Looking for mechanisms regulating lung growth in CDH: rat and human studies

Tese de Doutoramento em Ciências da Saúde

“PhenoWorld”: a new multidimensional strategy for studying behaviour in rodents

Tese de Doutoramento em Ciências da Saúde

Nickel(II) complexes of bidentate N-N′ ligands containing mixed pyrazole, pyrimidine and pyridine aromatic rings as catalysts for ethylene polymerisation

This work describes the synthesis and characterisation of Ni(II) complexes of the following neutral bidentate nitrogen ligands containing pyrazole (pz), pyrimidine (pm) and pyridine (py) aromatic rings: 2-pyrazol-1-yl-pyrimidine (pzpm), 2-(4-methyl-pyrazol-1-yl)-pyrimidine (4-Mepzpm), 2-(4-bromo-pyrazol-1-yl)-pyrimidine (4-Brpzpm), 2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidine (pz*pm), 2-pyrazol-1-yl-pyridine (pzpy) and bis(3,5-dimethylpyrazol-1-yl)phenylmethane (bpz*mph). The complexes [NiBr2(pzpm)] (1), [NiBr2(4-Mepzpm)] (2), [NiBr2(4-Brpzpm)] (3), [NiBr2(pz*pm)] (4), [NiBr2(pzpy)] (5) and [NiBr2(bpz*mph)] (6) were tested as catalysts for ethylene polymerisation, in the presence of the cocatalysts methylaluminoxane (MAO) or diethylaluminium chloride (AlEt2Cl), the catalyst systems 1-3/MAO showing moderate to high activities up to the temperature of 20 °C only in the presence of MAO, whereas 4-6/MAO revealed to be inactive. Other related Pd(II) complexes, already reported in previous works, such as [PdClMe(pzpm)], [PdClMe(pz*pm)], [PdClMe(pzpy)] and [PdClMe(bpz*mph)], also showed to be inactive in the polymerisation of ethylene, when activated by MAO or AlEt2Cl. Selected samples of polyethylene products were characterised by GPC/SEC, 1H and 13C NMR and DSC, showing to be low molecular weight polymers with Mn values ranging from ca. 550 to 1500 g mol−1 and unusually low dispersities of 1.2–1.7, with total branching degrees generally varying between 2 and 12%, melting temperatures from 40 to 120 °C and crystallinities from 40 to 70%.

Isolated noncompaction of the myocardium

We report the case of a 42-year-old female with fatigue on exertion and palpitation consequent to the existence of isolated noncompaction of the myocardium. We discuss clinical and familial findings, diagnostic possibilities, and prognostic and therapeutical implications of this rare disorder of endomyocardial morphogenesis.

Insights into bacterial colony morphology evolution and diversification during infection development in cystic fibrosis

Tese de Doutoramento em Engenharia Biomédica.

Análise de poliembrionia em Citrus, máxime em toranjas

1 - This paper is a joined publication of the Dept. of Genetics, Escola Superior de Agricultura "Luiz de Queiroz", University of São Paulo, and Secção de Citricultura e Frutas Tropicais, Instituto Agronômico, de Campinas, and deal with the number of seed per fruit and the polyembryony in Citrus, with special reference to the pummelos (C. grandis). 2 - For C. pectinifera, hibrid limon x acid lime, C. histrix and Citrus sp. the mean of seeds per fruit is 5,8 - 17,3 - 30,2 -94,6; for 14 pummelos the average was 100 and the range of variation 11 to 185 seeds per fruit. For the four above mentioned Citrus the cotyledons were classified into 3 types: big (near 8 mm.), medium (near 6 mm) and small (near 4 mm) and for the pummelos there was only one size of cotyledons, about 10 mm (table 1). 3 - The polyembryony was determined by two processes: a) counting of the embryos in the mature seed; b) counting after germination in flats or seed-beds. The rasults obtained are in table 2; the process a gave larger results than process b.The following pummelos are monoembryonics: melancia, inerme, Kaune Paune, sunshine, vermelha, Singapura, periforme, Zamboa, doce, Indochina, Lau-Tau, Shantenyau and Siamesa. Sometime it was found a branching of the main stem that gave a impression of polyembryonic seeds. 4 - It was shown by the x2 test that the distribution of embryo numbers fits the Poisson's series (table 2) in both processes. 5 - It is discussed in table 2 the variability of polyembryony for the following cases: a) between plants, within years. The teste for the differences of mean of polyembryony between 3 plants of C. pectinifera is statistically significant in 1948 and 1949; b) between yields of the same plant, within year. The same case of C. pectinifera may be used for this purpose; c) between process, within year. It is shown in table 3, for C. pectinifera and the hibrid "limon x acid lime" that there is a statistically signicicant between both process above mentioned.

Morfologia do Mycobacterium leprae hominis e do M. leprae muris: estudo baseado na microscopia electrônica e de contraste de fases

Hansen's Bacillus: By electron microscopy this bacillus shows membrane and halo, this being more visible when sorrounding the globi or bundles of bacilli; shows, also, free granules of various sizes which were before considered as dust of the dyes; shows external granules bound with the membrane and some times branching. By phases contrast microscopy examining leproma suspensions and subcataneous lymph at 400 x we saw many free granules with intense rotatory movement; granulated bacilli with screw, skip or stroke motion, producing slow progressive motion. All such elementes are surrounded by a halo, corresponding to the classical gloea. By a patient and delayed examination we were able to see that the internal granules are motile and help the progression of the bacilli, giving the impression that the cytoplasm is liquid. By a lasting observation we could see the larger granules form prolapse, like a pseudopode and abandon the bacilli and going in very rapid rotatory movement. There are branched bacilli; there are pedunculated fred granules like comets. The addition of a drop of formol at the preparation stops all movements. Stefansky's Bacillus: Repeated examination by RCA electron microscope, type EMU-25 of fresh suspensions of rat lepromas, led us to confirm the close relationship between human and murine leprosy agents. We examined also material from carabo (Lepra bubalorum) from Java, but due to fixation, the material was unsuitable for comparative studies. The Stefansky's bacilli showed also emmbranes and halos, internal or external granules (smaller than those of Hansen's bacillus). The bacilli shaded by chromium look thicker and shorter than those of Hansen. Due to electron bombardment both, Hansen's and Stefansky's baccilli suffer considerable alterations in their structure, showing black barrs of chromatin condensation at their extremities as also in their centers. By phase microscopy the Stefansky's bacilli showed elements with 1, 2 (bipolar), 3 or more internal small granules, developing identical movements as those of Hansen. The globi seem to be non-motile but the free bacilli appearing around the globi show intense movement. At 1000 x the examination is less satisfactory than at 400 x. The addition of formol solution in the preparation suppresses all movements, even the brownian, but the material becomes more suitable for the study of static morphology of the bacilli. CONCLUSION - The electron and phases contrast microscopy of leprous material from different types and phases of the disease may explain some of the unknown aspects of the biology and morphology of the bacilli.

Nuclear factor I-C links platelet-derived growth factor and transforming growth factor beta1 signaling to skin wound healing progression.

Transforming growth factor beta (TGF-beta) and platelet-derived growth factor A (PDGFAlpha) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-beta signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C(-/-) and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-beta1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C(-/-) mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C(-/-) mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-beta in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.

Anopheles (Nyssorhynchus) deaneorum: a new species in the albitarsis complex (Diptera: culicidae)

Anopheles (Nyssorhynchus) deaneorum sp. n. is described from specimens collected in Guajará-Mirim, Rondônia state and Rio Branco, Acre state, Brazil, on human and animal baits, inside dwellings and from the progenies of engorged females. A detailed description of the shape of egg, external appearance of adult female and male, genitalias, female cibarial armature and complete chaetotaxy of pupa and larva show that it can be distinguished from Anopheles albitarsis from the type-locality and other areas by the paler general external appearance of the adult, the posterolateral tufts of scales, on the female abdominal terga and the branching of the outer anterior clypeal seta (3-C) of the fourth instar larva (as shown in illustrations). If species can also be distinguished from An. albitarsis from the type locality by the allele frequencies at 11 enzymic loci as represented by Nei's Genetic Distance.

Shaping fission yeast with microtubules.

For cell morphogenesis, the cell must establish distinct spatial domains at specified locations at the cell surface. Here, we review the molecular mechanisms of cell polarity in the fission yeast Schizosaccharomyces pombe. These are simple rod-shaped cells that form cortical domains at cell tips for cell growth and at the cell middle for cytokinesis. In both cases, microtubule-based systems help to shape the cell by breaking symmetry, providing endogenous spatial cues to position these sites. The plus ends of dynamic microtubules deliver polarity factors to the cell tips, leading to local activation of the GTPase cdc42p and the actin assembly machinery. Microtubule bundles contribute to positioning the division plane through the nucleus and the cytokinesis factor mid1p. Recent advances illustrate how the spatial and temporal regulation of cell polarization integrates many elements, including historical landmarks, positive and negative controls, and competition between pathways.

Differentiation of rat striatal embryonic stem cells in vitro: monolayer culture vs. three-dimensional coculture with differentiated brain cells.

Several groups have demonstrated the existence of self-renewing stem cells in embryonic and adult mouse brain. In vitro, these cells proliferate in response to epidermal growth factor, forming clusters of nestin-positive cells that may be dissociated and subcultured repetitively. Here we show that, in stem cell clusters derived from rat embryonic striatum, cell proliferation decreased with increasing number of passages and in response to elevated concentrations of potassium (30 mM KCl). In monolayer culture, the appearance of microtubule-associated protein type-5-immunoreactive (MAP-5(+)) cells (presumptive neurons) in response to basic fibroblast growth factor (bFGF) was reduced at low cell density and with increasing number of passages. In the presence of bFGF, elevated potassium caused a more differentiated neuronal phenotype, characterized by an increased proportion of MAP-5(+) cells, extensive neuritic branching, and higher specific activity of glutamic acid decarboxylase. Dissociated stem cells were able to invade cultured brain cell aggregates containing different proportions of neurons and glial cells, whereas they required the presence of a considerable proportion of glial cells in the host cultures to become neurofilament H-positive. The latter observation supports the view that astrocyte-derived factors influence early differentiation of the neuronal cell lineage.

Plant lectins, chemical and biological aspects

Lectins, carbohydrate-binding proteins of non-immune origin, that agglutinate cells or precipitate polysaccharides and glycoconjugates, are well distributed in nature, mainly in the Plant Kingdom. The great majority of the plante lectins are present in seed cotyledons where they are found in the cytoplasm or int he protein bodies, although they have also been found in roots, stems and leaves. Due to their peculiar properties, the lectins are used as a tool both for analytical and preparative purposes in biochemistry, cellular biology, immunology and related areas. In agriculture and medicine the use of lectins greatly improved in the last few years. The lextins, with few exceptions, are glycoproteins, need divalent cations to display full activity and are, in general, oligomers with variable molecular weight. Although the studies on lectins have completed a century, their role in nature is yet ynknown . Several hypotheses on their physiological functions have been suggested. Thus, lectins could play important roles in defense against pathogens, plant-microorganism symbiosis, cell organization, embryo morphogenesis, phagocytosis, cell wall elongation, pollen recognition and as reserve proteins. A brief review on the general properties and roles of the lectins is given.

A cell-based model of extracellular-matrix-guided endothelial cell migration during angiogenesis.

Angiogenesis, the formation of new blood vessels sprouting from existing ones, occurs in several situations like wound healing, tissue remodeling, and near growing tumors. Under hypoxic conditions, tumor cells secrete growth factors, including VEGF. VEGF activates endothelial cells (ECs) in nearby vessels, leading to the migration of ECs out of the vessel and the formation of growing sprouts. A key process in angiogenesis is cellular self-organization, and previous modeling studies have identified mechanisms for producing networks and sprouts. Most theoretical studies of cellular self-organization during angiogenesis have ignored the interactions of ECs with the extra-cellular matrix (ECM), the jelly or hard materials that cells live in. Apart from providing structural support to cells, the ECM may play a key role in the coordination of cellular motility during angiogenesis. For example, by modifying the ECM, ECs can affect the motility of other ECs, long after they have left. Here, we present an explorative study of the cellular self-organization resulting from such ECM-coordinated cell migration. We show that a set of biologically-motivated, cell behavioral rules, including chemotaxis, haptotaxis, haptokinesis, and ECM-guided proliferation suffice for forming sprouts and branching vascular trees.

A new filaria of a lizard transmitted by sandflies

A description is given of Madathamugadia wanjii n. sp., a Splendidofilariinae parasite of the gecko Ptyodactylus hasselquistii, on the west bank of the River Jordan and of its life cycle in Phlebotomus duboscqi. The new species is close to M. ivaschkini (Annaev, 1976) n. comb., of Turkmenistan, wich is also transmitted by sandflies (Reznik, 1982). The genus Madathamugadia is now comprised of four species, two from Madagascar and two from the Mediterranean sub-region; it differs from the genus Thamugadia by the presence of a double row of papillae anterior to the cloaca of the male. The larval characters of Splendidofilarinae of lizards confirm the affinity of these parasites to the Splendidofilarinae of birds (Chandlerella and Splendidofilaria); the first group could have arisen from the second by "captures" wich could have occurred in several places.