447. AP20187-Inducible Insulin-Like Effects in Diabetic Muscle and Liver Transduced with AAV

Diabetes Mellitus, characterized by insulin deficiency (type I) or resistance (type II), derives from insulin action impairments in hormone target tissues: muscle, liver and adipocytes. Insulin regulates metabolism and glucose homeostasis through binding to a specific membrane receptor (IR) with tyrosine kinase activity. Induction of the insulin receptor signaling in hormone target cells may represent a tool to rescue glucose homeostasis in both insulin and insulin receptor deficiencies. Recently we have described that homodimerization of the chimeric insulin receptor LFv2IRE induced by the small dimerizer drug AP20187 results in insulin like actions in hepatocytes trasduced with adeno-associated viral vectors (AAV)

A Fungal Effector With Host Nuclear Localization and DNA-Binding Properties Is Required for Maize Anthracnose Development

Plant pathogens have the capacity to manipulate the host immune system through the secretion of effectors. We identified 27 putative effector proteins encoded in the genome of the maize anthracnose pathogen Colletotrichum graminicola that are likely to target the host’s nucleus, as they simultaneously contain sequence signatures for secretion and nuclear localization. We functionally characterized one protein, identified as CgEP1. This protein is synthesized during the early stages of disease development and is necessary for anthracnose development in maize leaves, stems, and roots. Genetic, molecular, and biochemical studies confirmed that this effector targets the host’s nucleus and defines a novel class of double-stranded DNA-binding protein. We show that CgEP1 arose from a gene duplication in an ancestor of a lineage of monocot-infecting Colletotrichum spp. and has undergone an intense evolution process, with evidence for episodes of positive selection. We detected CgEP1 homologs in several species of a grass-infecting lineage of Colletotrichum spp., suggesting that its function may be conserved across a large number of anthracnose pathogens. Our results demonstrate that effectors targeted to the host nucleus may be key elements for disease development and aid in the understanding of the genetic basis of anthracnose development in maize plants.Fil: Vargas, Walter Alberto. Universidad de Salamanca; España. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sanz Martín, José M.. Universidad de Salamanca; EspañaFil: Rech, Gabriel E.. Universidad de Salamanca; EspañaFil: Armijos Jaramillo, Vinicio D.. Universidad de Salamanca; EspañaFil: Rivera Rodriguez, Lina Patricia. Universidad de Salamanca; EspañaFil: Echeverria, María de Las Mercedes. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; ArgentinaFil: Díaz Mínguez, José M.. Universidad de Salamanca; EspañaFil: Thon, Michael R.. Universidad de Salamanca; EspañaFil: Sukno, Serenella A.. Universidad de Salamanca; Españ

Production of microbial transglutaminase on media made from sugar cane molasses and glycerol

Transglutaminase is an enzyme that catalyses an acyl transfer reaction between γ-carboxamide groups of glutaminyl residues and lysine residues in proteins. Due to this property, this enzyme is used for enhancing textural properties of protein-rich food. The transglutaminase used as food additive is obtained by microorganisms, mainly by Streptoverticillium ladakanum. On the other hand, sugar cane molasses is a viscous liquid rich in noncrystallized carbohydrates (saccharose, glucose and fructose). In this work, the feasibility of using sugar cane molasses as a carbon source for the production of microbial transglutaminase by Streptoverticillium ladakanum NRRL 3191 has been studied. Carbon sources including sugar cane molasses (60 g of total sugars per L), glycerol (60 g/L) and their mixture in a ratio of 1:1 (30 g/L of each) were evaluated. Time course of microbial growth, transglutaminase activity and carbon source consumption were determined every 24 h during 120 h of fermentations at three agitation speeds (200, 300 or 400 rpm). The results showed that with the increase in agitation speed, the biomass concentration increased up to 8.39 g/L in the medium containing sugar cane molasses alone or the mixture of molasses and glycerol. The highest transglutaminase activity was obtained at 400 rpm in the medium containing a mixture of molasses and glycerol, reaching 0.460 U/mL, while in the medium containing sugar cane molasses alone, the activity was 0.240 U/mL, and using glycerol alone it was 0.250 U/mL. These results show that sugar cane molasses is a suitable medium for transglutaminase production when it is combined with glycerolA grant from FOMIX CONACYT – Gobierno de Tamaulipas (Ref. 2004/1055) to author Portilla-Rivera is gratefully acknowledged. The authors are grateful to Ministerio de Educación y Ciencia (Spain) for the financial support of this work (Project: AGL2006-08250/ALI)S

Yttria-stabilized zirconia/SrTiO_(3) oxide heteroepitaxial interface with symmetry discontinuity

We show that yttria-stabilized zirconia (YSZ) films deposited on structurally dissimilar SrTiO_(3)(110) substrates exhibit two-dimensional layer-by-layer growth. We observed that, up to a thickness of about 15 nm, the square (001) basal plane of the cubic YSZ grows epitaxially on the rectangular (110) crystallographic plane of SrTiO3 substrates, with [110]YSZ(001)//[001]SrTiO_(3)(110) epitaxial relationship. Thus, the heterointerface presents symmetry discontinuity between the YSZ(001) film and the lower surface symmetry SrTiO_(3)(110) substrate. Beyond this specific case, we envisage similar approaches to develop other innovative oxide interfaces showing similar crystal symmetry discontinuities

Gain-of-function TLR7 and loss-of-function A20 gene variants identify a novel pathway for Mendelian lupus and lupus nephritis

Systemic lupus erythematosus (SLE) is a chronic and inflammatory autoimmune disease of unknown origin that may cause kidney disease, i.e. lupus nephritis (LN). Within a wider trend towards an expanding field of genetic causes of kidney disease, two recent reports have emphasized the role of Mendelian autoimmune disorders in causing LN both in children and in young adults. Loss-of-function (LOF) variants of tumor necrosis factor alpha-induced protein 3 (TNFAIP3) and gain of function (GOF) variants of Toll-like receptor 7 (TLR7) cause SLE and LN, respectively. Interestingly, both genes regulate the same signaling route, as A20, the protein encoded by TNFAIP3, inhibits nuclear factor KB (NF-KB) activation while TLR7 promoted NF-KB activation. Moreover, TNFAIP3 and TLR7 variants are relatively frequent, potentially contributing to polygenic risk for LN. Finally, they both may be expressed by kidney cells, potentially contributing to the severity of kidney injury in persons who have already developed autoimmunity. The fact that both genes regulate the same pathway may lead to novel therapeutic approaches targeting the shared molecular pathwayFIS/Fondos FEDER (PI18/01366, PI18/01133, PI19/00588, PI19/00815, DTS18/00032), ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009), Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina B2017/BMD-3686 CIFRA2-CM, Instituto de Salud Carlos III (ISCIII) RICORS program to RICORS2040 (RD21/0005/0001) and SPACKDc PMP21/00109, FEDER fund

Vertical leaping mechanics of the Lesser Egyptian Jerboa reveal specialization for maneuverability rather than elastic energy storage

Background Numerous historical descriptions of the Lesser Egyptian jerboa, Jaculus jaculus, a small bipedal mammal with elongate hindlimbs, make special note of their extraordinary leaping ability. We observed jerboa locomotion in a laboratory setting and performed inverse dynamics analysis to understand how this small rodent generates such impressive leaps. We combined kinematic data from video, kinetic data from a force platform, and morphometric data from dissections to calculate the relative contributions of each hindlimb muscle and tendon to the total movement. Results Jerboas leapt in excess of 10 times their hip height. At the maximum recorded leap height (not the maximum observed leap height), peak moments for metatarso-phalangeal, ankle, knee, and hip joints were 13.1, 58.4, 65.1, and 66.9 Nmm, respectively. Muscles acting at the ankle joint contributed the most work (mean 231.6 mJ / kg Body Mass) to produce the energy of vertical leaping, while muscles acting at the metatarso-phalangeal joint produced the most stress (peak 317.1 kPa). The plantaris, digital flexors, and gastrocnemius tendons encountered peak stresses of 25.6, 19.1, and 6.0 MPa, respectively, transmitting the forces of their corresponding muscles (peak force 3.3, 2.0, and 3.8 N, respectively). Notably, we found that the mean elastic energy recovered in the primary tendons of both hindlimbs comprised on average only 4.4% of the energy of the associated leap. Conclusions The limited use of tendon elastic energy storage in the jerboa parallels the morphologically similar heteromyid kangaroo rat, Dipodomys spectabilis. When compared to larger saltatory kangaroos and wallabies that sustain hopping over longer periods of time, these small saltatory rodents store and recover less elastic strain energy in their tendons. The large contribution of muscle work, rather than elastic strain energy, to the vertical leap suggests that the fitness benefit of rapid acceleration for predator avoidance dominated over the need to enhance locomotor economy in the evolutionary history of jerboas.Organismic and Evolutionary Biolog

Diversidad briológica en las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara (Santiago de Cuba, Cuba)

Introducción y Objetivos: Los inventarios briológicos en los espacios protegidos cubanos apoyan la actualización de los planes de manejos al inventariar las especies, detectar sus amenazas y diseñar acciones para su conservación. El objetivo de esta investigación es caracterizar la brioflora presente en las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara, Santiago de Cuba, Cuba.  M&M: En la recolecta de los especímenes se exploraron los hábitats adecuados para la instalación de los briófitos siguiendo el método del Muestro Florístico del Hábitat. En la determinación de los taxones se consultó la bibliografía especializada y las bases de datos. Todo el material colectado fue depositado en la colección Bryophyta del herbario BSC. Resultados: Se registraron para las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara 49 taxones infragenéricos de antocerotas, hepáticas y musgos. La reserva La Caoba fue la más diversa (73,5% del total) y los musgos la división mejor representada (55,1%). El sustrato epífito es el más diverso y el Bosque semideciduo mesófilo la formación vegetal mejor representada (83,3%). La totalidad de los taxones amenazados se registraron en la Reserva Florística Manejada La Caoba. Conclusiones: En las Reservas Florísticas Manejadas La Caoba y Charrascales de Mícara la brioflora se caracteriza por la presencia de taxones de amplia plasticidad ecológica y distribución geográfica. Las condiciones presentes en la reserva Charrascales de Mícara limitan el desarrollo de los briófitos. La diversidad briológica en La Caoba está amenazada por la fragmentación del hábitat debido a las alteraciones del paisaje

IFE Plant Technology Overview and contribution to HiPER proposal

HiPER is the European Project for Laser Fusion that has been able to join 26 institutions and signed under formal government agreement by 6 countries inside the ESFRI Program of the European Union (EU). The project is already extended by EU for two years more (until 2013) after its first preparatory phase from 2008. A large work has been developed in different areas to arrive to a design of repetitive operation of Laser Fusion Reactor, and decisions are envisioned in the next phase of Technology Development or Risk Reduction for Engineering or Power Plant facilities (or both). Chamber design has been very much completed for Engineering phase and starting of preliminary options for Reactor Power Plant have been established and review here

Ionic conductivity of nanocrystalline yttria-stabilized zirconia: grain boundary and size effects

We report on the effect of grain size on the ionic conductivity of yttria-stabilized zirconia samples synthesized by ball milling. Complex impedance measurements, as a function of temperature and frequency are performed on 10 mol % yttria-stabilized zirconia nanocrystalline samples with grain sizes ranging from 900 to 17 nm. Bulk ionic conductivity decreases dramatically for grain sizes below 100 nm, although its activation energy is essentially independent of grain size. The results are interpreted in terms of a space-charge layer resulting from segregation of mobile oxygen vacancies to the grain-boundary core. The thickness of this space-charge layer formed at the grain boundaries is on the order of 1 nm for large micron-sized grains but extends up to 7 nm when decreasing the grain size down to 17 nm. This gives rise to oxygen vacancies depletion over a large volume fraction of the grain and consequently to a significant decrease in oxide-ion conductivity