Evaluation of the bioaccumulation kinetics of gold nanorods in vital mammalian organs by mean of TXRF spectrometry

This work presents the first application of total-reflection X-ray fluorescence (TXRF) spectrometry, a new and powerful alternative analytical method, to evaluation of the bioaccumulation kinetics of gold nanorods (GNRs) in various tissues upon intravenous administration in mice. The analytical parameters for developed methodology by TXRF were evaluated by means of the parallel analysis of bovine liver certified reference material samples (BCR-185R) doped with 10 μg/g gold. The average values (n = 5) achieved for gold measurements in lyophilized tissue weight were as follows: recovery 99.7%, expanded uncertainty (k = 2) 7%, repeatability 1.7%, detection limit 112 ng/g, and quantification limit 370 ng/g. The GNR bioaccumulation kinetics was analyzed in several vital mammalian organs such as liver, spleen, brain, and lung at different times. Additionally, urine samples were analyzed to study the kinetics of elimination of the GNRs by this excretion route. The main achievement was clearly differentiating two kinds of behaviors. GNRs were quickly bioaccumulated by highly vascular filtration organs such as liver and spleen, while GNRs do not show a bioaccumulation rates in brain and lung for the period of time investigated. In parallel, urine also shows a lack of GNR accumulation. TXRF has proven to be a powerful, versatile, and precise analytical technique for the evaluation of GNRs content in biological systems and, in a more general way, for any kind of metallic nanoparticles.

Characterisation of the operation & maintenance phase in PV rural electrification programmes

Con 1.300 millones de personas en el mundo sin acceso a la electricidad (la mayoría en entornos rurales de países empobrecidos), la energía solar fotovoltaica constituye una solución viable técnica y económicamente para electrificar las zonas más remotas del planeta donde las redes eléctricas convencionales no llegan. Casi todos los países en el mundo han desarrollado algún tipo de programa de electrificación fotovoltaica rural durante los últimos 40 años, principalmente los países más pobres, donde a través de diferentes modelos de financiación, se han instalado millones de sistemas solares domiciliarios (pequeños sistemas fotovoltaicos para uso doméstico). Durante este largo período, se han ido superando muchas barreras, como la mejora de la calidad de los sistemas fotovoltaicos, la reducción de costes, la optimización del diseño y del dimensionado de los sistemas, la disponibilidad financiera para implantar programas de electrificación rural, etc. Gracias a esto, la electrificación rural descentralizada ha experimentado recientemente un salto de escala caracterizada por la implantación de grandes programas con miles de sistemas solares domiciliarios e integrando largos períodos de mantenimiento. Muchos de estos grandes programas se están llevando a cabo con limitado éxito, ya que generalmente parten de supuestos e hipótesis poco contrastadas con la realidad, comprometiendo así un retorno económico que permita el desarrollo de esta actividad a largo plazo. En este escenario surge un nuevo reto: el de cómo garantizar la sostenibilidad de los grandes programas de electrificación rural fotovoltaica. Se argumenta que la principal causa de esta falta de rentabilidad es el imprevisto alto coste de la fase de operación y mantenimiento. Cuestiones clave tales como la estructura de costes de operación y mantenimiento o la fiabilidad de los componentes del sistema fotovoltaico no están bien caracterizados hoy en día. Esta situación limita la capacidad de diseñar estructuras de mantenimiento capaces de asegurar la sostenibilidad y la rentabilidad del servicio de operación y mantenimiento en estos programas. Esta tesis doctoral tiene como objetivo responder a estas cuestiones. Se ha realizado varios estudios sobre la base de un gran programa de electrificación rural fotovoltaica real llevado a cabo en Marruecos con más de 13.000 sistemas solares domiciliarios instalados. Sobre la base de este programa se ha hecho una evaluación en profundidad de la fiabilidad de los sistemas solares a partir de los datos de mantenimiento recogidos durante 5 años con más de 80.000 inputs. Los resultados han permitido establecer las funciones de fiabilidad de los equipos tal y como se comportan en condiciones reales de operación, las tasas de fallos y los tiempos medios hasta el fallo para los principales componentes del sistema, siendo este el primer caso de divulgación de resultados de este tipo en el campo de la electrificación rural fotovoltaica. Los dos principales componentes del sistema solar domiciliario, la batería y el módulo fotovoltaico, han sido analizados en campo a través de una muestra de 41 sistemas trabajando en condiciones reales pertenecientes al programa solar marroquí. Por un lado se ha estudiado la degradación de la capacidad de las baterías y por otro la degradación de potencia de los módulos fotovoltaicos. En el caso de las baterías, los resultados nos han permitido caracterizar la curva de degradación en capacidad llegando a obtener una propuesta de nueva definición del umbral de vida útil de las baterías en electrificación rural. También sobre la base del programa solar de Marruecos se ha llevado a cabo un estudio de caracterización de los costes reales de operación y mantenimiento a partir de la base de datos de contabilidad del programa registrados durante 5 años. Los resultados del estudio han permitido definir cuáles son costes que más incidencia tienen en el coste global. Se han obtenido los costes unitarios por sistema instalado y se han calculado los montantes de las cuotas de mantenimiento de los usuarios para garantizar la rentabilidad de la operación y mantenimiento. Finalmente, se propone un modelo de optimización matemática para diseñar estructuras de mantenimiento basado en los resultados de los estudios anteriores. La herramienta, elaborada mediante programación lineal entera mixta, se ha aplicado al programa marroquí con el fin de validar el modelo propuesto. ABSTRACT With 1,300 million people worldwide deprived of access to electricity (mostly in rural environments), photovoltaic solar energy has proven to be a cost‐effective solution and the only hope for electrifying the most remote inhabitants of the planet, where conventional electric grids do not reach because they are unaffordable. Almost all countries in the world have had some kind of rural photovoltaic electrification programme during the past 40 years, mainly the poorer countries, where through different organizational models, millions of solar home systems (small photovoltaic systems for domestic use) have been installed. During this long period, many barriers have been overcome, such as quality enhancement, cost reduction, the optimization of designing and sizing, financial availability, etc. Thanks to this, decentralized rural electrification has recently experienced a change of scale characterized by new programmes with thousands of solar home systems and long maintenance periods. Many of these large programmes are being developed with limited success, as they have generally been based on assumptions that do not correspond to reality, compromising the economic return that allows long term activity. In this scenario a new challenge emerges, which approaches the sustainability of large programmes. It is argued that the main cause of unprofitability is the unexpected high cost of the operation and maintenance of the solar systems. In fact, the lack of a paradigm in decentralized rural services has led to many private companies to carry out decentralized electrification programmes blindly. Issues such as the operation and maintenance cost structure or the reliability of the solar home system components have still not been characterized. This situation does not allow optimized maintenance structure to be designed to assure the sustainability and profitability of the operation and maintenance service. This PhD thesis aims to respond to these needs. Several studies have been carried out based on a real and large photovoltaic rural electrification programme carried out in Morocco with more than 13,000 solar home systems. An in‐depth reliability assessment has been made from a 5‐year maintenance database with more than 80,000 maintenance inputs. The results have allowed us to establish the real reliability functions, the failure rate and the main time to failure of the main components of the system, reporting these findings for the first time in the field of rural electrification. Both in‐field experiments on the capacity degradation of batteries and power degradation of photovoltaic modules have been carried out. During the experiments both samples of batteries and modules were operating under real conditions integrated into the solar home systems of the Moroccan programme. In the case of the batteries, the results have enabled us to obtain a proposal of definition of death of batteries in rural electrification. A cost assessment of the Moroccan experience based on a 5‐year accounting database has been carried out to characterize the cost structure of the programme. The results have allowed the major costs of the photovoltaic electrification to be defined. The overall cost ratio per installed system has been calculated together with the necessary fees that users would have to pay to make the operation and maintenance affordable. Finally, a mathematical optimization model has been proposed to design maintenance structures based on the previous study results. The tool has been applied to the Moroccan programme with the aim of validating the model.

Aplicación de nuevas tecnologías en la Arqueología de la Guerra Civil Española: Los Yesares, Pinto (Madrid. Application of new technologies in archeology of the Civil War:The Yesares, Pinto (Madrid.

ABSTRACT: The surveys carried out in the municipality of Pinto (Madrid) have enabled us to locate various structural remains linked to the military operations that took place around the capital during the Spanish Civil War (1936-1939). In order to identify and record them, surveys were complemented with the use of GPS and air photographs from different time periods. Afterwards, and in collaboration with researchers from various universities, further methods aimed at generating a complete special representation of the area were applied directly to one of the sites which produced the best results, known as "los Yesares". These methods include topographic mapping that resulted in cartographic material at different scales, the photographic recording with flying Unmanned Aerial Vehicles, and the use of land scanners and GPS-corrected photogrammetrics with which to obtain 3D models.

Side effects of modern pesticides on adults of the predatory mite Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae) under laboratory conditions

Amblyseius swirskii (Athias-Henriot) is a polyphagous predatory mite which feeds on pollen and small arthropod preys like whiteflies, thrips and mites. This species is widely used in IPM programs in greenhouses, being essential for its success, to obtain information about the non target effects of the pesticides currently used in those crops where the mite is artificially released. This work describes a laboratory contact residual test for evaluating lethal (mortality after 72 hour exposure to fresh residues) and sublethal effects (fecundity and fertility of the surviving mites) of eleven modern pesticides to adults of A. swirskii. Spiromesifen is lipogenesis inhibitor; flonicamid a selective feeding inhibitor with a mode of action not totally known; flubendiamide a modulator of the rhyanodin receptor, sulfoxaflor has a complex mode of action not totally ascertained; metaflumizone is a voltage dependent sodium channel blocker; methoxyfenozide is an IGR, spirotetramat inhibits lipids; abamectin and emamectin activate the Cl- channel; spinosad is a neurotix naturalyte and deltamethrin a pyrethroid used as positive standard. Selected pesticides are effective against different key pests present in horticultural crop areas and were always applied at the maximum field recommended concentration in Spain if registered, or at the concentration recommended by the supplier. Out of the tested pesticides, spiromesifen, flonicamid, flubendiamide, sulfoxaflor, metaflumizone, methoxyfenozide and spirotetramat were harmless to adults of the predatory mite (IOBC toxicity class 1). The rest of pesticides exhibited some negative effects: emamectin was slightly harmful (IOBC 2), deltamethrin moderately harmful (IOBC 3) and spinosad and abamectin harmful (IOBC 4). Further testing under more realistic conditions is needed for those pesticides having some harmful effect on the mite prior deciding their joint use or not. Key words: Amblyseius swirskii, adults, laboratory, residual test, spiromesifen, flonicamid, flubendiamide, sulfoxaflor, metaflumizone, methoxyfenozide, spirotetramat, emamectin, deltamethrin, abamectin, spinosad.

Networked Utopia : the Architecture and Urbanism of the Bata Shoe Company Satellite Cities = Utopia en red : arquitectura y urbanismo en las ciudades satélite de la Bata Shoe Company, 1930 al presente

From its humble beginnings as a small workshop established by Tomáš Baťa in 1874, the Bata Shoe Company became a gigantic concern in the 1920s, built on the principles of scientific management and welfare capitalism. The growth of the company engulfed Zlín (in today’s Czech Republic), its hometown, and transformed it into a modern industrial garden city satisfying the needs of both a growing industrial population, and those of the company itself. As a reaction to the aftermath of the crisis of 1929, the enterprise began a strategy of decentralization and international expansion characterized by the design and construction of a series of modern industrial towns that replicated the model of Zlín around the globe. This study is an exhaustive survey of these cities, their rationale, design, and their postindustrial conditions; it is a comparative work that has used field trips, photography, interviews, and archival material to explain the logics behind Bata’s project, to document the design and implementation of the model to multiple contexts and geographies, and to evaluate of the urban legacy of this undertaking. Finally, the research explores the question of what can the design disciplines, and other parties involved, learn from a full synthesis on the history and urbanism of the Bata satellite cities with regard to the re-imagination and sustainability of contemporary industry-sponsored interventions in developing geographies. RESUMEN Con origen en un humilde y pequeño taller fundado en 1874 por Tomáš Baťa, la Bata Shoe Company creció hasta convertirse en una gigantesca empresa en los anos 20, fundada en principios de control científico de la producción y capitalismo de bienestar. El crecimiento de la compañía se extendió por Zlín (en la actual República Checa), su pueblo de nacimiento, y la transformó en una moderna ciudad jardín industrial capaz de satisfacer las necesidades tanto de una población en alza como de la propia empresa. Como reacción a la crisis de 1929, Bata inició una estrategia de descentralización y expansión internacional caracterizada por el proyecto y construcción de modernas ciudades industriales que replicaron el modelo de Zlín por el mundo. Esta tesis es un estudio exhaustivo de estas ciudades: las razones detrás del proyecto, su diseño, y su condición post-industrial; es un estudio comparativo que se ha servido de trabajo de campo, documentación fotográfica, entrevistas y materiales de archivo para explicar la lógica detrás del proyecto de Bata, documentar el diseño e implementación de tal modelo en múltiples contextos y geografías, y valorar el legado urbano de esta empresa. Finalmente, la investigación evalúa qué podrían aprender las disciplinas del diseño y otras partes implicadas de una síntesis completa de la historia y el urbanismo de las ciudades satélite de Bata, en lo relativo a la reinvención y sostenibilidad de proyectos contemporáneos de la industria en geografías en desarrollo.

Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site

The Pointed (PNT) domain and an adjacent mitogen-activated protein (MAP) kinase phosphorylation site are defined by sequence conservation among a subset of ets transcription factors and are implicated in two regulatory strategies, protein interactions and posttranslational modifications, respectively. By using NMR, we have determined the structure of a 110-residue fragment of murine Ets-1 that includes the PNT domain and MAP kinase site. The Ets-1 PNT domain forms a monomeric five-helix bundle. The architecture is distinct from that of any known DNA- or protein-binding module, including the helix-loop-helix fold proposed for the PNT domain of the ets protein TEL. The MAP kinase site is in a highly flexible region of both the unphosphorylated and phosphorylated forms of the Ets-1 fragment. Phosphorylation alters neither the structure nor monomeric state of the PNT domain. These results suggest that the Ets-1 PNT domain functions in heterotypic protein interactions and support the possibility that target recognition is coupled to structuring of the MAP kinase site.

Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin–proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3α, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3α-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

Identification of the endophilins (SH3p4/p8/p13) as novel binding partners for the β1-adrenergic receptor

Several G-protein coupled receptors, such as the β1-adrenergic receptor (β1-AR), contain polyproline motifs within their intracellular domains. Such motifs in other proteins are known to mediate protein–protein interactions such as with Src homology (SH)3 domains. Accordingly, we used the proline-rich third intracellular loop of the β1-AR either as a glutathione S-transferase fusion protein in biochemical “pull-down” assays or as bait in the yeast two-hybrid system to search for interacting proteins. Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the β1-AR. In vitro and in human embryonic kidney (HEK) 293 cells, SH3p4 specifically binds to the third intracellular loop of the β1-AR but not to that of the β2-AR. Moreover, this interaction is mediated by the C-terminal SH3 domain of SH3p4. Functionally, overexpression of SH3p4 promotes agonist-induced internalization and modestly decreases the Gs coupling efficacy of β1-ARs in HEK293 cells while having no effect on β2-ARs. Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in β1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling.

Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred

Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1, a member of the ATP-binding cassette family, recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1,084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mnl1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index case of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease.

A molecular level picture of the stabilization of A-DNA in mixed ethanol–water solutions

Advances in computer power, methodology, and empirical force fields now allow routine “stable” nanosecond-length molecular dynamics simulations of DNA in water. The accurate representation of environmental influences on structure remains a major, unresolved issue. In contrast to simulations of A-DNA in water (where an A-DNA to B-DNA transition is observed) and in pure ethanol (where disruption of the structure is observed), A-DNA in ≈85% ethanol solution remains in a canonical A-DNA geometry as expected. The stabilization of A-DNA by ethanol is likely due to disruption of the spine of hydration in the minor groove and the presence of ion-mediated interhelical bonds and extensive hydration across the major groove.

Loss of the maternal H19 gene induces changes in Igf2 methylation in both cis and trans

Recent investigations have shown that the maintenance of genomic imprinting of the murine insulin-like growth factor 2 (Igf2) gene involves at least two factors: the DNA (cytosine-5-)-methyltransferase activity, which is required to preserve the paternal specific expression of Igf2, and the H19 gene (lying 90 kb downstream of Igf2 gene), which upon inactivation leads to relaxation of the Igf2 imprint. It is not yet clear how these two factors are related to each other in the process of maintenance of Igf2 imprinting and, in particular, whether the latter is acting through cis elements or whether the H19 RNA itself is involved. By using Southern blots and the bisulfite genomic-sequencing technique, we have investigated the allelic methylation patterns (epigenotypes) of the Igf2 gene in two strains of mouse with distinct deletions of the H19 gene. The results show that maternal transmission of H19 gene deletions leads the maternal allele of Igf2 to adopt the epigenotype of the paternal allele and indicate that this phenomenon is influenced directly or indirectly by the H19 gene expression. More importantly, the bisulfite genomic-sequencing allowed us to show that the methylation pattern of the paternal allele of the Igf2 gene is affected in trans by deletions of the active maternal allele of the H19 gene. Selection during development for the appropriate expression of Igf2, dosage-dependent factors that bind to the Igf2 gene, or methylation transfer between the parental alleles could be involved in this trans effect.

Rational engineering of a miniprotein that reproduces the core of the CD4 site interacting with HIV-1 envelope glycoprotein

Protein–protein interacting surfaces are usually large and intricate, making the rational design of small mimetics of these interfaces a daunting problem. On the basis of a structural similarity between the CDR2-like loop of CD4 and the β-hairpin region of a short scorpion toxin, scyllatoxin, we transferred the side chains of nine residues of CD4, central in the binding to HIV-1 envelope glycoprotein (gp120), to a structurally homologous region of the scorpion toxin scaffold. In competition experiments, the resulting 27-amino acid miniprotein inhibited binding of CD4 to gp120 with a 40 μM IC50. Structural analysis by NMR showed that both the backbone of the chimeric β-hairpin and the introduced side chains adopted conformations similar to those of the parent CD4. Systematic single mutations suggested that most CD4 residues from the CDR2-like loop were reproduced in the miniprotein, including the critical Phe-43. The structural and functional analysis performed suggested five additional mutations that, once incorporated in the miniprotein, increased its affinity for gp120 by 100-fold to an IC50 of 0.1–1.0 μM, depending on viral strains. The resulting mini-CD4 inhibited infection of CD4+ cells by different virus isolates. Thus, core regions of large protein–protein interfaces can be reproduced in miniprotein scaffolds, offering possibilities for the development of inhibitors of protein–protein interactions that may represent useful tools in biology and in drug discovery.

Kinesin’s processivity results from mechanical and chemical coordination between the ATP hydrolysis cycles of the two motor domains

Kinesin is a processive motor protein: A single molecule can walk continuously along a microtubule for several micrometers, taking hundreds of 8-nm steps without dissociating. To elucidate the biochemical and structural basis for processivity, we have engineered a heterodimeric one-headed kinesin and compared its biochemical properties to those of the wild-type two-headed molecule. Our construct retains the functionally important neck and tail domains and supports motility in high-density microtubule gliding assays, though it fails to move at the single-molecule level. We find that the ATPase rate of one-headed kinesin is 3–6 s−1 and that detachment from the microtubule occurs at a similar rate (3 s−1). This establishes that one-headed kinesin usually detaches once per ATP hydrolysis cycle. Furthermore, we identify the rate-limiting step in the one-headed hydrolysis cycle as detachment from the microtubule in the ADP⋅Pi state. Because the ATPase and detachment rates are roughly an order of magnitude lower than the corresponding rates for two-headed kinesin, the detachment of one head in the homodimer (in the ADP⋅Pi state) must be accelerated by the other head. We hypothesize that this results from internal strain generated when the second head binds. This idea accords with a hand-over-hand model for processivity in which the release of the trailing head is contingent on the binding of the forward head. These new results, together with previously published ones, allow us to propose a pathway that defines the chemical and mechanical cycle for two-headed kinesin.

A mitogen-activated protein kinase of the corn leaf pathogen Cochliobolus heterostrophus is involved in conidiation, appressorium formation, and pathogenicity: Diverse roles for mitogen-activated protein kinase homologs in foliar pathogens

Fungal pathogens perceive and respond to molecules from the plant, triggering pathogenic development. Transduction of these signals may use heterotrimeric G proteins, and it is thought that protein phosphorylation cascades are also important. We have isolated a mitogen-activated protein kinase homolog from the corn pathogen Cochliobolus heterostrophus to test its role as a component of the transduction pathways. The new gene, CHK1, has a deduced amino acid sequence 90% identical to Pmk1 of the rice blast fungus Magnaporthe grisea and 59% identical to Fus3 of Saccharomyces cerevisiae. A series of chk1 deletion mutants has poorly developed aerial hyphae, autolysis, and no conidia. No pseudothecia are formed when a cross between two Δchk1 mutants is attempted. The ability of Δchk1 mutants to infect corn plants is reduced severely. The growth pattern of hyphae on a glass surface is strikingly altered from that of the wild type, forming coils or loops, but no appressoria. This set of phenotypes overlaps only partially with that of pmk1 mutants, the homologous gene of the rice blast fungus. In particular, sexual and asexual sporulation both require Chk1 function in Cochliobolus heterostrophus, in contrast to Pmk1, but perhaps more similar to yeast, where Fus3 transmits the mating signal. Chk1 is required for efficient colonization of leaf tissue, which can be compared with filamentous invasive growth of yeast, modulated through another closely related mitogen-activated protein kinase, Kss1. Ubiquitous signaling elements thus are used in diverse ways in different plant pathogens, perhaps the result of coevolution of the transducers and their targets.

Functional breakdown of the lipid bilayer of the myelin membrane in central and peripheral nervous system by disrupted galactocerebroside synthesis

The lipid bilayer of the myelin membrane of the central nervous system (CNS) and the peripheral nervous system (PNS) contains the oligodendrocyte- and Schwann cell-specific glycosphingolipids galactocerebrosides (GalC) and GalC-derived sulfatides (sGalC). We have generated a UDP-galactose ceramide galactosyltransferase (CGT) null mutant mouse (cgt−/−) with CNS and PNS myelin completely depleted of GalC and derived sGalC. Oligodendrocytes and Schwann cells are unable to restore the structure and function of these galactosphingolipids to maintain the insulator function of the membrane bilayer. The velocity of nerve conduction of homozygous cgt−/− mice is reduced to that of unmyelinated axons. This indicates a severely altered ion permeability of the lipid bilayer. GalC and sGalC are essential for the unperturbed lipid bilayer of the myelin membrane of CNS and PNS. The severe dysmyelinosis leads to death of the cgt−/− mouse at the end of the myelination period.