Structure and genetic relationships between Serrana de Teruel breed and other cattle breeds reared in Spain

En este trabajo se analiza la variabilidad genética de la raza autóctona en peligro de extinción Serrana de Teruel, así como su relación con las razas bovinas explotadas en España: Albera, Pajuna, Avileña-Negra Ibérica, Serrana Negra, Pirenaica y Parda de Montaña. La caracterización genética se ha realizado mediante marcadores microsatélites, todos han resultado polimórficos detectándose un total de 198 alelos con una media de 6,79 alelos por locus. Las heterocigosidades observadas y esperadas fueron altas y similares en el equilibrio, con valores de 0,67 y 0,68 respectivamente. A partir del estudio de las relaciones filogenéticas se ha podido observar la cercanía de la raza Serrana de Teruel con las razas de montaña Pirenaica y Parda de Montaña. Mediante el estudio de la estructura genética se observó que el porcentaje de animales correctamente asignados a la Serrana de Teruel para q>0,8 fue del 47,5%, apreciándose una clara influencia de la raza Parda de Montaña en los individuos mezclados.In this work we analyze by microsatellite markers the genetic diversity, structure and relationships of the indigenous endangered Serrana de Teruel cattle breed with different breeds reared in Spain. All loci were polymorphic and a total of 198 alleles were observed across loci, with a mean of 6.79. Observed and expected heterozygosities values shown the high variability of Serrana de Teruel breed with values of 0.67 and 0.68 respectively. The neighbour net based on Reynolds distances shown the close genetic relationship among Serrana de Teruel and the mountain Parda de Montaña and Pirenaica breeds. STRUCTURE results showed a 47.5% of correctly assigned individuals to Serrana de Teruel breed using a q>0.8 threshold. The admixed animals shown a clear influence of Parda de Montaña breed.Financiado con el proyecto PET2007-05-C03-01 (Caracterización zootécnica, genética y calidad de la canal y de la carne de la población bovina Serrana de Teruel) y RZ2006-00003-C02-02 Caracterización morfogenética y criopreservación del germoplasma de la Serrana de Teruel, población bovina en peligro de extinción)

The retinoid antagonist MX781 induces clusterin expression in prostate cancer cells via heat shock Factor-1 and activator protein-1 transcription factors

Producción CientíficaRetinoids mediate numerous biological responses through the transcriptional activation of nuclear retinoid receptors. Due to their antiproliferative activity, retinoids have shown promise as anticancer agents. Synthetic analogs have been described that selectively activate one subset of the retinoid receptors or inhibit their transcriptional activity. Some of these compounds exhibit strong anticancer activity, which is associated with their ability to induce apoptosis. Here we describe that the retinoid antagonist MX781 causes a substantial increase of clusterin mRNA and protein levels in prostate carcinoma cells. In contrast, retinoic acid and other synthetic agonists and antagonists show no effect on clusterin mRNA/protein levels. Induction of clusterin mRNA is associated with transcriptional activation of the clusterin promoter, which requires the proximal -218-bp region containing binding sites for heat shock factor (HSF)-1, activator protein (AP)-2, and AP-1 transcription factors. MX781 slightly induces AP-1 DNA binding activity, and mutation of the AP-1 site differentially affects the activation of the clusterin promoter in a cell type-specific manner. In contrast, a robust increase of HSF-1 DNA binding activity is observed in all cancer cell lines examined, and mutation of the heat shock element site in the clusterin promoter completely abolishes MX781-induced transcriptional activation in PC3 and DU145 cells. Other agonist retinoid-related molecules also induce AP-1 activity, but not HSF-1, and elicit no effect on clusterin expression levels. These data point to HSF-1 as an important factor regulating clusterin expression in response to MX781, although AP-1 activity may also participate in a cell type-specific manner

The digital ‘connected’ earth: open technology for providing location-based services on degraded communication environments

In the current world, it is easy to listen that everybody and everything is connected. Over this connected world, the concept of location-based services has grown in order to provide digital services in everyplace and at every time. Nevertheless, this is not 100% true because the connection is not guaranteed for many people and in many places. These are the Degraded Communications Environments (DCE), environments where the availability of high-speed communications is not guaranteed in at least the 75% of the time. This paper works over the experience of a previous work in developing light protocols that do not need broadband for communication. This work provides an extension of these protocols for the inclusion of mobile devices as elements of the communication process and a set of libraries to allow the development of applications in DCE. The work done has involved the development of two frameworks: an Android framework that makes the incorporation of Android devices easier and a server-based framework that provides the server side for the development of the referred applications. A use case that uses these two frameworks has been developed. Finally, all technology developed is available throw a public Git repository

Inhibition of IκB Kinase by a New Class of Retinoid-Related Anticancer Agents That Induce Apoptosis

The transcription factor NF-κB is overexpressed or constitutively activated in many cancer cells, where it induces expression of antiapoptotic genes correlating with resistance to anticancer therapies. Small molecules that inhibit the NF-κB signaling pathway could therefore be used to induce apoptosis in NF-κB-overexpressing tumors and potentially serve as anticancer agents. We found that retinoid antagonist MX781 inhibited the activation of NF-κB-dependent transcriptional activity in different tumor cell lines. MX781 was able to completely inhibit tumor necrosis factor alpha-mediated activation of IκB kinase (IKK), the upstream regulator of NF-κB. Inhibition of IKK activity resulted from direct binding of MX781 to the kinase, as demonstrated by in vitro inhibition studies. Two other molecules, MX3350-1 and CD2325, which are retinoic acid receptor gamma-selective agonists, were capable of inhibiting IKK in vitro, although they exerted variable inhibition of IKK and NF-κB activities in intact cells in a cell type-specific manner. However, N-(4-hydroxyphenyl)-retinamide, another apoptosis-inducing retinoid, and retinoic acid as well as other nonapoptotic retinoids did not inhibit IKK. Inhibition of IKK by the retinoid-related compounds and other small molecules correlated with reduced cell proliferation and increased apoptosis. Reduced cell viability was also observed after overexpression of an IKKβ kinase-dead mutant or the IκBα superrepressor. The induction of apoptosis by the retinoid-related molecules that inhibited IKK was dependent on caspase activity but independent of the retinoid receptors. Thus, the presence of an excess of retinoic acid or a retinoid antagonist did not prevent the inhibition of IKK activation by MX781 and CD2325, indicating a retinoid receptor-independent mechanism of action

Leveraging Atropisomerism to Obtain a Selective Inhibitor of RET Kinase with Secondary Activities Towards EGFR Mutants

Unstable atropisomerism is innate in many common scaffolds in drug discovery, commonly existing as freely rotating aryl-aryl bonds. Such compounds can access the majority of dihedral conformations around the bond axis, however most small-molecules bind their target within a narrow range of these available conformations. The remaining accessible conformations can interact with other proteins leading to compound promiscuity. Herein, we leverage atropisomerism to restrict the accessible low energy dihedral conformations available to a promiscuous kinase inhibitor and achieve highly selective and potent inhibitors of the oncogenic target RET kinase. We then evaluate our lead inhibitor against kinases that were predicted to bind compounds in a similar conformational window to RET, discovering a potent inhibitor of drug resistant EGFR mutants including L858R/T790M/C797S EGFR. Leveraging atropisomerism to restrict accessible conformational space should be a generally applicable strategy due to the prevalence of unstable atropisomerism in drug discovery.</p

Estructura y relaciones genéticas de la raza bovina serrana de teruel con razas explotadas en españa

In this work we analyze by microsatellite markers the genetic diversity, structure and relationships of the indigenous endangered Se- rrana de Teruel cattle breed with different breeds reared in Spain. All loci were polymorphic and a total of 198 alleles were observed across loci, with a mean of 6.79. Observed and expected heterozygosities values shown the high variability of Serrana de Teruel breed with values of 0.67 and 0.68 respectively. The neighbour net based on Reynolds distances shown the close genetic relationship among Serrana de Teruel and the mountain Parda de Montaña and Pirenaica breeds. STRUCTURE results showed a 47.5% of correctly assigned individuals to Serrana de Teruel breed using a q>0.8 threshold. The admixed animals shown a clear influence of Parda de Montaña breed.En este trabajo se analiza la variabilidad gené- tica de la raza autóctona en peligro de extinción Serrana de Teruel, así como su relación con las ra- zas bovinas explotadas en España: Albera, Pajuna, Avileña-Negra Ibérica, Serrana Negra, Pirenaica y Parda de Montaña. La caracterización genética se ha realizado mediante marcadores microsatélites, todos han resultado polimórficos detectándose un total de 198 alelos con una media de 6,79 alelos por locus. Las heterocigosidades observadas y es- peradas fueron altas y similares en el equilibrio, con valores de 0,67 y 0,68 respectivamente. A partir del estudio de las relaciones filogenéticas se ha podido observar la cercanía de la raza Serrana de Teruel con las razas de montaña Pirenaica y Parda de Montaña. Mediante el estudio de la estructura genética se observó que el porcentaje de animales correctamente asignados a la Serra- na de Teruel para q>0,8 fue del 47,5%, aprecián- dose una clara influencia de la raza Parda de Montaña en los individuos mezclados