Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis by recruitment of mononuclear cells

Notch is an intercellular signaling pathway related mainly to sprouting neo-angiogenesis. The objective of our study was to evaluate the angiogenic mechanisms involved in the vascular augmentation (sprouting/intussusception) after Notch inhibition within perfused vascular beds using the chick area vasculosa and MxCreNotch1(lox/lox) mice. In vivo monitoring combined with morphological investigations demonstrated that inhibition of Notch signaling within perfused vascular beds remarkably induced intussusceptive angiogenesis (IA) with resultant dense immature capillary plexuses. The latter were characterized by 40 % increase in vascular density, pericyte detachment, enhanced vessel permeability, as well as recruitment and extravasation of mononuclear cells into the incipient transluminal pillars (quintessence of IA). Combination of Notch inhibition with injection of bone marrow-derived mononuclear cells dramatically enhanced IA with 80 % increase in vascular density and pillar number augmentation by 420 %. Additionally, there was down-regulation of ephrinB2 mRNA levels consequent to Notch inhibition. Inhibition of ephrinB2 or EphB4 signaling induced some pericyte detachment and resulted in up-regulation of VEGFRs but with neither an angiogenic response nor recruitment of mononuclear cells. Notably, Tie-2 receptor was down-regulated, and the chemotactic factors SDF-1/CXCR4 were up-regulated only due to the Notch inhibition. Disruption of Notch signaling at the fronts of developing vessels generally results in massive sprouting. On the contrary, in the already existing vascular beds, down-regulation of Notch signaling triggered rapid augmentation of the vasculature predominantly by IA. Notch inhibition disturbed vessel stability and led to pericyte detachment followed by extravasation of mononuclear cells. The mononuclear cells contributed to formation of transluminal pillars with sustained IA resulting in a dense vascular plexus without concomitant vascular remodeling and maturation.

Taking a New Look at Neo-Assyrian Gates

The Assyrian capitals are not only known for their magnificent temples and palaces, but also for their monumental city walls. The most impressive and at the same time most delicate features of all the town defenses were the city gates. As they interrupted the line of defense, they were al-ways a vulnerable spot of every system of fortifications. However, the walled cities’ economic needs demanded these gateways to be built, in order to ensure the steady flow of goods and pro-visions. Apart from that, they also had a significant ideological meaning, which is emphasized by many cuneiform texts. During the excavations of the Assyrian capitals of Ashur, Dūr Šarrūkīn, and Nineveh, a fairly large number of Assyrian city gates were brought to light. By re-examining the archaeological reports and employing remote sensing, many details of these structures can still be revealed. The paper aims at illuminating the different considerations that went into constructing these gates, as well as the development Assyrian city gates underwent and what may have influenced this process.

Neo-Assyrian concepts of fortification

The major cities of the Neo-Assyrian Empire were not only home to impressive palaces and temples, but they were also equipped with strong fortifications. The city walls were not only meant to keep out potential enemies, but by demonstrating Assyria’s power to any approaching person, they served an ideological purpose, as well. However, military efficiency was just as crucial, since, over its entire history, the empire repeatedly faced internal and external threats and could not have afforded to lose any of its urban centers which were essential to maintaining control over the various provinces or geographic regions associated with them. The study of Neo-Assyrian fortifications relies on evidence provided by archaeological excavations, the study of Assyrian reliefs and information from cuneiform texts. Even though these sources help us reconstruct the appearance of the town defenses, the question of why the individual fortification systems were built in a specific way cannot be addressed by these means alone. Remote sensing offers an opportunity to view the course and placement of the city walls within their topographical context. Furthermore, geographical information systems (GIS) offer a tool to illustrate the distribution of the strongly fortified Assyrian towns, thereby allowing us to recognize patterns and functions of regional fortification systems during the Neo-Assyrian period.

Rapid divergence in physiological and life-history traits between northern and southern populations of the British introduced neo-species, Senecio squalidus

Alien plants provide a unique opportunity to study evolution in novel environments, but relatively little is known about the extent to which they become locally adapted to different environments across their new range. Here, we compare northern and southern populations of the introduced species Senecio squalidus in Britain; S. squalidus has been in southern Britain for approximately 200 years and reached Scotland only about 50 years ago. We conducted common garden experiments at sites in the north and south of the species’ range in Britain. We also conducted glasshouse and growth chamber experiments to test the hypothesis that southern genotypes flower later, are more drought-tolerant, germinate and establish better at warmer temperatures, and are less sensitive to cold stress than their more northern counterparts. Results from the common garden experiments are largely consistent with the hypothesis of rapid adaptive divergence of populations of the species within the introduced range, with genotypes typically showing a home-site advantage. Results from the glasshouse and growth chamber experiments demonstrate adaptive divergence in ability to tolerate drought stress and high temperatures, as well as in phenology. In particular, southern genotypes were more tolerant of dry conditions and high temperatures and they flowered later than northern genotypes. Our results show that rapid local adaptation can occur in alien species, and they have implications for our understanding of the ecological genetics of range expansion of introduced weeds.

Chronic stress promotes tumor growth through increased BDNF production and neo-innervation

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth. Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine whether chronic stress affects the density of nerves in the tumor, I utilized an orthotopic mouse model of ovarian cancer that was exposed to daily restraint stress. IHC analysis revealed that nerve density in tumors increased by more than three-fold in stressed animals versus non-stressed controls. IHC analysis suggested that this results from both recruitment of existing neurons (axonogenesis) as well as new neuron formation (neurogenesis) within the tumor. To determine how tumors are recruiting nerve growth, I utilized a PCR array analysis of 84 nerve growth related genes and their receptors, which showed that stimulation of the SKOV3 ovarian cancer cell line with norepinephrine (NE) leads to increased expression of several neurotrophins, including brain-derived neurotrophic factor (BDNF). Neurite extension assays showed that media conditioned by ovarian cancer cell lines is capable of inducing neurite outgrowth in differentiated neuron-like PC12 cells, and NE treatment of cancer cells potentiates this effect. Norepinephrine-induced neurite extension was abolished after BDNF silencing by siRNA, suggesting that BDNF is critical to tumor cell-induced nerve growth. in vivo BDNF inhibition resulted in complete abrogation of stress-induced increases in tumor weight and nerve density, as well as downstream markers of stress. Discussion: These studies indicate that adrenergic signalling induced by chronic stress promotes neo-innervation in the tumor microenvironment. This results in a mutually beneficial relationship between the tumor cells and neurons. This work is crucial for providing a link between chronic stress and its effects on the tumor and its microenvironment. The data shown here aims to open new venues that can be used in development of therapies designed to block the stress effects on tumor growth.

Politica social y trabajo social. La construcción de sentidos y practicas sobre la intervención social. De la filantropia a la neo filantropia. 16H191

Este proyecto focaliza su objeto de estudio en la relación política social – Trabajo Social. Más específicamente interesa la indagación de la producción discursiva sobre la cuestión social en distintos períodos históricos, la instalación de determinados sentidos y prácticas en torno de la misma y su vinculación con la configuración de la identidad y el quehacer profesional de los Trabajadores Sociales. Se parte del supuesto que los sentidos y prácticas en torno de la intervención sobre la cuestión social a lo largo de la historia argentina, contribuyeron a la construcción y consolidación de las características estructurales de la profesión. Tanto las características de las políticas sociales, como la configuración histórica del quehacer profesional en relación a ese campo, ayudan a entender sus actuales particularidades, a repensar sus posibilidades y límites en la construcción de ciudadanía, y a reflexionar sobre los sentidos y prácticas reproductoras de las condiciones que se pretenden atender, en el actual contexto de retracción de derechos. El tema de investigación es abordado a partir de cuatro grandes períodos, que a su vez suponen etapas en el desarrollo del proyecto. El primero coincidente con el surgimiento, desarrollo y posterior desaparición de la Sociedad de la Beneficencia, en el cual se gestaron las protoformas de la intervención social. El segundo asociado a la instalación del paradigma dominante de política social en el país y correspondiente con la profesionalización del Trabajo Social. El tercero vinculado al surgimiento del Desarrollismo, a partir cual la profesión modifica sus formas de intervención. Y el último correspondiente con la década del 90, en la que se instala un cambio paradigmático con relación a la política social en el país, reapareciendo con toda su fuerza la neofilantropía, a partir de la cual la profesión se ve interpelada a repensar su quehacer o a someterse a sus designios. Como unidad de estudio se abordará más específicamente el campo de actuación profesional en la provincia de Misiones. En el abordaje del objeto de estudio se prevé la utilización, principalmente, de métodos y técnicas cualitativas de investigación social. Además de los aportes teóricos de las ciencias sociales, especial interés para esta investigación, revisten los estudios del campo de la semiótica, la lingüística, la pragmática, las teorías del discurso, la teoría de las representaciones sociales, en el sentido que aportan herramientas teórico metodológicas para reflexionar en torno de la compleja relación entre lenguaje y sociedad, entre textualidades, discursos, representaciones, narrativas, y la constitución de sujetos, subjetividades, identidades, significaciones y valores compartidos, prácticas e imaginarios.

El "giro progresista". Apuntes sobre los alcances y límites del neo-desarrollismo argentino

Fil: Varesi, Gastón Angel. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

El fracaso de las políticas públicas del neo institucionalismo : El caso de los lajeros de la puna jujeña

Fil: Narodowski, Patricio. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.