Value of eight-amino-acid matches in predicting the allergenicity status of proteins: an empirical bioinformatic investigation

The use of biotechnological techniques to introduce novel proteins into food crops (transgenic or GM crops) has motivated investigation into the properties of proteins that favor their potential to elicit allergic reactions. As part of the allergenicity assessment, bioinformatic approaches are used to compare the amino-acid sequence of candidate proteins with sequences in a database of known allergens to predict potential cross reactivity between novel food proteins and proteins to which people have become sensitized. Two criteria commonly used for these queries are searches over 80-amino-acid stretches for >35% identity, and searches for 8-amino-acid contiguous matches. We investigated the added value provided by the 8-amino-acid criterion over that provided by the >35%-identity-over-80-amino-acid criterion, by identifying allergens pairs that only met the former criterion, but not the latter criterion. We found that the allergen-sequence pairs only sharing 8-amino-acid identity, but not >35% identity over 80 amino acids, were unlikely to be cross reactive allergens. Thus, the common search for 8-amino-acid identity between novel proteins and known allergens appears to be of little additional value in assessing the potential allergenicity of novel proteins

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Test of lepton universality in beauty-quark decays

The standard model of particle physics currently provides our best description of fundamental particles and their interactions. The theory predicts that the different charged leptons, the electron, muon and tau, have identical electroweak interaction strengths. Previous measurements have shown that a wide range of particle decays are consistent with this principle of lepton universality. This article presents evidence for the breaking of lepton universality in beauty-quark decays, with a significance of 3.1 standard deviations, based on proton–proton collision data collected with the LHCb detector at CERN’s Large Hadron Collider. The measurements are of processes in which a beauty meson transforms into a strange meson with the emission of either an electron and a positron, or a muon and an antimuon. If confirmed by future measurements, this violation of lepton universality would imply physics beyond the standard model, such as a new fundamental interaction between quarks and leptons

Bending Moment Decrease of Reinforced Concrete Beam Supported by Additional CFRP

<p>The calculation method of reinforced concrete beam with additional CFRP composite is proposed in this article. This method estimates tangential angular concrete deformations in tensioned beam layers between steel and bonded carbon fiber reinforced polymer. The horizontal slip of CFRP composite reduce beam bending moment capacity. An additional coefficient to reduce CFRP resultant force is necessary for better precision of bending moment capacity. Also, various calculation methods of bending moment capacity are considered. </p><div class="nav_keywords"><p>Article in Lithuanian</p></div

Protein Restriction In Early Life Is Associated With Changes In Insulin Sensitivity And Pancreatic β-cell Function During Pregnancy

Malnutrition in early life impairs glucose-stimulated insulin secretion in adulthood. Conversely, pregnancy is associated with a significant increase in glucose-stimulated insulin secretion under conditions of normoglycaemia. A failure in β-cell adaptive changes may contribute to the onset of diabetes. Thus, glucose homeostasis and β-cell function were evaluated in control-fed pregnant (CP) and non-pregnant (CNP) or protein-restricted pregnant (LPP) and non-pregnant (LPNP) rats, from fetal to adult life, and in protein-restricted rats that were recovered after weaning (RP and RNP). The typical insulin resistance of pregnancy was not observed in the RP rats, nor did pregnancy increase the insulin content/islet in the LPP group. The glucose dose-response curves from pregnant rats were shifted to the left in relation to the non-pregnant rats, except in the recovered group. Glucose utilisation but not oxidation in islets from the RP and LPP groups was reduced at a concentration of 8·3Â mm-glucose compared with islets from the CP group. Cyclic AMP content and the potentiation of glucose-stimulated insulin secretion by isobutylmethylxanthine at a concentration of 2·8Â mm-glucose indicated increased adenylyl cyclase 3 activity but reduced protein kinase A-α activity in islets from the RP and LPP rats. Protein kinase C (PKC)-α but not phospholipase C (PLC)-β1 expression was reduced in islets from the RP group. Phorbol-12-myristate 13-acetate produced a less potent stimulation of glucose-stimulated insulin secretion in the RP group. Thus, the alterations exhibited by islets from the LPP group appeared to be due to reduced islet mass and/or insulin biosynthesis. In the RP group the loss of the adaptive capacity apparently resulted from uncoupling between glucose metabolism and the amplifying signals of the secretory process, as well as a severe attenuation of the PLC/PKC pathway. Copyright © The Authors 2012.1092236247Oliveira, C.A., Latorraca, M.Q., De Mello, M.A., Mechanisms of insulin secretion in malnutrition: Modulation by amino acids in rodent models (2011) Amino Acids, 40, pp. 1027-1034Latorraca, M.Q., Reis, M.A., Carneiro, E.M., Protein deficiency and nutritional recovery modulate insulin secretion and the early steps of insulin action in rats (1998) J Nutr, 128, pp. 1643-1649Heywood, W.E., Mian, N., Milla, P.J., Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods (2004) Clin Sci, 107, pp. 37-45Latorraca, M.Q., Carneiro, E.M., Mello, M.A., Reduced insulin secretion in response to nutrients in islets from malnourished young rats is associated with a diminished calcium uptake (1999) J Nutr Biochem, 10, pp. 37-43Cherif, H., Reusens, B., Dahri, S., A proteinrestricted diet during pregnancy alters in vitro insulin secretion from islets of fetal Wistar rats (2001) J Nutr, 131, pp. 1555-1559Parsons, J.A., Brelje, T.C., Sorenson, R.L., Adaptation of islets to pregnancy: Increase in B-cell division and insulin secretion correlates with onset of placental lactogen secretion (1992) Endocrinology, 130, pp. 1459-1466Green, I.C., Taylor, K.W., Effects of pregnancy in the rat on size and insulin secretory response of islets of Langerhans (1972) J Endocrinol, 54, pp. 317-325Sorenson, R.L., Brelje, T.C., Adaptation of islets of Langerhans to pregnancy: Beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones (1997) Horm Metab Res, 29, pp. 301-307Weinhaus, A.J., Stout, L.E., Sorenson, R.L., Glucokinase, hexokinase, glucose transporter 2, and glucose metabolism in islets during pregnancy and prolactin-treated islets in vitro: Mechanisms for long term up-regulation of islets (1996) Endocrinology, 137, pp. 1640-1649Weinhaus, A.J., Stout, L.E., Bhagroo, N.V., Regulation of glucokinase in pancreatic islets by prolactin: A mechanism for increasing glucose-stimulated insulin secretion during pregnancy (2007) J Endocrinol, 193, pp. 367-381Weinhaus, A.J., Bhagroo, N.V., Brelje, T.C., Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy (1998) Diabetes, 47, pp. 1426-1435Milanski, M., Arantes, V.C., Ferreira, F., Low-protein diets reduce PKAalpha expression in islets from pregnant rats (2005) J Nutr, 135, pp. 1873-1878Leturque, A., Ferré, P., Sabatin, P., Vivo insulin resistance during pregnancy in the rat (1980) Diabetologia, 19, pp. 521-528Matthews, J.N., Altman, D.G., Campbell, M.J., Analysis of serial measurements in medical research (1990) BMJ, 300, pp. 230-235Lundbaek, K., Intravenous glucose tolerance as a tool in definition and diagnosis of diabetes mellitus (1962) Br Med J, 5291, pp. 1507-1513Trinder, P., Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen (1969) J Clin Pathol, 22, pp. 158-161Doumas, B.T., Watson, W.A., Biggs, H.G., Albumin standards measurements of serum albumin with bromocresol green (1971) Clin Chim Acta, 31, pp. 87-96Scott, A.M., Atwater, I., Rojas, E., A method for the simultaneous measurement of insulin release and b-cell membrane potential in single mouse islets of Langerhans (1981) Diabetologia, 21, pp. 470-475Boschero, A.C., Szpak-Glasman, N., Carneiro, E.M., Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors (1995) Am J Physiol, 268, pp. E336-E342Sokal, R.R., Rohlf, F.J., (1995) Biometry: The Principles and Practice of Statistics in Biological Research, , 3rd ed. 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Amyloid-β oligomers induce differential gene expression in adult human brain slices

Cognitive decline in Alzheimer disease (AD) is increasingly attributed to the neuronal impact of soluble oligomers of the amyloid-β peptide (AβOs). Current knowledge on the molecular and cellular mechanisms underlying the toxicity of AβOs stems largely from rodent-derived cell/tissue culture experiments or from transgenic models of AD, which do not necessarily recapitulate the complexity of the human disease. Here, we used DNA microarray and RT-PCR to investigate changes in transcription in adult human cortical slices exposed to sublethal doses of AβOs. The results revealed a set of 27 genes that showed consistent differential expression upon exposure of slices from three different donors to AβOs. Functional classification of differentially expressed genes revealed that AβOs impact pathways important for neuronal physiology and known to be dysregulated in AD, including vesicle trafficking, cell adhesion, actin cytoskeleton dynamics, and insulin signaling. Most genes (70%) were down-re