Resistance against strongylid nematodes in two high prevalence Equine Recurrent Airway Obstruction families has a genetic basis

A recent study showed increased resistance against strongylid nematodes in offspring of a stallion affected by recurrent airway obstruction (RAG) compared with unrelated pasture mates. Resistance against strongylid nematodes was associated with RAG affection. Hypothesis: Resistance against strongylid nematodes has a genetic basis. The genetic variants influencing strongylid resistance also influence RAG susceptibility. Faecal samples from the half-sibling offspring of two RAG-affected Warmblood stallions 98 offspring from the first family (family 1) and 79 from the second family (family 2) were analysed using a combined sedimentation-flotation method. The phenotype was defined as a binary trait - either positive or negative for egg shedding. The influence of non-genetic factors on egg shedding was analysed using SAS, the mode of inheritance was investigated using PAP and iBay, and the association between shedding of strongyle eggs and RAG was estimated by odds ratios. Previously established genotypes for 315 microsatellite markers were used for QTL analyses using GRID QTL. The inheritance of "strongylid egg shedding" is influenced by major genes on ECA15 and ECA20. Shedding of strongylid eggs is associated with RAG in family 1 but not in family 2. Conclusions: The status of "shedding of strongyle eggs" has a genetic background. The results were inconclusive as to whether "egg shedding" and RAG share common genetic components. Our results suggest that it may be possible to select for resistance against strongylid nematodes.

Reconstructive Dreams: A Pragmatic Fantastic After Postmodernism

This dissertation focuses on the use of fantastic elements in the work of a young generation of writers which explore the possibilities of literary development after and beyond postmodernism. By overtly declaring the fictionality of their fantastic stories by means of frame narratives, texts like Jonathan Safran Foer’s Everything is Illuminated (2002), Michael Chabon’s The Amazing Adventures of Kavalier and Clay (2000), Mark Danielewski’s House of Leaves (2000), David Mitchell’s number9dream (2001) and Yann Martel’s Life of Pi (2001) reassess the communicative value of genre boundaries in an attempt to move beyond postmodern relativity and breakdown of communicability. This clear focus on pragmatic concerns marks a shift in the use of the fantastic which calls for a reconsideration of some of the general critical assumptions about the workings of the mode. Though the relation between reality and fiction remains a central issue, the main concern shifts away from such epistemological and ontological considerations, towards questions concerning the pragmatic function of literary fiction in general and different genres in particular. Instead of dwelling on the typically postmodern concerns about the fictionality of reality and the instability of meaning, the works under discussion emphasise the constructive role fiction plays in dealing with reality, the uses to which it can be put and the functions it fulfils in fashioning our being in the world. Drawing on Iser’s theory of the fictive, Irmtraud Huber therefore suggests a reconceptualisation of the fantastic mode, which newly foregrounds its underlying pragmatic structure. She bring this adapted understanding to bear in a close textual analysis of the above mentioned literary texts, with the aim to account for their use of the mode in their commitment to a larger literary endeavour of a new generation that engages with the inheritance of postmodernism and struggles to come into its own.

Small quantity but large effect — How minor phases control strain localization in upper mantle shear zones

Low viscosity domains such as localized shear zones exert an important control on the geodynamics of the uppermost mantle. Grain size reduction and subsequent strain localization related to a switch from dislocation to diffusion creep is one mechanism to form low viscosity domains. To sustain strain localization, the grain size of mantle minerals needs to be kept small over geological timescales. One way to keep olivine grain sizes small is by pinning of mobile grain boundaries during grain growth by other minerals (second phases). Detailed microstructural studies based on natural samples from three shear zones formed at different geodynamic settings, allowed the derivation of the olivine grain-size dependence on the second-phase content. The polymineralic olivine grain-size evolution with increasing strain is similar in the three shear zones. If the second phases are to pin the mobile olivine grain boundary the phases need to be well mixed before grain growth. We suggest that melt-rock and metamorphic reactions are crucial for the initial phase mixing in mantle rocks. With ongoing deformation and increasing strain, grain boundary sliding combined with mass transfer processes and nucleation of grains promotes phase mixing resulting in fine-grained polymineralic mixtures that deform by diffusion creep. Strain localization due to the presence of volumetrically minor minerals in polymineralic mantle rocks is only important at high strain deformation (ultramylonites) at low temperatures (<~800°C). At smaller strain and stress conditions and/or higher temperatures other parameters like overall energy available to deform a given rock volume, the inheritance of mechanical anisotropies or the presence of water or melts needs to be considered to explain strain localization in the upper mantle.

A Nonsense Variant in COL6A1 in Landseer Dogs with Muscular Dystrophy.

A novel canine muscular dystrophy in Landseer dogs was observed. We had access to five affected dogs from two litters. The clinical signs started at a few weeks of age and the severe progressive muscle weakness led to euthanasia between 5 and 15 months of age. The pedigrees of the affected dogs suggested a monogenic autosomal recessive inheritance of the trait. Linkage and homozygosity mapping indicated two potential genome segments for the causative variant on chromosomes 10 and 31 harboring a total of 4.8 Mb of DNA or 0.2% of the canine genome. Using the illumina sequencing technology we obtained a whole genome sequence from one affected Landseer. Variants were called with respect to the dog reference genome and compared to the genetic variants of 170 control dogs from other breeds. The affected Landseer dog was homozygous for a single private non-synonymous variant in the critical intervals, a nonsense variant in the COL6A1 gene (Chr31:39,303,964G>T; COL6A1:c.289G>T; p.E97*). Genotypes at this variant showed perfect concordance with the muscular dystrophy phenotype in all five cases and more than one thousand control dogs. Variants in the human COL6A1 gene cause Bethlem myopathy or Ullrich congenital muscular dystrophy. We therefore conclude that the identified canine COL6A1 variant is most likely causative for the observed muscular dystrophy in Landseer dogs. Based on the nature of the genetic variant in Landseer dogs and their severe clinical phenotype these dogs represent a model for human Ullrich congenital muscular dystrophy.

What can a unicellular parasite tell us about mitochondrial biogenesis?

In the unicellular parasite Trypanosoma brucei, as in other eukaryotes, more than 95% of all mitochondrial proteins are imported from the cytosol. The recently characterized multisubunit ATOM complex, the functional analogue of the TOM complex of yeast, mediates import of essentially all proteins across the outer mitochondrial membrane in T. brucei. Moreover, an additional protein termed pATOM36, which is loosely associated with the ATOM complex, has been implicated in the import of only a subset of mitochondrial proteins. Here we have investigated more precisely which role pATOM36 plays in mitochondrial protein import. RNAi mediated ablation of pATOM36 specifically depletes a subset of outer mitochondrial membrane proteins including ATOM complex subunits and as a consequence results in the collapse of the ATOM complex as shown by Blue native PAGE. In addition, a SILAC-based global proteomic analysis of uninduced and induced pATOM36 RNAi cells together with in vitro import experiments suggest that pATOM36 might be a novel protein import factor acting on a subset of alpha-helically anchored mitochondrial outer membrane proteins. Identification of pATOM36 interaction partners by co-immunoprecipitation together with immunofluorescence analysis shows that unexpectedly a fraction of the protein is associated with the tripartite attachment complex (TAC). This complex is essential for proper inheritance of the mitochondrial DNA in T. brucei. It forms a physical connection between the single unit mitochondrial DNA and the basal body of the flagellum that is stable throughout the cell cycle. Thus, pATOM36 simultaneously mediates ATOM assembly, and thus protein import, as well as mitochondrial DNA inheritance since it is an essential component of the TAC.

Se nas pedras faz feguras parecer... Consideraciones sobre iconografía mariana y figuras poéticas en las Cantigas de Santa María de Alfonso X

La iconografía mariana ha quedado reflejada en la poesía hispánica medieval de muchas maneras: desde versos que describen a la Virgen y sus atributos hasta conceptos teológicos y mariológicos expresados plásticamente mediante formas retóricas. Por ejemplo, el jardín y las flores como ornamentos y símbolos personales de Santa María, o bien la imagen de la luz a través de un cristal o una ventana de vidrio en escenas de la Anunciación -con abundantes testimonios pictóricos en el arte medieval-, se encuentran en la poesía en forma de descripciones simbólicas de diversa extensión y género y, por otro lado, de advocaciones marianas o tópicos mariológicos (Ave/Eva, Flos, Hortus, Radix-Virga, Regina, Stella). Este artículo propone, pues, un estudio de conjunto y comparativo de algunos de estos procedimientos, concentrándose en las Cantigas de Santa María del rey Alfonso X. En este sentido, las figuras retóricas, como herramientas que tienden un puente entre lo pictórico y lo poético, dirigen necesariamente la lectura hacia una interpretación simbólica proporcionada por la figuración o typologia, tal como la ha postulado Erich Auerbach para la textualidad medieval. En última instancia, el valor sagrado de la imagen mariana (una herencia del arte icónico bizantino) se representa también en los milagros de las Cantigas de Santa María, obra maestra que evidencia una fuerte influencia de la doctrina iconodúlica.

Se nas pedras faz feguras parecer... Consideraciones sobre iconografía mariana y figuras poéticas en las Cantigas de Santa María de Alfonso X

La iconografía mariana ha quedado reflejada en la poesía hispánica medieval de muchas maneras: desde versos que describen a la Virgen y sus atributos hasta conceptos teológicos y mariológicos expresados plásticamente mediante formas retóricas. Por ejemplo, el jardín y las flores como ornamentos y símbolos personales de Santa María, o bien la imagen de la luz a través de un cristal o una ventana de vidrio en escenas de la Anunciación -con abundantes testimonios pictóricos en el arte medieval-, se encuentran en la poesía en forma de descripciones simbólicas de diversa extensión y género y, por otro lado, de advocaciones marianas o tópicos mariológicos (Ave/Eva, Flos, Hortus, Radix-Virga, Regina, Stella). Este artículo propone, pues, un estudio de conjunto y comparativo de algunos de estos procedimientos, concentrándose en las Cantigas de Santa María del rey Alfonso X. En este sentido, las figuras retóricas, como herramientas que tienden un puente entre lo pictórico y lo poético, dirigen necesariamente la lectura hacia una interpretación simbólica proporcionada por la figuración o typologia, tal como la ha postulado Erich Auerbach para la textualidad medieval. En última instancia, el valor sagrado de la imagen mariana (una herencia del arte icónico bizantino) se representa también en los milagros de las Cantigas de Santa María, obra maestra que evidencia una fuerte influencia de la doctrina iconodúlica.

Se nas pedras faz feguras parecer... Consideraciones sobre iconografía mariana y figuras poéticas en las Cantigas de Santa María de Alfonso X

La iconografía mariana ha quedado reflejada en la poesía hispánica medieval de muchas maneras: desde versos que describen a la Virgen y sus atributos hasta conceptos teológicos y mariológicos expresados plásticamente mediante formas retóricas. Por ejemplo, el jardín y las flores como ornamentos y símbolos personales de Santa María, o bien la imagen de la luz a través de un cristal o una ventana de vidrio en escenas de la Anunciación -con abundantes testimonios pictóricos en el arte medieval-, se encuentran en la poesía en forma de descripciones simbólicas de diversa extensión y género y, por otro lado, de advocaciones marianas o tópicos mariológicos (Ave/Eva, Flos, Hortus, Radix-Virga, Regina, Stella). Este artículo propone, pues, un estudio de conjunto y comparativo de algunos de estos procedimientos, concentrándose en las Cantigas de Santa María del rey Alfonso X. En este sentido, las figuras retóricas, como herramientas que tienden un puente entre lo pictórico y lo poético, dirigen necesariamente la lectura hacia una interpretación simbólica proporcionada por la figuración o typologia, tal como la ha postulado Erich Auerbach para la textualidad medieval. En última instancia, el valor sagrado de la imagen mariana (una herencia del arte icónico bizantino) se representa también en los milagros de las Cantigas de Santa María, obra maestra que evidencia una fuerte influencia de la doctrina iconodúlica.

Corteza y gravedad: el plano del suelo como estrategia en la arquitectura contemporánea

Es, en el encuentro de los edificios con el terreno, donde el suelo como realidad se transforma en cualidad arquitectónica. La presente tesis aborda el estudio del plano del suelo, haciendo una revisión crítica de la arquitectura como mecanismo de pensamiento proyectual. Este análisis se enmarca a partir de los años sesenta, por considerar que es cuando comienza a evidenciarse la ruptura respecto a la herencia del Movimiento Moderno. Es entonces cuando la arquitectura marca un punto de inflexión, y empiezan a surgir diferentes actitudes metodológicas respecto al suelo, totalmente nuevas. Las clásicas acciones de encuentro como posar, elevar o enterrar fueron poco a poco sustituidas por otras más complejas como plegar, inclinar o esponjar. Utilizando como marco de restricción los encuentros o desencuentros del objeto arquitectónico con el terreno, se analiza el suelo como estrategia arquitectónica tratando de demostrar como su manipulación puede ser una eficaz herramienta con la que establecer relaciones específicas con el lugar. La capacidad que presenta el suelo, como elemento arquitectónico, de explorar y modificar las características de cada entorno, hacen de esta superficie una eficiente forma de contextualización. Por tanto, la manipulación del suelo que aquí se plantea, opera transcodificando los elementos específicos de cada lugar y actúa como estrategia arquitectónica que pone en relación al edificio con el contexto, modificando las particularidades formales de dicho plano. Frente a la tendencia que reduce la expresión arquitectónica a una simple apariencia formal autónoma, se plantea la manipulación del plano del suelo como mecanismo de enraizamiento con el lugar, enfatizando para ello la condición terrestre de la arquitectura. El plano del suelo es el que ata al edificio mediante la gravedad a la corteza terrestre. En realidad se trata de realzar el carácter mediador del suelo en la arquitectura, definiendo para ello el establecimiento de elementos comunes entre realidades distintas, potenciando el valor del suelo como herramienta que puede transcodificar el entorno, trasformando su datos en elementos arquitectónicos concretos. En este proceso de traducción de información, el suelo pasa de ser un objeto pasivo a ser uno operativo, convirtiéndose en parte activa de las acciones que sobre él se ejercen. La tesis tiene también como propósito demostrar cómo, la clave de la rápida evolución que el suelo como estrategia arquitectónica ha sufrido en los últimos años, mucho debe a la expansión del suelo en otras artes como en la escultura, y mas concretamente en el landart. Surgen entonces nuevas disciplinas, en las que se propone la comprensión del lugar en los proyectos desarrollando una visión integral del mundo natural, convirtiéndolo en un tejido viviente y conector que pone en relación las actividades que sustenta. También encontramos en Utzon, y sus plataformas geológicas, al precursor de la importancia que más tarde se le daría al plano del suelo en la arquitectura, ya que inicia cierta actitud crítica, que hizo avanzar hacia una arquitectura más expresiva que requería nuevos mecanismos que la relacionasen con el suelo que los soportaba, proponiendo con sus plataformas una transformación infraestructural del suelo. Con su interpretación transcultural de las estructuras espaciales arquetípicas mayas, chinas y japonesas, irá enriqueciendo el panorama arquitectónico, adquiriendo de este modo más valor el contexto que acabará por ser entendido de forma más compleja. Los proyectos de arquitectura en muchas ocasiones se han convertido en territorios propicios de especulación donde construir teoría arquitectónica. Desde este contexto se analizan cuatro estrategias de suelo a través del estudio de cuatro posiciones arquitectónicas muy significativas desde el punto de vista de la manipulación del plano del suelo, que construyen una interesante metodología proyectual con la que operar. Los casos de estudio, propuestos son; la Terminal Pasajeros (1996-2002) en Yokohama del estudio FOA, la Casa de la Música (1999-2005) de OMA en Oporto, el Memorial Judío (1998-2005) de Berlín de Peter Eisenman, y por último el Museo MAXXI (1998-2009) de Zaha Hadid en Roma. Descubrir las reglas, referencias y metodologías que cada uno nos propone, nos permite descubrir cuáles son los principales posicionamientos en relación al proyecto y su relación con el lugar. Las propuestas aquí expuestas abordan una nueva forma de entender el suelo, que hizo avanzar a la arquitectura hacia nuevos modos de encuentro con el terreno. Nos permite también establecer cuáles son las principales aportaciones arquitectónicas del suelo, como estrategia arquitectónica, que han derivado en su reformulación. Dichas contribuciones abren nuevas formas de abordar la arquitectura basadas en el movimiento y en la flexibilidad funcional, o en la superposición de flujos de información y circulación. También plantean nuevas vías desdibujando la figura contra el fondo, y refuerzan la idea del suelo como plataforma infraestructural que ya había sido enunciada por Utzon. Se trata en definitiva de proponer la exploración de la superficie del suelo como el elemento más revelador de las formas emergentes del espacio. ABSTRACT Where the building hits the ground, it is where the latter as reality becomes architectural quality. This thesis presents the study of the ground plane, making a critical review of architecture as a mechanism of projectual thought. This analysis starts from the sixties, because it is when the break begins to be demonstrated with regard to the inheritance of the Modern Movement. It is then when architecture marks a point of inflexion, and different, completely new methodological attitudes to the ground start to emerge. The classic meeting action like place, raise or bury are gradually replaced by more complex operations such as fold, bend or fluff up. Framing it within the meetings or disagreements between architectural object and ground, we analyzed it as architectural strategy trying to show how handling can be an effective tool to establish a specific relationship with the place. The capacity ground has, as an architectural element, to explore and modify the characteristics of each environment, makes this area an efficient tool for contextualization. Therefore, the manipulation of ground that is analyzed here, operates transcoding the specifics of each place and acts as architectural strategy that relates to the building with the context, modifying the structural peculiarities of such plane. Opposite to the reductive tendency of the architectural expression to a simple formal autonomous appearance, the manipulation of the ground plane is considered as a rooting mechanism place that emphasises the earthly condition of architecture. The ground plane is the one that binds the building by gravity to the earth’s crust. In fact, it tries to study the mediating character of the ground in architecture, defining for it to establish commonalities among different realities, enhancing the value of the ground as a tool that can transcode the environment, transforming its data into specific architectural elements. In this process of translating information, the ground goes from being a liability, to become active part of the actions exerted on the object. The thesis also tries to demonstrate how the key of the rapid evolution that the ground likes architectural strategy has gone through recently, much due to its use expansion in other arts such as sculpture. New disciplines arise then, in which one proposes the local understanding in the projects, developing an integral vision of the natural world and turning it into an element linking the activities it supports. We also find in Utzon, and his geological platforms, the precursor of the importance that later would be given to the ground plane in architecture, since it initiates a certain critical attitude, which advances towards a more expressive architecture, with new mechanisms that relate to the ground that it sits in, proposing with its platforms an infrastructural transformation of the ground. With his transcultural interpretation of the spatial archetypal structures, he will enrich the architectural discourse, making the context become understood in more complex ways. Architectural projects in many cases have become territories prone to architectural theory speculation. Within this context, four strategies are analyzed through the study of four very significant architectural positions, from the point of view of handling the ground plane, and the project methodology within which to operate. The case studies analyzed are; Passenger Terminal (1996-2002) in Yokohama from FOA, The House of the music (1999-2005) the OMA in Oporto, The Jew monument (1998-2005) in Berlin the Peter Eisenman, and finally the MAXXI Museum (1998-2009) the Zaha Hadid in Rome. Discovering the rules, references and methodologies that each of those offer, it allows to discover what the main positions are regarding the building and its relationship with the place where it is located. The proposals exposed here try to shed a different light on the ground, which architecture advancing in new ways on how meet it. The crossing of the different studied positions, allows us to establish what the main contributions of ground as architectural strategy are. Such contributions open up new approaches to architecture based on movement and functional flexibility, overlapping information flow and circulation, consider new ways that blur the figure against the background, and reinforce the idea of ground as infrastructural platform, already raised by Utzon. Summarizing, it tries to propose the exploration of the ground plane as the most revealing form of spatial exploration.

A EXPECTATIVA DOS PAIS DIANTE DA EDUCAÇÃO INFANTIL: UM ESTUDO DE CASO

A partir do estudo de caso de uma unidade privada de educação infantil, a presente pesquisa pretendeu investigar, através das expectativas dos pais diante da educação infantil, a influência da herança cultural familiar na trajetória escolar da criança. O interesse teórico de uma pesquisa empírica sobre esse universo é atestado pelo fato de que, conforme Pierre Bourdieu, a valorização e a compreensão da escola, já nos primeiros anos de vida da criança são comuns entre as famílias que possuem um maior nível de escolarização e que conseqüentemente começam a traçar desde cedo a trajetória escolar de seus filhos. Assim, ao estudarmos os pais de alunos de uma unidade privada de educação infantil, estaremos abordando, sobretudo, as expectativas educacionais de famílias da classe média. Apoiados em algumas idéias básicas sobre a conexão entre capital cultural e estratégias educacionais apresentados por Bourdieu, trabalhamos com a hipótese de que as diferentes categorias sociais são desigualmente predispostas a compreender e a valorizar a escolarização em geral, e que este fato está diretamente relacionado ao capital cultural familiar. De acordo com o autor é o volume e o tipo de capital (econômico, social e cultural) que o indivíduo possui que irá definir sua posição na hierarquia social, bem como suas expectativas diante da escola. Nota-se, então, que a cultura de um modo geral opera como um patrimônio de diferenciação de classe.(AU)

A EXPECTATIVA DOS PAIS DIANTE DA EDUCAÇÃO INFANTIL: UM ESTUDO DE CASO

A partir do estudo de caso de uma unidade privada de educação infantil, a presente pesquisa pretendeu investigar, através das expectativas dos pais diante da educação infantil, a influência da herança cultural familiar na trajetória escolar da criança. O interesse teórico de uma pesquisa empírica sobre esse universo é atestado pelo fato de que, conforme Pierre Bourdieu, a valorização e a compreensão da escola, já nos primeiros anos de vida da criança são comuns entre as famílias que possuem um maior nível de escolarização e que conseqüentemente começam a traçar desde cedo a trajetória escolar de seus filhos. Assim, ao estudarmos os pais de alunos de uma unidade privada de educação infantil, estaremos abordando, sobretudo, as expectativas educacionais de famílias da classe média. Apoiados em algumas idéias básicas sobre a conexão entre capital cultural e estratégias educacionais apresentados por Bourdieu, trabalhamos com a hipótese de que as diferentes categorias sociais são desigualmente predispostas a compreender e a valorizar a escolarização em geral, e que este fato está diretamente relacionado ao capital cultural familiar. De acordo com o autor é o volume e o tipo de capital (econômico, social e cultural) que o indivíduo possui que irá definir sua posição na hierarquia social, bem como suas expectativas diante da escola. Nota-se, então, que a cultura de um modo geral opera como um patrimônio de diferenciação de classe.(AU)

Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice

Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel–Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated. While heterozygous VHL (+/−) mice appeared phenotypically normal, VHL −/− mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL −/− embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed to occur in VHL −/− mice, and hemorrhagic lesions developed in the placenta. Subsequent hemorrhage in VHL −/− embryos caused necrosis and death. These results indicate that VHL expression is critical for normal extraembryonic vascular development.

Chemical phenotype matching between a plant and its insect herbivore

Two potential outcomes of a coevolutionary interaction are an escalating arms race and stable cycling. The general expectation has been that arms races predominate in cases of polygenic inheritance of resistance traits and permanent cycling predominates in cases in which resistance is controlled by major genes. In the interaction between Depressaria pastinacella, the parsnip webworm, and Pastinaca sativa, the wild parsnip, traits for plant resistance to insect herbivory (production of defensive furanocoumarins) as well as traits for herbivore “virulence” (ability to metabolize furanocoumarins) are characterized by continuous heritable variation. Furanocoumarin production in plants and rates of metabolism in insects were compared among four midwestern populations; these traits then were classified into four clusters describing multitrait phenotypes occurring in all or most of the populations. When the frequency of plant phenotypes belonging to each of the clusters is compared with the frequency of the insect phenotypes in each of the clusters across populations, a remarkable degree of frequency matching is revealed in three of the populations. That frequencies of phenotypes vary among populations is consistent with the fact that spatial variation occurs in the temporal cycling of phenotypes; such processes contribute in generating a geographic mosaic in this coevolutionary interaction on the landscape scale. Comparisons of contemporary plant phenotype distributions with phenotypes of herbarium specimens collected 9–125 years ago from across a similar latitudinal gradient, however, suggest that for at least one resistance trait—sphondin concentration—interactions with webworms have led to escalatory change.

Somatic and germ cell parasitism in a colonial ascidian: Possible role for a highly polymorphic allorecognition system

A colonial protochordate, Botryllus schlosseri, undergoes a natural transplantation reaction in the wild that results alternatively in colony fusion (chimera formation) or inflammatory rejection. A single, highly polymorphic histocompatibility locus (called Fu/HC) is responsible for rejection versus fusion. Gonads are seeded and gametogenesis can occur in colonies well after fusion, and involves circulating germ-line progenitors. Buss proposed that colonial organisms might develop self/non-self histocompatibility systems to limit the possibility of interindividual germ cell “parasitism” (GCP) to histocompatible kin [Buss, L. W. (1982) Proc. Natl. Acad. Sci. USA 79, 5337–5341 and Buss, L. W. (1987) The Evolution of Individuality (Princeton Univ. Press, Princeton]. Here we demonstrate in laboratory and field experiments that both somatic cell and (more importantly) germ-line parasitism are a common occurrence in fused chimeras. These experiments support the tenet in Buss’s hypothesis that germ cell and somatic cell parasitism can occur in fused chimeras and that a somatic appearance may mask the winner of a gametic war. They also provide an interesting challenge to develop formulas that describe the inheritance of competing germ lines rather than competing individuals. The fact that fused B. schlosseri have higher rates of GCP than unfused colonies additionally provides a rational explanation for the generation and maintenance of a high degree of Fu/HC polymorphism, largely limiting GCP to sibling offspring.

Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin

Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the β-subunit of β-hexosaminidase. GM2 ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the GM2 gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N-butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.