A-superfamily of conotoxins: structural and functional divergence

Journal ArticleThe generation of functional novelty in proteins encoded by a gene superfamily is seldom well documented. In this report, we define the A-conotoxin superfamily, which is widely expressed in venoms of the predatory cone snails (Conus), and show how gene products that diverge considerably in structure and function have arisen within the same superfamily

The identification of anti-cancer molecular targets of COX-2 inhibitor Nimesulide

Non-steroidal anti inflammatory drugs which were primarily used for the treatment inflammation and pain have also shown anti-cancer activity in many studies. The mechanism of action of NSAIDs in cancer may involve cyclooxygenase (COX) dependent or independent pathways. According to studies, COX-2 is overexpressed in several cancers such as prostate, breast, nonsmall-cell lung, colon, and pancreas. Nimesulide is an NSAID with COX-2 inhibitory activity and investigations show that it could induce apoptosis in cancer. Previously, a library of compounds was synthesized using Nimesulide as a lead compound. However, they displayed different molecular targets: tubulin and heat shock protein 27 (HSP27). Since Nimesulide does not interfere with any of these proteins, the targets of it in cancer remain unclear. Therefore, it is necessary to identify the original anti-cancer targets of Nimesulide in order to understand the structure activity relationship that lead to target switching in the Nimesulide derivatives. For this purpose, a six carbon linker and biotin conjugated Nimesulide probe was designed and synthesized. A human prostate cancer cell line, LnCap, was used to perform protein pull-down assay in order to analyze the proteins that bind to the Nimesulide probe. This study provides insight into the structural interactions that are important for the anti-cancer activity which can be used to synthesize more potent analogs with the original target of Nimesulide.https://engagedscholarship.csuohio.edu/u_poster_2016/1016/thumbnail.jp

Heterodimeric structure of the spider toxin ω-Agatoxin IA revealed by precursor analysis and mass spectrometry

Journal ArticleWe report the first molecular characterization of a precursor sequence for a small, Ca2+ channel blocking, peptide spider toxin, ω-agatoxin IA. By integrating information generated from a molecular genetic approach using agatoxin cDNAs with data provided from mass spectrometry of the mature toxin, we were able to deduce the likely mechanisms by which the toxin precursor peptide is processed to its mature heterodimeric form

Stable p-branes in Chern-Simons AdS supergravities

We construct static codimension-two branes in any odd dimension D, with negative cosmological constant, and show that they are exact solutions of Chern-Simons (super)gravity theory for (super)AdS coupled to external sources. The stability of these solutions is analyzed by counting the number of preserved supersymmetries. It is shown that static massive (D-3)-branes are unstable unless some suitable gauge fields are added and the brane is extremal. In particular, in three dimensions, a 0-brane is recognized as the negative mass counterpart of the BTZ black hole. For these 0-branes, we write explicitly electromagnetically charged BPS states with various number of preserved supersymmetries within the OSp(p|2) x OSp(q|2) supergroups. In five dimensions, we prove that stable 2-branes with electromagnetic charge always exist for the generic supergroup SU(2,2|N), where N is different than 4. For the special case N=4, in which the CS supergravity requires the addition of a nontrivial gauge field configuration in order to preserve maximal number of degrees of freedom, we show for two different static 2-branes that they are BPS states (one of which is the ground state), and from the corresponding algebra of charges we show that the energy is bounded from below. In higher dimensions, our results admit a straightforward generalization, although there are presumably more solutions corresponding to different intersections of the elementary objects.Comment: 43 pages, revtex4.cls; v2: slight amendments and references added to match published versio

Vehicle routing for public transport with adapted simulated annealing

This paper presents an Adapted Simulated Annealing (ASA) algorithm to solve an instance of the vehicle routing problem (VRP): the intercity public transport problem (IPTP). This combinatorial optimization problem was effectively solved by means of a robust method. Its performance was achieved thanks to the incorporation of an auxiliary memory and a novel choice of the neighbours. The model is based on initial random solutions capable of generating appropriate bus routes and frequencies in a large solution space. We have established a search strategy that provides excellent responses at the process level. The intercity line linking Bahía Blanca and Punta Alta was chosen with the intention of evaluating ASA performance. The real traffic-behavior has been represented by means of the simulation software called SUMO. The computational results clearly indicate that the proposed approach constitutes an improvement in the ability to search for high quality solutions that facilitates the convergence.Fil: Rodriguez, D. A.. Universidad Nacional de Salta. Facultad de Ciencias Exactas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Planta Piloto de Ingeniería Química (I). Grupo Vinculado al Plapiqui - Investigación y Desarrollo en Tecnología Química; Argentina. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Laboratorio de Investigación y Desarrollo en Computación Científica; ArgentinaFil: Olivera, Ana Carolina. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Laboratorio de Investigación y Desarrollo en Computación Científica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brignole, Nélida Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahia Blanca. Planta Piloto de Ingeniería Química (I). Grupo Vinculado al Plapiqui - Investigación y Desarrollo en Tecnología Química; Argentina. Universidad Nacional del Sur. Departamento de Ciencias e Ingeniería de la Computación. Laboratorio de Investigación y Desarrollo en Computación Científica; Argentin

The nutritive value of poultry diets containing sunflower meal supplemented by enzymes

The international limitations imposed on the utilization of meat and bone meals in animal diets, together with the increasing demand for soybean meal, create a necessity to search for other protein sources to economically balance compound feeds. In this regard it is important to note that sunflower is the best adapted high-protein crop available in some European regions and that is useful to use it in poultry farming as the replacement of other protein sources. Protein and many other nutrients are “imprisoned” to variable degrees, inside sunflower meal fibrous structures, and remain less available for digestion by the poultry’s own proteases and other endogenous enzymes. Added exogenous enzymes (phytase, hemicellulase, cellulase, carbohydrase, protease, etc.) offer a number of creative possibilities for breakdown and “liberation” of these nutrients, their easier digestion and absorption, and thus development of new nutritional standards and new diets formulation. Supplementation of poultry diets containing sunflower meal by different enzymes increasingly contribute to sustainable poultry farming by enhancing production efficiency, increasing the effectiveness of nutrient utilization and upgrading in environmental protection. [Projekat Ministarstva nauke Republike Srbije, br. III46012

Stvaranje biogenih amina pod uticajem tkivnih enzima i pH smeše pripremljene za proizvodnju sirovih kobasica

The purpose of this paper was to clarify the influence of tissue enzymes and pH value in the mixture prepared for the production of raw sausages on the formation of biogenic amines (histamine and tyramine). A meat mixture very similar in composition to the typical fermented sausage (40% of beef, 40% of pork and 20% of pork fat tissue) was prepared, and divided in to three parts. The pH value of these portions was adjusted to 5,5; 6,0 and 7.0 through the addition of acetic acid, water and sodium hydrocarbonate solution, respectively. The samples were then radiodecontaminated (5 kGy) to exclude the possible influence of native microflora and stored at 18-22° C. The histamine and tyramine contents were determined immidiately and on the 0th, 5th, 10th and 15th days of storage. The obtained results showed that the initial contents of biogenic amines in the fresh meat mixtures were low: 1,05-1,16 μg of histamine and 1,82-2,04 μg of tyramine per gram of mixture. The final contents of these two biogenic amines, created after storing under conditions similar to the normal processing conditions in the production of this type of fermented sausages (two weeks at 18-22° C) also were low and unimportant for the hygienic safety of sausages (1,64-1,88 џд of histamine and 2,26-2.94 μg of tyramine per gram of the mixture). From the results presented the general conclusion could be drawn that enzymatic activity of the meat itself does not contribute very much to the total biogenic amines formed in the fermented sausages. However, comparison of the relative biogenic amine contents in the three groups of samples revealed that pH value of the meat exerts great influence on the intensity of amino acids decarboxylation and on the activity of enzymes which catalyze the formation of biogenic amines.Glavni cilj preduzetog istraživanja bio je da se sagleda uticaj tkivnih enzima i pH vrednosti smeše pripremljene za proizvodnju sirovih kobasica na obrazovanje biogenih amina (histamina i tiramina). Pripremljena je smeša, sirovinskog sastava tipičnog za nadevfermentisanih kobasica (40% govedine, 40% svinjetine i 20% svinjskog masnog tkiva) i podeljena u tri dela, a zatim je svakom delu posebno podešena pH vrednost dodatkom sirćetne kiseline (na pH 5,5), vode (na pH 6,0), odnosno rastvora natrijumbikarbonata (na pH 7,0). Sva tri dela smeše su zatim radiodekontaminirana jonizujućim zračenjem (5 kGy) kako bi se isključio uticaj postojeće mikroflore i uskladištena pri temperaturi od 18-22° C. Sadržaj histamina i tiramina u ovako uskladištenim uzorcima određivan je posle 5, 10 i 15 dana. Dobijeni rezultati su pokazali da je početni sadržaj ispitivanih biogenih amina u svežem mesu bio nizak: 1,05-1,16 mg histamina i 1,82-2,04 mg tiramina po gramu smeše. Krajnji sadržaj ovih amina, nakon skladištenja u uslovima bliskim onim u uobičajenoj proizvodnji ovih kobasica (dve sedmice pri 18-22° C) takođe je bio nizak i sa gledišta higijenske ispravnosti bez većeg značaja (1,64-1,88 mg histamina i 2,26-2.94 mg tiramina po gramu smee). Iz dobijenih rezultata može se izvesti opšti zaključak da enzimska aktivnost mesa ne doprinosi značajno obrazovanju biogenih amina u fermentisanim kobasicama. S druge strane, na osnovu poređenja relativnog sadržaja biogenih amina u tri grupe uzoraka različite pH vrednosti, može se zaključiti da pH ispoljava snažan uticaj na brzinu dekarboksilacije aminokiselina, odnosno na aktivnost enzima koji katalizuju obrazovanje biogenih amina

Molecular Phylogeny, Classification and Evolution of Conopeptides

Conopeptides are toxins expressed in the venom duct of cone snails (Conoidea, Conus). These are mostly well-structured peptides and mini-proteins with high potency and selectivity for a broad range of cellular targets. In view of these properties, they are widely used as pharmacological tools and many are candidates for innovative drugs. The conopeptides are primarily classified into superfamilies according to their peptide signal sequence, a classification that is thought to reflect the evolution of the multigenic system. However, this hypothesis has never been thoroughly tested. Here we present a phylogenetic analysis of 1,364 conopeptide signal sequences extracted from GenBank. The results validate the current conopeptide superfamily classification, but also reveal several important new features. The so-called "cysteine-poor” conopeptides are revealed to be closely related to "cysteine-rich” conopeptides; with some of them sharing very similar signal sequences, suggesting that a distinction based on cysteine content and configuration is not phylogenetically relevant and does not reflect the evolutionary history of conopeptides. A given cysteine pattern or pharmacological activity can be found across different superfamilies. Furthermore, a few conopeptides from GenBank do not cluster in any of the known superfamilies, and could represent yet-undefined superfamilies. A clear phylogenetically based classification should help to disentangle the diversity of conopeptides, and could also serve as a rationale to understand the evolution of the toxins in the numerous other species of conoideans and venomous animals at larg