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Background: The medicinally active plant Oroxylum indicum (OI) has drawn considerable research interest because of its many observed biological activities. Of particular interest is its antitumorigenic activity. The plant is a rich source of flavonoids and their glycosides. Recently flavonoids have been described as inhibitors of kexin-type proteases of superfamily Proprotein Convertase Subtilisin/ Kexins (PCSKs) which have been implicated in tumor growth and malignancy. These enzymes particularly furin (PCSK3) cleaves inactive precursor growth factors into their mature forms that promote tumor growth. As a result, finding furin-inhibitors became of high interest in cancer research. In this regard, the plant OI with known anticancer activities may provide an important source. Objective: The objective of this study is to examine and compare anti-tumorigenic activity of furin inhibitory flavonoid compounds from OI. Results: Studies were conducted to evaluate the effect on CT-26 cell proliferation and migration of 4 flavonoids baicalein, chrysin, oroxylin-A and its glycoside isolated from OI. Data revealed that baicalein exhibited most potent inhibitory effect on proliferation and migration on the analyzed tumor cell line. Baicalein at 10 M completely blocked the proliferation even after 5 days. The results are consistent with the observed in vitro anti-furin activity of baicalein as measured against a fluorogenic peptide and pro-hVEGF-C as substrates. Mature VEGF-C is a strong indicator and biomarker of tumor progression and therefore the antifurin activity may explain the observed anticancer properties of baicalein. Since baicalein is the major constituent of OI, our data provided scientific rationale for the observed anticancer activity of OI and also offered a new lead molecule for future exploration as potential antitumor agents.

Cores from the eastern part of the area bounded by the Kane and Atlantis fracture zones, in the NE Atlantic Ocean, have been studied for their mineralogical, biostratigraphical and radio-chronological characteristics. Two of them contain a systematic association of pure palygorskite layers with ferro-manganese oxide concretions, alternating with normal carbonaceous sedimentation. Another contains manganese nodules having a nucleus of palygorskite. The possible origins of the palygorskite are discussed, and it is concluded that it is of hydrothermal origin. The close association of the palygorskite with the Fe-Mn concretions suggests a hydrothermal origin for these too. The episodic character of the deposits shows that hydrothermal activity occurred during relatively short periods, and that the last episode probably took place less than 100,000 years ago.

Radiometric ages on discrete layers in some hydrothermally deposited Mn-oxide (birnessite) samples from the TAG hydrothermal field on the Mid-Atlantic Ridge, range from 16,000 to 4,000 years, with marked increased activity noted about 15,000 and 7,000 years ago. These observations, along with previously published data and inferences on different kinds of hydrothermal activity in the TAG field, suggest episodic, multistage hydrothermal events ranging from high temperature black smokers precipitating sulfides to low temperature events precipitating Fe and Mn oxides over this entire time range. Black smokers are presently active. The location of the various deposits on the eastern wall of the median valley at this latitude suggests that the high temperature events occur at greater depths.

In a previous study, the biphasic effect of increasing dosages of recombinant human insulin-like growth factor binding protein-3 (rhlGFBP-3) on proliferation in the prostate carcinoma PC-3 cell line (stimulation followed by depression) was shown to reflect changes in the bioavailability of IGF-II secreted by the cells, IGF-II being the major factor responsible for their autocrine growth. These changes depend on the extent of IGFBP-3 proteolysis induced by serine proteases, in particular, plasmin. In order to examine the mechanism of action of IGFBP-3, we investigated the effects of its two major fragments isolated by HPLC following limited proteolysis by plasmin in vitro. The predominant fragment with an apparent molecular mass of 22-25 kDa in SDS-PAGE (under non-reducing conditions) had previously been shown to retain weak affinity for IGFs, whereas the other fragment of 16 kDa lost all such affinity. From their recently determined amino acid sequences, these fragments correspond to the first 160 and 95 residues, respectively, of IGFBP-3. 0.5-5 nM intact rhlGFBP-3^1^-^2^6^4, when pre-incubated with 5 nM rhlGF-II, dose-dependently inhibited (up to 100%) its mitogenic effect, via sequestration owing to its strong affinity for IGF-II. The same concentrations of the larger fragment (IGFBP-3^1^-^1^6^0) elicited only weak inhibition (up to 30%), coherent with its weak affinity. The smaller fragment (IGFBP-3^1^-^9^5) provoked total inhibition despite its lack of affinity for IGFs and therefore by an IGF-independent mechanism. PC-3 cells in serum-free medium were weakly stimulated by 5 nM intact IGFBP-3. This had previously been shown to be related to its proteolysis and the ratio of proteolysed to intact IGFBP-3. At the same concentration, IGFBP-3^1^-^1^6^0 stimulated this proliferation by a factor of 5-7, whereas IGFBP-3^1^-^9^5 totally suppressed it. 5 nM IGFBP-3^1^-^9^5 inhibited the mitogenic action of 1% fetal calf serum by 80%, but by only 25% in the presence of an antibody blocking the type 1 IGF receptor. Its inhibition is therefore exerted principally, but not exclusively, via the IGF signalling pathway. Our data indicate that the IGFBP-3 fragments composed of residues 1-160 and 1-95 are biologically active on PC-3 cells and that their opposite actions may account for the events observed when IGFBP-3 is proteolysed in the cell environment. These proteolytic fragments may therefore play a role in the development of prostate adenocarcinomas in vivo.

Some manganese nodules from the Atlantic, Pacific and Indian Ocean have been studied. The structural study with Scanning Electron Microscope (SEM) as well as the mineralogical studies or leaching experiments show that the oxide layer is supported by a frame of material derived from the core, being amorphous silica when the core is made of silicates, and calcium phosphate when the core is made of calcium phosphate.

Les mesures du rapport isotopique 18O16Ole long de l'axe de stalagmites soigneusement choisies donnent u̇n enregistrement climatique continental qui peut être comparé aux données de la paléoclimatologie océanique. Les âges des différentes couches de la stalagmite sont établis soit par la méthode du carbone 14 pour la période de 0 à 35.000 ans b.p., soit par le rapport 230Th234Ujusqu'à 300.000 ans b.p.

CLIMATIC variations in the Quaternary have so far been described with some precision, in the range of 0 to 35,000 yr BP, by radiocarbon dating and by using the isotopic ratio 18O/16O to estimate temperature. The ratio was measured either in foraminifera1for the marine environment, or in stalagmites2–4for the continental environment.

Serum IGF-I levels in constitutionally tall children and adolescents are above normal on average, but variations between individuals are wide. However these cannot be interpreted without consideration of the IGFBPS, and IGFBP-3 in particular, to which serum IGFs are bound. Recent data from our laboratory indicate that limited proteolysis of IGFBP-3, first described in pregnancy serum, is a physiological mechanism occuring in the normal state, which seems to be essential in controlling IGF bioavailability. Western blot analyses were done of serum IGFBPs in 34 pre-pubertal, constitutionally tall children (1 to 10 years old) using 125I-IGF (ligand blot) and a polyclonal anti-IGFBP-3 antibody with a highly sensitive detection technique (immunoblot). Ligand blotting results were inconsistent. In 60% of cases, IGFBP-3 quantities based on size and density of the 42-39-kDa doublet were appropriate to IGF-I levels, whereas in 40%, they were abnormally low. In the latter, bands of 21.5 20 and 16 kDa were sometimes detectable, resembling the proteolytic fragments in pregnancy serum. With immunoblotting, the relative amounts of 42-39-kDa doublet were similar to those seen with ligand blotting. In all normal and tall children, a 30-kDa band corresponding to the major proteolytic fragment of IGFBP-3 was present. Its intensity was inversely related to that of the 42-39-kDa doublet. The smaller fragments sometimes seen by ligand blotting were more often detectable by immunoblotting in the tall children. These findings suggest that excess proteolysis of IGFBP-3 which increases the bioavailability of IGF-I (whose levels are generally high) may contribute towards the excessive growth in constitutionally tall children.