Bacillus thuringiensis Cry5B Protein Is Highly Efficacious as a Single-Dose Therapy against an Intestinal Roundworm Infection in Mice

Intestinal parasitic nematode diseases infect over one billion people and cause significant disease burden in children (growth and cognitive stunting, malnutrition), in pregnant women, and via their dampening of the immune system in infected individuals. In over thirty years, no new classes of anti-roundworm drugs (anthelmintics) for treating humans have been developed. Because of limitations of the current drugs and the threat of parasite resistance, new anthelmintics are needed. The soil bacterium Bacillus thuringiensis (Bt) produces crystal (Cry) proteins that specifically target and kill insects and nematodes and is used around the world as a safe insecticide. Here we test the effects of the Bt Cry protein Cry5B on a chronic, natural intestinal roundworm infection in mice, namely the helminth parasite Heligmosomoides bakeri. We find that a single dose of Cry5B can eliminate 70% of the parasites and can almost completely block the ability of the parasites to produce progeny. Comparisons of Cry5B's efficacy with known anthelmintics suggest its activity is as good as or perhaps even better than those currently used. Furthermore, this protein is rapidly digested by simulated stomach juices, suggesting that protecting it from these juices would reveal a superior anthelmintic

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

SpUpNIC (Spectrograph Upgrade: Newly Improved Cassegrain): a versatile and efficient low- to medium-resolution, long-slit spectrograph on the South African Astronomical Observatory's 1.9-m telescope

We report on the extensively upgraded Cassegrain spectrograph on the South African Astronomical Observatory (SAAO) 1.9-m telescope. The introduction of new collimator and camera optics, a new detector and controller, a rear-of-slit viewing camera to facilitate acquisition, and a new instrument control and quick-look data-reduction software (to take advantage of the entire system now being governed by a programmable logic controller) has revolutionized this workhorse instrument on Africa’s second largest optical telescope. The improvement in throughput over the previous incarnation of the spectrograph is ∼50  %   in the red, increasing to a factor of four at the blue end. A selection of 10 surface-relief diffraction gratings is available to users, offering a variety of wavelength ranges and resolutions, with resolving powers between ∼500 and 6500. SpUpNIC (Spectrograph Upgrade: Newly Improved Cassegrain) has been scheduled for ∼80  %   of the time available on the 1.9-m since being installed on the telescope in late October 2015, providing the single-object spectroscopic capability to support the broad research interests of the SAAO’s local and international user community. We present an assortment of data obtained for various observing programs to demonstrate different aspects of the instrument’s enhanced performance following this comprehensive upgrade