Characterization of humoral responses in mice immunized with plasmid DNAs encoding SARS-CoV spike gene fragments

The immunological characteristics of SARS-CoV spike protein were investigated by administering mice with plasmids encoding various S gene fragments. We showed that the secreting forms of S1, S2 subunits and the N-terminus of S1 subunit (residues 18-495) were capable of eliciting SARS-CoV specific antibodies and the region immediate to N-terminus of matured S1 protein contained an important immunogenic determinant for elicitation of SARS-CoV specific antibodies. In addition, mice immunized with plasmids encoding S1 fragment developed a Th1-mediated antibody isotype switching. Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. These results provide insights into understanding the immunological characteristics of spike protein and the development of subunit vaccines against SARS-CoV.     

Structural and electronic properties of the liver fluke hemoglobin heme cavity by nuclear magnetic resonance: hemin isotope labeling

Reconstitution of liver fluke (Dicrocoelium dendriticum) apo-hemoglobin with hemins selectively deuterated at specific positions has permitted the assignment of several heme resonances in the proton nuclear magnetic resonance spectrum of the Met-aquo and Met-cyano forms of the holoprotein. It was established that in the Met-aquo form the meso protons resonate at positions characteristic of a six-co-ordinated in-plane iron. From this, we deduced that the Met-aquo species retains a bound water molecule at pH values as low as 4.5. The orientation of the proximal histidine imidazole ring with respect to the heme group in the cavity was determined through the identification of the heme methyl signals and the analysis of the hyperfine shift pattern in the Met-cyano hemoglobin proton nuclear magnetic resonance spectrum. Compared to sperm whale myoglobin, the heme appears to be rotated by 180 degrees about the alpha, gamma meso-axis. Protein isomers with the heme group in a reversed orientation were not detected, even shortly after reconstitution. In the Met-cyano form, the resonances most affected by the Bohr transition were shown to arise from the heme propionates.     

Cell death induced by Pteris semipinnata L. is associated with p53 and oxidant stress in gastric cancer cells

In this study, we demonstrated that Ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) had stronger cytotoxicity against MKN-45, a gastric cancer cell line bearing wild-type p53 than MKN-28, another gastric cancer cell line containing missense mutation in p53. The rapid increase of ROS level was involved in the mechanism of cytotoxicity. Classical features of apoptosis induced by 5F were observed in MKN-45 cells only or more significant in MKN-45 cells than MKN-28 cells. Translocation of Bax from cytosol to mitochondria, reduction of delta psi m and DNA fragmentation were induced by 5F in the p53-dependent manner. We conclude that the expression of Bax and its downstream molecules requires the presentation of a wild-type p53 in the cells treated by 5F.     

Mobilisation of the major stored reserves in the embryo of fenugreek (Trigonella foenum-graecum L., Leguminosae), and correlated enzyme activities

Changes in total nitrogen, soluble amino nitrogen, lipid and phytate contents, and in the activities of proteinase (pH 7.0), isocitrate lyase and phytase were followed in the endosperm, cotyledons, and axis during germination of fenugreek seeds and subsequent growth of the seedlings. The endosperm is comprised largely of cell-wall galactomannans: the majority of the seed total nitrogen, lipid and phytate (5%, 8%, 0.44% of seed dry weight respectively) is localised within the cotyledons as stored reserves. Germination is completed after 10–14 h from the start of imbibition, but the major reserves are not mobilised during the first 24 h. Then the total nitrogen content of the cotyledons starts to decrease and that of the axis increases; there is a concomitant accumulation of soluble amino nitrogen in both cotyledons and axis. An increase in proteinase activity in the cotyledons correlates well with the depletion of total nitrogen therein. Depletion of lipid and phytate reserves in the different seed tissues constitutes a late event, occurring after 50 h from the start of imbibition, and is coincident with the final disintegration of the endosperm tissue. The depletion of phytate and stored lipids is accompanied by an increase in phytase and isocitrate lyase activity. It appears that the products of lipid hydrolysis are converted by gluconeogenesis to serve as the major source of sugars for the growing axis after the endosperm galactomannan has been completely mobilised.     

Tryptanthrin Inhibits Angiogenesis by Targeting the VEGFR2-Mediated ERK1/2 Signalling Pathway

Angiogenesis is a key step for tumour growth and metastasis, and anti-angiogenesis has been proposed as an important strategy for cancer therapy. Tryptanthrin is a weakly basic alkaloid isolated from the dried roots of medicinal indigo plants and has been shown to possess anti-tumour activities on various cancer cell types. This study aims to investigate the in vitro and in vivo anti-angiogenic activities of tryptanthrin and to unravel its underlying molecular action mechanisms. Our results show that tryptanthrin inhibited the in vitro proliferation, migration, and tube formation of the human microvascular endothelial cells (HMEC-1) in a concentration-dependent manner and significantly suppressed angiogenesis in Matrigel plugs in mice. Mechanistic studies indicated that tryptanthrin reduced the expression of several pro-angiogenic factors (Ang-1, PDGFB and MMP2). Tryptanthrin was also found to suppress the VEGFR2-mediated ERK1/2 signalling pathway in HMEC-1 cells and molecular docking simulation indicated that tryptanthrin could bound to the ATP-binding site of VEGFR2. Collectively, the present study demonstrated that tryptanthrin exhibited both in vitro and in vivo anti-angiogenic activities by targeting the VEGFR2-mediated ERK1/2 signalling pathway and might have therapeutic potential for the treatment of angiogenesis-related diseases.     

Trail traffic flow prediction by contact frequency among individual ants

Ants build a trail that leads to a new location when they move their colony. The trail’s traffic flows smoothly, regardless of the density on the trail. To the best of our knowledge, such a phenomenon has been reported only for ant species. The trail’s capacity is known as trail traffic flow. In this paper, we propose a probabilistic model of trail traffic flow, which overcomes some inadequacies of the kinetic model previously proposed in the literature. Our model answers a question unsolved by the previous model, namely, how many worker ants form such a density-independent trail. We focus on ants’ responses to mutual contacts that involve individuals in trail formation. We propose a model in which contact frequency predicts the number of worker ants that form a trail. We verify that our model’s estimates match the empirical data that ant experts reported in the literature. In modeling and evaluation, we discuss an intelligent ant species, the house-hunting ant Temnothorax albipennis, which is popular among the ant experts.     

Cestode regulation of inflammation and inflammatory diseases

Helminth parasites are masters of immune regulation; a likely prerequisite for long-term survival by circumventing their hosts’ attempt to eradicate them. From a translational perspective, knowledge of immune events as a response to infection with a helminth parasite could be used to reduce the intensity of unwanted inflammatory reactions. Substantial data have accumulated showing that inflammatory reactions that promote a variety of auto-inflammatory diseases are dampened as a consequence of infection with helminth parasites, via either the mobilization of an anti-worm spectrum of immune events or by the direct effect of secretory/excretory bioactive immunomodulatory molecules released from the parasite. However, many issues are outstanding in the definition of the mechanism(s) by which infection with helminth parasites can affect the outcome, positively or negatively, of concomitant disease. We focus on a subgroup of this complex group of metazoan parasites, the cestodes, summarizing studies from rodent models that illustrate if, and by what mechanisms, infection with tapeworms ameliorate or exaggerate disease in their host. The ability of infection with cestodes, or other classes of helminth, to worsen a disease course or confer susceptibility to intracellular pathogens should be carefully considered in the context of ‘helminth therapy’. In addition, poorly characterised cestode extracts can regulate murine and human immunocyte function, yet the impact of these in the context of autoimmune or allergic diseases is poorly understood. Thus, studies with cestodes, as representative helminths, have helped cement the concept that infection with parasitic helminths can inhibit concomitant disease; however, issues relating to long-term effects, potential side-effects, mixed pathogen infections and purification of immunomodulatory molecules from the parasite remain as challenges that need to be addressed in order to achieve the use of helminths as anti-inflammatory agents for human diseases.     

Social Patterning in Adiposity in Adolescence: Prospective Observations from the Chinese Birth Cohort ‘‘Children of 1997’’

Introduction

Low early life socio-economic position is more strongly associated with adiposity among women than men. We examined whether the sex difference of social patterning in general and central adiposity exists before adulthood.

Methods

In Hong Kong’s “Children of 1997” birth cohort, we used multivariable regression to examine the association of parental education, a marker of early life socio-economic position, with body mass index (BMI) (n = 7252, 88% follow-up) and waist-height ratio (n = 5636, 68% follow-up), at 14 years.

Results

Parental education of Grade 9 or below, compared to Grade 12 or above, was associated with higher waist-height ratio z-score particularly in girls (0.30, 95% confidence interval (CI) 0.19, 0.41) compared to boys (0.12, 95% CI 0.02, 0.22) (p for sex interaction = 0.02). Lower parental education was associated with greater BMI z-score in adolescents of locally born mothers, but not adolescents of migrant mothers, with no difference by sex.

Conclusions

Different social patterning in different markers of adiposity may imply different sociological and biological mediating pathways. A stronger association between low early life socio-economic position and waist-height ratio in adolescent girls may indicate sex-specific influences of SEP related early life exposures on central adiposity.