Roles of the twin-arginine translocase and associated chaperones in the biogenesis of the electron transport chains of the human pathogen Campylobacter jejuni.

Science.gov (United States)

Hitchcock, Andrew; Hall, Stephen J; Myers, Jonathan D; Mulholland, Francis; Jones, Michael A; Kelly, David J

2010-10-01

The zoonotic pathogen Campylobacter jejuni NCTC 11168 uses a complex set of electron transport chains to ensure growth with a variety of electron donors and alternative electron acceptors, some of which are known to be important for host colonization. Many of the key redox proteins essential for electron transfer in this bacterium have N-terminal twin-arginine translocase (TAT) signal sequences that ensure their transport across the cytoplasmic membrane in a folded state. By comparisons of 2D gels of periplasmic extracts, gene fusions and specific enzyme assays in wild-type, tatC mutant and complemented strains, we experimentally verified the TAT dependence of 10 proteins with an N-terminal twin-arginine motif. NrfH, which has a TAT-like motif (LRRKILK), was functional in nitrite reduction in a tatC mutant, and was correctly rejected as a TAT substrate by the tatfind and TatP prediction programs. However, the hydrogenase subunit HydA is also rejected by tatfind, but was shown to be TAT-dependent experimentally. The YedY homologue Cj0379 is the only TAT translocated molybdoenzyme of unknown function in C. jejuni; we show that a cj0379c mutant is deficient in chicken colonization and has a nitrosative stress phenotype, suggestive of a possible role for Cj0379 in the reduction of reactive nitrogen species in the periplasm. Only two potential TAT chaperones, NapD and Cj1514, are encoded in the genome. Surprisingly, despite homology to TorD, Cj1514 was shown to be specifically required for the activity of formate dehydrogenase, not trimethylamine N-oxide reductase, and was designated FdhM.

A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

DEFF Research Database (Denmark)

Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R

2016-01-01

Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome...... of inappropriate antidiuresis or congenital X-linked nephrogenic diabetes insipidus. We present a novel mutation in codon 137 within AVPR2 with substitution of glycine for arginine in male dizygotic twins. Nephrogenic diabetes insipidus was demonstrated by water deprivation test and resistance to vasopressin...

Identification of a novel antimicrobial peptide from human hepatitis B virus core protein arginine-rich domain (ARD.

Directory of Open Access Journals (Sweden)

Heng-Li Chen

Full Text Available The rise of multidrug-resistant (MDR pathogens causes an increasing challenge to public health. Antimicrobial peptides are considered a possible solution to this problem. HBV core protein (HBc contains an arginine-rich domain (ARD at its C-terminus, which consists of 16 arginine residues separated into four clusters (ARD I to IV. In this study, we demonstrated that the peptide containing the full-length ARD I-IV (HBc147-183 has a broad-spectrum antimicrobial activity at micro-molar concentrations, including some MDR and colistin (polymyxin E-resistant Acinetobacter baumannii. Furthermore, confocal fluorescence microscopy and SYTOX Green uptake assay indicated that this peptide killed Gram-negative and Gram-positive bacteria by membrane permeabilization or DNA binding. In addition, peptide ARD II-IV (HBc153-176 and ARD I-III (HBc147-167 were found to be necessary and sufficient for the activity against P. aeruginosa and K. peumoniae. The antimicrobial activity of HBc ARD peptides can be attenuated by the addition of LPS. HBc ARD peptide was shown to be capable of direct binding to the Lipid A of lipopolysaccharide (LPS in several in vitro binding assays. Peptide ARD I-IV (HBc147-183 had no detectable cytotoxicity in various tissue culture systems and a mouse animal model. In the mouse model by intraperitoneal (i.p. inoculation with Staphylococcus aureus, timely treatment by i.p. injection with ARD peptide resulted in 100-fold reduction of bacteria load in blood, liver and spleen, as well as 100% protection of inoculated animals from death. If peptide was injected when bacterial load in the blood reached its peak, the protection rate dropped to 40%. Similar results were observed in K. peumoniae using an IVIS imaging system. The finding of anti-microbial HBc ARD is discussed in the context of commensal gut microbiota, development of intrahepatic anti-viral immunity and establishment of chronic infection with HBV. Our current results suggested that

Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

KAUST Repository

Shah, Dhawal

2011-09-21

We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, Γ XP, contrary to conventional thinking that positive Γ XP\\'s indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine\\'s preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine\\'s interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on Γ XP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers (AIChE).

A novel Tc-99m and fluorescence-labeled arginine-arginine-leucine-containing peptide as a multimodal tumor imaging agent in a murine tumor model.

Science.gov (United States)

Kim, Myoung Hyoun; Kim, Seul-Gi; Kim, Dae-Weung

2018-06-15

We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The K d of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent. Copyright © 2018 John Wiley & Sons, Ltd.

Late onset of familial neurogenic diabetes insipidus in monozygotic twins.

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Cizmarova, M; Nagyova, G; Janko, V; Pribilincova, Z; Virgova, D; Ilencikova, D; Kovacs, L

2013-10-01

Autosomal dominant familial diabetes insipidus (FNDI) is a rare disease characterized by polydipsia and polyuria due to deficiency of the antidiuretic hormone, arginine vasopressin (AVP). We report the first Slovak family with the disease. Noteworthy is the concordantly belated debut of the disease symptoms in two monozygotic twin proband girls in the age of 17 years. Because of inconclusive results of water deprivation test consistent with partial diabetes insipidus (DI), missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. Molecular genetic testing of the AVP gene was proceeded, because of the inconclusive results of water deprivation test consistent with partial diabetes insipidus, missing "bright spot" of posterior pituitary gland in T1-weighted magnetic resonance imaging and family occurrence of polyuria and polydipsia on anamnestic evaluation. Genetic analysis revealed a heterozygous g.279G>A substitution that predicts a p.Ala19Thr substitution in the signal peptide of the AVP prohormone. The wide intrafamiliar variations (3 to 17 years) in disease onset together with the concordantly delayed debut of polyuria in two monozygotic twin girls suggest that individual differences in genetic influences family environmental factors may modify the penetrance of the mutation of the AVP gene. The present paper supports the notion that molecular genetic evaluation should be performed in all patients with familial occurrence of DI regardless of the clinical results.

Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan Interactions.

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Takechi-Haraya, Yuki; Saito, Hiroyuki

2018-01-01

Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet. Alternatively, CPPs favorably bind in a charge density- dependent manner to negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate and chondroitin sulfate, which are abundant on the cell surface and are involved in many biological functions. We have recently demonstrated that the interaction of CPPs with sulfated GAGs plays a critical role in their direct cell membrane penetration: the favorable enthalpy contribution drives the high-affinity binding of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane penetration. The favorable enthalpy gain is presumably mainly derived from a unique property of the guanidino group of arginine residues forming multidentate hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions can be accompanied with charge neutralization of arginine-rich CPPs, promoting their partition into cell membranes. This review summarizes the current understanding of the physicochemical mechanism for lipid membrane penetration of CPPs, and discusses the role of the GAG interactions on the cell membrane penetration of CPPs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function

KAUST Repository

Rydberg, Hanna A.

2012-10-01

Cell-penetrating peptides and antimicrobial peptides are two classes of positively charged membrane active peptides with several properties in common. The challenge is to combine knowledge about the membrane interaction mechanisms and structural properties of the two classes to design peptides with membrane-specific actions, useful either as transporters of cargo or as antibacterial substances. Membrane active peptides are commonly rich in arginine and tryptophan. We have previously designed a series of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations assay (MIC), circular dichroism (CD) and linear dichroism (LD). The results show that the arg/trp peptides inhibit the growth of the two gram positive strains Staphylococcus aureus and Staphylococcus pyogenes, with some individual variations depending on the position of the tryptophans. No inhibition of the gram negative strains Proteus mirabilis or Pseudomonas aeruginosa was noticed. CD indicated that when bound to lipid vesicles one of the peptides forms an α-helical like structure, whereas the other five exhibited rather random coiled structures. LD indicated that all six peptides were somehow aligned parallel with the membrane surface. Our results do not reveal any obvious connection between membrane interaction and antimicrobial effect for the studied peptides. By contrast cell-penetrating properties can be coupled to both the secondary structure and the degree of order of the peptides. © 2012 Elsevier Inc.

Intracellular Signalling by C-Peptide

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Claire E. Hills

2008-01-01

Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

Arginine-aromatic interactions and their effects on arginine-induced solubilization of aromatic solutes and suppression of protein aggregation

KAUST Repository

Shah, Dhawal; Li, Jianguo; Shaikh, Abdul Rajjak; Rajagopalan, Raj

2011-01-01

We examine the interaction of aromatic residues of proteins with arginine, an additive commonly used to suppress protein aggregation, using experiments and molecular dynamics simulations. An aromatic-rich peptide, FFYTP (a segment of insulin), and lysozyme and insulin are used as model systems. Mass spectrometry shows that arginine increases the solubility of FFYTP by binding to the peptide, with the simulations revealing the predominant association of arginine to be with the aromatic residues. The calculations further show a positive preferential interaction coefficient, Γ XP, contrary to conventional thinking that positive Γ XP's indicate aggregation rather than suppression of aggregation. Simulations with lysozyme and insulin also show arginine's preference for aromatic residues, in addition to acidic residues. We use these observations and earlier results reported by us and others to discuss the possible implications of arginine's interactions with aromatic residues on the solubilization of aromatic moieties and proteins. Our results also highlight the fact that explanations based purely on Γ XP, which measures average affinity of an additive to a protein, could obscure or misinterpret the underlying molecular mechanisms behind additive-induced suppression of protein aggregation. © 2011 American Institute of Chemical Engineers (AIChE).

Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

International Nuclear Information System (INIS)

York, Joanne; Nunberg, Jack H.

2007-01-01

The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junin virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions - 1 and - 3) reveals a pattern of side-chain preferences consistent with those of SPase. Although position - 2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junin virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position - 1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease

Signal peptide of eosinophil cationic protein is toxic to cells lacking signal peptide peptidase

International Nuclear Information System (INIS)

Wu, C.-M.; Chang, Margaret Dah-Tsyr

2004-01-01

Eosinophil cationic protein (ECP) is a toxin secreted by activated human eosinophils. The properties of mature ECP have been well studied but those of the signal peptide of ECP (ECPsp) are not clear. In this study, several chimeric proteins containing N-terminal fusion of ECPsp were generated, and introduced into Escherichia coli, Pichia pastoris, and human epidermoid carcinoma cell line A431 to study the function of ECPsp. We found that expression of ECPsp chimeric proteins inhibited the growth of E. coli and P. pastoris but not A431 cells. Primary sequence analysis and in vitro transcription/translation of ECPsp have revealed that it is a potential substrate for human signal peptide peptidase (hSPP), an intramembrane protease located in endoplasmic reticulum. In addition, knockdown of the hSPP mRNA expression in ECPsp-eGFP/A431 cells caused the growth inhibitory effect, whereas complementally expression of hSPP in P. pastoris system rescued the cell growth. Taken together, we have demonstrated that ECPsp is a toxic signal peptide, and expression of hSPP protects the cells from growth inhibition

Peptide pheromone signaling in Streptococcus and Enterococcus

Science.gov (United States)

Cook, Laura C.; Federle, Michael J.

2014-01-01

Intercellular chemical signaling in bacteria, commonly referred to as quorum sensing (QS), relies on the production and detection of compounds known as pheromones to elicit coordinated responses among members of a community. Pheromones produced by Gram-positive bacteria are comprised of small peptides. Based on both peptide structure and sensory system architectures, Gram-positive bacterial signaling pathways may be classified into one of four groups with a defining hallmark: cyclical peptides of the Agr type, peptides that contain Gly-Gly processing motifs, sensory systems of the RNPP family, or the recently characterized Rgg-like regulatory family. The recent discovery that Rgg family members respond to peptide pheromones increases substantially the number of species in which QS is likely a key regulatory component. These pathways control a variety of fundamental behaviors including conjugation, natural competence for transformation, biofilm development, and virulence factor regulation. Overlapping QS pathways found in multiple species and pathways that utilize conserved peptide pheromones provide opportunities for interspecies communication. Here we review pheromone signaling identified in the genera Enterococcus and Streptococcus, providing examples of all four types of pathways. PMID:24118108

Signal-BNF: A Bayesian Network Fusing Approach to Predict Signal Peptides

Directory of Open Access Journals (Sweden)

Zhi Zheng

2012-01-01

Full Text Available A signal peptide is a short peptide chain that directs the transport of a protein and has become the crucial vehicle in finding new drugs or reprogramming cells for gene therapy. As the avalanche of new protein sequences generated in the postgenomic era, the challenge of identifying new signal sequences has become even more urgent and critical in biomedical engineering. In this paper, we propose a novel predictor called Signal-BNF to predict the N-terminal signal peptide as well as its cleavage site based on Bayesian reasoning network. Signal-BNF is formed by fusing the results of different Bayesian classifiers which used different feature datasets as its input through weighted voting system. Experiment results show that Signal-BNF is superior to the popular online predictors such as Signal-3L and PrediSi. Signal-BNF is featured by high prediction accuracy that may serve as a useful tool for further investigating many unclear details regarding the molecular mechanism of the zip code protein-sorting system in cells.

NCBI nr-aa BLAST: CBRC-XTRO-01-0031 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-XTRO-01-0031 ref|YP_522550.1| Twin-arginine translocation pathway signal [Rhod...oferax ferrireducens T118] gb|ABD69019.1| Twin-arginine translocation pathway signal [Rhodoferax ferrireducens DSM 15236] YP_522550.1 1e-115 73% ...

Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline-Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays.

Science.gov (United States)

Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng

2016-06-01

Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription-related activities and several cellular carbohydrate biosynthetic processes, P-Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular

Systematic Analysis of Intracellular-targeting Antimicrobial Peptides, Bactenecin 7, Hybrid of Pleurocidin and Dermaseptin, Proline–Arginine-rich Peptide, and Lactoferricin B, by Using Escherichia coli Proteome Microarrays*

Science.gov (United States)

Ho, Yu-Hsuan; Shah, Pramod; Chen, Yi-Wen; Chen, Chien-Sheng

2016-01-01

Antimicrobial peptides (AMPs) act either through membrane lysis or by attacking intracellular targets. Intracellular targeting AMPs are a resource for antimicrobial agent development. Several AMPs have been identified as intracellular targeting peptides; however, the intracellular targets of many of these peptides remain unknown. In the present study, we used an Escherichia coli proteome microarray to systematically identify the protein targets of three intracellular targeting AMPs: bactenecin 7 (Bac7), a hybrid of pleurocidin and dermaseptin (P-Der), and proline-arginine-rich peptide (PR-39). In addition, we also included the data of lactoferricin B (LfcinB) from our previous study for a more comprehensive analysis. We analyzed the unique protein hits of each AMP in the Kyoto Encyclopedia of Genes and Genomes. The results indicated that Bac7 targets purine metabolism and histidine kinase, LfcinB attacks the transcription-related activities and several cellular carbohydrate biosynthetic processes, P-Der affects several catabolic processes of small molecules, and PR-39 preferentially recognizes proteins involved in RNA- and folate-metabolism-related cellular processes. Moreover, both Bac7 and LfcinB target purine metabolism, whereas LfcinB and PR-39 target lipopolysaccharide biosynthesis. This suggested that LfcinB and Bac7 as well as LfcinB and PR-39 have a synergistic effect on antimicrobial activity, which was validated through antimicrobial assays. Furthermore, common hits of all four AMPs indicated that all of them target arginine decarboxylase, which is a crucial enzyme for Escherichia coli survival in extremely acidic environments. Thus, these AMPs may display greater inhibition to bacterial growth in extremely acidic environments. We have also confirmed this finding in bacterial growth inhibition assays. In conclusion, this comprehensive identification and systematic analysis of intracellular targeting AMPs reveals crucial insights into the intracellular

Inhibition of protein aggregation: supramolecular assemblies of arginine hold the key.

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Utpal Das

Full Text Available BACKGROUND: Aggregation of unfolded proteins occurs mainly through the exposed hydrophobic surfaces. Any mechanism of inhibition of this aggregation should explain the prevention of these hydrophobic interactions. Though arginine is prevalently used as an aggregation suppressor, its mechanism of action is not clearly understood. We propose a mechanism based on the hydrophobic interactions of arginine. METHODOLOGY: We have analyzed arginine solution for its hydrotropic effect by pyrene solubility and the presence of hydrophobic environment by 1-anilino-8-naphthalene sulfonic acid fluorescence. Mass spectroscopic analyses show that arginine forms molecular clusters in the gas phase and the cluster composition is dependent on the solution conditions. Light scattering studies indicate that arginine exists as clusters in solution. In the presence of arginine, the reverse phase chromatographic elution profile of Alzheimer's amyloid beta 1-42 (Abeta(1-42 peptide is modified. Changes in the hydrodynamic volume of Abeta(1-42 in the presence of arginine measured by size exclusion chromatography show that arginine binds to Abeta(1-42. Arginine increases the solubility of Abeta(1-42 peptide in aqueous medium. It decreases the aggregation of Abeta(1-42 as observed by atomic force microscopy. CONCLUSIONS: Based on our experimental results we propose that molecular clusters of arginine in aqueous solutions display a hydrophobic surface by the alignment of its three methylene groups. The hydrophobic surfaces present on the proteins interact with the hydrophobic surface presented by the arginine clusters. The masking of hydrophobic surface inhibits protein-protein aggregation. This mechanism is also responsible for the hydrotropic effect of arginine on various compounds. It is also explained why other amino acids fail to inhibit the protein aggregation.

Length sensing and control of a Michelson interferometer with power recycling and twin signal recycling cavities.

Science.gov (United States)

Gräf, Christian; Thüring, André; Vahlbruch, Henning; Danzmann, Karsten; Schnabel, Roman

2013-03-11

The techniques of power recycling and signal recycling have proven as key concepts to increase the sensitivity of large-scale gravitational wave detectors by independent resonant enhancement of light power and signal sidebands within the interferometer. Developing the latter concept further, twin signal recycling was proposed as an alternative to conventional detuned signal recycling. Twin signal recycling features the narrow-band sensitivity gain of conventional detuned signal recycling but furthermore facilitates the injection of squeezed states of light, increases the detector sensitivity over a wide frequency band and requires a less complex detection scheme for optimal signal readout. These benefits come at the expense of an additional recycling mirror, thus increasing the number of degrees of freedom in the interferometer which need to be controlled.In this article we describe the development of a length sensing and control scheme and its successful application to a tabletop-scale power recycled Michelson interferometer with twin signal recycling. We were able to lock the interferometer in all relevant longitudinal degrees of freedom and thus laid the foundation for further investigations of this interferometer configuration to evaluate its viability for the application in gravitational wave detectors.

[Transduction peptides, the useful face of a new signaling mechanism].

Science.gov (United States)

Joliot, Alain; Prochiantz, Alain

2005-03-01

Transduction peptides that cross the plasma membrane of live cells are commonly used for the in vitro and in vivo targeting of hydrophilic drugs into the cell interior. Although this family of peptides has recently increased and will probably continue to do so, the two mainly used peptides are derived from transcription factors. Indeed, TAT is a 12 amino acid long arginine-rich peptide present in the HIV transcription factor, and penetratin - or its variants - corresponds to 16 amino acids that define the highly conserved third helix of the DNA-binding domain (homeodomain) of homeoprotein transcription factors. In this review, we shall recall the different steps that have led to the discovery of transduction peptides and present the most likely hypotheses concerning the mechanisms involved in their internalization. At the risk of being incomplete or, even, biased, we shall concentrate on penetratins and TAT. The reason is that these peptides have been studied for over ten years leading to the edification of robust knowledge regarding their properties. This attitude will not preclude comparisons with other peptides, if necessary. Our goal is to describe the mode of action of these transduction peptides, their range of activity in term of cell types that accept them and cargoes that they can transport, and, also, some of the limitations that one can encounter in their use. Finally, based on the idea that peptide transduction is the technological face of a physiological property of some transcription factors, we shall discuss the putative physiological function of homeoprotein transduction, and, as a consequence, the possibility to use these factors as therapeutic proteins.

Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.

Science.gov (United States)

Cheung, Adrian Wai-Hing; Danho, Waleed; Swistok, Joseph; Qi, Lida; Kurylko, Grazyna; Franco, Lucia; Yagaloff, Keith; Chen, Li

2002-09-02

A series of pentapeptides, based on Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and modified at the Arg(8) position, was prepared and pharmacologically characterized. Peptides containing either cyanoguanidine or acylguanidine, two substantially less basic arginine surrogates, were found to retain the agonist activity of the parent peptide at both hMC1R and hMC4R. This study unequivocally shows that the positive charge of Arg(8) is not essential for efficient interactions of our pentapeptide with both hMC1R and hMC4R.

Constructing bioactive peptides with pH-dependent activities.

Science.gov (United States)

Tu, Zhigang; Volk, Melanie; Shah, Khushali; Clerkin, Kevin; Liang, Jun F

2009-08-01

Many bioactive peptides are featured by their arginine and lysine rich contents. In this study, lysine and arginine residues in lytic peptides were selectively replaced by histidines. Although resulting histidine-containing lytic peptides had decreased activity, they did show pH-dependent cytotoxicity. The activity of the constructed histidine-containing lytic peptides increased 2-8 times as the solution pH changed from 7.4 to 5.5. More importantly, these histidine-containing peptides maintain the same cell killing mechanism as their parent peptides by causing cell lysis. Both the activity and pH-sensitivity of histidine-containing peptides are tunable by adjusting histidine substitution numbers and positions. This study has presented a general strategy to create bioactive peptides with desired pH-sensitivity to meet the needs of various applications such as cancer treatments.

Killing of Mycobacterium avium by lactoferricin peptides: improved activity of arginine- and D-amino-acid-containing molecules.

Science.gov (United States)

Silva, Tânia; Magalhães, Bárbara; Maia, Sílvia; Gomes, Paula; Nazmi, Kamran; Bolscher, Jan G M; Rodrigues, Pedro N; Bastos, Margarida; Gomes, Maria Salomé

2014-06-01

Mycobacterium avium causes respiratory disease in susceptible individuals, as well as disseminated infections in immunocompromised hosts, being an important cause of morbidity and mortality among these populations. Current therapies consist of a combination of antibiotics taken for at least 6 months, with no more than 60% overall clinical success. Furthermore, mycobacterial antibiotic resistance is increasing worldwide, urging the need to develop novel classes of antimicrobial drugs. One potential and interesting alternative strategy is the use of antimicrobial peptides (AMP). These are present in almost all living organisms as part of their immune system, acting as a first barrier against invading pathogens. In this context, we investigated the effect of several lactoferrin-derived AMP against M. avium. Short peptide sequences from both human and bovine lactoferricins, namely, hLFcin1-11 and LFcin17-30, as well as variants obtained by specific amino acid substitutions, were evaluated. All tested peptides significantly inhibited the axenic growth of M. avium, the bovine peptides being more active than the human. Arginine residues were found to be crucial for the display of antimycobacterial activity, whereas the all-d-amino-acid analogue of the bovine sequence displayed the highest mycobactericidal activity. These findings reveal the promising potential of lactoferricins against mycobacteria, thus opening the way for further research on their development and use as a new weapon against mycobacterial infections. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

High-level expression of nattokinase in Bacillus licheniformis by manipulating signal peptide and signal peptidase.

Science.gov (United States)

Cai, D; Wei, X; Qiu, Y; Chen, Y; Chen, J; Wen, Z; Chen, S

2016-09-01

Nattokinase is an enzyme produced by Bacillus licheniformis and has potential to be used as a drug for treating cardiovascular disease due to its beneficial effects of preventing fibrin clots etc. However, the low activity and titre of this protein produced by B. licheniformis often hinders its application of commercial production. The aim of this work is to improve the nattokinase production by manipulating signal peptides and signal peptidases in B. licheniformis. The P43 promoter, amyL terminator and AprN target gene were used to form the nattokinase expression vector, pHY-SP-NK, which was transformed into B. licheniformis and nattokinase was expressed successfully. A library containing 81 predicted signal peptides was constructed for nattokinase expression in B. licheniformis, with the maximum activity being obtained under the signal peptide of AprE. Among four type I signal peptidases genes (sipS, sipT, sipV, sipW) in B. licheniformis, the deletion of sipV resulted in a highest decrease in nattokinase activity. Overexpression of sipV in B. licheniformis led to a nattokinase activity of 35·60 FU ml(-1) , a 4·68-fold improvement over activity produced by the initial strain. This work demonstrates the potential of B. licheniformis for industrial production of nattokinase through manipulation of signal peptides and signal peptidases expression. This study has screened the signal peptides of extracellular proteins of B. licheniformis for nattokinase production. Four kinds of Type I signal peptidases genes have been detected respectively in B. licheniformis to identify which one played the vital role for nattokinase production. This study provided a promising strain for industry production of nattokinase. © 2016 The Society for Applied Microbiology.

Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

Science.gov (United States)

Bidwell, Gene L; Raucher, Drazen

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

Plant elicitor peptides are conserved signals regulating direct and indirect antiherbivore defense

OpenAIRE

Huffaker, Alisa; Pearce, Gregory; Veyrat, Nathalie; Erb, Matthias; Turlings, Ted C. J.; Sartor, Ryan; Shen, Zhouxin; Briggs, Steven P.; Vaughan, Martha M.; Alborn, Hans T.; Teal, Peter E. A.; Schmelz, Eric A.

2013-01-01

Insect-induced defenses occur in nearly all plants and are regulated by conserved signaling pathways. As the first described plant peptide signal, systemin regulates antiherbivore defenses in the Solanaceae, but in other plant families, peptides with analogous activity have remained elusive. In the current study, we demonstrate that a member of the maize (Zea mays) plant elicitor peptide (Pep) family, ZmPep3, regulates responses against herbivores. Consistent with being a signal, expression o...

Engineering signal peptides for enhanced protein secretion from Lactococcus lactis.

Science.gov (United States)

Ng, Daphne T W; Sarkar, Casim A

2013-01-01

Lactococcus lactis is an attractive vehicle for biotechnological production of proteins and clinical delivery of therapeutics. In many such applications using this host, it is desirable to maximize secretion of recombinant proteins into the extracellular space, which is typically achieved by using the native signal peptide from a major secreted lactococcal protein, Usp45. In order to further increase protein secretion from L. lactis, inherent limitations of the Usp45 signal peptide (Usp45sp) must be elucidated. Here, we performed extensive mutagenesis on Usp45sp to probe the effects of both the mRNA sequence (silent mutations) and the peptide sequence (amino acid substitutions) on secretion. We screened signal peptides based on their resulting secretion levels of Staphylococcus aureus nuclease and further evaluated them for secretion of Bacillus subtilis α-amylase. Silent mutations alone gave an increase of up to 16% in the secretion of α-amylase through a mechanism consistent with relaxed mRNA folding around the ribosome binding site and enhanced translation. Targeted amino acid mutagenesis in Usp45sp, combined with additional silent mutations from the best clone in the initial screen, yielded an increase of up to 51% in maximum secretion of α-amylase while maintaining secretion at lower induction levels. The best sequence from our screen preserves the tripartite structure of the native signal peptide but increases the positive charge of the n-region. Our study presents the first example of an engineered L. lactis signal peptide with a higher secretion yield than Usp45sp and, more generally, provides strategies for further enhancing protein secretion in bacterial hosts.

Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term.

Science.gov (United States)

Sales, Francisco; Pacheco, David; Blair, Hugh; Kenyon, Paul; McCoard, Sue

2013-01-01

Twin sheep fetuses have reduced skeletal muscle weight near birth relative to singles as a result of restricted muscle hypertrophy. Intracellular free amino acids (FAA) are reported to regulate metabolic pathways which control muscle protein accretion, whereby reduced intracellular content of specific FAA may reduce their activation and therefore, muscle hypertrophy. The aim of this study was to determine whether differences in muscle weight between singleton and twin fetuses, under different maternal conditions is associated with reduced concentration of specific FAA. The FAA content in the semitendinosus muscle (ST) in singleton and twin fetuses (rank) at 140 days of gestation from heavy (H) or light (L) ewes fed ad libitum (A) or maintenance (M) level of nutrition was measured. Muscle weight was reduced in twin fetuses compared to singletons in all groups. Reduced concentrations of leucine, threonine and valine, but higher concentrations of methionine, ornithine, lysine and serine were found in twin fetuses compared to singletons. Maternal size and nutrition interaction with rank resulted in reduced glutamine in twins from HM-ewes (H-ewes under M nutrition) compared to their singleton counterparts. Maternal weight interaction with pregnancy rank reduced the concentration of arginine in twins, with a larger effect on H-ewes compared with L-ewes. Maternal size interaction with pregnancy rank resulted in twins from M-ewes to have lower alanine, while twins from A-ewes had lower aspartic acid concentration compared to singletons. The ST muscle weight was positively correlated only with arginine concentration after taking into account rank, size and nutrition. The present results indicate that reduced concentrations of specific intracellular FAA, such as arginine, leucine, valine, glutamine, which are known to play a role in muscle growth, could be acting as limiting factors for muscle hypertrophy in twin fetuses during late gestation. Ewe size and nutrition can

Advantages of combined transmembrane topology and signal peptide prediction--the Phobius web server

DEFF Research Database (Denmark)

Käll, Lukas; Krogh, Anders; Sonnhammer, Erik L L

2007-01-01

. The method makes an optimal choice between transmembrane segments and signal peptides, and also allows constrained and homology-enriched predictions. We here present a web interface (http://phobius.cgb.ki.se and http://phobius.binf.ku.dk) to access Phobius. Udgivelsesdato: 2007-Jul......When using conventional transmembrane topology and signal peptide predictors, such as TMHMM and SignalP, there is a substantial overlap between these two types of predictions. Applying these methods to five complete proteomes, we found that 30-65% of all predicted signal peptides and 25-35% of all...

Exploiting Wireless Received Signal Strength Indicators to Detect Evil-Twin Attacks in Smart Homes

Directory of Open Access Journals (Sweden)

Zhanyong Tang

2017-01-01

Full Text Available Evil-Twin is becoming a common attack in smart home environments where an attacker can set up a fake AP to compromise the security of the connected devices. To identify the fake APs, The current approaches of detecting Evil-Twin attacks all rely on information such as SSIDs, the MAC address of the genuine AP, or network traffic patterns. However, such information can be faked by the attacker, often leading to low detection rates and weak protection. This paper presents a novel Evil-Twin attack detection method based on the received signal strength indicator (RSSI. Our approach considers the RSSI as a fingerprint of APs and uses the fingerprint of the genuine AP to identify fake ones. We provide two schemes to detect a fake AP in two different scenarios where the genuine AP can be located at either a single or multiple locations in the property, by exploiting the multipath effect of the Wi-Fi signal. As a departure from prior work, our approach does not rely on any professional measurement devices. Experimental results show that our approach can successfully detect 90% of the fake APs, at the cost of a one-off, modest connection delay.

Intravenous maternal -arginine administration to twin-bearing ewes during late pregnancy enhances placental growth and development.

Science.gov (United States)

van der Linden, D S; Sciascia, Q; Sales, F; Wards, N J; Oliver, M H; McCoard, S A

2015-10-01

This study aimed to investigate if intravenous maternal Arg administration to well-fed twin-bearing ewes, from 100 to 140 d of gestation or birth, could enhance placental development and placental nutrient transport. Ewes received intravenous infusions of saline (control) or 345 μmol Arg HCl/kg of BW 3 times daily from d 100 of pregnancy (P100) to d 140 of pregnancy (P140; cohort 1) or from P100 to birth (cohort 2). At P140, ewes in cohort 1 were euthanized and individual placentae per fetus were dissected and placentomes were classed per type (A to D) and size (light to heavy). Placentome number and individual weight were recorded. As an indicator of placental nutrient transport, blood plasma was collected from the uterine ovarian vein (UOV), uterine artery (UA), and umbilical vein and artery at the time of euthanasia and analyzed for metabolites and free AA concentrations. The ewes in cohort 2 were allowed to lamb and lambs were weighed at birth. The expelled placenta was dissected and number of cotyledons and weights of total cotyledons, remaining fetal membranes, and total placenta were recorded. At P140, Arg-infused ewes had a 63% ( = 0.03) greater number of unoccupied caruncles than control ewes. No differences were observed for placental weight at P140. At birth, lambs from Arg-infused ewes tended to have 11% ( = 0.09) greater placental weight and 34% ( = 0.03) greater total cotyledon weight compared with control lambs. Arginine-infused ewes (Arg-infused) had increased concentrations of Arg ( = 0.0001) and ornithine (Orn; = 0.004) but decreased concentrations of Met ( = 0.01) and His ( = 0.02 and = 0.09, respectively) compared with control ewes in plasma UOV and UA. Fetuses from Arg-infused ewes had increased concentrations of Orn ( = 0.005) and decreased concentrations of His ( = 0.006), Met ( = 0.003), and Lys ( = 0.01) but no differences in Arg ( > 0.10) concentrations were found compared with control fetuses in umbilical artery and vein plasma. This

Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

Science.gov (United States)

Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

2018-04-01

The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

Partial alanine scan of mast cell degranulating peptide (MCD): importance of the histidine- and arginine residues.

Science.gov (United States)

Buku, Angeliki; Mendlowitz, Milton; Condie, Barry A; Price, Joseph A

2004-06-01

The influence of the two histidine and two arginine residues of mast cell degranulating peptide (MCD) in activity and binding was studied by replacing these amino acids in the MCD sequence with L-alanine. Their histamine releasing activity was determined on rat peritoneal mast cells. Their binding affinity to the FcepsilonRIalpha binding subunit of the human mast cell receptor protein, was carried out using fluorescence polarization. The histamine assay showed that replacement of His13 by Ala o ccurred without loss of activity compared with the activity of MCD. Alanine substitutions for Arg7 and His8 resulted in an approximately 40 fold increase, and for Arg16 in a 14-fold increase in histamine-releasing activity of MCD. The binding affinities of the analogs were tested by competitive displacement of bound fluorescent MCD peptide from the FcepsilonRIalpha binding protein of the mast cell receptor by the Ala analogs using fluorescence polarization. The analogs Ala8 (for His) and Ala16 (for Arg) showed the same binding affinities as MCD, whereas analog Ala7 (for Arg) and analog Ala13 (for His) showed slightly better binding affinity than the parent compound. This study showed that the introduction of alanine residues in these positions resulted in MCD agonists of diverse potency. These findings will be useful in further MCD structure-activity studies.

Exotic quarks in Twin Higgs models

Energy Technology Data Exchange (ETDEWEB)

Cheng, Hsin-Chia [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Jung, Sunghoon [School of Physics, Korea Institute for Advanced Study,85 Hoegiro, Dongdaemun-gu, Seoul 130-722 (Korea, Republic of); SLAC National Accelerator Laboratory,2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Salvioni, Ennio [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Tsai, Yuhsin [Department of Physics, University of California, Davis,One Shields Avenue, Davis, CA 95616 (United States); Maryland Center for Fundamental Physics,Department of Physics, University of Maryland,College Park, MD 20742 (United States)

2016-03-14

The Twin Higgs model provides a natural theory for the electroweak symmetry breaking without the need of new particles carrying the standard model gauge charges below a few TeV. In the low energy theory, the only probe comes from the mixing of the Higgs fields in the standard model and twin sectors. However, an ultraviolet completion is required below ∼ 10 TeV to remove residual logarithmic divergences. In non-supersymmetric completions, new exotic fermions charged under both the standard model and twin gauge symmetries have to be present to accompany the top quark, thus providing a high energy probe of the model. Some of them carry standard model color, and may therefore be copiously produced at current or future hadron colliders. Once produced, these exotic quarks can decay into a top together with twin sector particles. If the twin sector particles escape the detection, we have the irreducible stop-like signals. On the other hand, some twin sector particles may decay back into the standard model particles with long lifetimes, giving spectacular displaced vertex signals in combination with the prompt top quarks. This happens in the Fraternal Twin Higgs scenario with typical parameters, and sometimes is even necessary for cosmological reasons. We study the potential displaced vertex signals from the decays of the twin bottomonia, twin glueballs, and twin leptons in the Fraternal Twin Higgs scenario. Depending on the details of the twin sector, the exotic quarks may be probed up to ∼ 2.5 TeV at the LHC and beyond 10 TeV at a future 100 TeV collider, providing a strong test of this class of ultraviolet completions.

Gas-phase salt bridge interactions between glutamic acid and arginine

NARCIS (Netherlands)

Jaeqx, S.; Oomens, J.; Rijs, A.M.

2013-01-01

The gas-phase side chain-side chain (SC-SC) interaction and possible proton transfer between glutamic acid (Glu) and arginine (Arg) residues are studied under low-temperature conditions in an overall neutral peptide. Conformation-specific IR spectra, obtained with the free electron laser FELIX, in

Guanylin peptides: cyclic GMP signaling mechanisms

Directory of Open Access Journals (Sweden)

Forte L.R.

1999-01-01

Full Text Available Guanylate cyclases (GC serve in two different signaling pathways involving cytosolic and membrane enzymes. Membrane GCs are receptors for guanylin and atriopeptin peptides, two families of cGMP-regulating peptides. Three subclasses of guanylin peptides contain one intramolecular disulfide (lymphoguanylin, two disulfides (guanylin and uroguanylin and three disulfides (E. coli stable toxin, ST. The peptides activate membrane receptor-GCs and regulate intestinal Cl- and HCO3- secretion via cGMP in target enterocytes. Uroguanylin and ST also elicit diuretic and natriuretic responses in the kidney. GC-C is an intestinal receptor-GC for guanylin and uroguanylin, but GC-C may not be involved in renal cGMP pathways. A novel receptor-GC expressed in the opossum kidney (OK-GC has been identified by molecular cloning. OK-GC cDNAs encode receptor-GCs in renal tubules that are activated by guanylins. Lymphoguanylin is highly expressed in the kidney and heart where it may influence cGMP pathways. Guanylin and uroguanylin are highly expressed in intestinal mucosa to regulate intestinal salt and water transport via paracrine actions on GC-C. Uroguanylin and guanylin are also secreted from intestinal mucosa into plasma where uroguanylin serves as an intestinal natriuretic hormone to influence body Na+ homeostasis by endocrine mechanisms. Thus, guanylin peptides control salt and water transport in the kidney and intestine mediated by cGMP via membrane receptors with intrinsic guanylate cyclase activity.

Improving N-terminal protein annotation of Plasmodium species based on signal peptide prediction of orthologous proteins

Directory of Open Access Journals (Sweden)

Neto Armando

2012-11-01

Full Text Available Abstract Background Signal peptide is one of the most important motifs involved in protein trafficking and it ultimately influences protein function. Considering the expected functional conservation among orthologs it was hypothesized that divergence in signal peptides within orthologous groups is mainly due to N-terminal protein sequence misannotation. Thus, discrepancies in signal peptide prediction of orthologous proteins were used to identify misannotated proteins in five Plasmodium species. Methods Signal peptide (SignalP and orthology (OrthoMCL were combined in an innovative strategy to identify orthologous groups showing discrepancies in signal peptide prediction among their protein members (Mixed groups. In a comparative analysis, multiple alignments for each of these groups and gene models were visually inspected in search of misannotated proteins and, whenever possible, alternative gene models were proposed. Thresholds for signal peptide prediction parameters were also modified to reduce their impact as a possible source of discrepancy among orthologs. Validation of new gene models was based on RT-PCR (few examples or on experimental evidence already published (ApiLoc. Results The rate of misannotated proteins was significantly higher in Mixed groups than in Positive or Negative groups, corroborating the proposed hypothesis. A total of 478 proteins were reannotated and change of signal peptide prediction from negative to positive was the most common. Reannotations triggered the conversion of almost 50% of all Mixed groups, which were further reduced by optimization of signal peptide prediction parameters. Conclusions The methodological novelty proposed here combining orthology and signal peptide prediction proved to be an effective strategy for the identification of proteins showing wrongly N-terminal annotated sequences, and it might have an important impact in the available data for genome-wide searching of potential vaccine and drug

The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

Science.gov (United States)

Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2012-08-03

N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase

Energy Technology Data Exchange (ETDEWEB)

Debler, Erik W.; Jain, Kanishk; Warmack, Rebeccah A.; Feng, You; Clarke, Steven G.; Blobel, Günter; Stavropoulos, Pete

2016-02-08

Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-L-homocysteine (AdoHcy) at 2.8 Å resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and β-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N-terminal extension, methyltransferase, and β-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active-site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs.

Conformations and orientations of a signal peptide interacting with phospholipid monolayers

International Nuclear Information System (INIS)

Cornell, D.G.; Dluhy, R.A.; Briggs, M.S.; McKnight, C.J.; Gierasch, L.M.

1989-01-01

The interaction of a chemically synthesized 25-residue signal peptide of LamB protein from Escherichia coli with phospholipids has been studied with a film balance technique. The conformation, orientation, and concentration of the peptides in lipid monolayers have been determined from polarized infrared spectroscopy, ultraviolet spectroscopy, and assay of 14 C-labeled peptide in transferred films. When the LamB signal peptide in injected into the subphase under a phosphatidylethanolamine-phosphatidylglycerol monolayer at low initial pressure, insertion of a portion of the peptide into the lipid film is evidenced by a rapid rise in film pressure. Spectroscopic results obtained on films transferred to quartz plates and Ge crystals show that the peptide is a mixture of α-helix and β-conformation where the long axis of the α-helix penetrates the monolayer plane and the β-structure which is coplanar with the film. By contrast, when peptide is injected under lipid at high initial pressure, no pressure rise is observed, and the spectroscopic results show the presence of only β-structure which is coplanar with the monolayer. The spectroscopic and radioassay results are all consistent with the picture of a peptide anchored to the monolayer through electrostatic binding with a helical portion inserted into the lipid region of the monolayer and a β-structure portion resident in the aqueous phase. The negative charges on the lipid molecules are roughly neutralized by the positive charges of the peptide

Exploitation of the Ornithine Effect Enhances Characterization of Stapled and Cyclic Peptides

Science.gov (United States)

Crittenden, Christopher M.; Parker, W. Ryan; Jenner, Zachary B.; Bruns, Kerry A.; Akin, Lucas D.; McGee, William M.; Ciccimaro, Eugene; Brodbelt, Jennifer S.

2016-05-01

A method to facilitate the characterization of stapled or cyclic peptides is reported via an arginine-selective derivatization strategy coupled with MS/MS analysis. Arginine residues are converted to ornithine residues through a deguanidination reaction that installs a highly selectively cleavable site in peptides. Upon activation by CID or UVPD, the ornithine residue cyclizes to promote cleavage of the adjacent amide bond. This Arg-specific process offers a unique strategy for site-selective ring opening of stapled and cyclic peptides. Upon activation of each derivatized peptide, site-specific backbone cleavage at the ornithine residue results in two complementary products: the lactam ring-containing portion of the peptide and the amine-containing portion. The deguanidination process not only provides a specific marker site that initiates fragmentation of the peptide but also offers a means to unlock the staple and differentiate isobaric stapled peptides.

Conformationally Constrained Peptidomimetics as Inhibitors of the Protein Arginine Methyl Transferases

DEFF Research Database (Denmark)

Knuhtsen, Astrid; Legrand, Baptiste; Van der Poorten, Olivier

2016-01-01

Protein arginine N-methyl transferases (PRMTs) belong to a family of enzymes that modulate the epigenetic code through modifications of histones. In the present study, peptides emerging from a phage display screening were modified in the search for PRMT inhibitors through substitution with non-pr...

Sequencing Lys-N Proteolytic Peptides by ESI and MALDI Tandem Mass Spectrometry

Science.gov (United States)

Dupré, Mathieu; Cantel, Sonia; Verdié, Pascal; Martinez, Jean; Enjalbal, Christine

2011-02-01

In this study, we explored the MS/MS behavior of various synthetic peptides that possess a lysine residue at the N-terminal position. These peptides were designed to mimic peptides produced upon proteolysis by the Lys-N enzyme, a metalloendopeptidase issued from a Japanese fungus Grifola frondosa that was recently investigated in proteomic studies as an alternative to trypsin digestion, as a specific cleavage at the amide X-Lys chain is obtained that provides N-terminal lysine peptide fragments. In contrast to tryptic peptides exhibiting a lysine or arginine residue solely at the C-terminal position, and are thus devoid of such basic amino acids within the sequence, these Lys-N proteolytic peptides can contain the highly basic arginine residue anywhere within the peptide chain. The fragmentation patterns of such sequences with the ESI-QqTOF and MALDI-TOF/TOF mass spectrometers commonly used in proteomic bottom-up experiments were investigated.

Pharmacological characterization of the oxytocic peptides in the pituitary of a marine teleost fish (pollachius virens) (1961); Caracterisation pharmacologique des peptides ocytociques dans la glande pituitaire d'un poisson marin teleost (pollachius virens) (1961)

Energy Technology Data Exchange (ETDEWEB)

Maetz, J; Morel, F [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Heller, H; Pickering, B T [Bristol Univ. (United Kingdom)

1961-07-01

Demonstration of the existence, in the neurohypophysis of a marine fish (pollachius virens), of an oxytocic-active peptide different to the oxytocin in mammals and to the arginine vasotocin. (authors) [French] Mise en evidence dans la neurohypophyse d'un poisson marin (pollachius virens) d'un peptide a activite ocytocique different de l'ocytocine des mammiferes et de l'arginine vasotocine. (auteurs)

Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.

Science.gov (United States)

Guizzunti, Gianni; Zurzolo, Chiara

2015-01-01

We previously reported that PrP GPI-anchor signal peptide (GPI-SP) is specifically degraded by the proteasome. Additionally, we showed that the point mutation P238S, responsible for a genetic form of prion diseases, while not affecting the GPI-anchoring process, results in the accumulation of PrP GPI-SP, suggesting the possibility that PrP GPI-anchor signal peptide could play a role in neurodegenerative prion diseases. We now show that PrP GPI-SP, when expressed as a cytosolic peptide, is able to localize to the mitochondria and to induce mitochondrial fragmentation and vacuolarization, followed by loss in mitochondrial membrane potential, ultimately resulting in apoptosis. Our results identify the GPI-SP of PrP as a novel candidate responsible for the impairment in mitochondrial function involved in the synaptic pathology observed in prion diseases, establishing a link between PrP GPI-SP accumulation and neuronal death.

Identification of diverse archaeal proteins with class III signal peptides cleaved by distinct archaeal prepilin peptidases

NARCIS (Netherlands)

Szabó, Zalán; Oliveira Stahl, Adriana; Albers, Sonja-V.; Kissinger, Jessica C.; Driessen, Arnold J.M.; Pohlschröder, Mechthild; Pohlschroder, M.

2007-01-01

Most secreted archaeal proteins are targeted to the membrane via a tripartite signal composed of a charged N terminus and a hydrophobic domain, followed by a signal peptidase-processing site. Signal peptides of archaeal flagellins, similar to class III signal peptides of bacterial type IV pilins,

The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together.

Science.gov (United States)

Brock, Roland

2014-05-21

Over the past 20 years, cell-penetrating peptides (CPPs) have captured the attention of biomedical researchers, biophysicists, and (bio)organic chemists. These molecules efficiently enter cells and mediate entry of (macro)molecules that by themselves do not cross the plasma membrane. Since their discovery, models on the mechanism by which uptake occurs have seen major revisions. Starting from direct penetration across the plasma membrane, it later became apparent that for large molecular weight cargos in particular, endocytosis plays a role in uptake and furthermore that the route of uptake is a function of CPP, cell-type, cargo, and concentration. For the class of arginine-rich CPPs, this dependence on conditions has been elucidated in particular. As I will discuss here for this class of CPPs, a downside of this multitude of possibilities has been a lack of attention for commonalities in the observation of apparently distinct phenomena. At the same time, differences of apparently similar observations were not appreciated sufficiently. In addition, there has been insufficient acknowledgment of observations that are incompatible with the proposed models. Nevertheless, a considerable amount of data can be assembled into a quite coherent picture and the data that is left creates the basis for concrete future lines of research to resolve the questions that remain. Moreover, any uptake mechanism has its distinct structure-activity relationship for uptake giving room for the molecular design of molecules to preferentially direct uptake to either of them.

Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

DEFF Research Database (Denmark)

Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

2013-01-01

Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

Positive and negative peptide signals control stomatal density.

Science.gov (United States)

Shimada, Tomoo; Sugano, Shigeo S; Hara-Nishimura, Ikuko

2011-06-01

The stoma is a micro valve found on aerial plant organs that promotes gas exchange between the atmosphere and the plant body. Each stoma is formed by a strict cell lineage during the early stages of leaf development. Molecular genetics research using the model plant Arabidopsis has revealed the genes involved in stomatal differentiation. Cysteine-rich secretory peptides of the EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family play crucial roles as extracellular signaling factors. Stomatal development is orchestrated by the positive factor STOMAGEN/EPFL9 and the negative factors EPF1, EPF2, and CHALLAH/EPFL6 in combination with multiple receptors. EPF1 and EPF2 are produced in the stomatal lineage cells of the epidermis, whereas STOMAGEN and CHALLAH are derived from the inner tissues. These findings highlight the complex cell-to-cell and intertissue communications that regulate stomatal development. To optimize gas exchange, particularly the balance between the uptake of carbon dioxide (CO(2)) and loss of water, plants control stomatal activity in response to environmental conditions. The CO(2) level and light intensity influence stomatal density. Plants sense environmental cues in mature leaves and adjust the stomatal density of newly forming leaves, indicating the involvement of long-distance systemic signaling. This review summarizes recent research progress in the peptide signaling of stomatal development and discusses the evolutionary model of the signaling machinery.

Pharmacological characterization of the oxytocic peptides in the pituitary of a marine teleost fish (pollachius virens) (1961); Caracterisation pharmacologique des peptides ocytociques dans la glande pituitaire d'un poisson marin teleost (pollachius virens) (1961)

Energy Technology Data Exchange (ETDEWEB)

Maetz, J.; Morel, F. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires; Heller, H.; Pickering, B.T. [Bristol Univ. (United Kingdom)

1961-07-01

Demonstration of the existence, in the neurohypophysis of a marine fish (pollachius virens), of an oxytocic-active peptide different to the oxytocin in mammals and to the arginine vasotocin. (authors) [French] Mise en evidence dans la neurohypophyse d'un poisson marin (pollachius virens) d'un peptide a activite ocytocique different de l'ocytocine des mammiferes et de l'arginine vasotocine. (auteurs)

Broadband squeezing of quantum noise in a Michelson interferometer with Twin-Signal-Recycling.

Science.gov (United States)

Thüring, André; Gräf, Christian; Vahlbruch, Henning; Mehmet, Moritz; Danzmann, Karsten; Schnabel, Roman

2009-03-15

Twin-Signal-Recycling (TSR) builds on the resonance doublet of two optically coupled cavities and efficiently enhances the sensitivity of an interferometer at a dedicated signal frequency. We report on what we believe to be the first experimental realization of a TSR Michelson interferometer and also its broadband enhancement by squeezed light injection. The complete setup was stably locked, and a broadband quantum noise reduction of the interferometers shot noise by a factor of up to 4 dB was demonstrated. The system was characterized by measuring its quantum noise spectra for several tunings of the TSR cavities. We found good agreement between the experimental results and numerical simulations.

Protein chaperones Q8ZP25_SALTY from Salmonella typhimurium and HYAE_ECOLI from Escherichia coli exhibit thioredoxin-like structures despite lack of canonical thioredoxin active site sequence motive

Science.gov (United States)

Parish, David; Benach, Jordi; Liu, Goahua; Singarapu, Kiran Kumar; Xiao, Rong; Acton, Thomas; Su, Min; Bansal, Sonal; Prestegard, James H.; Hunt, John; Montelione, Gaetano T.

2010-01-01

The structure of the 142-residue protein Q8ZP25_SALTY encoded in the genome of Salmonella typhimurium LT2 was determined independently by NMR and X-ray crystallography, and the structure of the 140-residue protein HYAE_ECOLI encoded in the genome of Eschericia coli was determined by NMR. The two proteins belong to Pfam [1] PF07449, which currently comprises 50 members, and belongs itself to the ‘thioredoxin-like clan’. However, protein HYAE_ECOLI and the other proteins of Pfam PF07449 do not contain the canonical Cys-X-X-Cys active site sequence motif of thioredoxin. Protein HYAE_ECOLI was previously classified as a [NiFe] hydrogenase-1 specific chaperone interacting with the twin-arginine translocation (Tat) signal peptide. The structures presented here exhibit the expected thioredoxin-like fold and support the view that members of Pfam family PF07449 specifically interact with Tat signal peptides. PMID:19039680

Protein chaperones Q8ZP25_SALTY from Salmonella typhimurium and HYAE_ECOLI from Escherichia coli exhibit thioredoxin-like structures despite lack of canonical thioredoxin active site sequence motif.

Science.gov (United States)

Parish, David; Benach, Jordi; Liu, Goahua; Singarapu, Kiran Kumar; Xiao, Rong; Acton, Thomas; Su, Min; Bansal, Sonal; Prestegard, James H; Hunt, John; Montelione, Gaetano T; Szyperski, Thomas

2008-12-01

The structure of the 142-residue protein Q8ZP25_SALTY encoded in the genome of Salmonella typhimurium LT2 was determined independently by NMR and X-ray crystallography, and the structure of the 140-residue protein HYAE_ECOLI encoded in the genome of Escherichia coli was determined by NMR. The two proteins belong to Pfam (Finn et al. 34:D247-D251, 2006) PF07449, which currently comprises 50 members, and belongs itself to the 'thioredoxin-like clan'. However, protein HYAE_ECOLI and the other proteins of Pfam PF07449 do not contain the canonical Cys-X-X-Cys active site sequence motif of thioredoxin. Protein HYAE_ECOLI was previously classified as a [NiFe] hydrogenase-1 specific chaperone interacting with the twin-arginine translocation (Tat) signal peptide. The structures presented here exhibit the expected thioredoxin-like fold and support the view that members of Pfam family PF07449 specifically interact with Tat signal peptides.

Protein Chaperones Q8ZP25_SALTY from Salmonella Typhimurium and HYAE_ECOLI from Escherichia coli Exhibit Thioredoxin-like Structures Despite Lack of Canonical Thioredoxin Active Site Sequence Motif

Energy Technology Data Exchange (ETDEWEB)

Parish, D.; Benach, J; Liu, G; Singarapu, K; Xiao, R; Acton, T; Hunt, J; Montelione, G; Szyperski, T; et. al.

2008-01-01

The structure of the 142-residue protein Q8ZP25 SALTY encoded in the genome of Salmonella typhimurium LT2 was determined independently by NMR and X-ray crystallography, and the structure of the 140-residue protein HYAE ECOLI encoded in the genome of Escherichia coli was determined by NMR. The two proteins belong to Pfam (Finn et al. 34:D247-D251, 2006) PF07449, which currently comprises 50 members, and belongs itself to the 'thioredoxin-like clan'. However, protein HYAE ECOLI and the other proteins of Pfam PF07449 do not contain the canonical Cys-X-X-Cys active site sequence motif of thioredoxin. Protein HYAE ECOLI was previously classified as a (NiFe) hydrogenase-1 specific chaperone interacting with the twin-arginine translocation (Tat) signal peptide. The structures presented here exhibit the expected thioredoxin-like fold and support the view that members of Pfam family PF07449 specifically interact with Tat signal peptides.

Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells.

Science.gov (United States)

Oufir, Mouhssin; Bisset, Leslie R; Hoffmann, Stefan R K; Xue, Gongda; Klauser, Stephan; Bergamaschi, Bianca; Gervaix, Alain; Böni, Jürg; Schüpbach, Jörg; Gutte, Bernd

2011-01-01

An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

Purification of free arginine from chickpea (Cicer arietinum) seeds.

Science.gov (United States)

Cortés-Giraldo, Isabel; Megías, Cristina; Alaiz, Manuel; Girón-Calle, Julio; Vioque, Javier

2016-02-01

Chickpea is a grain legume widely consumed in the Mediterranean region and other parts of the world. Chickpea seeds are rich in proteins but they also contain a substantial amount of free amino acids, especially arginine. Hence chickpea may represent a useful source of free amino acids for nutritional or pharmaceutical purposes. Arginine is receiving great attention in recent years because it is the substrate for the synthesis of nitric oxide, an important signaling molecule involved in numerous physiological and pathological processes in mammals. In this work we describe a simple procedure for the purification of arginine from chickpea seeds, using nanofiltration technology and an ion-exchange resin, Amberlite IR-120. Arginine was finally purified by precipitation or crystallization, yielding preparations with purities of 91% and 100%, respectively. Chickpea may represent an affordable green source of arginine, and a useful alternative to production by fermentation or protein hydrolysis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prediction of lipoprotein signal peptides in Gram-negative bacteria

DEFF Research Database (Denmark)

Juncker, Agnieszka; Willenbrock, Hanni; Von Heijne, G.

2003-01-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor ...

Effects of lactoferrin derived peptides on simulants of biological warfare agents.

Science.gov (United States)

Sijbrandij, Tjitske; Ligtenberg, Antoon J; Nazmi, Kamran; Veerman, Enno C I; Bolscher, Jan G M; Bikker, Floris J

2017-01-01

Lactoferrin (LF) is an important immune protein in neutrophils and secretory fluids of mammals. Bovine LF (bLF) harbours two antimicrobial stretches, lactoferricin and lactoferampin, situated in close proximity in the N1 domain. To mimic these antimicrobial domain parts a chimeric peptide (LFchimera) has been constructed comprising parts of both stretches (LFcin17-30 and LFampin265-284). To investigate the potency of this construct to combat a set of Gram positive and Gram negative bacteria which are regarded as simulants for biological warfare agents, the effect on bacterial killing, membrane permeability and membrane polarity were determined in comparison to the constituent peptides and the native bLF. Furthermore we aimed to increase the antimicrobial potency of the bLF derived peptides by cationic amino acid substitutions. Overall, the bactericidal activity of the peptides could be related to membrane disturbing effects, i.e. membrane permeabilization and depolarization. Those effects were most prominent for the LFchimera. Arginine residues were found to be crucial for displaying antimicrobial activity, as lysine to arginine substitutions resulted in an increased antimicrobial activity, affecting mostly LFampin265-284 whereas arginine to lysine substitutions resulted in a decreased bactericidal activity, predominantly in case of LFcin17-30.

Crystal structure of arginine methyltransferase 6 from Trypanosoma brucei.

Directory of Open Access Journals (Sweden)

Chongyuan Wang

Full Text Available Arginine methylation plays vital roles in the cellular functions of the protozoan Trypanosoma brucei. The T. brucei arginine methyltransferase 6 (TbPRMT6 is a type I arginine methyltransferase homologous to human PRMT6. In this study, we report the crystal structures of apo-TbPRMT6 and its complex with the reaction product S-adenosyl-homocysteine (SAH. The structure of apo-TbPRMT6 displays several features that are different from those of type I PRMTs that were structurally characterized previously, including four stretches of insertion, the absence of strand β15, and a distinct dimerization arm. The comparison of the apo-TbPRMT6 and SAH-TbPRMT6 structures revealed the fine rearrangements in the active site upon SAH binding. The isothermal titration calorimetry results demonstrated that SAH binding greatly increases the affinity of TbPRMT6 to a substrate peptide derived from bovine histone H4. The western blotting and mass spectrometry results revealed that TbPRMT6 methylates bovine histone H4 tail at arginine 3 but cannot methylate several T. brucei histone tails. In summary, our results highlight the structural differences between TbPRMT6 and other type I PRMTs and reveal that the active site rearrangement upon SAH binding is important for the substrate binding of TbPRMT6.

Musical Interests and Talent: Twin Jazz Musicians and Twin Studies/Twin Research: Loss of a Preterm Multiple; Conjoined Twin Conception; Depression in Fathers of Twins; Twin-to-Twin Transfusion Syndrome/Twin News: High-Achieving Twins; Twin Children of a Tennis Star; Conjoined Twin Separation; Twin Delivery to a Giant Panda.

Science.gov (United States)

Segal, Nancy L

2017-12-01

Findings from twin studies of musical interests and talent are reviewed as a backdrop to the lives and careers of twin jazz musicians, Peter and Will Anderson. The Anderson twins exemplify many aspects of twin research, namely their matched musical abilities, shared musical interests, and common career. This overview is followed by reviews of studies and case reports of bereavement in families who have lost a preterm multiple birth infant, the conception of conjoined twins following in vitro fertilization (IVF), depression in fathers of twins, and twin-to-twin transfusion incidence in monochorionic-diamniotic IVF twin pairs. Twins highlighted in the media include high-achieving identical female twins with nearly identical academic standing, tennis star Roger Federer's two sets of identical twin children, surgical separation of craniopagus conjoined twins, and the rare delivery of twins to a 23-year-old giant panda.

Artificial 64-Residue HIV-1 Enhancer-Binding Peptide Is a Potent Inhibitor of Viral Replication in HIV-1-Infected Cells

Directory of Open Access Journals (Sweden)

Mouhssin Oufir

2011-01-01

Full Text Available An artificial HIV-1 enhancer-binding peptide was extended by nine consecutive arginine residues at the C-terminus and by the nuclear localization signal of SV40 large T antigen at the N-terminus. The resulting synthetic 64-residue peptide was found to bind to the two enhancers of the HIV-1 long terminal repeat, cross the plasma membrane and the nuclear envelope of human cells, and suppress the HIV-1 enhancer-controlled expression of a green fluorescent protein reporter gene. Moreover, HIV-1 replication is inhibited by this peptide in HIV-1-infected CEM-GFP cells as revealed by HIV-1 p24 ELISA and real-time RT-PCR of HIV-1 RNA. Rapid uptake of this intracellular stable and inhibitory peptide into the cells implies that this peptide may have the potential to attenuate HIV-1 replication in vivo.

Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor

International Nuclear Information System (INIS)

Kimura, Shuhei; Sawatsubashi, Shun; Ito, Saya; Kouzmenko, Alexander; Suzuki, Eriko; Zhao, Yue; Yamagata, Kaoru; Tanabe, Masahiko; Ueda, Takashi; Fujiyama, Sari; Murata, Takuya; Matsukawa, Hiroyuki; Takeyama, Ken-ichi; Yaegashi, Nobuo

2008-01-01

Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressed EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly

An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide 'stapling' technology.

Science.gov (United States)

He, Y; Chen, D; Zheng, W

2015-11-12

Specific protein-protein interactions (PPIs) constitute a key underlying mechanism for the presence of a multitude of intracellular signaling pathways, which are essential for the survival of normal and cancer cells. Specific molecular blockers for a crucial PPI would therefore be invaluable tools for an enhanced functional interrogation of the signaling pathway harboring this particular PPI. On the other hand, if a particular PPI is essential for the survival of cancer cells but is absent in or dispensable for the survival of normal cells, its specific molecular blockers could potentially be developed into effective anticancer therapeutics. Due to the flat and extended PPI interface, it would be conceivably difficult for small molecules to achieve an effective blockade, a problem which could be potentially circumvented with peptides or proteins. However, the well-documented proteolytic instability and cellular impermeability of peptides and proteins in general would make their developing into effective intracellular PPI blockers quite a challenge. With the advent of the peptide 'stapling' technology which was demonstrated to be able to stabilize the α-helical conformation of a peptide via bridging two neighboring amino-acid side chains with a 'molecular staple', a linear parent peptide could be transformed into a stronger PPI blocker with enhanced proteolytic stability and cellular permeability. This review will furnish an account on the peptide 'stapling' technology and its exploitation in efforts to achieve an enhanced functional interrogation or manipulation of intracellular signaling pathways especially those that are cancer relevant.

The Conserved Arginine Cluster in the Insert of the Third Cytoplasmic Loop of the Long Form of the D2 Dopamine Receptor (D2L-R Acts as an Intracellular Retention Signal

Directory of Open Access Journals (Sweden)

Valentina Kubale

2016-07-01

Full Text Available This study examined whether the conserved arginine cluster present within the 29-amino acid insert of the long form of the D2 dopamine receptor (D2L-R confers its predominant intracellular localization. We hypothesized that the conserved arginine cluster (RRR located within the insert could act as an RXR-type endoplasmic reticulum (ER retention signal. Arginine residues (R within the cluster at positions 267, 268, and 269 were charge-reserved to glutamic acids (E, either individually or in clusters, thus generating single, double, and triple D2L-R mutants. Through analyses of cellular localization by confocal microscopy and enzyme-linked immunosorbent assay (ELISA, radioligand binding assay, bioluminescence resonance energy transfer (BRET2 β-arrestin 2 (βarr2 recruitment assay, and cAMP signaling, it was revealed that charge reversal of the R residues at all three positions within the motif impaired their colocalization with ER marker calnexin and led to significantly improved cell surface expression. Additionally, these data demonstrate that an R to glutamic acid (E substitution at position 2 within the RXR motif is not functionally permissible. Furthermore, all generated D2L-R mutants preserved their functional integrity regarding ligand binding, agonist-induced βarr2 recruitment and Gαi-mediated signaling. In summary, our results show that the conserved arginine cluster within the 29-amino acid insert of third cytoplasmic loop (IC3 of the D2L-R appears to be the ER retention signal.

Synthesis of specific deuterium labeled tyrosine and phenylalanine derivatives and their use in the total synthesis of [8-arginine]vasopressin derivatives: the separation of diastereomeric [8-arginine]vasopressin derivatives by partition chromatography

International Nuclear Information System (INIS)

Yamamoto, D.M.; Upson, D.A.; Linn, D.K.; Hruby, V.J.

1977-01-01

Derivatives of tyrosine specifically deuterated at the α carbon ([α- 2 H 1 ]tyrosine) and at both the α and β carbons ([α,β,β- 2 H 3 ]tyrosine) and a derivative of phenylalanine specifically deuterated at the α carbon ([α- 2 H 1 ]phenylalanine) have been synthesized in high yield. These labeled compounds have been resolved enzymatically, and the enantiomers and racemates have been converted to N-tert-butyloxycarbonyl derivatives. The deuterium labels were not exchanged under the conditions of the syntheses. The protected derivatives as well as specifically deuterated derivatives of S-benzylcysteine and of glycine were used to prepare specifically deuterated analogues of [8-arginine] vasopressin using solid phase peptide procedures. The use of improved synthetic procedures resulted in considerable improvements in the yields of [8-arginine]vasopressin compared with previous reports. In addition, new solvent systems for partition chromatography purification of [8-arginine]vasopressin on Sephadex were developed which allowed a facile one-step separation of diastereomers of [8-arginine]vasopressin containing a racemic amino acid at either the 1-hemicystine or the 2-tyrosine positions of the hormone

Enhanced recombinant factor VII expression in Chinese hamster ovary cells by optimizing signal peptides and fed-batch medium.

Science.gov (United States)

Peng, Lin; Yu, Xiao; Li, Chengyuan; Cai, Yanfei; Chen, Yun; He, Yang; Yang, Jianfeng; Jin, Jian; Li, Huazhong

2016-04-01

Signal peptides play an important role in directing and efficiently transporting secretory proteins to their proper locations in the endoplasmic reticulum of mammalian cells. The aim of this study was to enhance the expression of recombinant coagulation factor VII (rFVII) in CHO cells by optimizing the signal peptides and type of fed-batch culture medium used. Five sub-clones (O2, I3, H3, G2 and M3) with different signal peptide were selected by western blot (WB) analysis and used for suspension culture. We compared rFVII expression levels of 5 sub-clones and found that the highest rFVII expression level was obtained with the IgK signal peptide instead of Ori, the native signal peptide of rFVII. The high protein expression of rFVII with signal peptide IgK was mirrored by a high transcription level during suspension culture. After analyzing culture and feed media, the combination of M4 and F4 media yielded the highest rFVII expression of 20 mg/L during a 10-day suspension culture. After analyzing cell density and cell cycle, CHO cells feeding by F4 had a similar percentage of cells in G0/G1 and a higher cell density compared to F2 and F3. This may be the reason for high rFVII expression in M4+F4. In summary, rFVII expression was successfully enhanced by optimizing the signal peptide and fed-batch medium used in CHO suspension culture. Our data may be used to improve the production of other therapeutic proteins in fed-batch culture.

Efficient secretory expression of recombinant proteins in Escherichia coli with a novel actinomycete signal peptide.

Science.gov (United States)

Cui, Yanbing; Meng, Yiwei; Zhang, Juan; Cheng, Bin; Yin, Huijia; Gao, Chao; Xu, Ping; Yang, Chunyu

2017-01-01

In well-established heterologous hosts, such as Escherichia coli, recombinant proteins are usually intracellular and frequently found as inclusion bodies-especially proteins possessing high rare codon content. In this study, successful secretory expression of three hydrolases, in a constructed inducible or constitutive system, was achieved by fusion with a novel signal peptide (Kp-SP) from an actinomycete. The signal peptide efficiently enabled extracellular protein secretion and also contributed to the active expression of the intracellular recombinant proteins. The thermophilic α-amylase gene of Bacillus licheniformis was fused with Kp-SP. Both recombinants, carrying inducible and constitutive plasmids, showed remarkable increases in extracellular and intracellular amylolytic activity. Amylase activity was observed to be > 10-fold in recombinant cultures with the constitutive plasmid, pBSPPc, compared to that in recombinants lacking Kp-SP. Further, the signal peptide enabled efficient secretion of a thermophilic cellulase into the culture medium, as demonstrated by larger halo zones and increased enzymatic activities detected in both constructs from different plasmids. For heterologous proteins with a high proportion of rare codons, it is difficult to obtain high expression in E. coli owing to the codon bias. Here, the fusion of an archaeal homologue of the amylase encoding gene, FSA, with Kp-SP resulted in > 5-fold higher extracellular activity. The successful extracellular expression of the amylase indicated that the signal peptide also contributed significantly to its active expression and signified the potential value of this novel and versatile signal peptide in recombinant protein production. Copyright © 2016 Elsevier Inc. All rights reserved.

Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death.

Science.gov (United States)

Movafegh, Bahareh; Jalal, Razieh; Mohammadi, Zobeideh; Aldaghi, Seyyede Araste

2018-04-11

Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin (0.5 μM) and poly-L-arginine (1 μg ml-1) caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prediction of lipoprotein signal peptides in Gram-negative bacteria.

Science.gov (United States)

Juncker, Agnieszka S; Willenbrock, Hanni; Von Heijne, Gunnar; Brunak, Søren; Nielsen, Henrik; Krogh, Anders

2003-08-01

A method to predict lipoprotein signal peptides in Gram-negative Eubacteria, LipoP, has been developed. The hidden Markov model (HMM) was able to distinguish between lipoproteins (SPaseII-cleaved proteins), SPaseI-cleaved proteins, cytoplasmic proteins, and transmembrane proteins. This predictor was able to predict 96.8% of the lipoproteins correctly with only 0.3% false positives in a set of SPaseI-cleaved, cytoplasmic, and transmembrane proteins. The results obtained were significantly better than those of previously developed methods. Even though Gram-positive lipoprotein signal peptides differ from Gram-negatives, the HMM was able to identify 92.9% of the lipoproteins included in a Gram-positive test set. A genome search was carried out for 12 Gram-negative genomes and one Gram-positive genome. The results for Escherichia coli K12 were compared with new experimental data, and the predictions by the HMM agree well with the experimentally verified lipoproteins. A neural network-based predictor was developed for comparison, and it gave very similar results. LipoP is available as a Web server at www.cbs.dtu.dk/services/LipoP/.

Lepton number violating signals of the top quark partners in the left-right twin Higgs model

International Nuclear Information System (INIS)

Goh, Hock-Seng; Krenke, Christopher A.

2010-01-01

We study the collider signatures of the left-right twin Higgs model in the case that the right-handed neutrino mass is less than the mass of the right-handed gauge boson. In this scenario, new leptonic decay chains open up, allowing the particles which cancel the one-loop quadratic divergences of the Higgs, the right-handed gauge bosons and top-partners, to be discovered. Half of these events contain same-sign leptons without missing energy, which have no genuine standard model background and for which the backgrounds are purely instrumental. These signals may be used to complement other collider searches and, in certain regions of parameter space, may be the only way to observe the particles responsible for natural electroweak symmetry breaking in the left-right twin Higgs model.

The GlaA signal peptide substantially increases the expression and secretion of α-galactosidase in Aspergillus niger.

Science.gov (United States)

Xu, Yue; Wang, Yan-Hui; Liu, Tian-Qi; Zhang, Hui; Zhang, He; Li, Jie

2018-03-31

α-Galactosidases are widely used in many fields. It is necessary to improve the production of enzymes through microbiological processes. The aim of this study was to construct recombinant Aspergillus niger strains with high α-galactosidase production. Two recombinant A. niger strains were constructed: AB and AGB. The recombinant AB strain contained the α-galactosidase aglB gene from A. niger with its native AglB signal peptide regulated by the glucoamylase promoter. In the AGB recombinant strain, the AglB signal peptide was replaced with the glucoamylase (GlaA) signal peptide. The extracellular maximum α-galactosidase activity of the AGB strain was 215.7 U/ml and that of the AB strain was 9.8 U/mL. The optimal conditions for α-galactosidase were pH 3.5 and 35 °C. The GlaA signal peptide substantially increased the yield of secreted α-galactosidase in A. niger. This recombinant strain holds great potential for industrial applications.

Peak effect in twinned superconductors

International Nuclear Information System (INIS)

Larkin, A.I.; Marchetti, M.C.; Vinokur, V.M.

1995-01-01

A sharp maximum in the critical current J c as a function of temperature just below the melting point of the Abrikosov flux lattice has recently been observed in both low- and high-temperature superconductors. This peak effect is strongest in twinned crystals for fields aligned with the twin planes. We propose that this peak signals the breakdown of the collective pinning regime and the crossover to strong pinning of single vortices on the twin boundaries. This crossover is very sharp and can account for the steep drop of the differential resistivity observed in experiments. copyright 1995 The American Physical Society

Reconciling structural and thermodynamic predictions using all-atom and coarse-grain force fields: the case of charged oligo-arginine translocation into DMPC bilayers.

Science.gov (United States)

Hu, Yuan; Sinha, Sudipta Kumar; Patel, Sandeep

2014-10-16

Using the translocation of short, charged cationic oligo-arginine peptides (mono-, di-, and triarginine) from bulk aqueous solution into model DMPC bilayers, we explore the question of the similarity of thermodynamic and structural predictions obtained from molecular dynamics simulations using all-atom and Martini coarse-grain force fields. Specifically, we estimate potentials of mean force associated with translocation using standard all-atom (CHARMM36 lipid) and polarizable and nonpolarizable Martini force fields, as well as a series of modified Martini-based parameter sets. We find that we are able to reproduce qualitative features of potentials of mean force of single amino acid side chain analogues into model bilayers. In particular, modifications of peptide-water and peptide-membrane interactions allow prediction of free energy minima at the bilayer-water interface as obtained with all-atom force fields. In the case of oligo-arginine peptides, the modified parameter sets predict interfacial free energy minima as well as free energy barriers in almost quantitative agreement with all-atom force field based simulations. Interfacial free energy minima predicted by a modified coarse-grained parameter set are -2.51, -4.28, and -5.42 for mono-, di-, and triarginine; corresponding values from all-atom simulations are -0.83, -3.33, and -3.29, respectively, all in units of kcal/mol. We found that a stronger interaction between oligo-arginine and the membrane components and a weaker interaction between oligo-arginine and water are crucial for producing such minima in PMFs using the polarizable CG model. The difference between bulk aqueous and bilayer center states predicted by the modified coarse-grain force field are 11.71, 14.14, and 16.53 kcal/mol, and those by the all-atom model are 6.94, 8.64, and 12.80 kcal/mol; those are of almost the same order of magnitude. Our simulations also demonstrate a remarkable similarity in the structural aspects of the ensemble of

Optimizing the identification of citrullinated peptides by mass spectrometry

DEFF Research Database (Denmark)

Bennike, Tue; Lauridsen, Kasper B.; Olesen, Michael Kruse

2013-01-01

Citrullinated proteins have been associated with several diseases and citrullination can most likely function as a target for novel diagnostic agents and unravel disease etiologies. The correct identification of citrullinated proteins is therefore of most importance. Mass spectrometry (MS) driven...... of trypsin, digestion was performed on synthetic peptide sets containing either arginine or citrulline. The peptide sequences originated from disease-associated in vivo citrullinated proteins; some reported as being C-terminal tryptic citrullinated peptides. Furthermore, the proteolytic activity was verified...

Specific expression of GFPuv-β1,3-N-acetylglucosaminyltransferase 2 fusion protein in fat body of Bombyx mori silkworm larvae using signal peptide

International Nuclear Information System (INIS)

Kato, Tatsuya; Park, Enoch Y.

2007-01-01

Bombyxin (bx) and prophenoloxidase-activating enzyme (ppae) signal peptides from Bombyx mori, their modified signal peptides, and synthetic signal peptides were investigated for the secretion of GFP uv -β1,3-N-acetylglucosaminyltransferase 2 (GGT2) fusion protein in B. mori Bm5 cells and silkworm larvae using cysteine protease deficient B. mori multiple nucleopolyhedrovirus (BmMNPV-CP - ) and its bacmid. The secretion efficiencies of all signal peptides were 15-30% in Bm5 cells and 24-30% in silkworm larvae, while that of the +16 signal peptide was 0% in Bm5 cells and 1% in silkworm larvae. The fusion protein that contained the +16 signal peptide was expressed specifically in the endoplasmic reticulum (ER) and in the fractions of cell precipitations. Ninety-four percent of total intracellular β1,3-N-acetylglucosaminyltransferase (β3GnT) activity was detected in cell precipitations following the 600, 8000, and 114,000g centrifugations. In the case of the +38 signal peptide, 60% of total intracellular activity was detected in the supernatant from the 114,000g spin, and only 1% was found in the precipitate. Our results suggest that the +16 signal peptide might be situated in the transmembrane region and not cleaved by signal peptidase in silkworm or B. mori cells. Therefore, the fusion protein connected to the +16 signal peptide stayed in the fat body of silkworm larvae with biological function, and was not secreted extracellularly

Oliver Sacks: Our Correspondence About Twins/Twin Research: Vanishing Twins Syndrome; Discordant Sex in MZ Twins; Pregnancy Outcomes in IVF and ICSI Conceived Twins/Print and Media: Superfetated Twins; Twins Discordant for Smoking; Twins in Fashion; Yale University Twin Hockey Players; Conjoined Twin-Visiting Professor.

Science.gov (United States)

Segal, Nancy L

2017-08-01

The late neurologist and author, Oliver Sacks, published an insightful 1986 review of Marjorie Wallace's book, The Silent Twins, in the New York Times. Taking exception to his assertion about Sir Francis Galton, I wrote a letter to the Times' editor. The letter was unpublished, but it brought a wonderful response from Sacks himself that is reproduced and examined. Next, brief reviews of twin research concerning the vanishing twin syndrome (VTS), discordant sex in a monozygotic (MZ) twin pair, and multiple pregnancy outcomes from assisted reproductive technology (ART) are presented. This section is followed by popular coverage of superfetated twins, smoking-discordant co-twins, twins in fashion, Yale University twin hockey players, and a visiting professor who was a conjoined twin.

L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

International Nuclear Information System (INIS)

Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

2012-01-01

Highlights: ► L-Arginine treatment reduced the metabolic disturbances in diabetic animals. ► Antioxidant marker proteins were found high in myocardium by L-arginine treatment. ► Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. ► L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. ► Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg −1 body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be

L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

Energy Technology Data Exchange (ETDEWEB)

Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India); Selvam, Govindan Sadasivam, E-mail: drselvamgsbiochem@rediffmail.com [Molecular Cardiology Unit, Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai 625 021, Tamilnadu (India)

2012-11-23

Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

Ocean acidification affects marine chemical communication by changing structure and function of peptide signalling molecules.

Science.gov (United States)

Roggatz, Christina C; Lorch, Mark; Hardege, Jörg D; Benoit, David M

2016-12-01

Ocean acidification is a global challenge that faces marine organisms in the near future with a predicted rapid drop in pH of up to 0.4 units by the end of this century. Effects of the change in ocean carbon chemistry and pH on the development, growth and fitness of marine animals are well documented. Recent evidence also suggests that a range of chemically mediated behaviours and interactions in marine fish and invertebrates will be affected. Marine animals use chemical cues, for example, to detect predators, for settlement, homing and reproduction. But, while effects of high CO 2 conditions on these behaviours are described across many species, little is known about the underlying mechanisms, particularly in invertebrates. Here, we investigate the direct influence of future oceanic pH conditions on the structure and function of three peptide signalling molecules with an interdisciplinary combination of methods. NMR spectroscopy and quantum chemical calculations were used to assess the direct molecular influence of pH on the peptide cues, and we tested the functionality of the cues in different pH conditions using behavioural bioassays with shore crabs (Carcinus maenas) as a model system. We found that peptide signalling cues are susceptible to protonation in future pH conditions, which will alter their overall charge. We also show that structure and electrostatic properties important for receptor binding differ significantly between the peptide forms present today and the protonated signalling peptides likely to be dominating in future oceans. The bioassays suggest an impaired functionality of the signalling peptides at low pH. Physiological changes due to high CO 2 conditions were found to play a less significant role in influencing the investigated behaviour. From our results, we conclude that the change of charge, structure and consequently function of signalling molecules presents one possible mechanism to explain altered behaviour under future oceanic p

Independent component analysis of normal and abnormal rhythm in twin pregnancies

International Nuclear Information System (INIS)

Mensah-Brown, Nana Aba; Lutter, William J; Wakai, Ronald T; Comani, Silvia; Strasburger, Janette F

2011-01-01

We investigated the utility of ICA for evaluation of fetal rhythm in five uncomplicated twin pregnancies and in five twin pregnancies complicated by fetal arrhythmia. Using objective and subjective criteria, we sought to determine how the signal-to-noise ratio, signal fidelity and interference rejection are affected when synthesizing the fetal signal using all the signal-containing ICA components (rank-p ICA) versus using the single dominant component (rank-1 ICA). The signal of each fetus was most commonly distributed over 1 or 2 ICA components, as previously observed in studies of singleton pregnancies; however, in 8 of 26 (31%) cases the signal of each fetus was distributed over 3, 4 or even 5 ICA components. Rank-1 ICA provided the highest SNR and interference rejection, but at the cost of reduced signal fidelity. Our results corroborate that in twin pregnancies, including twin pregnancies complicated by fetal arrhythmia, rank-1 ICA is very effective in isolating the QRS complexes of each fetus; however, it has some limitations when used for fetal rhythm evaluation due to signal distortion. Occasionally, rank-1 ICA completely separates the P-wave and the T-wave from the QRS complex, thus requiring the mixing of several ICA components to achieve acceptable signal fidelity

Reared-Apart Chinese Twins: Chance Discovery/Twin-Based Research: Twin Study of Media Use; Twin Relations Over the Life Span; Breast-Feeding Opposite-Sex Twins/Print and Online Media: Twins in Fashion; Second Twin Pair Born to Tennis Star; Twin Primes; Twin Pandas.

Science.gov (United States)

Segal, Nancy L

2017-04-01

A January 2017 reunion of 10-year-old reared-apart Chinese twin girls was captured live on ABC's morning talk show Good Morning America, and rebroadcast on their evening news program Nightline. The twins' similarities and differences, and their participation in ongoing research will be described. This story is followed by reviews of twin research concerning genetic and environmental influences on media use, twin relations across the lifespan and the breast-feeding of opposite-sex twins. Popular interest items include twins in fashion, the second twin pair born to an internationally renowned tennis star, twin primes and twin pandas.

A Genetic Programming Method for the Identification of Signal Peptides and Prediction of Their Cleavage Sites

Directory of Open Access Journals (Sweden)

David Lennartsson

2004-01-01

Full Text Available A novel approach to signal peptide identification is presented. We use an evolutionary algorithm for automatic evolution of classification programs, so-called programmatic motifs. The variant of evolutionary algorithm used is called genetic programming where a population of solution candidates in the form of full computer programs is evolved, based on training examples consisting of signal peptide sequences. The method is compared with a previous work using artificial neural network (ANN approaches. Some advantages compared to ANNs are noted. The programmatic motif can perform computational tasks beyond that of feed-forward neural networks and has also other advantages such as readability. The best motif evolved was analyzed and shown to detect the h-region of the signal peptide. A powerful parallel computer cluster was used for the experiment.

Rhizobial peptidase HrrP cleaves host-encoded signaling peptides and mediates symbiotic compatibility.

Science.gov (United States)

Price, Paul A; Tanner, Houston R; Dillon, Brett A; Shabab, Mohammed; Walker, Graham C; Griffitts, Joel S

2015-12-08

Legume-rhizobium pairs are often observed that produce symbiotic root nodules but fail to fix nitrogen. Using the Sinorhizobium meliloti and Medicago truncatula symbiotic system, we previously described several naturally occurring accessory plasmids capable of disrupting the late stages of nodule development while enhancing bacterial proliferation within the nodule. We report here that host range restriction peptidase (hrrP), a gene found on one of these plasmids, is capable of conferring both these properties. hrrP encodes an M16A family metallopeptidase whose catalytic activity is required for these symbiotic effects. The ability of hrrP to suppress nitrogen fixation is conditioned upon the genotypes of both the host plant and the hrrP-expressing rhizobial strain, suggesting its involvement in symbiotic communication. Purified HrrP protein is capable of degrading a range of nodule-specific cysteine-rich (NCR) peptides encoded by M. truncatula. NCR peptides are crucial signals used by M. truncatula for inducing and maintaining rhizobial differentiation within nodules, as demonstrated in the accompanying article [Horváth B, et al. (2015) Proc Natl Acad Sci USA, 10.1073/pnas.1500777112]. The expression pattern of hrrP and its effects on rhizobial morphology are consistent with the NCR peptide cleavage model. This work points to a symbiotic dialogue involving a complex ensemble of host-derived signaling peptides and bacterial modifier enzymes capable of adjusting signal strength, sometimes with exploitative outcomes.

Transcriptional Profiling of the Oral Pathogen Streptococcus mutans in Response to Competence Signaling Peptide XIP.

Science.gov (United States)

Wenderska, Iwona B; Latos, Andrew; Pruitt, Benjamin; Palmer, Sara; Spatafora, Grace; Senadheera, Dilani B; Cvitkovitch, Dennis G

2017-01-01

In the cariogenic Streptococcus mutans , competence development is regulated by the ComRS signaling system comprised of the ComR regulator and the ComS prepeptide to the competence signaling peptide XIP (ComX-inducing peptide). Aside from competence development, XIP signaling has been demonstrated to regulate cell lysis, and recently, the expression of bacteriocins, small antimicrobial peptides used by bacteria to inhibit closely related species. Our study further explores the effect of XIP signaling on the S. mutans transcriptome. RNA sequencing revealed that XIP induction resulted in a global change in gene expression that was consistent with a stress response. An increase in several membrane-bound regulators, including HdrRM and BrsRM, involved in bacteriocin production, and the VicRKX system, involved in acid tolerance and biofilm formation, was observed. Furthermore, global changes in gene expression corresponded to changes observed during the stringent response to amino acid starvation. Effects were also observed on genes involved in sugar transport and carbon catabolite repression and included the levQRST and levDEFG operons. Finally, our work identified a novel heat shock-responsive intergenic region, encoding a small RNA, with a potential role in competence shutoff. IMPORTANCE Genetic competence provides bacteria with an opportunity to increase genetic diversity or acquire novel traits conferring a survival advantage. In the cariogenic pathogen Streptococcus mutans , DNA transformation is regulated by the competence stimulating peptide XIP (ComX-inducing peptide). The present study utilizes high-throughput RNA sequencing (RNAseq) to provide a greater understanding of how global gene expression patterns change in response to XIP. Overall, our work demonstrates that in S. mutans , XIP signaling induces a response that resembles the stringent response to amino acid starvation. We further identify a novel heat shock-responsive intergenic region with a

A role of TDIF peptide signaling in vascular cell differentiation is conserved among euphyllophytes

Directory of Open Access Journals (Sweden)

Yuki eHirakawa

2015-11-01

Full Text Available Peptide signals mediate a variety of cell-to-cell communication crucial for plant growth and development. During Arabidopsis thaliana vascular development, a CLE (CLAVATA3/EMBRYO SURROUNDING REGION-related family peptide hormone, TDIF (tracheary element differentiation inhibitory factor, regulates procambial cell fate by its inhibitory activity on xylem differentiation. To address if this activity is conserved among vascular plants, we performed comparative analyses of TDIF signaling in non-flowering vascular plants (gymnosperms, monilophytes and lycophytes. We identified orthologs of TDIF/CLE as well as its receptor TDR/PXY (TDIF RECEPTOR/PHLOEM INTERCALATED WITH XYLEM in Ginkgo biloba, Adiantum aethiopicum and Selaginella kraussiana by RACE-PCR. The predicted TDIF peptide sequences in seed plants and monilophytes were identical to that of A. thaliana TDIF. We examined the effects of exogenous CLE peptide-motif sequences of TDIF in these species. We found that liquid culturing of dissected leaves or shoots was useful for examining TDIF activity during vascular development. TDIF treatment suppressed xylem/tracheary element differentiation of procambial cells in G. bioloba and A. aethiopicum leaves. In contrast, neither TDIF nor putative endogenous TDIF inhibited xylem differentiation in developing shoots and rhizophores of S. kraussiana. These data suggest that activity of TDIF in vascular development is conserved among extant euphyllophytes. In addition to the conserved function, via liquid culturing of its bulbils, we found a novel inhibitory activity on root growth in the monilophyte Asplenium x lucrosum suggesting lineage-specific co-option of peptide signaling occurred during the evolution of vascular plant organs.

The 16th International Twin Congress: Highlights from Madrid/Twin Research: Twin Study of Partner Aggression; ABO Incompatibility in Dizygotic Twins; Growth Discordance in a Monoamniotic Twin Pair; Quick Note on Twin Implantation/In the Media: Long-Lost Twins Found; NASA Twin Experiment; Twin Brothers and the Las Vegas Attack; Retired Twin Airline Pilots; Twin Film Clips.

Science.gov (United States)

Segal, Nancy L

2018-02-01

Highlights from the 16th International Twin Congress, held in Madrid, Spain from November 16-18, 2017, are presented. The Twin Congress, formerly held every three years, now takes place biennially with a single-day meeting organized during the off years. This meeting is the largest gathering of scientific twin researchers, medical personnel, and representatives of multiple birth organizations in the world. This overview is followed by reviews of recent twin research and commentary concerning partner aggression, ABO incompatibility in dizygotic twins, growth discordance in a monoamniotic twin pair and twin implantation. The article closes with summaries of timely topics in the media, namely a father's finding of his long-lost twin children, early results from the NASA twin experiment, twin brothers at the center of the October 2017 Las Vegas attack, retired twin airline pilots, and clips from recent films with twin-based themes.

Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

DEFF Research Database (Denmark)

Molnos, Sophie; Wahl, Simone; Haid, Mark

2018-01-01

) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes. Methods: We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families......Aims/hypothesis: Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1...... (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277...

Overcoming the Refractory Expression of Secreted Recombinant Proteins in Mammalian Cells through Modification of the Signal Peptide and Adjacent Amino Acids.

Science.gov (United States)

Güler-Gane, Gülin; Kidd, Sara; Sridharan, Sudharsan; Vaughan, Tristan J; Wilkinson, Trevor C I; Tigue, Natalie J

2016-01-01

The expression and subsequent purification of mammalian recombinant proteins is of critical importance to many areas of biological science. To maintain the appropriate tertiary structure and post-translational modifications of such proteins, transient mammalian expression systems are often adopted. The successful utilisation of these systems is, however, not always forthcoming and some recombinant proteins prove refractory to expression in mammalian hosts. In this study we focussed on the role of different N-terminal signal peptides and residues immediately downstream, in influencing the level of secreted recombinant protein obtained from suspension HEK293 cells. Using secreted alkaline phosphatase (SEAP) as a model protein, we identified that the +1/+2 downstream residues flanking a heterologous signal peptide significantly affect secreted levels. By incorporating these findings we conducted a comparison of different signal peptide sequences and identified the most productive as secrecon, a computationally-designed sequence. Importantly, in the context of the secrecon signal peptide and SEAP, we also demonstrated a clear preference for specific amino acid residues at the +1 position (e.g. alanine), and a detrimental effect of others (cysteine, proline, tyrosine and glutamine). When proteins that naturally contain these "undesirable" residues at the +1 position were expressed with their native signal peptide, the heterologous secrecon signal peptide, or secrecon with an additional alanine at the +1 or +1 and +2 position, the level of expression differed significantly and in an unpredictable manner. For each protein, however, at least one of the panel of signal peptide/adjacent amino acid combinations enabled successful recombinant expression. In this study, we highlight the important interplay between a signal peptide and its adjacent amino acids in enabling protein expression, and we describe a strategy that could enable recombinant proteins that have so far

Brazilian Twin Registry: A Bright Future for Twin Studies/Twin Research: Twin Study of Alcohol Consumption and Mortality; Oxygen Uptake in Adolescent Twins/In the News: Superfecundated Twins In Vietnam; Adolescent Twin Relations; Twin and Triplet Co-Workers; A Special Twin Ultrasound; Monozygotic Twins With Different Skin Color; Identical Twin Returns from Space.

Science.gov (United States)

Segal, Nancy L

2016-06-01

The establishment of the Brazilian Twin Registry for the study of genetic, social, and cultural influences on behavior is one of eleven newly funded projects in the Department of Psychology at the University of São Paulo. These 11 interrelated projects form the core of the university's Center for Applied Research on Well-Being and Human Behavior. An overview of the planned twin research and activities to date is presented. Next, two recent twin studies are reviewed, one on the relationship between alcohol consumption and mortality, and the other on factors affecting maximal oxygen uptake. Twins cited in the media include the first identified superfecundated twins in Vietnam, adolescent twin relations, twins and triplets who work together, monozygotic twins with different skin tones and a co-twin control study that addresses the effects of space travel.

The Effect of Carbohydrates and Arginine on Arginine Metabolism by Excised Bean Leaves in the Dark

Science.gov (United States)

Stewart, Cecil R.

1975-01-01

The effect of carbohydrate on arginine utilization by excised bean (Phaseolus vulgaris L. var. Tendergreen) leaves in the dark was studied by adding arginine to leaves differing in carbohydrate levels, and measuring the arginine content of the leaves at intervals. In nonstarved leaves, the arginine content decreased steadily after vacuum infiltration of 10 mm arginine and was essentially completely utilized by 36 hours after infiltration. In starved leaves, the arginine content did not decrease except for a brief period of about 4 hours after infiltration. The distribution of 14C after adding 14C-arginine to starved and nonstarved leaves indicated that the presence of carbohydrates in the leaves stimulates the utilization of arginine for protein synthesis and conversion to other amino acids, organic acids, and CO2 (catabolism). Adding sucrose along with arginine to starved leaves stimulated this utilization of arginine for both protein synthesis and catabolism. This effect of sugar on catabolism is different than results of similar studies done previously with proline. Increasing the concentration of added arginine greatly increased arginine catabolism but had a relatively small effect on utilization of arginine for protein synthesis. This result is the same as similar results from adding different concentrations of proline to excised leaves. PMID:16659159

Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2 Agonists

Directory of Open Access Journals (Sweden)

Fabio Cattaneo

2013-04-01

Full Text Available The formyl peptide receptor 2 (FPR2 is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ-42 and prion protein (Prp106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP and pituitary adenylate cyclase activating polypeptide (PACAP-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger several agonist-dependent signal transduction pathways, including activation of phospholipase C (PLC, protein kinase C (PKC isoforms, the phosphoinositide 3-kinase (PI3K/protein kinase B (Akt pathway, the mitogen-activated protein kinase (MAPK pathway, p38MAPK, as well as the phosphorylation of cytosolic tyrosine kinases, tyrosine kinase receptor transactivation, phosphorylation and nuclear translocation of regulatory transcriptional factors, release of calcium and production of oxidants. FPR2 is an attractive therapeutic target, because of its involvement in a range of normal physiological processes and pathological diseases. Here, we review and discuss the most significant findings on the intracellular pathways and on the cross-communication between FPR2 and tyrosine kinase receptors triggered by different FPR2

High-resolution mass spectrometry driven discovery of peptidic danger signals in insect immunity.

Directory of Open Access Journals (Sweden)

Arton Berisha

Full Text Available The 'danger model' is an alternative concept for immune response postulating that the immune system reacts to entities that do damage (danger associated molecular patterns, DAMP and not only to entities that are foreign (pathogen-associated molecular patterns, PAMP as proposed by classical immunology concepts. In this study we used Galleria mellonella to validate the danger model in insects. Hemolymph of G. mellonella was digested with thermolysin (as a representative for virulence-associated metalloproteinases produced by humanpathogens followed by chromatographic fractionation. Immune-stimulatory activity was tested by measuring lysozyme activity with the lytic zone assays against Micrococcus luteus cell wall components. Peptides were analyzed by nano-scale liquid chromatography coupled to high-resolution Fourier transform mass spectrometers. Addressing the lack of a genome sequence we complemented the rudimentary NCBI protein database with a recently established transcriptome and de novo sequencing methods for peptide identification. This approach led to identification of 127 peptides, 9 of which were identified in bioactive fractions. Detailed MS/MS experiments in comparison with synthetic analogues confirmed the amino acid sequence of all 9 peptides. To test the potential of these putative danger signals to induce immune responses we injected the synthetic analogues into G. mellonella and monitored the anti-bacterial activity against living Micrococcus luteus. Six out of 9 peptides identified in the bioactive fractions exhibited immune-stimulatory activity when injected. Hence, we provide evidence that small peptides resulting from thermolysin-mediated digestion of hemolymph proteins function as endogenous danger signals which can set the immune system into alarm. Consequently, our study indicates that the danger model also plays a role in insect immunity.

Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain

DEFF Research Database (Denmark)

Koppelhus, Uffe; Shiraishi, Takehiko; Zachar, Vladimir

2008-01-01

Conjugation to cationic cell penetrating peptides (such as Tat, Penetratin, or oligo arginines) efficiently improves the cellular uptake of large hydrophilic molecules such as oligonucleotides and peptide nucleic acids, but the cellular uptake is predominantly via an unproductive endosomal pathway...... for future in vivo applications. We find that simply conjugating a lipid domain (fatty acid) to the cationic peptide (a CatLip conjugate) increases the biological effect of the corresponding PNA (CatLip) conjugates in a luciferase cellular antisense assay up to 2 orders of magnitude. The effect increases...... with increasing length of the fatty acid (C8-C16) but in parallel also results in increased cellular toxicity, with decanoic acid being optimal. Furthermore, the relative enhancement is significantly higher for Tat peptide compared to oligoarginine. Confocal microscopy and chloroquine enhancement indicates...

Expression of TLP-3 gene without signal peptide in tobacco plants ...

African Journals Online (AJOL)

Expression of TLP-3 gene without signal peptide in tobacco plants using Agrobacterium mediated transformation. ... Plants are exploited as a source of food by a wide range of parasites, including viruses, bacteria, fungi, nematodes, insects and even other plants. So paying attention to their protection is very important.

Expression of the cationic antimicrobial peptide lactoferricin fused with the anionic peptide in Escherichia coli.

Science.gov (United States)

Kim, Ha-Kun; Chun, Dae-Sik; Kim, Joon-Sik; Yun, Cheol-Ho; Lee, Ju-Hoon; Hong, Soon-Kwang; Kang, Dae-Kyung

2006-09-01

Direct expression of lactoferricin, an antimicrobial peptide, is lethal to Escherichia coli. For the efficient production of lactoferricin in E. coli, we developed an expression system in which the gene for the lysine- and arginine-rich cationic lactoferricin was fused to an anionic peptide gene to neutralize the basic property of lactoferricin, and successfully overexpressed the concatemeric fusion gene in E. coli. The lactoferricin gene was linked to a modified magainin intervening sequence gene by a recombinational polymerase chain reaction, thus producing an acidic peptide-lactoferricin fusion gene. The monomeric acidic peptide-lactoferricin fusion gene was multimerized and expressed in E. coli BL21(DE3) upon induction with isopropyl-beta-D-thiogalactopyranoside. The expression levels of the fusion peptide reached the maximum at the tetramer, while further increases in the copy number of the fusion gene substantially reduced the peptide expression level. The fusion peptides were isolated and cleaved to generate the separate lactoferricin and acidic peptide. About 60 mg of pure recombinant lactoferricin was obtained from 1 L of E. coli culture. The purified recombinant lactoferricin was found to have a molecular weight similar to that of chemically synthesized lactoferricin. The recombinant lactoferricin showed antimicrobial activity and disrupted bacterial membrane permeability, as the native lactoferricin peptide does.

Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

Science.gov (United States)

Buku, A; Price, J A

2001-12-01

Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

Protein arginine methyltransferase 5 is an essential component of the hypoxia-inducible factor 1 signaling pathway

International Nuclear Information System (INIS)

Lim, Ji-Hong; Choi, Yong-Joon; Cho, Chung-Hyun; Park, Jong-Wan

2012-01-01

Highlights: ► HIF-1α is expressed PRMT5-dependently in hypoxic cancer cells. ► The HIF-1 regulation of hypoxia-induced genes is attenuated in PRMT5-knocked-down cells. ► The de novo synthesis of HIF-1α depends on PRMT5. ► PRMT5 is involved in the HIF-1α translation initiated by 5′ UTR of HIF-1α mRNA. -- Abstract: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that transfers one or two methyl groups to the arginine residues of histones or non-histone proteins, and that plays critical roles in cellular processes as diverse as receptor signaling and gene expression. Furthermore, PRMT5 is highly expressed in tumors, where it may be associated with tumor growth. Although much research has been conducted on PRMT5, little is known regarding its role in adaption to hypoxia. As hypoxia-inducible factor 1 (HIF-1) is a key player in hypoxic response, we examined the possible involvement of PRMT5 in the HIF-1 signaling pathway. Of the siRNAs targeting PRMT1–8, only PRMT5 siRNA attenuated the hypoxic induction of HIF-1α in A549 cells, and this result was reproducible in all three cancer cell lines examined. PRMT5 knock-down also repressed the promoter activities and the transcript levels of HIF-1-governed genes. Mechanistically, de novo synthesis of HIF-1α protein was reduced in PRMT5-knocked-down A549 cells, and this was rescued by PRMT5 restoration. In contrast, HIF-1α transcription, RNA processing, and protein stability were unaffected by PRMT5 knock-down. Furthermore, PRMT5 was found to be essential for the HIF-1α translation initiated by the 5′ UTR of HIF-1α mRNA. Given our results and previous reports, we believe that PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation.

The use of mass spectrometry in peptide chemistry

NARCIS (Netherlands)

Leclercq, P.A.; White, P.A.; Hägele, K.; Desiderio, D.M.; Meienhofer, J.

1972-01-01

A review with 16 refs. Methods are detailed for derivatizing peptides (mg quantities) in order to provide sufficient volatility for mass spectrometry (at least 10-5 mm vapor pressure at 300 Deg is required). Three steps are used in producing the desired derivs.: (a) arginine side chains are

Twin-twin transfusion syndrome - diagnosis and prognosis

Directory of Open Access Journals (Sweden)

Hajrić-Egić Amira

2003-01-01

Full Text Available Twin-twin transfusion syndrome is a serious complication of monozygotic, monochorionic, diamniotic twins resulting from transplacental vascular communications. In this syndrome blood is thought to be shunted from one twin - donor,who develops anaemia,growth retardation and oligoamnios, to the other twin - recipient,who becomes plethoric,macrosomic and develops polyhydroamnios. The incidence of twin-twin transfusion syndrome ranges from 5-15% of all twin pregnancies. If this condition develops in the second trimester, it is usually associated with spontaneous abortion and death of one or both fetuses before viability. Developing the syndrome in the third trimester has better perinatal outcome. Mortality rates ranging from 56%-100%, depending on gestational age and severity of the syndrome. The ultrasound criterias for diagnosis, in this study,were the presence of twins of the same sex with discordant growth, with oligohydroamnios in one twin sac and polyhydroamnios in the other one, one placenta and thin membrane between twins. The present study shows clinical course of 14 cases and value of Doppler ultrasound to analyze the usefulness of umbilical artery blood flow velocimetry for predicting the risk of twin-twin transfusion syndrome. 14 twin pregnancies with twin-twin transfusion syndrome were diagnosed during the last four years period and prospectivelly followed. 9 cases were diagnosed before the completion od 28 weeks of gestation.The mean gestational age was 21,6_+4,2 weeks at diagnosis and 23,2+_3,6 weeks at delivery. 5 cases were diagnosed after 28 weeks of gestation. The mean gestational age in this group was 29,6+_2,1 weeks at diagnosis and 33+_3,3 weeks at delivery. The survival rate in this study was 29%(8/28.9 cases ended in spontaneous abortion between 18th and 27th weeks of pregnancy (table 1 and 5 in premature labor (table 2.There were 7 intrauterine death (5 at admission and 2 few days after admission and 13 neonatal deaths

The USC Adult Twin Cohorts: International Twin Study and California Twin Program.

Science.gov (United States)

Cozen, Wendy; Hwang, Amie E; Cockburn, Myles G; Hamilton, Ann S; Zadnick, John; Mack, Thomas M

2013-02-01

The study of twin subjects permits the documentation of crude heritability and may promote the identification of specific causal alleles. We believe that at the current time, the chief research advantage of twins as subjects, especially monozygotic twins, is that the commonality of their genetic and cultural identity simplifies the interpretation of biological associations. In order to study genetic and environmental determinants of cancer and chronic diseases, we developed two twin registries, maintained at the University of Southern California: The International Twin Study (ITS) and the California Twin Program (CTP). The ITS is a volunteer registry of twins with cancer and chronic disease consisting of 17,245 twin pairs affected by cancer and chronic disease, respectively, ascertained by advertising in periodicals from 1980-1991. The CTP is a population-based registry of California-born twin pairs ascertained by linking the California birth records to the State Department of Motor Vehicles. Over 51,000 individual California twins representing 36,965 pairs completed and returned 16-page questionnaires. Cancer diagnoses in the California twins are updated by regular linkage to the California Cancer Registry. Over 5,000 cancer patients are represented in the CTP. Twins from both registries have participated extensively in studies of breast cancer, melanoma, lymphoma, multiple sclerosis, systemic lupus erythematosus, diabetes mellitus type 1, mammographic density, smoking, and other traits and conditions.

Truncated Glucagon-like Peptide-1 and Exendin-4 α-Conotoxin pl14a Peptide Chimeras Maintain Potency and α-Helicity and Reveal Interactions Vital for cAMP Signaling in Vitro*

Science.gov (United States)

Swedberg, Joakim E.; Schroeder, Christina I.; Mitchell, Justin M.; Fairlie, David P.; Edmonds, David J.; Griffith, David A.; Ruggeri, Roger B.; Derksen, David R.; Loria, Paula M.; Price, David A.; Liras, Spiros; Craik, David J.

2016-01-01

Glucagon-like peptide-1 (GLP-1) signaling through the glucagon-like peptide 1 receptor (GLP-1R) is a key regulator of normal glucose metabolism, and exogenous GLP-1R agonist therapy is a promising avenue for the treatment of type 2 diabetes mellitus. To date, the development of therapeutic GLP-1R agonists has focused on producing drugs with an extended serum half-life. This has been achieved by engineering synthetic analogs of GLP-1 or the more stable exogenous GLP-1R agonist exendin-4 (Ex-4). These synthetic peptide hormones share the overall structure of GLP-1 and Ex-4, with a C-terminal helical segment and a flexible N-terminal tail. Although numerous studies have investigated the molecular determinants underpinning GLP-1 and Ex-4 binding and signaling through the GLP-1R, these have primarily focused on the length and composition of the N-terminal tail or on how to modulate the helicity of the full-length peptides. Here, we investigate the effect of C-terminal truncation in GLP-1 and Ex-4 on the cAMP pathway. To ensure helical C-terminal regions in the truncated peptides, we produced a series of chimeric peptides combining the N-terminal portion of GLP-1 or Ex-4 and the C-terminal segment of the helix-promoting peptide α-conotoxin pl14a. The helicity and structures of the chimeric peptides were confirmed using circular dichroism and NMR, respectively. We found no direct correlation between the fractional helicity and potency in signaling via the cAMP pathway. Rather, the most important feature for efficient receptor binding and signaling was the C-terminal helical segment (residues 22–27) directing the binding of Phe22 into a hydrophobic pocket on the GLP-1R. PMID:27226591

Perinatal hepatic infarction in twin-twin transfusion.

LENUS (Irish Health Repository)

O'Sullivan, M J

2012-02-03

We report a case of a twin pregnancy which was complicated by a twin-twin transfusion in which the recipient twin was noted to have an intra-abdominal echogenic mass. This twin died at two days of age of hepatic infarction. The donor twin was healthy at birth, at thirty weeks\\' gestation, and did not have any subsequent problems. Fetal intra-abdominal echogenicity may be a marker of hepatic infarction.

The Ergogenic Potential of Arginine

Directory of Open Access Journals (Sweden)

La Bounty Paul M

2004-12-01

Full Text Available Abstract Arginine is a conditionally essential amino acid that is involved in protein synthesis, the detoxification of ammonia, and its conversion to glucose as well as being catabolized to produce energy. In addition to these physiological functions, arginine has been purported to have ergogenic potential. Athletes have taken arginine for three main reasons: 1 its role in the secretion of endogenous growth hormone; 2 its involvement in the synthesis of creatine; 3 its role in augmenting nitric oxide. These aspects of arginine supplementation will be discussed as well as a review of clinical investigations involving exercise performance and arginine ingestion.

Protective effect of C-peptide on experimentally induced diabetic nephropathy and the possible link between C-peptide and nitric oxide.

Science.gov (United States)

Elbassuoni, Eman A; Aziz, Neven M; El-Tahawy, Nashwa F

2018-06-01

Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by N G -nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.

Real-time trafficking and signaling of the glucagon-like peptide-1 receptor

DEFF Research Database (Denmark)

Roed, Sarah Noerklit; Wismann, Pernille; Underwood, Christina Rye

2014-01-01

The glucagon-like peptide-1 incretin receptor (GLP-1R) of family B G protein-coupled receptors (GPCRs) is a major drug target in type-2-diabetes due to its regulatory effect on post-prandial blood-glucose levels. The mechanism(s) controlling GLP-1R mediated signaling are far from fully understood....... A fundamental mechanism controlling the signaling capacity of GPCRs is the post-endocytic trafficking of receptors between recycling and degradative fates. Here, we combined microscopy with novel real-time assays to monitor both receptor trafficking and signaling in living cells. We find that the human GLP-1R...

Deciphering the Arginine-binding preferences at the substrate-binding groove of Ser/Thr kinases by computational surface mapping.

Directory of Open Access Journals (Sweden)

Avraham Ben-Shimon

2011-11-01

Full Text Available Protein kinases are key signaling enzymes that catalyze the transfer of γ-phosphate from an ATP molecule to a phospho-accepting residue in the substrate. Unraveling the molecular features that govern the preference of kinases for particular residues flanking the phosphoacceptor is important for understanding kinase specificities toward their substrates and for designing substrate-like peptidic inhibitors. We applied ANCHORSmap, a new fragment-based computational approach for mapping amino acid side chains on protein surfaces, to predict and characterize the preference of kinases toward Arginine binding. We focus on positions P-2 and P-5, commonly occupied by Arginine (Arg in substrates of basophilic Ser/Thr kinases. The method accurately identified all the P-2/P-5 Arg binding sites previously determined by X-ray crystallography and produced Arg preferences that corresponded to those experimentally found by peptide arrays. The predicted Arg-binding positions and their associated pockets were analyzed in terms of shape, physicochemical properties, amino acid composition, and in-silico mutagenesis, providing structural rationalization for previously unexplained trends in kinase preferences toward Arg moieties. This methodology sheds light on several kinases that were described in the literature as having non-trivial preferences for Arg, and provides some surprising departures from the prevailing views regarding residues that determine kinase specificity toward Arg. In particular, we found that the preference for a P-5 Arg is not necessarily governed by the 170/230 acidic pair, as was previously assumed, but by several different pairs of acidic residues, selected from positions 133, 169, and 230 (PKA numbering. The acidic residue at position 230 serves as a pivotal element in recognizing Arg from both the P-2 and P-5 positions.

Delayed nootropic effects of arginine vasopressin after early postnatal chronic administration to albino rat pups.

Science.gov (United States)

Kim, P A; Voskresenskaya, O G; Kamensky, A A

2009-06-01

Intranasal administration of arginine vasopressin (10 microg/kg) to albino rat pups had a strong nootropic effect during training with positive and negative reinforcement. This effect was different in animals of various age groups: training with positive reinforcement was improved in "adolescent" rats and pubertal animals, while during training with negative reinforcement, the nootropic effect of the peptide was more prolonged and persisted also in adult animals.

Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.

Energy Technology Data Exchange (ETDEWEB)

Misono, K. S.; Philo, J. S.; Arakawa, T.; Ogata, C. M.; Qiu, Y.; Ogawa, H.; Young, H. S. (Biosciences Division); (Univ. of Nevada); (Alliance Protein Labs.)

2011-06-01

Atrial natriuretic peptide (ANP) and the homologous B-type natriuretic peptide are cardiac hormones that dilate blood vessels and stimulate natriuresis and diuresis, thereby lowering blood pressure and blood volume. ANP and B-type natriuretic peptide counterbalance the actions of the renin-angiotensin-aldosterone and neurohormonal systems, and play a central role in cardiovascular regulation. These activities are mediated by natriuretic peptide receptor-A (NPRA), a single transmembrane segment, guanylyl cyclase (GC)-linked receptor that occurs as a homodimer. Here, we present an overview of the structure, possible chloride-mediated regulation and signaling mechanism of NPRA and other receptor GCs. Earlier, we determined the crystal structures of the NPRA extracellular domain with and without bound ANP. Their structural comparison has revealed a novel ANP-induced rotation mechanism occurring in the juxtamembrane region that apparently triggers transmembrane signal transduction. More recently, the crystal structures of the dimerized catalytic domain of green algae GC Cyg12 and that of cyanobacterium GC Cya2 have been reported. These structures closely resemble that of the adenylyl cyclase catalytic domain, consisting of a C1 and C2 subdomain heterodimer. Adenylyl cyclase is activated by binding of G{sub s}{alpha} to C2 and the ensuing 7{sup o} rotation of C1 around an axis parallel to the central cleft, thereby inducing the heterodimer to adopt a catalytically active conformation. We speculate that, in NPRA, the ANP-induced rotation of the juxtamembrane domains, transmitted across the transmembrane helices, may induce a similar rotation in each of the dimerized GC catalytic domains, leading to the stimulation of the GC catalytic activity.

Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

Science.gov (United States)

Feng, Mei; Bell, David R.; Zhou, Ruhong

2017-12-01

The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

Effects of linker variation on the in vitro and in vivo characteristics of an 111In-labeled RGD peptide.

NARCIS (Netherlands)

Dijkgraaf, I.; Liu, S.; Kruijtzer, J.A.; Soede, A.C.; Oyen, W.J.G.; Liskamp, R.M.; Corstens, F.H.M.; Boerman, O.C.

2007-01-01

INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive candidates for tumor targeting. Minor modifications of these peptides could have a major impact on in vivo characteristics. In this study,

Death and Survival in Streptococcus mutans: Differing Outcomes of a Quorum-Sensing Signalling Peptide

Directory of Open Access Journals (Sweden)

Vincent eLeung

2015-10-01

Full Text Available Bacteria are considered ‘social’ organisms able to communicate with one another using small hormone-like molecules (pheromones in a process called quorum-sensing. These signalling molecules increase in concentration as a function of bacterial cell density. For most human pathogens, quorum-sensing is critical for virulence and biofilm formation, and the opportunity to interfere with bacterial quorum-sensing could provide a sophisticated means for manipulating the composition of pathogenic biofilms, and possibly eradicating the infection. Streptococcus mutans is a well-characterized resident of the dental plaque biofilm, and is the major pathogen of dental caries (tooth decay. In S. mutans, its CSP quorum-sensing signalling peptide does not act as a classical quorum-sensing signal by accumulating passively in proportion to cell density. In fact, particular stresses such as those encountered in the oral cavity, induces the production of the CSP pheromone, suggesting that the pheromone most probably functions as a stress-inducible alarmone by triggering the signalling to the bacterial population to initiate an adaptive response that results in different phenotypic outcomes. This mini-review discusses two different CSP-induced phenotypes, bacterial ‘suicide’ and dormancy, and the underlying mechanisms by which S. mutans utilizes the same quorum-sensing signalling peptide to regulate two opposite phenotypes.

Collision-Induced Dissociation of Deprotonated Peptides. Relative Abundance of Side-Chain Neutral Losses, Residue-Specific Product Ions, and Comparison with Protonated Peptides.

Science.gov (United States)

Liang, Yuxue; Neta, Pedatsur; Yang, Xiaoyu; Stein, Stephen E

2018-03-01

High-accuracy MS/MS spectra of deprotonated ions of 390 dipeptides and 137 peptides with three to six residues are studied. Many amino acid residues undergo neutral losses from their side chains. The most abundant is the loss of acetaldehyde from threonine. The abundance of losses from the side chains of other amino acids is estimated relative to that of threonine. While some amino acids lose the whole side chain, others lose only part of it, and some exhibit two or more different losses. Side-chain neutral losses are less abundant in the spectra of protonated peptides, being significant mainly for methionine and arginine. In addition to the neutral losses, many amino acid residues in deprotonated peptides produce specific negative ions after peptide bond cleavage. An expanded list of fragment ions from protonated peptides is also presented and compared with those of deprotonated peptides. Fragment ions are mostly different for these two cases. These lists of fragments are used to annotate peptide mass spectral libraries and to aid in the confirmation of specific amino acids in peptides. Graphical Abstract ᅟ.

Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

Energy Technology Data Exchange (ETDEWEB)

Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Kang, Misun [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); Rho, Jaerang, E-mail: jrrho@cnu.ac.kr [Department of Microbiology, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); BK21 Bio Brain Center, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of); GRAST, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejon 305-764 (Korea, Republic of)

2010-01-01

Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

Fractal and twin SVM-based handgrip recognition for healthy subjects and trans-radial amputees using myoelectric signal.

Science.gov (United States)

Arjunan, Sridhar Poosapadi; Kumar, Dinesh Kant; Jayadeva J

2016-02-01

Identifying functional handgrip patterns using surface electromygram (sEMG) signal recorded from amputee residual muscle is required for controlling the myoelectric prosthetic hand. In this study, we have computed the signal fractal dimension (FD) and maximum fractal length (MFL) during different grip patterns performed by healthy and transradial amputee subjects. The FD and MFL of the sEMG, referred to as the fractal features, were classified using twin support vector machines (TSVM) to recognize the handgrips. TSVM requires fewer support vectors, is suitable for data sets with unbalanced distributions, and can simultaneously be trained for improving both sensitivity and specificity. When compared with other methods, this technique resulted in improved grip recognition accuracy, sensitivity, and specificity, and this improvement was significant (κ=0.91).

Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma.

Science.gov (United States)

Nguyen, Dan-Vinh; Linderholm, Angela; Haczku, Angela; Kenyon, Nicholas

2017-12-01

Alterations in arginine metabolism and accelerated formation of advanced glycation end-products (AGEs), crucial mechanisms in obesity-related asthma, can be modulated by glucagon-like peptide 1 (GLP-1). l-arginine dysregulation in obesity promotes inflammation and bronchoconstriction. Prolonged hyperglycemia, dyslipidemia, and oxidative stress leads to production of AGEs, that bind to their receptor (RAGE) further potentiating inflammation. By binding to its widely distributed receptor, GLP-1 blunts the effects of RAGE activation and arginine dysregulation. The GLP-1 pathway, while comprehensively studied in the endocrine and cardiovascular literature, is under-recognized in pulmonary research. Insights into GLP-1 and the lung may lead to novel treatments for obesity-related asthma. Published by Elsevier Inc.

Protein arginine methyltransferase 5 is an essential component of the hypoxia-inducible factor 1 signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Lim, Ji-Hong; Choi, Yong-Joon; Cho, Chung-Hyun [Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of); Park, Jong-Wan, E-mail: parkjw@snu.ac.kr [Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 110-799 (Korea, Republic of)

2012-02-10

Highlights: Black-Right-Pointing-Pointer HIF-1{alpha} is expressed PRMT5-dependently in hypoxic cancer cells. Black-Right-Pointing-Pointer The HIF-1 regulation of hypoxia-induced genes is attenuated in PRMT5-knocked-down cells. Black-Right-Pointing-Pointer The de novo synthesis of HIF-1{alpha} depends on PRMT5. Black-Right-Pointing-Pointer PRMT5 is involved in the HIF-1{alpha} translation initiated by 5 Prime UTR of HIF-1{alpha} mRNA. -- Abstract: Protein arginine methyltransferase 5 (PRMT5) is an enzyme that transfers one or two methyl groups to the arginine residues of histones or non-histone proteins, and that plays critical roles in cellular processes as diverse as receptor signaling and gene expression. Furthermore, PRMT5 is highly expressed in tumors, where it may be associated with tumor growth. Although much research has been conducted on PRMT5, little is known regarding its role in adaption to hypoxia. As hypoxia-inducible factor 1 (HIF-1) is a key player in hypoxic response, we examined the possible involvement of PRMT5 in the HIF-1 signaling pathway. Of the siRNAs targeting PRMT1-8, only PRMT5 siRNA attenuated the hypoxic induction of HIF-1{alpha} in A549 cells, and this result was reproducible in all three cancer cell lines examined. PRMT5 knock-down also repressed the promoter activities and the transcript levels of HIF-1-governed genes. Mechanistically, de novo synthesis of HIF-1{alpha} protein was reduced in PRMT5-knocked-down A549 cells, and this was rescued by PRMT5 restoration. In contrast, HIF-1{alpha} transcription, RNA processing, and protein stability were unaffected by PRMT5 knock-down. Furthermore, PRMT5 was found to be essential for the HIF-1{alpha} translation initiated by the 5 Prime UTR of HIF-1{alpha} mRNA. Given our results and previous reports, we believe that PRMT5 probably promotes tumor growth by stimulating cell proliferation and by participating in the construction of a tumor-favorable microenvironment via HIF-1 activation.

Effects of diet and arginine treatment during the luteal phase on ovarian NO/PGC-1α signaling in ewes.

Science.gov (United States)

Guo, Yi-Xuan; Nie, Hai-Tao; Sun, Ling-Wei; Zhang, Guo-Min; Deng, Kai-Ping; Fan, Yi-Xuan; Wang, Feng

2017-07-01

The aim of this study was to determine whether arginine (Arg) supplementation of malnourished ewes affects the expression of key NO/PGC-1α signaling pathway genes in the ovary. On Day 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.53 kg) were randomly assigned to three groups: control group (CG; n = 6), restriction group (RG; n = 9) and l-arginine group (AG; n = 9), and administered Arg treatment (or vehicle) three times per day. The ewes were slaughtered at the end of treatment, and blood samples and ovaries were collected for analysis. The results of our analyses showed that both short-term feed-restriction and/or supplementation with L-Arg-HCl affected the number of different size follicles observed in the ovary, and the relative day of estrus behavior initiation of ewes. Specifically, the relative day of estrus behavior initiation was significantly advanced in AG compared with that in RG ewes (P ewes. RG ewes exhibited a higher proportion of ≤2 mm (P 5 mm follicles than did CG ewes (P ewes. Furthermore, the expression of eNOS, nNOS, iNOS, PDE5A, PDE9A, PRKG2, and PPARGC1A varied significantly among the treatment groups (P ewes (P ewes (P ewes (P ewes (P ewes (P ewes. In conclusion, the results of the present study indicate that feed-restriction negatively affects follicular development, and that Arg-supplementation may modulate the expression of key NO/PGC-1α signaling pathway genes in the ovary and thereby accelerate ovulatory processes and the estrous rate. Elucidation of mechanisms underlying these effects of Arg on gene expression in the ewe ovary requires further investigation. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

DEFF Research Database (Denmark)

Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren

1997-01-01

We have developed a new method for the identification of signal peptides and their cleavage based on neural networks trained on separate sets of prokaryotic and eukaryotic sequence. The method performs significantly better than previous prediction schemes and can easily be applied on genome...

Chimeric peptides as modulators of CK2-dependent signaling: Mechanism of action and off-target effects.

Science.gov (United States)

Zanin, Sofia; Sandre, Michele; Cozza, Giorgio; Ottaviani, Daniele; Marin, Oriano; Pinna, Lorenzo A; Ruzzene, Maria

2015-10-01

Protein kinase CK2 is a tetrameric enzyme composed of two catalytic (α/α') and two regulatory (β) subunits. It has a global prosurvival function, especially in cancer, and represents an attractive therapeutic target. Most CK2 inhibitors available so far are ATP-competitive compounds; however, the possibility to block only the phosphorylation of few substrates has been recently explored, and a compound composed of a Tat cell-penetrating peptide and an active cyclic peptide, selected for its ability to bind to the CK2 substrate E7 protein of human papilloma virus, has been developed [Perea et al., Cancer Res. 2004; 64:7127-7129]. By using a similar chimeric peptide (CK2 modulatory chimeric peptide, CK2-MCP), we performed a study to dissect its molecular mechanism of action and the signaling pathways that it affects in cells. We found that it directly interacts with CK2 itself, counteracting the regulatory and stabilizing functions of the β subunit. Cell treatment with CK2-MCP induces a rapid decrease of the amount of CK2 subunits, as well as of other signaling proteins. Concomitant cell death is observed, more pronounced in tumor cells and not accompanied by apoptotic events. CK2 relocalizes to lysosomes, whose proteases are activated, while the proteasome machinery is inhibited. Several sequence variants of the chimeric peptide have been also synthesized, and their effects compared to those of the parental peptide. Intriguingly, the Tat moiety is essential not only for cell penetration but also for the in vitro efficacy of the peptide. We conclude that this class of chimeric peptides, in addition to altering some properties of CK2 holoenzyme, affects several other cellular targets, causing profound perturbations of cell biology. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases. Copyright © 2015 Elsevier B.V. All rights reserved.

A Novel Membrane-Permeable Breast-Targeting Pro-Apoptotic Peptide for Treatment of Breast Cancer

National Research Council Canada - National Science Library

Guo, Bin

2005-01-01

.... The BH3 peptide of Bid (EDIIRNIARHLAQVGDSMDR) was synthesized with eight d-arginine residues at the N-terminus with a glycine linker residue, followed by a breast-homing sequence (CPGPEGAGC) at the C-terminal...

Minimal mirror twin Higgs

Energy Technology Data Exchange (ETDEWEB)

Barbieri, Riccardo [Institute of Theoretical Studies, ETH Zurich,CH-8092 Zurich (Switzerland); Scuola Normale Superiore,Piazza dei Cavalieri 7, 56126 Pisa (Italy); Hall, Lawrence J.; Harigaya, Keisuke [Department of Physics, University of California,Berkeley, California 94720 (United States); Theoretical Physics Group, Lawrence Berkeley National Laboratory,Berkeley, California 94720 (United States)

2016-11-29

In a Mirror Twin World with a maximally symmetric Higgs sector the little hierarchy of the Standard Model can be significantly mitigated, perhaps displacing the cutoff scale above the LHC reach. We show that consistency with observations requires that the Z{sub 2} parity exchanging the Standard Model with its mirror be broken in the Yukawa couplings. A minimal such effective field theory, with this sole Z{sub 2} breaking, can generate the Z{sub 2} breaking in the Higgs sector necessary for the Twin Higgs mechanism. The theory has constrained and correlated signals in Higgs decays, direct Dark Matter Detection and Dark Radiation, all within reach of foreseen experiments, over a region of parameter space where the fine-tuning for the electroweak scale is 10-50%. For dark matter, both mirror neutrons and a variety of self-interacting mirror atoms are considered. Neutrino mass signals and the effects of a possible additional Z{sub 2} breaking from the vacuum expectation values of B−L breaking fields are also discussed.

'Biracial'-Looking Twins: A New Twin Type?/Twin Research: Twins with Cystic Teratomas; Sleep Quality and Body Mass Index; Previable Membrane Rupture/Print and Online Reports: Twins Born to a Sister Surrogate; NASA Twin Study; African-Cosmopolitan Twin Fashion Inspirations; Triplet Hockey Stars.

Science.gov (United States)

Segal, Nancy L

2017-06-01

Dizygotic (DZ) co-twins born to mothers and fathers from different racial or ethnic backgrounds often resemble one parent much more than the other. As such, these pairs comprise a unique subset of twins for investigating how others' responses to their different looks may affect their personalities and self-esteem. This article describes some of these twin pairs and some challenges of raising them, and suggests ways they may be used in research. Next, recent twin research on cystic teratomas, relations between sleep quality and body mass index, and previable membrane rupture is described. The final section concerns twins, twin studies, and related events in the media, namely: twins born to a sister surrogate, the NASA twin investigation, inspiring African-Cosmopolitan twins in fashion, and triplet Hockey Stars.

L-arginine biosensors: A comprehensive review

Directory of Open Access Journals (Sweden)

Neelam Verma

2017-12-01

Full Text Available Arginine has been considered as the most potent nutraceutics discovered ever, due to its powerful healing property, and it's been known to scientists as the Miracle Molecule. Arginine detection in fermented food products is necessary because, high level of arginine in foods forms ethyl carbamate (EC during the fermentation process. Therefore, L-arginine detection in fermented food products is very important as a control measure for quality of fermented foods, food supplements and beverages including wine. In clinical analysis arginine detection is important due to their enormous inherent versatility in various metabolic pathways, topmost in the synthesis of Nitric oxide (NO and tumor growth. A number of methods are being used for arginine detection, but biosensors technique holds prime position due to rapid response, high sensitivity and high specificity. However, there are many problems still to be addressed, including selectivity, real time analysis and interference of urea presence in the sample. In the present review we aim to emphasize the significant role of arginine in human physiology and foods. A small attempt has been made to discuss the various techniques used for development of arginine biosensor and how these techniques affect their performance. The choice of transducers for arginine biosensor ranges from optical, pH sensing, ammonia gas sensing, ammonium ion-selective, conductometric and amperometric electrodes because ammonia is formed as a final product.

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics

OpenAIRE

Morris, May C.; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

2007-01-01

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficien...

The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma

DEFF Research Database (Denmark)

Christoffersen, Christina; Ahnström, Josefin; Axler, Olof

2008-01-01

Lipoproteins consist of lipids solubilized by apolipoproteins. The lipid-binding structural motifs of apolipoproteins include amphipathic alpha-helixes and beta-sheets. Plasma apolipoprotein (apo) M lacks an external amphipathic motif but, nevertheless, is exclusively associated with lipoproteins...... (mainly high density lipoprotein). Uniquely, however, apoM is secreted to plasma without cleavage of its hydrophobic NH(2)-terminal signal peptide. To test whether the signal peptide serves as a lipoprotein anchor for apoM in plasma, we generated mice expressing a mutated apoM(Q22A) cDNA in the liver (apoM......(Q22A)-Tg mice (transgenic mice)) and compared them with mice expressing wild-type human apoM (apoM-Tg mice). The substitution of the amino acid glutamine 22 with alanine in apoM(Q22A) results in secretion of human apoM without a signal peptide. The human apoM mRNA level in liver and the amount...

A specific scenario for the origin of life and the genetic code based on peptide/oligonucleotide interdependence.

Science.gov (United States)

Griffith, Robert W

2009-12-01

Among various scenarios that attempt to explain how life arose, the RNA world is currently the most widely accepted scientific hypothesis among biologists. However, the RNA world is logistically implausible and doesn't explain how translation arose and DNA became incorporated into living systems. Here I propose an alternative hypothesis for life's origin based on cooperation between simple nucleic acids, peptides and lipids. Organic matter that accumulated on the prebiotic Earth segregated into phases in the ocean based on density and solubility. Synthesis of complex organic monomers and polymerization reactions occurred within a surface hydrophilic layer and at its aqueous and atmospheric interfaces. Replication of nucleic acids and translation of peptides began at the emulsified interface between hydrophobic and aqueous layers. At the core of the protobiont was a family of short nucleic acids bearing arginine's codon and anticodon that added this amino acid to pre-formed peptides. In turn, the survival and replication of nucleic acid was aided by the peptides. The arginine-enriched peptides served to sequester and transfer phosphate bond energy and acted as cohesive agents, aggregating nucleic acids and keeping them at the interface.

Remembering Irving I. Gottesman: Twin Research Colleague and Friend Extraordinaire/Research Studies: Face-Lift Technique Comparison in Identical Twins; Raising Preterm Twins; Fetal Behavior in Dichorionic Twin Pregnancies; Co-Bedding and Stress Reduction in Twins/Public Interest: Identical Co-Twins' Same Day Delivery; Teaching Twins in Bosnia; Twin Auctioneers; Sister, the Play.

Science.gov (United States)

Segal, Nancy L

2016-12-01

Dr Irving I. Gottesman, a colleague, friend, and long-time member of the International Society of Twin Studies passed away on June 29, 2016. His contributions to twin research and some personal reflections are presented to honor both the man and the memory. This tribute is followed by short reviews of twin research concerning differences between cosmetic surgical techniques, the rearing of preterm twins, behavioral observations of dichorionic fetal twins, and the outcomes of co-bedding twins with reference to stress reduction. Interesting and informative articles in the media describe identical co-twins who delivered infants on the same day, educational policies regarding twins in Bosnia and the United Kingdom, unusual practices of twin auctioneers, and a theatrical production, Sister, featuring identical twins in the leading roles.

[Adult twins].

Science.gov (United States)

Charlemaine, Christiane

2006-12-31

This paper explores the deep roots of closeness that twins share in their youngest age and their effect on their destiny at the adult age. Psychologists believe the bond between twins begins in utero and develops throughout the twins' lives. The four patterns of twinship described show that the twin bond is determined by the quality of parenting that twins receive in their infancy and early childhood. Common problems of adult twins bring about difficulties to adapt in a non-twin world. The nature versus nurture controversy has taken on new life focusing on inter-twin differences and the importance of parent-child interaction as fundamental to the growth and development of personality.

Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine

DEFF Research Database (Denmark)

Orskov, C; Jeppesen, J; Madsbad, S

1991-01-01

We investigated the major products of proglucagon (PG) processing in plasma in the fasting state, after intravenous arginine and after an oral glucose load in noninsulin-dependent diabetics (NIDDM) and in weight matched controls using specific radioimmunoassays and analytical gel filtration...... integrated incremental responses after intravenous arginine were identical in the two groups. After oral glucose the insulin concentrations in plasma were lower and the concentrations of all proglucagon products were higher in the NIDDM group compared to the control group. The gel filtration analysis showed....... In the fasting state the glucagonlike peptide-1 (GLP-1) immunoreactivity was significantly elevated in the NIDDM group compared with the control group. Both after intravenous arginine and after an oral glucose load a rise in the plasma concentrations of all immunoreactive moieties measured was seen. All...

Synthesis and evaluation of amphiphilic peptides as nanostructures and drug delivery tools

Science.gov (United States)

Sayeh, Naser Ali

conjugates although one limitation lies in the effort of controlling the rate of drug release. The encapsulated or complexed drugs tend to be released rapidly (before reaching the target site) and in the dendrimer--drug conjugates, it is the chemical linkage that controls the drug release. Thus, future studies in this field are urgently required to create more efficient and stable biomaterials. Peptides are considered as efficient vectors for achieving optimal cellular uptake. The potential use of peptides as drug delivery vectors received much attention by the discovery of several cell-penetrating peptides (CPPs). The first CPPs discovered in 1988, that were sequences from HIV-1 encoded TAT protein, TAT (48--60), and penetrated very efficiently through cell membranes of cultured mammalian cells. CPPs are a class of diverse peptides, typically with 8--25 amino acids, and unlike most peptides, they can cross the cellular membrane with more efficiency. CPPs have also shown to undergo self-assembly and generate nanostructures. The generation of self-assembled peptides and nanostructures occur through various types of interactions between functional groups of amino acid residues, such as electrostatic, hydrophobic, and hydrogen bonding. Appropriate design and functionalization of peptides are critical for generating nanostructures. Chemically CPPs are classified into two major groups: linear and cyclic peptides. It has been previously reported that linear peptides containing hydrophilic and hydrophobic amino acids could act as membrane protein stabilizers. These compounds are short hydrophilic or amphiphilic peptides that have positively charged amino acids, such as arginine, lysine or histidine, which can interact with the negative charge phospholipids layer on the cell membrane and translocate the cargo into the cells. Conjugation to cationic linear CPPs, such as TAT, penetratin, or oligoarginine efficiently improves the cellular uptake of large hydrophilic molecules, but the

Receiver sensitivity improvement in spectrally-efficient guard-band twin-SSB-OFDM using an optical IQ modulator

Science.gov (United States)

Chen, Ming; Peng, Miao; Zhou, Hui; Zheng, Zhiwei; Tang, Xionggui; Maivan, Lap

2017-12-01

To further improve receiver sensitivity of spectrally-efficient guard-band direct-detection optical orthogonal frequency-division multiplexing (OFDM) with twin single-side-band (SSB) modulation technique, an optical IQ modulator (IQM) is employed to optimize optical carrier-to-signal power ratio (CSPR). The CSPRs for the guard-band twin-SSB-OFDM signal generated by using dual-drive Mach-Zehnder modulator (DD-MZM) and optical IQM are theoretically analyzed and supported by simulations. The optimal CSPR for the two types of guard-band twin-SSB-OFDM are identified. The simulations exhibit that the error vector magnitude (EVM) performance of the IQM-enabled guard-band twin-SSB-OFDM is improved by more than 4-dB compared to that of the twin-SSB-OFDM enabled by DD-MZM after 80-km single-mode fiber (SMF) transmission. In addition, more than 3-dB and 10 dB receiver sensitivity improvements in terms of received optical power (ROP) and optical signal-to-noise ratio (OSNR) are also achieved, respectively.

Dietary arginine and linear growth

DEFF Research Database (Denmark)

van Vught, Anneke J A H; Dagnelie, Pieter C; Arts, Ilja C W

2013-01-01

Child Intervention Study during 2001-2 (baseline), and at 3-year and 7-year follow-up, were used. Arginine intake was estimated via a 7 d precoded food diary at baseline and 3-year follow-up. Data were analysed in a multilevel structure in which children were embedded within schools. Random intercept......The amino acid arginine is a well-known growth hormone (GH) stimulator and GH is an important modulator of linear growth. The aim of the present study was to investigate the effect of dietary arginine on growth velocity in children between 7 and 13 years of age. Data from the Copenhagen School...... and slopes were defined to estimate the association between arginine intake and growth velocity, including the following covariates: sex; age; baseline height; energy intake; puberty stage at 7-year follow-up and intervention/control group. The association between arginine intake and growth velocity...

A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

Directory of Open Access Journals (Sweden)

Iana Parvanova

Full Text Available The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.

Aging and communication in the twin paradox

International Nuclear Information System (INIS)

De Wolf, David A

2016-01-01

The twin paradox of the special theory of relativity has given rize to a large body of literature discussing its implications. In its standard form, the traveler changes velocity only at the destination of the trip, so that he appears to perceive an improbably instantaneous and non-continuous change in age of the stationary twin. In this work, a smooth velocity/acceleration profile is used that allows the abrupt velocity-change case as a limit. All gravitational effects are ignored in this treatment. Aside from mutual perception of simultaneous clock times in an accelerating frame, constant communication of clock times between the twins by means of (digital) light signals is shown to be possible, in principle if not in practice. (paper)

The Fourth International Network of Twin Registries: Overview from Osaka/Research Reviews: Familial Fraternal Twinning; Twin Study of Masculine Faces; Physical Aggression and Epigenetics; Prenatal Education for Parents of Twins/Current Events: 2016 Guinness Book of World Records; Oldest Living Male Twins; Twins Reunited at Sixty-Nine; Panda Twins; Twins.com.

Science.gov (United States)

Segal, Nancy L

2015-12-01

The 4th International Network of Twin Registries (INTR) Consortium Meeting took place in Osaka, Japan, September 28-29, 2015. The venue was the Osaka Medical Center for Medical Innovation and Translational Research. An overview of presentations and other activities is provided. Next, 1930s research on familial fraternal twinning, preference for masculine faces, physical aggression and epigenetics, and a prenatal education program for parents of multiples are described. Current twin-related events include the 2016 Guinness Book of World Records (GWR), the oldest living male twins, newly reunited twins, the birth of panda twins and a controversial twin-based website.

The Placenta in Twin-to-Twin Transfusion Syndrome and Twin Anemia Polycythemia Sequence.

Science.gov (United States)

Couck, Isabel; Lewi, Liesbeth

2016-06-01

Twin-to-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are complications unique to monochorionic twin pregnancies and their shared circulation. Both are the result of the transfusion imbalance in the intertwin circulation. TTTS is characterized by an amniotic fluid discordance, whereas in TAPS, there is a severe discordance in hemoglobin levels. The article gives an overview of the typical features of TTTS and TAPS placentas.

IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

Directory of Open Access Journals (Sweden)

E. A. Starikova

2015-01-01

Full Text Available Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme.

A novel strategy to improve protein secretion via overexpression of the SppA signal peptide peptidase in Bacillus licheniformis.

Science.gov (United States)

Cai, Dongbo; Wang, Hao; He, Penghui; Zhu, Chengjun; Wang, Qin; Wei, Xuetuan; Nomura, Christopher T; Chen, Shouwen

2017-04-24

Signal peptide peptidases play an important role in the removal of remnant signal peptides in the cell membrane, a critical step for extracellular protein production. Although these proteins are likely a central component for extracellular protein production, there has been a lack of research on whether protein secretion could be enhanced via overexpression of signal peptide peptidases. In this study, both nattokinase and α-amylase were employed as prototypical secreted target proteins to evaluate the function of putative signal peptide peptidases (SppA and TepA) in Bacillus licheniformis. We observed dramatic decreases in the concentrations of both target proteins (45 and 49%, respectively) in a sppA deficient strain, while the extracellular protein yields of nattokinase and α-amylase were increased by 30 and 67% respectively in a strain overexpressing SppA. In addition, biomass, specific enzyme activities and the relative gene transcriptional levels were also enhanced due to the overexpression of sppA, while altering the expression levels of tepA had no effect on the concentrations of the secreted target proteins. Our results confirm that SppA, but not TepA, plays an important functional role for protein secretion in B. licheniformis. Our results indicate that the sppA overexpression strain, B. licheniformis BL10GS, could be used as a promising host strain for the industrial production of heterologous secreted proteins.

Antenatal management of twin-twin transfusion syndrome and twin anemia-polycythemia sequence.

Science.gov (United States)

Slaghekke, Femke; Zhao, Depeng P; Middeldorp, Johanna M; Klumper, Frans J; Haak, Monique C; Oepkes, Dick; Lopriore, Enrico

2016-08-01

Twin-twin transfusion syndrome (TTTS) and twin anemia polycythemia sequence (TAPS) are severe complications in monochorionic twin pregnancies associated with high mortality and morbidity risk if left untreated. Both diseases result from imbalanced inter-twin blood transfusion through placental vascular anastomoses. This review focuses on the differences in antenatal management between TTTS and TAPS. Expert commentary: The optimal management for TTTS is fetoscopic laser coagulation of the vascular anastomoses, preferably using the Solomon technique in which the whole vascular equator is coagulated. The Solomon technique is associated with a reduction of residual anastomosis and a reduction in post-operative complications. The optimal management for TAPS is not clear and includes expectant management, intra-uterine transfusion with or without partial exchange transfusion and fetoscopic laser surgery.

Promotion of double-duplex invasion of peptide nucleic acids through conjugation with nuclear localization signal peptide.

Science.gov (United States)

Aiba, Yuichiro; Honda, Yuta; Komiyama, Makoto

2015-03-02

Pseudo-complementary peptide nucleic acid (pcPNA), as one of the most widely used synthetic DNA analogues, invades double-stranded DNA according to Watson-Crick rules to form invasion complexes. This unique mode of DNA recognition induces structural changes at the invasion site and can be used for a range of applications. In this paper, pcPNA is conjugated with a nuclear localization signal (NLS) peptide, and its invading activity is notably promoted both thermodynamically and kinetically. Thus, the double-duplex invasion complex is formed promptly at low pcPNA concentrations under high salt conditions, where the invasion otherwise never occurs. Furthermore, NLS-modified pcPNA is successfully employed for site-selective DNA scission, and the targeted DNA is selectively cleaved under conditions that are not conducive for DNA cutters using unmodified pcPNAs. This strategy of pcPNA modification is expected to be advantageous and promising for a range of in vitro and in vivo applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Arginine depletion by arginine deiminase does not affect whole protein metabolism or muscle fractional protein synthesis rate in mice

Science.gov (United States)

Due to the absolute need for arginine that certain cancer cells have, arginine depletion is a therapy in clinical trials to treat several types of cancers. Arginine is an amino acids utilized not only as a precursor for other important molecules, but also for protein synthesis. Because arginine depl...

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

International Nuclear Information System (INIS)

Baldwin, Michael; Russo, Crystal; Li, Xuerong; Chishti, Athar H.

2014-01-01

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle

Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

Energy Technology Data Exchange (ETDEWEB)

Baldwin, Michael; Russo, Crystal; Li, Xuerong [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Chishti, Athar H., E-mail: athar.chishti@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Sackler School of Graduate Biomedical Sciences, Programs in Physiology, Pharmacology, and Microbiology, Tufts University School of Medicine, Boston, MA 02111 (United States)

2014-08-08

Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.

A Possible Twin: The 1960s Twin Study Revisited/Twin Research: Twin-to-Twin Heart Transplantation; Distinguishing Monozygotic Twins; Twin Conceptions via Oocyte Donation; Factors Affecting Craniofacial Traits/In the Media: Triplet Delivery in the UK; Conjoined Twins and the Concept of Self; Colombian Twin Trainers; Skin Grafting to Save an Identical Co-Twin; Lack of Physical Flaws in Dolly the Cloned Sheep; Possible Conjoined Twins of Opposite-Sex; Passing of the Remaining Twin From the World's Longest Separated Pair.

Science.gov (United States)

Segal, Nancy L

2018-04-01

This article begins with the story of a 51-year-old Los Angeles, California man, Justin Goldberg, whose daughter caught a glimpse of his striking look-alike at a popular market. Many people have so-called doppelgängers, but this occurrence is especially intriguing - the individual in question, born in New York City in the mid-1960s to an unwed mother, was an adoptee placed by the Louise Wise Adoption Agency. This agency, under the guidance of a prominent psychiatrist, decided to place twins in separate homes. Some of these twin children were part of a controversial child development study that was hidden from them and their parents. Next, recent and current twin research on heart transplantation, distinguishing monozygotic co-twins, twin conceptions via oocyte donation and factors affecting craniofacial traits are summarized. The article concludes with highlights on twins in the media, specifically, a triplet delivery in the United Kingdom, self-concept and consciousness in conjoined twins, Colombian twin trainers, skin grafting to save an identical co-twin, lack of physical flaws in Dolly the cloned sheep, possible opposite-sex conjoined twins, and the passing of the remaining twin from the world's longest separated pair.

Oxidative Stressors Modify the Response of Streptococcus mutans to Its Competence Signal Peptides.

Science.gov (United States)

De Furio, Matthew; Ahn, Sang Joon; Burne, Robert A; Hagen, Stephen J

2017-11-15

The dental caries pathogen Streptococcus mutans is continually exposed to several types of stress in the oral biofilm environment. Oxidative stress generated by reactive oxygen species has a major impact on the establishment, persistence, and virulence of S. mutans Here, we combined fluorescent reporter-promoter fusions with single-cell imaging to study the effects of reactive oxygen species on activation of genetic competence in S. mutans Exposure to paraquat, which generates superoxide anion, produced a qualitatively different effect on activation of expression of the gene for the master competence regulator, ComX, than did treatment with hydrogen peroxide (H 2 O 2 ), which can yield hydroxyl radical. Paraquat suppressed peptide-mediated induction of comX in a progressive and cumulative fashion, whereas the response to H 2 O 2 displayed a strong threshold behavior. Low concentrations of H 2 O 2 had little effect on induction of comX or the bacteriocin gene cipB , but expression of these genes declined sharply if extracellular H 2 O 2 exceeded a threshold concentration. These effects were not due to decreased reporter gene fluorescence. Two different threshold concentrations were observed in the response to H 2 O 2 , depending on the gene promoter that was analyzed and the pathway by which the competence regulon was stimulated. The results show that paraquat and H 2 O 2 affect the S. mutans competence signaling pathway differently, and that some portions of the competence signaling pathway are more sensitive to oxidative stress than others. IMPORTANCE Streptococcus mutans inhabits the oral biofilm, where it plays an important role in the development of dental caries. Environmental stresses such as oxidative stress influence the growth of S. mutans and its important virulence-associated behaviors, such as genetic competence. S. mutans competence development is a complex behavior that involves two different signaling peptides and can exhibit cell

Pharmacological characterization of the oxytocic peptides in the pituitary of a marine teleost fish (pollachius virens) (1961)

International Nuclear Information System (INIS)

Maetz, J.; Morel, F.

1961-01-01

Demonstration of the existence, in the neurohypophysis of a marine fish (pollachius virens), of an oxytocic-active peptide different to the oxytocin in mammals and to the arginine vasotocin. (authors) [fr

Anti-aging effects of l-arginine

Directory of Open Access Journals (Sweden)

Mohamed Z. Gad

2010-07-01

Full Text Available l-Arginine is one of the most metabolically versatile amino acids. In addition to its role in the synthesis of nitric oxide, l-arginine serves as a precursor for the synthesis of polyamines, proline, glutamate, creatine, agmatine and urea. Several human and experimental animal studies have indicated that exogenous l-arginine intake has multiple beneficial pharmacological effects when taken in doses larger than normal dietary consumption. Such effects include reduction in the risk of vascular and heart diseases, reduction in erectile dysfunction, improvement in immune response and inhibition of gastric hyperacidity. This review summarises several positive studies and personal experiences of l-arginine. The demonstrated anti-aging benefits of l-arginine show greater potential than any pharmaceutical or nutraceutical agent ever previously discovered.

Tuning interionic interaction by rationally controlling solution pH for highly selective colorimetric sensing of arginine.

Science.gov (United States)

Qian, Qin; Hao, Jie; Ma, Wenjie; Yu, Ping; Mao, Lanqun

2016-04-01

Direct selective sensing of arginine in central nervous systems remains very essential to understanding of the molecular basis of some physiological events. This study presents the first demonstration on a simple yet effective method for arginine sensing with gold nanoparticles (Au-NPs) as the signal readout. The rationale for the method is based on the pH-dependent feature of the interionic interaction between cysteine and arginine. At pH 6.0, cysteine can only interact with arginine through the ion-pair interaction and such interaction can lead to the changes in both the solution color and UV-vis spectrum of the cysteine-protected Au-NPs upon the addition of arginine. These changes are further developed into an analytical strategy for effective sensing of arginine by rationally controlling the pH values of Au-NP dispersions with the ratio of the absorbance at 650 nm (A 650) to that at 520 nm (A 520) (A 650/A 520) as a parameter for analysis. The method is responsive to arginine without the interference from other species in the cerebral system; under the optimized conditions, the A 650/A 520 values are linear with the concentration of arginine within a concentration range from 0.80 to 64 μM, yet remain unchanged with the addition of other kinds of amino acids or the species in the central nervous system into the Au-NPs dispersion containing cysteine. The method demonstrated here is reliable and robust and could thus be used for detection of the increase of arginine in central nervous systems.

Highlights from the 15th International Congress of Twin Studies/Twin Research: Differentiating MZ Co-twins Via SNPs; Mistaken Infant Twin-Singleton Hospital Registration; Narcolepsy With Cataplexy; Hearing Loss and Language Learning/Media Mentions: Broadway Musical Recalls Conjoined Hilton Twins; High Fashion Pair; Twins Turn 102; Insights From a Conjoined Twin Survivor.

Science.gov (United States)

Segal, Nancy L

2015-02-01

Highlights from the 15th International Congress of Twin Studies are presented. The congress was held November 16-19, 2014 in Budapest, Hungary. This report is followed by summaries of research addressing the differentiation of MZ co-twins by single nucleotide polymorphisms (SNPs), an unusual error in infant twin-singleton hospital registration, twins with childhood-onset narcolepsy with cataplexy, and the parenting effects of hearing loss in one co-twin. Media interest in twins covers a new Broadway musical based on the conjoined twins Violet and Daisy Hilton, male twins becoming famous in fashion, twins who turned 102 and unique insights from a conjoined twin survivor. This article is dedicated to the memory of Elizabeth (Liz) Hamel, DZA twin who met her co-twin for the first time at age seventy-eight years. Liz and her co-twin, Ann Hunt, are listed in the 2015 Guinness Book of Records as the longest separated twins in the world.

Effect of signal peptide on stability and folding of Escherichia coli thioredoxin.

Directory of Open Access Journals (Sweden)

Pranveer Singh

Full Text Available The signal peptide plays a key role in targeting and membrane insertion of secretory and membrane proteins in both prokaryotes and eukaryotes. In E. coli, recombinant proteins can be targeted to the periplasmic space by fusing naturally occurring signal sequences to their N-terminus. The model protein thioredoxin was fused at its N-terminus with malE and pelB signal sequences. While WT and the pelB fusion are soluble when expressed, the malE fusion was targeted to inclusion bodies and was refolded in vitro to yield a monomeric product with identical secondary structure to WT thioredoxin. The purified recombinant proteins were studied with respect to their thermodynamic stability, aggregation propensity and activity, and compared with wild type thioredoxin, without a signal sequence. The presence of signal sequences leads to thermodynamic destabilization, reduces the activity and increases the aggregation propensity, with malE having much larger effects than pelB. These studies show that besides acting as address labels, signal sequences can modulate protein stability and aggregation in a sequence dependent manner.

Effect of signal peptide on stability and folding of Escherichia coli thioredoxin.

Science.gov (United States)

Singh, Pranveer; Sharma, Likhesh; Kulothungan, S Rajendra; Adkar, Bharat V; Prajapati, Ravindra Singh; Ali, P Shaik Syed; Krishnan, Beena; Varadarajan, Raghavan

2013-01-01

The signal peptide plays a key role in targeting and membrane insertion of secretory and membrane proteins in both prokaryotes and eukaryotes. In E. coli, recombinant proteins can be targeted to the periplasmic space by fusing naturally occurring signal sequences to their N-terminus. The model protein thioredoxin was fused at its N-terminus with malE and pelB signal sequences. While WT and the pelB fusion are soluble when expressed, the malE fusion was targeted to inclusion bodies and was refolded in vitro to yield a monomeric product with identical secondary structure to WT thioredoxin. The purified recombinant proteins were studied with respect to their thermodynamic stability, aggregation propensity and activity, and compared with wild type thioredoxin, without a signal sequence. The presence of signal sequences leads to thermodynamic destabilization, reduces the activity and increases the aggregation propensity, with malE having much larger effects than pelB. These studies show that besides acting as address labels, signal sequences can modulate protein stability and aggregation in a sequence dependent manner.

Signal Peptide and Denaturing Temperature are Critical Factors for Efficient Mammalian Expression and Immunoblotting of Cannabinoid Receptors*

Science.gov (United States)

WANG, Chenyun; WANG, Yingying; WANG, Miao; CHEN, Jiankui; YU, Nong; SONG, Shiping; KAMINSKI, Norbert E.; ZHANG, Wei

2013-01-01

Summary Many researchers employed mammalian expression system to artificially express cannabinoid receptors, but immunoblot data that directly prove efficient protein expression can hardly be seen in related research reports. In present study, we demonstrated cannabinoid receptor protein was not able to be properly expressed with routine mammalian expression system. This inefficient expression was rescued by endowing an exogenous signal peptide ahead of cannabinoid receptor peptide. In addition, the artificially synthesized cannabinoid receptor was found to aggregate under routine sample denaturing temperatures (i.e., ≥95°C), forming a large molecular weight band when analyzed by immunoblotting. Only denaturing temperatures ≤75°C yielded a clear band at the predicted molecular weight. Collectively, we showed that efficient mammalian expression of cannabinoid receptors need a signal peptide sequence, and described the requirement for a low sample denaturing temperature in immunoblot analysis. These findings provide very useful information for efficient mammalian expression and immunoblotting of membrane receptors. PMID:22528237

Reduced ability of C-type natriuretic peptide (CNP) to activate natriuretic peptide receptor B (NPR-B) causes dwarfism in lbab−/− mice

Science.gov (United States)

Yoder, Andrea R.; Kruse, Andrew C.; Earhart, Cathleen A.; Ohlendorf, Douglas H.; Potter, Lincoln R.

2015-01-01

C-type natriuretic peptide (CNP) stimulates endochondrial ossification by activating the transmembrane guanylyl cyclase, natriuretic peptide receptor-B (NPR-B). Recently, a spontaneous autosomal recessive mutation that causes severe dwarfism in mice was identified. The mutant, called long bone abnormality (lbab), contains a single point mutation that converts an arginine to a glycine in a conserved coding region of the CNP gene, but how this mutation affects CNP activity has not been reported. Here, we determined that thirty to greater than one hundred-fold more CNPlbab was required to activate NPR-B as compared to wild-type CNP in whole cell cGMP elevation and membrane guanylyl cyclase assays. The reduced ability of CNPlbab to activate NPR-B was explained, at least in part, by decreased binding since ten-fold more CNPlbab than wild-type CNP was required to compete with [125I][Tyr0]CNP for receptor binding. Molecular modeling suggested that the conserved arginine is critical for binding to an equally conserved acidic pocket in NPR-B. These results indicate that reduced binding to and activation of NPR-B causes dwarfism in lbab−/− mice. PMID:18554750

PRmePRed: A protein arginine methylation prediction tool.

Directory of Open Access Journals (Sweden)

Pawan Kumar

Full Text Available Protein methylation is an important Post-Translational Modification (PTMs of proteins. Arginine methylation carries out and regulates several important biological functions, including gene regulation and signal transduction. Experimental identification of arginine methylation site is a daunting task as it is costly as well as time and labour intensive. Hence reliable prediction tools play an important task in rapid screening and identification of possible methylation sites in proteomes. Our preliminary assessment using the available prediction methods on collected data yielded unimpressive results. This motivated us to perform a comprehensive data analysis and appraisal of features relevant in the context of biological significance, that led to the development of a prediction tool PRmePRed with better performance. The PRmePRed perform reasonably well with an accuracy of 84.10%, 82.38% sensitivity, 83.77% specificity, and Matthew's correlation coefficient of 66.20% in 10-fold cross-validation. PRmePRed is freely available at http://bioinfo.icgeb.res.in/PRmePRed/.

Molecular dynamics simulation of albite twinning and pericline twinning in low albite

International Nuclear Information System (INIS)

Li, Bin; Knowles, Kevin M

2013-01-01

Two twinning laws, the albite law and the pericline law, are the predominant growth twinning modes in triclinic plagioclase feldspars such as low albite, NaAlSi 3 O 8 , in which the aluminum and silicon atoms are in an ordered arrangement on the tetrahedral sites of the aluminosilicate framework. In the terminology used formally to describe deformation twinning in a triclinic lattice, these twin laws can be described as Type I and Type II twin laws, respectively, with the pericline twin law being conjugate to the albite twin law. In this study, twin boundaries have been constructed for low albite according to these two twinning laws and studied by molecular dynamics simulation. The results show that suitably constructed twin boundary models are quite stable for both albite twinning and pericline twinning during molecular dynamics simulation. The calculated twin boundary energy of an albite twin is significantly lower than that of a pericline twin, in accord with the experimental observation that albite twinning is the more commonly observed mode seen in plagioclase feldspars. The results of the molecular dynamics simulations also agree with conclusions from the prior work of Starkey that glide twinning in low albite is not favoured energetically. (paper)

Art for twins: Yorùbá artists and their statues/twin research studies: twins' education and conceptions; diurnal preference; inherited eye diseases; ultrasound counseling when twins are conjoined/popular twin reports: twin sisters (the film); rare pregnancy; diet test; French twins reared apart and reunited.

Science.gov (United States)

Segal, Nancy L

2014-06-01

The Yorùbá of Nigeria are well known for their high twinning rate and the statues they create to commemorate deceased twins. An impressive collection of this artwork was displayed at the University of California's Fowler Museum in Los Angeles between October 13, 2013 and March 2, 2014. An overview of this exhibit is provided. Next, twin research on maternal education and conception, diurnal preference, inherited eye diseases, and ultrasound counseling for couples with conjoined twins are briefly summarized. This article concludes with a discussion of media-based items related to twins. The topics include an award-winning twin film, a rare pregnancy, a diet test, and the separation and chance reunion of monozygotic female twins.

Molding a peptide into an RNA site by in vivo peptide evolution

OpenAIRE

Harada, Kazuo; Martin, Shelley S.; Tan, Ruoying; Frankel, Alan D.

1997-01-01

Short peptides corresponding to the arginine-rich domains of several RNA-binding proteins are able to bind to their specific RNA sites with high affinities and specificities. In the case of the HIV-1 Rev-Rev response element (RRE) complex, the peptide forms a single α-helix that binds deeply in a widened, distorted RNA major groove and makes a substantial set of base-specific and backbone contacts. Using a reporter system based on antitermination by the bacteriophage λ N protein, it has been ...

[l-arginine efficiency in MELAS syndrome. A case report].

Science.gov (United States)

Moutaouakil, F; El Otmani, H; Fadel, H; Sefrioui, F; Slassi, I

2009-05-01

Mitochondrial encephalomyopathy lactic acidosis and stoke-like episodes (MELAS) is a rare neurodegenerative disease caused by mutations of mitochondrial DNA. We report the case of a 12-year-old child with MELAS syndrome who presented with recurrent migraine-like headache and sudden blindness suggesting stroke-like episodes. Furthermore, he developed progressive muscular impairment with bilateral hearing loss. Serum lactate and pyruvate levels were elevated and the muscle biopsy showed an aspect of red-ragged fibers with Gomori trichrome. Brain imaging showed calcifications of basal ganglia on the CT scan and a parieto-occipital high signal on diffusion-weighted MRI. A genetic analysis was not performed but the presence of hearing loss in the patient's mother was suggestive of maternal transmission. Stroke-like episodes in the form of migraine-like headache and blindness were the patient's major complaint and did not improve despite analgesic drugs. After oral administration of l-arginine at the dose of 0.4mg/kg per day, stroke-like symptoms totally and rapidly disappeared. The efficiency of l-arginine in stroke-like episodes was initially reported then confirmed in a controlled study. The pathophysiology of stoke-like episodes and the mechanisms underlying the action of l-arginine are discussed.

Competition between Sec- and TAT-dependent protein translocation in Escherichia coli

DEFF Research Database (Denmark)

Cristóbal, S.; de Gier, J.-W.; Nielsen, Henrik

1999-01-01

-routed into the TAT pathway, suggesting that Sec-targeting signals in Lep can override TAT-targeting information in the TorA signal peptide. We also show that the TorA signal peptide can be converted into a Sec-targeting signal peptide by increasing the hydrophobicity of its h-region. Thus, beyond the twin...... the TorA TAT-targeting signal peptide to the Sec-dependent inner membrane protein leader peptidase (Lep). We find that the soluble, periplasmic P2 domain from Lep is re-routed by the TorA signal peptide into the TAT pathway. In contrast, the full-length TorA–Lep fusion protein is not re...

Principles of protein targeting to the nucleolus.

Science.gov (United States)

Martin, Robert M; Ter-Avetisyan, Gohar; Herce, Henry D; Ludwig, Anne K; Lättig-Tünnemann, Gisela; Cardoso, M Cristina

2015-01-01

The nucleolus is the hallmark of nuclear compartmentalization and has been shown to exert multiple roles in cellular metabolism besides its main function as the place of rRNA synthesis and assembly of ribosomes. Nucleolar proteins dynamically localize and accumulate in this nuclear compartment relative to the surrounding nucleoplasm. In this study, we have assessed the molecular requirements that are necessary and sufficient for the localization and accumulation of peptides and proteins inside the nucleoli of living cells. The data showed that positively charged peptide entities composed of arginines alone and with an isoelectric point at and above 12.6 are necessary and sufficient for mediating significant nucleolar accumulation. A threshold of 6 arginines is necessary for peptides to accumulate in nucleoli, but already 4 arginines are sufficient when fused within 15 amino acid residues of a nuclear localization signal of a protein. Using a pH sensitive dye, we found that the nucleolar compartment is particularly acidic when compared to the surrounding nucleoplasm and, hence, provides the ideal electrochemical environment to bind poly-arginine containing proteins. In fact, we found that oligo-arginine peptides and GFP fusions bind RNA in vitro. Consistent with RNA being the main binding partner for arginines in the nucleolus, we found that the same principles apply to cells from insects to man, indicating that this mechanism is highly conserved throughout evolution.

NGR-peptide-drug conjugates with dual targeting properties.

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Kata Nóra Enyedi

Full Text Available Peptides containing the asparagine-glycine-arginine (NGR motif are recognized by CD13/aminopeptidase N (APN receptor isoforms that are selectively overexpressed in tumor neovasculature. Spontaneous decomposition of NGR peptides can result in isoAsp derivatives, which are recognized by RGD-binding integrins that are essential for tumor metastasis. Peptides binding to CD13 and RGD-binding integrins provide tumor-homing, which can be exploited for dual targeted delivery of anticancer drugs. We synthesized small cyclic NGR peptide-daunomycin conjugates using NGR peptides of varying stability (c[KNGRE]-NH2, Ac-c[CNGRC]-NH2 and the thioether bond containing c[CH2-CO-NGRC]-NH2, c[CH2-CO-KNGRC]-NH2. The cytotoxic effect of the novel cyclic NGR peptide-Dau conjugates were examined in vitro on CD13 positive HT-1080 (human fibrosarcoma and CD13 negative HT-29 (human colon adenocarcinoma cell lines. Our results confirm the influence of structure on the antitumor activity and dual acting properties of the conjugates. Attachment of the drug through an enzyme-labile spacer to the C-terminus of cyclic NGR peptide resulted in higher antitumor activity on both CD13 positive and negative cells as compared to the branching versions.

Therapeutic modalities of twin to twin transfusion syndrome

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Šulović N.

2015-01-01

Full Text Available Twin to twin transfusion syndrome (TTTTS accounts for approximately 10% of monochorionic twin pregnancies and, if left untreated, is associated with high morbidity and mortality rate. A net transfusion of blood flow from one fetus (donor twin to the other (recipient twin via placental vascular anastomoses has been supposed as the major etiology of TTTTS. The donor twin becomes hypovolemic and oliguria, oligohydramnios, and a variable degree of growth restriction develop, whereas the recipient twin manifests polyuria, polyhydramnios, and hydrops in response to hypervolemia. TTTTS can be treated by either serial amniocentesis or selective fetoscopic laser coagulation of the communicating vessels. The rationale for removal of large volumes of amniotic fluid is to prevent preterm delivery secondary to polyhydramnios and to improve fetal circulation by reducing pressure on the chorionic plate. On the other hand, the goal of laser therapy is to occlude vascular anastomoses, thereby interrupting intertwin blood exchange. Although laser treatment is associated with increased survival rate and reduced neurologic complications, compared with amnioreduction, it requires highly specialized centers, whereas serial amniocentesis has the advantage of being performed worldwide. Therefore, the optimal treatment for pregnancies complicated with TTTTS is still controversial.

The effect of chorionicity and twin-to-twin delivery time interval on short-term outcome of the second twin

DEFF Research Database (Denmark)

Hjortø, Sofie; Nickelsen, Carsten; Petersen, Janne

2013-01-01

Abstract Objectives: To investigate the effect of chorionicity and twin-to-twin delivery time interval on short-term outcome in the second twin. Additionally, to investigate predictors of adverse outcome in both twins. Methods: Data included vaginally delivered twins (≥ 36 weeks) from Copenhagen ...

Radioimmunoassay of 1-Deamino-8-D-Arginine Vasopressin and related peptides with special condsideration to their gastrointestinal absorption

International Nuclear Information System (INIS)

Lundin, S.

1986-01-01

A sensitive and specific radioimminoassy for 1-deamino-8-D-arginine vasopressin (DDAVP) was developed. Measurements of the analogue in extracted and non-extracted plasma yielded indentical results, the sensitivity was reduced with non-extracted samples. The assay was validated by correlating DDAVP blood levels to a biologic response (antidiuretic). Dilutions of plasma extracts containing DDAVP were parallel with the standard curve. Fractionations of extracted plasma DDAVP samples on HPLC revealed that immunoreactivity eluted as standard DDAVP. Prolonged infusion of DDAVP in rats did not alter pituitary secretion of oxytocin and vasopressin and urine osmolatity and volume changes were modest. DDAVP was absorbed from the gastrointestinal tract of humans, rats, rabbits and dogs in quantities sufficient to induce a biological response. Peak plasma concentrations were reached between 30-90 min after peptide administration. By the use of an in vitro model, the everted rat intestine, the transmucosal passage of a number of vasopressin analogues were tested. There was no clear-cut correlation between hydrophobicity and intestinal transport rates. Metabolic inhibitors and N/sub2/ did not decrease DDAVP transport. No transport maximum could be demonstrated over a 10/sup4/ fold concentration range. The distribution volume of /sup3/H-polyethyleneglycol was greater. then that of DDAVP in mucosal flakes. There was a close correlation between immunoassayable DDAVP levels and those found after HPLC analyses. It is proposed that DDAVP absorption occurs mainly by passive diffusion. The bioavailability of perorally ingested DDAVP in humans was about 1 percent. Minor amounts were excreted in urine

Microfluidic Isoelectric Focusing of Amyloid Beta Peptides Followed by Micropillar-Matrix-Assisted Laser Desorption Ionization-Mass Spectrometry.

Science.gov (United States)

Mikkonen, Saara; Jacksén, Johan; Roeraade, Johan; Thormann, Wolfgang; Emmer, Åsa

2016-10-18

A novel method for preconcentration and purification of the Alzheimer's disease related amyloid beta (Aβ) peptides by isoelectric focusing (IEF) in 75 nL microchannels combined with their analysis by micropillar-matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) is presented. A semiopen chip-based setup, consisting of open microchannels covered by a lid of a liquid fluorocarbon, was used. IEF was performed in a mixture of four small and chemically well-defined amphoteric carriers, glutamic acid, aspartyl-histidine (Asp-His), cycloserine (cSer), and arginine, which provided a stepwise pH gradient tailored for focusing of the C-terminal Aβ peptides with a pI of 5.3 in the boundary between cSer and Asp-His. Information about the focusing dynamics and location of the foci of Aβ peptides and other compounds was obtained using computer simulation and by performing MALDI-MS analysis directly from the open microchannel. With the established configuration, detection was performed by direct sampling of a nanoliter volume containing the focused Aβ peptides from the microchannel, followed by deposition of this volume onto a chip with micropillar MALDI targets. In addition to purification, IEF preconcentration provides at least a 10-fold increase of the MALDI-MS-signal. After immunoprecipitation and concentration of the eluate in the microchannel, IEF-micropillar-MALDI-MS is demonstrated to be a suitable platform for detection of Aβ peptides in human cerebrospinal fluid as well as in blood plasma.

DIVERSE POTENTIAL AND PHARMACOLOGICAL STUDIES OF ARGININE

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Anju Meshram

2015-09-01

Full Text Available Arginine is metabolically flexible amino acid with major role in protein synthesis and detoxification of ammonia. It is involved in several metabolic pathways for the production of biologically active compounds such as creatine, nitric oxide, ornithine, glutamate, agmatine, citrulline and polyamines. Regarding this all, we review the crucial role of arginine in metabolism, diversified prospective uses and pharmacological applications. Arginine plays an important role in the treatment of tumorigenesis, asthama, gastric, erectile dysfunction, apoptosis, melanoma and congestive heart failure. Ability to produce nitric oxide offers various applications as in the prevention of age and hair loss. It serves as a precursor of creatine with ergogenic potential. The ability to increase endogenous growth hormone makes arginine a preferred supplement for the improvement of physical performance. In the present study details about the pharmacological applications of arginine based on modern scientific investigations have been discussed. There are immense properties hidden in arginine that need to be explored using the scientific investigations to make it beneficial for the medicine and human health. More research is needed to evaluate the role of arginine supplementation on exercise performance and training adaptations in healthy and diseased populations before taking any conclusions.

Homologies between the amino acid sequences of some vertebrate peptide hormones and peptides isolated from invertebrate sources.

Science.gov (United States)

De Loof, A; Schoofs, L

1990-01-01

1. The 4K-prothoracicotropic hormone (PTTH) or bombyxin and the melanization-reddish coloration hormone of the silkworm Bombyx mori resemble insulin and insulin-like growth factors. 2. The family of adipokinetic/red pigment concentrating hormones has some similarity with glucagon. 3. Members of the FMRFamide family are found in vertebrates as well as in invertebrates. 4. In Locusta, a molecule immunologically and biologically related to amphibian melanophore stimulating hormone has been partially characterized. 5. Enkephalins and enkephalin-related peptides occur in insects and other invertebrates. 6. Peptides belonging to the tachykinin family have been isolated from molluscan (Octopus) salivary glands and from insect nervous tissue (Locusta migratoria). 7. Invertebrate arginine-vasotocin homologs have been isolated from an insect (Locusta migratoria) and from a mollusc (Conus). 8. In Leucophaea, Locusta and Drosophila, peptides resembling those of the vertebrate gastrin/cholecystokinin family have been identified. 9. As the number of different neuro-/gut peptides with possible function(s) as hormone, neurotransmitter or neuromodulator is now estimated to be of the order of a few hundred, more similarities will probably show up in the near future.

Twin Research and the Arts: Interconnections / Twin Research: Twin Studies of Sexual Orientation; A Historical Biological Twin Gem; GWAS Approach to Who Has Twins / Newsworthy: Twins on College Campuses; 'Brainprint': Personal Identification by Brain Waves.

Science.gov (United States)

Segal, Nancy L

2016-08-01

The interrelatedness between twin research and the arts is explored via a new play about a famous case. In the 1960s, identical twin David Bruce Reimer was accidentally castrated as an infant during circumcision to correct a urinary problem. The decision to raise him as a girl, and the consequences of that decision, are explored in the new theatrical production of Boy. Other examples of the arts mirroring science, and vice versa, are described. Next, brief reviews and summaries of twin research on sexual orientation, 1860s' knowledge of placental arrangements and twinning mechanisms, and genes underlying multiple birth conception and fertility related measures are provided. This article concludes with a look at twins on college campuses and the identification of individuals by their brain waves. A correction and clarification regarding my article on the Brazilian Twin Registry in the last issue of THG (Segal, 2016) is also provided.

Radiopharmaceutical development of radiolabelled peptides

Energy Technology Data Exchange (ETDEWEB)

Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

2012-02-15

Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

Polyglutamate directed coupling of bioactive peptides for the delivery of osteoinductive signals on allograft bone

Science.gov (United States)

Culpepper, Bonnie K.; Bonvallet, Paul P.; Reddy, Michael S.; Ponnazhagan, Selvarangan; Bellis, Susan L.

2012-01-01

Allograft bone is commonly used as an alternative to autograft, however allograft lacks many osteoinductive factors present in autologous bone due to processing. In this study, we investigated a method to reconstitute allograft with osteoregenerative factors. Specifically, an osteoinductive peptide from collagen I, DGEA, was engineered to express a heptaglutamate (E7) domain, which binds the hydroxyapatite within bone mineral. Addition of E7 to DGEA resulted in 9× greater peptide loading on allograft, and significantly greater retention after a 5-day interval with extensive washing. When factoring together greater initial loading and retention, the E7 domain directed a 45-fold enhancement of peptide density on the allograft surface. Peptide-coated allograft was also implanted subcutaneously into rats and it was found that E7DGEA was retained in vivo for at least 3 months. Interestingly, E7DGEA peptides injected intravenously accumulated within bone tissue, implicating a potential role for E7 domains in drug delivery to bone. Finally, we determined that, as with DGEA, the E7 modification enhanced coupling of a bioactive BMP2-derived peptide on allograft. These results suggest that E7 domains are useful for coupling many types of bone-regenerative molecules to the surface of allograft to reintroduce osteoinductive signals and potentially advance allograft treatments. PMID:23182349

Effects of arginine on multimodal anion exchange chromatography.

Science.gov (United States)

Hirano, Atsushi; Arakawa, Tsutomu; Kameda, Tomoshi

2015-12-01

The effects of arginine on binding and elution properties of a multimodal anion exchanger, Capto adhere, were examined using bovine serum albumin (BSA) and a monoclonal antibody against interleukin-8 (mAb-IL8). Negatively charged BSA was bound to the positively charged Capto adhere and was readily eluted from the column with a stepwise or gradient elution using 1M NaCl at pH 7.0. For heat-treated BSA, small oligomers and remaining monomers were also eluted using a NaCl gradient, whereas larger oligomers required arginine for effective elution. The positively charged mAb-IL8 was bound to Capto adhere at pH 7.0. Arginine was also more effective for elution of the bound mAb-IL8 than was NaCl. The results imply that arginine interacts with the positively charged Capto adhere. The mechanism underlying the interactions of arginine with Capto adhere was examined by calculating the binding free energy between an arginine molecule and a Capto adhere ligand in water through molecular dynamics simulations. The overall affinity of arginine for Capto adhere is attributed to the hydrophobic and π-π interactions between an arginine side chain and the aromatic moiety of the ligand as well as hydrogen bonding between arginine and the ligand hydroxyl group, which may account for the characteristics of protein elution using arginine. Copyright © 2015 Elsevier Inc. All rights reserved.

Peptide signalling during the pollen tube journey and double fertilization.

Science.gov (United States)

Qu, Li-Jia; Li, Ling; Lan, Zijun; Dresselhaus, Thomas

2015-08-01

Flowering seed plants (angiosperms) have evolved unique ways to protect their gametes from pathogen attack and from drying out. The female gametes (egg and central cell) are deeply embedded in the maternal tissues of the ovule inside the ovary, while the male gametes (sperm cells) are enclosed in the vegetative pollen tube cell. After germination of the pollen tube at the surface of papilla cells of the stigma the two immobile sperm cells are transported deep inside the sporophytic maternal tissues to be released inside the ovule for double fertilization. Angiosperms have evolved a number of hurdles along the pollen tube journey to prevent inbreeding and fertilization by alien sperm cells, and to maximize reproductive success. These pre-zygotic hybridization barriers require intensive communication between the male and female reproductive cells and the necessity to distinguish self from non-self interaction partners. General molecules such as nitric oxide (NO) or gamma-aminobutyric acid (GABA) therefore appear to play only a minor role in these species-specific communication events. The past 20 years have shown that highly polymorphic peptides play a leading role in all communication steps along the pollen tube pathway and fertilization. Here we review our current understanding of the role of peptides during reproduction with a focus on peptide signalling during self-incompatibility, pollen tube growth and guidance as well as sperm reception and gamete activation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Intragranular twinning, detwinning, and twinning-like lattice reorientation in magnesium alloys

International Nuclear Information System (INIS)

Wu, Wei; Gao, Yanfei; Li, Nan; Parish, Chad M.; Liu, Wenjun; Liaw, Peter K.; An, Ke

2016-01-01

Deformation twinning plays a critical role on improving metals or alloys ductility, especially for hexagonal close-packed materials with low symmetry crystal structure. A rolled Mg alloy was selected as a model system to investigate the extension twinning behaviors and characteristics of parent-twin interactions by nondestructive in situ 3D synchrotron X-ray microbeam diffraction. Besides twinning-detwinning process, the “twinning-like” lattice reorientation process was captured within an individual grain inside a bulk material during the strain reversal. The distributions of parent, twin, and reorientated grains and sub-micron level strain variation across the twin boundary are revealed. A theoretical calculation of the lattice strain confirms that the internal strain distribution in parent and twinned grains correlates with the experimental setup, grain orientation of parent, twin, and surrounding grains, as well as the strain path changes. The study suggests a novel deformation mechanism within the hexagonal close-packed structure that cannot be determined from surface-based characterization methods.

Arginine de novo and nitric oxide production in disease states

OpenAIRE

Luiking, Yvette C.; Ten Have, Gabriella A. M.; Wolfe, Robert R.; Deutz, Nicolaas E. P.

2012-01-01

Arginine is derived from dietary protein intake, body protein breakdown, or endogenous de novo arginine production. The latter may be linked to the availability of citrulline, which is the immediate precursor of arginine and limiting factor for de novo arginine production. Arginine metabolism is highly compartmentalized due to the expression of the enzymes involved in arginine metabolism in various organs. A small fraction of arginine enters the NO synthase (NOS) pathway. Tetrahydrobiopterin ...

Rational design of DKK3 structure-based small peptides as antagonists of Wnt signaling pathway and in silico evaluation of their efficiency.

Directory of Open Access Journals (Sweden)

Mansour Poorebrahim

Full Text Available Dysregulated Wnt signaling pathway is highly associated with the pathogenesis of several human cancers. Dickkopf proteins (DKKs are thought to inhibit Wnt signaling pathway through binding to lipoprotein receptor-related protein (LRP 5/6. In this study, based on the 3-dimensional (3D structure of DKK3 Cys-rich domain 2 (CRD2, we have designed and developed several peptide inhibitors of Wnt signaling pathway. Modeller 9.15 package was used to predict 3D structure of CRD2 based on the Homology modeling (HM protocol. After refinement and minimization with GalaxyRefine and NOMAD-REF servers, the quality of selected models was evaluated utilizing VADAR, SAVES and ProSA servers. Molecular docking studies as well as literature-based information revealed two distinct boxes located at CRD2 which are actively involved in the DKK3-LRP5/6 interaction. A peptide library was constructed conducting the backrub sequence tolerance scanning protocol in Rosetta3.5 according to the DKK3-LRP5/6 binding sites. Seven tolerated peptides were chosen and their binding affinity and stability were improved by some logical amino acid substitutions. Molecular dynamics (MD simulations of peptide-LRP5/6 complexes were carried out using GROMACS package. After evaluation of binding free energies, stability, electrostatic potential and some physicochemical properties utilizing computational approaches, three peptides (PEP-I1, PEP-I3 and PEP-II2 demonstrated desirable features. However, all seven improved peptides could sufficiently block the Wnt-binding site of LRP6 in silico. In conclusion, we have designed and improved several small peptides based on the LRP6-binding site of CRD2 of DKK3. These peptides are highly capable of binding to LRP6 in silico, and may prevent the formation of active Wnt-LRP6-Fz complex.

THE ARGININE AND PREARGININE GROUPS IN EDESTIN.

Science.gov (United States)

Simms, H S

1930-09-20

The author corroborates the data of Schmidt showing that the dissociation index of the third group of arginine is pK(3)' = 12.5. New titration data of edestin have been obtained in very alkaline solutions and show that there is a corresponding group with a titration index of pG' = 12.0, but present in much less quantity than can account for the arginine found on hydrolysis. The data support the theory that the combination of strong base or strong acid with proteins is produced by the formation of salts with the "extra groups" of those trivalent amino acids which can be isolated from the protein, with the exception of arginine. Arginine contributes to the titration curve in much smaller amount than is found on hydrolysis. This deficiency in the arginine group may be accounted for by the basic group in proteins having a titration index of pG' = 3.8 to 4.6 (depending on the protein), which apparently yields arginine on hydrolysis, and may properly be called prearginine.

Self-association of a highly charged arginine-rich cell-penetrating peptide

Czech Academy of Sciences Publication Activity Database

Tesei, G.; Vazdar, M.; Jensen, M. R.; Cragnell, C.; Mason, Philip E.; Heyda, J.; Skepö, M.; Jungwirth, Pavel; Lund, M.

2017-01-01

Roč. 114, č. 43 (2017), s. 11428-11433 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA16-01074S Institutional support: RVO:61388963 Keywords : cell-penetrating peptide * self-association * MD simulations * SAXS * NMR Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry Impact factor: 9.661, year: 2016

Simulations of stress-induced twinning and de-twinning: A phase field model

International Nuclear Information System (INIS)

Hu Shenyang; Henager, Chuck H.; Chen Longqing

2010-01-01

Twinning in certain metals or under certain conditions is a major plastic deformation mode. Here we present a phase field model to describe twin formation and evolution in a polycrystalline fcc metal under loading and unloading. The model assumes that twin nucleation, growth and de-twinning is a process of partial dislocation nucleation and slip on successive habit planes. Stacking fault energies, energy pathways (γ surfaces), critical shear stresses for the formation of stacking faults and dislocation core energies are used to construct the thermodynamic model. The simulation results demonstrate that the model is able to predict the nucleation of twins and partial dislocations, as well as the morphology of the twin nuclei, and to reasonably describe twin growth and interaction. The twin microstructures at grain boundaries are in agreement with experimental observation. It was found that de-twinning occurs during unloading in the simulations, however, a strong dependence of twin structure evolution on loading history was observed.

Twins and Kindergarten Separation: Divergent Beliefs of Principals, Teachers, Parents, and Twins

Science.gov (United States)

Gordon, Lynn Melby

2015-01-01

Should principals enforce mandatory separation of twins in kindergarten? Do school separation beliefs of principals differ from those of teachers, parents of twins, and twins themselves? This survey questioned 131 elementary principals, 54 kindergarten teachers, 201 parents of twins, and 112 twins. A majority of principals (71%) believed that…

Twin-twin transfusion syndrome: etiology, severity and rational management

NARCIS (Netherlands)

van Gemert, M. J.; Umur, A.; Tijssen, J. G.; Ross, M. G.

2001-01-01

The twin-twin transfusion syndrome is a serious complication of monochorionic twin pregnancies. Partly as a result of an inadequate understanding of the pathophysiology of the syndrome, there is a lack of consensus in clinical management. We sought to review the available information on the etiology

Ablation of arginase II spares arginine and abolishes the arginine requirement for growth in male mice

Science.gov (United States)

Arginine is considered a semi-essential amino acid in many species, including humans, because under certain conditions its demand exceeds endogenous production. Arginine availability, however, is not only determined by its production, but also by its disposal. Manipulation of disposal pathways has t...

The mobility of growth twins synthesized by sputtering: Tailoring the twin thickness

International Nuclear Information System (INIS)

Velasco, Leonardo; Hodge, Andrea M.

2016-01-01

The current work presents a protean twin thickness contour zone map that illustrates how the nucleation and the mobility of twin boundaries affects the twin thickness of sputtered films. The twin thickness contour zone map can be used as a versatile guide to synthesize fully nanotwinned films with tailored twin thicknesses in materials with a wide range of stacking fault energies. The nucleation and mobility of twin boundaries was studied in four Cu alloys of different compositions (Cu-6wt.%Al, Cu-4wt.%Al, Cu-2wt.%Al, and Cu-10wt.%Ni), having stacking fault energies ranging from 6 mJ/m 2 to 60 mJ/m 2 . The films were synthesized by magnetron sputtering and characterized by transmission electron microscopy, where the twin thickness varied from 2 nm to 35 nm. Our experimental results show that it is possible to control the twin thickness. Three main mechanisms are explained to describe twin nucleation and twin boundary mobility, which are correlated to the interplay of specific sputtering conditions and the deposition temperature.

Occurrence of C-Terminal Residue Exclusion in Peptide Fragmentation by ESI and MALDI Tandem Mass Spectrometry

Science.gov (United States)

Dupré, Mathieu; Cantel, Sonia; Martinez, Jean; Enjalbal, Christine

2012-02-01

the high mass range of the MS/MS spectra. The mass difference between this signal and the protonated molecular ion corresponds to the mass of the C-terminal residue. It allowed a straightforward identification of the amino acid positioned at this extremity. It must be emphasized that a neutral residue loss can be misattributed to the formation of a ym-1 ion, i.e., to the loss of the N-terminal residue following the a1-ym-1 fragmentation channel. Extreme caution must be adopted when reading the direct sequence ion on the positive ion MS/MS spectra of singly charged peptides not to mix up the attribution of the N- and C-terminal amino acids. Although such peculiar fragmentation behavior is of obvious interest for de novo peptide sequencing, it can also be exploited in proteomics, especially for studies involving digestion protocols carried out with proteolytic enzymes other than trypsin (Lys-N, Glu-C, and Asp-N) that produce arginine-containing peptides.

Cascading reaction of arginase and urease on a graphene-based FET for ultrasensitive, real-time detection of arginine.

Science.gov (United States)

Berninger, Teresa; Bliem, Christina; Piccinini, Esteban; Azzaroni, Omar; Knoll, Wolfgang

2018-09-15

Herein, a biosensor based on a reduced graphene oxide field effect transistor (rGO-FET) functionalized with the cascading enzymes arginase and urease was developed for the detection of L-arginine. Arginase and urease were immobilized on the rGO-FET sensing surface via electrostatic layer-by-layer assembly using polyethylenimine (PEI) as cationic building block. The signal transduction mechanism is based on the ability of the cascading enzymes to selectively perform chemical transformations and prompt local pH changes, that are sensitively detected by the rGO-FET. In the presence of L-arginine, the transistors modified with (PEI/urease(arginase)) multilayers showed a shift in the Dirac point due to the change in the local pH close to the graphene surface, produced by the catalyzed urea hydrolysis. The transistors were able to monitor L-arginine in the 10-1000 μM linear range with a LOD of 10 μM, displaying a fast response and a good long-term stability. The sensor showed stereospecificity and high selectivity in the presence of non-target amino acids. Taking into account the label-free, real-time measurement capabilities and the easily quantifiable, electronic output signal, this biosensor offers advantages over state-of-the-art L-arginine detection methods. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Circadian integration of glutamatergic signals by little SAAS in novel suprachiasmatic circuits.

Science.gov (United States)

Atkins, Norman; Mitchell, Jennifer W; Romanova, Elena V; Morgan, Daniel J; Cominski, Tara P; Ecker, Jennifer L; Pintar, John E; Sweedler, Jonathan V; Gillette, Martha U

2010-09-07

Neuropeptides are critical integrative elements within the central circadian clock in the suprachiasmatic nucleus (SCN), where they mediate both cell-to-cell synchronization and phase adjustments that cause light entrainment. Forward peptidomics identified little SAAS, derived from the proSAAS prohormone, among novel SCN peptides, but its role in the SCN is poorly understood. Little SAAS localization and co-expression with established SCN neuropeptides were evaluated by immunohistochemistry using highly specific antisera and stereological analysis. Functional context was assessed relative to c-FOS induction in light-stimulated animals and on neuronal circadian rhythms in glutamate-stimulated brain slices. We found that little SAAS-expressing neurons comprise the third most abundant neuropeptidergic class (16.4%) with unusual functional circuit contexts. Little SAAS is localized within the densely retinorecipient central SCN of both rat and mouse, but not the retinohypothalamic tract (RHT). Some little SAAS colocalizes with vasoactive intestinal polypeptide (VIP) or gastrin-releasing peptide (GRP), known mediators of light signals, but not arginine vasopressin (AVP). Nearly 50% of little SAAS neurons express c-FOS in response to light exposure in early night. Blockade of signals that relay light information, via NMDA receptors or VIP- and GRP-cognate receptors, has no effect on phase delays of circadian rhythms induced by little SAAS. Little SAAS relays signals downstream of light/glutamatergic signaling from eye to SCN, and independent of VIP and GRP action. These findings suggest that little SAAS forms a third SCN neuropeptidergic system, processing light information and activating phase-shifts within novel circuits of the central circadian clock.

Cancer therapy with alpha-emitters labeled peptides.

Science.gov (United States)

Dadachova, Ekaterina

2010-05-01

Actively targeted alpha-particles offer specific tumor cell killing action with less collateral damage to surrounding normal tissues than beta-emitters. During the last decade, radiolabeled peptides that bind to different receptors on the tumors have been investigated as potential therapeutic agents both in the preclinical and clinical settings. Advantages of radiolabeled peptides over antibodies include relatively straightforward chemical synthesis, versatility, easier radiolabeling, rapid clearance from the circulation, faster penetration and more uniform distribution into tissues, and less immunogenicity. Rapid internalization of the radiolabeled peptides with equally rapid re-expression of the cell surface target is a highly desirable property that enhances the total delivery of these radionuclides into malignant sites. Peptides, such as octreotide, alpha-melanocyte-stimulating hormone analogues, arginine-glycine-aspartic acid-containing peptides, bombesin derivatives, and others may all be feasible for use with alpha-emitters. The on-going preclinical work has primarily concentrated on octreotide and octreotate analogues labeled with Bismuth-213 and Astatine-211. In addition, alpha-melanocyte-stimulating hormone analogue has been labeled with Lead-212/Bismuth-212 in vivo generator and demonstrated the encouraging therapeutic efficacy in treatment of experimental melanoma. Obstacles that continue to obstruct widespread acceptance of alpha-emitter-labeled peptides are primarily the supply of these radionuclides and concerns about potential kidney toxicity. New sources and methods for production of these medically valuable radionuclides and better understanding of mechanisms related to the peptide renal uptake and clearance should speed up the introduction of alpha-emitter-labeled peptides into the clinic. Copyright 2010 Elsevier Inc. All rights reserved.

Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling

DEFF Research Database (Denmark)

Holst, Birgitte; Brandt, Erik; Bach, Anders

2005-01-01

Two nonpeptide (L692,429 and MK-677) and two peptide [GH-releasing peptide (GHRP)-6 and ghrelin] agonists were compared in binding and in signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), and serum-responsive element (SRE) controlled tra...

On the mechanism of arginine requirement for adenovirus synthesis

International Nuclear Information System (INIS)

Plaat, D.; Weber, J.

1979-01-01

The effects of arginine deprivation on the synthesis and processing of viral proteins and the assembly of incomplete and complete virions were studied during infection with human adenovirus type 2. Arginine deprivation greatly reduced the synthesis of all viral proteins, particularly the precursor to core protein VII. The inhibition was completely reversible by the addition of arginine to the medium. Arginine deprivation between 7 and 20 hours post-infection inhibited the processing of PVII to VII, suggesting that PVII is not cleaved autocatalytically. The assembly of incomplete virions was sensitive to arginine deprivation only prior to 20 hours, while the assembly of complete virions was dependent on the continuous presence of arginine. This observation supports the hypothesis that incomplete virions are precursors of complete virions. The experiments on the PVII-specific endoprotease activity showed that arginine deprivation caused only slight reduction in the in vitro activity, although no activity was observed in vivo. The present results lead to the hypothesis that arginine deficiency inhibits the synthesis of a functional protein essential for virion maturation, other than the synthesis of processing of PVII. (author)

Arginine side chain interactions and the role of arginine as a gating charge carrier in voltage sensitive ion channels

Science.gov (United States)

Armstrong, Craig T.; Mason, Philip E.; Anderson, J. L. Ross; Dempsey, Christopher E.

2016-02-01

Gating charges in voltage-sensing domains (VSD) of voltage-sensitive ion channels and enzymes are carried on arginine side chains rather than lysine. This arginine preference may result from the unique hydration properties of the side chain guanidinium group which facilitates its movement through a hydrophobic plug that seals the center of the VSD, as suggested by molecular dynamics simulations. To test for side chain interactions implicit in this model we inspected interactions of the side chains of arginine and lysine with each of the 19 non-glycine amino acids in proteins in the protein data bank. The arginine guanidinium interacts with non-polar aromatic and aliphatic side chains above and below the guanidinium plane while hydrogen bonding with polar side chains is restricted to in-plane positions. In contrast, non-polar side chains interact largely with the aliphatic part of the lysine side chain. The hydration properties of arginine and lysine are strongly reflected in their respective interactions with non-polar and polar side chains as observed in protein structures and in molecular dynamics simulations, and likely underlie the preference for arginine as a mobile charge carrier in VSD.

The plant natriuretic peptide receptor is a guanylyl cyclase and enables cGMP-dependent signaling

KAUST Repository

Turek, Ilona

2016-03-05

The functional homologues of vertebrate natriuretic peptides (NPs), the plant natriuretic peptides (PNPs), are a novel class of peptidic hormones that signal via guanosine 3′,5′-cyclic monophosphate (cGMP) and systemically affect plant salt and water balance and responses to biotrophic plant pathogens. Although there is increasing understanding of the complex roles of PNPs in plant responses at the systems level, little is known about the underlying signaling mechanisms. Here we report isolation and identification of a novel Leucine-Rich Repeat (LRR) protein that directly interacts with A. thaliana PNP, AtPNP-A. In vitro binding studies revealed that the Arabidopsis AtPNP-A binds specifically to the LRR protein, termed AtPNP-R1, and the active region of AtPNP-A is sufficient for the interaction to occur. Importantly, the cytosolic part of the AtPNP-R1, much like in some vertebrate NP receptors, harbors a catalytic center diagnostic for guanylyl cyclases and the recombinant AtPNP-R1 is capable of catalyzing the conversion of guanosine triphosphate to cGMP. In addition, we show that AtPNP-A causes rapid increases of cGMP levels in wild type (WT) leaf tissue while this response is significantly reduced in the atpnp-r1 mutants. AtPNP-A also causes cGMP-dependent net water uptake into WT protoplasts, and hence volume increases, whereas responses of the protoplasts from the receptor mutant are impaired. Taken together, our results suggest that the identified LRR protein is an AtPNP-A receptor essential for the PNP-dependent regulation of ion and water homeostasis in plants and that PNP- and vertebrate NP-receptors and their signaling mechanisms share surprising similarities. © 2016 Springer Science+Business Media Dordrecht

The Qingdao Twin Registry

DEFF Research Database (Denmark)

Duan, Haiping; Ning, Feng; Zhang, Dongfeng

2013-01-01

In 1998, the Qingdao Twin Registry was initiated as the main part of the Chinese National Twin Registry. By 2005, a total of 10,655 twin pairs had been recruited. Since then new twin cohorts have been sampled, with one longitudinal cohort of adolescent twins selected to explore determinants of me...

Twins and non-twin siblings: different estimates of shared environmental influence in early childhood.

Science.gov (United States)

Koeppen-Schomerus, Gesina; Spinath, Frank M; Plomin, Robert

2003-04-01

Twin studies typically indicate shared environmental influence for cognitive abilities, especially in early childhood. However, across studies, DZ twin correlations tend to be greater than non-twin sibling correlations, suggesting that twin estimates of shared environment are to some extent specific to twins. We tested this hypothesis in a sample of more than 1800 MZ and 1800 same-sex DZ pairs from the Twins Early Development Study (TEDS), a study of twins born in England and Wales in 1994 and 1995. For this analysis, we obtained comparable data from more than 130 same-sex younger siblings of the twins. Twins and their younger siblings were assessed for language, cognitive abilities and behavior problems by their parents at 2 and 3 years of age. For language and cognitive measures at both 2 and 3 years, but not for behavior problems, estimates of shared environment were more than twice as large for twins as compared to non-twin siblings. We conclude that about half of twin study estimates of shared environment for cognitive abilities in early childhood are specific to twins. Although many possibilities exist for explaining the special shared environment effect for twins, we suggest that cognitive-relevant experiences that are not shared by siblings are shared by twins because they are exactly the same age.

Chemical modification of arginine residues in the lactose repressor

International Nuclear Information System (INIS)

Whitson, P.A.; Matthews, K.S.

1987-01-01

The lactose repressor protein was chemically modified with 2,3-butanedione and phenylglyoxal. Arginine reaction was quantitated by either amino aced analysis or incorporation of 14 C-labeled phenylglyoxal. Inducer binding activity was unaffected by the modification of arginine residues, while both operator and nonspecific DNA binding activities were diminished, although to differing degrees. The correlation of the decrease in DNA binding activities with the modification of ∼ 1-2 equiv of arginine per monomer suggests increased reactivity of a functionally essential residue(s). For both reagents, operator DNA binding activity was protected by the presence of calf thymus DNA, and the extent of reaction with phenylglyoxal was simultaneously diminished. This protection presumably results from steric restriction of reagent access to an arginine(s) that is (are) essential for DNA binding interactions. These experiments suggest that there is (are) an essential reactive arginine(s) critical for repressor binding to DNA

Effect of co-twin gender on neurodevelopmental symptoms: a twin register study.

Science.gov (United States)

Eriksson, Jonna Maria; Lundström, Sebastian; Lichtenstein, Paul; Bejerot, Susanne; Eriksson, Elias

2016-01-01

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are neurodevelopmental disorders thought to have both genetic and environmental causes. It has been hypothesized that exposure to elevated levels of prenatal testosterone is associated with elevated traits of ASD and ADHD. Assuming that testosterone levels from a dizygotic male twin fetus may lead to enhanced testosterone exposure of its co-twins, we aimed to test the prenatal testosterone hypothesis by comparing same-sex with opposite-sex dizygotic twins with respect to neurodevelopmental symptoms. Neuropsychiatric traits were assessed in a population-based twin cohort from the Child and Adolescent Twin Study in Sweden (CATSS). Parental interviews were conducted for 16,312 dizygotic twins, 9 and 12 years old, with the Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC). Girls with a female co-twin had an increased risk of reaching the cut-off score for ADHD compared with girls with a male co-twin. Both boys and girls with a female co-twin displayed a larger number of traits related to attention deficit and repetitive and stereotyped behaviors than those with a male twin. In girls, this also extended to social interaction and the combined measures for ASD and ADHD, however, with small effect sizes. Our results are reverse to what would have been expected from the prenatal testosterone hypothesis but consistent with a previous study of ASD and ADHD traits in dizygotic twins. The seemingly protective effect for girls of having a twin brother may be an effect of parent report bias, but may also be an unexpected effect of sharing the intrauterine environment with a male co-twin.

The do's and don'ts of arginine supplementation

African Journals Online (AJOL)

to meet the body's nutritional needs for energy, protein and micronutrients. ... inflammatory response syndrome (SIRS) and therefore the use of arginine in this ... smooth muscle cell proliferation12 and controlling vascular oxidative stress and the ... reduced arginine levels in sepsis that reflect the specific changes in arginine ...

The uptake of arginine-rich cell-penetrating peptides: putting the puzzle together

NARCIS (Netherlands)

Brock, R.E.

2014-01-01

Over the past 20 years, cell-penetrating peptides (CPPs) have captured the attention of biomedical researchers, biophysicists, and (bio)organic chemists. These molecules efficiently enter cells and mediate entry of (macro)molecules that by themselves do not cross the plasma membrane. Since their

Signal peptide-dependent inhibition of MHC class I heavy chain translation by rhesus cytomegalovirus.

Directory of Open Access Journals (Sweden)

Colin J Powers

2008-10-01

Full Text Available The US2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit MHC-I assembly with viral peptides, thus preventing cytotoxic T cell recognition. Since HCMV lacking US2-11 is no longer able to block assembly and transport of MHC-I, we examined whether this is also observed for RhCMV lacking the corresponding region. Unexpectedly, recombinant RhCMV lacking US2-11 was still able to inhibit MHC-I expression in infected fibroblasts, suggesting the presence of an additional MHC-I evasion mechanism. Progressive deletion analysis of RhCMV-specific genomic regions revealed that MHC-I expression is fully restored upon additional deletion of rh178. The protein encoded by this RhCMV-specific open reading frame is anchored in the endoplasmic reticulum membrane. In the presence of rh178, RhCMV prevented MHC-I heavy chain (HC expression, but did not inhibit mRNA transcription or association of HC mRNA with translating ribosomes. Proteasome inhibitors stabilized a HC degradation intermediate in the absence of rh178, but not in its presence, suggesting that rh178 prevents completion of HC translation. This interference was signal sequence-dependent since replacing the signal peptide with that of CD4 or murine HC rendered human HCs resistant to rh178. We have identified an inhibitor of antigen presentation encoded by rhesus cytomegalovirus unique in both its lack of homology to any other known protein and in its mechanism of action. By preventing signal sequence-dependent HC translocation, rh178 acts prior to US2, US3 and US11 which attack MHC-I proteins after protein synthesis is completed. Rh178 is the first viral protein known to interfere at this step of the MHC-I pathway, thus taking advantage of the conserved nature of HC leader peptides, and represents a new mechanism of translational interference.

Attractiveness Differences Between Twins Predicts Evaluations of Self and Co-Twin

Science.gov (United States)

Principe, Connor P.; Rosen, Lisa H.; Taylor-Partridge, Teresa; Langlois, Judith H.

2012-01-01

One of the most consistent findings in psychology shows that people prefer and make positive attributions about attractive compared with unattractive people. The goal of the current study was to determine the power of attractiveness effects by testing whether these social judgments are made where attractiveness differences are smallest: between twins. Differences in facial attractiveness predicted twins’ evaluations of self and their co-twin (n = 158; 54 male). In twin pairs, the more attractive twin judged their less attractive sibling as less physically attractive, athletic, socially competent, and emotionally stable. The less attractive twin did the reverse. Given that even negligible differences in facial attractiveness predicted self and co-twin attitudes, these results provide the strongest test yet of appearance-based stereotypes. PMID:23467329

Ecological Effect of Arginine on Oral Microbiota.

Science.gov (United States)

Zheng, Xin; He, Jinzhi; Wang, Lin; Zhou, Shuangshuang; Peng, Xian; Huang, Shi; Zheng, Liwei; Cheng, Lei; Hao, Yuqing; Li, Jiyao; Xu, Jian; Xu, Xin; Zhou, Xuedong

2017-08-03

Dental caries is closely associated with the microbial dybiosis between acidogenic/aciduric pathogens and alkali-generating commensal bacteria colonized in the oral cavity. Our recent studies have shown that arginine may represent a promising anti-caries agent by modulating microbial composition in an in vitro consortium. However, the effect of arginine on the oral microbiota has yet to be comprehensively delineated in either clinical cohort or in vitro biofilm models that better represent the microbial diversity of oral cavity. Here, by employing a clinical cohort and a saliva-derived biofilm model, we demonstrated that arginine treatment could favorably modulate the oral microbiota of caries-active individuals. Specifically, treatment with arginine-containing dentifrice normalized the oral microbiota of caries-active individuals similar to that of caries-free controls in terms of microbial structure, abundance of typical species, enzymatic activities of glycolysis and alkali-generation related enzymes and their corresponding transcripts. Moreover, we found that combinatory use of arginine with fluoride could better enrich alkali-generating Streptococcus sanguinis and suppress acidogenic/aciduric Streptococcus mutans, and thus significantly retard the demineralizing capability of saliva-derived oral biofilm. Hence, we propose that fluoride and arginine have a potential synergistic effect in maintaining an eco-friendly oral microbial equilibrium in favor of better caries management.

Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target.

Science.gov (United States)

Watson, Gabrielle M; Lucas, William A H; Gunzburg, Menachem J; Wilce, Jacqueline A

2017-01-01

Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

Directory of Open Access Journals (Sweden)

Gabrielle M. Watson

2017-09-01

Full Text Available Growth factor receptor bound protein 7 (Grb7 is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine, however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors.

Insight into the Selectivity of the G7-18NATE Inhibitor Peptide for the Grb7-SH2 Domain Target

Science.gov (United States)

Watson, Gabrielle M.; Lucas, William A. H.; Gunzburg, Menachem J.; Wilce, Jacqueline A.

2017-01-01

Growth factor receptor bound protein 7 (Grb7) is an adaptor protein with established roles in the progression of both breast and pancreatic cancers. Through its C-terminal SH2 domain, Grb7 binds to phosphorylated tyrosine kinases to promote proliferative and migratory signaling. Here, we investigated the molecular basis for the specificity of a Grb7 SH2-domain targeted peptide inhibitor. We identified that arginine 462 in the BC loop is unique to Grb7 compared to Grb2, another SH2 domain bearing protein that shares the same consensus binding motif as Grb7. Using surface plasmon resonance we demonstrated that Grb7-SH2 binding to G7-18NATE is reduced 3.3-fold when the arginine is mutated to the corresponding Grb2 amino acid. The reverse mutation in Grb2-SH2 (serine to arginine), however, was insufficient to restore binding of G7-18NATE to Grb2-SH2. Further, using a microarray, we confirmed that G7-18NATE is specific for Grb7 over a panel of 79 SH2 domains, and identified that leucine at the βD6 position may also be a requirement for Grb7-SH2 binding. This study provides insight into the specificity defining features of Grb7 for the inhibitor molecule G7-18NATE, that will assist in the development of improved Grb7 targeted inhibitors. PMID:29018805

UV resonance Raman finds peptide bond-Arg side chain electronic interactions.

Science.gov (United States)

Sharma, Bhavya; Asher, Sanford A

2011-05-12

We measured the UV resonance Raman excitation profiles and Raman depolarization ratios of the arginine (Arg) vibrations of the amino acid monomer as well as Arg in the 21-residue predominantly alanine peptide AAAAA(AAARA)(3)A (AP) between 194 and 218 nm. Excitation within the π → π* peptide bond electronic transitions result in UVRR spectra dominated by amide peptide bond vibrations. The Raman cross sections and excitation profiles indicate that the Arg side chain electronic transitions mix with the AP peptide bond electronic transitions. The Arg Raman bands in AP exhibit Raman excitation profiles similar to those of the amide bands in AP which are conformation specific. These Arg excitation profiles distinctly differ from the Arg monomer. The Raman depolarization ratios of Arg in monomeric solution are quite simple with ρ = 0.33 indicating enhancement by a single electronic transition. In contrast, we see very complex depolarization ratios of Arg in AP that indicate that the Arg residues are resonance enhanced by multiple electronic transitions.

The signal peptide-like segment of hpaXm is required for its association to the cell wall in transgenic tobacco plants.

Science.gov (United States)

Li, Le; Miao, Weiguo; Liu, Wenbo; Zhang, Shujian

2017-01-01

Harpins, encoded by hrp (hypersensitive response and pathogenicity) genes of Gram-negative plant pathogens, are elicitors of hypersensitive response (HR). HpaXm is a novel harpin-like protein described from cotton leaf blight bacteria, Xanthomonas citri subsp. malvacearum-a synonym of X. campestris pv. malvacearum (Smith 1901-1978). A putative signal peptide (1-MNSLNTQIGANSSFL-15) of hpaXm was predicted in the nitroxyl-terminal (N-terminal)by SignalP (SignalP 3.0 server). Here, we explored the function of the N-terminal leader peptide like segment of hpaXm using transgenic tobacco (Nicotiana tabacum cv. Xanthi nc.). Transgenic tobacco lines expressing the full-length hpaXm and the signal peptide-like segment-deleted mutant hpaXmΔLP were developed using transformation mediated by Agrobacterium tumefaciens. The target genes were confirmed integrated into the tobacco genomes and expressed normally. Using immune colloidal-gold detection technique, hpaXm protein was found to be transferred to the cytoplasm, the cell membrane, and organelles such as chloroplasts, mitochondria, and nucleus, as well as the cell wall. However, the deletion mutant hpaXmΔLP expressed in transgenic tobacco was found unable to cross the membrane to reach the cell wall. Additionally, soluble proteins extracted from plants transformed with hpaXm and hpaXmΔLP were bio-active. Defensive micro-HR induced by the transgene expression of hpaXm and hpaXmΔLP were observed on transgenic tobacco leaves. Disease resistance bioassays to tobacco mosaic virus (TMV) showed that tobacco plants transformed with hpaXm and with hpaXmΔLP exhibited enhanced resistance to TMV. In summary, the N-terminal signal peptide-like segment (1-45 bp) in hpaXm sequence is not necessary for transgene expression, bioactivity of hpaXm and resistance to TMV in transgenic tobacco, but is required for the protein to be translocated to the cell wall.

Methyleneation of peptides by N,N,N,N-tetramethylethylenediamine (TEMED) under conditions used for free radical polymerization: a mechanistic study.

Science.gov (United States)

Shirangi, Mehrnoosh; Sastre Toraño, Javier; Sellergren, Börje; Hennink, Wim E; Somsen, Govert W; van Nostrum, Cornelus F

2015-01-21

Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS(2) and LC-MS(3) were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization.

Calcium Sensing Receptor Mutations Implicated in Pancreatitis and Idiopathic Epilepsy Syndrome Disrupt an Arginine-rich Retention Motif

Science.gov (United States)

Stepanchick, Ann; McKenna, Jennifer; McGovern, Olivia; Huang, Ying; Breitwieser, Gerda E.

2010-01-01

Calcium sensing receptor (CaSR) mutations implicated in familial hypocalciuric hypercalcemia, pancreatitis and idiopathic epilepsy syndrome map to an extended arginine-rich region in the proximal carboxyl terminus. Arginine-rich motifs mediate endoplasmic reticulum retention and/or retrieval of multisubunit proteins so we asked whether these mutations, R886P, R896H or R898Q, altered CaSR targeting to the plasma membrane. Targeting was enhanced by all three mutations, and Ca2+-stimulated ERK1/2 phosphorylation was increased for R896H and R898Q. To define the role of the extended arginine-rich region in CaSR trafficking, we independently determined the contributions of R890/R891 and/or R896/K897/R898 motifs by mutation to alanine. Disruption of the motif(s) significantly increased surface expression and function relative to wt CaSR. The arginine-rich region is flanked by phosphorylation sites at S892 (protein kinase C) and S899 (protein kinase A). The phosphorylation state of S899 regulated recognition of the arginine-rich region; S899D showed increased surface localization. CaSR assembles in the endoplasmic reticulum as a covalent disulfide-linked dimer and we determined whether retention requires the presence of arginine-rich regions in both subunits. A single arginine-rich region within the dimer was sufficient to confer intracellular retention comparable to wt CaSR. We have identified an extended arginine-rich region in the proximal carboxyl terminus of CaSR (residues R890 - R898) which fosters intracellular retention of CaSR and is regulated by phosphorylation. Mutation(s) identified in chronic pancreatitis and idiopathic epilepsy syndrome therefore increase plasma membrane targeting of CaSR, likely contributing to the altered Ca2+ signaling characteristic of these diseases. PMID:20798521

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms.

Science.gov (United States)

Zhang, Hong-Feng; Dai, Yu-Chuan; Wu, Jing; Jia, Mei-Xiang; Zhang, Ji-Shui; Shou, Xiao-Jing; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2016-10-01

Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The "twin" nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

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Saskia J. H. Brinkmann

2015-05-01

Full Text Available Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS and thereby nitric oxide (NO, respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9, standard rabbit chow plus atorvastatin (group S, n = 8, standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8 or standard rabbit chow (group C, n = 9 as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques.

Strategies for the solid-phase diversification of poly-L-proline-type II peptide mimic scaffolds and peptide scaffolds through guanidinylation.

Science.gov (United States)

Flemer, Stevenson; Wurthmann, Alexander; Mamai, Ahmed; Madalengoitia, José S

2008-10-03

A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.

NCBI nr-aa BLAST: CBRC-MEUG-01-2295 [SEVENS

Lifescience Database Archive (English)

Full Text Available CBRC-MEUG-01-2295 ref|ZP_05041983.1| twin arginine-targeting protein translocase Ta...tC [Alcanivorax sp. DG881] gb|EDX89404.1| twin arginine-targeting protein translocase TatC [Alcanivorax sp. DG881] ZP_05041983.1 0.30 30% ...

Bioinformatic evaluation of L-arginine catabolic pathways in 24 cyanobacteria and transcriptional analysis of genes encoding enzymes of L-arginine catabolism in the cyanobacterium Synechocystis sp. PCC 6803

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Pistorius Elfriede K

2007-11-01

Full Text Available Abstract Background So far very limited knowledge exists on L-arginine catabolism in cyanobacteria, although six major L-arginine-degrading pathways have been described for prokaryotes. Thus, we have performed a bioinformatic analysis of possible L-arginine-degrading pathways in cyanobacteria. Further, we chose Synechocystis sp. PCC 6803 for a more detailed bioinformatic analysis and for validation of the bioinformatic predictions on L-arginine catabolism with a transcript analysis. Results We have evaluated 24 cyanobacterial genomes of freshwater or marine strains for the presence of putative L-arginine-degrading enzymes. We identified an L-arginine decarboxylase pathway in all 24 strains. In addition, cyanobacteria have one or two further pathways representing either an arginase pathway or L-arginine deiminase pathway or an L-arginine oxidase/dehydrogenase pathway. An L-arginine amidinotransferase pathway as a major L-arginine-degrading pathway is not likely but can not be entirely excluded. A rather unusual finding was that the cyanobacterial L-arginine deiminases are substantially larger than the enzymes in non-photosynthetic bacteria and that they are membrane-bound. A more detailed bioinformatic analysis of Synechocystis sp. PCC 6803 revealed that three different L-arginine-degrading pathways may in principle be functional in this cyanobacterium. These are (i an L-arginine decarboxylase pathway, (ii an L-arginine deiminase pathway, and (iii an L-arginine oxidase/dehydrogenase pathway. A transcript analysis of cells grown either with nitrate or L-arginine as sole N-source and with an illumination of 50 μmol photons m-2 s-1 showed that the transcripts for the first enzyme(s of all three pathways were present, but that the transcript levels for the L-arginine deiminase and the L-arginine oxidase/dehydrogenase were substantially higher than that of the three isoenzymes of L-arginine decarboxylase. Conclusion The evaluation of 24

Monochorionic twin pregnancies

NARCIS (Netherlands)

Hack, K.E.A.

2008-01-01

Following widespread application of assisted reproductive technology modalities and the increased age of motherhood, the incidence of twin gestations has increased markedly. Twins are either monozygotic or dizygotic. Dizygotic (i.e. fraternal) twins result from the fertilization of two different

Membrane interaction and secondary structure of de novo designed arginine-and tryptophan peptides with dual function

KAUST Repository

Rydberg, Hanna A.; Carlsson, Nils; Nordé n, Bengt

2012-01-01

of arg/trp peptides and investigated how the position and number of tryptophans affect cellular uptake. Here we explore the antimicrobial properties and the interaction with lipid model membranes of these peptides, using minimal inhibitory concentrations

Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

Science.gov (United States)

Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2016-11-01

Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

Estimating twin concordance for bivariate competing risks twin data

DEFF Research Database (Denmark)

Scheike, Thomas; Holst, Klaus K.; Hjelmborg, Jacob B.

2014-01-01

For twin time-to-event data, we consider different concordance probabilities, such as the casewise concordance that are routinely computed as a measure of the lifetime dependence/correlation for specific diseases. The concordance probability here is the probability that both twins have experience...... events with the competing risk death. We thus aim to quantify the degree of dependence through the casewise concordance function and show a significant genetic component...... the event of interest. Under the assumption that both twins are censored at the same time, we show how to estimate this probability in the presence of right censoring, and as a consequence, we can then estimate the casewise twin concordance. In addition, we can model the magnitude of within pair dependence...... over time, and covariates may be further influential on the marginal risk and dependence structure. We establish the estimators large sample properties and suggest various tests, for example, for inferring familial influence. The method is demonstrated and motivated by specific twin data on cancer...

The role of arginine and the modified arginine deiminase enzyme ADI-PEG 20 in cancer therapy with special emphasis on Phase I/II clinical trials.

Science.gov (United States)

Synakiewicz, Anna; Stachowicz-Stencel, Teresa; Adamkiewicz-Drozynska, Elzbieta

2014-11-01

The metabolic differences between normal, healthy cells and neoplastic cells have been exploited by anticancer therapies targeting metabolic pathways. Various studies of malignant processes have demonstrated disturbances in both arginine synthesis and metabolism that enhance or inhibit tumor cell growth. Consequently, there has been an increased interest in the arginine-depleting enzyme arginine deiminase (ADI) as a potential antineoplastic therapy. This review summarizes the literature on the potential anti-cancer therapeutics arginine and ADI, an arginine-catabolizing enzyme. The authors searched the MEDLINE database PubMed using the key words: 'arginine, 'ADI', 'arginine in cancer' and 'ADI and cancer'. The authors evaluate prospective randomized studies on cancer patients between 2004 and 2013 as well as ongoing research found through the US National Institutes of Health trial database. The results of current studies are promising but do not give unequivocal answers and so it is impossible to recommend arginine or its enzyme ADI as a therapeutic. In the opinion of the authors, further identification of arginine-dependent malignant tumors and their metabolism should be investigated. Furthermore, the use of these chemicals, in combination with other chemotherapeutics drugs, should be investigated and indeed may improve the success of arginine-depleting enzymes such as pegylated ADI (ADI-PEG20).

Predicting Secretory Proteins with SignalP

DEFF Research Database (Denmark)

Nielsen, Henrik

2017-01-01

SignalP is the currently most widely used program for prediction of signal peptides from amino acid sequences. Proteins with signal peptides are targeted to the secretory pathway, but are not necessarily secreted. After a brief introduction to the biology of signal peptides and the history...

Modeling acardiac twin pregnancies

NARCIS (Netherlands)

de Groot, Rosa; van den Wijngaard, Jeroen P. H. M.; Umur, Asli; Beek, Johan F.; Nikkels, Peter G. J.; van Gemert, Martin J. C.

2007-01-01

Acardiac twin pregnancies are a rare but severe complication of monochorionic twinning, where the acardiac twin lacks cardiac function but nevertheless grows during pregnancy because it is perfused by the pump twin through a set of placental arterioarterial and venovenous anastomoses. Because the

Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres

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Chang R

2015-05-01

Full Text Available Run Chang,1 Linlin Sun,1 Thomas J Webster1,2 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs with diameters of 10–20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective

L-Arginine Supplementation and Metabolism in Asthma

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Angela Linderholm

2011-01-01

Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

Arginine Adjunctive Therapy in Active Tuberculosis

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Aliasghar Farazi

2015-01-01

Full Text Available Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18. Results. Arginine supplementation reduced constitutional symptoms (P=0.032 in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P=0.032 and P=0.04 and a reduced CRP at the end of the first month of treatment (P=0.03 versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2.

New dendrimer - Peptide host - Guest complexes: Towards dendrimers as peptide carriers

DEFF Research Database (Denmark)

Boas, Ulrik; Sontjens, S.H.M.; Jensen, Knud Jørgen

2002-01-01

Adamantyl urea and adamantyl thiourea modified poly(propylene imine) dendrimers act as hosts for N-terminal tert-butoxycarbonyl (Boc)-protected peptides and form chloroform-soluble complexes. investigations with NMR spectroscopy show that the peptide is bound to the dendrimer by ionic interactions...... between the dendrimer outer shell tertiary amines and the C-terminal carboxylic acid of the peptide, and also through host-urea to peptide-amide hydrogen bonding. The hydrogen-bonding nature of the peptide dendrimer interactions was further confirmed by using Fourier transform IR spectroscopy, for which...... the NH- and CO-stretch signals of the peptide amide moieties shift towards lower wave-numbers upon complexation with the dendrimer. Spatial analysis of the complexes with NOESY spectroscopy generally shows close proximity of the N-terminal Boc group of the peptide to the peripheral adamantyl groups...

Personality and birth order in monozygotic twins adopted apart: a test of Sulloway's theory; Research Reviews: twin births and cancer risk in mothers, male sexual dysfunction, twin study of ultimatum game behavior; Human Interest: 'The Land of Twins', twin-like reunion-I, twin-like reunion-II.

Science.gov (United States)

Segal, Nancy L

2008-02-01

A brief overview of Sulloway's (1996) theory of birth order and personality is presented. A reared apart twin approach for testing his personality findings regarding openness to experience and conscientiousness in first borns and later borns is described. This is followed by summaries of three recent twin studies. The topics include cancer risk in mother of twins, sexual dysfunction in males and responder behavior during ultimatum games. This article concludes with a discussion of twinning rates and rituals among the Yoruba of western Nigeria, and descriptions of two unusual reunions between siblings and twins.

The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution fixes the conformation of the C-terminal peptide

DEFF Research Database (Denmark)

Charrel-Dennis, Marie; Terrazzini, Nadia; McBride, Jeffrey D

2005-01-01

Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross...

Signaling pathways involved in renal oxidative injury: role of the vasoactive peptides and the renal dopaminergic system.

Science.gov (United States)

Rukavina Mikusic, N L; Kravetz, M C; Kouyoumdzian, N M; Della Penna, S L; Rosón, M I; Fernández, B E; Choi, M R

2014-01-01

The physiological hydroelectrolytic balance and the redox steady state in the kidney are accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between antinatriuretic and natriuretic factors. Angiotensin II, atrial natriuretic peptide and intrarenal dopamine play a pivotal role in this interactive network. The balance between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide, by one side, and the prooxidant effect of the renin angiotensin system, by the other side, contributes to ensuring the normal function of the kidney. Different pathological scenarios, as nephrotic syndrome and hypertension, where renal sodium excretion is altered, are associated with an impaired interaction between two natriuretic systems as the renal dopaminergic system and atrial natriuretic peptide that may be involved in the pathogenesis of renal diseases. The aim of this review is to update and comment the most recent evidences about the intracellular pathways involved in the relationship between endogenous antioxidant agents like the renal dopaminergic system and atrial natriuretic peptide and the prooxidant effect of the renin angiotensin system in the pathogenesis of renal inflammation.

Neuropeptide delivery to the brain: a von Willebrand factor signal peptide to direct neuropeptide secretion

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de Backer Marijke WA

2010-08-01

Full Text Available Abstract Background Multiple neuropeptides, sometimes with opposing functions, can be produced from one precursor gene. To study the roles of the different neuropeptides encoded by one large precursor we developed a method to overexpress minigenes and establish local secretion. Results We fused the signal peptide from the Von Willebrand Factor (VWF to a furin site followed by a processed form of the Agouti related protein (AgRP, AgRP83-132 or α-melanocyte stimulating hormone. In vitro, these minigenes were secreted and biologically active. Additionally, the proteins of the minigenes were not transported into projections of primary neurons, thereby ensuring local release. In vivo administration of VWF-AgRP83-132 , using an adeno-associated viral vector as a delivery vehicle, into the paraventricular hypothalamus increased body weight and food intake of these rats compared to rats which received a control vector. Conclusions This study demonstrated that removal of the N-terminal part of full length AgRP and addition of a VWF signal peptide is a successful strategy to deliver neuropeptide minigenes to the brain and establish local neuropeptide secretion.

Arginine affects appetite via nitric oxide in ducks.

Science.gov (United States)

Wang, C; Hou, S S; Huang, W; Xu, T S; Rong, G H; Xie, M

2014-08-01

The objective of the study was to investigate the mechanism by which arginine regulates feed intake in Pekin ducks. In experiment 1, one hundred forty-four 1-d-old male Pekin ducks were randomly allotted to 3 dietary treatments with 6 replicate pens of 8 birds per pen. Birds in each group were fed a corn-corn gluten meal diet containing 0.65, 0.95, and 1.45% arginine. Ducks fed the diet containing 0.65% arginine had lower feed intake and plasma nitric oxide level (P ducks were allotted to 1 of 2 treatments. After 2 h fasting, birds in the 2 groups were intraperitoneally administrated saline and l-NG-nitro-arginine methyl ester HCl (L-NAME) for 3 d, respectively. Feed intake (P study implied that arginine modifies feeding behavior possibly through controlling endogenous synthesis of nitric oxide in Pekin ducks. © Poultry Science Association Inc.

Secretion of a recombinant protein without a signal peptide by the exocrine glands of transgenic rabbits.

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Andrea Kerekes

Full Text Available Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG promoter. Despite the absence of a signal peptide, the fluorophore protein was readily detected in milk, tear, saliva and seminal fluids. The expression pattern was verified by Western blot analysis. Mammary gland epithelial cells of SB-CAG-Venus transgenic lactating does also showed Venus-specific expression by tissue histology and fluorescence microscopy. In summary, the SB-CAG-Venus transgenic rabbits secrete the recombinant protein by different glands. This finding has relevance not only for the understanding of the biological function of exocrine glands, but also for the design of constructs for expression of recombinant proteins in dairy animals.

Secretion of a recombinant protein without a signal peptide by the exocrine glands of transgenic rabbits.

Science.gov (United States)

Kerekes, Andrea; Hoffmann, Orsolya Ivett; Iski, Gergely; Lipták, Nándor; Gócza, Elen; Kues, Wilfried A; Bősze, Zsuzsanna; Hiripi, László

2017-01-01

Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB) transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG) promoter. Despite the absence of a signal peptide, the fluorophore protein was readily detected in milk, tear, saliva and seminal fluids. The expression pattern was verified by Western blot analysis. Mammary gland epithelial cells of SB-CAG-Venus transgenic lactating does also showed Venus-specific expression by tissue histology and fluorescence microscopy. In summary, the SB-CAG-Venus transgenic rabbits secrete the recombinant protein by different glands. This finding has relevance not only for the understanding of the biological function of exocrine glands, but also for the design of constructs for expression of recombinant proteins in dairy animals.

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

Science.gov (United States)

Rana, Brinda K.; Stenger, Michael B.; Lee, Stuart M. C.; Macias, Brandon R.; Siamwala, Jamila; Piening, Brian Donald; Hook, Vivian; Ebert, Doug; Patel, Hemal; Smith, Scott;

Compartmentalization of NO signaling cascade in skeletal muscles

International Nuclear Information System (INIS)

Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

2005-01-01

Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

The nature of pseudo-twinning modes on the basis of a twin classification scheme

International Nuclear Information System (INIS)

Singh, Jung B.; Sundararaman, M.; Krishnan, M.

2011-01-01

Pseudo-twins can form in ordered structures under high stress conditions. These twins are defined by lattice sites that are at twin positions but are incorrectly occupied by different species of atoms. The present note discusses if it is possible to further classify pseudo-twins into different modes based on the nature of associated twinning elements.

Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

International Nuclear Information System (INIS)

Wang, Biao; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Liu, Yang

2015-01-01

Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

Copper-induced tight junction mRNA expression changes, apoptosis and antioxidant responses via NF-κB, TOR and Nrf2 signaling molecules in the gills of fish: Preventive role of arginine

Energy Technology Data Exchange (ETDEWEB)

Wang, Biao [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Feng, Lin; Jiang, Wei-Dan [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Wu, Pei [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Kuang, Sheng-Yao [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Jiang, Jun [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Tang, Ling; Tang, Wu-Neng [Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan (China); Zhang, Yong-An [Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Liu, Yang, E-mail: kyckgk@hotmail.com [Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu 611130, Sichuan (China); and others

2015-01-15

Highlights: • Cu exposure induced oxidative stress via disruption of antioxidant system. • Cu exposure disrupted TJ mRNA expression through regulation of cytokines in fish. • Cu induced gill apoptosis partly via intrinsic pathway but not extrinsic pathway. • Cu exposure can regulate Nrf2, NF-κB and TOR signaling molecules in fish. • Arginine can effectively prevent Cu-induced fish gill damage. - Abstract: This study explored the possible preventive effects of dietary arginine on copper (Cu)-induced tight junction mRNA expression changes, apoptosis and antioxidant responses in the gills of young grass carp (Ctenopharyngodon idella). The results indicated that exposure to 0.7 mg/L (11.01 μmol/L) Cu for 96 h induced the production of reactive oxygen species (ROS), thereby increasing protein oxidation, lipid peroxidation and DNA damage in the gills of fish. However, these oxidative effects were prevented by arginine supplementation. Arginine also prevented the toxic effects of Cu on the activities of copper/zinc superoxide dismutase (SOD1), glutathione-S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR) and the glutathione (GSH) content (P < 0.05). However, Cu induced an adaptive increase in the activity of catalase (CAT), and arginine supplementation further increased CAT activity (P < 0.05). Moreover, Cu induced increases in the relative mRNA expressions of SOD1, CAT, GPx, GST, caspase-3, caspase-9, NF-E2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1a (Keap1a), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8), transforming growth factor-β (TGF-β) and nuclear transcription factor-κB p65 (NF-κB p65) in the gills of grass carp (P < 0.05). In contrast, the relative mRNA expression levels of occludin, zonula occludens-1 (ZO-1), claudin b, claudin 3, claudin 12, target of rapamycin (TOR) and inhibitor factor κBα (IκBα) in the gills were decreased by Cu (P < 0.05). However, pre

Clinical significance of the radioimmunological determination of C-peptide

International Nuclear Information System (INIS)

Dudczak, R.; Waldhaeusl, W.

1979-01-01

The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg,t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419 - 0.33 g/kg intravenously). In the majority of ''stable'' diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In ''unstable'' diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in ''stable'' diabetics (p < 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially ''unstable'' diabetics in need of strict observation, which would minimize the risks of bad metabolic control. (author)

Clinical significance of the radioimmunological determination of C-peptide

Energy Technology Data Exchange (ETDEWEB)

Dudczak, R; Waldhaeusl, W [Vienna Univ. (Austria). 1. Medizinische Klinik

1979-10-12

The aim of this study was to investigate the relationship of metabolic control to insulinogenic reserve in insulin-dependent diabetics. Thus, the secretory reserve of the pancreatic beta cell was estimated in insulin-dependent diabetics by measuring changes in peripheral serum immunoreactive C-peptide (IRCP) concentrations in response to intravenous arginine (n = 19; 0.5 g/kg,t = 30 min) or glibenclamide-glucose (n = 6; 2 mg HB 419 - 0.33 g/kg intravenously). In the majority of stable diabetics a small secretory reserve of the beta cell was demonstrated, but both the absolute and relative increase in IRCP was reduced after intravenous arginine or glibenclamide-glucose in comparison with normal controls. In unstable diabetics a decreased basal concentration of IRCP, significantly smaller than that seen in stable diabetics (p < 0.01), was accompanied by a complete lack of IRCP release on intravenous arginine administration. Thus, we conclude that the radioimmunological determination of IRCP is of clinical interest in assessing the residual secretory capacity of the beta cell in insulin-dependent diabetics. In revealing a lack of insulin this diagnostic tool seems to detect a group of potentially unstable diabetics in need of strict observation, which would minimize the risks of bad metabolic control.

Combinatorial effects of arginine and fluoride on oral bacteria.

Science.gov (United States)

Zheng, X; Cheng, X; Wang, L; Qiu, W; Wang, S; Zhou, Y; Li, M; Li, Y; Cheng, L; Li, J; Zhou, X; Xu, X

2015-02-01

Dental caries is closely associated with the microbial disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal residents within the dental plaque. Fluoride is a widely used anticaries agent, which promotes tooth hard-tissue remineralization and suppresses bacterial activities. Recent clinical trials have shown that oral hygiene products containing both fluoride and arginine possess a greater anticaries effect compared with those containing fluoride alone, indicating synergy between fluoride and arginine in caries management. Here, we hypothesize that arginine may augment the ecological benefit of fluoride by enriching alkali-generating bacteria in the plaque biofilm and thus synergizes with fluoride in controlling dental caries. Specifically, we assessed the combinatory effects of NaF/arginine on planktonic and biofilm cultures of Streptococcus mutans, Streptococcus sanguinis, and Porphyromonas gingivalis with checkerboard microdilution assays. The optimal NaF/arginine combinations were selected, and their combinatory effects on microbial composition were further examined in single-, dual-, and 3-species biofilm using bacterial species-specific fluorescence in situ hybridization and quantitative polymerase chain reaction. We found that arginine synergized with fluoride in suppressing acidogenic S. mutans in both planktonic and biofilm cultures. In addition, the NaF/arginine combination synergistically reduced S. mutans but enriched S. sanguinis within the multispecies biofilms. More importantly, the optimal combination of NaF/arginine maintained a "streptococcal pressure" against the potential growth of oral anaerobe P. gingivalis within the alkalized biofilm. Taken together, we conclude that the combinatory application of fluoride and arginine has a potential synergistic effect in maintaining a healthy oral microbial equilibrium and thus represents a promising ecological approach to caries management. © International & American

Primary assimilation process of triply (/sup 15/N, /sup 14/C and /sup 3/H) labeled arginine in the roots of arginine-fed barley

Energy Technology Data Exchange (ETDEWEB)

Mori, Satoshi [Tokyo Univ. (Japan). Faculty of Agriculture

1981-03-01

To clarify the mechanism of arginine utilization in barley roots, triply labeled (ureido-/sup 15/N, ureido-/sup 14/C and 5-/sup 3/H) arginine was applied to plants precultured with arginine (Arg-plants). (5-/sup 3/H) Arginine was incorporated mainly into ornithine, suggesting that arginase contributes in the first step of arginine metabolism. The arginase activity in the tissues was greatly enhanced by continuous supply of arginine, whereas urease activity was not by the same treatment. The amount of /sup 14/CO/sub 2/ evolved from (ureido-/sup 14/C) arginine in the Arg-plants was several times higher than that in plants treated with NO/sub 3//sup -/(NO/sub 3/-plants), and most /sup 14/C-urea exogenously supplied to detached roots of Arg-plants was immediately decomposed to /sup 14/CO/sub 2/. The urea released from arginine by arginase was cleaved to /sup 15/NH/sub 4//sup +/ + /sup 14/CO/sub 2/ by urease. Most of the /sup 14/CO/sub 2/ was then lost from the root system. On the other hand, the released /sup 15/NH/sub 4//sup +/ was reassimilated into amino acids probably through the pathway of ammonia assimilation. Released (5-/sup 3/H) ornithine was metabolized dominantly to proline.

Twin-to-twin transfusion syndrome : from placental anastomoses to long-term outcome

NARCIS (Netherlands)

Lopriore, Enrico

2006-01-01

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies associated with high perinatal mortality and morbidity rates. Placental vascular anastomoses, almost invariably present in monochorionic placentas, are the essential anatomical substrate for the

Is that me or my twin? Lack of self-face recognition advantage in identical twins.

Directory of Open Access Journals (Sweden)

Matteo Martini

Full Text Available Despite the increasing interest in twin studies and the stunning amount of research on face recognition, the ability of adult identical twins to discriminate their own faces from those of their co-twins has been scarcely investigated. One's own face is the most distinctive feature of the bodily self, and people typically show a clear advantage in recognizing their own face even more than other very familiar identities. Given the very high level of resemblance of their faces, monozygotic twins represent a unique model for exploring self-face processing. Herein we examined the ability of monozygotic twins to distinguish their own face from the face of their co-twin and of a highly familiar individual. Results show that twins equally recognize their own face and their twin's face. This lack of self-face advantage was negatively predicted by how much they felt physically similar to their co-twin and by their anxious or avoidant attachment style. We speculate that in monozygotic twins, the visual representation of the self-face overlaps with that of the co-twin. Thus, to distinguish the self from the co-twin, monozygotic twins have to rely much more than control participants on the multisensory integration processes upon which the sense of bodily self is based. Moreover, in keeping with the notion that attachment style influences perception of self and significant others, we propose that the observed self/co-twin confusion may depend upon insecure attachment.

Twin RSA

OpenAIRE

Lenstra, Arjen K.; Weger, De; Benjamin, M. M.

2005-01-01

We introduce Twin RSA, pairs of RSA moduli (n, n+ 2), and formulate several questions related to it. Our main questions are: is Twin RSA secure, and what is it good for? © Springer-Verlag Berlin Heidelberg 2005.

Effective intracellular inhibition of the cAMP-dependent protein kinase by microinjection of a modified form of the specific inhibitor peptide PKi in living fibroblasts.

Science.gov (United States)

Fernandez, A; Mery, J; Vandromme, M; Basset, M; Cavadore, J C; Lamb, N J

1991-08-01

In order to obtain a peptide retaining its biological activity following microinjection into living cells, we have modified a synthetic peptide [PKi(m)(6-24)], derived from the specific inhibitor protein of the cAMP-dependent protein kinase (A-kinase) in two ways: (1) substitution of the arginine at position 18 for a D-arginine; (2) blockade of the side chain on the C-terminal aspartic acid by a cyclohexyl ester group. In an in vitro assay, PKi(m) has retained a specific inhibitory activity against A-kinase as assessed against six other kinases, with similar efficiency to that of the unmodified PKi(5-24) peptide. Microinjection of PKi(m) into living fibroblasts reveals its capacity to prevent the changes in cell morphology and cytoskeleton induced by drugs which activate endogenous A-kinase, whereas the original PKi peptide failed to do so. This inhibition of A-kinase in vivo by PKi(m) lasts between 4 and 6 h after injection. In light of its effective half-life, this modified peptide opens a route for the use of biologically active peptides in vivo, an approach which has been hampered until now by the exceedingly short half-life of peptides inside living cells. By providing a direct means of inhibiting A-kinase activity for sufficiently long periods to observe effects on cellular functions in living cells, PKi(m) represents a powerful tool in studying the potential role of cAMP-dependent phosphorylation in vivo.

Arginine Improves pH Homeostasis via Metabolism and Microbiome Modulation.

Science.gov (United States)

Agnello, M; Cen, L; Tran, N C; Shi, W; McLean, J S; He, X

2017-07-01

Dental caries can be described as a dysbiosis of the oral microbial community, in which acidogenic, aciduric, and acid-adapted bacterial species promote a pathogenic environment, leading to demineralization. Alkali generation by oral microbes, specifically via arginine catabolic pathways, is an essential factor in maintaining plaque pH homeostasis. There is evidence that the use of arginine in dentifrices helps protect against caries. The aim of the current study was to investigate the mechanistic and ecological effect of arginine treatment on the oral microbiome and its regulation of pH dynamics, using an in vitro multispecies oral biofilm model that was previously shown to be highly reflective of the in vivo oral microbiome. Pooled saliva from 6 healthy subjects was used to generate overnight biofilms, reflecting early stages of biofilm maturation. First, we investigated the uptake of arginine by the cells of the biofilm as well as the metabolites generated. We next explored the effect of arginine on pH dynamics by pretreating biofilms with 75 mM arginine, followed by the addition of sucrose (15 mM) after 0, 6, 20, or 48 h. pH was measured at each time point and biofilms were collected for 16S sequencing and targeted arginine quantification, and supernatants were prepared for metabolomic analysis. Treatment with only sucrose led to a sustained pH drop from 7 to 4.5, while biofilms treated with sucrose after 6, 20, or 48 h of preincubation with arginine exhibited a recovery to higher pH. Arginine was detected within the cells of the biofilms, indicating active uptake, and arginine catabolites citrulline, ornithine, and putrescine were detected in supernatants, indicating active metabolism. Sequencing analysis revealed a shift in the microbial community structure in arginine-treated biofilms as well as increased species diversity. Overall, we show that arginine improved pH homeostasis through a remodeling of the oral microbial community.

Penetration of the signal sequence of Escherichia coli PhoE protein into phospholipid model membranes leads to lipid-specific changes in signal peptide structure and alterations of lipid organization

International Nuclear Information System (INIS)

Batenburg, A.M.; Demel, R.A.; Verkleij, A.J.; de Kruijff, B.

1988-01-01

In order to obtain more insight in the initial steps of the process of protein translocation across membranes, biophysical investigations were undertaken on the lipid specificity and structural consequences of penetration of the PhoE signal peptide into lipid model membranes and on the conformation of the signal peptide adopted upon interaction with the lipids. When the monolayer technique and differential scanning calorimetry are used, a stronger penetration is observed for negatively charged lipids, significantly influenced by the physical state of the lipid but not by temperature or acyl chain unsaturation as such. Although the interaction is principally electrostatic, as indicated also by the strong penetration of N-terminal fragments into negatively charged lipid monolayers, the effect of ionic strength suggests an additional hydrophobic component. Most interestingly with regard to the mechanism of protein translocation, the molecular area of the peptide in the monolayer also shows lipid specificity: the area in the presence of PC is consistent with a looped helical orientation, whereas in the presence of cardiolipin a time-dependent conformational change is observed, most likely leading from a looped to a stretched orientation with the N-terminus directed toward the water. This is in line also with the determined peptide-lipid stoichiometry. Preliminary 31 P NMR and electron microscopy data on the interaction with lipid bilayer systems indicate loss of bilayer structure

Sports pairs: insights on athletic talent; research reviews: twins with leukemia; parents and twins.

Science.gov (United States)

Segal, Nancy L

2007-06-01

Twin research exploring genetic and environmental influences on athletic interests and talents is reviewed. Illustrative examples of twin athletes representing a variety of sports activities are presented. This is followed by an overview of twin studies offering critical insights into the onset and progress of leukemia. In the last section, timely events involving twins and parents of twins will be described--each case provides a new look at an old question.

The effect of arginine on oral biofilm communities.

Science.gov (United States)

Nascimento, M M; Browngardt, C; Xiaohui, X; Klepac-Ceraj, V; Paster, B J; Burne, R A

2014-02-01

Alkali production by oral bacteria via the arginine deiminase system (ADS) increases the pH of oral biofilms and reduces the risk for development of carious lesions. This study tested the hypothesis that increased availability of arginine in the oral environment through an exogenous source enhances the ADS activity levels in saliva and dental plaque. Saliva and supra-gingival plaque samples were collected from 19 caries-free (CF) individuals (DMFT = 0) and 19 caries-active (CA) individuals (DMFT ≥ 2) before and after treatment, which comprised the use of a fluoride-free toothpaste containing 1.5% arginine, or a regular fluoride-containing toothpaste twice daily for 4 weeks. ADS activity was measured by quantification of ammonia produced from arginine by oral samples at baseline, after washout period, 4 weeks of treatment, and 2 weeks post-treatment. Higher ADS activity levels were observed in plaque samples from CF compared to those of CA individuals (P = 0.048) at baseline. The use of the arginine toothpaste significantly increased ADS activity in plaque of CA individuals (P = 0.026). The plaque microbial profiles of CA treated with the arginine toothpaste showed a shift in bacterial composition to a healthier community, more similar to that of CF individuals. Thus, an anti-caries effect may be expected from arginine-containing formulations due in large part to the enhancement of ADS activity levels and potential favorable modification to the composition of the oral microbiome. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Brazilian Twin Registry.

Science.gov (United States)

Ferreira, Paulo H; Oliveira, Vinicius C; Junqueira, Daniela R; Cisneros, Lígia C; Ferreira, Lucas C; Murphy, Kate; Ordoñana, Juan R; Hopper, John L; Teixeira-Salmela, Luci F

2016-12-01

The Brazilian Twin Registry (BTR) was established in 2013 and has impelled twin research in South America. The main aim of the initiative was to create a resource that would be accessible to the Brazilian scientific community as well as international researchers interested in the investigation of the contribution of genetic and environmental factors in the development of common diseases, phenotypes, and human behavior traits. The BTR is a joint effort between academic and governmental institutions from Brazil and Australia. The collaboration includes the Federal University of Minas Gerais (UFMG) in Brazil, the University of Sydney and University of Melbourne in Australia, the Australian Twin Registry, as well as the research foundations CNPq and CAPES in Brazil. The BTR is a member of the International Network of Twin Registries. Recruitment strategies used to register twins have been through participation in a longitudinal study investigating genetic and environmental factors for low back pain occurrence, and from a variety of sources including media campaigns and social networking. Currently, 291 twins are registered in the BTR, with data on demographics, zygosity, anthropometrics, and health history having been collected from 151 twins using a standardized self-reported questionnaire. Future BTR plans include the registration of thousands of Brazilian twins identified from different sources and collaborate nationally and internationally with other research groups interested on twin studies.

A neural network method for identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites

DEFF Research Database (Denmark)

Nielsen, Henrik; Engelbrecht, Jacob; Brunak, Søren

1997-01-01

We have developed a new method for the identication of signal peptides and their cleavage sites based on neural networks trained on separate sets of prokaryotic and eukaryotic sequences. The method performs signicantly better than previous prediction schemes, and can easily be applied to genome...

Twin Loss: Implications for Counselors Working with Surviving Twins.(practice & Theory)

Science.gov (United States)

Withrow, Rebecca; Schwiebert, Valerie L.

2005-01-01

Multiple births are becoming increasingly prevalent due to the use of fertility drugs and women choosing to wait until later life to conceive. With the growth in the twin population, little research has been done to investigate the effects on the grief process when 1 twin dies. Counselors must understand the unique experience of twins to formulate…

Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides.

Science.gov (United States)

El Shafey, Nelly; Guesnon, Mickaël; Simon, Françoise; Deprez, Eric; Cosette, Jérémie; Stockholm, Daniel; Scherman, Daniel; Bigey, Pascal; Kichler, Antoine

2016-02-15

Myostatin, also known as growth differentiation factor 8, is a member of the transforming growth factor-beta superfamily that has been shown to play a key role in the regulation of the skeletal muscle mass. Indeed, while myostatin deletion or loss of function induces muscle hypertrophy, its overexpression or systemic administration causes muscle atrophy. Since myostatin blockade is effective in increasing skeletal muscle mass, myostatin inhibitors have been actively sought after. Decorin, a member of the small leucine-rich proteoglycan family is a metalloprotein that was previously shown to bind and inactivate myostatin in a zinc-dependent manner. Furthermore, the myostatin-binding site has been shown to be located in the decorin N-terminal domain. In the present study, we investigated the anti-myostatin activity of short and soluble fragments of decorin. Our results indicate that the murine decorin peptides DCN48-71 and 42-65 are sufficient for inactivating myostatin in vitro. Moreover, we show that the interaction of mDCN48-71 to myostatin is strictly zinc-dependent. Binding of myostatin to activin type II receptor results in the phosphorylation of Smad2/3. Addition of the decorin peptide 48-71 decreased in a dose-dependent manner the myostatin-induced phosphorylation of Smad2 demonstrating thereby that the peptide inhibits the activation of the Smad signaling pathway. Finally, we found that mDCN48-71 displays a specificity towards myostatin, since it does not inhibit other members of the transforming growth factor-beta family. Copyright © 2016 Elsevier Inc. All rights reserved.

Anticancer Activity of Bacterial Proteins and Peptides.

Science.gov (United States)

Karpiński, Tomasz M; Adamczak, Artur

2018-04-30

Despite much progress in the diagnosis and treatment of cancer, tumour diseases constitute one of the main reasons of deaths worldwide. The side effects of chemotherapy and drug resistance of some cancer types belong to the significant current therapeutic problems. Hence, searching for new anticancer substances and medicines are very important. Among them, bacterial proteins and peptides are a promising group of bioactive compounds and potential anticancer drugs. Some of them, including anticancer antibiotics (actinomycin D, bleomycin, doxorubicin, mitomycin C) and diphtheria toxin, are already used in the cancer treatment, while other substances are in clinical trials (e.g., p28, arginine deiminase ADI) or tested in in vitro research. This review shows the current literature data regarding the anticancer activity of proteins and peptides originated from bacteria: antibiotics, bacteriocins, enzymes, nonribosomal peptides (NRPs), toxins and others such as azurin, p28, Entap and Pep27anal2. The special attention was paid to the still poorly understood active substances obtained from the marine sediment bacteria. In total, 37 chemical compounds or groups of compounds with antitumor properties have been described in the present article.

The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides.

Science.gov (United States)

Tsirigos, Konstantinos D; Peters, Christoph; Shu, Nanjiang; Käll, Lukas; Elofsson, Arne

2015-07-01

TOPCONS (http://topcons.net/) is a widely used web server for consensus prediction of membrane protein topology. We hereby present a major update to the server, with some substantial improvements, including the following: (i) TOPCONS can now efficiently separate signal peptides from transmembrane regions. (ii) The server can now differentiate more successfully between globular and membrane proteins. (iii) The server now is even slightly faster, although a much larger database is used to generate the multiple sequence alignments. For most proteins, the final prediction is produced in a matter of seconds. (iv) The user-friendly interface is retained, with the additional feature of submitting batch files and accessing the server programmatically using standard interfaces, making it thus ideal for proteome-wide analyses. Indicatively, the user can now scan the entire human proteome in a few days. (v) For proteins with homology to a known 3D structure, the homology-inferred topology is also displayed. (vi) Finally, the combination of methods currently implemented achieves an overall increase in performance by 4% as compared to the currently available best-scoring methods and TOPCONS is the only method that can identify signal peptides and still maintain a state-of-the-art performance in topology predictions. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Needle twins and right-angled twins in minerals: comparison between experiment and theory

Science.gov (United States)

Salje, E.K.H.; Buckley, A.; Van Tendeloo, G.; Ishibashi, Y.; Nord, G.L.

1998-01-01

Transformation twinning in minerals forms isolated twin walls, intesecting walls with corner junctions, and wedge-shaped twins as elements of hierarchical patterns. When cut perpendicular to the twin walls, the twins have characteristic shapes, right-angled and needle-shaped wall traces, which can be observed by transmission electron microscopy or by optical microscopy. Theoretical geometries of wall shapes recently derived for strain-related systems should hold for most displacive and order-disorder type phase transitions: 1) right-angled twins show curved junctions; 2) needle-shaped twins contain flat wall segments near the needle tip if the elastic behaviour of the mineral is dominated by its anisotroyp; 3) additional bending forces and pinning effects lead to curved walls near the junction that make the needle tip appear more blunt. Bent right-angled twins were analyzed in Gd2(MoO4)3. Linear needle tips were found in WO3, [N(CH3)4]2.ZnBr4 CrAl, BiVO4, GdBa2Cu3O7, and PbZrO. Parabolic tips occur in K2Ba(NO2)4, and GeTe whereas exponential curvatures appear in BaTiO3, KSCN, Pb3(PO4)2, CaTiO3, alkali feldspars, YBa2Cu3O7, and MnAl. The size and shape of the twin microstructure relates to its formation during the phase transition and the subsequent annealing history. The mobility of the twin walls after formation depends not only on the thermal activation but also on the structure of the wall, which may be pinned to impurities on a favorable structural site. Depinnign energies are often large compared with thermal energies for diffusion. This leads to kinetic time scales for twin coarsening that are comparable to geological time scales. Therefore, transformation twins that exhibit needle domains not only indicate that the mineral underwent a structural phase transition but also contain information about its subsequent geological history.

Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

Science.gov (United States)

Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

2018-01-01

The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

Retrieval of ion distributions in RC from TWINS ENA images by CT technique

Science.gov (United States)

Ma, S.; Yan, W.; Xu, L.; Goldstein, J.; McComas, D. J.

2010-12-01

The Two Wide-angle Imaging Neutral-atom Spectrometers (TWINS) mission is the first constellation to employ imagers on two separate spacecraft to measure energetic neutral atoms (ENA) produced by charge exchange between ring current energetic ions and cold exospheric neutral atoms. By applying the 3-D volumetric pixel (voxel) computed tomography (CT) inversion method to TWINS images, parent ion populations in the ring current (RC) and auroral regions are retrieved from their ENA signals. This methodology is implemented for data obtained during the main phase of a moderate geomagnetic storm on 11 October 2008. For this storm the two TWINS satellites were located in nearly the same meridian plane at vantage points widely separated in magnetic local time, and both more than 5 RE geocentric distance from the Earth. In the retrieval process, the energetic ion fluxes to be retrieved are assumed being isotropic with respect to pitch angle. The ENA data used in this study are differential fluxes averaged over 12 sweeps (corresponding to an interval of 16 min.) at different energy levels ranging throughout the full 1--100 keV energy range of TWINS. The ENA signals have two main components: (1) a low-latitude/ high-altitude signal from trapped RC ions and (2) a low-altitude signal from precipitating ions in the auroral/subauroral ionosphere. In the retrieved ion distributions, the main part of the RC component is located around midnight toward dawn sector with L from 3 to 7 or farther, while the subauroral low-altitude component is mainly at pre-midnight. It seems that the dominant energy of the RC ions for this storm is at the lowest energy level of 1-2 keV, with another important energy band centered about 44 keV. The low-altitude component is consistent with in situ observations by DMSP/SSJ4. The result of this study demonstrates that with satellite constellations such as TWINS, using all-sky ENA imagers deployed at multiple vantage points, 3-D distribution of RC ion

Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

Science.gov (United States)

Flynn, K M; Kellihan, H B; Trepanier, L A

2017-08-01

To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the “L-arginine paradox”

International Nuclear Information System (INIS)

Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung

2011-01-01

Highlights: ► Our findings provide a possible solution to the “L-arginine paradox”. ► Extracellular L-arginine concentration is the major determinant of NO production. ► Cellular L-arginine action is limited by cellular ARG transport, not the K m of NOS. ► We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of 15 N 4 -ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, 15 N 4 -ARG, dimethylarginines, and L-citrulline by an LC–MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by 15 N-nitrite or estimated 15 N 3 -citrulline concentrations when 15 N 4 -ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced 15 N 4 -ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by 15 N-nitrite, total nitrite and 15 N 3 -citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside the cell, ARG can no longer gain access to the membrane-bound eNOS. These observations indicate that the “L-arginine paradox” should not consider intracellular ARG

Molecular imaging of a cell-penetrating peptide labeled fluorescein-5-isothiocyanate and MR contrast agents: gadopentetate dimeglumine

International Nuclear Information System (INIS)

Liu Min; Guo Youmin; Duan Xiaoyi; Guo Xiaojuan; Yang Junle; Xu Min

2006-01-01

Objective: To study the value of a new intracellular contrast agent--cell penetrating peptide labeled Fluorescein-5-isothiocyanate (FITC) and MRI contrast agent, Gadopentetate dimeglumine in molecular imaging. Methods: A new cell penetration peptides (CPPs)sequence LAGRRRRRRRRRK were synthesized in solid phase on the base of arginine (9) and were labelled with FITC (CPP 13 -FITC) and Gd - DTPA (CPP 13 -DTPA-Gd). Hepatic carcinoma cell line-HEPG 2 and mouse bone marrow stem cell was respectively stained by CPP 13 -FITC for different time intervals for observing the uptake and intracellular distribution. HEPG 2 in three l00 mm 2 culture plates was respectively incubated with CPP 13 -DTPA-Gd, Gd- DTPA and Dulbecco minimum essential medium for 30 min and imaged by 1.5 T MRI for studying the intracellular uptake and T 1 WI signal characteristics. Results: The peptide was synthesized by the manual solid-phase method successfully. The calculated molecular weight was 1792.78 and the chemical purity was over 95%. By inverted fluorescence microscope, HEPG 2 and mouse stem cell could transport CPP-FITC in cytoplasm and nuclear in 10 min. By MR imaging, CPP-DTPA-Gd could be uptake by HEPG 2 in 30 min and had a short T 1 short T 2 signal, furthermore. T 1 WI signal intensity ratio between in-tube (Ii) and out-tube (Io) in three groups of three scan slices were shown below: Iil/Io of group 1 (Group 1 was the cell incubated by CPP 13 -DTPA-Gd ) respectively was 2.84, 2.60, 2. 48; Iil/Io of group 2 (Group 2 was the cell incubated by DTPA-Gd) respectively is 1.15, 1.11, 1.12; Iil/Io of group 3 (Group 3 was the controled cell ) respectively was 1.15, 1.11, 1.11. By ANVOA analysis, the signal intensity among group 1, group 2 and group 3 had significant difference(F (1,2) = 201.88 P (1,3) =206.37 P (2,3) =0.529 P=0.507). Conclusion: The new constructed cell penetration peptide on the base of the polyargnine can translocate cell by carting FITC and MRI contrast agent-DTPA-Gd and the

Peptide regulators of peripheral taste function.

Science.gov (United States)

Dotson, Cedrick D; Geraedts, Maartje C P; Munger, Steven D

2013-03-01

The peripheral sensory organ of the gustatory system, the taste bud, contains a heterogeneous collection of sensory cells. These taste cells can differ in the stimuli to which they respond and the receptors and other signaling molecules they employ to transduce and encode those stimuli. This molecular diversity extends to the expression of a varied repertoire of bioactive peptides that appear to play important functional roles in signaling taste information between the taste cells and afferent sensory nerves and/or in processing sensory signals within the taste bud itself. Here, we review studies that examine the expression of bioactive peptides in the taste bud and the impact of those peptides on taste functions. Many of these peptides produced in taste buds are known to affect appetite, satiety or metabolism through their actions in the brain, pancreas and other organs, suggesting a functional link between the gustatory system and the neural and endocrine systems that regulate feeding and nutrient utilization. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diversity and subcellular distribution of archaeal secreted proteins

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Mechthild ePohlschroder

2012-07-01

Full Text Available Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell-wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as archaeal kingdom-specific pathways. A more comprehensive understanding of the transport pathways and post-translational modifications of secreted archaeal proteins will also generate invaluable insights that will facilitate the identification of commercially valuable archaeal enzymes and the development of heterologous systems in which to efficiently express them.

Diversity and subcellular distribution of archaeal secreted proteins.

Science.gov (United States)

Szabo, Zalan; Pohlschroder, Mechthild

2012-01-01

Secreted proteins make up a significant percentage of a prokaryotic proteome and play critical roles in important cellular processes such as polymer degradation, nutrient uptake, signal transduction, cell wall biosynthesis, and motility. The majority of archaeal proteins are believed to be secreted either in an unfolded conformation via the universally conserved Sec pathway or in a folded conformation via the Twin arginine transport (Tat) pathway. Extensive in vivo and in silico analyses of N-terminal signal peptides that target proteins to these pathways have led to the development of computational tools that not only predict Sec and Tat substrates with high accuracy but also provide information about signal peptide processing and targeting. Predictions therefore include indications as to whether a substrate is a soluble secreted protein, a membrane or cell wall anchored protein, or a surface structure subunit, and whether it is targeted for post-translational modification such as glycosylation or the addition of a lipid. The use of these in silico tools, in combination with biochemical and genetic analyses of transport pathways and their substrates, has resulted in improved predictions of the subcellular localization of archaeal secreted proteins, allowing for a more accurate annotation of archaeal proteomes, and has led to the identification of potential adaptations to extreme environments, as well as phyla-specific pathways among the archaea. A more comprehensive understanding of the transport pathways used and post-translational modifications of secreted archaeal proteins will also facilitate the identification and heterologous expression of commercially valuable archaeal enzymes.

Analysis of an Alanine/Arginine Mixture by Using TLC/FTIR Technique

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Jun Liu

2014-01-01

Full Text Available We applied TLC/FTIR coupled with mapping technique to analyze an alanine/arginine mixture. Narrow band TLC plates prepared by using AgI as a stationary phase were used to separate alanine and arginine. The distribution of alanine and arginine spots was manifested by a 3D chromatogram. Alanine and arginine can be successfully separated by the narrow band TLC plate. In addition, the FTIR spectra of the separated alanine and arginine spots on the narrow band TLC plate are roughly the same as the corresponding reference IR spectra.

Impaired Cleavage of Preproinsulin Signal Peptide Linked to Autosomal-Dominant Diabetes

Science.gov (United States)

Liu, Ming; Lara-Lemus, Roberto; Shan, Shu-ou; Wright, Jordan; Haataja, Leena; Barbetti, Fabrizio; Guo, Huan; Larkin, Dennis; Arvan, Peter

2012-01-01

Recently, missense mutations upstream of preproinsulin’s signal peptide (SP) cleavage site were reported to cause mutant INS gene-induced diabetes of youth (MIDY). Our objective was to understand the molecular pathogenesis using metabolic labeling and assays of proinsulin export and insulin and C-peptide production to examine the earliest events of insulin biosynthesis, highlighting molecular mechanisms underlying β-cell failure plus a novel strategy that might ameliorate the MIDY syndrome. We find that whereas preproinsulin-A(SP23)S is efficiently cleaved, producing authentic proinsulin and insulin, preproinsulin-A(SP24)D is inefficiently cleaved at an improper site, producing two subpopulations of molecules. Both show impaired oxidative folding and are retained in the endoplasmic reticulum (ER). Preproinsulin-A(SP24)D also blocks ER exit of coexpressed wild-type proinsulin, accounting for its dominant-negative behavior. Upon increased expression of ER–oxidoreductin-1, preproinsulin-A(SP24)D remains blocked but oxidative folding of wild-type proinsulin improves, accelerating its ER export and increasing wild-type insulin production. We conclude that the efficiency of SP cleavage is linked to the oxidation of (pre)proinsulin. In turn, impaired (pre)proinsulin oxidation affects ER export of the mutant as well as that of coexpressed wild-type proinsulin. Improving oxidative folding of wild-type proinsulin may provide a feasible way to rescue insulin production in patients with MIDY. PMID:22357960

PEPTIDE SOLUBILITY, STRUCTURE AND CHARGE POSITION EFFECT ON ADSORPTION BY ALUMINIUM HYDROXIDE

Directory of Open Access Journals (Sweden)

Mary Trujillo

2008-04-01

Full Text Available Solubility, structure and position of charges in a peptide antigen sequence can be mentioned as being amongst the basic features of adsorption. In order to study their effect on adsorption, seven analogue series were synthesized from a MSP-1 peptide sequence by systematically replacing each one of the positions in the peptide sequence by aspartic acid, glutamic acid, serine, alanine, asparagine, glutamine or lysine. Such modifications in analogue peptide sequences showed a non-regular tendency regarding solubility and adsorption data. Aspartic acid and Glutamic acid analogue series showed great improvements in adsorption, especially in peptides where Lysine in position 6 and Arginine in position 13 were replaced. Solubility of position 5 analogue was greater than the position 6 analogue in Aspartic acid series; however, the position 6 analogue showed best adsorption results whilst the Aspartic acid in position 5 analogue showed no adsorption in the same conditions. Nuclear Magnetic Resonance structural analysis revealed differences in the -helical structureextension between these analogues. The Aspartic acid in position 6, located in the polar side of the helix, may allow this analogueto fit better onto the adsorption regions suggesting that the local electrostatic charge is responsible for this behavior.

The Arabidopsis thaliana natriuretic peptide AtPNP-A is a systemic regulator of leaf dark respiration and signals via the phloem

KAUST Repository

Ruzvidzo, Oziniel

2011-09-01

Plant natriuretic peptides (PNPs) belong to a novel class of peptidic signaling molecules that share some structural similarity to the N-terminal domain of expansins and affect physiological processes such as water and ion homeostasis at nano-molar concentrations. Here we show that a recombinant Arabidopsis thaliana PNP (AtPNP-A) rapidly increased the rate of dark respiration in treated leaves after 5 min. In addition, we observed increases in lower leaves, and with a lag time of 10 min, the effect spread to the upper leaves and subsequently (after 15 min) to the opposite leaves. This response signature is indicative of phloem mobility of the signal, a hypothesis that was further strengthened by the fact that cold girdling, which affects phloem but not xylem or apoplastic processes, delayed the long distance AtPNP-A effect. We conclude that locally applied AtPNP-A can induce a phloem-mobile signal that rapidly modifies plant homeostasis in distal parts. © 2011 Elsevier GmbH.

Study of the affinity between the protein kinase PKA and homoarginine-containing peptides derived from kemptide: Free energy perturbation (FEP) calculations.

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Mena-Ulecia, Karel; Gonzalez-Norambuena, Fabian; Vergara-Jaque, Ariela; Poblete, Horacio; Tiznado, William; Caballero, Julio

2018-02-05

Protein kinases (PKs) discriminate between closely related sequences that contain serine, threonine, and/or tyrosine residues. Such specificity is defined by the amino acid sequence surrounding the phosphorylatable residue, so that it is possible to identify an optimal recognition motif (ORM) for each PK. The ORM for the protein kinase A (PKA), a well-known member of the PK family, is the sequence RRX(S/T)X, where arginines at the -3 and -2 positions play a key role with respect to the primed phosphorylation site. In this work, differential affinities of PKA for the peptide substrate Kemptide (LRRASLG) and mutants that substitute the arginine residues by the unnatural peptide homoarginine were evaluated through molecular dynamics (MD) and free energy perturbation (FEP) calculations. The FEP study for the homoarginine mutants required previous elaboration of a CHARMM "arginine to homoarginine" (R2B) hybrid topology file which is available in this manuscript as Supporting Information. Mutants substituting the arginine residues by alanine, lysine, and histidine were also considered in the comparison by using the same protocol. FEP calculations allowed estimating the free energy changes from the free PKA to PKA-substrate complex (ΔΔG E→ES ) when Kemptide structure was mutated. Both ΔΔG S→ES values for homoarginine mutants were predicted with a difference below 1 kcal/mol. In addition, FEP correctly predicted that all the studied mutations decrease the catalytic efficiency of Kemptide for PKA. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Stress, sex, and addiction: potential roles of corticotropin-releasing factor, oxytocin, and arginine-vasopressin.

Science.gov (United States)

Bisagno, Verónica; Cadet, Jean Lud

2014-09-01

Stress sensitivity and sex are predictive factors for the development of neuropsychiatric disorders. Life stresses are not only risk factors for the development of addiction but also are triggers for relapse to drug use. Therefore, it is imperative to elucidate the molecular mechanisms underlying the interactions between stress and drug abuse, as an understanding of this may help in the development of novel and more effective therapeutic approaches to block the clinical manifestations of drug addiction. The development and clinical course of addiction-related disorders do appear to involve neuroadaptations within neurocircuitries that modulate stress responses and are influenced by several neuropeptides. These include corticotropin-releasing factor, the prototypic member of this class, as well as oxytocin and arginine-vasopressin that play important roles in affiliative behaviors. Interestingly, these peptides function to balance emotional behavior, with sexual dimorphism in the oxytocin/arginine-vasopressin systems, a fact that might play an important role in the differential responses of women and men to stressful stimuli and the specific sex-based prevalence of certain addictive disorders. Thus, this review aims to summarize (i) the contribution of sex differences to the function of dopamine systems, and (ii) the behavioral, neurochemical, and anatomical changes in brain stress systems.

Ventricular strain changes in monochorionic twins with and without twin-to-twin transfusion syndrome.

Science.gov (United States)

Taylor-Clarke, Marisa C; Matsui, Hikoro; Roughton, Michael; Wimalasundera, Ruwan C; Gardiner, Helena M

2013-06-01

The objective of the study was to investigate whether vector velocity imaging (VVI), a non-Doppler speckle tracking ultrasound technology, is feasible in twin pregnancies and can aid management of twin-twin transfusion syndrome (TTTS). Twenty-seven women pregnant with monochorionic diamniotic twins affected by TTTS and 28 monochorionic pregnancies that did not develop TTTS were included in a prospective case-control study at a fetal medicine center. Fetal echocardiograms were recorded with dummy electrocardiography to retain original frame rates when exported for offline speckle tracking analysis using Syngo-VVI software (Siemens Corp, Munich, Germany). Right and left ventricular (LV) free wall Lagrangian strain was measured from the original coordinates. Within-twin pair ventricular strain differences including relationship to Quintero staging and response to laser therapy for TTTS were analyzed by Wilcoxon signed-rank test. The VVI strain measurements could be analyzed in 182 of 200 TTTS and 96 of 112 non-TTTS control ventricles. Within-pair strain was concordant in non-TTTS controls. Recipient LV strain was reduced at all Quintero stages compared with donors (P < .01). Recipient right ventricular strain was reduced only in stages 3 and 4 (P < .01). Strain improved at a median of 2 weeks following successful laser therapy. Intertwin differences in strain were independent of weight discordance. Recipient LV strain is reduced in stages 1 and 2 TTTS. Within-pair strain discordance may distinguish early TTTS from growth discordance and guide timing of and management following treatment. Copyright © 2013 Mosby, Inc. All rights reserved.

The Asia 2 specific signal peptide region and other domains in fusion protein genes characterized Asia 1 and Asia 2 canine distemper viruses

Science.gov (United States)

Sultan, Serageldeen; Charoenvisal, Nataya; Lan, Nguyen Thi; Yamaguchi, Ryoji; Maeda, Ken; Kai, Kazushige

2009-01-01

Background Although the presence of Asia 2 group of canine distemper virus (CDV) was known by the sequencing and phylogenetic analysis of hemagglutinin (H) gene, the fusion (F) protein gene sequence of Asia 2 group had not been identified. So, the sequence analysis of F gene was carried out to elucidate the genotypic varaitons among Asian isolates. Results The phylogenetic analysis of F and H gene sequences from fourteen CDV isolates obtained from diseased dogs in Japan and Thailand indicated that the F genes had a new initiation codon and extra 27 nucleotides upstream of the usual open reading frame (ORF) and the F proteins had extra 9 amino acids at the N-terminal position only in Asia 2 isolates. On the contrary, the Asia 1 isolates had three extra putative N-glycosylation sites (two sites in the signal peptide region and one site in the F1 region) except for two strains of Th12 and Ac96I (two sites in signal peptide region) adding to four putative N-glycosylation sites that were conserved among all Asian isolates and Onderstepoort strain. In addition to this difference in N-glycosylation sites, the signal peptide region had a great diversity between Asia 1 and Asia 2 isolates. Also, characteristic amino acids were detected for some strains. Conclusion Asia 2 isolates were distinguished from other CDV lineages by the extra 27 nucleotide sequence. The signal peptide region of F gene gives a remarkable differentiation between Asia 1 and Asia 2 isolates. Strains Th12 and Ac96I were differentiated from other Asia 1 strains by the F protein glycosylation sites. PMID:19807927

Twin pregnancy

DEFF Research Database (Denmark)

Sperling, Lene; Tabor, A

2001-01-01

Determination of chorionicity is one of the most important issues in the management of twin pregnancy. Modern ultrasound equipment has made it possible to accurately assess placentation already in the first trimester with the lambda sign. With regard to prenatal diagnosis, it is important to know...... for clinicians caring for twin pregnancies....

Synthesis of the arginine labelled by {sup 15}N on the amidine group; Synthese de l'arginine marquee par {sup 15}N dans le groupe amidine

Energy Technology Data Exchange (ETDEWEB)

Pichat, L; Clement, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

1955-07-01

For some biologic studies, it was necessarily to have (+) arginine marked by nitrogen 15 in the amidine group. This report describes the synthesis of the labelled arginine. The first step is the synthesis of the methyl-isourated hydro-chlorate, the intermediate reactive, from the ClNH{sub 4} isotope. The arginine is obtained from the ornithine which we previously blocked the amino group as cupric complex. The mean yield in arginine reaches 30%, based on the ammonium chloride uses. (M.B.) [French] Pour certaines etudes biologiques, il etait indispensable de disposer de (+) arginine marquee par l'azote 15 dans le groupement amidine. Ce rapport decrit la synthese de l'ariginine marquee. La premiere etape est la synthese du chlorhydrate de methylisouree, intermediaire reactif, a partir du ClNH{sub 4} isotopique. L'obtention de l'arginine est obtenue a partir de l'ornithine dont on a prealablement bloque le groupe amino sous forme de complexe cuivrique. Le rendement global moyen en arginine atteint 30 %, base sur le chlorure d'ammonium utilise. (M.B.)

Modulators of arginine metabolism support cancer immunosurveillance

Directory of Open Access Journals (Sweden)

Freschi Massimo

2009-01-01

Full Text Available Abstract Background Tumor-associated accrual of myeloid derived suppressor cells (MDSC in the blood, lymphoid organs and tumor tissues may lead to perturbation of the arginine metabolism and impairment of the endogenous antitumor immunity. The objective of this study was to evaluate whether accumulation of MDSC occurred in Th2 prone BALB/c and Th1 biased C57BL/6 mice bearing the C26GM colon carcinoma and RMA T lymphoma, respectively, and to investigate whether N(G nitro-L-arginine methyl ester (L-NAME and sildenafil, both modulators of the arginine metabolism, restored antitumor immunity. Results We report here that MDSC accumulate in the spleen and blood of mice irrespective of the mouse and tumor model used. Treatment of tumor-bearing mice with either the phosphodiesterase-5 inhibitor sildenafil or the nitric-oxide synthase (NOS inhibitor L-NAME significantly restrained tumor growth and expanded the tumor-specific immune response. Conclusion Our data emphasize the role of MDSC in modulating the endogenous tumor-specific immune response and underline the anti-neoplastic therapeutic potential of arginine metabolism modulators.

Gliclazide directly inhibits arginine-induced glucagon release

DEFF Research Database (Denmark)

Cejvan, Kenan; Coy, David H; Holst, Jens Juul

2002-01-01

Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect of glicl......Arginine-stimulated insulin and somatostatin release is enhanced by the sulfonylurea gliclazide. In contrast, gliclazide inhibits the glucagon response. The aim of the present study was to investigate whether this inhibition of glucagon release was mediated by a direct suppressive effect....... In islet perifusions with DC-41-33, arginine-induced glucagon release was inhibited by 66%. We therefore concluded that gliclazide inhibits glucagon release by a direct action on the pancreatic A cell....

Formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations - A review.

Science.gov (United States)

Zhao, Cindy J; Schieber, Andreas; Gänzle, Michael G

2016-11-01

Fermented foods are valued for their rich and complex odour and taste. The metabolic activity of food-fermenting microorganisms determines food quality and generates odour and taste compounds. This communication reviews the formation of taste-active amino acids, amino acid derivatives and peptides in food fermentations. Pathways of the generation of taste compounds are presented for soy sauce, cheese, fermented meats, and bread. Proteolysis or autolysis during food fermentations generates taste-active amino acids and peptides; peptides derived from proteolysis particularly impart umami taste (e.g. α-glutamyl peptides) or bitter taste (e.g. hydrophobic peptides containing proline). Taste active peptide derivatives include pyroglutamyl peptides, γ-glutamyl peptides, and succinyl- or lactoyl amino acids. The influence of fermentation microbiota on proteolysis, and peptide hydrolysis, and the metabolism of glutamate and arginine is well understood, however, the understanding of microbial metabolic activities related to the formation of taste-active peptide derivatives is incomplete. Improved knowledge of the interactions between taste-active compounds will enable the development of novel fermentation strategies to develop tastier, less bitter, and low-salt food products, and may provide novel and "clean label" ingredients to improve the taste of other food products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiclass Posterior Probability Twin SVM for Motor Imagery EEG Classification.

Science.gov (United States)

She, Qingshan; Ma, Yuliang; Meng, Ming; Luo, Zhizeng

2015-01-01

Motor imagery electroencephalography is widely used in the brain-computer interface systems. Due to inherent characteristics of electroencephalography signals, accurate and real-time multiclass classification is always challenging. In order to solve this problem, a multiclass posterior probability solution for twin SVM is proposed by the ranking continuous output and pairwise coupling in this paper. First, two-class posterior probability model is constructed to approximate the posterior probability by the ranking continuous output techniques and Platt's estimating method. Secondly, a solution of multiclass probabilistic outputs for twin SVM is provided by combining every pair of class probabilities according to the method of pairwise coupling. Finally, the proposed method is compared with multiclass SVM and twin SVM via voting, and multiclass posterior probability SVM using different coupling approaches. The efficacy on the classification accuracy and time complexity of the proposed method has been demonstrated by both the UCI benchmark datasets and real world EEG data from BCI Competition IV Dataset 2a, respectively.

Clathrin-dependent internalization, signaling, and metabolic processing of guanylyl cyclase/natriuretic peptide receptor-A.

Science.gov (United States)

Somanna, Naveen K; Mani, Indra; Tripathi, Satyabha; Pandey, Kailash N

2018-04-01

Cardiac hormones, atrial and brain natriuretic peptides (ANP and BNP), have pivotal roles in renal hemodynamics, neuroendocrine signaling, blood pressure regulation, and cardiovascular homeostasis. Binding of ANP and BNP to the guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) induces rapid internalization and trafficking of the receptor via endolysosomal compartments, with concurrent generation of cGMP. However, the mechanisms of the endocytotic processes of NPRA are not well understood. The present study, using 125 I-ANP binding assay and confocal microscopy, examined the function of dynamin in the internalization of NPRA in stably transfected human embryonic kidney-293 (HEK-293) cells. Treatment of recombinant HEK-293 cells with ANP time-dependently accelerated the internalization of receptor from the cell surface to the cell interior. However, the internalization of ligand-receptor complexes of NPRA was drastically decreased by the specific inhibitors of clathrin- and dynamin-dependent receptor internalization, almost 85% by monodansylcadaverine, 80% by chlorpromazine, and 90% by mutant dynamin, which are specific blockers of endocytic vesicle formation. Visualizing the internalization of NPRA and enhanced GFP-tagged NPRA in HEK-293 cells by confocal microscopy demonstrated the formation of endocytic vesicles after 5 min of ANP treatment; this effect was blocked by the inhibitors of clathrin and by mutant dynamin construct. Our results suggest that NPRA undergoes internalization via clathrin-mediated endocytosis as part of its normal itinerary, including trafficking, signaling, and metabolic degradation.

Marital status and twins' health and behavior: an analysis of middle-aged Danish twins

DEFF Research Database (Denmark)

Osler, Merete; McGue, Matt; Lund, Rikke

2008-01-01

mass index (BMI), depression symptoms, self-rated health, cognitive function, physical activity, smoking, and alcohol intake. RESULTS: Among all 2350 individual twins, men who were divorced/widowed or never married had higher depression scores, lower cognitive test scores, lower physical activity....../widowed twin had higher average depression scores and was more likely to be a smoker. Never married twins had lower physical activity scores and never married male twins had higher BMI and higher depression scores than their married co-twin. CONCLUSION: This study suggests that the relationships of adult...... divorce with depression and smoking in Danish twins are due to the stressful effects of marital dissolution, but that marital differences in other health and behavioral outcomes are most consistent with selection effects related to genetic or rearing environmental factors....

Acellular matrix of bovine pericardium bound with L-arginine

International Nuclear Information System (INIS)

Kim, Hyo Joo; Bae, Jin Woo; Kim, Chun Ho; Lee, Jin Woo; Shin, Jung Woog; Park, Ki Dong

2007-01-01

Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses

Acellular matrix of bovine pericardium bound with L-arginine

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyo Joo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Bae, Jin Woo [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of); Kim, Chun Ho [Laboratory of Tissue Engineering, Korea Cancer Center Hospital, Seoul 139-240 (Korea, Republic of); Lee, Jin Woo [Department of Orthopaedic Surgery, College of Medicine, Yonsei University, Seoul 120-749 (Korea, Republic of); Shin, Jung Woog [Department of Biomedical Engineering, Inje University, Gimhae 621-749 (Korea, Republic of); Park, Ki Dong [Department of Molecular Science and Technology, Ajou University, Suwon 443-749 (Korea, Republic of)

2007-09-15

Surface immobilization of bioactive molecules onto natural tissues has been interestingly studied for the development of new functional matrices for the replacement of lost or malfunctioning tissues. In this study, an acellular matrix of bovine pericardium (ABP) was chemically modified by the direct coupling of L-arginine after glutaraldehyde (GA) cross-linking. The effects of L-arginine coupling on durability and calcification were investigated and the biocompatibility was evaluated in vitro and in vivo. A four-step detergent and enzymatic extraction process has been utilized to remove cellular components from fresh bovine pericardium (BP). Microscopic observation confirmed that nearly all cellular constituents are removed. Thermal and mechanical properties showed that the durability of L-arginine-treated matrices increased as compared with control ABP and GA-treated ABP. Resistance to collagenase digestion revealed that modified matrices have greater resistance to enzyme digestion than control ABP and GA-treated ABP. The in vivo calcification study demonstrated much less calcium deposition on L-arginine-treated ABP than GA-treated one. In vitro cell viability results showed that ABP modified with L-arginine leads to a significant increase in attachment of human dermal fibroblasts. The obtained results attest to the usefulness of L-arginine-treated ABP matrices for cardiovascular bioprostheses.

Endoplasmic reticulum protein targeting of phospholamban: a common role for an N-terminal di-arginine motif in ER retention?

Directory of Open Access Journals (Sweden)

Parveen Sharma

2010-07-01

Full Text Available Phospholamban (PLN is an effective inhibitor of the sarco(endoplasmic reticulum Ca(2+-ATPase, which transports Ca(2+ into the SR lumen, leading to muscle relaxation. A mutation of PLN in which one of the di-arginine residues at positions 13 and 14 was deleted led to a severe, early onset dilated cardiomyopathy. Here we were interested in determining the cellular mechanisms involved in this disease-causing mutation.Mutations deleting codons for either or both Arg13 or Arg14 resulted in the mislocalization of PLN from the ER. Our data show that PLN is recycled via the retrograde Golgi to ER membrane traffic pathway involving COP-I vesicles, since co-immunoprecipitation assays determined that COP I interactions are dependent on an intact di-arginine motif as PLN RDelta14 did not co-precipitate with COP I containing vesicles. Bioinformatic analysis determined that the di-arginine motif is present in the first 25 residues in a large number of all ER/SR Gene Ontology (GO annotated proteins. Mutations in the di-arginine motif of the Sigma 1-type opioid receptor, the beta-subunit of the signal recognition particle receptor, and Sterol-O-acyltransferase, three proteins identified in our bioinformatic screen also caused mislocalization of these known ER-resident proteins.We conclude that PLN is enriched in the ER due to COP I-mediated transport that is dependent on its intact di-arginine motif and that the N-terminal di-arginine motif may act as a general ER retrieval sequence.

Arginine, citrulline and nitric oxide metabolism in sepsis

Science.gov (United States)

Arginine has vasodilatory effects, via its conversion by nitric oxide (NO) synthase into NO, and immunomodulatory actions that play important roles in sepsis. Protein breakdown affects arginine availability, and the release of asymmetric dimethylarginine, an inhibitor of NO synthase, may therefore a...

Register-based research on twins

DEFF Research Database (Denmark)

Christensen, Kaare; Ohm Kyvik, Kirsten; Holm, Niels V

2011-01-01

Introduction: The Danish Twin Registry (DTR) has for more than 50 years been based on surveys and clinical investigations and over the two last decades also on register linkage. Currently these two approaches are merged within Statistics Denmark. Research topics: Here we report on three major...... groups of register-based research in the DTR that used the uniqueness of twinning. First, we focus on the ''long-term prognosis'' of being a twin compared with being a singleton and show that Danish twins have health trajectories in adulthood similar to singletons, which is a result of interest for twins...... illustrate how the co-twin control method in a register setting can be used to control for the effect of rearing environment and genetic factors in studies of the association between exposures and health. CONCLUSION: The spectrum of register-based twin studies is very wide and have changed in accordance...

The effects of L-arginine, D-arginine, L-name and methylene blue on channa striatus-induced peripheral antinociception in mice.

Science.gov (United States)

Zakaria, Zainul Amiruddin; Sulaiman, Mohd Rosian; Somchit, Muhammad Nazrul; Jais, Abdul Manan Mat; Ali, Daud Israf

2005-08-03

To determine the involvement of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway in aqueous supernatant of haruan (Channa striatus) fillet (ASH) antinociception using the acetic acid-induced abdominal constriction test. The ASH was prepared by soaking fresh haruan fillet in chloroform:methanol (CM) (2/1 (v/v)) for 72 h followed by evaporation of the upper layer supernatant to remove any solvent residues. The supernatant was then subjected to a freeze-drying process (48 h) followed by doses preparation. Subcutaneous (SC) administration of ASH alone (0.170, 0.426 and 1.704 mg/kg) exhibited a dose-dependent antinociception. On the other hand, 20 mg/kg (SC) of L-arginine and MB exhibited a significant nociception and antinociception, while D-arginine and L-NAME did not produce any effect at all. Pre-treatment with L-arginine was found to significantly reverse the three respective doses of ASH antinociception; pre-treatment with D-arginine did not produce any significant change in the ASH activity; pre-treatment with L-NAME only significantly increased the 0.170 and 0.426 mg/kg ASH antinociception; and pre-treatment with MB significantly enhanced the respective doses of ASH antinociception, respectively. Furthermore, co-treatment with L-NAME significantly enhanced the L-arginine reversal effect on 0.426 mg/kg ASH antinociception. In addition, MB significantly reversed the L-arginine nociception on 0.426 mg/kg ASH. These finding suggest ASH antinociception involves the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. The presence of NO was found to reverse ASH antinociceptive activity while blocking of cGMP system enhanced it.

The role of insulin C-peptide in the coevolution analyses of the insulin signaling pathway: a hint for its functions.

Directory of Open Access Journals (Sweden)

Shuai Wang

Full Text Available As the linker between the A chain and B chain of proinsulin, C-peptide displays high variability in length and amino acid composition, and has been considered as an inert byproduct of insulin synthesis and processing for many years. Recent studies have suggested that C-peptide can act as a bioactive hormone, exerting various biological effects on the pathophysiology and treatment of diabetes. In this study, we analyzed the coevolution of insulin molecules among vertebrates, aiming at exploring the evolutionary characteristics of insulin molecule, especially the C-peptide. We also calculated the correlations of evolutionary rates between the insulin and the insulin receptor (IR sequences as well as the domain-domain pairs of the ligand and receptor by the mirrortree method. The results revealed distinctive features of C-peptide in insulin intramolecular coevolution and correlated residue substitutions, which partly supported the idea that C-peptide can act as a bioactive hormone, with significant sequence features, as well as a linker assisting the formation of mature insulin during synthesis. Interestingly, the evolution of C-peptide exerted the highest correlation with that of the insulin receptor and its ligand binding domain (LBD, implying a potential relationship with the insulin signaling pathway.

Inhibition of Chondrocyte Hypertrophy of Osteoarthritis by Disruptor Peptide

Science.gov (United States)

2017-07-01

with PTHR and inhibits the pathogenic beta-catenin- mediated PTHR signaling switch. In Aim 2, we will define the role of disruptor peptide in...confirmed that disruptor peptide conjugated to penetratin can enter cells. Importantly, disruptor peptide can reverse the beta-catenin- mediated PTH... mediated PTHR signaling switch in chondrocytes. Mouse primary chondrocytes express both β-catenin and PTHR. Our data showed that Pen-dis- pep

Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

DEFF Research Database (Denmark)

Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jørgensen, Nils Bruun

2013-01-01

Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones...

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal 19 F MRI Agents.

Science.gov (United States)

Kirberger, Steven E; Maltseva, Sofia D; Manulik, Joseph C; Einstein, Samuel A; Weegman, Bradley P; Garwood, Michael; Pomerantz, William C K

2017-06-01

19 F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient 19 F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as 19 F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate 19 F NMR signal. 19 F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Birth size and gestational age in opposite-sex twins as compared to same-sex twins

DEFF Research Database (Denmark)

Jelenkovic, Aline; Sund, Reijo; Yokoyama, Yoshie

2018-01-01

It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project of Develo......It is well established that boys are born heavier and longer than girls, but it remains unclear whether birth size in twins is affected by the sex of their co-twin. We conducted an individual-based pooled analysis of 21 twin cohorts in 15 countries derived from the COllaborative project....... In girls, birth size was not associated (5 g birth weight; 95% CI -8 to -18 and -0.089 cm birth length; 95% CI -0.202 to 0.025) with the sex of the co-twin. Gestational age was slightly shorter in boy-boy pairs than in boy-girl and girl-girl pairs. When birth size was standardized by gestational age......, the magnitude of the associations was attenuated in boys, particularly for birth weight. In conclusion, boys with a co-twin sister are heavier and longer at birth than those with a co-twin brother. However, these differences are modest and partly explained by a longer gestation in the presence of a co...

Altered brain arginine metabolism in schizophrenia.

Science.gov (United States)

Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

2016-08-16

Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease.

Fetal growth disorders in twin gestations.

LENUS (Irish Health Repository)

Breathnach, Fionnuala M

2012-06-01

Twin growth is frequently mismatched. This review serves to explore the pathophysiologic mechanisms that underlie growth aberrations in twin gestations, the prenatal recognition of abnormal twin growth, and the critical importance of stratifying management of abnormal twin growth by chorionicity. Although poor in utero growth of both twins may reflect maternal factors resulting in global uteroplacental dysfunction, discordant twin growth may be attributed to differences in genetic potential between co-twins, placental dysfunction confined to one placenta only, or one placental territory within a shared placenta. In addition, twin-twin transfusion syndrome represents a distinct entity of which discordant growth is a common feature. Discordant growth is recognized as an independent risk factor for adverse perinatal outcome. Intertwin birth weight disparity of 18% or more should be considered to represent a discordance threshold, which serves as an independent risk factor for adverse perinatal outcome. At this cutoff, perinatal morbidity is found to increase both for the larger and the smaller twin within a discordant pair. There remains uncertainty surrounding the sonographic parameters that are most predictive of discordance. Although heightening of fetal surveillance in the face of discordant twin growth follows the principles applied to singleton gestations complicated by fetal growth restriction, the timing of intervention is largely influenced by chorionicity.

Neonatal status of twins

Directory of Open Access Journals (Sweden)

Božinović Dragica

2012-01-01

Full Text Available Multiple pregnancy is a pregnancy where more than one fetus develops simultaneously in the womb, as a result of the ovulation and fertilization of more than one egg. It is relatively rare in humans and represents the rest of the phylogenetic stages. The most common are twins and they indicate the development of two fetuses in the womb. The frequency of twin pregnancies is about 1%. Multiple pregnancies belong to a group of high-risk pregnancies because of the many complications that occur during the pregnancy: higher number of premature deliveries, bleeding, early neonatal complications and higher perinatal morbidity and mortality. Such pregnancies and infants require greater supervision and monitoring. The aim of this study was to determine the percentage of baby twins born at the maternity ward of the General Hospital in Prokuplje and their morbidity and mortality. Data on the total number of deliveries, number of twins, parity and maternal age, gestational age, body weight of twins, method of delivery, Apgar score and perinatal mortality were collected and statistically analyzed by means of retrospective analysis of operative birth and neonatal protocol for 6 years (2005 of 2010. Out of 4527 mothers who gave birth 43 were pairs of twins, or 0.95% of women gave birth to twins. These babies are more likely born by Caesarean section, but delivered with slightly lower birth weight.

Cohort Profile : The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry)

NARCIS (Netherlands)

Gatz, Margaret; Harris, Jennifer R.; Kaprio, Jaakko; McGue, Matt; Smith, Nicholas L.; Snieder, Harold; Spiro, Avron; Butler, David A.

The National Academy of Sciences-National Research Council Twin Registry (NAS-NRC Twin Registry) is a comprehensive registry of White male twin pairs born in the USA between 1917 and 1927, both of the twins having served in the military. The purpose was medical research and ultimately improved

Enhancement of mouse sperm motility by trophinin-binding peptide

Directory of Open Access Journals (Sweden)

Park Seong

2012-11-01

Full Text Available Abstract Background Trophinin is an intrinsic membrane protein that forms a complex in the cytoplasm with bystin and tastin, linking it microtubule-associated motor dynein (ATPase in some cell types. Previously, we found that human sperm tails contain trophinin, bystin and tastin proteins, and that trophinin-binding GWRQ (glycine, tryptophan, arginine, glutamine peptide enhanced motility of human sperm. Methods Immunohistochemistry was employed to determine trophinin protein in mouse spermatozoa from wild type mouse, by using spermatozoa from trophinin null mutant mice as a negative control. Multivalent 8-branched GWRQ (glycine, tryptophan, arginine, glutamine peptide or GWRQ-MAPS, was chemically synthesized, purified by HPLC and its structure was confirmed by MALDI-TOF mass spectrometry. Effect of GWRQ-MAPS on mouse spermatozoa from wild type and trophinin null mutant was assessed by a computer-assisted semen analyzer (CASA. Results Anti-trophinin antibody stained the principal (central piece of the tail of wild type mouse sperm, whereas the antibody showed no staining on trophinin null sperm. Phage particles displaying GWRQ bound to the principal piece of sperm tail from wild type but not trophinin null mice. GWRQ-MAPS enhanced motility of spermatozoa from wild type but not trophinin null mice. CASA showed that GWRQ-MAPS enhanced both progressive motility and rapid motility in wild type mouse sperm. Conclusions Present study established the expression of trophinin in the mouse sperm tail and trophinin-dependent effect of GWRQ-MAPS on sperm motility. GWRQ causes a significant increase in sperm motility.

Monozygotic twins with discordant intestinal rotation

International Nuclear Information System (INIS)

Smith, Vance L.; Nwomeh, Benedict C.; Long, Frederick

2006-01-01

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)

Monozygotic twins with discordant intestinal rotation

Energy Technology Data Exchange (ETDEWEB)

Smith, Vance L.; Nwomeh, Benedict C. [Ohio State University College of Medicine and Public Health, Department of Pediatric Surgery, Columbus Children' s Hospital, Columbus, OH (United States); Long, Frederick [Ohio State University College of Medicine and Public Health, Department of Radiology, Columbus Children' s Hospital, Columbus, OH (United States)

2006-04-15

Previous case reports have suggested a strong concordance of intestinal malrotation among identical twins. This has led to the recommendation that the asymptomatic twin undergo screening when malrotation is discovered in the identical sibling. We present a case of monozygotic twins in which one twin presented with intestinal malrotation with midgut volvulus while the other twin was found to have normal gastrointestinal anatomy. (orig.)

Sorting of a HaloTag protein that has only a signal peptide sequence into exocrine secretory granules without protein aggregation.

Science.gov (United States)

Fujita-Yoshigaki, Junko; Matsuki-Fukushima, Miwako; Yokoyama, Megumi; Katsumata-Kato, Osamu

2013-11-15

The mechanism involved in the sorting and accumulation of secretory cargo proteins, such as amylase, into secretory granules of exocrine cells remains to be solved. To clarify that sorting mechanism, we expressed a reporter protein HaloTag fused with partial sequences of salivary amylase protein in primary cultured parotid acinar cells. We found that a HaloTag protein fused with only the signal peptide sequence (Met(1)-Ala(25)) of amylase, termed SS25H, colocalized well with endogenous amylase, which was confirmed by immunofluorescence microscopy. Percoll-density gradient centrifugation of secretory granule fractions shows that the distributions of amylase and SS25H were similar. These results suggest that SS25H is transported to secretory granules and is not discriminated from endogenous amylase by the machinery that functions to remove proteins other than granule cargo from immature granules. Another reporter protein, DsRed2, that has the same signal peptide sequence also colocalized with amylase, suggesting that the sorting to secretory granules is not dependent on a characteristic of the HaloTag protein. Whereas Blue Native PAGE demonstrates that endogenous amylase forms a high-molecular-weight complex, SS25H does not participate in the complex and does not form self-aggregates. Nevertheless, SS25H was released from cells by the addition of a β-adrenergic agonist, isoproterenol, which also induces amylase secretion. These results indicate that addition of the signal peptide sequence, which is necessary for the translocation in the endoplasmic reticulum, is sufficient for the transportation and storage of cargo proteins in secretory granules of exocrine cells.

A Computational Discriminability Analysis on Twin Fingerprints

Science.gov (United States)

Liu, Yu; Srihari, Sargur N.

Sharing similar genetic traits makes the investigation of twins an important study in forensics and biometrics. Fingerprints are one of the most commonly found types of forensic evidence. The similarity between twins’ prints is critical establish to the reliability of fingerprint identification. We present a quantitative analysis of the discriminability of twin fingerprints on a new data set (227 pairs of identical twins and fraternal twins) recently collected from a twin population using both level 1 and level 2 features. Although the patterns of minutiae among twins are more similar than in the general population, the similarity of fingerprints of twins is significantly different from that between genuine prints of the same finger. Twins fingerprints are discriminable with a 1.5%~1.7% higher EER than non-twins. And identical twins can be distinguished by examine fingerprint with a slightly higher error rate than fraternal twins.

The utility of twins in developmental cognitive neuroscience research: How twins strengthen the ABCD research design.

Science.gov (United States)

Iacono, William G; Heath, Andrew C; Hewitt, John K; Neale, Michael C; Banich, Marie T; Luciana, Monica M; Madden, Pamela A; Barch, Deanna M; Bjork, James M

2018-08-01

The ABCD twin study will elucidate the genetic and environmental contributions to a wide range of mental and physical health outcomes in children, including substance use, brain and behavioral development, and their interrelationship. Comparisons within and between monozygotic and dizygotic twin pairs, further powered by multiple assessments, provide information about genetic and environmental contributions to developmental associations, and enable stronger tests of causal hypotheses, than do comparisons involving unrelated children. Thus a sub-study of 800 pairs of same-sex twins was embedded within the overall Adolescent Brain and Cognitive Development (ABCD) design. The ABCD Twin Hub comprises four leading centers for twin research in Minnesota, Colorado, Virginia, and Missouri. Each site is enrolling 200 twin pairs, as well as singletons. The twins are recruited from registries of all twin births in each State during 2006-2008. Singletons at each site are recruited following the same school-based procedures as the rest of the ABCD study. This paper describes the background and rationale for the ABCD twin study, the ascertainment of twin pairs and implementation strategy at each site, and the details of the proposed analytic strategies to quantify genetic and environmental influences and test hypotheses critical to the aims of the ABCD study. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Arginine as an adjuvant to chemotherapy improves clinical outcome in active tuberculosis

DEFF Research Database (Denmark)

Schön, T; Elias, D; Moges, F

2003-01-01

, and clinical symptoms after week 8. Secondary outcomes were sedimentation rate and levels of NO metabolites, arginine, citrulline, and tumour necrosis factor-a. Compared with the human immunodeficiency virus (HIV)-/TB+ placebo group, the HIV-/TB+ patients in the arginine group showed significant improvement......, defined as increased weight gain, higher sputum conversion rate and faster reduction of symptoms, such as cough. The arginine level increased after week 2 in the HIV-/TB+ arginine group (100.2 microM (range 90.5-109.9) versus 142.1 microM (range 114.1-170.1)) compared with the HIV-/TB+ placebo group (105.......5 microM (range 93.7-117.3) versus 95.7 microM (range 82.4-108.9)). HIV seroprevalence was 52.5%. No clinical improvement or increase in serum arginine was detected in arginine supplemented HIV+/TB+ patients compared with placebo. Arginine is beneficial as an adjuvant treatment in human immunodeficiency...

Conjoined (Siamese) Twins in Zambia

African Journals Online (AJOL)

year-old Zambian multiparous mother gave birth to a set of twins with two heads ... (symmetric or mirror image) but one twin attached with an incomplete foetus is known as hetropagtrs. (asymmetrical). Thoracopagus twins (joined at the chest).

Ferrobielastic twinning in irradiated quartz

International Nuclear Information System (INIS)

Shiau, S.M.

1986-01-01

Cultured quartz is usually free from electrical twinning; however, it may occur if the seed crystal is twinned or if undue applied forces are exerted on the crystal. Ferrobielastic twinning was studied optically (photoelastic effect) and electrically (piezoelectric effect). At room temperature, twins were perceptible at stresses of about 2.l5 x 10 8 N/m 2 , and crystals switched from their original states to the alternative twin states at stresses about 5.0 x 10 8 N/m 2 (called coercive stress). The decrease in coercive stress with increasing temperature was observed, and these coercive stresses become very low as temperatures reach to 300 0 C. The effects of irradiation on the twinning in quartz were also studied. The presence of defects produced by irradiation was utilized to pin the domain wall motion. Both neutrons and gamma rays were employed. The stress required to nucleate an appreciable volume of twins is about twice as high for irradiated crystals than for those unirradiated. This result demonstrated that the irradiated crystals can tolerate higher stresses. However, the coercive stress for complete switch-over was not much different for irradiated and unirradiated crystals. It appears that the defects caused by irradiation eliminate the initial twinning events but do not affect switch-over

Voice similarity in identical twins.

Science.gov (United States)

Van Gysel, W D; Vercammen, J; Debruyne, F

2001-01-01

If people are asked to discriminate visually the two individuals of a monozygotic twin (MT), they mostly get into trouble. Does this problem also exist when listening to twin voices? Twenty female and 10 male MT voices were randomly assembled with one "strange" voice to get voice trios. The listeners (10 female students in Speech and Language Pathology) were asked to label the twins (voices 1-2, 1-3 or 2-3) in two conditions: two standard sentences read aloud and a 2.5-second midsection of a sustained /a/. The proportion correctly labelled twins was for female voices 82% and 63% and for male voices 74% and 52% for the sentences and the sustained /a/ respectively, both being significantly greater than chance (33%). The acoustic analysis revealed a high intra-twin correlation for the speaking fundamental frequency (SFF) of the sentences and the fundamental frequency (F0) of the sustained /a/. So the voice pitch could have been a useful characteristic in the perceptual identification of the twins. We conclude that there is a greater perceptual resemblance between the voices of identical twins than between voices without genetic relationship. The identification however is not perfect. The voice pitch possibly contributes to the correct twin identifications.

Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes

Directory of Open Access Journals (Sweden)

Carbone Maria

2006-09-01

Full Text Available Abstract Background Mammalian sperm-oocyte interaction at fertilization involves several combined interactions between integrins on the oocyte and integrin ligands (disintegrins on the sperm. Recent research has indicated the ability of peptides containing the RGD sequence that characterized several sperm disintegrins, to induce intracellular Ca2+ transients and to initiate parthenogenetic development in amphibian and bovine oocytes. In the present study, we investigate the hypothesis that an integrin-associated signalling may participate in oocyte activation signalling by determining the ability of a cyclic RGD-containing peptide to stimulate the activation of protein kinase C (PKC and the exocytosis of cortical granules in mouse oocytes. Methods An In-Vitro-Fertilization assay (IVF was carried in order to test the condition under which a peptide containing the RGD sequence, cyclo(Arg-Gly-Asp-D-Phe-Val, was able to inhibit sperm fusion with zona-free mouse oocytes at metaphase II stage. PKC activity was determined by means of an assay based on the ability of cell lysates to phosphorylate MARKS peptide, a specific PKC substrate. Loss of cortical granules was evaluated by measuring density in the oocyte cortex of cortical granules stained with LCA-biotin/Texas red-streptavidin. In all the experiments, effects of a control peptide containing a non RGD sequence, cyclo(Arg-Ala-Asp-D-Phe-Val, were evaluated. Results The IVF assay revealed that the fusion rate declined significantly when insemination was carried out in the presence of cyclic RGD peptide at concentrations > or = 250 microM (P Conclusion The presents results provide evidence that a cyclic RGD peptide highly effective in inhibiting sperm-oocyte interaction stimulates in mouse oocytes the activation of PKC and the exocytosis of cortical granules. These data support the view that RGD-binding receptors may function as signalling receptors giving rise integrated signalling not sufficient for

Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

Energy Technology Data Exchange (ETDEWEB)

Shin, Soyoung; Mohan, Srinidi [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States); Fung, Ho-Leung, E-mail: hlfung@buffalo.edu [Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY 14260 (United States)

2011-11-04

Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h. To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

Dietary arginine depletion reduces depressive-like responses in male, but not female, mice.

Science.gov (United States)

Workman, Joanna L; Weber, Michael D; Nelson, Randy J

2011-09-30

Previous behavioral studies have manipulated nitric oxide (NO) production either by pharmacological inhibition of its synthetic enzyme, nitric oxide synthase (NOS), or by deletion of the genes that code for NOS. However manipulation of dietary intake of the NO precursor, L-arginine, has been understudied in regard to behavioral regulation. L-Arginine is a common amino acid present in many mammalian diets and is essential during development. In the brain L-arginine is converted into NO and citrulline by the enzyme, neuronal NOS (nNOS). In Experiment 1, paired mice were fed a diet comprised either of an L-arginine-depleted, L-arginine-supplemented, or standard level of L-arginine during pregnancy. Offspring were continuously fed the same diets and were tested in adulthood in elevated plus maze, forced swim, and resident-intruder aggression tests. L-Arginine depletion reduced depressive-like responses in male, but not female, mice and failed to significantly alter anxiety-like or aggressive behaviors. Arginine depletion throughout life reduced body mass overall and eliminated the sex difference in body mass. Additionally, arginine depletion significantly increased corticosterone concentrations, which negatively correlated with time spent floating. In Experiment 2, adult mice were fed arginine-defined diets two weeks prior to and during behavioral testing, and again tested in the aforementioned tests. Arginine depletion reduced depressive-like responses in the forced swim test, but did not alter behavior in the elevated plus maze or the resident intruder aggression test. Corticosterone concentrations were not altered by arginine diet manipulation in adulthood. These results indicate that arginine depletion throughout development, as well as during a discrete period during adulthood ameliorates depressive-like responses. These results may yield new insights into the etiology and sex differences of depression. Copyright © 2011 Elsevier B.V. All rights reserved.

Secretory signal peptide modification for optimized antibody-fragment expression-secretion in Leishmania tarentolae

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Klatt Stephan

2012-07-01

Full Text Available Abstract Background Secretory signal peptides (SPs are well-known sequence motifs targeting proteins for translocation across the endoplasmic reticulum membrane. After passing through the secretory pathway, most proteins are secreted to the environment. Here, we describe the modification of an expression vector containing the SP from secreted acid phosphatase 1 (SAP1 of Leishmania mexicana for optimized protein expression-secretion in the eukaryotic parasite Leishmania tarentolae with regard to recombinant antibody fragments. For experimental design the online tool SignalP was used, which predicts the presence and location of SPs and their cleavage sites in polypeptides. To evaluate the signal peptide cleavage site as well as changes of expression, SPs were N-terminally linked to single-chain Fragment variables (scFv’s. The ability of L. tarentolae to express complex eukaryotic proteins with highly diverse post-translational modifications and its easy bacteria-like handling, makes the parasite a promising expression system for secretory proteins. Results We generated four vectors with different SP-sequence modifications based on in-silico analyses with SignalP in respect to cleavage probability and location, named pLTEX-2 to pLTEX-5. To evaluate their functionality, we cloned four individual scFv-fragments into the vectors and transfected all 16 constructs into L. tarentolae. Independently from the expressed scFv, pLTEX-5 derived constructs showed the highest expression rate, followed by pLTEX-4 and pLTEX-2, whereas only low amounts of protein could be obtained from pLTEX-3 clones, indicating dysfunction of the SP. Next, we analysed the SP cleavage sites by Edman degradation. For pLTEX-2, -4, and -5 derived scFv’s, the results corresponded to in-silico predictions, whereas pLTEX-3 derived scFv’s contained one additional amino-acid (AA. Conclusions The obtained results demonstrate the importance of SP-sequence optimization for efficient

Hilbert-Twin – A Novel Hilbert Transform-Based Method To Compute Envelope Of Free Decaying Oscillations Embedded In Noise, And The Logarithmic Decrement In High-Resolution Mechanical Spectroscopy HRMS

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Magalas L.B.

2015-06-01

Full Text Available In this work, we present a novel Hilbert-twin method to compute an envelope and the logarithmic decrement, δ, from exponentially damped time-invariant harmonic strain signals embedded in noise. The results obtained from five computing methods: (1 the parametric OMI (Optimization in Multiple Intervals method, two interpolated discrete Fourier transform-based (IpDFT methods: (2 the Yoshida-Magalas (YM method and (3 the classic Yoshida (Y method, (4 the novel Hilbert-twin (H-twin method based on the Hilbert transform, and (5 the conventional Hilbert transform (HT method are analyzed and compared. The fundamental feature of the Hilbert-twin method is the efficient elimination of intrinsic asymmetrical oscillations of the envelope, aHT (t, obtained from the discrete Hilbert transform of analyzed signals. Excellent performance in estimation of the logarithmic decrement from the Hilbert-twin method is comparable to that of the OMI and YM for the low- and high-damping levels. The Hilbert-twin method proved to be robust and effective in computing the logarithmic decrement and the resonant frequency of exponentially damped free decaying signals embedded in experimental noise. The Hilbert-twin method is also appropriate to detect nonlinearities in mechanical loss measurements of metals and alloys.

Growth curves for twins in Slovenia.

Science.gov (United States)

Bricelj, Katja; Blickstein, Isaac; Bržan-Šimenc, Gabrijela; Janša, Vid; Lučovnik, Miha; Verdenik, Ivan; Trojner-Bregar, Andreja; Tul, Nataša

2017-02-01

Abnormalities of fetal growth are more common in twins. We introduce the growth curves for monitoring fetal growth in twin pregnancies in Slovenia. Slovenian National Perinatal Information System for the period between 2002 and 2010 was used to calculate birth weight percentiles for all live born twins for each week from 22nd to 40th week. The calculated percentiles of birth weight for all live-born twins in Slovenia served as the basis for drawing 'growth' curves. The calculated growth curves for twins will help accurately diagnose small or large twin fetuses for their gestational age in the native central European population.

Deformation twinning: Influence of strain rate

Energy Technology Data Exchange (ETDEWEB)

Gray, G.T. III

1993-11-01

Twins in most crystal structures, including advanced materials such as intermetallics, form more readily as the temperature of deformation is decreased or the rate of deformation is increased. Both parameters lead to the suppression of thermally-activated dislocation processes which can result in stresses high enough to nucleate and grow deformation twins. Under high-strain rate or shock-loading/impact conditions deformation twinning is observed to be promoted even in high stacking fault energy FCC metals and alloys, composites, and ordered intermetallics which normally do not readily deform via twinning. Under such conditions and in particular under the extreme loading rates typical of shock wave deformation the competition between slip and deformation twinning can be examined in detail. In this paper, examples of deformation twinning in the intermetallics TiAl, Ti-48Al-lV and Ni{sub 3}A as well in the cermet Al-B{sub 4}C as a function of strain rate will be presented. Discussion includes: (1) the microstructural and experimental variables influencing twin formation in these systems and twinning topics related to high-strain-rate loading, (2) the high velocity of twin formation, and (3) the influence of deformation twinning on the constitutive response of advanced materials.

Effect of methylation on the side-chain pKa value of arginine.

Science.gov (United States)

Evich, Marina; Stroeva, Ekaterina; Zheng, Yujun George; Germann, Markus W

2016-02-01

Arginine methylation is important in biological systems. Recent studies link the deregulation of protein arginine methyltransferases with certain cancers. To assess the impact of methylation on interaction with other biomolecules, the pKa values of methylated arginine variants were determined using NMR data. The pKa values of monomethylated, symmetrically dimethylated, and asymmetrically dimethylated arginine are similar to the unmodified arginine (14.2 ± 0.4). Although the pKa value has not been significantly affected by methylation, consequences of methylation include changes in charge distribution and steric effects, suggesting alternative mechanisms for recognition. © 2015 The Protein Society.

Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

Science.gov (United States)

Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

2018-03-01

Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p L-arginine than patients with LVSD (p L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

Fingerprint recognition with identical twin fingerprints.

Science.gov (United States)

Tao, Xunqiang; Chen, Xinjian; Yang, Xin; Tian, Jie

2012-01-01

Fingerprint recognition with identical twins is a challenging task due to the closest genetics-based relationship existing in the identical twins. Several pioneers have analyzed the similarity between twins' fingerprints. In this work we continue to investigate the topic of the similarity of identical twin fingerprints. Our study was tested based on a large identical twin fingerprint database that contains 83 twin pairs, 4 fingers per individual and six impressions per finger: 3984 (83*2*4*6) images. Compared to the previous work, our contributions are summarized as follows: (1) Two state-of-the-art fingerprint identification methods: P071 and VeriFinger 6.1 were used, rather than one fingerprint identification method in previous studies. (2) Six impressions per finger were captured, rather than just one impression, which makes the genuine distribution of matching scores more realistic. (3) A larger sample (83 pairs) was collected. (4) A novel statistical analysis, which aims at showing the probability distribution of the fingerprint types for the corresponding fingers of identical twins which have same fingerprint type, has been conducted. (5) A novel analysis, which aims at showing which finger from identical twins has higher probability of having same fingerprint type, has been conducted. Our results showed that: (a) A state-of-the-art automatic fingerprint verification system can distinguish identical twins without drastic degradation in performance. (b) The chance that the fingerprints have the same type from identical twins is 0.7440, comparing to 0.3215 from non-identical twins. (c) For the corresponding fingers of identical twins which have same fingerprint type, the probability distribution of five major fingerprint types is similar to the probability distribution for all the fingers' fingerprint type. (d) For each of four fingers of identical twins, the probability of having same fingerprint type is similar.

Fingerprint recognition with identical twin fingerprints.

Directory of Open Access Journals (Sweden)

Xunqiang Tao

Full Text Available Fingerprint recognition with identical twins is a challenging task due to the closest genetics-based relationship existing in the identical twins. Several pioneers have analyzed the similarity between twins' fingerprints. In this work we continue to investigate the topic of the similarity of identical twin fingerprints. Our study was tested based on a large identical twin fingerprint database that contains 83 twin pairs, 4 fingers per individual and six impressions per finger: 3984 (83*2*4*6 images. Compared to the previous work, our contributions are summarized as follows: (1 Two state-of-the-art fingerprint identification methods: P071 and VeriFinger 6.1 were used, rather than one fingerprint identification method in previous studies. (2 Six impressions per finger were captured, rather than just one impression, which makes the genuine distribution of matching scores more realistic. (3 A larger sample (83 pairs was collected. (4 A novel statistical analysis, which aims at showing the probability distribution of the fingerprint types for the corresponding fingers of identical twins which have same fingerprint type, has been conducted. (5 A novel analysis, which aims at showing which finger from identical twins has higher probability of having same fingerprint type, has been conducted. Our results showed that: (a A state-of-the-art automatic fingerprint verification system can distinguish identical twins without drastic degradation in performance. (b The chance that the fingerprints have the same type from identical twins is 0.7440, comparing to 0.3215 from non-identical twins. (c For the corresponding fingers of identical twins which have same fingerprint type, the probability distribution of five major fingerprint types is similar to the probability distribution for all the fingers' fingerprint type. (d For each of four fingers of identical twins, the probability of having same fingerprint type is similar.

Proteome-wide analysis of arginine monomethylation reveals widespread occurrence in human cells

DEFF Research Database (Denmark)

Larsen, Sara C; Sylvestersen, Kathrine B; Mund, Andreas

2016-01-01

to the frequency of somatic mutations at arginine methylation sites throughout the proteome, we observed that somatic mutations were common at arginine methylation sites in proteins involved in mRNA splicing. Furthermore, in HeLa and U2OS cells, we found that distinct arginine methyltransferases differentially...... kidney 293 cells, indicating that the occurrence of this modification is comparable to phosphorylation and ubiquitylation. A site-level conservation analysis revealed that arginine methylation sites are less evolutionarily conserved compared to arginines that were not identified as modified...... as coactivator-associated arginine methyltransferase 1 (CARM1)] or PRMT1 increased the RNA binding function of HNRNPUL1. High-content single-cell imaging additionally revealed that knocking down CARM1 promoted the nuclear accumulation of SRSF2, independent of cell cycle phase. Collectively, the presented human...

The classical twin study and beyond

NARCIS (Netherlands)

Boomsma, D.I.; Busjahn, A.; Peltonen, L.

2002-01-01

Twin studies have been a valuable source of information about the genetic basis of complex traits. To maximize the potential of twin studies, large, worldwide registers of data on twins and their relatives have been established. Here, we provide an overview of the current resources for twin

The arginine-ornithine antiporter ArcD contributes to biological fitness of Streptococcus suis

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Marcus eFulde

2014-08-01

Full Text Available The arginine-ornithine antiporter (ArcD is part of the Arginine Deiminase System (ADS, a catabolic, energy-providing pathway found in a variety of different bacterial species, including the porcine zoonotic pathogen Streptococcus suis. The ADS has recently been shown to play a role in the pathogenicity of S. suis, in particular in its survival in host cells. The contribution of arginine and arginine transport mediated by ArcD, however, has yet to be clarified. In the present study, we showed by experiments using [U-13C6]arginine as a tracer molecule that S. suis is auxotrophic for arginine and that bacterial growth depends on the uptake of extracellular arginine. To further study the role of ArcD in arginine metabolism, we generated an arcD-specific mutant strain and characterized its growth compared to the wild-type (WT strain, a virulent serotype 2 strain. The mutant strain showed a markedly reduced growth rate in chemically defined media supplemented with arginine when compared to the WT strain, indicating that ArcD promotes arginine uptake. To further evaluate the in vivo relevance of ArcD, we studied the intracellular bacterial survival of the arcD mutant strain in an epithelial cell culture infection model. The mutant strain was substantially attenuated, and its reduced intracellular survival rate correlated with a lower ability to neutralize the acidified environment. Based on these results, we propose that ArcD, by its function as an arginine-ornithine antiporter, is important for supplying arginine as substrate of the ADS and, thereby, contributes to biological fitness and virulence of S. suis in the host.

Arginine and Polyamines Fate in Leishmania Infection

Science.gov (United States)

Muxel, Sandra M.; Aoki, Juliana I.; Fernandes, Juliane C. R.; Laranjeira-Silva, Maria F.; Zampieri, Ricardo A.; Acuña, Stephanie M.; Müller, Karl E.; Vanderlinde, Rubia H.; Floeter-Winter, Lucile M.

2018-01-01

Leishmania is a protozoan parasite that alternates its life cycle between the sand fly and the mammalian host macrophages, involving several environmental changes. The parasite responds to these changes by promoting a rapid metabolic adaptation through cellular signaling modifications that lead to transcriptional and post-transcriptional gene expression regulation and morphological modifications. Molecular approaches such as gene expression regulation, next-generation sequencing (NGS), microRNA (miRNA) expression profiling, in cell Western blot analyses and enzymatic activity profiling, have been used to characterize the infection of murine BALB/c and C57BL/6 macrophages, as well as the human monocytic cell-lineage THP-1, with Leishmania amazonensis wild type (La-WT) or arginase knockout (La-arg-). These models are being used to elucidate physiological roles of arginine and polyamines pathways and the importance of arginase for the establishment of the infection. In this review, we will describe the main aspects of Leishmania-host interaction, focusing on the arginine and polyamines pathways and pointing to possible targets to be used for prognosis and/or in the control of the infection. The parasite enzymes, arginase and nitric oxide synthase-like, have essential roles in the parasite survival and in the maintenance of infection. On the other hand, in mammalian macrophages, defense mechanisms are activated inducing alterations in the mRNA, miRNA and enzymatic profiles that lead to the control of infection. Furthermore, the genetic background of both parasite and host are also important to define the fate of infection. PMID:29379478

Sensing lymphoma cells based on a cell-penetrating/apoptosis-inducing/electron-transfer peptide probe

International Nuclear Information System (INIS)

Sugawara, Kazuharu; Shinohara, Hiroki; Kadoya, Toshihiko; Kuramitz, Hideki

2016-01-01

To electrochemically sense lymphoma cells (U937), we fabricated a multifunctional peptide probe that consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. Electron-transfer peptides derive from cysteine residue combined with the C-terminals of four tyrosine residues (Y_4). A peptide whereby Y_4C is bound to the C-terminals of protegrin 1 (RGGRLCYCRRRFCVCVGR-NH_2) is known to be an apoptosis-inducing agent against U937 cells, and is referred to as a peptide-1 probe. An oxidation response of the peptide-1 probe has been observed due to a phenolic hydroxyl group, and this response is decreased by the uptake of the peptide probe into the cells. To improve the cell membrane permeability against U937 cells, the RGGR at the N-terminals of the peptide-1 probe was replaced by RRRR (peptide-2 probe). In contrast, RNRCKGTDVQAWY_4C (peptide-3 probe), which recognizes ovalbumin, was constructed as a control. Compared with the other probes, the change in the peak current of the peptide-2 probe was the greatest at low concentrations and occurred in a short amount of time. Therefore, the cell membrane permeability of the peptide-2 probe was increased based on the arginine residues and the apoptosis-inducing peptides. The peak current was linear and ranged from 100 to 1000 cells/ml. The relative standard deviation of 600 cells/ml was 5.0% (n = 5). Furthermore, the membrane permeability of the peptide probes was confirmed using fluorescent dye. - Highlights: • We constructed a multifunctional peptide probe for the electrochemical sensing of lymphoma cells. • The peptide probe consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. • The electrode response of the peptide probe changes due to selective uptake into the cells.

Sensing lymphoma cells based on a cell-penetrating/apoptosis-inducing/electron-transfer peptide probe

Energy Technology Data Exchange (ETDEWEB)

Sugawara, Kazuharu, E-mail: kzsuga@maebashi-it.ac.jp [Maebashi Institute of Technology, Gunma 371-0816 (Japan); Shinohara, Hiroki; Kadoya, Toshihiko [Maebashi Institute of Technology, Gunma 371-0816 (Japan); Kuramitz, Hideki [Department of Environmental Biology and Chemistry, Graduate School of Science and Engineering for Research, University of Toyama, Toyama 930-8555 (Japan)

2016-06-14

To electrochemically sense lymphoma cells (U937), we fabricated a multifunctional peptide probe that consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. Electron-transfer peptides derive from cysteine residue combined with the C-terminals of four tyrosine residues (Y{sub 4}). A peptide whereby Y{sub 4}C is bound to the C-terminals of protegrin 1 (RGGRLCYCRRRFCVCVGR-NH{sub 2}) is known to be an apoptosis-inducing agent against U937 cells, and is referred to as a peptide-1 probe. An oxidation response of the peptide-1 probe has been observed due to a phenolic hydroxyl group, and this response is decreased by the uptake of the peptide probe into the cells. To improve the cell membrane permeability against U937 cells, the RGGR at the N-terminals of the peptide-1 probe was replaced by RRRR (peptide-2 probe). In contrast, RNRCKGTDVQAWY{sub 4}C (peptide-3 probe), which recognizes ovalbumin, was constructed as a control. Compared with the other probes, the change in the peak current of the peptide-2 probe was the greatest at low concentrations and occurred in a short amount of time. Therefore, the cell membrane permeability of the peptide-2 probe was increased based on the arginine residues and the apoptosis-inducing peptides. The peak current was linear and ranged from 100 to 1000 cells/ml. The relative standard deviation of 600 cells/ml was 5.0% (n = 5). Furthermore, the membrane permeability of the peptide probes was confirmed using fluorescent dye. - Highlights: • We constructed a multifunctional peptide probe for the electrochemical sensing of lymphoma cells. • The peptide probe consists of cell-penetrating/apoptosis-inducing/electron-transfer peptides. • The electrode response of the peptide probe changes due to selective uptake into the cells.

Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

DEFF Research Database (Denmark)

Staalsø, Jonatan Myrup; Bergström, Anita; Edsen, Troels

2013-01-01

Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine...

Anti-Inflammatory Action of an Antimicrobial Model Peptide That Suppresses the TRIF-Dependent Signaling Pathway via Inhibition of Toll-Like Receptor 4 Endocytosis in Lipopolysaccharide-Stimulated Macrophages.

Directory of Open Access Journals (Sweden)

Do-Wan Shim

Full Text Available Antimicrobial peptides (AMPs, also called host defense peptides, particularly those with amphipathic helical structures, are emerging as target molecules for therapeutic development due to their immunomodulatory properties. Although the antimicrobial activity of AMPs is known to be exerted primarily by permeation of the bacterial membrane, the mechanism underlying its anti-inflammatory activity remains to be elucidated. We report potent anti-inflammatory activity of WALK11.3, an antimicrobial model peptide with an amphipathic helical conformation, in lipopolysaccharide (LPS-stimulated RAW264.7 cells. This peptide inhibited the expression of inflammatory mediators, including nitric oxide, COX-2, IL-1β, IL-6, INF-β, and TNF-α. Although WALK11.3 did not exert a major effect on all downstream signaling in the MyD88-dependent pathway, toll-like receptor 4 (TLR4- mediated pro-inflammatory signals were markedly attenuated in the TRIF-dependent pathway due to inhibition of the phosphorylation of STAT1 by attenuation of IRF3 phosphorylation. WALK11.3 specifically inhibited the endocytosis of TLR4, which is essential for triggering TRIF-mediated signaling in macrophage cells. Hence, we suggest that specific interference with TLR4 endocytosis could be one of the major modes of the anti-inflammatory action of AMPs. Our designed WALK11 peptides, which possess both antimicrobial and anti-inflammatory activities, may be promising molecules for the development of therapies for infectious inflammation.

Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation.

Science.gov (United States)

El-Hattab, Ayman W; Hsu, Jean W; Emrick, Lisa T; Wong, Lee-Jun C; Craigen, William J; Jahoor, Farook; Scaglia, Fernando

2012-04-01

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most common mitochondrial disorders. Although the pathogenesis of stroke-like episodes remains unclear, it has been suggested that mitochondrial proliferation may result in endothelial dysfunction and decreased nitric oxide (NO) availability leading to cerebral ischemic events. This study aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control subjects and subjects with MELAS syndrome before and after arginine or citrulline supplementation. The results showed that subjects with MELAS had lower NO synthesis rate associated with reduced citrulline flux, de novo arginine synthesis rate, and plasma arginine and citrulline concentrations, and higher plasma asymmetric dimethylarginine (ADMA) concentration and arginine clearance. We conclude that the observed impaired NO production is due to multiple factors including elevated ADMA, higher arginine clearance, and, most importantly, decreased de novo arginine synthesis secondary to decreased citrulline availability. Arginine and, to a greater extent, citrulline supplementation increased the de novo arginine synthesis rate, the plasma concentrations and flux of arginine and citrulline, and NO production. De novo arginine synthesis increased markedly with citrulline supplementation, explaining the superior efficacy of citrulline in increasing NO production. The improvement in NO production with arginine or citrulline supplementation supports their use in MELAS and suggests that citrulline may have a better therapeutic effect than arginine. These findings can have a broader relevance for other disorders marked by perturbations in NO metabolism. Copyright © 2012 Elsevier Inc. All rights reserved.

A non-covalent peptide-based carrier for in vivo delivery of DNA mimics.

Science.gov (United States)

Morris, May C; Gros, Edwige; Aldrian-Herrada, Gudrun; Choob, Michael; Archdeacon, John; Heitz, Frederic; Divita, Gilles

2007-01-01

The dramatic acceleration in identification of new nucleic-acid-based therapeutic molecules has provided new perspectives in pharmaceutical research. However, their development is limited by their poor cellular uptake and inefficient trafficking. Here we describe a short amphipathic peptide, Pep-3, that combines a tryptophan/phenylalanine domain with a lysine/arginine-rich hydrophilic motif. Pep-3 forms stable nano-size complexes with peptide-nucleic acid analogues and promotes their efficient delivery into a wide variety of cell lines, including primary and suspension lines, without any associated cytotoxicity. We demonstrate that Pep-3-mediated delivery of antisense-cyclin B1-charged-PNA blocks tumour growth in vivo upon intratumoral and intravenous injection. Moreover, we show that PEGylation of Pep-3 significantly improves complex stability in vivo and consequently the efficiency of antisense cyclin B1 administered intravenously. Given the biological characteristics of these vectors, we believe that peptide-based delivery technologies hold a true promise for therapeutic applications of DNA mimics.

Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

International Nuclear Information System (INIS)

Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

2016-01-01

We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

Energy Technology Data Exchange (ETDEWEB)

Sunatkari, A. L., E-mail: ashok.sunatkari@rediffmail.com [Department of Physics, Siddhartha College of Arts, Science and Commerce, Fort, Mumbai-400001, India. Email: ashok.sunatkari@rediffmail.com (India); Talwatkar, S. S. [Department of Physics, N.G. Aacharya and D.K. Maratha College of Arts, Science and Commerce, Chembur, Mumbai-400071, India. Email: swarna-81@rediffmail.com (India); Tamgadge, Y. S. [Department of Physics, Mahatma Phule Arts, Commerce & S.R.C. Science College, Warud-444906, India. Email: ystamgadge@gmail.com (India); Muley, G. G., E-mail: gajananggm@yahoo.co.in [Department of Physics, Sant Gadge Baba Amravati University, Amravati-444602 India. Email: gajananggm@yahoo.co.in (India)

2016-05-06

We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

Twin Higgs Asymmetric Dark Matter.

Science.gov (United States)

García García, Isabel; Lasenby, Robert; March-Russell, John

2015-09-18

We study asymmetric dark matter (ADM) in the context of the minimal (fraternal) twin Higgs solution to the little hierarchy problem, with a twin sector with gauged SU(3)^{'}×SU(2)^{'}, a twin Higgs doublet, and only third-generation twin fermions. Naturalness requires the QCD^{'} scale Λ_{QCD}^{'}≃0.5-20  GeV, and that t^{'} is heavy. We focus on the light b^{'} quark regime, m_{b^{'}}≲Λ_{QCD}^{'}, where QCD^{'} is characterized by a single scale Λ_{QCD}^{'} with no light pions. A twin baryon number asymmetry leads to a successful dark matter (DM) candidate: the spin-3/2 twin baryon, Δ^{'}∼b^{'}b^{'}b^{'}, with a dynamically determined mass (∼5Λ_{QCD}^{'}) in the preferred range for the DM-to-baryon ratio Ω_{DM}/Ω_{baryon}≃5. Gauging the U(1)^{'} group leads to twin atoms (Δ^{'}-τ^{'}[over ¯] bound states) that are successful ADM candidates in significant regions of parameter space, sometimes with observable changes to DM halo properties. Direct detection signatures satisfy current bounds, at times modified by dark form factors.

Hepatic adaptation compensates inactivation of intestinal arginine biosynthesis in suckling mice.

Directory of Open Access Journals (Sweden)

Vincent Marion

Full Text Available Suckling mammals, including mice, differ from adults in the abundant expression of enzymes that synthesize arginine from citrulline in their enterocytes. To investigate the importance of the small-intestinal arginine synthesis for whole-body arginine production in suckling mice, we floxed exon 13 of the argininosuccinate synthetase (Ass gene, which codes for a key enzyme in arginine biosynthesis, and specifically and completely ablated Ass in enterocytes by crossing Ass (fl and Villin-Cre mice. Unexpectedly, Ass (fl/fl /VilCre (tg/- mice showed no developmental impairments. Amino-acid fluxes across the intestine, liver, and kidneys were calculated after determining the blood flow in the portal vein, and hepatic and renal arteries (86%, 14%, and 33%, respectively, of the transhepatic blood flow in 14-day-old mice. Relative to control mice, citrulline production in the splanchnic region of Ass (fl/fl /VilCre (tg/- mice doubled, while arginine production was abolished. Furthermore, the net production of arginine and most other amino acids in the liver of suckling control mice declined to naught or even changed to consumption in Ass (fl/fl /VilCre (tg/- mice, and had, thus, become remarkably similar to that of post-weaning wild-type mice, which no longer express arginine-biosynthesizing enzymes in their small intestine. The adaptive changes in liver function were accompanied by an increased expression of genes involved in arginine metabolism (Asl, Got1, Gpt2, Glud1, Arg1, and Arg2 and transport (Slc25a13, Slc25a15, and Slc3a2, whereas no such changes were found in the intestine. Our findings suggest that the genetic premature deletion of arginine synthesis in enterocytes causes a premature induction of the post-weaning pattern of amino-acid metabolism in the liver.

Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

DEFF Research Database (Denmark)

Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina

2010-01-01

This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5 g...... intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4+/-0.5 mM in the first 90 min (period 1) and raised 1.5 times the fasting...

DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins

DEFF Research Database (Denmark)

Tsai, Pei-Chien; Van Dongen, Jenny; Tan, Qihua

2015-01-01

persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg...... were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect...... was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent...

Attachment to the Romantic Partner and Sibling: Attachment Hierarchies of Twins and Non-Twin Siblings

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Sascha Schwarz

2015-12-01

Full Text Available Previous studies have shown that romantic partners and siblings are important attachment figures. This study compares the attachment to the romantic partner with the attachment to the sibling as a function of the participant’s sibling type among monozygotic (MZ twins, dizygotic (DZ twins, and non-twin (NT siblings. The results show that MZ twins prefer their sibling to their romantic partner whereas DZ twins are equally attached to their sibling and romantic partner. In contrast, NT siblings are more attached to their romantic partner compared to their sibling. These results indicate that genetic relatedness has profound impact on a person’s attachment hierarchy and the relative rank of the romantic partner and the sibling.

Novel epigenetic changes unveiled by monozygotic twins discordant for smoking habits.

Science.gov (United States)

Allione, Alessandra; Marcon, Francesca; Fiorito, Giovanni; Guarrera, Simonetta; Siniscalchi, Ester; Zijno, Andrea; Crebelli, Riccardo; Matullo, Giuseppe

2015-01-01

Exposure to cigarette smoking affects the epigenome and could increase the risk of developing diseases such as cancer and cardiovascular disorders. Changes in DNA methylation associated with smoking may help to identify molecular pathways that contribute to disease etiology. Previous studies are not completely concordant in the identification of differentially methylated regions in the DNA of smokers. We performed an epigenome-wide DNA methylation study in a group of monozygotic (MZ) twins discordant for smoking habits to determine the effect of smoking on DNA methylation. As MZ twins are considered genetically identical, this model allowed us to identify smoking-related DNA methylation changes independent from genetic components. We investigated the whole blood genome-wide DNA methylation profiles in 20 MZ twin pairs discordant for smoking habits by using the Illumina HumanMethylation450 BeadChip. We identified 22 CpG sites that were differentially methylated between smoker and non-smoker MZ twins by intra-pair analysis. We confirmed eight loci already described by other groups, located in AHRR, F2RL3, MYOG1 genes, at 2q37.1 and 6p21.33 regions, and also identified several new loci. Moreover, pathway analysis showed an enrichment of genes involved in GTPase regulatory activity. Our study confirmed the evidence of smoking-related DNA methylation changes, emphasizing that well-designed MZ twin models can aid the discovery of novel DNA methylation signals, even in a limited sample population.

Biologically Active and Antimicrobial Peptides from Plants

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Carlos E. Salas

2015-01-01

Full Text Available Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application.

Biologically Active and Antimicrobial Peptides from Plants

Science.gov (United States)

Salas, Carlos E.; Badillo-Corona, Jesus A.; Ramírez-Sotelo, Guadalupe; Oliver-Salvador, Carmen

2015-01-01

Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application. PMID:25815307

Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation

International Nuclear Information System (INIS)

Sheng, Xiumei; Wang, Zhengxin

2016-01-01

Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation. The online version of this article (doi:10.1186/s12885-016-2632-3) contains supplementary material, which is available to authorized users

Neurodevelopmental outcome at 2 years in twin-twin transfusion syndrome survivors randomized for the Solomon trial.

Science.gov (United States)

van Klink, Jeanine M M; Slaghekke, Femke; Balestriero, Marina A; Scelsa, Barbara; Introvini, Paola; Rustico, Mariangela; Faiola, Stefano; Rijken, Monique; Koopman, Hendrik M; Middeldorp, Johanna M; Oepkes, Dick; Lopriore, Enrico

2016-01-01

The preferred treatment for twin-twin transfusion syndrome is fetoscopic laser coagulation of inter-twin vascular anastomoses on the monochorionic placenta. Severe postoperative complications can occur when inter-twin vascular anastomoses remain patent including twin-anemia polycythemia sequence or recurrent twin-twin transfusion syndrome. To minimize the occurrence of residual anastomoses, a modified laser surgery technique, the Solomon technique, was developed in which the entire vascular equator is coagulated. In the Solomon randomized controlled trial (NTR1245), the Solomon technique was associated with a significant reduction in twin-anemia polycythemia sequence and recurrence of twin-twin transfusion syndrome when compared with the standard laser surgery technique. Although a significant improvement in perinatal outcome was shown after the Solomon technique, the clinical importance should also be ascertained with long-term follow-up evaluation of the surviving children. The purpose of this study was to compare the long-term neurodevelopmental outcome in surviving children with twin-twin transfusion syndrome who were included in the Solomon randomized trial and treated with either the Solomon technique or standard laser surgery technique. Routine standardized follow-up evaluation in survivors, at least 2 years after the estimated date of delivery, was performed at 2 of the 5 centers that participated in the Solomon trial: Buzzi Hospital Milan (Italy) and Leiden University Medical Center (The Netherlands). The primary outcome of this follow-up study was survival without long-term neurodevelopmental impairment at age 2 years. Neurodevelopmental impairment was defined as cerebral palsy, cognitive and/or motor development score of neurodevelopmental impairment) was detected in 95 of 141 cases (67%) in the Solomon group and in 99 of 146 cases (68%) in the standard group (P = .92). Neurodevelopmental impairment in long-term survivors who were included for follow

Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

Science.gov (United States)

Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

2017-06-25

Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Low twinning rate and seasonal effects on twinning in a fertile population, the Hutterites

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Nonaka, K.; Miura, T.; Peter, K.

1993-09-01

This paper analyzes from the mid 18th century to 1987 the birth records of the “Dariusleut,” one of the three subgroups of the Hutterite population. The aim of this study is to describe several aspects of the twinning rate in a fertile population. The overall rate of twinning was 0.90%:103 twins among all 11492 maternities. The rate peaked at the 7th birth order and at the maternal age of 40 years and over. Until the mid 19th century when the Hutterites lived in Russia, the twinning rate was higher (1.5%), and it decreased during the migration period in the second half of the 19th century (0.7%). After the group had settled in the USA and Canada, the population maintained a twinning rate of 1.0% until 1965. After 1965 the rate decreased to 0.7%, partly due to a decline in fertility among women aged 30 years and over. There was a significant seasonal variation: the twinning rate decreased to 0.5% in May July compared to 1.2% for the other three seasons during the years up to 1965 ( P<0.01), while more recent mothers did not show such a seasonal variation. The incidence of twin births in this population seems to have been influenced by environmental factors, which would change their effect seasonally and secularly.

Cleavage specificity analysis of six type II transmembrane serine proteases (TTSPs using PICS with proteome-derived peptide libraries.

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Olivier Barré

Full Text Available Type II transmembrane serine proteases (TTSPs are a family of cell membrane tethered serine proteases with unclear roles as their cleavage site specificities and substrate degradomes have not been fully elucidated. Indeed just 52 cleavage sites are annotated in MEROPS, the database of proteases, their substrates and inhibitors.To profile the active site specificities of the TTSPs, we applied Proteomic Identification of protease Cleavage Sites (PICS. Human proteome-derived database searchable peptide libraries were assayed with six human TTSPs (matriptase, matriptase-2, matriptase-3, HAT, DESC and hepsin to simultaneously determine sequence preferences on the N-terminal non-prime (P and C-terminal prime (P' sides of the scissile bond. Prime-side cleavage products were isolated following biotinylation and identified by tandem mass spectrometry. The corresponding non-prime side sequences were derived from human proteome databases using bioinformatics. Sequencing of 2,405 individual cleaved peptides allowed for the development of the family consensus protease cleavage site specificity revealing a strong specificity for arginine in the P1 position and surprisingly a lysine in P1' position. TTSP cleavage between R↓K was confirmed using synthetic peptides. By parsing through known substrates and known structures of TTSP catalytic domains, and by modeling the remainder, structural explanations for this strong specificity were derived.Degradomics analysis of 2,405 cleavage sites revealed a similar and characteristic TTSP family specificity at the P1 and P1' positions for arginine and lysine in unfolded peptides. The prime side is important for cleavage specificity, thus making these proteases unusual within the tryptic-enzyme class that generally has overriding non-prime side specificity.

Chemical mechanisms of histone lysine and arginine modifications

OpenAIRE

Smith, Brian C.; Denu, John M.

2008-01-01

Histone lysine and arginine residues are subject to a wide array of post-translational modifications including methylation, citrullination, acetylation, ubiquitination, and sumoylation. The combinatorial action of these modifications regulates critical DNA processes including replication, repair, and transcription. In addition, enzymes that modify histone lysine and arginine residues have been correlated with a variety of human diseases including arthritis, cancer, heart disease, diabetes, an...

Effect of introduction of chondroitin sulfate into polymer-peptide conjugate responding to intracellular signals

Science.gov (United States)

Tomiyama, Tetsuro; Toita, Riki; Kang, Jeong-Hun; Koga, Haruka; Shiosaki, Shujiro; Mori, Takeshi; Niidome, Takuro; Katayama, Yoshiki

2011-09-01

We recently developed a novel tumor-targeted gene delivery system responding to hyperactivated intracellular signals. Polymeric carrier for gene delivery consists of hydrophilic neutral polymer as main chains and cationic peptide substrate for target enzyme as side chains, and was named polymer-peptide conjugate (PPC). Introduction of chondroitin sulfate (CS), which induces receptor-medicated endocytosis, into polymers mainly with a high cationic charge density such as polyethylenimine can increase tumor-targeted gene delivery. In the present study, we examined whether introduction of CS into PPC containing five cationic amino acids can increase gene expression in tumor cells. Size and zeta potential of plasmid DNA (pDNA)/PPC/CS complex were <200 nm and between -10 and -15 mV, respectively. In tumor cell experiments, pDNA/PPC/CS complex showed lower stability and gene regulation, compared with that of pDNA/PPC. Moreover, no difference in gene expression was identified between positive and negative polymer. These results were caused by fast disintegration of pDNA/PPC/CS complexes in the presence of serum. Thus, we suggest that introduction of negatively charged CS into polymers with a low charge density may lead to low stability and gene regulation of complexes.

Gastro-Resistant Insulin Receptor-Binding Peptide from Momordica charantia Improved the Glucose Tolerance in Streptozotocin-Induced Diabetic Mice via Insulin Receptor Signaling Pathway.

Science.gov (United States)

Lo, Hsin-Yi; Li, Chia-Cheng; Chen, Feng-Yuan; Chen, Jaw-Chyun; Hsiang, Chien-Yun; Ho, Tin-Yun

2017-10-25

Momordica charantia is a commonly used food and has been used for the management of diabetes. Our previous study has identified an insulin receptor (IR)-binding protein (mcIRBP) from Momordica charantia. Here we identified the gastro-resistant hypoglycemic bioactive peptides from protease-digested mcIRBP. By in vitro digestion and IR kinase activity assay, we found that a 9-amino-acid-residue peptide, mcIRBP-9, was a gastro-resistant peptide that enhanced IR kinase activities. mcIRBP-9 activated IR signaling transduction pathway, which resulted in the phosphorylation of IR, the translocation of glucose transporter 4, and the uptake of glucose in cells. Intraperitoneal and oral administration of mcIRBP-9 stimulated the glucose clearance by 30.91 ± 0.39% and 32.09 ± 0.38%, respectively, in streptozotocin-induced diabetic mice. Moreover, a pilot study showed that daily ingestion of mcIRBP-9 for 30 days decreased the fasting blood glucose levels and glycated hemoglobin (HbA1c) levels by 23.62 ± 6.14% and 24.06 ± 1.53%, respectively. In conclusion, mcIRBP-9 is a unique gastro-resistant bioactive peptide generated after the digestion of mcIRBP. Furthermore, oral administration of mcIRBP-9 improves both the glucose tolerance and the HbA1c levels in diabetic mice via targeting IR signaling transduction pathway.

'Twin2twin' an innovative method of empowering midwives to strengthen their professional midwifery organisations.

Science.gov (United States)

Cadée, Franka; Perdok, Hilde; Sam, Betty; de Geus, Myrte; Kweekel, Liselotte

2013-10-01

midwives need professional support from a national midwifery organisation to be able to provide the services that are by regulatory mechanisms and accreditation expected of them. Not all midwives in the world are united in a professional organisation. The aim of this project was to strengthen the midwifery organisations of Sierra Leone and the Netherlands. During the process of the project it was realised that the development of a platform of exchange at organisational level would be enhanced by introducing personal exchange between individual midwives. In response to this new insight the original project plan was adjusted by incorporating the twin2twin method. twin2twin is a feminist methodology of mutual exchange between twenty pairs of midwives from different organisations (in this case Sierra Leone and the Netherlands). The method can be distinguished by 10 specific steps. It was developed, used and (re)evaluated through focus group discussions, storytelling and written evaluations. twinning of organisations was strengthened by adding a human component to the process. With the use of the 'twin2twin' method, midwives were encouraged to invested in a professional and personal bond with their 'twin sister'. This bond was independent and went beyond the relatively short four year project period. Through personal engagement and mutual exchange of knowledge and skills, midwives empowered each other to build and strengthen their midwifery organisations both in Sierra Leone and the Netherlands. (Empowerment refers to the expansion in people's ability to make strategic life choices in a context where this ability was previously denied to them (Narayan, 2005); organisational empowerment includes processes and structures that enhance members' skills and provides them with the mutual support necessary to effect community level change (Zimmerman, 1995).). despite challenges we are convinced that twin2twin can be of additional benefit for the success of other projects

The subcellular compartmentalization of arginine metabolizing enzymes and their role in endothelial dysfunction

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Feng eChen

2013-07-01

Full Text Available The endothelial production of nitric oxide (NO mediates endothelium-dependent vasorelaxation and restrains vascular inflammation, smooth muscle proliferation and platelet aggregation. Impaired production of NO is a hallmark of endothelial dysfunction and promotes the development of cardiovascular disease. In endothelial cells, NO is generated by endothelial nitric oxide synthase (eNOS through the conversion of its substrate, L-arginine to L-citrulline. Reduced access to L-arginine has been proposed as a major mechanism underlying reduced eNOS activity and NO production in cardiovascular disease. The arginases (Arg1 and Arg2 metabolize L-arginine to generate L-ornithine and urea and increased expression of arginase has been proposed as a mechanism of reduced eNOS activity secondary to the depletion of L-arginine. Indeed, supplemental L-arginine and suppression of arginase activity has been shown to improve endothelium-dependent relaxation and ameliorate cardiovascular disease. However, L-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis suggesting additional mechanisms. The compartmentalization of intracellular L-arginine into poorly interchangeable pools has been proposed to allow for the local depletion of L-arginine. Indeed the subcellular location of L-arginine metabolizing enzymes plays important functional roles. In endothelial cells, eNOS is found in discrete intracellular locations and the capacity to generate NO is heavily influenced by its localtion. Arg1 and Arg2 also reside in different subcellular environments and are thought to differentially influence endothelial function. The plasma membrane solute transporter, CAT-1 and the arginine recycling enzyme, ASL, co-localize with eNOS and facilitate NO release. This review highlights the importance of the subcellular location of eNOS and arginine transporting and metabolizing enzymes to NO release and cardiovascular disease.

An engineered genetic selection for ternary protein complexes inspired by a natural three-component hitchhiker mechanism.

Science.gov (United States)

Lee, Hyeon-Cheol; Portnoff, Alyse D; Rocco, Mark A; DeLisa, Matthew P

2014-12-22

The bacterial twin-arginine translocation (Tat) pathway is well known to translocate correctly folded monomeric and dimeric proteins across the tightly sealed cytoplasmic membrane. We identified a naturally occurring heterotrimer, the Escherichia coli aldehyde oxidoreductase PaoABC, that is co-translocated by the Tat translocase according to a ternary "hitchhiker" mechanism. Specifically, the PaoB and PaoC subunits, each devoid of export signals, are escorted to the periplasm in a piggyback fashion by the Tat signal peptide-containing subunit PaoA. Moreover, export of PaoA was blocked when either PaoB or PaoC was absent, revealing a surprising interdependence for export that is not seen for classical secretory proteins. Inspired by this observation, we created a bacterial three-hybrid selection system that links the formation of ternary protein complexes with antibiotic resistance. As proof-of-concept, a bispecific antibody was employed as an adaptor that physically crosslinked one antigen fused to a Tat export signal with a second antigen fused to TEM-1 β-lactamase (Bla). The resulting non-covalent heterotrimer was exported in a Tat-dependent manner, delivering Bla to the periplasm where it hydrolyzed β-lactam antibiotics. Collectively, these results highlight the remarkable flexibility of the Tat system and its potential for studying and engineering ternary protein interactions in living bacteria.

Atropine and ODQ antagonize tetanic fade induced by L-arginine in cats

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J.M. Cruciol-Souza

1999-10-01

Full Text Available Although it has been demonstrated that nitric oxide (NO released from sodium nitrite induces tetanic fade in the cat neuromuscular preparations, the effect of L-arginine on tetanic fade and its origin induced by NO have not been studied in these preparations. Furthermore, atropine reduces tetanic fade induced by several cholinergic and anticholinergic drugs in these preparations, whose mechanism is suggested to be mediated by the interaction of acetylcholine with inhibitory presynaptic muscarinic receptors. The present study was conducted in cats to determine the effects of L-arginine alone or after pretreatment with atropine or 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ on neuromuscular preparations indirectly stimulated at high frequency. Drugs were injected into the middle genicular artery. L-arginine (2 mg/kg and S-nitroso-N-acetylpenicillamine (SNAP; 16 µg/kg induced tetanic fade. The Nw-nitro-L-arginine (L-NOARG; 2 mg/kg alone did not produce any effect, but reduced the tetanic fade induced by L-arginine. D-arginine (2 mg/kg did not induce changes in tetanic fade. The tetanic fade induced by L-arginine or SNAP was reduced by previous injection of atropine (1.0 µg/kg or ODQ (15 µg/kg. ODQ alone did not change tetanic fade. The data suggest that the NO-synthase-GC pathway participates in the L-arginine-induced tetanic fade in cat neuromuscular preparations. The tetanic fade induced by L-arginine probably depends on the action of NO at the presynaptic level. NO may stimulate guanylate cyclase increasing acetylcholine release and thereby stimulating presynaptic muscarinic receptors.

Plasma glucagon responses to L-arginine in various diseases

International Nuclear Information System (INIS)

Morita, Nobuto; Hayakawa, Hiroyuki; Kawai, Kohzo; Noto, Yutaka; Ohno, Taro

1978-01-01

To clarify the mechanism of abnormal glucose metabolism in the secondary diabetes, we examined the dynamics of plasma glucagon levels in various diseases which may accompany glucose intolerance. Plasma glucagon responses to L-arginine were observed in 20 liver cirrhotics, 8 patients with chronic renal failure, 6 patients with chronic pancreatitis, 4 patients, with hyperthyroidism, 22 diabetics and 9 normal controls. Plasma glucagon levels were determined by the radioimmunoassay method of Unger using 125 I-glucagon and antiserum 30K which is specific for pancreatic glucagon. In the cirrhotics, the plasma glucagon responses to L-arginine were significantly higher than in normal controls. The patients whose BSP retention at 45 minutes were above 30% showed higher plasma glucagon responses than in the patients whose BSP retention at 45 minutes were below 30%, suggesting that the more severely the liver was damaged, the more the plasma glucagon levels were elevated. In the patients with chronic renal failure, the plasma glucagon responses to L-arginine were also significantly higher than in normal controls. These abnormal levels were not improved by a hemodialysis, although serum creatinine levels were fairly decreased. In the patients with chronic pancreatitis, the plasma glucagon responses to L-arginine were the same as those in normal controls. In the patients with hyperthyroidism the plasma glucagon responses to L-arginine seemed to be lower than normal controls. In the diabetics, the plasma glucagon responses to L-arginine were almost the same as in normal controls. However their glucagon levels seemed to be relatively high, considering the fact that diabetics had high blood glucose levels. (auth.)

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

Science.gov (United States)

Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti; Sund, Reijo; Yokoyama, Yoshie; Ullemar, Vilhelmina; Almqvist, Catarina; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Kandler, Christian; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Rebato, Esther; Stazi, Maria A; Fagnani, Corrado; Brescianini, Sonia; Hur, Yoon-Mi; Jeong, Hoe-Uk; Cutler, Tessa L; Hopper, John L; Busjahn, Andreas; Saudino, Kimberly J; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rose, Richard J; Koskenvuo, Markku; Heikkilä, Kauko; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Nelson, Tracy L; Whitfield, Keith E; Tan, Qihua; Zhang, Dongfeng; Llewellyn, Clare H; Fisher, Abigail; Burt, S Alexandra; Klump, Kelly L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Medland, Sarah E; Martin, Nicholas G; Montgomery, Grant W; Magnusson, Patrik K E; Pedersen, Nancy L; Dahl Aslan, Anna K; Corley, Robin P; Huibregtse, Brooke M; Öncel, Sevgi Y; Aliev, Fazil; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Catharina E M; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Rasmussen, Finn; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Gatz, Margaret; Butler, David A; Lichtenstein, Paul; Goldberg, Jack H; Harden, K Paige; Tucker-Drob, Elliot M; Duncan, Glen E; Buchwald, Dedra; Tarnoki, Adam D; Tarnoki, David L; Franz, Carol E; Kremen, William S; Lyons, Michael J; Maia, José A; Freitas, Duarte L; Turkheimer, Eric; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko

2017-10-01

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Novel Approach to Prepare {sup 99m}Tc-Based Multivalent RGD Peptides

Energy Technology Data Exchange (ETDEWEB)

Shuang Liu

2012-10-24

This project presents a novel approach to prepare the {sup 99m}Tc-bridged multivalent RGD (arginine-glycine-aspartate) peptides. This project will focus on fundamentals of {sup 99m}Tc radiochemistry. The main objective of this project is to demonstrate the proof-of-principle for the proposed radiotracers. Once a kit formulation is developed for preparation of the {sup 99m}Tc-bridged multivalent RGD peptides, various tumor-bearing animal models will be used to evaluate their potential for SPECT (single photon-emission computed tomography) imaging of cancer. We have demonstrated that (1) multimerization of cyclic RGD peptides enhances the integrin {alpha}{sub v}{beta}{sub 3} bonding affinity and radiotracer tumor uptake; (2) addition of G{sub 3} or PEG{sub 4} linkers makes it possible for two RGD motifs in 3P-RGD{sub 2} and 3G-RGD{sub 2} to achieve simultaneous integrin {alpha}{sub v}{beta}{sub 3} binding; and (3) multimers are actually bivalent (not multivalent), the presence of extra RGD motifs can enhance the tumor retention time of the radiotracer.

Perturbation of estrogen receptor α localization with synthetic nona-arginine LXXLL-peptide coactivator binding inhibitors

NARCIS (Netherlands)

Carraz, M.; Zwart, W.; Phan, T.; Michalides, R.; Brunsveld, L.

2009-01-01

The interaction of estrogen receptor a (ERa) with the consensus LXXLL motifs of transcriptional coactivators provides an entry for functional ERa inhibition. Here, synthetic cell-permeable LXXLL peptide probes are brought forward that allow evaluation of the interaction of specific recognition

A tale of twin Higgs: natural twin two Higgs doublet models

International Nuclear Information System (INIS)

Yu, Jiang-Hao

2016-01-01

In original twin Higgs model, vacuum misalignment between electroweak and new physics scales is realized by adding explicit ℤ 2 breaking term. Introducing additional twin Higgs could accommodate spontaneous ℤ 2 breaking, which explains origin of this misalignment. We introduce a class of twin two Higgs doublet models with most general scalar potential, and discuss general conditions which trigger electroweak and ℤ 2 symmetry breaking. Various scenarios on realising the vacuum misalignment are systematically discussed in a natural composite two Higgs double model framework: explicit ℤ 2 breaking, radiative ℤ 2 breaking, tadpole-induced ℤ 2 breaking, and quartic-induced ℤ 2 breaking. We investigate the Higgs mass spectra and Higgs phenomenology in these scenarios.

Database-Guided Discovery of Potent Peptides to Combat HIV-1 or Superbugs

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Guangshun Wang

2013-05-01

Full Text Available Antimicrobial peptides (AMPs, small host defense proteins, are indispensable for the protection of multicellular organisms such as plants and animals from infection. The number of AMPs discovered per year increased steadily since the 1980s. Over 2,000 natural AMPs from bacteria, protozoa, fungi, plants, and animals have been registered into the antimicrobial peptide database (APD. The majority of these AMPs (>86% possess 11–50 amino acids with a net charge from 0 to +7 and hydrophobic percentages between 31–70%. This article summarizes peptide discovery on the basis of the APD. The major methods are the linguistic model, database screening, de novo design, and template-based design. Using these methods, we identified various potent peptides against human immunodeficiency virus type 1 (HIV-1 or methicillin-resistant Staphylococcus aureus (MRSA. While the stepwise designed anti-HIV peptide is disulfide-linked and rich in arginines, the ab initio designed anti-MRSA peptide is linear and rich in leucines. Thus, there are different requirements for antiviral and antibacterial peptides, which could kill pathogens via different molecular targets. The biased amino acid composition in the database-designed peptides, or natural peptides such as θ-defensins, requires the use of the improved two-dimensional NMR method for structural determination to avoid the publication of misleading structure and dynamics. In the case of human cathelicidin LL-37, structural determination requires 3D NMR techniques. The high-quality structure of LL-37 provides a solid basis for understanding its interactions with membranes of bacteria and other pathogens. In conclusion, the APD database is a comprehensive platform for storing, classifying, searching, predicting, and designing potent peptides against pathogenic bacteria, viruses, fungi, parasites, and cancer cells.

Using Twins to Better Understand Sibling Relationships.

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Mark, Katharine M; Pike, Alison; Latham, Rachel M; Oliver, Bonamy R

2017-03-01

We compared the nature of the sibling relationship in dyads of varying genetic relatedness, employing a behavioural genetic design to estimate the contribution that genes and the environment have on this familial bond. Two samples were used-the Sisters and Brothers Study consisted of 173 families with two target non-twin children (mean ages = 7.42 and 5.22 years respectively); and the Twins, Family and Behaviour study included 234 families with two target twin children (mean age = 4.70 years). Mothers and fathers reported on their children's relationship with each other, via a postal questionnaire (the Sisters and Brothers Study) or a telephone interview (the Twins, Family and Behaviour study). Contrary to expectations, no mean level differences emerged when monozygotic twin pairs, dizygotic twin pairs, and non-twin pairs were compared on their sibling relationship quality. Behavioural genetic analyses also revealed that the sibling bond was modestly to moderately influenced by the genetic propensities of the children within the dyad, and moderately to substantially influenced by the shared environment common to both siblings. In addition, for sibling negativity, we found evidence of twin-specific environmental influence-dizygotic twins showed more reciprocity than did non-twins. Our findings have repercussions for the broader application of results from future twin-based investigations.

Incidence of spontaneous twin anemia-polycythemia sequence in monochorionic-diamniotic twin pregnancies: Single-center prospective study.

Science.gov (United States)

Yokouchi, Tae; Murakoshi, Takeshi; Mishima, Takashi; Yano, Hiroko; Ohashi, Madoka; Suzuki, Takashi; Shinno, Takashi; Matsushita, Mitsuru; Nakayama, Satoru; Torii, Yuichi

2015-06-01

The purpose of this study was to prospectively estimate the incidence of spontaneous twin anemia-polycythemia sequence (TAPS) in monochorionic-diamniotic twin pregnancies. We prospectively examined umbilical cord hemoglobin (Hb) and reticulocyte count of consecutive monochorionic-diamniotic twin pregnancies delivered at Seirei Hamamatsu General Hospital from December 2006 to September 2013. We excluded cases of twin-twin transfusion syndrome, intrauterine fetal demise, and missing data (Hb and reticulocyte count missing from the medical record). TAPS was diagnosed using the postnatal criteria of intertwin Hb difference >8.0 g/dL and reticulocyte count ratio >1.7. Acute feto-fetal hemorrhage was defined as Hb difference >7 g/dL and reticulocyte count ratio <1.7. A total of 185 monochorionic-diamniotic twin pregnancies were included in this study. Three fulfilled the diagnostic criteria for postnatal TAPS, and one fulfilled the diagnostic criteria for acute feto-fetal hemorrhage. The incidence of spontaneous TAPS in monochorionic-diamniotic twin pregnancies was 1.6% (3/185) at Seirei Hamamatsu General Hospital. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

DmsD, a Tat system specific chaperone, interacts with other general chaperones and proteins involved in the molybdenum cofactor biosynthesis

OpenAIRE

Li, Haiming; Chang, Limei; Howell, Jenika M.; Turner, Raymond J.

2010-01-01

Many bacterial oxidoreductases depend on the Tat translocase for correct cell localization. Substrates for the Tat translocase possess twin-arginine leaders. System specific chaperones or redox enzyme maturation proteins (REMPs) are a group of proteins implicated in oxidoreductase maturation. DmsD is a REMP discovered in Escherichia coli, which interacts with the twin-arginine leader sequence of DmsA, the catalytic subunit of DMSO reductase. In this study, we identified several potential inte...

Stationary phase expression of the arginine biosynthetic operon argCBH in Escherichia coli

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Sun Yuan

2006-02-01

Full Text Available Abstract Background Arginine biosynthesis in Escherichia coli is elevated in response to nutrient limitation, stress or arginine restriction. Though control of the pathway in response to arginine limitation is largely modulated by the ArgR repressor, other factors may be involved in increased stationary phase and stress expression. Results In this study, we report that expression of the argCBH operon is induced in stationary phase cultures and is reduced in strains possessing a mutation in rpoS, which encodes an alternative sigma factor. Using strains carrying defined argR, and rpoS mutations, we evaluated the relative contributions of these two regulators to the expression of argH using operon-lacZ fusions. While ArgR was the main factor responsible for modulating expression of argCBH, RpoS was also required for full expression of this biosynthetic operon at low arginine concentrations (below 60 μM L-arginine, a level at which growth of an arginine auxotroph was limited by arginine. When the argCBH operon was fully de-repressed (arginine limited, levels of expression were only one third of those observed in ΔargR mutants, indicating that the argCBH operon is partially repressed by ArgR even in the absence of arginine. In addition, argCBH expression was 30-fold higher in ΔargR mutants relative to levels found in wild type, fully-repressed strains, and this expression was independent of RpoS. Conclusion The results of this study indicate that both derepression and positive control by RpoS are required for full control of arginine biosynthesis in stationary phase cultures of E. coli.

SUSY meets her twin

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Katz, Andrey [Theory Division, CERN,CH-1211 Geneva 23 (Switzerland); Département de Physique Théorique and Center for Astroparticle Physics (CAP),Université de Genève,24 quai Ansermet, CH-1211 Genève 4 (Switzerland); Mariotti, Alberto [Theoretische Natuurkunde and IIHE/ELEM, Vrije Universiteit Brussel,and International Solvay Institutes,Pleinlaan 2, B-1050 Brussels (Belgium); Pokorski, Stefan [Institute of Theoretical Physics, Faculty of Physics, University of Warsaw,ul. Pasteura 5, PL-02-093 Warsaw (Poland); Redigolo, Diego [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University,Tel-Aviv 69978 (Israel); Department of Particle Physics and Astrophysics, Weizmann Institute of Science,Rehovot 7610001 (Israel); Ziegler, Robert [Institute for Theoretical Particle Physics (TTP), Karlsruhe Institute of Technology,Engesserstraße 7, D-76128 Karlsruhe (Germany)

2017-01-31

We investigate the general structure of mirror symmetry breaking in the Twin Higgs scenario. We show, using the IR effective theory, that a significant gain in fine tuning can be achieved if the symmetry is broken hardly. We emphasize that weakly coupled UV completions can naturally accommodate this scenario. We analyze SUSY UV completions and present a simple Twin SUSY model with a tuning of around 10% and colored superpartners as heavy as 2 TeV. The collider signatures of general Twin SUSY models are discussed with a focus on the extended Higgs sectors.

Arginine- and Polyamine-Induced Lactic Acid Resistance in Neisseria gonorrhoeae.

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Zheng Gong

Full Text Available Microbe-derived lactic acid protects women from pathogens in their genital tract. The purpose of this study was to determine lactic acid susceptibility of Neisseria gonorrhoeae, and identify potential acid resistance mechanisms present in this pathogen. Tested in vitro, lactic acid killed all 10 gonococcal strains analyzed in a low pH-dependent manner. Full inactivation occurred at pH 4.5. At low pH, lactic acid treatment resulted in the entry of the DNA-binding fluorochrome propidium iodide into the microbial cells, suggesting that hydrogen ions from lactic acid compromise the integrity of the bacterial cell wall/membrane. Most likely, hydrogen ions also inactivate intracellular proteins since arginine rendered significant protection against lactic acid presumably through action of the gonococcal arginine decarboxylase, an enzyme located in the bacterial cytoplasm. Surprisingly, arginine also lessened lactic acid-mediated cell wall/membrane disruption. This effect is probably mediated by agmatine, a triamine product of arginine decarboxylase, since agmatine demonstrated a stronger protective effect on GC than arginine at equal molar concentration. In addition to agmatine, diamines cadaverine and putrescine, which are generated by bacterial vaginosis-associated microbes, also induced significant resistance to lactic acid-mediated GC killing and cell wall/membrane disruption. These findings suggest that the arginine-rich semen protects gonococci through both neutralization-dependent and independent mechanisms, whereas polyamine-induced acid resistance contributes to the increased risk of gonorrhea in women with bacterial vaginosis.

From monster to twin reversed arterial perfusion: a history of acardiac twins.

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Obladen, Michael

2010-05-01

A human being born without heart and head, i.e., the acardius/acranius malformation, has been described since antiquity. Superstition and fear made it a mystical disorder, a sign of God's wrath. The inquisition ruled that acranic infants should not be baptized and located the soul in the brain. Acardia was not associated with twin gestation until the reports of Mery in 1720 and Winslow in 1740. In 1850, Meckel identified the pathogenetic mechanism as reversed perfusion due to large arterio-arterial and veno-venous anastomoses; he believed the heart would fail to develop or arrest during development, and the acardiac fetus would be maintained by arterial perfusion from the pump twin. In 1859, Claudius articulated that after normal initial development, the heart degenerates when reversed flow in the aorta leads to thrombosis. Today, it is assumed that both mechanisms may exist. With the advent of prenatal ultrasound diagnosis and radiofrequency ablation of the acardiac twin's circulation, it became possible to save the pump twin.

Monochorionic twin pregnancies: a systematic approach to ...

African Journals Online (AJOL)

Complications unique to these pregnancies include Twin-To-Twin Transfusion Syndrome (TTTS), Twin Polycythaemia Anaemia Sequence (TAPS), Selective Intrauterine Growth Restriction (sIUGR) and death of the co-twin. Adhering to a systematic and objective approach of management, can lead to early recognition and ...

Genome-wide association study in Finnish twins highlights the connection between nicotine addiction and neurotrophin signaling pathway.

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Hällfors, Jenni; Palviainen, Teemu; Surakka, Ida; Gupta, Richa; Buchwald, Jadwiga; Raevuori, Anu; Ripatti, Samuli; Korhonen, Tellervo; Jousilahti, Pekka; Madden, Pamela A F; Kaprio, Jaakko; Loukola, Anu

2018-03-13

The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we detected genome-wide significant association on 16p12 with smoking quantity (P = 8.5 × 10 -9 ), near CLEC19A. The lead-SNP stands 22 kb from a binding site for NF-κB transcription factors, which play a role in the neurotrophin signaling pathway. However, the signal was not replicated in an independent Finnish population-based sample, FINRISK (n = 6763). Second, nicotine withdrawal showed association on 2q21 in an intron of TMEM163 (P = 2.1 × 10 -9 ), and on 11p15 (P = 6.6 × 10 -8 ) in an intron of AP2A2, and P = 4.2 × 10 -7 for a missense variant in MUC6, both involved in the neurotrophin signaling pathway). Third, association was detected on 3p22.3 for maximum number of cigarettes smoked per day (P = 3.1 × 10 -8 ) near STAC. Associating CLEC19A and TMEM163 SNPs were annotated to influence gene expression or methylation. The neurotrophin signaling pathway has previously been associated with smoking behavior. Our findings further support the role in nicotine addiction. © 2018 The Authors. Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

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S.C.F. Olinto

2012-11-01

Full Text Available The amino acid arginine (Arg is a recognized secretagogue of growth hormone (GH, and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO, which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g were removed, divided into two halves, pooled (three hemi-pituitaries and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM, the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM and a cyclic guanosine monophosphate (cGMP analogue (8-Br-cGMP, 1 mM increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS inhibitor, 55 mM abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

Energy Technology Data Exchange (ETDEWEB)

Olinto, S.C.F. [Faculdade de Ciências Integradas do Pontal, Universidade Federal de Uberlândia, Ituiutaba, MG (Brazil); Adrião, M.G. [Departamento de Morfologia e Fisiologia, Universidade Federal Rural de Pernambuco, Recife, PE (Brazil); Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-06-01

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

International Nuclear Information System (INIS)

Olinto, S.C.F.; Adrião, M.G.; Castro-Barbosa, T.; Goulart-Silva, F.; Nunes, M.T.

2012-01-01

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (∼250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (an NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression

Selective inhibition of MG-63 osteosarcoma cell proliferation induced by curcumin-loaded self-assembled arginine-rich-RGD nanospheres.

Science.gov (United States)

Chang, Run; Sun, Linlin; Webster, Thomas J

2015-01-01

Osteosarcoma is the most frequent primary malignant form of bone cancer, comprising 30% of all bone cancer cases. The objective of this in vitro study was to develop a treatment against osteosarcoma with higher selectivity toward osteosarcoma cells and lower cytotoxicity toward normal healthy osteoblast cells. Curcumin (or diferuloylmethane) has been found to have antioxidant and anticancer effects by multiple cellular pathways. However, it has lower water solubility and a higher degradation rate in alkaline conditions. In this study, the amphiphilic peptide C18GR7RGDS was used as a curcumin carrier in aqueous solution. This peptide contains a hydrophobic aliphatic tail group leading to their self-assembly by hydrophobic interactions, as well as a hydrophilic head group composed of an arginine-rich and an arginine-glycine-aspartic acid structure. Through characterization by transmission electron microscopy, self-assembled structures of spherical amphiphilic nanoparticles (APNPs) with diameters of 10-20 nm in water and phosphate-buffered saline were observed, but this structure dissociated when the pH value was reduced to 4. Using a method of codissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and a homogeneous solution was formed in the presence of APNPs. Successful encapsulation of curcumin in APNPs was then confirmed by Fourier transform infrared and X-ray diffraction analyses. The cytotoxicity and cellular uptake of the APNP/curcumin complexes on both osteosarcoma and normal osteoblast cell lines were also evaluated by methyl-thiazolyl-tetrazolium assays and confocal fluorescence microscopy. The results showed that the curcumin-loaded APNPs had significant selective cytotoxicity against MG-63 osteosarcoma cells when compared with normal osteoblasts. We have demonstrated for the first time that APNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and curcumin-loaded APNPs could be an innovative treatment

PRE-EXERCISE ARGININE SUPPLEMENTATION INCREASES TIME TO EXHAUSTION IN ELITE MALE WRESTLERS

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H.U. Yavuz

2014-08-01

Full Text Available Dietary supplements containing arginine are among the most popular ergogenics intended to enhance strength, power and muscle recovery associated with both anaerobic and aerobic exercise. The aim of the present study was to evaluate the possible effect of pre-exercise acute intake of arginine on performance and exercise metabolism during incremental exhaustive exercise in elite male wrestlers. Nine volunteer elite male wrestlers (24.7±3.8 years participated in this study. The test-retest protocol was used on the same subjects. The study was conducted using a cross-over design. A single dose of arginine (1.5 g · 10 kg-1 body weight or placebo was given to the subjects after 12 hours fasting (during the night for both test and retest. Subjects were allowed to drink water but not allowed to eat anything between arginine or placebo ingestion and the exercise protocol. An incremental exercise protocol was applied and oxygen consumption was measured during the exercise. Heart rate and plasma lactate levels were measured during the exercise and recovery. Results showed that in the same working loads there was no significant difference for the mean lactate levels and no difference in maximum oxygen consumption (arginine 52.47±4.01 mL · kg-1 · min-1, placebo 52.07±5.21 mL · kg-1 · min-1 or in maximum heart rates (arginine 181.09±13.57 bpm, placebo 185.89±7.38 bpm between arginine and placebo trials. Time to exhaustion was longer with arginine supplementation (1386.8±69.8 s compared to placebo (1313±90.8 s (p<0.05. These results suggest that L-arginine supplementation can have beneficial effects on exercise performance in elite male wrestlers but cannot explain the metabolic pathways which are responsible from these effects.

Integration of reward signalling and appetite regulating peptide systems in the control of food-cue responses.

Science.gov (United States)

Reichelt, A C; Westbrook, R F; Morris, M J

2015-11-01

Understanding the neurobiological substrates that encode learning about food-associated cues and how those signals are modulated is of great clinical importance especially in light of the worldwide obesity problem. Inappropriate or maladaptive responses to food-associated cues can promote over-consumption, leading to excessive energy intake and weight gain. Chronic exposure to foods rich in fat and sugar alters the reinforcing value of foods and weakens inhibitory neural control, triggering learned, but maladaptive, associations between environmental cues and food rewards. Thus, responses to food-associated cues can promote cravings and food-seeking by activating mesocorticolimbic dopamine neurocircuitry, and exert physiological effects including salivation. These responses may be analogous to the cravings experienced by abstaining drug addicts that can trigger relapse into drug self-administration. Preventing cue-triggered eating may therefore reduce the over-consumption seen in obesity and binge-eating disorder. In this review we discuss recent research examining how cues associated with palatable foods can promote reward-based feeding behaviours and the potential involvement of appetite-regulating peptides including leptin, ghrelin, orexin and melanin concentrating hormone. These peptide signals interface with mesolimbic dopaminergic regions including the ventral tegmental area to modulate reactivity to cues associated with palatable foods. Thus, a novel target for anti-obesity therapeutics is to reduce non-homeostatic, reward driven eating behaviour, which can be triggered by environmental cues associated with highly palatable, fat and sugar rich foods. © 2015 The British Pharmacological Society.

RGD-conjugated iron oxide magnetic nanoparticles for magnetic resonance imaging contrast enhancement and hyperthermia.

Science.gov (United States)

Zheng, S W; Huang, M; Hong, R Y; Deng, S M; Cheng, L F; Gao, B; Badami, D

2014-03-01

The purpose of this study was to develop a specific targeting magnetic nanoparticle probe for magnetic resonance imaging and therapy in the form of local hyperthermia. Carboxymethyl dextran-coated ultrasmall superparamagnetic iron oxide nanoparticles with carboxyl groups were coupled to cyclic arginine-glycine-aspartic peptides for integrin α(v)β₃ targeting. The particle size, magnetic properties, heating effect, and stability of the arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide were measured. The arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide demonstrates excellent stability and fast magneto-temperature response. Magnetic resonance imaging signal intensity of Bcap37 cells incubated with arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide was significantly decreased compared with that incubated with plain ultrasmall superparamagnetic iron oxide. The preferential uptake of arginine-glycine-aspartic-ultrasmall superparamagnetic iron oxide by target cells was further confirmed by Prussian blue staining and confocal laser scanning microscopy.

Interaction of amyloid inhibitor proteins with amyloid beta peptides: insight from molecular dynamics simulations.

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Payel Das

Full Text Available Knowledge of the detailed mechanism by which proteins such as human αB- crystallin and human lysozyme inhibit amyloid beta (Aβ peptide aggregation is crucial for designing treatment for Alzheimer's disease. Thus, unconstrained, atomistic molecular dynamics simulations in explicit solvent have been performed to characterize the Aβ17-42 assembly in presence of the αB-crystallin core domain and of lysozyme. Simulations reveal that both inhibitor proteins compete with inter-peptide interaction by binding to the peptides during the early stage of aggregation, which is consistent with their inhibitory action reported in experiments. However, the Aβ binding dynamics appear different for each inhibitor. The binding between crystallin and the peptide monomer, dominated by electrostatics, is relatively weak and transient due to the heterogeneous amino acid distribution of the inhibitor surface. The crystallin-bound Aβ oligomers are relatively long-lived, as they form more extensive contact surface with the inhibitor protein. In contrast, a high local density of arginines from lysozyme allows strong binding with Aβ peptide monomers, resulting in stable complexes. Our findings not only illustrate, in atomic detail, how the amyloid inhibitory mechanism of human αB-crystallin, a natural chaperone, is different from that of human lysozyme, but also may aid de novo design of amyloid inhibitors.

The role of the arginine metabolome in pain: implications for sickle cell disease

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Bakshi N

2016-03-01

Full Text Available Nitya Bakshi,1–2 Claudia R Morris3–6 1Division of Pediatric Hematology-Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 2Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 3Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 4Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA; 5Emory-Children’s Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA; 6Pediatric Emergency Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA Abstract: Sickle cell disease (SCD is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO, polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its

A tale of twin Higgs: natural twin two Higgs doublet models

Energy Technology Data Exchange (ETDEWEB)

Yu, Jiang-Hao [Amherst Center for Fundamental Interactions, Department of Physics,University of Massachusetts Amherst,710 North Pleasant St., Amherst, MA 01002 (United States)

2016-12-28

In original twin Higgs model, vacuum misalignment between electroweak and new physics scales is realized by adding explicit ℤ{sub 2} breaking term. Introducing additional twin Higgs could accommodate spontaneous ℤ{sub 2} breaking, which explains origin of this misalignment. We introduce a class of twin two Higgs doublet models with most general scalar potential, and discuss general conditions which trigger electroweak and ℤ{sub 2} symmetry breaking. Various scenarios on realising the vacuum misalignment are systematically discussed in a natural composite two Higgs double model framework: explicit ℤ{sub 2} breaking, radiative ℤ{sub 2} breaking, tadpole-induced ℤ{sub 2} breaking, and quartic-induced ℤ{sub 2} breaking. We investigate the Higgs mass spectra and Higgs phenomenology in these scenarios.

Efficient Secretion of Recombinant Proteins from Rice Suspension-Cultured Cells Modulated by the Choice of Signal Peptide.

Science.gov (United States)

Huang, Li-Fen; Tan, Chia-Chun; Yeh, Ju-Fang; Liu, Hsin-Yi; Liu, Yu-Kuo; Ho, Shin-Lon; Lu, Chung-An

2015-01-01

Plant-based expression systems have emerged as a competitive platform in the large-scale production of recombinant proteins. By adding a signal peptide, αAmy3sp, the desired recombinant proteins can be secreted outside transgenic rice cells, making them easy to harvest. In this work, to improve the secretion efficiency of recombinant proteins in rice expression systems, various signal peptides including αAmy3sp, CIN1sp, and 33KDsp have been fused to the N-terminus of green fluorescent protein (GFP) and introduced into rice cells to explore the efficiency of secretion of foreign proteins. 33KDsp had better efficiency than αAmy3sp and CIN1sp for the secretion of GFP from calli and suspension-cultured cells. 33KDsp was further applied for the secretion of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) from transgenic rice suspension-cultured cells; approximately 76%-92% of total rice-derived mGM-CSF (rmGM-CSF) was detected in the culture medium. The rmGM-CSF was bioactive and could stimulate the proliferation of a murine myeloblastic leukemia cell line, NSF-60. The extracellular yield of rmGM-CSF reached 31.7 mg/L. Our study indicates that 33KDsp is better at promoting the secretion of recombinant proteins in rice suspension-cultured cell systems than the commonly used αAmy3sp.

L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

Science.gov (United States)

Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

1997-01-21

The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

Radioimmunoassay of [8-D-arginine] deamino-vasopressin (dDAVP)

International Nuclear Information System (INIS)

Slaninova, J.; Barth, T.

1978-01-01

Specific antibodies to [8-D-arginine] deamino-vasopressin (dDAVP) were prepared by immunizing pigs with the conjugate of [8-D-arginine] vasopressin (DVAP) and rabbit immunoglobulin. The specificity of the antibodies was studied by comparing their cross-reactivity with 20 analogues of neurohypophysial hormones. The sensitivity of the developed radioimmunoassay was 30 pg/ml. (authors)

Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

International Nuclear Information System (INIS)

Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo; Kim, So Young; Jang, Hwan-Hee; Ryu, Sung Ho; Kim, Beom Joon; Lee, Taehoon G.

2012-01-01

Highlights: ► We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. ► YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. ► There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. ► The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. ► The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929–933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

Calcitonin gene related family peptides: importance in normal placental and fetal development.

Science.gov (United States)

Yallampalli, Chandra; Chauhan, Madhu; Endsley, Janice; Sathishkumar, Kunju

2014-01-01

Synchronized molecular and cellular events occur between the uterus and the implanting embryo to facilitate successful pregnancy outcome. Nevertheless, the molecular signaling network that coordinates strategies for successful decidualization, placentation and fetal growth are not well understood. The discovery of calcitonin/calcitonin gene-related peptides (CT/CGRP) highlighted new signaling mediators in various physiological processes, including reproduction. It is known that CGRP family peptides including CGRP, adrenomedulin and intermedin play regulatory functions during implantation, trophoblast proliferation and invasion, and fetal organogenesis. In addition, all the CGRP family peptides and their receptor components are found to be expressed in decidual, placental and fetal tissues. Additionally, plasma levels of peptides of the CGRP family were found to fluctuate during normal gestation and to induce placental cellular differentiation, proliferation, and critical hormone signaling. Moreover, aberrant signaling of these CGRP family peptides during gestation has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the CGRP family peptides in these critical processes is explored and discussed.

Establishing a Twin Registry in Guinea-Bissau

DEFF Research Database (Denmark)

Bjerregaard-Andersen, Morten; Gomes, Margarida A; Joaquím, Luis C

2013-01-01

represent a powerful tool. Though twin studies have been carried out by the Bandim Health Project for more than 30 years, the renewed registry described here was officially established in 2009 and includes both a cohort of newborn twins and a cohort of young and adult twins. Currently more than 1,500 twins...

Arginine Vasotocin, the Social Neuropeptide of Amphibians and Reptiles.

Science.gov (United States)

Wilczynski, Walter; Quispe, Maricel; Muñoz, Matías I; Penna, Mario

2017-01-01

Arginine vasotocin (AVT) is the non-mammalian homolog of arginine vasopressin (AVP) and, like vasopressin, serves as an important modulator of social behavior in addition to its peripheral functions related to osmoregulation, reproductive physiology, and stress hormone release. In amphibians and reptiles, the neuroanatomical organization of brain AVT cells and fibers broadly resembles that seen in mammals and other taxa. Both parvocellular and magnocellular AVT-containing neurons are present in multiple populations located mainly in the basal forebrain from the accumbens-amygdala area to the preoptic area and hypothalamus, from which originate widespread fiber connections spanning the brain with a particularly heavy innervation of areas associated with social behavior and decision-making. As for mammalian AVP, AVT is present in greater amounts in males in many brain areas, and its presence varies seasonally, with hormonal state, and in males with differing social status. AVT's social influence is also conserved across herpetological taxa, with significant effects on social signaling and aggression, and, based on the very small number of studies investigating more complex social behaviors in amphibians and reptiles, AVT may also modulate parental care and social bonding when it is present in these vertebrates. Within this conserved pattern, however, both AVT anatomy and social behavior effects vary significantly across species. Accounting for this diversity represents a challenge to understanding the mechanisms by which AVT exerts its behavioral effects, as well are a potential tool for discerning the structure-function relationships underlying AVT's many effects on behavior.

Anorexia and bulimia nervosa in same-sex and opposite-sex twins: lack of association with twin type in a nationwide study of Finnish twins.

Science.gov (United States)

Raevuori, Anu; Kaprio, Jaakko; Hoek, Hans W; Sihvola, Elina; Rissanen, Aila; Keski-Rahkonen, Anna

2008-12-01

The authors tested the hypothesis that either prenatal feminization or masculinization hormone influences in utero or later socialization affects the risk for anorexia and bulimia nervosa and disordered eating in members of opposite-sex twin pairs. Finnish twins (N=2,426 women, N=1,962 men with known zygosity) from birth cohorts born 1974-1979 were assessed at age 22 to 28 years with a questionnaire for eating disorder symptoms. Based on the questionnaire screen, women (N=292), men (N=53), and their cotwins were interviewed to assess diagnoses of anorexia nervosa and bulimia nervosa (per DSM-IV and broad criteria). In women from opposite-sex twin pairs, the prevalence of DSM-IV or broad anorexia nervosa was not significantly different than that of women from monozygotic pairs or same-sex dizygotic pairs. Of the five male anorexia nervosa probands, only one was from an opposite-sex twin pair. Bulimia nervosa in men was too rare to be assessed by zygosity; the prevalence of DSM-IV or broad bulimia nervosa did not differ in women from opposite- versus same-sex twin pairs. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite- and same-sex pairs. The authors found little evidence that the risk for anorexia nervosa, bulimia nervosa, or disordered eating was associated with zygosity or sex composition of twin pairs, thus making it unlikely that in utero femininization or masculinization or socialization effects of growing up with an opposite-sex twin have a major influence on the later development of eating disorders.

Heteropagus twinning on back -- a case report.

Science.gov (United States)

Debnath, Bidyut; Biswas, Sumitra Kumar

2011-07-01

Heteropagus twins, also called parasitic twins, are malformation of the foetus where the development of one twin is incomplete. They are attached most commonly to the lower chest and upper abdomen. We report a case of heteropagus twin, where the parasite possessed well-formed limb as well as blind ending intestine. It was attached to the back of the host by a broad pedicle. We take this opportunity to classify areas of confusion prevailing regarding twinning, foetus in foetu, teratoma and caudal duplication.

Time trends in the natural dizygotic twinning rate.

Science.gov (United States)

Derom, Catherine; Gielen, Marij; Peeters, Hilde; Frijns, Jean-Pierre; Zeegers, Maurice P A

2011-08-01

The natural dizygotic (DZ) twinning rate has been proposed as a reliable and useful measure of human fecundity, if adjusted for maternal age at twin birth. The aim of this study was to analyze age-adjusted trends in natural DZ twinning rates over the past 40 years using data from the 'East Flanders Prospective Twin Survey (EFPTS)'. This study involved 4835 naturally conceived twin pregnancies between 1969 and 2009 from the population-based Belgian 'EFPTS'. Age-adjusted trends in the incidence of natural DZ twin pregnancies were calculated using a generalized linear model with Poisson distribution. Both the natural DZ twinning rates and maternal age at twin birth increased in a linear fashion from 1969 to 2009. When age-adjusted, we found that the trend in the natural DZ twinning rate was stable during the whole time period. According to our population-based data and after age-adjustment, a stable natural DZ twinning rate could be observed over the last four decades. Under the assumption that the spontaneous DZ twinning rate is a sensor of fecundity, this indicates a stable 'high' fecundity for this population.

The ArcD1 and ArcD2 arginine/ornithine exchangers encoded in the arginine deiminase (ADI) pathway gene cluster of Lactococcus lactis

NARCIS (Netherlands)

Noens, Elke E E; Kaczmarek, Michał B; Żygo, Monika; Lolkema, Juke S

2015-01-01

The arginine deiminase pathway (ADI) gene cluster in Lactococcus lactis contains two copies of a gene encoding an L-arginine/L-ornithine exchanger, the arcD1 and arcD2 genes. The physiological function of ArcD1 and ArcD2 was studied by deleting the two genes. Deletion of arcD1 resulted in loss of

Relationship between refractive error and ocular biometrics in twin children: the Guangzhou Twin Eye Study.

Science.gov (United States)

Wang, Decai; Liu, Bin; Huang, Shengsong; Huang, Wenyong; He, Mingguang

2014-09-01

A cross-sectional study was conducted to explore the relationship between refractive error and ocular biometrics in children from the Guangzhou twin eye study. Twin participants aged 7-15 years were selected from Guangzhou Twin Eye Study. Ocular examinations included visual acuity measurement, ocular motility evaluation, autorefraction under cycloplegia, and anterior segment, media, and fundus examination. Axial length (AL), anterior chamber depth (ACD), and corneal curvature radius were measured using partial coherence laser interferometry. A multivariate linear regression model was used for statistical analysis. Twin children from Guangzhou city showed a decreased spherical equivalent with age, whereas both AL and ACD were increased and corneal curvature radius remained unchanged. When adjusted by age and gender, the data from 77% of twins presenting with spherical equivalent changes indicated that these were caused by predictable variables (R2 = 0.77, P biometrics. Refractive status is largely determined by axial length as the major factor.

Twins with omphalocele in Denmark (1970-1989)

DEFF Research Database (Denmark)

Bugge, Merete

2010-01-01

Seven pairs of twins, two monozygotic (MZ), two dizygotic (DZ), and three like-sex pairs of unknown zygosity are described. The twin pairs were all discordant for omphalocele except for one pair of conjoined twins. The 8 infants with omphalocele represent 3.1% of the 253 infants with omphalocele......, ascertained in an almost complete nationwide data set of live- and stillborn infants with abdominal wall defects in two decades in Denmark (1970-1989). The occurrence of twins with omphalocele was not significantly different from the occurrence of twins in the Danish population in the same period. To our...... knowledge this is the first report of the occurrence of twins with omphalocele in a systematic nationwide epidemiological study....

Twin anemia polycythemia sequence

NARCIS (Netherlands)

Slaghekke, Femke

2014-01-01

In this thesis we describe that Twin Anemia Polycythemia Sequence (TAPS) is a form of chronic feto-fetal transfusion in monochorionic (identical) twins based on a small amount of blood transfusion through very small anastomoses. For the antenatal diagnosis of TAPS, Middle Cerebral Artery – Peak

The Danish Twin Registry

DEFF Research Database (Denmark)

Skytthe, Axel; Ohm Kyvik, Kirsten; Vilstrup Holm, Niels

2011-01-01

Introduction: The Danish Twin Registry is a unique source for studies of genetic, familial and environmental factors on life events, health conditions and diseases. Content: More than 85,000 twin pairs born 1870-2008 in Denmark. Validity and coverage: Four main ascertainment methods have been emp...

Nature versus nurture: identical twins and bariatric surgery.

Science.gov (United States)

Hagedorn, Judith C; Morton, John M

2007-06-01

Genetics and environment both play a role in weight maintenance. Twin studies may help clarify the influence of nature vs nurture in weight loss. We present the largest U.S. experience with monozygotic (MZ) twins undergoing bariatric surgery. We retrospectively reviewed the charts of four sets of MZ twins who underwent Roux-en-Y gastric bypass (RYGBP) surgery and laparoscopic adjustable gastric band (LAGB) placement at three different institutions. BMI and co-morbidities were examined pre- and postoperatively, and laboratory values were recorded. All four sets of twins are female, live together, and have similar professions. Twin cohort 1 had near identical weight loss patterns after open RYGBP surgery in 1996 (preop 146/142 kg; 2 years 82/82; and 10 years 108/107). Twin cohort 1 also both underwent cholecystectomies within the first year postoperatively. Twin cohort 2 underwent laparoscopic RYGBP surgery and also required cholecystectomies in the first postoperative year. Cohort 2 also experienced nearly identical weight loss at 1 year (36.7% vs 37.0% BMI loss). Twin cohort 3 underwent LAGB placement with two different surgeons with differing amounts of weight loss at 6 months (6.5% vs 15.7% BMI loss). Finally, twin cohort 4 underwent laparoscopic RYGBP with 2-year BMI loss of 39% vs 34%. In twin cohort 4, the twin who lost less weight lived apart from her twin and extended family, and her weight loss was less than the twin living with her family. Two sets of MZ twins had identical responses to bariatric surgery. The other two sets of identical twins had differential weight loss results, possibly due to differences in surgical approach and social support. While genetics do exert a strong influence on weight loss and maintenance, this case series demonstrates the potential effect of social support and postoperative management upon postoperative weight loss in the presence of identical genetics.

Signal peptide prediction suggests Mycobacterium tuberculosis curli pilin subunit secretion via the Sec pathway may hinder MTP overexpression in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Naidoo, N.; Pillay, B.; Bubb, M.; Kumar, A.; Chiliza, T.; Pillay, M.

2017-07-01

Introduction Mycobacterium tuberculosis curli pili (MTP) are novel, potential TB diagnostic biomarkers as they are important virulence attributes, unique to the M. tuberculosis complex (MTBC). The production of high quality recombinant transmembrane and secretory proteins that can serve as biomarkers may be challenging due to their secretion attributes. For example, the signal peptide of MTP governed by the classical secretion pathway may hinder the purification of the protein in E. coli systems. In this study, the secretion characteristics of MTP were determined and the cloning, expression and purification of MTP was attempted in E.coli. Materials and methods A fragment of MTP unique to MTBC was cloned into pet101 and pGEX-6P-1 vectors. The clones were confirmed by nucleotide sequencing and expression of the protein was attempted at IPTG concentrations ranging from 0.1mM to 1mM and at temperatures between 25 °C to 37 °C. The pGEX-6P-1/mtp clone expressed protein was purified, yielding a MTP-GST fusion protein and a free GST band that were analysed by LC/MS mass spectrometry. Inclusion body preparation attempted from the pet101/mtp clone yielded two bands at 10 kDa and below 10 kDa, both of which were analysed by LC/MS mass spectrometry. Transcription activity of both the clones was interrogated by real time PCR on the cDNA derived from the induced clones at various time points after induction with IPTG. The signal peptide and protein secretion characteristics of the MTP protein were determined by bioinformatics analysis of the amino acid sequence using publically available software. Results The truncated MTP fragments were successfully cloned in both the vectors as confirmed by nucleotide sequencing. Expression of the pGEX-6P-1/mtp clone using 0.5 mM IPTG at 27 °C demonstrated the presence of the expected fragment at approximately 35 kDa. This was confirmed by Western Blotting using anti-GST antibodies. However, purification of MTP in adequate quantities as a

Signal peptide prediction suggests Mycobacterium tuberculosis curli pilin subunit secretion via the Sec pathway may hinder MTP overexpression in Escherichia coli

International Nuclear Information System (INIS)

Naidoo, N.; Pillay, B.; Bubb, M.; Kumar, A.; Chiliza, T.; Pillay, M.

2017-01-01

Introduction Mycobacterium tuberculosis curli pili (MTP) are novel, potential TB diagnostic biomarkers as they are important virulence attributes, unique to the M. tuberculosis complex (MTBC). The production of high quality recombinant transmembrane and secretory proteins that can serve as biomarkers may be challenging due to their secretion attributes. For example, the signal peptide of MTP governed by the classical secretion pathway may hinder the purification of the protein in E. coli systems. In this study, the secretion characteristics of MTP were determined and the cloning, expression and purification of MTP was attempted in E.coli. Materials and methods A fragment of MTP unique to MTBC was cloned into pet101 and pGEX-6P-1 vectors. The clones were confirmed by nucleotide sequencing and expression of the protein was attempted at IPTG concentrations ranging from 0.1mM to 1mM and at temperatures between 25 °C to 37 °C. The pGEX-6P-1/mtp clone expressed protein was purified, yielding a MTP-GST fusion protein and a free GST band that were analysed by LC/MS mass spectrometry. Inclusion body preparation attempted from the pet101/mtp clone yielded two bands at 10 kDa and below 10 kDa, both of which were analysed by LC/MS mass spectrometry. Transcription activity of both the clones was interrogated by real time PCR on the cDNA derived from the induced clones at various time points after induction with IPTG. The signal peptide and protein secretion characteristics of the MTP protein were determined by bioinformatics analysis of the amino acid sequence using publically available software. Results The truncated MTP fragments were successfully cloned in both the vectors as confirmed by nucleotide sequencing. Expression of the pGEX-6P-1/mtp clone using 0.5 mM IPTG at 27 °C demonstrated the presence of the expected fragment at approximately 35 kDa. This was confirmed by Western Blotting using anti-GST antibodies. However, purification of MTP in adequate quantities as a

Isoform-Selective Disruption of AKAP-Localized PKA Using Hydrocarbon Stapled Peptides

Science.gov (United States)

2015-01-01

A-kinase anchoring proteins (AKAPs) play an important role in the spatial and temporal regulation of protein kinase A (PKA) by scaffolding critical intracellular signaling complexes. Here we report the design of conformationally constrained peptides that disrupt interactions between PKA and AKAPs in an isoform-selective manner. Peptides derived from the A Kinase Binding (AKB) domain of several AKAPs were chemically modified to contain an all-hydrocarbon staple and target the docking/dimerization domain of PKA-R, thereby occluding AKAP interactions. The peptides are cell-permeable against diverse human cell lines, are highly isoform-selective for PKA-RII, and can effectively inhibit interactions between AKAPs and PKA-RII in intact cells. These peptides can be applied as useful reagents in cell-based studies to selectively disrupt AKAP-localized PKA-RII activity and block AKAP signaling complexes. In summary, the novel hydrocarbon-stapled peptides developed in this study represent a new class of AKAP disruptors to study compartmentalized RII-regulated PKA signaling in cells. PMID:24422448

Illustrations of the twin paradox