFP-fusion protein to be transported and fully retained in the nucleolus. When the peptide was fused with cMyc epitope and expressed in the cells, a cMyc epitope was then detected in the nucleolus. Nop25 did not localize in the nucleolus by deletion of the peptide from Nop25. Furthermore, deletion of a subdomain (KRKHPRRAQ) in the ...

British Library Electronic Table of Contents (United Kingdom)

Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not...

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, ...

UK PubMed Central (United Kingdom)

BackgroundIn chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid...Full Text Available

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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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Diethylene glycol (DEG) is an industrial chemical, the misuse of which has led to numerous epidemic poisonings worldwide. The mechanism of its toxicity has not been defined as to the precise relationship between the metabolism of DEG and target organ toxicity. The purpose of this study was to investigate the mechanism for the acute toxicity of DEG, and the effect of the alcohol dehydrogenase inhibitor 4-methylpyrazole (fomepizole), by determining the relationship between accumulation of DEG or its metabolites and the resulting kidney and liver toxicity. Rats were treated by oral gavage with water, 2 g/kg DEG (low dose), 10 g/kg DEG (high dose), or 10 g/kg DEG + fomepizole, and blood and urine were collected over 48 h. Rats treated with high-dose DEG had metabolic acidosis, increased BUN an...

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In the present study, the immunomodulatory effect of {beta}-endorphin ({beta}-E) and shorter pro-opiomelancortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity and their non-opioid derivatives were tested. With the exception of {alpha}-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10{sup {minus}17}M and higher than 10{sup {minus}8}M were without effect. {beta}-E and dT{beta}E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations. {gamma}-E and dT{gamma}E proved to be less potent inhibitors, reaching maximal ...

British Library Electronic Table of Contents (United Kingdom)

Adipose tissue plays an essential role in energy homeostasis as a metabolic and endocrine organ. Accordingly, adipocytes are emerging as a major drug target for obesity and obesity-mediated metabolic syndrome. Dysfunction of enlarged adipocytes in obesity is involved in obesity-mediated metabolic syndrome. Adipocytokines, such as adiponectin released from small adipocytes, are able to prevent these disorders. In this study, we found that honokiol, an ingredient of Magnolia officinalis used in traditional Chinese and Japanese medicines, enhanced adipocyte differentiation in 3T3-L1 preadipocytes. Oil Red O staining showed that treatment with honokiol in the presence of insulin dose-dependently increased lipid accumulation in 3T3-L1 preadipoyctes although its activity was weak compared with r...

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Background In chordates, retinoid metabolism is an important target of short-chain dehydrogenases/reductases (SDRs). It is not known whether SDRs play a role in retinoid metabolism of protostomes, such as Drosophila melanogaster. Methods Drosophila genome was searched for genes encoding proteins with ?50% identity to human retinol dehydrogenase 12 (RDH12). The corresponding proteins were expressed in Sf9 cells and biochemically characterized. Their phylogenetic relationships were analyzed using PHYLIP software. Results A total of six Drosophila SDR genes were identified. Five of these genes are clustered on chromosome 2 and one is located on chromosome X. The deduced proteins are 300 to 406 amino acids long and are associated with microsomal membranes. They recognize all-trans-retinaldehyd...

British Library Electronic Table of Contents (United Kingdom)

Abstract Many solute carrier transporters that interact with anticancer agents and contribute to their pharmacokinetics have been shown to be differentially upregulated in cancer cells as a result of adaptive response to altered nutritional requirements. This review focuses on pathophysiological function of membrane transporters responsible for the influx of physiological substances including oligopeptides, amino acids, and organic cations and anions, and summarizes the recent knowledge regarding mechanisms in their gene expressions. Broad substrate specificity of enhanced oligopeptide H+/peptide cotransporter 1 activity in cancer cells is useful for tumor tissue-specific delivery of chemotherapeutic agents and positron emission tomography diagnostic probes. Amino acid transporters such as...

British Library Electronic Table of Contents (United Kingdom)

Summation Copper-64 (T1/2?=?12.7 hours; ?+, 0.653?MeV [17.8 %]; ??, 0.579?MeV [38.4 %]) has decay characteristics that allow for positron emission tomography (PET) imaging and targeted radiotherapy of cancer. The well-established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to peptides and other biologically relevant small molecules, antibodies, proteins, and nanoparticles. The 12.7-hours half-life of 64Cu provides the flexibility to image both smaller molecules and larger, slower clearing proteins and nanoparticles. In a practical sense, the radionuclide or the 64Cu-radiopharmaceuticals can be easily shipped for PET imaging studies at sites remote to the production facility. Due to the versatility of 64Cu, ...

UK PubMed Central (United Kingdom)

A general method is described to sequester peptides containing azides from complex peptide mixtures, aimed at facilitating mass spectrometric analysis to study different aspects of proteome...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. All three ...

UK PubMed Central (United Kingdom)

AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.METHODS:...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

Transcriptional regulation of the galactose-metabolizing genes in Saccharomyces cerevisiae depends on three core proteins: Gal4p, the transcriptional activator that binds to upstream activating DNA sequences (UASGAL); Gal80p, a repressor that binds to the carboxyl terminus of Gal4p and inhibits transcription; and Gal3p, a cytoplasmic transducer that, upon binding galactose and adenosine 5'-triphosphate, relieves Gal80p repression. The current model of induction relies on Gal3p sequestering Gal80p in the cytoplasm. However, the rapid induction of this system implies that there is a missing factor. Our structure of Gal80p in complex with a peptide from the carboxyl-terminal activation domain of Gal4p reveals the existence of a dinucleotide that mediates the interaction between the two. Biochemical and in vivo experiments suggests that nicotinamide adenine dinucleotide phosphate (NADP) plays a key role in the initial induction event.

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The response of Desulfovibrio vulgaris Hildenborough (DvH),a sulphate-reducing bacterium, to nitrate stress was examined usingquantitative proteomic analysis. DvH was stressed with 105 m M sodiumnitrate(NaNO3), a level that caused a 50 percent inhibition in growth.The protein profile of stressed cells was compared with that of cellsgrown in the absence of nitrate using the iTRAQ peptide labellingstrategy and tandem liquid chromatography separation coupled with massspectrometry (quadrupoletime-of-flight) detection. A total of 737 uniqueproteins were identified by two or more peptides, representing 22 percentof the total DvH proteome and spanning every functional category. Theresults indicate that this was a mild stress, as proteins involved incentral metabolism and the sulphate reduction pathway were unperturbed.Proteins involved in the nitrate reduction pathway increased. Increasesseen in transport systems for proline, ...

International Nuclear Information System (INIS)

The long and resource intensive process of drug discovery and development is confronted with the basic challenge of providing effective and safe therapies at reasonably low costs. The better the mechanism of a disease is known, the higher the probability to find an appropriate therapy. Also, the better and earlier a disease can be diagnosed and characterized, the higher the chance to be able to interfere in this process with a chemical entity. This reasoning sets the framework for the use of imaging in drug discovery. We discuss the relevance of magnetic resonance imaging and spectroscopy to derive anatomical, functional, metabolic and target-related information in the context of pharmacological research in vivo. (author)

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 ...

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C-type natriuretic peptide (CNP) is a member of the small family of natriuretic peptides that also includes atrial natriuretic peptide (ANP) and brain, or B-type natriuretic peptide (BNP). Unlike them, it performs its major functions in an autocrine or paracrine manner. Those functions, mediated through binding to the membrane guanylyl cyclase natriuretic peptide receptor B (NPR-B), or by signaling through the non-enzyme natriuretic peptide receptor C (NPR-C), include the regulation of endochondral ossification, reproduction, nervous system development, and the maintenance of cardiovascular health. To date, the regulation of CNP gene expression has not received the attention that has been paid to regulation of the ANP and BNP genes. CNP expression in vitro is regulated by TGF-b and recepto...

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 ...

UK PubMed Central (United Kingdom)

Sustained metabolic rates (SusMR) are time-averaged metabolic rates that are measured in free-ranging animals maintaining constant body mass over periods long enough that metabolism is fueled by food...Full Text Available

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Lung Diseases; Cancer

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PMID:5924644

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UK PubMed Central (United Kingdom)

Glucagon-like peptide-2 (GLP-2) is a nutrient-regulated intestinotrophic hormone derived from proglucagon in the distal intestine. Enteral nutrients (EN) potentiate the action of GLP-2 to reverse parenteral...Full Text Available

UK PubMed Central (United Kingdom)

OBJECTIVEThis randomized, four-arm, placebo-controlled, dose-ranging phase 2 trial was conducted to determine whether repeated subcutaneous injections of the altered peptide ligand,...Full Text Available

UK PubMed Central (United Kingdom)

High-density lipoproteins (HDL) were examined as potential carriers of small peptides in plasma. HDL purified by density gradient centrifugation was delipidated and fractionated by size-exclusion...Full Text Available

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

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

Science.gov (United States)

In this work, we query the Chlamydomonas reinhardtii copper regulon at a whole-genome level. Our RNA-Seq data simulation and analysis pipeline validated a 2-fold cutoff and 10 RPKM (reads per kilobase of mappable length per million mapped reads) (~1 mRNA per cell) to reveal 63 CRR1 targets plus another 86 copper-responsive genes. Proteomic and immunoblot analyses captured 25% of the corresponding proteins, whose abundance was also dependent on copper nutrition, validating transcriptional regulation as a major control mechanism for copper signaling in Chlamydomonas. The impact of copper deficiency on the expression of several O2-dependent enzymes included steps in lipid modification pathways. Quantitative lipid profiles indicated increased polyunsaturation of fatty acids on thylakoid membrane digalactosyldiglycerides, indicating a global impact of copper deficiency on the photosynthetic apparatus. Discovery of a putative plastid copper chaperone and a membrane ...

International Nuclear Information System (INIS)

Perinatal exposure to cadmium (Cd) or methylmercury (MeHg) results in impaired neurodevelopment. Thyroid hormone is essential for normal brain development. However, the issue whether Cd or MeHg, especially at low doses, interrupts thyroid hormone action remains to be investigated. In the present study, effects of perinatal exposure to low levels of Cd or MeHg on thyroid hormone metabolism were examined using metallothionein I and II (MT-I/II) null or wild-type neonatal mice. Dams were exposed to 10 mg/L water of Cd or 5 mg/kg chow of MeHg from gestational day 0 to post-natal day 10 (PND 10). Sera, livers and brains were collected from neonates on PND 10. Iodothyronine deiodinase activities and serum thyroxine (T4) concentrations were measured. MeHg exposure failed to induce changes in serum T4 levels and liver type 1 deiodinase (D1) and brain type 2 deiodinase (D2) activities regardless of the MT genotype. However, exposure to MeHg resulted in a decrease in brain ...

British Library Electronic Table of Contents (United Kingdom)

Abstract Lyme neuroborreliosis (LNB) is a serious but treatable disease. The diagnosis of LNB poses a challenge to clinicians, and improved tests are needed. The C6-peptide ELISA is frequently used on serum but not on cerebrospinal fluid (CSF). Data on the sensitivity of the C6-peptide ELISA in CSF in patients suffering from LNB have been conflicting. Serum-CSF pairs from 59 LNB patients, 36 Lyme non-neuroborreliosis cases, 69 infectious meningitis/encephalitis controls and 74 neurological controls were tested in a C6-peptide ELISA. With the optimal cut-off of 1.1, the sensitivity of the C6-peptide ELISA for LNB patients in CSF was 95%, and the specificity was 83% in the Lyme non-neuroborreliosis patients, 96% in the infectious controls, and 97% in the neurological controls. These results ...

Science.gov (United States)

The natriuretic peptides are considered to be cardioprotective; however, their receptors have not been identified in human myocardium using radiolabeled analogs. Dendroaspis natriuretic peptide (DNP) has been recently identified as a new member of this peptide family and is thought to be less susceptible to enzymatic degradation. Therefore, we have developed the novel radiolabeled analog [125I]-DNP and used this to localize high-affinity (K(D)=0.2 nmol/L), saturable, specific binding sites in adult human heart (n=6) and coronary artery (n=8). In competition binding experiments, atrial natriuretic peptide and brain type natriuretic peptide had greater affinity for [125I]-DNP binding sites than C-type natriuretic peptide and the natriuretic peptide receptor (NPR)-C ligand, cANF. This rank order of potency suggested binding of [125I]-DNP was ...

International Nuclear Information System (INIS)

A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content or the absorption, metabolism, or excretion of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific ...

UK PubMed Central (United Kingdom)

AMP-activated-protein-kinase (AMPK) is a key sensor and regulator of cellular and whole-body energy metabolism and plays a key role in regulation of lipid metabolism. Since lipid metabolism...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundMicroorganisms display vast diversity, and each one has its own set of genes, cell components and metabolic reactions. To assess their huge unexploited metabolic potential...Full Text Available

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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)

To evaluate the contribution of genetic influences on the individual variation in plateau serum salicylate levels, salicylate metabolism was studied in seven pairs of identical and six pairs of fraternal...Full Text Available

UK PubMed Central (United Kingdom)

Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which...Full Text Available

UK PubMed Central (United Kingdom)

Endogenous opioid peptides are substances involved in cell communication. They are present in various organs and tissues of the male and female reproductive tract, suggesting that they may regulate...Full Text Available

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Technology is being developed for preparing functional materials by synthesizing new functional peptides in which non-natural amino acid needed for the functional manifestation is introduced, and by modifying the surface of a base plate such as silica glass by using such peptides. Activities were conducted in the three areas of (1) creation of functional molecules, (2) materialization technology, and (3) comprehensive investigation and research; the activities were carried out independently and parallelly in the first two areas. In (1), design technique for the structures and functions of peptides was developed, as were conformational control technique, synthesis of peptides having optical/electronic functions, peptide synthesis by an enzyme method, and R and D on introduction of non-natural amino acid into peptides; in (2), element technologies were developed ...

Science.gov (United States)

Amyloid aggregation starts with the initial misfolding of peptide/protein precursors, with subsequent structural rearrangement into oligomers and protofibrils; the latter eventually organize into fibrils with shared basic structural features, found deposited in amyloid diseases. Mounting evidence indicates early oligomers as the most toxic amyloid species; accordingly, the search of inhibitors of their growth is considered a promising target to prevent amyloid toxicity. We recently showed that oleuropein aglycon, a polyphenol abundant in the extra virgin olive oil, interferes with the aggregation of amylin (involved in type-2 diabetes), eliminating its cytotoxicity. Here we report that oleuropein aglycon also hinders amyloid aggregation of A?(1-42) and its cytotoxicity, suggesting a general effect of such polyphenol. In particular, by using a wide panel of different spectroscopic, immunologic, cell viability and imaging techniques we provide a ...

CERN Document Server

Constraints on target chamber first wall and target designs that will enable NIF debris shields to survive

International Nuclear Information System (INIS)

The effects of D-amino acids at Asp"2"3 and Ser"2"6 residues on the conformational preference of #beta#-amyloid (A#beta#) peptide fragment (A#beta#_2_0_-_2_9) have been studied using different spectroscopic techniques, namely vibrational circular dichroism (VCD), vibrational absorption, and electronic circular dichroism. To study the structure of the A#beta#_2_0_-_2_9, [D-Asp"2"3]A#beta#_2_0_-_2_9, and [D-Ser"2"6]A#beta#_2_0_-_2_9 peptides under different conditions, the spectra were measured in 10 mM acetate buffer (pH 3) and in 2,2,2-trifluoroethanol (TFE). The spectroscopic results indicated that at pH 3, A#beta#_2_0_-_2_9 peptide takes random coil with #beta#-turn structure, while [D-Ser"2"6]A#beta#_2_0_-_2_9 peptide adopts significant amount of polyproline II (PPII) type structure along with #beta#-turn contribution and D-Asp-substituted peptide ([D-Asp"2"3]A#beta#_2_0_-_2_9) ...

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No abstract prepared.

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Published in summary form only.

International Nuclear Information System (INIS)

Short communication.

International Nuclear Information System (INIS)

Japanese (Jan 1986). Japan Taniguchi, Yoshiyuki Torizumi, Kazutami Katu,

DEFF Research Database (Denmark)

Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism.

International Nuclear Information System (INIS)

Neurotensin (NT) and its high affinity receptor (NTR1) are involved in several neoplastic processes. Thus, NT-based radiopharmaceuticals are potential tracers for targeted diagnosis and therapy of NTR-positive tumours. A new analogue based on NT(8-13), NT-XIX, with the three enzymatic cleavage sites stabilised, was synthesised and tested. The synthesis was performed by Boc strategy. Labelling with "9"9"mTc/"1"8"8Re was performed using the tricarbonyl technique. Metabolic stability was tested in vitro and in vivo. NT-XIX was further characterised in vitro in HT-29 cells and in vivo in nude mice with HT-29 xenografts. NT-XIX showed much longer half-lives than non-stabilised analogues. Binding to NTR1 was highly specific, although the affinity was lower than that of natural NT. Bound activity rapidly internalised into HT-29 cells and 50% remained trapped after 24 h. In the time-course biodistribution, the highest uptake was found in the tumour at ...

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)

In APCs, presentation by MHC II molecules of the chemically dominant peptide from the protein hen egg white lysozyme (HEL) generates different conformational isomers of the peptide-MHC II complexes (pMHC). Type B pMHCs are formed in early endosomes from exogenous peptides in the absence of H2-DM, whereas in contrast, type A pMHC complexes are formed from HEL protein in late vesicles after editing by H2-DM. Thus, H2-DM edits off the more unstable pMHC complexes, which are not presented from HEL. In this study, we show that type B pMHC complexes were presented from HEL protein only after stimulation of dendritic cells (DC) with TLR ligands or type I IFN. Type I IFN contributed to most TLR ligand-induced type B pMHC generation, as presentation decreased in DC lacking the receptor for type I IFNs (IFNAR1(-/-)). In contrast, presentation of type A pMHC from HEL and from peptide was minimally affected by TLR ...

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In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate that stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic ...

British Library Electronic Table of Contents (United Kingdom)

Introduction: Tumor-derived heat shock protein (HSP)-peptide complexes (HSPPCs) induced immunity against malignancies in preclinical trials, working across tumor types and bypassing the need to identify single immunogenic peptides. These results paved the way for the use of human gp96 obtained from autologous tumor samples as an anti-cancer vaccine. Areas covered: Autologous tumor-derived HSP gp96 peptide complex (HSPPC-96) vaccine is emerging as a tumor- and patient-specific cancer vaccine, with confirmed activity in several malignancies. It has been tested in Phase III clinical trials in advanced melanoma and kidney cancer with evidence for efficacy in patients with earlier stage disease. HSPPC-96-based vaccine demonstrated an excellent safety profile, thus emerging as a novel therapeuti...

British Library Electronic Table of Contents (United Kingdom)

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.

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Analyses of food-borne pathogens are of great importance in order to minimize the health risk for customers. Thus, very sensitive and rapid detection methods are required. Current conventional culture techniques are very time consuming. Modern immunoassays and biochemical analysis also require pre-enrichment steps resulting in a turnaround time of at least 24 h. Biomagnetic separation (BMS) is a promising more rapid method. In this study we describe the isolation of high affine and specific peptides from a phage-peptide library, which combined with BMS allows the detection of Salmonella spp. with a similar sensitivity as that of immunomagnetic separation using antibodies.

UK PubMed Central (United Kingdom)

The effect of 5,5′-diphenylhydantoin on thyroxine metabolism was examined in five normal volunteers. Intravenous injection of radiothyroxine was followed by a 10-12 day control and subsequent...Full Text Available

UK PubMed Central (United Kingdom)

The metabolism of ¹⁴C-labeled fatty acids and triacylglycerols was followed in intact germinating oil palm seedlings as well as in tissue slices. In the germinating seedling, the shoot contained...Full Text Available

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Six genes involved in the heparan sulfate and heparin metabolism pathway, DSEL (dermatan sulfate epimerase-like), EXTL1 (exostoses (multiple)-like 1), HS6ST1...Full Text Available

UK PubMed Central (United Kingdom)

The current obesity pandemic is expected to result in considerable downstream morbidity, mortality and incremental costs to health care systems around the world. The major metabolic complications of...Full Text Available

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BackgroundComplex etiology and pathogenesis of pathophysiological components of the cardio-metabolic syndrome have been demonstrated in humans and animal models.Methodology/Principal...Full Text Available

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As part of the study of cytokinin metabolic pathways, an enzyme, adenosine phosphorylase (EC 2.4.2.-), which catalyzed the ribosylation of N⁶-(Δ²-isopentenyl)adenine,...Full Text Available

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Choline (Cho)-containing phospholipids are the most abundant phospholipids in cellular membranes and play fundamental structural as well as regulatory roles in cell metabolism and signaling. Although...Full Text Available

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The mechanism of metabolic energy production by malolactic fermentation in Lactococcus lactis has been investigated. In the presence of L-malate, a proton motive force composed of a membrane potential...Full Text Available

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Host cells use metabolic signaling through the LXRα nuclear receptor to defend against Listeria monocytogenes infection. 25-Hydroxycholesterol is a natural ligand of LXRs that...Full Text Available

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The influence of obesity on the metabolism of apolipoprotein B (apo B) in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was investigated...Full Text Available

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Histamine has been proposed to be an important regulator of energy intake and expenditure. The aim of this study was to evaluate histamine regulation of glucose and lipid metabolism and development...Full Text Available

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Hydrolytic exoenzymes as indicators of metabolically active bacteria were investigated in four consecutive sapropel layers collected from bathyal sediments of the eastern Mediterranean Sea. For comparison,...Full Text Available

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A commercial blend of essential oil (EO) compounds was added to a grass, maize silage, and concentrate diet fed to dairy cattle in order to determine their influence on protein metabolism by ruminal...Full Text Available

UK PubMed Central (United Kingdom)

Energetically costly behaviours, such as flight, push physiological systems to their limits requiring metabolic rates (MR) that are highly elevated above the resting MR (RMR). Both RMR and MR during...Full Text Available

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Calcium requirements of North American adolescents were set at 1300 mg/day based on data from white girls. Calcium requirements for Asian-American adolescents have not been studied. Using metabolic...Full Text Available

UK PubMed Central (United Kingdom)

There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically...Full Text Available

UK PubMed Central (United Kingdom)

The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as ...Full Text Available

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BackgroundObesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates...Full Text Available

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Background and RationaleAtypical antipsychotics exhibit metabolic side effects including diabetes mellitus and obesity. The adverse events are preceded by acute worsening of oral...Full Text Available

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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 ...

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... AUREMN), Rio de Janeiro, RJ (Brazil) [vp.] APPLIED LIFE SCIENCES cpb

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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

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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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Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel coronavirus that cost nearly 800 lives. While there have been no recent outbreaks of the disease, the threat...Full Text Available

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We have developed a method for dissecting single neurons from the nematode Ascaris suum, in order to determine their peptide content by mass spectrometry (MS). In this paper,...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

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.

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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

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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

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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

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Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including...Full Text Available

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Isotope ratios of cellulose and cellulose nitrate from aquatic Crassulacean acid metabolism (CAM) and non-CAM plants were determined. Cellulose oxygen istope ratios for all plants that grew together...Full Text Available

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All microRNA (miRNA) target—finder algorithms return lists of candidate target genes. How valid is that output in a biological setting? Transcriptome analysis has proven to be a useful approach...Full Text Available

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The GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and ?-lactams, such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) ...

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Aims.- To examine the relationships between depression, coronary artery disease, type 2 diabetes, metabolic syndrome and quality of life in Taiwanese adults from a cardiovascular department of a major hospital in Taiwan. Background.- Research suggests associations between depression, metabolic syndrome and quality of life. Despite this fact, few studies have investigated these relationships among Taiwanese. Design.- A cross-sectional descriptive correlational design was used to conduct this study. Methods.- A convenience sample of 140 adults participated in the study. Data were analysed with descriptive statistics, Pearson-s correlations, hierarchical regression and t-tests. Results.- Almost a half of the subjects (465%) had metabolic syndrome. The most common combination of metabolic synd...

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 ...

Science.gov (United States)

Metabolic carbon labelling experiments enable a large amount of extracellular fluxes and intracellular carbon isotope enrichments to be measured. Since the relation between the measured quantities and the unknown intracellular metabolic fluxes is given by bilinear balance equations, flux determination from this data set requires the numerical solution of a nonlinear inverse problem. To this end, a general algorithm for flux estimation from metabolic carbon labelling experiments based on the least squares approach is developed in this contribution and complemented by appropriate tools for statistical analysis. The linearization technique usually applied for the computation of nonlinear confidence regions is shown to be inappropriate in the case of large exchange fluxes. For this reason a sophisticated compactification transformation technique for nonlinear statistical analysis is developed. Statistical analysis is then ...

CERN Document Server

Zinc-fingers, which widely exist in eukaryotic cell and play crucial roles in life processes, depend on the binding of zinc ion for their proper folding. To computationally study the zinc coupled folding of the zinc-fingers, charge transfer and metal induced protonation/deprotonation effects have to be considered. Here, by attempting to implicitly account for such effects in classical molecular dynamics and performing intensive simulations with explicit solvent for the peptides with and without zinc binding, we investigate the folding of the Cys2His2 type zinc-finger motif and the coupling between the peptide folding and zinc binding. We find that zinc ion not only stabilizes the native structure, but also participates in the whole folding process. It binds to the peptide at early stage of folding, and directs or modulates the folding and stabilizations of the component beta-hairpin and alpha-helix. Such a crucial role of ...

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The photoelectron resonance capture ionization (PERCI) of cysteine (Cys) and small gas-phase neutral peptides that contain the Cys residue (Cys-Gly, g-Glu-Cys, and glutathione (g-Glu-Cys-Gly)) is reported. At an ionization energy less than 1eV two types of dissociative electron attachment ionization were observed for Cys: hydrogen atom loss, resulting in formation of the ion [Cys-H]-, and dissociation of the CH2-SH bond, resulting in formation of the ion [SH]-. The presence of these ions suggests that both the p*(-CO2H) and *(C-S) orbitals can act as low energy electrophores on Cys. This ionization trend was observed for the dipeptides Cys-Gly and g-Glu-Cys as well as glutathione, with evidence that dissociation of the CH2-SH bond in these peptides can also result in ions of the form [M-SH...

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Abstract Neurodegenerative and neurometabolic disorders may cause significant morbidity and mortality in children. Imaging is important in early diagnosis of metabolic disorders and in determining the extent of brain injury. Especially after the development of new techniques such as diffusion-weighted magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), neuroimaging plays more important role in the diagnosis and management of these disorders. In these disorders, usually a mutation causes a clinically significant block in one or more metabolic pathways. This blockage usually results in either a deficiency of the product or in an accumulation of substrate with damage induced by either storage or toxicity. The presenting symptoms are usually nonspecific. In some of the ...

International Nuclear Information System (INIS)

[F-18]FDG PET brain imaging is an accurate predictor of primary brain tumor grading and prognosis. The purpose of this study was to evaluate simplified [F-18]FDG PET metabolic indices as indicators of proliferative activity of brain tumor cells. Twenty-five patients with glioma were studied with [F-18]FDG PET. From the tissue radioactivity ratios, following tumor metabolic indices were calculated: 1) the tumor-to-whole brain ratio (T/WB), 2) the ratio of tumor-to-contralateral gray matter at the level of centrum semiovale (T/GM), 3) the ratio of tumor-to-contralateral white matter at the level of centrum semiovale (T/WM), 4) the tumor-to-ipsilateral cerebella ratio (T/iCB) and 5) the tumor-to-contralateral cerebellar ratio (T/cCB). A standardized threshold method was used to define ROIs in the tumor areas having representative metabolic activites. Correlations of the tumor metabolic indices with ...

UK PubMed Central (United Kingdom)

A diagnosis of dementia is devastating at any age but diagnosis in younger patients presents a particular challenge. The differential diagnosis is broad as late presentation of metabolic disease...Full Text Available

UK PubMed Central (United Kingdom)

High resolution of NMR spectroscopic data of biosamples are a rich source of information on the metabolic response to physiological variation or pathological events. There are many advantages...Full Text Available

UK PubMed Central (United Kingdom)

The quest to understand why we age has given rise to numerous lines of investigation that have gradually converged to include metabolic control by mitochondrial activity as a major player. That...Full Text Available

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Summary: Analysis of biological networks requires assessing the statistical significance of network-based predictions by using a realistic null model. However, the existing network null model, switch randomization, is unsuitable for metabolic networks, as it does not include physical constraints and generates unrealistic reactions. We present JMassBalance, a tool for mass-balanced randomization and analysis of metabolic networks. The tool allows efficient generation of large sets of randomized networks under the physical constraint of mass balance. In addition, various structural properties of the original and randomized networks can be calculated, facilitating the identification of the salient properties of metabolic networks with a biologically meaningful null model. Availability and Imp...

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... elevated blood sugar levels, but not full-blown diabetes. What are the keys to preventing the disease? ... been well studied, in a study called The Diabetes Prevention Program, in several thousand people with this ...

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MD, Chief, Division of Endocrinology, Diabetes and Metabolism, Trinitas Regional Medical Center, Elizabeth, NJ. Review provided by VeriMed Healthcare Network. Also reviewed...

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An elderly man receiving chlorambucil for chronic lymphatic leukaemia developed focal fits. The onset and frequency were dose related. There was no evidence of metabolic disturbance or of meningeal...Full Text Available

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diet and genetic obesity metabolic defects and inflammation. To determine the role of adipocyte death in promoting adipose tissue inflammation and insulin resistance in animal...

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Background: Apheresis is a procedure to selectively obtain blood components. For the collection process citrate is routinely used. It inhibits coagulation by binding to ionized calcium and leads to metabolic alkalosis. Objective: Whether regular apheresis affects bone and mineral metabolism is unknown. The intention of this study was to investigate 1) the acute effects of apheresis on acid-base balance, bone and mineral metabolism and 2) to compare bone mineral density (BMD) at the lumbar spine and hip of donors to matched control subjects. Design: In this open, observational, single-center, cross-sectional study we enrolled 102 regular plasma and thrombocyte donors to pursue objective 1) and compared those to 102 matched controls (CTR) for objective 2). Results: Platelet donation led to s...

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... reactions selenium 74 target selenium 77 target strontium 84 target strontium

UK PubMed Central (United Kingdom)

In order to identify novel high value antibacterial targets it is desirable to delineate whether the inactivation of the target enzyme will lead to bacterial death or stasis. This knowledge is particularly...Full Text Available

International Nuclear Information System (INIS)

Two peptide ligands conjugated adenine, [9-N-(tritylmercapto acetyl diglycyl aminoethyl) adenine, Tr-MAG_2-Ade] and [9-N-(tritylmercapto acetyl triglycyl aminoethyl) adenine, Tr-MAG3-Ade], are synthesized and labeled with "9"9"mTc by directly labeling method. The stability of "9"9"mTc-MAG_2- adenine and "9"9"mTc-MAG_3-adenine in vitro is measured. The uptake radios of tumor to muscle at 3h post-injection are 5.70 and 4.92, respectively. The biodistribution and scintigraphic imaging studies show that the two complexes have high localization in tumor and high contrasted tumor images can be obtained, which suggest their potential utility as tumor imaging agents. But the high radioactivity of abdomen could prevent the tumor imaging in this area. (author)

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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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Abstract In 46 febrile neutropenic patients who had undergone haematopoietic stem cell transplantation, the fluorescence in situ hybridisation using peptide nucleic acid probes (PNA FISH), Gram stain/acridine orange leukocyte cytospin (Gram/AOLC), and differential time to positivity (DTP) methods were performed for detection of catheter related bloodstream infections (CRBSIs). As compared with the DTP method (which detected 11 patients with CRBSI), the PNA FISH and the Gram/AOLC methods detected ten of 11 CRBSI patients, resulting in a sensitivity, specificity, negative predictive value and positive predictive value of 91%, 100%, 97% and 100%, respectively, for the PNA FISH method as well as for the Gram/AOLC method.

Energy Technology Data Exchange (ETDEWEB)

Computational fluid dynamics(CFD) code FLUENT was used to simulate the thermal hydraulic processes occurring in conceptual design of the accelerator-driven subcritical reactor(ADSR) liquid lead target. The purpose of the analysis is to investigate the thermal hydraulic characteristics of liquid lead as ADSR target material with various target geometries and injection locations of proton beam. In the calculation analysis, the local temperature of the liquid lead target rises to the boiling temperature very rapidly. When the proton beam is injected from the bottom of the target system, the duration time to reach the boiling temperature is longer and the temperature distribution is flatter than other cases.

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The design of the absorber blocks for internal and external dumping of the SPS proton beam is discussed. In addition, the external target stations for slow and fast extracted proton beams are described.

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Nato SCI-12 on Camouflage Evaluation Workshop on Search and Target Acquisition The Netherlands, June 1999. Image Discrimination Models for Object Detection ...

International Nuclear Information System (INIS)

The National Ignition Facility (NIF) is a proposed Department of Energy facility which will contribute to the resolution of important Defense Program and inertial fusion energy issues for energy production in the future. The NIF will consist of a laser system with 192 independent beamlets transported to a target chamber. The target chamber is a multi-purpose structure that provides the interface between the target and the laser optics. The chamber must be capable of achieving moderate vacuum levels in reasonable times; it must remain dimensionally stable within micron tolerances, provide support for the optics, diagnostics, and target positioner; it must minimize the debris from the x-ray and laser light environments; and it must be capable of supporting external neutron shielding. The chamber must also be fabricated from a low neutron activation material. The fusion reaction in the ...

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The effective half-life based on urine bioassay results of Wolsung NPP's worker was calculated. The effective half-life for tritiated water vapour obtained was 5 {approx} 9 days. In comparison to 10 days reported for ICRP-30, it is lower than the corresponding half-life for Reference Man. Also, the half-life was calculated based on intake amount of daily water. According to this result, the metabolism was reviewed.

UK PubMed Central (United Kingdom)

Although peroxisome proliferator-activated receptor alpha (PPARα) is closely associated with myocardial fatty acid metabolism, the pathophysiological role of PPARα in myocardial infarction...Full Text Available

UK PubMed Central (United Kingdom)

Metabolism of [¹⁴C]gibberellin (GA) A₁₂ (GA₁₂) and [¹⁴C]gibberellin A₁₂-aldehyde (GA₁₂-aldehyde) was examined in cotyledons and seed...Full Text Available

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Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG)...Full Text Available

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Transcription activation of sulfur metabolism in yeast is dependent on two DNA binding factors, the centromere binding factor 1 (Cbf1) and Met4. While the role of Met4 was clearly established by showing...Full Text Available

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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

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With the aim of an experimental check on the validity of the theory of molecular recognition, the authors have carried out the chemical-enzymatic synthesis and cloning of the gene of human calcitonin and also of the genes of antisense polypeptides to human calcitonin and miniproinsulin. It has been shown that recombinant plasmids obtained on the basis of these synthetic genes are capable of ensuring the biosynthesis of the given polypeptides in E. coli cells as hybrid proteins with the IgG-binding domain of staphylococcal protein A.

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Transforming growth factor (TGF)-βs are secreted in large latent complexes consisting of TGF-β, its N-terminal latency-associated peptide (LAP) propeptide, and latent TGF-β...Full Text Available

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CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the...Full Text Available

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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.

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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.

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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This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary...Full Text Available

UK PubMed Central (United Kingdom)

We have purified and characterized two peptides, named KAaH1 and KAaH2 (AaH polypeptides 1 and 2 active on K⁺ channels, where AaH stands for Androctonus australis Hector),...Full Text Available

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We proposed a solid and a mercury target concepts through the preliminary conceptual design. To feasible these concepts, analysis and experimental works are being carried out. This paper introduces an outline of present status of target R and D such as heat transfer augmentation experiments for the solid target, mercury flow tests with a loop of maximum flow rate of 15L/min, flow pattern measurements for a cold source moderator etc. as well as preliminary conceptual design works. (author)

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Short communication.

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To determine a rat strain appropriate for carcinogenicity testing of FYX-051, a xanthine oxidoreductase inhibitor, we performed a 4-week oral toxicity study by administering 0.3, 1 and 3?mg/kg, and 1, 3 and 10?mg/kg of FYX-051 to male Sprague-Dawley (SD) and Fischer (F344) rats, respectively. Histopathology revealed that the degree of FYX-051-induced nephropathy was 3-fold stronger in SD rats than in F344 rats. Our previous study demonstrated that the key factor of species differences in FYX-051-induced nephropathy is purine metabolism. This observation led us to examine the involvement of purine metabolism in differences among two strains of rats. However, purine metabolism was proven not to be implicated as an important factor. Subsequently, other factors responsible for the strain diffe...

British Library Electronic Table of Contents (United Kingdom)

Carotenoids are highly beneficial for human nutrition and health because they provide essential nutrients and important antioxidants in our diets. However, many food crops, especially the major staple crops contain only trace to low amounts of carotenoids. Although significant progress has been made in developing food crops rich in carotenoids by altering the expression of carotenoid biosynthetic genes, in many cases it has proved to be difficult to reach the desired levels of carotenoid enrichment. The recent identification and characterization of a novel gene mutation in cauliflower reveals that creating a metabolic sink to sequester carotenoids is an important mechanism to control carotenoid accumulation in plants. The successful demonstration of increased carotenoid accumulation in ass...

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The present study was designed to determine the exercise intensity equivalent to the metabolic aerobic/anaerobic transition of alloxan diabetic rats, through lactate minimum test (LMT), and to evaluate the effects of swimming exercise at this intensity (LM) on the glucose and protein metabolism of these animals. Adult male Wistar rats received alloxan (SD, alloxan-injected rats that remained sedentary) intravenously (30 mg kg?1 body weight) for diabetes induction. As controls (SC, vehicle-injected rats that remained sedentary), vehicle-injected rats were utilized. Two weeks later, the animals were submitted to oral glucose tolerance test (oGTT) and LMT. After the tests, some of the animals were submitted to swimming exercise training [TC (vehicle-injected rats that performed a 6-week exerc...

British Library Electronic Table of Contents (United Kingdom)

Acidification is one of the most common and serious problems inducing process failure in anaerobic digesters. The production of volatile fatty acids (VFAs) mainly triggers acidic shock. However, little is known about the bacteria involved in the processes of acidogenic metabolism, such as fermentation and reductive acetogenesis. Here, the metabolic responses of a methanogenic community to the acidification and resulting process deterioration were investigated using transcriptional profiling of both the 16S rRNA and formyltetrahydrofolate synthetase (FTHFS) genes. The 16S rRNA-based analyses demonstrated that the dynamic shift of bacterial populations was closely correlated with reactor performance, especially with VFA accumulation levels. The pH drop accompanied by an increase in VFAs stim...

British Library Electronic Table of Contents (United Kingdom)

Abstract Background- Cyclosporine is used for treatment of transplanted patients and for immune-mediated diseases. Cyclosporine is known to cause a combination of metabolic side effects including hypertension, hyperkalemia, hypercalciuria and hypomagnesemia. These side effects except for hypomagnesemia are the cardinal features of familial hyperkalemia and hypertension (FHHt), also called pseudohypoaldosteronism type II (PHA II). FHHt is caused by mutations in the kinases WNK1 and WNK4 resulting in an increase in renal Na-Cl cotransporter (NCC) apical distribution and function. Therefore, we studied whether cyclosporine-s metabolic side effects are mediated by WNK4 and NCC. Design- Sprague-Dawley (SD) rats were treated by cyclosporine 25-mg-kg-1 subcutaneously for 14-days. Blood pressure, ...

British Library Electronic Table of Contents (United Kingdom)

Circadian rhythms affect several processes in the body physiology. This commentary revisits the topic of `metabolic basis of diseases' with a view to shed light on how cellular energy requirements feed-forward to a sequential signaling of hormonal response, blood glucose metabolism, antioxidant activities, and pathophysiology. Attempt is made to explain how diseases that may not appear to be closely related, such as bone metabolism and vasculopathy, have an increase in oxidative damage as a common underlying biochemistry. Importantly, this article identifies oxidative damage as an outcome of sleep disturbance and hypothesize that sleep complaint is not merely one of many resulting symptoms of PTSD, but a core feature that arise from trauma and gives rise to the stress biochemistry, which i...

International Nuclear Information System (INIS)

The use of municipal sewage sludge as a fertilizer in agriculture is a convenient method of disposal. However, sludge is often contaminated with toxic organic compounds such as dioxins, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs), with implications for soil fertility and quality of crops for human and animal consumption. These compounds can be assimilated by intact plants or in-vitro cell-Culture systems. The amount of uptake depends on the plant species and on the physico-chemical conditions that influence, for example, molecular configuration; uptake rates are higher with low-molecular-weight and polar compounds. The xenobiotic can be converted to polar conjugates and hydroxylated metabolites that may also be toxic. In some cases, large amounts of the compound and/or its metabolic products are incorporated into non-extractable residues. The bound residues, especially those associated with carbohydrate fractions of the cell wall, ...

UK PubMed Central (United Kingdom)

SummaryBrown fat is specialized in energy expenditure, a process that is principally controlled by the transcriptional co-activator PGC-1α. Here we describe a molecular...Full Text Available

UK PubMed Central (United Kingdom)

Mitochondria and peroxisomes execute some analogous, nonredundant functions including fatty acid oxidation and detoxification of reactive oxygen species, and, in response to select metabolic cues, undergo...Full Text Available

UK PubMed Central (United Kingdom)

Sixty-five patients operated with total pancreatectomy were reviewed with respect to factors influencing operative mortality and morbidity, long-term survival, and metabolic sequelae. The diagnoses...Full Text Available

UK PubMed Central (United Kingdom)

Purpose of ReviewThe vertebrate cap’n’collar family transcription factor Nrf2 and its invertebrate homologs SKN-1 (in worms) and CncC (in flies) function...Full Text Available

UK PubMed Central (United Kingdom)

Reactive oxygen species (ROS), inevitable byproducts of aerobic metabolism, are known to cause oxidative damage to cells and molecules. This, in turn, is widely accepted as a pivotal determinant of...Full Text Available

UK PubMed Central (United Kingdom)

Peripheral subunit binding domains (PSBDs) are integral parts of large multienzyme complexes involved in carbohydrate metabolism. PSBDs facilitate shuttling of prosthetic groups between different catalytic...Full Text Available

UK PubMed Central (United Kingdom)

The metabolism of DDT has been followed in pure lines of laboratory-reared resistant and susceptible anophelines using gas-liquid chromatography. Relatively large amounts of DDE were formed in...Full Text Available

UK PubMed Central (United Kingdom)

Many of the gene products that participate in nitrogen metabolism are sensitive to nitrogen catabolite repression (NCR), i.e., their expression is decreased to low levels when readily used nitrogen...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe pregnane X receptor (PXR; NR1I2), a member of the nuclear receptor superfamily, regulates the expression of metabolic enzymes and transporters involved...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundEpidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear....Full Text Available

UK PubMed Central (United Kingdom)

Disorders of mitochondrial fat metabolism lead to sudden death in infants and children. Although survival is possible, the underlying molecular mechanisms which enable this outcome have not yet been...Full Text Available

UK PubMed Central (United Kingdom)

Experiments were carried out to clarify problems encountered in measuring metabolic and storage pool sizes of nitrate in wheat leaf sections with an in vivo nitrate reductase assay....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundCurrently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties...Full Text Available

UK PubMed Central (United Kingdom)

Hibernators are unique among mammals in their ability to survive extended periods of time with core body temperatures near freezing and with dramatically reduced heart, respiratory, and metabolic rates...Full Text Available

UK PubMed Central (United Kingdom)

The levels of glucose, sugar phosphates, and adenosine phosphates were determined in primary leaves of intact bean plants during normal senescence and compared to leaves in which senescence was delayed...Full Text Available

UK PubMed Central (United Kingdom)

The prevalence of obesity among children, adolescents and adults has been dramatically increasing worldwide during the last several decades. The obesity epidemic has been recognized as one of...Full Text Available

UK PubMed Central (United Kingdom)

This study was designed to determine the effects of red and far red irradiation on ATP metabolism in etiolated bean buds (Phaseolus vulgaris L. var. Red Kidney). Compared to dark controls,...Full Text Available

Energy Technology Data Exchange (ETDEWEB)

When oxygen is limiting, animals can ferment glucose via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, succinate, or propionate). Because the pH dependence of H/sup +/ production by fermentation is opposite to that by hydrolysis of adenosine triphosphate formed in the fermentation, the total number of moles of protons generated is always two per mole of fermentable substrate. However, two and three times more adenosine triphosphate can be turned over per mole of protons produced in succinate and propionate fermentations, respectively, than in lactate fermentation. At its limit, this advantage would achieve the same balance between H/sup +/ production and H/sup +/ consumption during ATP cycling that is observed in aerobic metabolism, a situation observed in certain alcohol fermentations. Since proton balance during anaerobiosis is clearly adaptable, we consider possible impact ...

UK PubMed Central (United Kingdom)

In vivo plasminogen responses to various stimuli were studied. Plasminogen-¹²⁵I was prepared and used first for metabolic studies of plasminogen in control dogs. The average results were:...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundIn Saccharomyces cerevisiae galactose is initially metabolized through the Leloir pathway after which glucose 6-phosphate enters glycolysis. Galactose...Full Text Available

UK PubMed Central (United Kingdom)

While specific signalling cascades involved in aging, such as the insulin/IGF-1 pathway, are well-described, the actual metabolic changes they elicit to prolong lifespan remain obscure. Nevertheless,...Full Text Available

UK PubMed Central (United Kingdom)

IntroductionSeizures with or without trauma may cause fractures that occur commonly in epileptic seizures. Fracture risk is less reported in non-epileptic seizures. Some metabolic...Full Text Available

UK PubMed Central (United Kingdom)

The polarity of biological mediums controls a host of physiological processes such as digestion, signaling, transportation, metabolism, and excretion. With the recent widespread use of near-infrared...Full Text Available

UK PubMed Central (United Kingdom)

The response of the dissimilatory metal-reducing bacterium Shewanella alga BrY to carbon and nitrogen starvation was examined. Starvation resulted in a gradual decrease in the mean cell volume from...Full Text Available

UK PubMed Central (United Kingdom)

Chemical reactions in living cells are under strict enzyme control and conform to a tightly regulated metabolic program. However, uncontrolled and potentially deleterious endogenous reactions occur,...Full Text Available

UK PubMed Central (United Kingdom)

1. The LD₅₀ of iodomethane orally administered to rats is 76mg./kg. body wt. but repeated daily doses of 30–50mg./kg. body wt. are without effect. 2. Oral doses of iodomethane to...Full Text Available

UK PubMed Central (United Kingdom)

Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyesters that have potential applications as conventional plastics, specifically thermoplastic elastomers. A wealth of biological...Full Text Available

Science.gov (United States)

Sources of manganese are identified. Uptake and distribution of manganese in plants and man are discussed, and the role of manganese in metabolism is described. The epidemiology of manganese toxicity is outlined, permissible air concentrations are listed, and the symptoms of manganese toxicity and deficiency are described. 555 references, 32 tables.

UK PubMed Central (United Kingdom)

Sirtuins are highly conserved NAD⁺-dependent protein deacetylases and/or ADP-ribosyltransferases that can extend the lifespan of several lower model organisms including yeast, worms and flies....Full Text Available

UK PubMed Central (United Kingdom)

BackgroundMacrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized...Full Text Available

UK PubMed Central (United Kingdom)

Nitric oxide (NO) and related reactive nitrogen species (RNS) play a major role in the pathophysiology of stroke and other neurodegenerative diseases. One of the poorly understood consequences...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundHigh serum uric acid concentration (hyperuricemia) has been studied for its relationship with multiple adverse health outcomes, such as metabolic syndrome. Intervention...Full Text Available