Multipotent Adult Progenitor Cells (MAPC) contribute to hepatocarcinoma neovasculature

The use of stem cells as a vehicle of therapeutic genes is an attractive approach for the development of new antitumoral strategies based on gene therapy. The aim of our study was to assess the potential of bone marrow-derived Multipotent Adult Progenitor Cells (rMAPCs) to differentiate in vitro and in vivo into endothelial cells and to be recruited to areas of tumor vasculogenesis. In vitro, rMAPCs obtained from Buffalo rats differentiated into cells expressing endothelial markers and demonstrated functional endothelial capacity. Intravenous injection of undifferentiated rMAPC transduced with a lentivirus expressing GFP in an orthotopic rat model of hepatocellular carcinoma, resulted in tumor recruitment of the injected cells and in vivo differentiation into endothelial cells in the tumor area with contribution to vasculogenesis. In summary, our results suggest that rMAPCs can be efficiently recruited by vascularized tumors and differentiate to endothelium and thus may represent a useful vehicle for delivery of therapeutic genes to sites of active tumor neovascularization.     

A Cholesterol Recognition Motif in Human Phospholipid Scramblase 1

Human phospholipid scramblase 1 (SCR) catalyzes phospholipid transmembrane (flip-flop) motion. This protein is assumed to bind the membrane hydrophobic core through a transmembrane domain (TMD) as well as via covalently bound palmitoyl residues. Here, we explore the possible interaction of the SCR TMD with cholesterol by using a variety of experimental and computational biophysical approaches. Our findings indicate that SCR contains an amino acid segment at the C-terminal region that shows a remarkable affinity for cholesterol, although it lacks the CRAC sequence. Other 3-OH sterols, but not steroids lacking the 3-OH group, also bind this region of the protein. The newly identified cholesterol-binding region is located partly at the C-terminal portion of the TMD and partly in the first amino acid residues in the SCR C-terminal extracellular coil. This finding could be related to the previously described affinity of SCR for cholesterol-rich domains in membranes.     

GlialCAM,a CLC-2 Cl Channel Subunit,Activates the Slow Gate of CLC Chloride Channels

GlialCAM, a glial cell adhesion molecule mutated in megalencephalic leukoencephalopathy with subcortical cysts, targets the CLC-2 Cl^- channel to cell contacts in glia and activates CLC-2 currents in vitro and in vivo. We found that GlialCAM clusters all CLC channels at cell contacts in vitro and thus studied GlialCAM interaction with CLC channels to investigate the mechanism of functional activation. GlialCAM slowed deactivation kinetics of CLC-Ka/barttin channels and increased CLC-0 currents opening the common gate and slowing its deactivation. No functional effect was seen for common gate deficient CLC-0 mutants. Similarly, GlialCAM targets the common gate deficient CLC-2 mutant E211V/H816A to cell contacts, without altering its function. Thus, GlialCAM is able to interact with all CLC channels tested, targeting them to cell junctions and activating them by stabilizing the open configuration of the common gate. These results are important to better understand the physiological role of GlialCAM/CLC-2 interaction.     

Interaction of alcohols with serum LDL An infrared study

The interaction of low molecular weight alcohols with low density lipoprotein (LDL) has been studied using amide I band-fitting, thermal profiling and two-dimensional infrared correlation spectroscopy (2D-IR). At 0.3 M alcohol, no changes in secondary structure are observed. In the presence of 1 M alcohol, ethanol and propanol decreases protein denaturation temperature and produces changes in the amide I thermal profiles of protein components and in the lipid bands. The 2D-IR synchronous map corresponding to protein or lipid component at 20-37 degrees C suggests differences in the presence of propanol. The asynchronous map corresponding to the lipid component indicates changes in bandwidth, compatible with a more fluid environment. In the 37-80 degrees C temperature range the thermal profile is different in the presence of propanol, both for the lipid and protein components. The results presented show that when alcohols affect the protein component, the lipid spectrum also varies pointing to an effect on the lipid-protein interaction.     

In Vitro Antifungal Susceptibility of Oral <Emphasis Type="Italic">Candida</Emphasis> Isolates from Patients Suffering from Caries and Chronic Periodontitis

Caries and chronic periodontitis are common oral diseases where a higher Candida colonization is reported. Antifungal agents could be adjuvant drugs for the therapy of both clinical conditions. The aim of the current study has been to evaluate the in vitro activities of conventional and new antifungal drugs against oral Candida isolates from patients suffering from caries and/or chronic periodontitis. In vitro activities of amphotericin B, fluconazole, itraconazole, miconazole, nystatin, posaconazole and voriconazole against 126 oral Candida isolates (75 Candida albicans, 18 Candida parapsilosis, 11 Candida dubliniensis, six Candida guilliermondii, five Candida lipolytica, five Candida glabrata, four Candida tropicalis and two Candida krusei) from 61 patients were tested by the CLSI M27-A3 method. Most antifungal drugs were highly active, and resistance was observed in less than 5% of tested isolates. Miconazole was the most active antifungal drug, being more than 98% of isolates susceptible. Fluconazole, itraconazole, and the new triazoles, posaconazole and voriconazole, were also very active. Miconazole, fluconazole and voriconazole have excellent in vitro activities against all Candida isolates and could represent suitable treatment for a hypothetically adjunctive therapy of caries and chronic periodontitis.     

A hierarchical ecological classification system along the NE Atlantic coast: focusing on the local scale (Cantabria,N Spain)

An ecological classification at the local scale may be a useful tool for conservation planning and for the implementation of specific management programmes in a region. For this purpose, a methodology previously applied on a small scale has been adapted to classify the coast of Cantabria (N Spain). This methodology includes a physical classification and biological validation. The shoreline was divided into 1 km stretches, and the abiotic variables (sea surface temperature, photosynthetically active radiation, significant wave height and coastal morphology) were recorded for each stretch. A hierarchical classification was proposed, with a first level that encompassed a grouping of quantitative variables based on SOM and k-mean analysis and a second level that subdivided the previous groups according to the categorical variable ‘coastal morphology’. To validate the classification using biological data, cover of intertidal macroalgal species was obtained at 14 sites along the study area, and several statistical analyses were applied to test the ecological significance of this classification. Three physical units were obtained (western (W), central (C) and eastern (E) coast), based on abiotic variables. Each group was then subdivided into subunits according to its coastal morphology (cliffs or wave-cut platforms). A general agreement between the macroalgal distribution and physical units was accomplished. In the lower intertidal, Bifurcaria bifurcata and Halopteris scoparia dominated the western and central areas, whereas Corallina spp./Ellisolandia elongata and Gelidium spp. were most abundant towards the east. In contrast, throughout the middle intertidal, Corallina. spp./E. elongata were the dominant taxa. The classification system developed in this study completes a hierarchical framework for classifying the NE Atlantic coast, a promising approach that permits the application of the most suitable resolution in each case study that could be applicable to a wide range of coastal areas.     

A new mosasauroid (Squamata) from the Late Cretaceous (Turonian) of Morocco

Tethysaurus nopcsai gen. et sp. nov. is described on the basis of both cranial and postcranial material from the Late Cretaceous (Early Turonian) of the Goulmima region, southern Morocco. This new mosasauroid is mainly characterized by a parietal table ending posteriorly in two pointed pegs; jugal with a large ascending ramus; splenial with a large and notched dorsomedial process; surangular exposed medially ventral to the coronoid; large paracotylar and parazygosphenal foramina on vertebrae. A phylogenetic analysis shows that Tethysaurus is the sister-group of Mosasauridae. It fills the gap between the aigialosaurids (mainly Cenomanian) and the mosasaurids (known from the Middle-Late Turonian to the Latest Maastrichtian). To cite this article: N. Bardet et al., C. R. Palevol 2 (2003).     

Mosasaurus beaugei Arambourg, 1952 (Squamata, Mosasauridae) from the Late Cretaceous phosphates of Morocco

Mosasaurus beaugei Arambourg, 1952 was based on isolated teeth from the Maastrichtian phosphatic deposits of Morocco. The recent discovery of new material, including skull and mandibular remains, improves our knowledge of this species. M. beaugei shares the following synapomorphies with the genus Mosasaurus: large teeth bearing two prominent carinae and with asymmetrical labial and lingual surfaces, the labial one being flattened and strongly facetted and the lingual one being convex; premaxillae with a small pointed rostrum and dentary without rostrum; palatal elements closely united; coronoid with very large ventromedial process overlying the prearticular. M. beaugei is characterised by the following autapomorphies: 12-13 maxillary teeth; marginal teeth bearing 3-5 prisms on the labial surface and 8-9 on the lingual one; palatine with posterior border concave and perpendicular to the long axis of the skull; splenial visible laterally on half of the dentary ventral surface; coronoid with anterior wing well developed and bearing two notches. M. beaugei is only known to date in the Maastrichtian phosphates of Morocco.