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Desintegrinas de Bothrops alternatus: biologia molecular, estudos in vitro, in vivo e bioinformática estrutural
(Universidade Federal de São Carlos, 2005-11-28) Ramos, Oscar Henrique Pereira; Araújo, Heloísa Sobreiro Selistre de; https://lattes.cnpq.br/4065824911933203
Disintegrins are toxins frequently found in snake venoms. Their biological effects are due to their binding to cell receptors known as integrins. Aiming to isolate new disintegrins from Bothrops alternatus snake, a cDNA library was constructed upon the transcripts expressed in the venom gland from one specimen. Two disintegrins, called DisBa-01 and DisBa-02 were cloned and sequenced. The amplification of other medium-size disintegrins and metalloprotease-disintegrins was also achieved. The recombinant toxin, DisBa-01, was expressed in an optimized bacterial system (Escherichia coli BL21(DE3) pET28a+DisBa-01) and tested in several biological assays. The toxin inhibited the platelet aggregation (IC50= 235nM) induced by collagen in rabbit s platelets rich plasma (PRP). Using ADP as inductor, the platelet aggregation inhibition was also observed in PRP from rabbits (IC50= 124nM) and human (IC50= 475nM), as well as in washed platelets from mice (IC50= 25nM). Competition assays for the αIIbβ3 integrin using specific ligands, fibrinogen and a specific antibody against activated αIIbβ3, revealed that the toxin strongly binds to this receptor (respectively IC50=18nM and IC50=70nM). Furthermore, the toxin inhibited the proliferation of cells that representatively express αVβ3 integrin, HMEC-1 and B16F10-2B8, in a dose/time dependent manner and the adhesion of B16F10-2B8 to vitronectin (IC50= 225nM). In vivo, the toxin significantly inhibited the thrombus formation in arterioles (Treated: 58,4 ± 1,6 min.; Control: 24,3 ± 2,8 min., p<0,002) and venules (Treated: 46,6 ± 6,8min.; Control: 27,1 ± 1,3min., p<0,002), prolonged the bleeding time (Treated: 989 ± 140 sec.; Control: 202 ± 22 sec.; p<0,008) and inhibited the pulmonary mestastasis of B16F10-2B8 (~92%, 12 days after the tumor cells injection). These results, as well as structural bioinformatics studies strongly suggest the binding of the toxin with αIIbβ3 and αVb3 integrins, what motivates further studies aiming the therapeutic/laboratorial application of DisBa-01 or its derivatives.
A privatização do setor elétrico paulista: suicídio de um grupo.
(Universidade Federal de São Carlos, 2005-11-28) Pedroso Neto, Antonio José; Grün, Roberto; https://lattes.cnpq.br/6028266827740491; https://lattes.cnpq.br/8781436602934292
As from 1995, the companies of the electric sector in São Paulo underwent organizational changes that both preceded and made privatization viable. They were carried out by their own workers under the label modernization . The problem to be studied in this research was to understand how they unleashed the dynamics of change, since they were aware that the changes would lead to the dismantle of their own body. In the changing process, the guidelines they adopted depended on the external demands. However, under bourdieusian sociology perspective, we consider that they also depended on the measures adopted in each company, that is, they resulted from the interpretation and redefinitions of these demands by the agents interacting under the constraints of company s field of the power. The empirical research was centered in one of the companies: in its unions and professionals, fundamentally, in the modernization agents, which was led by a limited group of workers in higher ranks. The main sources of data were interviews, questionnaires, documents, and newspapers. In this research we verified that the cardinals from the higher clergy decided for the possibility of carrying out a downsizing conducted by themselves before they were exposed to a takeover in near future. We tried to present the constraints and the instigating perspectives that touched them, and also, how some of their actions concerted with some demands from union entities and professionals. We also verified that, in the presentation and justification of modernization, the cardinals from the higher clergy spread principles of reclassification and ranking of the company and of workers, as well as the idea of rescuing and transferring part of them to a new company . Modernizing would be the bridge. In this context of speech, they called upon the workers who would work on the modernization and selected those who would take part in a training program. In both of them, the offer of posts, beneath the demand, pointed to the establishment of a frontier between those who would be participants and those who would not, a symbolic line which separated those who had the ticket to join in the new company and those with an uncertain future. This border implied in the division and ranking of the whole of the workers, with consequences such as increasing differentiation, of individualization and internal competition crowned by a realignment with the cardinals from the higher clergy. Finally, it created social conditions of reception of speech and became a mechanism that allowed them to impose their prescriptions by means of symbolic violence. Yet, we verified that with modernization, the cardinals from the higher clergy had something to demonstrate to the possible buyers: a reengineering under study and implementation. With it, they had diagnoses and bases to give continuity to potential achievements: redesign of processes, gains in productivity and efficiency, redimensioning of staff, formalization of activities and know-how of the workers. In conclusion, the cardinals from the higher clergy initiated a changing process which involved the workers and acquired its own dynamic. Further to that, everybody realized that the studies and the implementations carried out had produced and would produce unpredictable and undesired consequences: The reengineering and the lack of definition as to the future, as a matter if fact, apply to all.