Anti-cancer study and whey protein complexation of new lanthanum(III) complex with the aim of achieving bioactive anticancer metal-based drugs

In this study, a new lanthanum (III)-amino acid complex utilizing cysteine has been synthesized and characterized. The anticancer activities of the prepared La(III) complex against MCF-7 cell lines were studied. Results of MTT assay showed that at all three incubation times, the cytotoxic effect of prepared La(III) complex on MCF-7 breast cancer cell lines displays a time- and dose-dependent inhibitory effects. The interactions of the La(III) complex with two whey proteins (bovine serum albumin, BSA, and Bovine β-lactoglobulin, βLG) have been explored by using spectroscopic and molecular dicking methods. The obtained results indicated that La(III) complex strongly quenched the fluorescence of two carrier proteins in static quenching mode and also, BSA hah stronger binding affinity toward studied complex than βLG whit binding constant values of K_{BSA-La?Complex}?～?0.11?×?10⁴ M^?1 and K_{βLG-La?Complex}?～?0.63?×?10³ M^?1 at 300 K. The thermodynamic parameters revealed the contribution of hydrogen bond and Vander Waals interactions in both systems. The distances of the La(III) complex whit whey proteins were calculated using Förster energy transfer theory and proved existence of the energy transfer between two proteins and prepared La(III) complex with a high probability. FT-IR and UV–Vis absorption measurements indicated that the binding of the La(III) to BSA and βLG may induce conformational and micro-environmental changes of the proteins. The docking results indicate that the La(III) complex bind to residues located in the site II of BSA and second site of βLG.

Communicated by Ramaswamy H. Sarma     

A role for CD44 in the production of IFN-gamma and immunopathology during infection with Toxoplasma gondii

The interaction of activated CD44 with its ligand, low m.w. hyaluronan, is involved in inflammation, but no role has been identified for this interaction in the regulation of an immune response to infection. In these studies, infection of C57BL/6 mice with Toxoplasma gondii resulted in increased expression of CD44 on T cells, B cells, NK cells, and macrophages, and a small percentage of CD4(+) T cells express an activated form of CD44. Administration of anti-CD44 to infected mice prevented the development of a CD4(+) T cell-dependent, infection-induced inflammatory response in the small intestine characterized by the overproduction of IFN-gamma. The protective effect of anti-CD44 treatment was associated with reduced production of IFN-gamma, but not IL-12, in vivo and in vitro. Furthermore, the addition of low m.w. hyaluronan to cultures of splenocytes or purified CD4(+) T cells from infected mice resulted in the production of high levels of IFN-gamma, which was dependent on IL-12 and TCR stimulation. Together, these results identify a novel role for CD44 in the regulation of IFN-gamma production by CD4(+) T cells during infection and demonstrate a role for CD44 in the regulation of infection-induced immune pathology.     

Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia

Targeted gene disruption or overexpression of 12/15-lipoxygenase in mice on the genetic background of apolipoprotein E or low density lipoprotein-receptor (LDL-R) deficiency has implicated 12/15-lipoxygenase in atherogenesis. The data support indirectly a role for 12/15-lipoxygenase in the oxidative modification of low density lipoprotein. In this study we set out to explore other potential mechanisms for 12/15-lipoxygenase in atherosclerosis using apolipoprotein B mRNA editing catalytic polypeptide-1/LDL-R double-deficient mice, a model highly related to the human condition of familial hypercholesterolemia. 12/15-Lipoxygenase deficiency in this strain led to approximately 50% decrease in aortic lesions in male and female mice at 8 months on a chow diet in the absence of cholesterol differences. While studying 12/15-lipoxygenase-deficient macrophages in culture, we discovered a remarkable selective defect (75-90% decrease) in interleukin-12 production but not in tumor necrosis factor-alpha or nitric oxide release, in response to lipopolysaccharide in the presence or absence of interferon-gamma priming. The lipopolysaccharide/interferon-gamma response was associated with a 33-50% decrease in nuclear interferon consensus sequence-binding protein, which is consistent with interferon consensus sequence-binding protein containing protein complex-dependent regulation of the interleukin-12 p40 gene. The decrease in interleukin-12 production was recapitulated in vivo in mouse aortas of the triple knockout group and was reflected in a marked decrease in interferon-gamma expression. The data provide support for a novel mechanism linking the 12/15-lipoxygenase pathway to a known immunomodulatory Th1 cytokine in atherogenesis.     

NetCooperate: a network-based tool for inferring host-microbe and microbe-microbe cooperation

Background

Host-microbe and microbe-microbe interactions are often governed by the complex exchange of metabolites. Such interactions play a key role in determining the way pathogenic and commensal species impact their host and in the assembly of complex microbial communities. Recently, several studies have demonstrated how such interactions are reflected in the organization of the metabolic networks of the interacting species, and introduced various graph theory-based methods to predict host-microbe and microbe-microbe interactions directly from network topology. Using these methods, such studies have revealed evolutionary and ecological processes that shape species interactions and community assembly, highlighting the potential of this reverse-ecology research paradigm.

Results

NetCooperate is a web-based tool and a software package for determining host-microbe and microbe-microbe cooperative potential. It specifically calculates two previously developed and validated metrics for species interaction: the Biosynthetic Support Score which quantifies the ability of a host species to supply the nutritional requirements of a parasitic or a commensal species, and the Metabolic Complementarity Index which quantifies the complementarity of a pair of microbial organisms’ niches. NetCooperate takes as input a pair of metabolic networks, and returns the pairwise metrics as well as a list of potential syntrophic metabolic compounds.

Conclusions

The Biosynthetic Support Score and Metabolic Complementarity Index provide insight into host-microbe and microbe-microbe metabolic interactions. NetCooperate determines these interaction indices from metabolic network topology, and can be used for small- or large-scale analyses. NetCooperate is provided as both a web-based tool and an open-source Python module; both are freely available online at http://elbo.gs.washington.edu/software_netcooperate.html.     

SDF2XYZ2SDF: how to exploit TINKER power in cheminformatics projects

An open-source tool capable of converting SD files (and virtually any other format through OpenBabel) into MMFF-typed XYZ coordinate files to be used with TINKER is described. SDF2XYZ2SDF allows including the power of TINKER molecular mechanics computations in automated cheminformatics workflows, such as conformational searches and virtual screening protocols.     

A stable biologically motivated learning mechanism for visual feature extraction to handle facial categorization

The brain mechanism of extracting visual features for recognizing various objects has consistently been a controversial issue in computational models of object recognition. To extract visual features, we introduce a new, biologically motivated model for facial categorization, which is an extension of the Hubel and Wiesel simple-to-complex cell hierarchy. To address the synaptic stability versus plasticity dilemma, we apply the Adaptive Resonance Theory (ART) for extracting informative intermediate level visual features during the learning process, which also makes this model stable against the destruction of previously learned information while learning new information. Such a mechanism has been suggested to be embedded within known laminar microcircuits of the cerebral cortex. To reveal the strength of the proposed visual feature learning mechanism, we show that when we use this mechanism in the training process of a well-known biologically motivated object recognition model (the HMAX model), it performs better than the HMAX model in face/non-face classification tasks. Furthermore, we demonstrate that our proposed mechanism is capable of following similar trends in performance as humans in a psychophysical experiment using a face versus non-face rapid categorization task.