EGF-R signaling through Fyn kinase disrupts the function of integrin α6β4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion

We have examined the mechanism and functional significance of hemidesmosome disassembly during normal epithelial cell migration and squamous carcinoma invasion. Our findings indicate that a fraction of EGF receptor (EGF-R) combines with the hemidesmosomal integrin α6β4 in both normal and neoplastic keratinocytes. Activation of the EGF-R causes tyrosine phosphorylation of the β4 cytoplasmic domain and disruption of hemidesmosomes. The Src family kinase inhibitors PP1 and PP2 prevent tyrosine phosphorylation of β4 and disassembly of hemidesmosomes without interfering with the activation of EGF-R. Coimmunoprecipitation experiments indicate that Fyn and, to a lesser extent, Yes combine with α6β4. By contrast, Src and Lck do not associate with α6β4 to a significant extent. A dominant negative form of Fyn, but not Src, prevents tyrosine phosphorylation of β4 and disassembly of hemidesmosomes. These observations suggest that the EGF-R causes disassembly of hemidesmosomes by activating Fyn, which in turn phosphorylates the β4 cytoplasmic domain. Neoplastic cells expressing dominant negative Fyn display increased hemidesmosomes and migrate poorly in vitro in response to EGF. Furthermore, dominant negative Fyn decreases the ability of squamous carcinoma cells to invade through Matrigel in vitro and to form lung metastases following intravenous injection in nude mice. These results suggest that disruption of hemidesmosomes mediated by Fyn is a prerequisite for normal keratinocyte migration and squamous carcinoma invasion

Land Cover Change in the Andes of Southern Ecuador — Patterns and Drivers

In the megadiverse tropical mountain forest in the Andes of southern Ecuador, a global biodiversity hotspot, the use of fire to clear land for cattle ranching is leading to the invasion of an aggressive weed, the bracken fern, which is threatening diversity and the provisioning of ecosystem services. To find sustainable land use options adapted to the local situation, a profound knowledge of the long-term spatiotemporal patterns of land cover change and its drivers is necessary, but hitherto lacking. The complex topography and the high cloud frequency make the use of remote sensing in this area a challenge. To deal with these conditions, we pursued specific pre-processing steps before classifying five Landsat scenes from 1975 to 2001. Then, we quantified land cover changes and habitat fragmentation, and we investigated landscape changes in relation to key spatial elements (altitude, slope, and distance from roads). Good classification results were obtained with overall accuracies ranging from 94.5% to 98.5% and Kappa statistics between 0.75 and 0.98. Forest was strongly fragmented due to the rapid expansion of the arable frontier and the even more rapid invasion by bracken. Unexpectedly, more bracken-infested areas were converted to pastures than vice versa, a practice that could alleviate pressure on forests if promoted. Road proximity was the most important spatial element determining forest loss, while for bracken the altitudinal range conditioned the degree of invasion in deforested areas. The annual deforestation rate changed notably between periods: ~1.5% from 1975 to 1987, ~0.8% from 1987 to 2000, and finally a very high rate of ~7.5% between 2000 and 2001. We explained these inconstant rates through some specific interrelated local and national political and socioeconomic drivers, namely land use policies, credit and tenure incentives, demography, and in particular, a severe national economic and bank crisis

Why dig looted tombs? Two examples and some answers from Keushu (Ancash highlands, Peru)

Looted tombs at Andean archaeological sites are largely the result of a long tradition of trade in archaeological artefacts coupled with the 17th century policy of eradicating ancestor veneration and destroying mortuary evidence in a bid to “extirpate idolatry”. On the surface, looted funerary contexts often present abundant disarticulated and displaced human remains as well as an apparent absence of mortuary accoutrements. What kind of information can archaeologists and biological anthropologists hope to gather from such contexts? In order to gauge the methodological possibilities and interpretative limitations of targeting looted tombs, we fully excavated two collective funerary contexts at the archaeological site of Keushu (district and province of Yungay, Ancash, Peru; c. 2000 B.C.-A.D. 1600), which includes several dozen tombs, many built under large boulders or rock shelters, all of which appear disturbed by looting. The first is located in the ceremonial sector and excavation yielded information on four individuals; the second, in the funerary and residential sector, held the remains of seventy individuals - adults and juveniles. Here, we present and discuss the recovered data and suggest that careful, joint excavations by archaeologists and biological anthropologists can retrieve evidence of past mortuary practices, aid the biological characterisation of mortuary populations and help distinguish between a broad range of looting practices and post-depositional processes

Compositional diversity of rehabilitated tropical lands supports multiple ecosystem services and buffers uncertainties

High landscape diversity is assumed to increase the number and level of ecosystem services. However, the interactions between ecosystem service provision, disturbance and landscape composition are poorly understood. Here we present a novel approach to include uncertainty in the optimization of land allocation for improving the provision of multiple ecosystem services. We refer to the rehabilitation of abandoned agricultural lands in Ecuador including two types of both afforestation and pasture rehabilitation, together with a succession option. Our results show that high compositional landscape diversity supports multiple ecosystem services (multifunction effect). This implicitly provides a buffer against uncertainty. Our work shows that active integration of uncertainty is only important when optimizing single or highly correlated ecosystem services and that the multifunction effect on landscape diversity is stronger than the uncertainty effect. This is an important insight to support a land-use planning based on ecosystem services

Compositional diversity of rehabilitated tropical lands supports multiple ecosystem services and buffers uncertainties

High landscape diversity is assumed to increase the number and level of ecosystem services. However, the interactions between ecosystem service provision, disturbance and landscape composition are poorly understood. Here we present a novel approach to include uncertainty in the optimization of land allocation for improving the provision of multiple ecosystem services. We refer to the rehabilitation of abandoned agricultural lands in Ecuador including two types of both afforestation and pasture rehabilitation, together with a succession option. Our results show that high compositional landscape diversity supports multiple ecosystem services (multifunction effect). This implicitly provides a buffer against uncertainty. Our work shows that active integration of uncertainty is only important when optimizing single or highly correlated ecosystem services and that the multifunction effect on landscape diversity is stronger than the uncertainty effect. This is an important insight to support a land-use planning based on ecosystem services

Elongation, proliferation & migration differentiate endothelial cell phenotypes and determine capillary sprouting

<p>Abstract</p> <p>Background</p> <p>Angiogenesis, the growth of capillaries from preexisting blood vessels, has been extensively studied experimentally over the past thirty years. Molecular insights from these studies have lead to therapies for cancer, macular degeneration and ischemia. In parallel, mathematical models of angiogenesis have helped characterize a broader view of capillary network formation and have suggested new directions for experimental pursuit. We developed a computational model that bridges the gap between these two perspectives, and addresses a remaining question in angiogenic sprouting: how do the processes of endothelial cell elongation, migration and proliferation contribute to vessel formation?</p> <p>Results</p> <p>We present a multiscale systems model that closely simulates the mechanisms underlying sprouting at the onset of angiogenesis. Designed by agent-based programming, the model uses logical rules to guide the behavior of individual endothelial cells and segments of cells. The activation, proliferation, and movement of these cells lead to capillary growth in three dimensions. By this means, a novel capillary network emerges out of combinatorially complex interactions of single cells. Rules and parameter ranges are based on literature data on endothelial cell behavior in vitro. The model is designed generally, and will subsequently be applied to represent species-specific, tissue-specific in vitro and in vivo conditions.</p> <p>Initial results predict tip cell activation, stalk cell development and sprout formation as a function of local vascular endothelial growth factor concentrations and the Delta-like 4 Notch ligand, as it might occur in a three-dimensional in vitro setting. Results demonstrate the differential effects of ligand concentrations, cell movement and proliferation on sprouting and directional persistence.</p> <p>Conclusion</p> <p>This systems biology model offers a paradigm closely related to biological phenomena and highlights previously unexplored interactions of cell elongation, migration and proliferation as a function of ligand concentration, giving insight into key cellular mechanisms driving angiogenesis.</p

Complessità e multifattorietà dei DSA. Un approccio pedagogico II Parte: I Disturbi Specifici di Apprendimento nel sistema scolastico italiano

I Disturbi specifici di apprendimento nel sistema scolastico italiano, viene illustrata la più ampia classificazione di Bisogni Educativi Speciali che racchiude i disturbi evolutivi specifici, nell'ambito del nuovo approccio introdotto nel mondo della scuola. Vengono inoltre trattati aspetti relativi alla formazione del personale docente, il piano didattico personalizzato, la valutazione ed il progetto nuove tecnologie e disabiltà. Il secondo capitolo è una disamina completa della normativa in Italia sui DSA, dalle prime circolari del MIUR alla linee guida, compresi i documenti della Consensus Conference e gli accordi sulla diagnosi