Asia: Ground Zero for the Next Pandemic?

The world has experienced three cases of pandemic influenza over the past century, all of which are thought to have originated in East Asia. More recently there has been a serious outbreak of severe acute respiratory syndrome (SARS) in South-East Asia. Because of very consistent action, the SARS outbreak was contained before it reached a pandemic scale but, nevertheless, it managed to affect people in countries across the globe in a matter of weeks. Now, only a couple of years after the SARS scare, the WHO has issued a new pandemic alert. This time the threat is known as avian influenza. Hence, it is fair to say that East Asia, and particularly South-East Asia, is a breeding ground for new types of severe human illness. This paper assesses the potential threat of pandemic influenza and the measures adopted for its prevention. We conclude by pointing out that even if avian influenza does not cause a human influenza pandemic, it is probably time to invest more resources in Asian (and African) countries if our aim is to prevent such pandemics from emerging in the future

Highly Irregular Verbs

Most English adjectives take on the suffixes -er and est as they journey from their base forms to their comparative and superlative incarnations, as in smart smarter smartest and funny funnier funniest. Some intrepid logologists have created sequences of unrelated words that look like adjectival progressions but aren\u27t

The Development of a Dual-ligand PEGylated Liposome Nanotechnology for Cell-selective Targeted Vascular Gene Therapy

Percutaneous transluminal angioplasty (PTA) is a common endovascular procedure that restores blood flow in peripheral vascular disease. Unfortunately, endovascular procedures inherently cause injury to intimal layer. This exposing the medial layer and vascular smooth muscle cells (VSMCs) to hemodynamic flow. The injury response induces dysfunctional VSMC phenotypes, leading to thickening of the vessel wall known as intimal hyperplasia (IH). Eventually, IH leads to restenosis, a common complication of PTA.Most therapeutic strategies for IH are aimed at reducing VSMC migration and proliferation. However, recent studies have shown healing of the VEC layer is crucial mitigating factor in IH. We postulate that an optimal intervention could be achieved by employing both therapeutic strategies simultaneously in a cell-type specific manner at the site of PTA-induced injury. Gene therapy techniques provide an opportunity to accomplish this goal. Many IH-associated genetic targets have been successfully modulated to improve reendothelialization of VECs and inhibit the proliferation of VSMCs. However, clinical success of vascular gene therapy is limited due to the lack of a translational delivery vehicle.Liposomes have been shown to be effective gene vectors with translational efficacy. The addition of polyethylene glycol (PEG) to liposomes (PLP) can improve in vivo pharmacokinetics, but reduces cellular uptake of liposomal cargo. Ligand-modified liposomes provide an opportunity to enhance transfection of neutral PLPs and target specific cell types for gene delivery. Cell-penetrating peptides (CPPs) containing arginine-rich motifs have the ability to enhance membrane translocation of their conjugated cargo. Cell-targeting peptides (CTP) can also be used to decorate the liposome surface, providing cell-type specificity. In this in vitro proof-of-concept study, we aim to develop a modified PLP comprised of neutral lipids and capable of enhanced transfection and cell-type specific delivery to VSMCs and VECs, respectively.Using a Ca2+-mediated ethanol injection technique, a novel method for the self-assembly of CPP-modified PLPs with enhanced transfection, optimized siRNA loading efficiency, minimal cytotoxicity, and cell-targeting capabilities was developed. These nanocarriers convey chemical stability to siRNA in the presence of nuclease activity. This liposomal delivery system could provide the foundation necessary to increase the bench-to-bedside success of systemically administered vascular gene therapy

Don\u27t Turn My Picture To The Wall

https://digitalcommons.library.umaine.edu/mmb-vp/5666/thumbnail.jp

Essential histidine pairs indicate conserved haem binding in epsilonproteobacterial cytochrome c haem lyases

Bacterial cytochrome c maturation occurs at the outside of the cytoplasmic membrane, requires transport of haem b across the membrane, and depends on membrane-bound cytochrome c haem lyase (CCHL), an enzyme that catalyses covalent attachment of haem b to apocytochrome c. Epsilonproteobacteria such as Wolinella succinogenes use the cytochrome c biogenesis system II and contain unusually large CCHL proteins of about 900 amino acid residues that appear to be fusions of the CcsB and CcsA proteins found in other bacteria. CcsBA-type CCHLs have been proposed to act as haem transporters that contain two haem b coordination sites located at different sides of the membrane and formed by histidine pairs. W. succinogenes cells contain three CcsBA-type CCHL isoenzymes (NrfI, CcsA1 and CcsA2) that are known to differ in their specificity for apocytochromes and apparently recognize different haem c binding motifs such as CX2CH (by CcsA2), CX2CK (by NrfI) and CX15CH (by CcsA1). In this study, conserved histidine residues were individually replaced by alanine in each of the W. succinogenes CCHLs. Characterization of NrfI and CcsA1 variants in W. succinogenes demonstrated that a set of four histidines is essential for maturing the dedicated multihaem cytochromes c NrfA and MccA, respectively. The function of W. succinogenes CcsA2 variants produced in Escherichia coli was also found to depend on each of these four conserved histidine residues. The presence of imidazole in the growth medium of both W. succinogenes and E. coli rescued the cytochrome c biogenesis activity of most histidine variants, albeit to different extents, thereby implying the presence of two functionally distinct histidine pairs in each CCHL. The data support a model in which two conserved haem b binding sites are involved in haem transport catalysed by CcsBA-type CCHLs

Normal-Metal Aharonov-Bohm Effect in the Presence of a Transverse Electric Field

The effects of transverse electric fields on the conductance fluctuations in an Sb loop have been studied. We show that the electric field can be used to tune the position (or phase) of Aharonov-Bohm oscillations as well as to alter the aperiodic conductance fluctuation patterns. We disucss two mechanisms which might cause the observed dependence of the fluctuation pattern on transverse electric field. The first is the electrostatic Aharonov-Bohm effect, and the second is the spatial shifting of the electron trajectories by the electric field

The development and applications of ultrafast electron nanocrystallography

We review the development of ultrafast electron nanocrystallography as a method for investigating structural dynamics for nanoscale materials and interfaces. Its sensitivity and resolution are demonstrated in the studies of surface melting of gold nanocrystals, nonequilibrium transformation of graphite into reversible diamond-like intermediates, and molecular scale charge dynamics, showing a versatility for not only determining the structures, but also the charge and energy redistribution at interfaces. A quantitative scheme for three-dimensional retrieval of atomic structures is demonstrated with few-particle (< 1000) sensitivity, establishing this nanocrystallographic method as a tool for directly visualizing dynamics within isolated nanomaterials with atomic scale spatio-temporal resolution.Comment: 33 pages, 17 figures (Review article, 2008 conference of ultrafast electron microscopy conference and ultrafast sciences