A corresponding states approach to Small-Angle-Scattering for polydisperse ionic colloidal fluids

Approximate scattering functions for polydisperse ionic colloidal fluids are obtained by a corresponding states approach. This assumes that all pair correlation functions $g_{\alpha \beta}(r)$ of a polydisperse fluid are conformal to those of an appropriate monodisperse binary fluid (reference system) and can be generated from them by scaling transformations. The correspondence law extends to ionic fluids a {\it scaling approximation} (SA) successfully proposed for nonionic colloids in a recent paper. For the primitive model of charged hard spheres in a continuum solvent, the partial structure factors of the monodisperse binary reference system are evaluated by solving the Orstein-Zernike (OZ) integral equations coupled with an approximate closure. The SA is first tested within the mean spherical approximation (MSA) closure, which allows analytical solutions. The results are found in good overall agreement with exact MSA predictions up to relevant polidispersity. The SA is shown to be an improvement over the ``decoupling approximation'' extended to the ionic case. The simplicity of the SA scheme allows its application also when the OZ equations can be solved only numerically. An example is then given by using the hypernetted chain (HNC) closure. Shortcomings of the SA approach, its possible use in the analysis of experimental scattering data and other related points are also briefly addressed.Comment: 29 pages, 7 postscript figures (included), Latex 3.0, uses aps.sty, to appear in Phys. Rev. E (1999

Scientific, sustainability and regulatory challenges of cultured meat

Producing meat without the drawbacks of conventional animal agriculture would greatly contribute to future food and nutrition security. This Review Article covers biological, technological, regulatory and consumer acceptance challenges in this developing field of biotechnology. Cellular agriculture is an emerging branch of biotechnology that aims to address issues associated with the environmental impact, animal welfare and sustainability challenges of conventional animal farming for meat production. Cultured meat can be produced by applying current cell culture practices and biomanufacturing methods and utilizing mammalian cell lines and cell and gene therapy products to generate tissue or nutritional proteins for human consumption. However, significant improvements and modifications are needed for the process to be cost efficient and robust enough to be brought to production at scale for food supply. Here, we review the scientific and social challenges in transforming cultured meat into a viable commercial option, covering aspects from cell selection and medium optimization to biomaterials, tissue engineering, regulation and consumer acceptance

JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells

Rhabdomyosarcomas (RMS) are the most frequent soft-tissue sarcoma in children and characteristically show features of developing skeletal muscle. The alveolar subtype is frequently associated with a PAX3-FOXO1 fusion protein that is known to contribute to the undifferentiated myogenic phenotype of RMS cells. Histone methylation of lysine residues controls developmental processes in both normal and malignant cell contexts. Here we show that JARID2, that encodes a protein known to recruit various complexes with histone methylating activity to their target genes, is significantly overexpressed in RMS with PAX3-FOXO1 compared to fusion gene negative RMS (t test p<0.0001). Multivariate analyses showed higher JARID2 levels are also associated with metastases at diagnosis, independent of fusion gene status and RMS subtype (n= 120; p=0.039). JARID2 levels were altered by silencing or over-expressing PAX3-FOXO1 in RMS cell lines with and without the fusion gene, respectively. Consistent with this, we demonstrated that JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein. Silencing JARID2 resulted in reduced cell proliferation coupled with myogenic differentiation including increased expression of MYOGENIN (MYOG) and MYOSIN LIGHT CHAIN (MYL1) in RMS cell lines representative of both the alveolar and embryonal subtypes. Induced myogenic differentiation was associated with a decrease in JARID2 levels and this phenotype could be rescued by overexpressing JARID2. Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent upon EED, a core component of the Polycomb Repressive Complex 2 (PRC2). Therefore JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS. JARID2 and other components of PRC2 may represent novel therapeutic targets for treating RMS patients

Biochemical analysis of human ovarian cancer-associated antigens defined by murine monoclonal antibodies.

Two monoclonal antibodies (MOv1 and MOv2) raised against a membrane preparation of a human surgical specimen from a mucinous ovarian cystoadenocarcinoma were used to biochemically define their target antigens. The heating of peritumoral mucus-soluble extracts and the sialidase treatment of crude membrane preparations did not affect the binding capacity of MOv1 and MOv2, which, on the contrary, was significantly reduced by periodate oxidation of the same materials. Pronase digestion completely solubilized MOv1-defined antigens, whereas MOv2-defined antigens were only partially solubilized. This, however, did not affect antibody binding with digested products. These data suggest that carbohydrate residues of recognized molecules constitute the antigenic determinants and that sialic acid residues are not involved. Gel filtration on Sepharose 4B of the peritumoral mucus, solubilized either by 200 mM NaCl or Pronase, revealed that most of the antigenic activity eluted in the void-volume fractions with a high carbohydrate content and in the included fractions before the elution volume of the ferritin standard protein. When CsCl gradient equilibrium ultracentrifugation of the solubilized mucus was used, MOv1-recognized antigens sedimented with a density of 1.45 g/ml, while the MOv2-defined epitope was carried by molecules with a density of 1.52 g/ml as well as by molecules with a lower density. Using thin-layer chromatography of organic solvent extracts obtained from mucus and crude membrane preparations, only MOv2-positive molecules could be resolved as a single band of glycolipid. Altogether, these data suggest that the antigens detected by MOv1 are mainly mucins whereas the determinant recognized by MOv2 is carried by both mucins and a glycolipid. To analyze the diagnostic potential of MOv1- and MOv2-recognized molecules, we tested their presence, as soluble products, in supernatants of tumor cell lines and in peritoneal effusions from cancer patients. To this aim, we developed an immunoradiometric assay using the same monoclonal antibody in insolubilized and soluble form. Whereas MOv1-immunoradiometric assay was always negative, by MOv2-immunoradiometric assay it was possible to detect the relevant antigen in 8 of the 10 effusions from patients with well-differentiated ovarian tumors and in 5 of the 11 effusions from patients with poorly differentiated ovarian tumors, whereas the 10 control effusions from patients with various diseases were negative

Ricin A chain conjugated with monoclonal antibodies selectively killing human carcinoma cells in vitro.

Ricin A chain was coupled to murine monoclonal antibodies MBr1 and MOv2 respectively raised against human breast and ovarian carcinomas. Inhibition of protein synthesis only occurred in those cultured human tumor cells bearing the appropriate target antigens, demonstrating that both components of the conjugate were unchanged in regards to specificity and toxicity. Conjugates were 125-200 times more efficient in inhibiting [3H]proline incorporation than the uncoupled ricin A chain. They were however unable to kill the entire population of the appropriate cells even after repeated treatment. Although the two monoclonal antibodies had similar binding kinetics, the conjugates differed in their cytotoxicity kinetics. The MBr1-ricin A chain conjugate had slow kinetics, and about 20 hours were needed to obtain a protein synthesis inhibition above 50% on the appropriate line (mammary carcinoma MCF-7). In contrast, the MOv2-ricin A chain conjugate showed very fast kinetics, reaching 50% inhibition after only 30 minutes of treatment on both appropriate cell lines SW626 and HT-29 from ovarian and colon carcinomas, respectively. Growth conditions of cell lines, i.e., adherent cells versus suspended cells, and plating time were found to greatly influence the conjugates' killing efficiencies. These studies confirm the possibility of preparing ricin A chain-antibody conjugates, which retain specific cytotoxicity against tumor cells; but they also underline the need for further in vitro studies of various parameters before one considers a therapeutic use of such conjugates