A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

Resumen El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia. Abstract Usher syndrome is an autosomal recessive disease characterized by retinitis pigmentosa, congenital sensorineural hearing loss and vestibular dysfunction. The purpose of this work was to characterize hla in an inbred Colombian family that presents Usher Syndrome. The Methodology consisted in that a genealogy of the family was made and previous informed consent, from four patients clinically confirmed with Usher Syndrome and four phenotypically healthy patients 5 ml of peripheral blood were taken in venipuncture tubes with edta and then the dna isolation was performed with the technique of salting out, preserved in te buffer at -8 °C and adjusted the sample to a concentration of 8 μg/ml. The hla *A, *B, *DRB1 and *DQB1 antigens were then characterized by the medium-resolution pcr-ssp techniqu

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

Resumen El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia. Abstract Usher syndrome is an autosomal recessive disease characterized by retinitis pigmentosa, congenital sensorineural hearing loss and vestibular dysfunction. The purpose of this work was to characterize hla in an inbred Colombian family that presents Usher Syndrome. The Methodology consisted in that a genealogy of the family was made and previous informed consent, from four patients clinically confirmed with Usher Syndrome and four phenotypically healthy patients 5 ml of peripheral blood were taken in venipuncture tubes with edta and then the dna isolation was performed with the technique of salting out, preserved in te buffer at -8 °C and adjusted the sample to a concentration of 8 μg/ml. The hla *A, *B, *DRB1 and *DQB1 antigens were then characterized by the medium-resolution pcr-ssp techniqu

Caracterización del HLA en una familia colombiana endogámica con síndrome de Usher

El síndrome de Usher es una enfermedad autosómica recesiva que se caracteriza por presentar retinitis pigmentosa, hipoacusia neurosensorial congénita y disfunción vestibular. El propósito de este trabajo es realizar la caracterización de hla en una familia colombiana endogámica que presenta síndrome de Usher. La metodología consiste en que con un previo consentimiento informado se realizó una genealogía de la familia y a cuatro pacientes confirmados clínicamente con síndrome de Usher y a cuatro fenotípicamente sanos se les tomó 5 ml de sangre periférica en tubos de venopunción con edta para luego realizar el aislamiento del dna por la técnica de salting out, conservados en buffer te a -8 °C y ajustada la muestra a una concentración de 8 μg/ml. Posteriormente a través de la técnica de pcr-ssp de mediana resolución se caracterizaron los antígenos de hla *a, *b, *drb1 y *dqb1. Los resultados obtenidos indican que la familia oriunda del Departamento del Huila presenta una marcada endogamia detectándose que todos los hermanos afectados, sus padres son hermanos también y una de las parejas a su vez tuvo una niña afectada, por lo que sus abuelos y padres son hermanos. En lo referente al hla, los alelos más frecuentemente encontrados fueron a30 b42 dr1 dq5 y a3 b45 dr12 y dq7, que no están asociados a la enfermedad. Estos resultados sugieren que dada la endogamia que muestra esta familia se presenta una gran acumulación de polimorfismos y mutaciones, por lo que es necesario realizar un proceso de asesoría genética para disminuir el riesgo de recurrencia

Monovarietal extra-virgin olive oil classification: a fusion of human sensory attributes and an electronic tongue

Olive oil quality grading is traditionally assessed by human sensory evaluation of positive and negative attributes (olfactory, gustatory, and final olfactorygustatory sensations). However, it is not guaranteed that trained panelist can correctly classify monovarietal extra-virgin olive oils according to olive cultivar. In this work, the potential application of human (sensory panelists) and artificial (electronic tongue) sensory evaluation of olive oils was studied aiming to discriminate eight single-cultivar extra-virgin olive oils. Linear discriminant, partial least square discriminant, and sparse partial least square discriminant analyses were evaluated. The best predictive classification was obtained using linear discriminant analysis with simulated annealing selection algorithm. A low-level data fusion approach (18 electronic tongue signals and nine sensory attributes) enabled 100 % leave-one-out cross-validation correct classification, improving the discrimination capability of the individual use of sensor profiles or sensory attributes (70 and 57 % leave-one-out correct classifications, respectively). So, human sensory evaluation and electronic tongue analysis may be used as complementary tools allowing successful monovarietal olive oil discrimination.This work was co-financed by FCT/MEC and FEDER under Program PT2020 (Project UID/EQU/50020/2013); by Fundacao para a Ciencia e Tecnologia under the strategic funding of UID/BIO/04469/2013 unit; and by Project POCTEP through Project RED/AGROTEC-Experimentation network and transfer for development of agricultural and agro industrial sectors between Spain and Portugal

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004