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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
361

Respostas fisiológicas induzidas por estresse hídrico e infecção por Meloidogyne javanica (Treub) Chitwood em portaenxertos de Prunus spp / Physiological responses induced by water stress and infection by Meloidogyne javanica (Treub) Chitwood on rootstocks of Prunus spp

Messchmidt, Aline Alves 20 December 2013 (has links)
Made available in DSpace on 2014-08-20T13:59:07Z (GMT). No. of bitstreams: 1 dissertacao_aline_alves_messchmidt.pdf: 535406 bytes, checksum: d041feac45e14506cfa6fba63d16e35c (MD5) Previous issue date: 2013-12-20 / The Rio Grande do Sul has the largest peach producing area of the country, but its productivity is still low when compared with other Brazil´s states. One of the problems related to low productivity are soils with poor drainage and low water storage capacity, mainly in the producing region of Pelotas, as well as the presence of root-knot nematodes (Meloidogyne spp.) on the orchards, whose damages have great importance because the novice action on the root system, affecting the nutrient and water absorption and translocation. These stresses can cause physiological changes in plants affecting fruit quality and productivity of orchards. The objective of this study was to evaluate the effects of these stresses on peach plants of rootstock cv. Capdeboscq, Flordaguard and plum rootstock cv. Mirabolano 29-C. The study was divided into two experiments. At first, we evaluated gas exchange and antioxidant enzymes activity of Prunus rootstocks submitted to the following stresses treatments: a) Waterlogging, for eight days; b) drought for eight days; and c) control, with regular plant watering. After the stresses period, plants returned to normal water regime. The Mirabolano 29-C rootstock shown to be more susceptible to drought than waterlogging, compared to the two peach rootstocks evaluated. On the other hand, Flordaguard and Capdeboscq shown more damages when the plants were subjected to waterlogging, verified by the higher rate of lipid peroxidation in relation to the control plants of these cultivars. The second experiment evaluated the effects of M. javanica plant-inoculation on the reproduction factor (RF) and gas exchange. 150 days after inoculation, the plants of cvs. Capdeboscq, Flordaguard, and Mirabolano C-29 were susceptible (FR = 1.77), resistant, and immune, respectively. In relation to gas exchange, only the inoculated plants of cv. Capdeboscq showed higher stomatal conductance, internal CO2 concentration and transpiration, and reduced efficiency in water use. For other genotypes there were no significant effects on the variables analyzed. / O Rio Grande do Sul possui a maior área de produção de pêssego do Brasil, porém sua produtividade ainda é baixa quando comparado com outros estados. Um dos problemas relacionados à baixa produtividade são os solos com problemas de drenagem e baixa capacidade de armazenar água, principalmente na região produtora de Pelotas, assim como a presença de nematóides causadores de galhas nas raízes (Meloidogyne spp.), cujos danos têm grande importância em virtude da ação nociva sobre o sistema radicular, afetando a absorção e a translocação de água e nutrientes. Esses estresses podem causar alterações fisiológicas nas plantas, comprometendo a qualidade dos frutos e a produtividade dos pomares. O objetivo do presente trabalho foi avaliar os efeitos destes fatores de estresse nos portaenxertos de pessegueiro cv. Capdeboscq, Flordaguard e ameixeira cv. Mirabolano 29-C. O trabalho foi dividido em dois experimentos. No primeiro, avaliou-se as trocas gasosas e atividade antioxidante de portaenxertos do gênero Prunus submetidos aos seguintes tratamentos de estresse: a) alagamento do solo, por oito dias b) seca, por oito dias e c) controle, com irrigação conforme necessidade das plantas. Após o período de estresse, as plantas retornaram às condições normais de regime hídrico. O portaenxerto Mirabolano 29-C demonstrou ser mais suscetível ao déficit hídrico do que ao alagamento, quando comparado as duas cultivares de pessegueiro avaliadas. Por outro lado, nas cvs. Flordaguard e Capdeboscq ocorreram maiores danos quando as plantas foram submetidas ao alagamento, verificado por meio da maior taxa de peroxidação lipídica, em relação as plantas controle destas cultivares. No segundo experimento, avaliaram-se os efeitos da inoculação de Meloidogyne javanica sobre o fator de reprodução (FR) e das trocas gasosas. Aos 150 dias após a inoculação, as plantas das cvs. Capdeboscq, Flordaguard e Mirabolano 29-C mostraram-se suscetíveis (FR=1,77), resistentes e imunes, respectivamente. Em relação às trocas gasosas, apenas as plantas inoculadas da cv. Capdeboscq apresentaram maiores valores de condutância estomática, concentração intracelular de CO2 e de transpiração, e uma menor eficiência no uso da água. Para os demais genótipos não houve efeitos significativos nas variáveis analisadas.
362

Caracterização da descendência híbrida e segregação de marcadores microssatélites em uma população F2 de Prunus sp / Characterization of hybrid offspring and segregation of microsatellite markers in an F2 population of Prunus sp..

MACHADO, Luciana Rodrigues Nogueira 15 April 2011 (has links)
Made available in DSpace on 2014-08-20T13:59:13Z (GMT). No. of bitstreams: 1 dissertacao_luciana_nogueira_machado.pdf: 513011 bytes, checksum: 7c2764a3f1c5001fdbbcf496c8d8702f (MD5) Previous issue date: 2011-04-15 / The peach (Prunus persica (L) Batsch) is the predominant stone fruit around the world, but in Brazil, due to factors such as incidence of pests in orchards, low quality plant propagation material and the lack of suitable rootstocks culture, the productivity is still considered low. In this context, is necessary to develop new rootstocks of Prunus, more adapted to the ecological conditions of the Southern region of Brazil and carrying genes for pests resistance such as nematodes. In this study, microsatellite loci (SSR) were used to verify the hybrid offspring of genotypes and makers segregation in an F2 population of peach rootstocks, obtained from controlled crosses, generating data to marker-assisted selection (MAS) of new genotypes carrying genes for nematode resistance. This work was divided in two articles; the first was a paternity test to verify the paternal and maternal offspring of 13 hybrids from controlled crosses between several rootstocks and scion with desirable agronomic traits. We obtained confirmation of paternity for 11 of the 13 hybrids analyzed. Two genotypes, presumably descendants of Prunus mume as male parent, were confirmed as being generated by selfing of genotipe Aldrighi P1. In the second article, a linkage map was constructed for a population of 50 F2 plants obtained by selfing of F1 hybrid, derived from a cross between the peaches Capdeboscq‟ x Flordaguard'. The segregation of 37 SSR loci was evaluated and 11 markers showed a link, allowing us to build a map with two groups. It was found that the markers BPPCT004, CPDCT044, BPPCT034 and BPPCT002 were grouped in a manner similar to that found in the GL2 Prunus reference map. With the data obtained suggests that these SSR loci are associated with genes for resistance to Meloidogyne spp. in different mapping populations, in which case inherited from the rootstock 'Flordaguard', and may be used directly in SAM and improvement genetic peach rootstocks derived from a cross between Capdeboscq‟ x Flordaguard‟. / O pessegueiro (Prunus persica (L) Batsch) é a frutífera de caroço mais predominante em todo mundo, porém, no Brasil, devido a fatores como incidência de pragas nos pomares, baixa qualidade fitossanitária do material propagativo e falta de porta-enxertos adequados para a cultura, a produção ainda é considerada baixa. Neste contexto, existe a grande necessidade de desenvolver novos porta-enxertos de Prunus, mais adaptados as condições edafoclimáticas da Região Sul do Brasil e portadores de genes de resistência a pragas, dentre as quais os fitonematóides. No presente trabalho, locos de microssatélites (SSR) foram utilizados com o objetivo de verificar a descendência e a segregação de marcadores em genótipos híbridos da população F2 de porta-enxertos de pessegueiro, obtida a partir de cruzamento controlado, gerando dados para auxiliar na seleção assistida por marcadores (SAM) de novos genótipos portadores de genes de resistência a nematóides das galhas. Esta dissertação foi dividida em dois artigos, no primeiro, foi realizado um teste de paternidade, para verificar a descendência de 13 híbridos provenientes de diversos cruzamentos controlados entre diversos porta-enxertos e copas com características agronômicas desejáveis. Obteve-se confirmação da paternidade para 11 dos 13 híbridos analisados. Dois genótipos, supostamente descendentes de Prunus mume como parental masculino, foram confirmados como sendo gerados por autofecundação da cultivar Aldrighi. No segundo artigo, foi construído um mapa de ligação para uma população de 50 plantas F2 obtidas por autofecundação de um híbrido F1, proveniente do cruzamento entre os pessegueiros cv. Capdeboscq‟ x Flordaguard‟, onde a segregação de 37 locos SSR foi avaliada e 11 marcadores apresentaram ligação, permitindo a elaboração de um mapa com dois grupos. Verificou-se que os marcadores BPPCT004, CPDCT044, BPPCT034 e BPPCT002 foram agrupados de forma similar ao encontrado no GL2 do mapa de referência de Prunus. Com os dados obtidos, sugere-se que estes locos SSR, estejam associados a genes de resistência a Meloidogyne spp., em diferentes populações de mapeamento, sendo neste caso herdados do porta-enxerto Flordaguard‟ e poderão ser utilizados diretamente em SAM e melhoramento genético de porta-enxertos do cruzamento entre os pessegueiros cv. Capdeboscq‟ x Flordaguard‟.
363

Relative Symplectic Caps, Fibered Knots And 4-Genus

Kulkarni, Dheeraj 07 1900 (has links) (PDF)
The 4-genus of a knot in S3 is an important measure of complexity, related to the unknotting number. A fundamental result used to study the 4-genus and related invariants of homology classes is the Thom conjecture, proved by Kronheimer-Mrowka, and its symplectic extension due to Ozsv´ath-Szab´o, which say that closed symplectic surfaces minimize genus. In this thesis, we prove a relative version of the symplectic capping theorem. More precisely, suppose (X, ω) is a symplectic 4-manifold with contact type bounday ∂X and Σ is a symplectic surface in X such that ∂Σ is a transverse knot in ∂X. We show that there is a closed symplectic 4-manifold Y with a closed symplectic submanifold S such that the pair (X, Σ) embeds symplectically into (Y, S). This gives a proof of the relative version of Symplectic Thom Conjecture. We use this to study 4-genus of fibered knots in S3 . We also prove a relative version of the sufficiency part of Giroux’s criterion for Stein fillability, namely, we show that a fibered knot whose mondoromy is a product of positive Dehn twists bounds a symplectic surface in a Stein filling. We use this to study 4-genus of fibered knots in S3 . Using this result, we give a criterion for quasipostive fibered knots to be strongly quasipositive. Symplectic convexity disc bundles is a useful tool in constructing symplectic fillings of contact manifolds. We show the symplectic convexity of the unit disc bundle in a Hermitian holomorphic line bundle over a Riemann surface.
364

"Eu vinha rodando pela rua": que ponto de ancoragem para o sujeito adolescente em situação de rua?

Barros, Paula Cristina Monteiro de 01 December 2015 (has links)
Made available in DSpace on 2017-06-01T18:29:28Z (GMT). No. of bitstreams: 1 paula_cristina_monteiro_barros.pdf: 2055403 bytes, checksum: 3c7f35ad65bc4a12df93679e44163bf6 (MD5) Previous issue date: 2015-12-01 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The presence of "street kids" denounces the social exclusion of children and adolescents that wander the streets, in a trajectory that prevails transgression, violence, destructivity, through which the subject persists to exist for the Other. This thesis is a result of questionings from a clinical practice in an institution. This thesis envisions to analyze what could be related to an anchorage and enlacing in the wander of homeless adolescents, based on the traces that make them unique and detached from the universe of street kids . We propose the hypothesis that the wander, regardless of the subjective degradation and the expulsion, could constitute a movement of life and resistance, an emergence of the subject. Based on the psychoanalytic Trace of the Case, this research was guided by two clinical cases, from what constituted an intervention s stumble and its effects in the listening process. Guided by the Freudian Aufhebung and the Lacanian borromean knot, we highlight a reality characterized by the fraying of time and space, a dilution of boundaries, a prevalence of the Real. The proposition of a borromean clinic places the institution as a symbolic reference; a substitute that functions, utilizing the word as a resource, as a repair to the lapses of the knot. This is about a construction that transgresses what is institutionalized about exclusion, knowledge, and established clinical practice. It aims, through an inventive act, a trajectory from the wound of the exclusion to the draft of a trace, through a symbolic nomination; a between space that promotes the knot and the social engagement; a source of anchorage for whom used to go rolling through the street . / Os meninos de rua constituem uma problemática que denuncia a exclusão social de crianças e adolescentes, os quais vagueiam pelas ruas, numa trajetória em que prevalecem a transgressão, a violência, a destruição de si e do outro, por meio dos quais o sujeito insiste em existir para o Outro. Esta tese resulta das inquietações de uma prática clínico-institucional e visou a analisar o que pode indicar uma ancoragem e enodamento na errância do sujeito adolescente em situação de rua a partir dos traços que o singularizam e o destacam do universo meninos de rua . Sustentamos a hipótese de que a errância, apesar da degradação subjetiva e da radical expulsão, pode constituir um movimento de vida e resistência, uma tomada de posição do sujeito. Baseando-se na proposição psicanalítica do Traço do Caso, a pesquisa foi norteada pela construção de dois casos clínicos, a partir do que fez tropeço na intervenção e de seus efeitos na escuta. À luz da Aufhebung freudiana e da topologia lacaniana do nó borromeu, destacamos uma realidade marcada por um esgarçamento do tempo e do espaço, uma diluição das fronteiras, uma prevalência do Real. A proposição de uma clínica borromeana situa a instituição como referente simbólico; suplência que opera, no recurso à palavra, reparos nos lapsos do nó. Trata-se de uma construção do adolescente e da instituição que transgride o instituído da exclusão, do saber, das práticas sedimentadas, buscando, num ato inventivo e de autoria do sujeito, uma ultrapassagem da marca da exclusão para a rasura de um traço, por meio de uma nominação simbólica; um entre que enoda e faz laço social; um ponto de ancoragem para quem vinha rodando pela rua .
365

Identification de marques épigénétiques chez le nématode à galles parasite de plantes Meloidogyne incognita / Identification of epigenetic marks in the plant-parasitic root-knot nematode Meloidogyne incognita

Pratx, Loris 04 May 2017 (has links)
Meloidogyne incognita est le nématode causant le plus de dégâts en agriculture. Sa particularité est d'être un organisme à reproduction asexuée obligatoire. Une femelle engendre des clones a priori 100% identiques génétiquement. Pourtant, M. incognita est capable de faire preuve d'une grande plasticité phénotypique lui permettant de répondre à de nouveaux environnements. Un exemple est le déterminisme du sexe, un phénotype lié aux conditions environnementales et semblant impliquer des régulations chromatiniennes. Un autre exemple est la capacité à contourner les résistances des plantes (virulence), un caractère héréditaire mais non-Mendelien. Dans le cadre de cette thèse, j'ai cherché à tester l'implication des mécanismes épigénétiques dans la plasticité phénotypique en absence de sexe de M. incognita. A ces fins, j'ai évalué la conservation des mécanismes épigénétiques chez les nématodes à galles. Cette approche a permis de pointer que les mécanismes connus chez C. elegans sont conservés chez les nématodes parasites de plantes. Puis, une méthodologie de ChIP-seq a été mise en place afin de comparer les profils d'accumulation des marques d'histones chez M. incognita au cours de la réponse aux conditions environnementales. Cette stratégie a permis la mise en évidence 1- de patrons d'histones modifiées marquant le développement du parasite et 2- de régions génomiques comportant plus de 300 gènes dont des candidats facteurs d'avirulence déjà décrits dans la littérature spécifiquement perdue entre M. incognita (a)virulents. Ces travaux de thèse présentent un intérêt fondamental sur la compréhension de l'évolution d'un organisme en absence de reproduction sexuée. / Meloidogyne incognita is the most damaging plant-parasitic nematode in agriculture. M. incognita reproduces in an asexual way by obligatory parthenogenesis. Genetically identical individuals develop from females and form clonal populations. Although these clones share the same genetic heritage, modifications of their phenotype can be observed when they are exposed to unfavorable environments. This phenotypic plasticity is characterized through two phenotypes of interest: sex-differentiation and virulence (i.e. capacity to parasite a resistant crop). Sex-differentiation varies among environmental conditions and was reported to be linked to decondensed chromatin regions. Virulence is an heritable character transmitted in a non-Mendelian way. Our study focuses on identifying the role of epigenome in the generation of phenotypic variability. To this end we detailed the presence of proteins involved in epigenetic regulations in Meloidogyne spp. We also developed a ChIP-seq assay to compare histone modifications between different developmental stages and between virulent and avirulent parasites. Our results allow to detect specific histone patterns associated with M. incognita development. These results lead us to propose a model that could explain sex determination in M. incognita. We also could link virulence acquisition with the loss of some specific genomic regions that contains more than 300 genes including already described potential avirulence factors. This study opens the way for analyzing the role of epigenetic mechanisms at a whole genome scale, and allows to identify novel biological processes involved in phenotypic variation in asexual organisms.
366

Alternativní ontologie: topologická imaginace a topologický materialismus / Alternative Ontology: topological Imagination and Topological Materialism

Mrva, Jozef January 2022 (has links)
The dissertation Alternative Ontology, subtitled Topological Imagination and Topological Materialism, focuses on the analysis of spatial phenomena and space in the intentions of the mathematical discipline of topology, which is interested in spaces from the point of view of set theory. My goal is to present topology as a tool not only for contemporary philosophy, but also for artistic creation. For the purpose of the dissertation, I formulate two concepts: Topological imagination and Topological materialism. Topological imagination is a tool and method for creating and thinking with the consciousness of space as a dynamic structure, which is not bound only by fixed laws of geometry. This method originated as the name of my long-term artistic practice, which is largely based on the study of space, topology, knot theory and the search for ways of their application in artistic and theoretical work. I propose Topological materialism as a concept that combines the thinking of networks and multi-dimensional spaces with the philosophical currents of the materialist tradition, especially the New Materialism. My basic thesis is that these cannot be perceived separately. Materialism cannot be thought without its spatial dimension, and topology without anchoring in the material world becomes a mere abstraction. The second part of the dissertation is devoted to the analysis of specific spaces: the space we inhabit, which I call phenomenological, infrastructure, logistics space, information space and the space of capital. In addition to individual analyzes, I also focus on their intersections, connections and joint operation.
367

Effective control of neem (Azadirachta indica A. Juss) cake to plant parasitic nematodes and fungi in black pepper diseases in vitro: Research article

Duong, Duc Hieu, Ngo, Xuan Quang, Do, Dang Giap, Le, Thi Anh Hong, Nguyen, Vu Thanh, Smol, Nic 09 December 2015 (has links)
Neem cake is a product of the cold pressing from the neem kernels to obtain neem oil. Bio-active substances from neem cake extracted solutions were evaluated for their potential to control the root knot nematodes and other pests of plants. In this study different concentrations of the solution extracted from neem cake was tested against the second stage juveniles of the plant parasitic nematode Meloidogyne spp. and four phytopathogenic fungi: Rhizoctonia solani, Sclerotium rolfsii, Collectotrichum spp. and Phytopthora capsici. Toxicity of neem cake extractions is represented by the EC50 value for the second-stage juvenile (J2) of Meloidogyne spp. and the four phytopathogenic fungi via Probit analysis. A 5% dilution of the solvent extracting from neem cake already caused 100% larval mortality after 24 hours exposure. Undiluted neem cake extraction effectively inhibited the growth of the four phytopathogenic fungi. The EC50 value of neem cake on J2-larvae of Meloidogyne nematode and on the fungi Rhizoctonia solani, Sclerotium rolfsii, Collectotrichum spp. and Phytophthora capsici was 0.51, 0.74, 0.30, 0.51 and 4.33%, respectively. / Bánh dầu neem là sản phẩm của quá trình ép nhân hạt neem để lấy dầu. Các hoạt chất sinh học từ dịch chiết bánh dầu neem đã được đánh giá có tiềm năng lớn trong phòng trừ tuyến trùng nốt sưng và các loài dịch hại khác của nhiều loại cây trồng. Trong nghiên cứu này các nồng độ dịch chiết khác nhau của bánh dầu neem đã được thử nghiệm khả năng diệt tuyến trùng (ấu trùng tuổi 2 thuộc giống Meloidogyne spp.) và ức chế 4 loài nấm bệnh như: Rhizoctonia solani, Sclerotium rolfsii, Collectotrichum spp. và Phytopthora capsici. Độc tính của dịch chiết bánh dầu neem được biểu diễn bởi giá trị EC50 đối với ấu trùng tuổi 2 của tuyến trùng Meloidogyne spp. và các loài nấm bệnh thông qua phân tích Probit. Dịch chiết bánh dầu neem ở nồng độ 5% đã làm chết 100% cá thể IJ2 của Meloidogyne spp sau 24 giờ phơi nhiễm. Dịch nguyên chất bánh dầu neem ức chế cả 4 loài nấm bệnh. Giá trị EC50 của bánh dầu neem lên ấu trùng tuổi 2 của Meloidogyne spp và các loài nấm bệnh Rhizoctonia solani, Sclerotium rolfsii, Collectotrichum spp. and Phytophthora capsici tương ứng là 0.51, 0.74, 0.30, 0.51 và 4.33%.
368

Soybean QTL Mapping and Candidate Gene Identification for Pythium irregulare and Phytophthora sojae Partial Resistance; and Root-Knot Nematode Induced Suppression of Gene Silencing

Nauth, Brittany J. 29 October 2014 (has links)
No description available.
369

Managing Weeds and Soilborne Pests with Fumigant and Non-Fumigant Alternatives to Methyl Bromide

McAvoy, Theodore Porter 06 June 2012 (has links)
Methyl bromide (MBr) was widely used as a soil fumigant to manage soilborne pests in plasticulture vegetable production; however, it has been banned by the United Nations Environment Programme. Alternatives to MBr must be implemented to sustain fresh market tomato productivity. Possible MBr alternatives include new fumigant compounds, improved plastic mulch, and grafting. Methyl iodide (MeI) and dimethyl disulfide (DMDS) were tested as fumigant alternatives to MBr for the control of yellow nutsedge and soilborne pathogens of tomato. Virtually impermeable film (VIF) and totally impermeable film (TIF) were tested for fumigant retention and yellow nutsedge control in tomato. Grafting onto resistant rootstocks was tested for bacterial wilt and nematode management in tomato. In the absence of a soil fumigant, TIF suppressed yellow nutsedge better than VIF. TIF increased fumigant retention compared to VIF at similar application rates. Reduced fumigant application rates could be used in combination with TIF while maintaining fumigant concentrations, weed control, and crop yields comparable to greater use rates with VIF. Shank applied DMDS rates could be lowered to 281 L/ha under TIF from 468 L/ha under VIF; shank applied MeI application rates could be reduced to 56 L/ha under TIF compared to 93 L/ha under VIF and drip applied DMDS could be reduced from 561 L/ha under VIF film to 374 L/ha under TIF. Grafting susceptible commercial tomato cultivars onto resistant tomato hybrid rootstocks increased yields and plant survival in bacterial wilt infested fields. "Cheong Gang", "BHN 998", and "BHN 1054" were the best performing rootstocks for bacterial wilt resistance and tomato fruit yield in severely infested fields. Grafting increased tomato yield and decreased root galling from root-knot nematodes in an infested field. Hybrid rootstock "RST 106" resulted in the lowest root-knot nematode galling. In conclusion, TIF with reduced rates of DMDS or MeI is a viable MBr alternative for fresh market tomato production to retain effective doses of fumigant, manage yellow nutsedge and maintain yields. Grafting is an effective MBr alternative to manage bacterial wilt and root-knot nematode and maintain tomato yields. / Ph. D.
370

Structural studies of Norrin dependent Wnt/beta-catenin signaling

Chang, Tao-Hsin January 2014 (has links)
Norrin is a secreted cystine-knot growth factor that plays critical roles in vascular development in the brain, retina, and cochlea, as well as the uterus. Although Norrin is unrelated to the lipid-modified morphogens Wnts, Norrin activates the canonical Wnt/β-catenin pathway by binding to receptor Frizzled4 cysteine-rich domain (Fz4-CRD) and co-receptors of low density lipoprotein receptor related protein 5/6 ectodomain (Lrp5/6-ECD) in conjunction with Tetraspanin-12 (Tspan-12). Like Wnts, Norrin has limited extracellular diffusion properties as a result of associating with heparan sulfate proteoglycans (HSPGs). Mutations lead to inherited disordered retinal vascularization diseases such as Norrie disease, familial exudative vitreoretinopathy and coats' disease. However, the molecular mechanism of how Norrin initiates signalling by engagement with Fz4, Lrp5/6, and HSPGs has remained unresolved. Here, novel strategies for protein production of recombinant human Norrin and Fz4-CRD as well as the complex are developed. The crystal structures of Norrin and its complex with Fz4-CRD, plus complex bound with the heparin mimic sucrose octasulphate, and unliganded structures of Fz4-CRD are presented. These structural data together with biophysical and cellular assays not only reveal the Fz4 and Lrp5/6 binding sites on distinct patches of the Norrin surface, but also indicate the HSPGs binding site on Norrin and Fz4-CRD as well as providing a framework to explain numerous disease-related mutations. Structural comparison with Xenopus Wnt8 in complex with mouse Fz8-CRD provides molecular insights for our understanding of ligand-receptor binding specificity and promiscuity, which has important implications for developing therapeutic strategies against Norrin dependent retinal disorders, and cancers caused by abnormal Wnt signaling.

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