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Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5'-CGGG-3' spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters.

We have observed that systemic administration of cannabinoid CB1 antagonists exerts antiparkinsonian effects in rats with very severe nigral lesion (>95% cell loss), but not in rats with less severe lesion (85–95% cell loss). Local injections into denervated striatum and corresponding globus pallidus reduced parkinsonian asymmetry. Infusions into lesioned substantia nigra enhanced motor asymmetries, but this effect was absent after very severe nigral lesion. At the striatal level, CB1 antagonists act enhancing dopamine D1 receptor function and reducing D2 receptor function. Striatal dopaminergic denervation did not affect cannabinoid CB1 receptor coupling to G proteins. These results suggest that (i) systemic administration of CB1 antagonists in rats with severe nigral degeneration is ineffective because striatopallidal-mediated motor effects are antagonized by nigra-mediated activity, and (ii) CB1 antagonists exert antiparkinsonian effects after very severe nigral degeneration because nigra-mediated inhibition disappears. CB1 receptor antagonists that lack psychoactive effects might be of therapeutic value in the control of very advanced stage of Parkinson's disease in humans.

Reseña del libro "Amistades imperfectas" de J. P. Gil-Osle

Developing teaching practices that meet the needs of Second Language Learners (SLL) calls for models of apprenticeship in which teacher candidates acquire competency on how to create learning spaces where students discover, experience and construct knowledge rather than solely practicing skills. The aforesaid argument has an implication when defining the competency of highly qualified teachers as framed by the No Child Left Behind (NCLB) Act. This article presents a three-step teacher development process requiring teacher candidates first to observe and analyze exemplary teaching practices. Secondly, to help them build expertise on how to question students to ignite their inquiry. And, thirdly, to develop and implement their practices to create a classroom as the wespace. The outcomes of this model suggest that highly qualified teachers could be better prepared to work with SLL when they are competent in creating inclusive, participatory learning environments, in which students are able to utilize, experiment, synthesize and evaluate knowledge.

Arellano, Ignacio, El ingenio de Lope de Vega. Escolios a las “Rimas humanas y divinas del licenciado Tomé de Burguillos”, Nueva York, IDEAS/IGAS, 2012. (ISBN: 978-1-938795-84-8)

Recent evidences have demonstrated that the presence of low pathogenic avian influenza viruses (LPAIV) may play an important role in host ecology and transmission of avian influenza viruses (AIV). While some authors have clearly demonstrated that LPAIV can mutate to render highly pathogenic avian influenza viruses (HPAIV), others have shown that their presence could provide the host with enough immunological memory to resist re-infections with HPAIV. In order to experimentally study the role of pre-existing host immunity, chickens previously infected with H7N2 LPAIV were subsequently challenged with H7N1 HPAIV. Pre-infection of chickens with H7N2 LAPIV conferred protection against the lethal challenge with H7N1 HPAIV, dramatically reducing the viral shedding, the clinical signs and the pathological outcome. Correlating with the protection afforded, sera from chickens primed with H7N2 LPAIV reacted with the H7-AIV subtype in hemagglutination inhibition assay and specifically with the N2-neuraminidase antigen. Conversely, subsequent exposure to H5N1 HPAIV resulted in a two days-delay on the onset of disease but all chickens died by 7 days post-challenge. Lack of protection correlated with the absence of H5-hemagglutining inhibitory antibodies prior to H5N1 HPAIV challenge. Our data suggest that in naturally occurring outbreaks of HPAIV, birds with pre-existing immunity to LPAIV could survive lethal infections with HA-homologous HPAIV but not subsequent re-infections with HA-heterologous HPAIV. These results could be useful to better understand the dynamics of AIV in chickens and might help in future vaccine formulations.

Endothelin 1 (ET-1) is a key regulator of vascular homeostasis. We have recently reported that the presence of Human antigen class I, HLA-B35, contributes to human dermal microvascular endothelial cell (HDMEC) dysfunction by upregulating ET-1 and proinflammatory genes. Likewise, a Toll-like receptor 3 (TLR3) ligand, Poly(I:C), was shown to induce ET-1 expression in HDMECs. The goal of this study was to determine the molecular mechanism of ET-1 induction by these two agonists. Because HLA-B35 expression correlated with induction of Binding Immunoglobulin Protein (BiP/GRP78) and several heat shock proteins, we first focused on ER stress and unfolded protein response (UPR) as possible mediators of this response. ER stress inducer, Thapsigargin (TG), HLA-B35, and Poly(I:C) induced ET-1 expression with similar potency in HDMECs. TG and HLA-B35 activated the PERK/eIF2α/ATF4 branch of the UPR and modestly increased the spliced variant of XBP1, but did not affect the ATF6 pathway. Poly(I:C) also activated eIF2α/ATF4 in a protein kinase R (PKR)-dependent manner. Depletion of ATF4 decreased basal expression levels of ET-1 mRNA and protein, and completely prevented upregulation of ET-1 by all three agonists. Additional experiments have demonstrated that the JNK and NF-κB pathways are also required for ET-1 upregulation by these agonists. Formation of the ATF4/c-JUN complex, but not the ATF4/NF-κB complex was increased in the agonist treated cells. The functional role of c-JUN in responses to HLA-B35 and Poly(I:C) was further confirmed in ET-1 promoter assays. This study identified ATF4 as a novel activator of the ET-1 gene. The ER stress/UPR and TLR3 pathways converge on eIF2α/ATF4 during activation of endothelial cells.

TCF7L2 rs7903146 is an important genetic factor predicting type 2 diabetes (T2DM) which has also been linked to higher cardiovascular risk. To date, there is little information about the additional impact of this single nucleotide polymorphism (SNP) beyond glucose metabolism.We studied whether rs7903146 influenced postprandial lipid metabolism in three different populations (healthy young men, metabolic syndrome (MetS) patients and elderly persons). Eighty-eight healthy males were submitted to a single saturated fatty acid-rich test meal. Additionally, 110 middle-aged MetS patients and 20 healthy elderly persons (≥ 65 years) were submitted to three different dietary models followed by test meals. Minor allele homozygotes for rs7903146 showed a worse postprandial lipemia profile in young males, as seen by a lower HDL-cholesterol and Apo A1 concentration during the postprandial lipemia and a trend towards higher triglycerides (TG), than the other genotypes. In healthy elderly persons, carriers of the minor allele showed higher total cholesterol, LDL-cholesterol, Apo B and TG in the fasting state, and a higher postprandial area under the curve for total cholesterol, Apo B, small-triglyceride rich lipoprotein (TRL) cholesterol and small-(TRL) triglycerides. These results were accompanied by differential changes in adipokines. We did not observe any influence of rs7903146 on the postprandium of MetS patients.Healthy young males and elderly persons who are carriers of the mutant allele for rs7903146 have an impaired postprandial lipid metabolism that may be mediated by an alteration in adipokine regulation, and may be related to the higher cardiovascular risk observed in these persons.ClinicalTrials.gov NCT00429195.

Objetivo. Establecer un ensayo de PCR-TR para determinar el tamaño poblacional y la composición de bacterias totales y de ácido lácticas, en particular las pertenecientes a los géneros Lactobacillus y Bifidobacterium. Materiales y métodos. La especificidad de los iniciadores fue verificada utilizando la técnica de PCR convencional. Diluciones de 101 a 10- 4 ng/µl de ADN fueron preparadas a partir de cada cultivo microbiano y utilizadas en las curvas de calibración. La temperatura de disociación y la eficiencia de cada reacción de PCR-TR se determinaron con el software del iQCycler (Bio Rad®), versión 3.1. Resultados. Los juegos de iniciadores utilizados resultaron específicos para cada grupo microbiano, sin detectar reacción cruzada. Las eficiencias de las reacciones de la PCR-TR para bacterias totales, acidolácticas, Lactobacillus y Bifidobacterium fueron 104.4%, 98.1%, 113.3% y 103.3%, respectivamente. Conclusiones. Al obtener reacciones específicas y eficiencias cercanas al 100%, es posible cuantificar las poblaciones bacterianas totales, acidolácticas, Lactobacillus y Bifidobacterium con una alta especificidad. Por lo tanto, la técnica de PCRTR puede utilizarse para monitorear cambios poblacionales bacterianos en ambientes como el tracto gastrointestinal de pollos de engorde, donde las bacterias acidolácticas, Lactobacillus y Bifidobacterium son habitantes comunes.

Let $\Gamma$ be a quiver on $n$ vertices $v_1, v_2, \ldots , v_n$ with $g_{ij}$ edges between $v_i$ and $v_j$, and let $\boldsymbol{\alpha} \in \mathbb{N}^n$. Hua gave a formula for $A_{\Gamma}(\boldsymbol{\alpha}, q)$, the number of isomorphism classes of absolutely indecomposable representations of $\Gamma$ over the finite field $\mathbb{F}_q$ with dimension vector $\boldsymbol{\alpha}$. We use Hua's formula to show that the derivatives of $A_{\Gamma}(\boldsymbol{\alpha}, q)$ with respect to $q$, when evaluated at $q = 1$, are polynomials in the variables $g_{ij}$, and we can compute the highest degree terms in these polynomials. The formulas for these coefficients depend on the enumeration of certain families of connected graphs. This note simply gives an overview of these results; a complete account of this research is available on the arXiv and has been submitted for publication.

En el Centro Nacional de Investigaciones “Tibaitatá” de Corpoica, localizado en un ecosistema trópical a una altura de 2550 m.s.n.m, se adelantó un estudio para caracterizar la población de bacterias celulolíticas ruminales de bovinos. Cinco cepas de bacterias anaerobias celulolíticas fueron aisladas a partir del contenido ruminal de bovinos alimentados con heno de raigrás (Lolium multijlorum). Las pruebas bioquímicas, el patrón de fermentación de carbohidratos y la caracterización morfológica, incluyendo los estudios de microscopía electrónica de transmisión de la membrana celular y el glicocáliz, permitieron clasificar las cepas aisladas como: Fibrobacter succinogenes succinogenes (F31 y F32), Fibrobacter succinogenes elongata(F33), Ruminococcus albus (R38) y Ruminococcus flavefaciens (R39). La cepa de R. albus fermentó un mayor número de fuentes de carbono que la cepa de R. flavefaciens, pero ambas, fermentaron celobiosa, pectina y xilano. Ninguna de las dos subespecies de Fibrobacter aisladas fermentó pentosas. Las cepas de Fibrobacter presentaron morfologías de colonia en roll-tube de agar celobiosa, no repor­ tadas en la literatura. La apariencia, tamaño y distribución del glicocáliz en las células de las cepas del género Ruminococcus hicieron posible la diferenciación de sus dos espe­ cies R. albus y R. flavefaciens y la confirmación del status taxonómico de las otras cepas celulolíticas. Las cepas aisladas constituyen las primeras entradas al banco de germoplasma microbial de referencia para bovinos en Colombia. Actualmente se adelantan los estudios de actividad enzimática celulolítica de estas cepas.

Objective: To identify critical periods in the variation in body composition during a school year and determine possible causes. Methods: A total of 363 boys and girls aged between 10 and 14 years participated in the study. Before and after the Winter Holidays (WIH) and National Holidays (NAH) (July and September, respectively), measurements were taken of body weight, body fat percentage, waist perimeter, time spent on physical activity and hours of sleep in order to determine the variations. The normality of the data was confirmed and the means were compared with an alpha significance level of p