Polymorphism at the Apical Membrane Antigen 1 Gene (AMA1) of the Malaria Parasite Plasmodium falciparum in a Vietnamese Population

The patterns of molecular evolution of the most diverse region of the apical membrane antigen 1 (AMA1) gene in Plasmodium falciparum from a Vietnamese subpopulation (Bao Loc) were investigated. Within the Bao Loc population, the sequenced gene region showed relatively high allelic and nucleotide diversity (0.985 and 0.02694, respectively). Further, the level of population recombination was substantial, resulting in a significant decay of linkage disequilibrium along the gene region. The results suggest that AMA1 is a useful genetic marker for studying the relationships between adaptation of parasite populations (to the human host immune system) and malaria epidemiology.     

Liposome membrane can act like molecular and metal chaperones for oxidized and fragmented superoxide dismutase

A mechanism for liposome-recruited activity of oxidized and fragmented superoxide dismutase (Fr.-SOD) [Tuan LQ, Umakoshi H, Shimanouchi T, Kuboi R. Liposome-recruited activity of oxidized and fragmented superoxide dismutase. Langmuir 2008;24:350–4] was further investigated, focusing on the secondary structure of Fr.-SOD. Liposome membrane was found to assist the conformational change of Fr.-SOD and reactivate the enzymatic activity, like molecular and metal chaperones. The loss of SOD activity and its secondary structure was observed during 6 h oxidation in 2 mM hydrogen peroxide. The contents of the α-helix and β-sheet structures in the oxidized and fragmented SOD (2 μM) were increased only in the presence of 10 μM Cu²⁺ and Zn²⁺ together, or in the presence of 2 mM POPC liposomes. The mixture of all of these elements (fragmented SOD and POPC liposomes with Cu²⁺ and Zn²⁺) gave not only the increase of the α-helix and β-sheet contents but also the mediation of the high SOD-like activity.     

Dammarane-type saponins from Gynostemma pentaphyllum

Dammarane-type saponins, gypenosides VN1–VN7 (1–7), were isolated from the total saponin extract of Gynostemma pentaphyllum aerial parts, with their structures elucidated on the basis of spectroscopic and chemical methods. These compounds showed moderate cytotoxic activity against four human cancer cell lines, A549 (lung), HT-29 (colon), MCF-7 (breast), and SK-OV-3 (ovary), with IC₅₀ values ranging from 19.6 ± 1.1 to 43.1 ± 1.0 μM. Regarding the HL-60 (acute promyelocytic leukemia) cell line, compounds 1, 5, and 6 showed weakly active with IC₅₀ values of 62.8 ± 1.9, 72.6 ± 3.6, and 82.4 ± 3.2 nM, respectively, while 2, 3, 4, and 7 were less active with IC₅₀ values >100 μM.     

The evolutionary landscape of the chromatin modification machinery reveals lineage specific gains,expansions, and losses

Model organisms such as yeast, fly, and worm have played a defining role in the study of many biological systems. A significant challenge remains in translating this information to humans. Of critical importance is the ability to differentiate those components where knowledge of function and interactions may be reliably inferred from those that represent lineage‐specific innovations. To address this challenge, we use chromatin modification (CM) as a model system for exploring the evolutionary properties of their components in the context of their known functions and interactions. Collating previously identified components of CM from yeast, worm, fly, and human, we identified a “core” set of 50 CM genes displaying consistent orthologous relationships that likely retain their interactions and functions across taxa. In addition, we catalog many components that demonstrate lineage specific expansions and losses, highlighting much duplication within vertebrates that may reflect an expanded repertoire of regulatory mechanisms. Placed in the context of a high‐quality protein–protein interaction network, we find, contrary to existing views of evolutionary modularity, that CM complex components display a mosaic of evolutionary histories: a core set of highly conserved genes, together with sets displaying lineage specific innovations. Although focused on CM, this study provides a template for differentiating those genes which are likely to retain their functions and interactions across species. As such, in addition to informing on the evolution of CM as a system, this study provides a set of comparative genomic approaches that can be generally applied to any biological systems. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Inhibitors of osteoclastogenesis from Lawsonia inermis leaves

Ten phenolic compounds (1–10) were isolated from a methanol extract of Lawsonia inermis leaves including two new ones, lawsoniasides A (1) and B (2). Their structures were elucidated by spectroscopic methods (NMR and FTICRMS) in combination with acid hydrolysis and GC analyses. Compounds 4 and 5 showed a significant inhibition on receptor activator for nuclear factor-κB ligand-induced osteoclast formation in murine bone-marrow macrophages.     

Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis

Human mesenchymal stem cells (MSCs) derived from adult tissues have been considered a candidate cell type for cell‐based tissue engineering and regenerative medicine. These multipotent cells have the ability to differentiate along several mesenchymal lineages and possibly along non‐mesenchymal lineages. MSCs possess considerable immunosuppressive properties that can influence the surrounding tissue positively during regeneration, but perhaps negatively towards the pathogenesis of cancer and metastasis. The balance between the naïve stem state and differentiation is highly dependent on the stem cell niche. Identification of stem cell niche components has helped to elucidate the mechanisms of stem cell maintenance and differentiation. Ultimately, the fate of stem cells is dictated by their microenvironment. In this review, we describe the identification and characterization of bone marrow‐derived MSCs, the properties of the bone marrow stem cell niche, and the possibility and likelihood of MSC involvement in cancer progression and metastasis. J. Cell. Physiol. 222: 268–277, 2010. © 2009 Wiley‐Liss, Inc.     

Expression of collagen type transcripts in chick embryonic bone detected by in situ cDNA-mRNA hybridization

The development of the chick embryonic calvarium, an intramembranous bone, is characterized by direct differentiation of cranial ectomesenchymal cells into osteoblasts without the formation of a cartilage anlage. Collagen biosynthesis remains predominantly as type I in the calvaria. However, in severely calcium-deficient chick embryos maintained in shell-less (SL) culture, cartilage-specific type II collagen is synthesized by the calvaria. Immunohistochemistry localized the cells expressing type II collagen to undermineralized regions of the SL bone. In this study, collagen gene expression in bones of normal (N) and calcium-deficient SL chick embryos was examined at Incubation Day 14 by in situ cDNA-mRNA hybridization. A critical step in the procedure, which used biotinylated cDNA probes, was the selection of fixation conditions which maximized RNA retention and maintenance of tissue morphology. Tissues fixed in modified Carnoy's fixative (58% ethanol, 30% choloroform, 10% acetic acid, 2% formaldehyde) for 2-4 hr at -20 degrees C sectioned well and retained their cell morphology and cytoplasmic RNA. Other treatments important for the procedure included demineralization in 0.25 M HCl and removal of matrix by hyaluronidase digestion. In situ hybridization with type-specific collagen cDNA probes revealed that type II collagen mRNA was present in cells throughout the SL calvaria. More importantly, cells with type II collagen mRNA were also present in N calvaria which do not synthesize the protein. The overall abundance of type II-positive cells in N calvaria was not significantly different from that in SL calvaria, but their distribution throughout the bones differed. In general, the regional distribution of type II cells was inversely correlated with the extent of matrix mineralization. In the N calvaria, cells containing collagen type II mRNA were absent in the extensively mineralized superior zone, but were found in the temporal zone which showed limited mineralization. On the other hand, in the SL calvaria, which were substantially undermineralized overall, cells with type II mRNA were found throughout the tissue. Interestingly, the overall ratio of type I cells to type II cells was approximately 50% higher in N calvaria. These findings suggest that collagen type mRNA expression in the chick embryonic calvarium is correlated with, and perhaps dependent on, the extent of tissue matrix mineralization.     

N-Cadherin expression and signaling in limb mesenchymal chondrogenesis: stimulation by poly-L-lysine

Cellular condensation is a requisite step in the initiation of mesenchymal chondrogenesis in the embryonic limb bud. We have previously shown that cellular condensation of limb chondroprogenitor mesenchymal cells is accompanied by elevated expression of N-cadherin during chondrogenesis both in vivo and in vitro. N-Cadherin-mediated cell-cell interaction is also functionally required for proper mesenchymal chondrogenesis both in vivo and in vitro. In this report, we have further analyzed the functional importance of N-cadherin in the cellular condensation-chondrogenesis pathway by examining N-cadherin expression and related activities in high density micromass cultures of chick limb mesenchymal cells in which chondrogenesis is being stimulated with the cationic polymer, poly-L-lysine (PL). The chondrogenesis-promoting action of PL is thought to involve the clustering of cells via ionic cross-linking, perhaps mimicking the action of an endogenous matrix component. Immunohistochemistry, immunoblotting, and Northern blot analysis all show that PL treatment results in a time-dependent increase in N-cadherin expression at both the protein and mRNA levels. In addition, inhibition of N-cadherin function with a neutralizing monoclonal antibody directed to its extracellular domain inhibits the chondrogenesis-stimulating effect of PL. PL treatment also alters the tyrosine-phosphorylation state of the N-cadherin associated signaling protein, beta-catenin. These results suggest that N-cadherin-mediated cell adhesion is a requisite regulatory component of the limb mesenchymal chondrogenic differentiation program, involving at least in part beta-catenin tyrosine phosphorylation as a signaling step.