Angiotensin Ii As A General Growth Factor

Angiotensin II (Ang II), a key protein in the renin-angiotensin system, can induce cardiac hypertrophy through an intracrine system as well as affect gene transcription. The receptor to Ang II responsible for this effect, AT1, has been localized to the nucleus of cell types in addition to cardiomyocytes. In this study, we induced expression of Ang II in MC3T3 osteoblasts and K7M2 osteosarcomas and measured changes in protein expression of Annexin V and matrix metalloproteinase 2 (MMP2), proteins identified previously through mass spectrometry analysis as being regulated by Ang II. Annexin V is downregulated in both immortalized murine bone (MC3T3) cells and in cancerous immortalized murine (K7M2) cells induced to express Ang II. MC3T3 cells which express Ang II show a downregulation of MMP2 expression, but Ang II-expressing K7M2 cells show an upregulation of MMP2. The differential regulation of MMP2 between the cancerous cells and noncancerous cells implicates a role for Ang in in tumor metastasis, as MMP2 is a metastatic protein. Annexin V is used as a marker for apoptosis, but nothing is known of the function of the endogenous protein. That Annexin V is potentially regulated by Ang II provides more information with which to characterize the protein and could suggest a function for Annexin V as part of a signal transduction pathway inside of the cell.

EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology

Equine penile papillomas, in situ carcinomas, and invasive carcinomas are hypothesized to belong to a continuum of papillomavirus-induced diseases. The former ones clinically present as small grey papules, while the latter 2 lesions are more hyperplasic or alternatively ulcerated. To test the hypothesis that these lesions are papillomavirus-induced, samples of 24 horses with characteristic clinical and histologic findings of penile papillomas or in situ or invasive squamous cell carcinomas were collected. As controls, 11 horses with various lesions--namely, Balanoposthitis (6 cases), melanoma (3 cases), follicular cyst (1 case), and amyloidosis (1 case)--were included. DNA was extracted and polymerase chain reaction applied to amplify papillomavirus DNA. The respective primers were designed to amplify DNA of the recently discovered equine papillomavirus EcPV2. All tested papilloma and squamous cell carcinoma samples were found to contain DNA of either of 2 previously published EcPV2 variants. Among the other samples 6 of 11 were found to contain EcPV2 DNA. To further support the findings and to determine where the papillomavirus DNA was located within the lesions, an in situ hybridization for the detection of EcPV2 DNA was established. The samples tested by this technique were found to clearly contain papillomavirus nucleic acid concentrated in the nucleus of the koilocytes. The findings of this study support previous data and the hypothesis that papillomaviruses induce the described penile lesions in horses.

Hsp90 nuclear accumulation in quiescence is linked to chaperone function and spore development in yeast.

The 90-kDa heat-shock protein (Hsp90) operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent Saccharomyces cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sba1. Translocation of both chaperones was dependent on the alpha/beta importin SRP1/KAP95. Hsp90 nuclear retention was coincident with glucose exhaustion and seems to be a starvation-specific response, as heat shock or 10% ethanol stress failed to elicit translocation. We generated nuclear accumulation-defective HSP82 mutants to probe the nature of this targeting event and identified a mutant with a single amino acid substitution (I578F) sufficient to retain Hsp90 in the cytoplasm in quiescent cells. Diploid hsp82-I578F cells exhibited pronounced defects in spore wall construction and maturation, resulting in catastrophic sporulation. The mislocalization and sporulation phenotypes were shared by another previously identified HSP82 mutant allele. Pharmacological inhibition of Hsp90 with macbecin in sporulating diploid cells also blocked spore formation, underscoring the importance of this chaperone in this developmental program.

Directional deep brain stimulation: an intraoperative double-blind pilot study.

Deep brain stimulation of different targets has been shown to drastically improve symptoms of a variety of neurological conditions. However, the occurrence of disabling side effects may limit the ability to deliver adequate amounts of current necessary to reach the maximal benefit. Computed models have suggested that reduction in electrode size and the ability to provide directional stimulation could increase the efficacy of such therapies. This has never been demonstrated in humans. In the present study, we assess the effect of directional stimulation compared to omnidirectional stimulation. Three different directions of stimulation as well as omnidirectional stimulation were tested intraoperatively in the subthalamic nucleus of 11 patients with Parkinson's disease and in the nucleus ventralis intermedius of two other subjects with essential tremor. At the trajectory chosen for implantation of the definitive electrode, we assessed the current threshold window between positive and side effects, defined as the therapeutic window. A computed finite element model was used to compare the volume of tissue activated when one directional electrode was stimulated, or in case of omnidirectional stimulation. All but one patient showed a benefit of directional stimulation compared to omnidirectional. A best direction of stimulation was observed in all the patients. The therapeutic window in the best direction was wider than the second best direction (P = 0.003) and wider than the third best direction (P = 0.002). Compared to omnidirectional direction, the therapeutic window in the best direction was 41.3% wider (P = 0.037). The current threshold producing meaningful therapeutic effect in the best direction was 0.67 mA (0.3-1.0 mA) and was 43% lower than in omnidirectional stimulation (P = 0.002). No complication as a result of insertion of the directional electrode or during testing was encountered. The computed model revealed a volume of tissue activated of 10.5 mm(3) in omnidirectional mode, compared with 4.2 mm(3) when only one electrode was used. Directional deep brain stimulation with a reduced electrode size applied intraoperatively in the subthalamic nucleus as well as in the nucleus ventralis intermedius of the thalamus significantly widened the therapeutic window and lowered the current needed for beneficial effects, compared to omnidirectional stimulation. The observed side effects related to direction of stimulation were consistent with the anatomical location of surrounding structures. This new approach opens the door to an improved deep brain stimulation therapy. Chronic implantation is further needed to confirm these findings.

67P/Churyumov-Gerasimenko: Activity between March and June 2014 as observed from Rosetta/OSIRIS

Aims. 67P/Churyumov-Gerasimenko is the target comet of the ESA’s Rosetta mission. After commissioning at the end of March 2014, the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) onboard Rosetta, started imaging the comet and its dust environment to investigate how they change and evolve while approaching the Sun. Methods. We focused our work on Narrow Angle Camera (NAC) orange images and Wide Angle Camera (WAC) red and visible-610 images acquired between 2014 March 23 and June 24 when the nucleus of 67P was unresolved and moving from approximately 4.3 AU to 3.8 AU inbound. During this period the 67P – Rosetta distance decreased from 5 million to 120 thousand km. Results. Through aperture photometry, we investigated how the comet brightness varies with heliocentric distance. 67P was likely already weakly active at the end of March 2014, with excess flux above that expected for the nucleus. The comet’s brightness was mostly constant during the three months of approach observations, apart from one outburst that occurred around April 30 and a second increase in flux after June 20. Coma was resolved in the profiles from mid-April. Analysis of the coma morphology suggests that most of the activity comes from a source towards the celestial north pole of the comet, but the outburst that occurred on April 30 released material in a different direction.

NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway

Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.

AN ASCENDING SEROTONERGIC PAIN MODULATION SYSTEM

This dissertation describes an ascending serotonergic pain modulation system projecting from the dorsal raphe (DR) nucleus of the midbrain to the parafascicularis (PF) nucleus of the thalamus. Previous studies by other investigators have led to the hypothesis that the DR would modulate responses to noxious stimuli in the PF by using 5HT. These other studies have shown that the DR contains serotonergic (5HT) cell bodies which project to many areas of the forebrain including the PF, that the PF is involved in pain perception, that electrical stimulation of the DR causes analgesia, and 5HT is necessary for this type of analgesia. One theory of the mechanisms of an endogenous pain modulation system is that brainstem nuclei have a decsending projection to the spinal cord to inhibit responses to noxious input at this level. The present study tests the hypothesis that there is also an ascending pain modulation pathway from the brainstem to the thalamus.^ To test this hypothesis, several types of experiments were performed on anesthetised rats. The major results of the experiments are as follows: (1) Three types of spontaneously active PF neurons were found: slow units firing at 1-10 spikes/sec, bursting units firing 2-5 times in 10-20 msec, pattern repeating every 1-2 sec, and fast units firing at 15-40 spikes/sec. The first two groups showed similar results to the treatments and were analysed together. The fast firing units did not respond to any of the treatments. (2) Noxious stimuli primarily increased neuronal firing rates in the PF, where as DR stimulation primarily decreased neuronal activity. DR stimulation applied simultaneously with noxious stimuli decreased the responses to the noxious stimuli as recorded in the PF units. (3) Microiontophoretically applied 5HT in the PF decreased spontaneous activity in the PF in a dose dependent manner and decreases responses to noxious stimuli in the PF. (4) Reduction of brain 5HT by 5,7 dihydroxytryptamine, a potent 5HT neurotoxin, caused PF units to be hypersensitive to both noxious and non noxious stimuli, reversed the effects of DR stimulation so that DR stimulation increased single units activity in the PF, and prolonged and intensified the depressant action of microiontophoretically applied 5HT. The results of this study are consistent with the hypothesis that the DR uses 5HT in a direct ascending pathway to the PF to modulate pain in the thalamus. ^

Kant y la modernidad : un enfoque desde el trabajo social

En el trabajo se pretende analizar las principales categorías sobre las que se fundamenta la modernidad, a través del pensamiento de Kant. El núcleo del proyecto moderno es la idea de universalidad, individualidad y autonomía, que junto a la distinción entre hombre y Naturaleza y su interrelación, dan origen a la perspectiva de la razón emancipadora. Los debates filosóficos de la época incorporaron una mirada sobre los problemas sociales y resultan de singular importancia para demostrar que el Trabajo Social en su origen tuvo un claro carácter antimoderno. Las primeras organizaciones donde encontramos los antecedentes de la profesión avanzan con un carácter conservador, mediado por una alianza entre burguesía, iglesia y estado, aceptando el modo capitalista de producción y de pensar a través de prácticas tutelares, disciplinarias y moralizantes que aún perduran en la actualidad y que se alejan del pensamiento originario de Kant.

Filosofía, mito y nación en el Prometeo de Leopoldo Lugones

Si bien el pensamiento de Leopoldo Lugones ha sido interpretado como autoritario y monológico, esta mirada puede ser puesta en cuestión desde la imbricación entre nacionalismo y universalismo que atraviesa sus obras de inspiración modernista. Su libro Prometeo (un proscripto del sol) –obra de pedagogía estética y homenaje al Centenario de la Patria– liga una "estética de la nacionalidad" con la defensa de los valores de la Ilustración. Sobre todo con el valor de la libertad y, desde el plano del poeta, de la libertad creadora. Este trabajo pretende interpretar, desde una hermenéutica en la cual dialoga la filosofía con el pensamiento mítico, los posibles usos del mito en la escritura lugoniana del Prometeo. Usos que pueden dar lugar tanto al núcleo constitutivo de lo que será su discurso nacionalista más excluyente a partir las conferencias de 1913 sobre el poema Martín Fierro, como a una defensa de la autonomía poética ante el mundo burgués vinculada a cierta forma de pensamiento utópico.

Juego y tradición folklórica en una novela de Mario Vargas Llosa

La relación entre la tradición oral y la literatura escrita existe desde antiguo. En este caso, las cancioncillas, las retahílas que acompañan a este tradicional, y universal, juego infantil de Las cuatro esquinas sirven al novelista Mario Vargas Llosa como núcleo generador del relato El paraíso en la otra esquina a la vez que como epítome de la andadura vital de Paul Gauguin. Esta relación entre la vida y la canción nos permite profundizar en la historia del juego de Las cuatro esquinas desde sus orígenes hasta el siglo xxi

El discurso de Polinices (vv. 1284-1345) en Edipo en Colono de Sófocles

Edipo en Colono de Sófocles resulta una obra fuertemente argumentativa por los debates dialécticos que se presentan entre los Episodios II a IV, cuya función dramática consiste en demorar el destino de Edipo y, a su vez, desplegar una densidad intratextual muy rica. Easterling (1999: 95-107) afirma que hay tres rasgos que definen el estilo de Sófocles, ellos son, por un lado, la tensión de opuestos o contradicciones; en segundo lugar, la oscilación entre el sentido literal y el sentido metafórico y, por último, la concentración junto con el uso de repeticiones. En el presente estudio analizamos el discurso de Polinices como el ejemplo de las características mencionadas, las que convierten la intervención del joven guerrero en el punto cultimante de las escenas agonales, que constituyen el núcleo de la obra. Estas instancias disonantes que los enfrentamientos producen son atemperadas por la presencia de Teseo.

El valor de la lectura o cómo eludir el engaño. La trascendencia del romance de la esposa infiel como una lucha indicial

Mediante el estudio de la tradición americana del romance de La esposa infiel, se resalta la importancia que en dicho romance tiene la lucha, por el desciframiento y el encubrimiento de indicios, librada entre el hombre y la mujer. A partir de tal planteo, se propone que su núcleo de interés radica en la problemática del engaño en general y la necesidad de descubrirlo.

Da Apollonio Rodio ad Aristeneto : Persistenze e innovazioni di un paradigma mitico

La principal característica de la quinta carta de las Epistolaí de Aristéneto proviene de la identidad literaria de Medea en el tercer libro de Argonautica de Apolonio Rodio. De tal manera, la carta se observa como un ejemplo interesante de un texto "re-escrito" del tercer libro del poema, el cual, abastecido por la memoria sáfica de los síntomas del amor, es considerado un punto de expansión y difusión de un núcleo teorético de la literatura erótica greco-latina.

Juego y tradición folklórica en una novela de Mario Vargas Llosa

La relación entre la tradición oral y la literatura escrita existe desde antiguo. En este caso, las cancioncillas, las retahílas que acompañan a este tradicional, y universal, juego infantil de Las cuatro esquinas sirven al novelista Mario Vargas Llosa como núcleo generador del relato El paraíso en la otra esquina a la vez que como epítome de la andadura vital de Paul Gauguin. Esta relación entre la vida y la canción nos permite profundizar en la historia del juego de Las cuatro esquinas desde sus orígenes hasta el siglo xxi

Da Apollonio Rodio ad Aristeneto : Persistenze e innovazioni di un paradigma mitico

La principal característica de la quinta carta de las Epistolaí de Aristéneto proviene de la identidad literaria de Medea en el tercer libro de Argonautica de Apolonio Rodio. De tal manera, la carta se observa como un ejemplo interesante de un texto "re-escrito" del tercer libro del poema, el cual, abastecido por la memoria sáfica de los síntomas del amor, es considerado un punto de expansión y difusión de un núcleo teorético de la literatura erótica greco-latina.