Breaking Functional Connectivity into Components: A Novel Approach Using an Individual-Based Model, and First Outcomes

Landscape connectivity is a key factor determining the viability of populations in fragmented landscapes. Predicting ‘functional connectivity’, namely whether a patch or a landscape functions as connected from the perspective of a focal species, poses various challenges. First, empirical data on the movement behaviour of species is often scarce. Second, animal-landscape interactions are bound to yield complex patterns. Lastly, functional connectivity involves various components that are rarely assessed separately. We introduce the spatially explicit, individual-based model FunCon as means to distinguish between components of functional connectivity and to assess how each of them affects the sensitivity of species and communities to landscape structures. We then present the results of exploratory simulations over six landscapes of different fragmentation levels and across a range of hypothetical bird species that differ in their response to habitat edges. i) Our results demonstrate that estimations of functional connectivity depend not only on the response of species to edges (avoidance versus penetration into the matrix), the movement mode investigated (home range movements versus dispersal), and the way in which the matrix is being crossed (random walk versus gap crossing), but also on the choice of connectivity measure (in this case, the model output examined). ii) We further show a strong effect of the mortality scenario applied, indicating that movement decisions that do not fully match the mortality risks are likely to reduce connectivity and enhance sensitivity to fragmentation. iii) Despite these complexities, some consistent patterns emerged. For instance, the ranking order of landscapes in terms of functional connectivity was mostly consistent across the entire range of hypothetical species, indicating that simple landscape indices can potentially serve as valuable surrogates for functional connectivity. Yet such simplifications must be carefully evaluated in terms of the components of functional connectivity they actually predict

Effect Of Combined Treatment Of Hydrolysis And Polymerization With Transglutaminase On β-lactoglobulin Antigenicity

The effect of combined treatments of hydrolysis with different proteases, and subsequent polymerization with transglutaminase on the antigenic activity of β-Lg was studied. For the hydrolysis of β-Lg using Alcalase, Neutrase or bromelain, the reaction conditions were 3 % β-Lg and enzyme:substrate 25 U g -1 of protein, as was defined using factorial study. Under these conditions, the degree of hydrolysis (DH) of the hydrolysates was 12. 6 % when obtained with Alcalase and approximately 4 % with Neutrase or bromelain. Post-hydrolysis polymerization did not result in an increase in molecular mass of the protein, but these samples presented a lower DH, determined by trinitrobenzenosulfonic acid (TNBS) method, suggesting that polymerization had occurred. Hydrolysis with the three enzymes reduced the β-Lg antigenicity, as evaluated by ELISA and immunoblotting analyses. The IgE-binding responses were practically null (<9 μg mL -1), 22. 82 and 55. 73 μg mL -1 towards the hydrolysates obtained with Alcalase, bromelain, and Neutrase, respectively. The post-hydrolysis polymerization increased or had no significant effect (P ≥ 0. 05) on the antigenic response of the hydrolysates. © 2012 Springer-Verlag.2355801809Helm, R.M., Burks, A.W., Mechanism of food allergy (2000) Curr Opin Immunol, 12, pp. 647-653Malik, Z., Bottomley, R., Austen, B.M., Allergenic properties of the genetic variants A & B of bovine beta-lactoglobulin (1988) Int Arch Aller A Imm, 2, pp. 245-248Wal, J.M., Cow's milk allergens (1998) Allergy, 53, pp. 1013-1022Chatchatee, P., Jarvinen, K.M., Bardina, L., Beyer, K., Sampson, H.A., Identification of IgE- and IgG-binding epitopes on αs1-casein: differences in patients with persistent and transient cow's milk allergy (2001) J Allergy Clin Immunol, 107, pp. 379-383Ruitier, B., Rozemuller, E.H., van Dick, A.J., Garsen, J., Bruijnzeel-Koomen, C.A., Tilanus, M.G., Knol, E.F., van Hoffen, E., Role of human leucocyte antigen DQ in the presentation of T cell epitopes in the major cow's milk allergen α s1-casein (2007) Int Arch Allergy Immunol, 143, pp. 119-126Monaci, L., Tregoat, V., van Hengel, A.J., Anklam, E., Milk allergens, their characteristics and their detection in food: a review (2006) Eur Food Res Technol, 223, pp. 149-179Svenning, C., Brynhildsvold, J., Molland, T., Langsrud, T., Vegarud, G.E., Antigenic response of whey proteins and genetic variants of β-lactoglobulin-the effect of proteolysis and processing (2000) Int Dairy J, 10, pp. 699-711El-Ghaisha, S., Ahmadovaa, A., Hadji-Sfaxia, I., Mecherfia, K.E.E., Bazukyane, I., Choiseta, Y., Rabesonaa, H., Haertlé, T., Potential use of lactic acid bacteria for reduction of allergenicity and for longer conservation of fermented foods (2011) Trends Food Sci Technol, 22, pp. 509-516Peyron, S., Mouécoucou, J., Frémont, S., Sanchez, C., Gontard, N., Effects of heat treatment and pectin addition on β-lactoglobulin allergenicity (2006) J Agric Food Chem, 54, pp. 5643-5650Mierzejewska, D., Kubicka, E., Effect of temperature on immunoreactive properties of the cow milk whey protein β-lactoglobulin (2006) Milchwissenschaft, 61, pp. 69-72Lee, J.W., Kim, J.H., Yook, H.S., Kang, K.O., Lee, S.Y., Hwang, H.J., Byun, M.W., Effects of gamma radiation on the allergenic and antigenic properties of milk proteins (2001) J Food Prot, 64, pp. 272-276Reddy, I.M., Kella, K.D., Kinsella, J.E., Structural and conformational basis of resistance of β-lactoglobulin to peptic and chymotryptic digestion (1988) J Agric Food Chem, 36, pp. 737-741Bonomi, F., Fiocchi, A., Frøkiær, H., Gaiaschi, A., Iametti, S., Poiesi, C., Rasmussen, P., Rovere, P., Reduction of immunoreactivity of β-Lactoglobulin upon combined physical and proteolytic treatment (2003) J Dairy Res, 70, pp. 51-59Peñas, E., Enel, H., Floris, R., Préstamo, G., Gomez, R., High pressure can reduce the antigenicity of bovine whey protein hydrolysates (2006) Int Dairy J, 16, pp. 969-975Jost, R., Monti, J.C., Pahud, J.J., Whey proteins allergenicity and its reduction by technological means (1987) Food Technol, 41, pp. 128-129O'Sullivan, D., FitzGerald, R.J., Physicochemical properties and residual antigenicity of transglutaminase cross-linked sodium caseinate hydrolysates (2012) Int Dairy J, 23, pp. 18-23Watanabe, M., Suzuki, T., Ikezawa, Z., Arai, S., Controlled enzymatic treatment of wheat proteins for production of hypoallergenic flour (1994) Biosci Biotech Bioch, 58, pp. 388-390Babiker, E.E., Hiroyuki, A., Matsudomi, N., Iwata, H., Ogawa, T., Bando, N., Kato, A., Effect of polysaccharide conjugation or transglutaminase treatment on the allergenicity and functional properties of soy protein (1998) J Agric Food Chem, 46, pp. 866-871Clare, D.A., Gharst, G., Sanders, T.H., Transglutaminase polymerization of peanut proteins (2008) J Agric Food Chem, 55, pp. 432-438Eissa, A.S., Puhl, C., Kadla, J.F., Khan, S.A., Enzymatic cross-linking of β-lactoglobulin: conformational properties using FTIR spectroscopy (2006) Biomacromolecules, 7, pp. 1707-1713Faergemand, M., Otte, J., Qvist, K.B., Enzynmatic croos-linking of whey protein by Ca2 + -independent microbial transglutaminase from Streptomyces lydicus (1997) Food Hydrocoll, 11, pp. 19-25Fort, N., Carretero, C., Parés, D., Toldra, M., Saguer, E., Combined treatment of porcine plasma with microbial transglutaminase and cysteine: effects on the heat-induced gel properties (2007) Food Hydrocoll, 21, pp. 463-471Mahmoud, R., Savello, P.A., Mechanical-properties of and water-vapor transferability through whey-protein films (1992) J Dairy Sci, 75, pp. 942-946Villas-Boas, M.B., Vieira, K.P., Trevisan, G., Zollner, R.L., Netto, F.M., The effect of transglutaminase-induced polymerization in the presence of cysteine on β-Lactoglobulin antigenicity (2010) Int Dairy J, 20, pp. 386-392Wróblewska, B., Jedrychowski, L., Hajós, G., Szabó, E., Influence of alcalase and transglutaminase on immunoreactivity of cow milk whey proteins (2008) Czech J Food Sci, 26, pp. 15-23Walker-Smith, J., Hypoallergenic formulas: are they really hypoallergenic? (2003) Ann Allergy Asthma Immunol, 90, pp. 112-114Rosendal, A., Barkholt, V., Detection of potentially allergenic material in 12 hydrolysed milk formulas (2000) J Dairy Sci, 83, pp. 2200-2210Emi, S., Myers, D.V., Iacobucci, G.A., Purification and properties of the thermostable acid protease of Penicillium duponti (1976) Biochemistry, 15, pp. 842-848Adler-Nissen, J., Olsen, H.S., (1986) Enzymatic Hydrolysis of Food Proteins, , London: Elsevier Applied Science PublishersStǎnciuc, N., Plancken, I.V.D., Rotaru, G., Hendrickx, M., Denaturation impact in susceptibility of beta-lactoglobulin to enzymatic hydrolysis: a kinetic study (2008) Rev Roum Chim, 53, pp. 921-929Adler-Nissen, J., Determination of the degree of hydrolysis of food protein hydrolysates by trinitrobenzenesulfonic acid (1979) J Agric Food Chem, 27, pp. 1256-1262Schagger, H., von Jagow, G., Tricine sodium dodecyl-sulfate polyacrylamide-gel electrophoresis for the separation of proteins in the range from 1-KDa to 100-KDa (1987) Anal Biochem, 166, pp. 368-379Sharma, R., Zakora, M., Qvist, K.B., Susceptibility of an industrial α-lactalbumin concentrate to cross-linking by microbial transglutaminase (2002) Int Dairy J, 12, pp. 1005-1012Rodriguez-Nogales, J.M., Enhancement of transglutaminase-induced protein cross-linking by preheat treatment of cows' milk: a statistical approach (2006) Int Dairy J, 16, pp. 26-32Schmidt, D.G., Poll, J.K., Enzymatic hydrolysis of whey proteins. Hydrolysis of α-lactoalbumin and β-lactoglobulin in buffer solutions by proteolytic enzymes (1991) Neth Milk Dairy, 45, pp. 225-240Otte, J., Zakora, M., Qvist, K.B., Olsen, C.E., Barkholt, V., Hydrolysis of bovine β-lactoglobulin by various proteases and identification of selected peptides (1997) Int Dairy J, 7, pp. 835-848Markland, F.S., Smith, E., Subtilisins: primary structure, chemical and physical properties (1971) The Enzymes, , 3rd edn., P. D. Boyer (Ed.), New York: Academic PressFox, P.F., (1991) Food Enzymology, , London: Elsevier Applied ScienceMadsen, J.S., Ahmta, T.Ø., Ottea, J., Halkierb, T., Qvist, K.B., Hydrolysis of β-lactoglobulin by four different proteinases monitored by capillary electrophoresis and high performance liquid chromatography (1997) Int Dairy J, 7, pp. 399-409Siriporn, D., Kongpob, R., Kittinan, K., Wiwut, T., Enzymatic hydrolysis of rawhide using papain and neutrase (2008) J Ind Eng Chem, 14, pp. 202-206Kim, S.B., Seo, I.S., Khan, M.A., Ki, K.S., Nam, M.S., Kim, H.S., Separation of iron-binding protein from whey through enzymatic hydrolysis (2007) Int Dairy J, 17, pp. 625-631Chicón, R., Belloque, J., Alonso, E., López-Fandiño, R., Immunoreactivity and digestibility of high-pressure-treated whey proteins (2008) Int Dairy J, 18, pp. 367-376Chicón, R., López-Fandiño, R., Alonso, E., Belloque, J., Proteolytic pattern, antigenicity, and serum immunoglobulin E binding of beta-lactoglobulin hydrolysates obtained by pepsin and high-pressure treatments (2008) J Dairy Sci, 91, pp. 928-938Ball, G., Shelton, M.J., Walsh, B.J., Hill, D.J., Hosking, C.S., Howden, M.E., A major continuous allergenic epitope of bovine beta-lactoglobulin recognized by human IgE binding (1994) Clin Exp Allergy, 24, pp. 758-764Heinzmann, A., Blattmann, S., Spuergin, P., Forster, J., Deichman, K.A., The recognition pattern of sequential B cell epitopes of beta-lactoglobulin does not vary with the clinical manifestations of cow's milk allergy (1999) Int Arch Allergy Imm, 120, pp. 280-286Sélo, I., Clement, G., Bernard, H., Chatel, J., Creminon, C., Peltre, G., Wal, J., Allergy to bovine beta-lactoglobulin: specificity of human IgE to tryptic peptides (1999) Clin Exp Allergy, 29, pp. 1055-106

Whey protein isolate hydrolysates obtained with free and immobilized alcalase: characterization and detection of residual allergens

Protein antigenicity can be reduced by enzymatic hydrolysis, which can be performed either by free or immobilized enzyme. The immobilized enzyme is removed from the reaction medium and reused, while the free enzyme must be inactivated to stop the reaction83112120FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2013/08552-2sem informaçã

Oxidative Stress And Susceptibility To Mitochondrial Permeability Transition Precedes The Onset Of Diabetes In Autoimmune Non-obese Diabetic Mice.

Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H2O2 production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.481494-50

Recombinant phospholipase A1 from Polybia paulista (hymenoptera: vespidae) for specific diagnosis and immunotherapy of venom allergy

sem informaçãosem informação72103136136sem informaçãosem informaçãosem informaçãoCongress of the European-Academy-of-Allergy-and-Clinical-Immunolog

Hyaluronidase From The Venom Of The Social Wasp Polybia Paulista (hymenoptera, Vespidae): Cloning, Structural Modeling, Purification, And Immunological Analysis

In this study, we describe the cDNA cloning, sequencing, and 3-D structure of the allergen hyaluronidase from Polybia paulista venom (Pp-Hyal). Using a proteomic approach, the native form of Pp-Hyal was purified to homogeneity and used to produce a Pp-specific polyclonal antibody. The results revealed that Pp-Hyal can be classified as a glycosyl hydrolase and that the full-length Pp-Hyal cDNA (1315 bp; GI: 302201582) is similar (80-90%) to hyaluronidase from the venoms of endemic Northern wasp species. The isolated mature protein is comprised of 338 amino acids, with a theoretical pI of 8.77 and a molecular mass of 39,648.8 Da versus a pI of 8.13 and 43,277.0 Da indicated by MS. The Pp-Hyal 3D-structural model revealed a central core (α/β)7 barrel, two sulfide bonds (Cys 19-308 and Cys 185-197), and three putative glycosylation sites (Asn79, Asn187, and Asn325), two of which are also found in the rVes v 2 protein. Based on the model, residues Ser299, Asp107, and Glu109 interact with the substrate and potential epitopes (five conformational and seven linear) located at surface-exposed regions of the structure. Purified native Pp-Hyal showed high similarity (97%) with hyaluronidase from Polistes annularis venom (Q9U6V9). Immunoblotting analysis confirmed the specificity of the Pp-Hyal-specific antibody as it recognized the Pp-Hyal protein in both the purified fraction and P. paulista crude venom. No reaction was observed with the venoms of Apis mellifera, Solenopsis invicta, Agelaia pallipes pallipes, and Polistes lanio lanio, with the exception of immune cross-reactivity with venoms of the genus Polybia (sericea and ignobilis). Our results demonstrate cross-reactivity only between wasp venoms from the genus Polybia. The absence of cross-reactivity between the venoms of wasps and bees observed here is important because it allows identification of the insect responsible for sensitization, or at least of the phylogenetically closest insect, in order to facilitate effective immunotherapy in allergic patients. © 2013 Elsevier Ltd.647080Al-Ghouleh, A., Johal, R., Sharquie, I.K., Emara, M., Harrington, H., Shakib, F., Ghaemmaghami, A.M., The glycosylation pattern of common allergens: the recognition and uptake of Der p 1 by epithelial and dendritic cells is carbohydrate dependent (2012) PLoS ONE, 7 (3), pp. e33929Barbaro, K.C., Knysak, I., Martins, R., Hogan, C., Winkel, K., Enzymatic characterization, antigenic cross-reactivity and neutralization of dermonecrotic activity of five loxosceles spider venoms of medical importance in the Americas (2005) Toxicon, 45, pp. 489-499Cevallos, M.A., Navarro-Duque, C., Varela-Julia, M., Alagon, A.C., Molecular mass determination and assay of venom hyaluronidases by sodium dodecyl sulfate-polyacrilamide gel electrophoresis (1992) Toxicon, 30, pp. 925-930Cherr, G.N., Meyers, S.A., Yudin, A.I., Van de Voort, C.A., Myles, D.G., Primakoff, P., Overstreet, J.W., The PH-20 protein in Cynomolgus macaque spermatozoa: identification of two different forms exhibiting hyaluronidase activity (1996) Dev. Biol., 175, pp. 142-153Cramer, J.A., Bailey, L.C., Bailey, C.A., Miller, R.T., Kinetic and mechanistic studies with bovine testicular hyaluronidase (1994) Biochim. Biophys. Acta B, 1200, pp. 315-321Csóka, A.B., Scherer, S.W., Stern, R., Expression analysis of six paralogous human hyaluronidase genes clustered on chromosomes 3p21 and 7q31 (1999) Genomics, 60, pp. 356-361Delano, W.L., (2002) The PyMOL Molecular Graphics System DeLano Scientific, , Palo Alto, CaliforniaEberlein, B., Krischan, L., Darsow, U., Ollert, M., Ring, J., Double positivity to bee and wasp venom: improved diagnostic procedure by recombinant allergen-based IgE testing and basophil activation test including data about cross-reactive carbohydrate determinants (2012) J. Allergy Clin. Immunol., 130, pp. 155-161Fiszer-Szafarz, B., Hyaluronidase polymorphism detected by polyacrylamide gel electrophoresis. Application to hyaluronidases from bacteria, slime molds, bee and snake venoms, bovine testes, rat liver lysosomes, and human serum (1984) Anal. Biochem., 143, pp. 76-81Fiszer-Szafarz, B., Szafarz, D., Vannier, P., Polymorphism of hyaluronidase in serum from man, various mouse strains and other vertebrate species revealed by electrophoresis (1990) Biol. Cell., 68, pp. 95-100Gmachl, M., Kreil, G., Bee venom hyaluronidase is homologous to a membrane protein of mammalian sperm (1993) Proc. Natl. Acad. Sci. U. S. A., 90, pp. 3569-3573Hemmer, W., Cross-reactivity to honeybee and wasp venom (2008) Hautarzt, 59, pp. 194-199Henrissat, B., Bairoch, A., Updating the sequence-based classification of glycosyl hidrolases (1996) Biochem. J., 316, pp. 695-696Hotez, P., Cappello, M., Hawdon, J., Beckers, C., Sakanari, J., Hyaluronidases of the gastrointestinal invasive nematodes Ancylostoma conium and Anisakissimplex: possible functions in the pathogenesis of human zoonoses (1994) J. Infect. Dis., 170, pp. 918-926Jin, C., Hantusch, B., Hemmer, W., Stadlmann, J., Altmann, F., Affinity of IgE and IgG against cross-reactive carbohydrate determinants on plant and insect glycoproteins (2008) J. Allergy Clin. Immunol., 121, pp. 185-190Jin, C., Focke, M., Léonard, R., Jarisch, R., Altmann, F., Hemmer, W., Reassessing the role of hyaluronidase in yellow jacket venom allergy (2010) J. Allergy Clin. Immunol., 125, pp. 184-190e1Kemeny, D.M., Dalton, N., Lawrence, A.J., Pearce, F.L., Vernon, C.A., The purification and characterization of hyaluronidase from the venom of the honey bee, Apis mellijera (1984) Eur. J. Biochem., 139, pp. 217-233Kemparaju, K., Girish, K.S., Snake venom hyaluronidase: a therapeutic target (2006) Cell Biochem. Funct., 24, pp. 7-12Kolarich, D., Altmann, F., N-glycan analysis by matrix-assisted laser desorption/ionization mass spectrometry of electrophoretically separated nonmammalian proteins: application to peanut allergen Ara h 1 and olive pollen allergen Ole e 1 (2000) Anal. Biochem., 285, pp. 64-75Kolarich, D., Léonard, R., Hemmer, W., Altman, F., The N-glycans of yellow jacket venom hyaluronidases and the protein sequence of its major isoform in Vespula vulgaris (2005) FEBS J., 272, pp. 5182-5190Kreil, G., Hyaluronidases - a group of neglected enzymes (1995) Protein Sci., 4, pp. 1666-1669Kubelka, V., Altmann, F., März, L., The asparagine-linked carbohydrate of honeybee venom hyaluronidase (1995) Glycoconj. J., 12, pp. 77-83Kulkarni-Kale, U., Bhosle, S., Kolaskar, A.S., CEP: a conformational epitope prediction server (2005) Nucleic Acids Res., 33, pp. 168-171Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., PROCHECK: a program to check the stereochemical quality of protein structures (1993) J. Appl. Cryst., 26, pp. 238-291Laurent, T.C., The Biology of Hyaluronan (1989) Ciba Foundation Symp. 143, pp. 1-298. , John Wiley & Sons, New YorkLong-Rowe, K.O., Burnett, J.W., Characteristics of hyaluronidase and hemolytic activity in fishing tentacle nematocyst venom of Chrysaora quinquecirrha (1994) Toxicon, 32, pp. 165-174Lu, G., Kochoumian, L., King, T.P., Sequence identity and antigenic crossreactivity of hite face hornet venom allergen, also a hyaluronidase, with other proteins (1995) J. Biol. Chem., 270, pp. 4457-4465Markovic-Housley, Z., Miglierini, G., Soldatova, L., Rizkallah, P.J., Muller, U., Schirmer, T., Crystal structure of hyaluronidase, a major allergen of bee venom (2000) Structure, 8, pp. 1025-1035McConkey, B.J., Sobolev, V., Edelman, M., Quantification of protein surfaces, volumes and atom-atom contacts using a constrained Voronoi procedure (2002) Bioinformatics, 18, pp. 1365-1373Meyer, K., Hyaluronidases (1971) The Enzymes, 5, pp. 307-320. , Academic Press, New YorkPalma, M.S., Insect venom peptides (2006) Handbook of Biologically Active Peptides, pp. 389-396. , Academic Press, Burlington, A.J. Kastin (Ed.)Pinto, J.R., Santos, L.D., Arcuri, H.A., Dias, N.B., Palma, M.S., Proteomic characterization of the hyaluronidase (E.C. 3.2.1.35) from the venom of the social wasp Polybia paulista (2012) Protein Pep. Lett., 19, pp. 624-634Senff-Ribeiro, A., Henrique Da Silva, P., Chaim, O.M., Gremski, L.H., Paludo, K.S., Bertoni Da Silveira, R., Gremski, W., Veiga, S.S., Biotechnological applications of brown spider (Loxosceles genus) venom toxins (2008) Biotechnol. Adv., 26, pp. 210-218Sanchez, R., Sali, A., Advances in comparative protein-structure modeling (1997) Curr. Opin. Struct. Biol., 7, pp. 206-214Santos, L.D., Santos, K.S., Pinto, J.R., Dias, N.B., Souza, B.M., Santos, M.F., Perales, J., Palma, M.S., Profiling the proteome of the venom from the social wasp Polybia paulista: a clue to understand the envenoming mechanism (2010) J. Proteome Res., 9, pp. 3867-3877Sedmak, J.J., Grossberg, S.E., A rapid, sensitive and versatile assay for protein using Coomassie brilliant blue G250 (1977) Anal. Biochem., 79, pp. 544-552Seo, J., Lee, K.J., Post-translational modifications and their biological functions: proteomic analysis and systematic approaches (2004) J. Biochem. Mol. Biol., 37, pp. 35-44Silva, G.P., Brochetto-Braga, M.R., Ruberti, M., Ternero, M.L., Gobbi, N., A comparative study of protein and enzymatic activity in venoms of some common wasps (hymenoptera: vespidae) from São Paulo State (2004) Sociobiology, 44, pp. 271-282Skov, L.K., Seppala, U., Coen, J.J., Crickmore, N., King, T.P., Monsalve, R., Kastrup, J.S., Gajhede, M., Structure of recombinant Ves v 2 at 2.0 angstrom resolution: structural analysis of an allergenic hyaluronidase from wasp venom (2006) Acta Crystallogr. D. Biol. Crystallogr., 62, pp. 595-604Steinberg, T.H., Pretty On Top, K., Berggren, K.N., Kemper, C., Jones, L., Diwu, Z., Haugland, R.P., Patton, W.F., Rapid and simple single nanogram detection of glycoproteins in polyacrylamide gels and on electroblots (2001) Proteomics, 7, pp. 841-855Stern, R., Jedrzejas, M.J., Hyaluronidases: their genomics, structures, and mechanisms of action (2006) Chem. 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Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3–7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease