Mathematical and numerical analysis for a model of growing metastatic tumors

In cancer diseases, the appearance of metastases is a very pejorative forecast. Chemotherapies are systemic treatments which aim at the elimination of the micrometastases produced by a primitive tumour. The efficiency of chemotherapies closely depends on the protocols of administration. Mathematical modeling is an invaluable tool to help in evaluating the best treatment strategy. Iwata et al. [K. Iwata, K. Kawasaki, N. Shigesad, A dynamical model for the growth and size distribution of multiple metastatic tumors, J. Theor. Biol. 203 (2000) 177.] proposed a partial differential equation (PDE) that describes the metastatic evolution of an untreated tumour. In this article, we conducted a thorough mathematical analysis of this model. Particularly, we provide an explicit formula for the growth rate parameter, as well as a numerical resolution of this PDE. By increasing our understanding of the existing model, this work is crucial for further extension and refinement of the model. It settles down the framework necessary for the consideration of drugs administration effects on tumour development.     

Dp71f Modulates GSK3-β Recruitment to the β1-Integrin Adhesion Complex

Previously, it was shown that Dp71f binds to the β1-integrin adhesion complex to modulate PC12 cell adhesion. The absence of Dp71f led to a failure in the β1-integrin adhesion complex formation. One of the structural proteins which links the β1-integrin cytoplasmic domain to the actin cytoskeleton is ILK. GSK3-β is an ILK substrate and the carboxi-terminal region of dystrophin 427 is a substrate for hierarchical phosphorylation by GSK3-β. Dp71f contains the carboxi-terminal domain present in dystrophin 427. By using co-immunoprecipitation assays, in the present work it is demonstrated that in the neuronal PC12 cell line an interaction between Dp71f and GSK3-β occurs. This interaction was corroborated by in vitro pulldown assays. We show that GSK3-β is recruited to the β1-integrin complex and that a reduced expression of Dp71f induces a reduced GSK3-β recruitment to the β1-integrin complex. In addition, the present work establishes that adhesion of PC12 cells to laminin does not influence the phosphorylation status of Dp71f.     

Transformation of iron sulfide to greigite by nitrite produced by oil field bacteria

Nitrate, injected into oil fields, can oxidize sulfide formed by sulfate-reducing bacteria (SRB) through the action of nitrate-reducing sulfide-oxidizing bacteria (NR-SOB). When reservoir rock contains siderite (FeCO₃), the sulfide formed is immobilized as iron sulfide minerals, e.g. mackinawite (FeS). The aim of our study was to determine the extent to which oil field NR-SOB can oxidize or transform FeS. Because no NR-SOB capable of growth with FeS were isolated, the well-characterized oil field isolate Sulfurimonas sp. strain CVO was used. When strain CVO was presented with a mixture of chemically formed FeS and dissolved sulfide (HS⁻), it only oxidized the HS⁻. The FeS remained acid soluble and non-magnetic indicating that it was not transformed. In contrast, when the FeS was formed by adding FeCl₂ to a culture of SRB which gradually produced sulfide, precipitating FeS, and to which strain CVO and nitrate were subsequently added, transformation of the FeS to a magnetic, less acid-soluble form was observed. X-ray diffraction and energy-dispersive spectrometry indicated the transformed mineral to be greigite (Fe₃S₄). Addition of nitrite to cultures of SRB, containing microbially formed FeS, was similarly effective. Nitrite reacts chemically with HS⁻ to form polysulfide and sulfur (S⁰), which then transforms SRB-formed FeS to greigite, possibly via a sulfur addition pathway (3FeS + S⁰ → Fe₃S₄). Further chemical transformation to pyrite (FeS₂) is expected at higher temperatures (>60°C). Hence, nitrate injection into oil fields may lead to NR-SOB-mediated and chemical mineral transformations, increasing the sulfide-binding capacity of reservoir rock. Because of mineral volume decreases, these transformations may also increase reservoir injectivity. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

New proteins orthologous to cerato-platanin in various <Emphasis Type="Italic">Ceratocystis</Emphasis> species and the purification and characterization of cerato-populin from <Emphasis Type="Italic">Ceratocystis populicola</Emphasis>

Natural variants of cerato-platanin (CP), a pathogen associated molecular pattern (PAMP) protein produced by Ceratocystis platani (the causal agent of the plane canker stain), have been found to be produced by other four species of the genus Ceratocystis, including five clones of Ceratocystis fimbriata isolated from different hosts. All these fungal strains were known to be pathogenic to plants with considerable importance in agriculture, forestry, and as ornamental plants. The putative premature proteins were deduced on the basis of the nucleotide sequence of genes orthologous to the cp gene of C. platani; the deduced premature proteins of Ceratocystis populicola and Ceratocystis variospora reduced the total identity of all the others from 87.3% to 60.3%. Cerato-populin (Pop1), the CP-orthologous protein produced by C. populicola, was purified and characterized. Pop1 was a well-structured α/β protein with a different percentage of the α-helix than CP, and it self-assembled in vitro in ordered aggregates. Moreover, Pop1 behaved as PAMP, since it stimulated poplar leaf tissues to activate defence responses able to reduce consistently the C. populicola growth. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus

Siderophores are iron-scavenging molecules produced by many microbes. In general, they are synthesized using either non-ribosomal peptide synthetase (NRPS) or NRPS-independent siderophore (NIS) pathways. Staphylococcus aureus produces siderophores, of which the structures of staphyloferrin A and staphyloferrin B are known. Recently, the NIS biosynthetic pathway for staphyloferrin A was characterized. Here we show that, in S. aureus , the previously identified sbn ( s iderophore b iosy n thesis) locus encodes enzymes required for the synthesis of staphyloferrin B, an α-hydroxycarboxylate siderophore comprised of l -2,3-diaminopropionic acid, citric acid, 1,2-diaminoethane and α-ketoglutaric acid. Staphyloferrin B NIS biosynthesis was recapitulated in vitro , using purified recombinant Sbn enzymes and the component substrates. In vitro synthesized staphyloferrin B readily promoted the growth of iron-starved S. aureus , via the ABC transporter SirABC. The SbnCEF synthetases and a decarboxylase, SbnH, were necessary and sufficient to produce staphyloferrin B in reactions containing component substrates l -2,3-diaminopropionic acid, citric acid and α-ketoglutaric acid. Since 1,2-diaminoethane was not required, this component of the siderophore arises from the SbnH-dependent decarboxylation of a 2,3-diaminoproprionic acid-containing intermediate. Liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) analyses of a series of enzyme reactions identified mass ions corresponding to biosynthetic intermediates, allowing for the first proposed biosynthetic pathway for staphyloferrin B.     

Molecular data indicate that Rhytidhysteron rufulum (ascomycetes, Patellariales) in Costa Rica consists of four distinct lineages corroborated by morphological and chemical characters

Rhytidhysteron rufulum is a poorly known, common, pantropical species, capable of utilizing different substrata and occupying diverse habitats, and is the only species of its genus in Costa Rica. We have employed molecular, morphological, and chemical data to assess the variability and differentiation of R. rufulum in Costa Rica, including sites from the Pacific and Atlantic coast. Phylogenetic analyses of nuclear ITS rDNA sequences revealed the presence of four distinct lineages in the R. rufulum complex. Re-examination of the morphology and anatomy showed differences between these lineages in ascomatal, ascal, and ascospore size that have previously been regarded as intraspecific variations. In addition, there was a correlation between molecular phylogenies and chemical components as determined by hplc and nuclear magnetic resonance (NMR). Two lineages (clades I and II) produced the palmarumycins MK-3018, CJ-12372, and CR₁, whereas clade III produced dehydrocurvularin, and clade IV unidentified compounds. Our results based on a polyphasic approach contradict previous taxonomic interpretations of one morphologically variable species.     

Microbial reductive dechlorination of trichloroethene to ethene with electrodes serving as electron donors without the external addition of redox mediators

In situ bioremediation of industrial chlorinated solvents, such as trichloroethene (TCE), is typically accomplished by providing an organic electron donor to naturally occurring dechlorinating populations. In the present study, we show that TCE dechlorinating bacteria can access the electrons required for TCE dechlorination directly from a negatively polarized (?450 mV vs. SHE) carbon paper electrode. In replicated batch experiments, a mixed dechlorinating culture, also containing Dehalococcoides spp., dechlorinated TCE to cis‐dichloroethene (cis‐DCE) and lower amounts of vinyl chloride (VC) and ethene using the polarized electrode as the sole electron donor. Conversely, neither VC nor ethene formation occurred when a pure culture of the electro‐active microorganism Geobacter lovleyi was used, under identical experimental conditions. Cyclic voltammetry tests, carried out on the filter‐sterilized supernatant of the mixed culture revealed the presence of a self‐produced redox mediator, exhibiting a midpoint potential of around ?400 mV (vs. SHE). This yet unidentified redox‐active molecule appeared to be involved in the extracellular electron transfer from the electrode to the dechlorinating bacteria. The ability of dechlorinating bacteria to use electrodes as electron donors opens new perspectives for the development of clean, versatile, and efficient bioremediation systems based on a controlled subsurface delivery of electrons in support of biodegradative metabolisms and provides further evidence on the possibility of using conductive materials to manipulate and control a range of microbial bioprocesses. Biotechnol. Bioeng. 2009;103: 85–91. © 2008 Wiley Periodicals, Inc.     

Apoptosis in CADASIL: An in vitro study of lymphocytes and fibroblasts from a cohort of Italian patients

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease affecting vascular smooth muscle cells of nearly all tissues. Clinical manifestations mainly concern the central nervous system with repeated TIA/stroke, migraine, psychiatric disturbances, and cognitive decline. Minor findings have been reported in muscle, nerve, and skin. CADASIL is due to NOTCH3 gene mutations. This gene has been identified as an up‐regulator of c‐FLIP, an inhibitor of Fas‐ligand‐induced apoptosis. The aim of this study was to assess the involvement of oxidative stress‐induced apoptosis in cells from 16 Italian CADASIL patients. Peripheral blood lymphocytes (PBLs) and fibroblasts from CADASIL patients were exposed to 2‐deoxy‐D ‐ribose (dRib), which induces apoptosis by oxidative stress. Apoptosis was analyzed by flow cytometry, agarose gel electrophoresis and fluorescence microscopy for caspase‐3 activation, phosphatidylserine exposure and mitochondrial membrane depolarization. PBLs and fibroblasts from CADASIL patients showed a significantly higher response to dRib‐induced apoptosis than those of controls. PBLs from CADASIL patients also showed a significantly higher percentage of apoptotic cells than PBLs from controls, even when cultured without dRib. The greater susceptibility of PBLs and fibroblasts from CADASIL patients to dRib‐induced apoptosis suggests that NOTCH3 mutations are an important apoptotic trigger. Since PBLs from patients showed higher levels of apoptosis even in the absence of an apoptotic stimulus, cells from CADASIL patients appear to be physiologically prone to apoptotic cell death. J. Cell. Physiol. 219: 494–502, 2009. © 2009 Wiley‐Liss, Inc.