On the Global Stability of a Generalized Cholera Epidemiological Model

In this paper, we conduct a careful global stability analysis for a generalized cholera epidemiological model originally proposed in [J. Wang and S. Liao, A generalized cholera model and epidemic/endemic analysis, J. Biol. Dyn. 6 (2012), pp. 568-589]. Cholera is a water-and food-borne infectious disease whose dynamics are complicated by the multiple interactions between the human host, the pathogen, and the environment. Using the geometric approach, we rigorously prove the endemic global stability for the cholera model in three-dimensional (when the pathogen component is a scalar) and four-dimensional (when the pathogen component is a vector) systems. This work unifies the study of global dynamics for several existing deterministic cholera models. The analytical predictions are verified by numerical simulation results

Highly Pathogenic H5N1 Avian Influenza: Entry Pathways into North America via Bird Migration

Given the possibility of highly pathogenic H5N1 avian influenza arriving in North America and monitoring programs that have been established to detect and track it, we review intercontinental movements of birds. We divided 157 bird species showing regular intercontinental movements into four groups based on patterns of movement—one of these groups (breed Holarctic, winter Eurasia) fits well with the design of the monitoring programs (i.e., western Alaska), but the other groups have quite different movement patterns, which would suggest the importance of H5N1 monitoring along the Pacific, Atlantic, and Gulf coasts of North America

Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells

<p>Abstract</p> <p>Background</p> <p>Celastrol is an active ingredient of the traditional Chinese medicinal plant <it>Tripterygium Wilfordii</it>, which exhibits significant antitumor activity in different cancer models <it>in vitro </it>and <it>in vivo</it>; however, the lack of information on the target and mechanism of action of this compound have impeded its clinical application. In this study, we sought to determine the mode of action of celastrol by focusing on the processes that mediate its anticancer activity.</p> <p>Methods</p> <p>The downregulation of heat shock protein 90 (HSP90) client proteins, phosphorylation of c-Jun NH2-terminal kinase (JNK), and cleavage of PARP, caspase 9 and caspase 3 were detected by western blotting. The accumulation of reactive oxygen species (ROS) was analyzed by flow cytometry and fluorescence microscopy. Cell cycle progression, mitochondrial membrane potential (MMP) and apoptosis were determined by flow cytometry. Absorption spectroscopy was used to determine the activity of mitochondrial respiratory chain (MRC) complexes.</p> <p>Results</p> <p>Celastrol induced ROS accumulation, G2-M phase blockage, apoptosis and necrosis in H1299 and HepG2 cells in a dose-dependent manner. N-acetylcysteine (NAC), an antioxidative agent, inhibited celastrol-induced ROS accumulation and cytotoxicity. JNK phosphorylation induced by celastrol was suppressed by NAC and JNK inhibitor SP600125 (SP). Moreover, SP significantly inhibited celastrol-induced loss of MMP, cleavage of PARP, caspase 9 and caspase 3, mitochondrial translocation of Bad, cytoplasmic release of cytochrome c, and cell death. However, SP did not inhibit celastrol-induced ROS accumulation. Celastrol downregulated HSP90 client proteins but did not disrupt the interaction between HSP90 and cdc37. NAC completely inhibited celastrol-induced decrease of HSP90 client proteins, catalase and thioredoxin. The activity of MRC complex I was completely inhibited in H1299 cells treated with 6 μM celastrol in the absence and presence of NAC. Moreover, the inhibition of MRC complex I activity preceded ROS accumulation in H1299 cells after celastrol treatment.</p> <p>Conclusion</p> <p>We identified ROS as the key intermediate for celastrol-induced cytotoxicity. JNK was activated by celastrol-induced ROS accumulation and then initiated mitochondrial-mediated apoptosis. Celastrol induced the downregulation of HSP90 client proteins through ROS accumulation and facilitated ROS accumulation by inhibiting MRC complex I activity. These results identify a novel target for celastrol-induced anticancer activity and define its mode of action.</p

Proteomic Analyses Reveal Common Promiscuous Patterns of Cell Surface Proteins on Human Embryonic Stem Cells and Sperms

BACKGROUND: It has long been proposed that early embryos and reproductive organs exhibit similar gene expression profiles. However, whether this similarity is propagated to the protein level remains largely unknown. We have previously characterised the promiscuous expression pattern of cell surface proteins on mouse embryonic stem (mES) cells. As cell surface proteins also play critical functions in human embryonic stem (hES) cells and germ cells, it is important to reveal whether a promiscuous pattern of cell surface proteins also exists for these cells. METHODS AND PRINCIPAL FINDINGS: Surface proteins of hES cells and human mature sperms (hSperms) were purified by biotin labelling and subjected to proteomic analyses. More than 1000 transmembrane or secreted cell surface proteins were identified on the two cell types, respectively. Proteins from both cell types covered a large variety of functional categories including signal transduction, adhesion and transporting. Moreover, both cell types promiscuously expressed a wide variety of tissue specific surface proteins, and some surface proteins were heterogeneously expressed. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that the promiscuous expression of functional and tissue specific cell surface proteins may be a common pattern in embryonic stem cells and germ cells. The conservation of gene expression patterns between early embryonic cells and reproductive cells is propagated to the protein level. These results have deep implications for the cell surface signature characterisation of pluripotent stem cells and germ cells and may lead the way to a new area of study, i.e., the functional significance of promiscuous gene expression in pluripotent and germ cells

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HPV16/18 L1 VLP vaccine induces cross-neutralizing antibodies that may mediate cross-protection

View of the cliffs, looking south, showing the town of Thira along the cliff's edge; Santorini is a small, circular group of volcanic islands located in the Aegean Sea, about 200 km south-east from the mainland of Greece. It is also known by the name of the largest island in the archipelago, Thera (or Thira). It is the southernmost member of the Cyclades group of islands, with an area of approximately 73 sq km (28 sq mi), and in 2001 had an estimated population of 13,600. A giant central lagoon, more or less rectangular and measuring about 12 km by 7 km (8 mi by 4 mi), is surrounded by 300 m (984 ft) high sheer cliffs on three sides. The island slopes downward from the cliffs to the surrounding Mediterranean sea. On the fourth side, the lagoon is separated from the Mediterranean by another much smaller island called Therasia, also with cliffs. The lagoon is joined to the sea in two places, in the northwest and southwest. The water in the centre of the lagoon is nearly 400 m (1,300 ft) deep, so it is an ideal safe harbour for even the biggest ships. The island's ports are all in the lagoon and there are no ports on the outside of the island. The towns of Santorini cling to the top of the cliff looking down on the lagoon. It is the most active volcanic centre in the Aegean Arc, though what remains today is largely a water-filled caldera. The name Santorini was given to it by the Latin empire in the thirteenth century and is a reference to Saint Irene. Before then it was called Kallistē ("the most beautiful one"), Strongylē ("the circular one"), or Thera. The island was the site of one of the largest volcanic eruptions of the last several thousand years when it erupted cataclysmically about 3,500 years ago. The eruption left a large caldera surrounded by volcanic ash deposits hundreds of feet deep, and its effects may have indirectly led to the collapse of the Minoan civilization on the island of Crete, 110 km (70 mi) to the south. One popular theory holds that the Thera eruption is the source of the legend of Atlantis. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 7/16/2008