Cardiocladius oliffi (Diptera: Chironomidae) as a potential biological control agent against Simulium squamosum (Diptera: Simuliidae)

<p>Abstract</p> <p>Background</p> <p>The control of onchocerciasis in the African region is currently based mainly on the mass drug administration of ivermectin. Whilst this has been found to limit morbidity, it does not stop transmission. In the absence of a macrofilaricide, there is a need for an integrated approach for disease management, which includes vector control. Vector control using chemical insecticides is expensive to apply, and therefore the use of other measures such as biological control agents is needed. Immature stages of <it>Simulium squamosum</it>, reared in the laboratory from egg masses collected from the field at Boti Falls and Huhunya (River Pawnpawn) in Ghana, were observed to be attacked and fed upon by larvae of the chironomid <it>Cardiocladius oliffi </it>Freeman, 1956 (Diptera: Chironomidae).</p> <p>Methods</p> <p><it>Cardiocladius oliffi </it>was successfully reared in the rearing system developed for <it>S. damnosum </it>s.l. and evaluated for its importance as a biological control agent in the laboratory.</p> <p>Results</p> <p>Even at a ratio of one <it>C. oliffi </it>to five <it>S. squamosum</it>, they caused a significant decrease in the number of adult <it>S. squamosum </it>emerging from the systems (treatments). Predation was confirmed by the amplification of <it>Simulium </it>DNA from <it>C. oliffi </it>observed to have fed on <it>S. squamosum </it>pupae. The study also established that the chironomid flies could successfully complete their development on a fish food diet only.</p> <p>Conclusion</p> <p><it>Cardiocladius oliffi </it>has been demonstrated as potential biological control agent against <it>S. squamosum</it>.</p

Propagating the fear of witchcraft: Pentecostal prophecies in the new prophetic churches in South Africa

Pentecostal prophecy is one of the major themes of the theology and practice of religion among the prophets of New Prophetic Churches in South Africa and a major factor to the growth and expansion of Pentecostalism in Southern Africa. This paper offers a reflection on the role of prophecy in relation to the fear of witchcraft in the region. The contribution is that Pentecostal prophecy is not always in confrontation but sometime propels the fear of witchcraft. Through media analysis, the paper illustrates with some examples of Pentecostal prophecies on witchcraft how Pentecostal prophecy can aid rather than dispel fear of witchcraft. These prophecies raise several challenges to the discernment of Pentecostal prophetic ministry.Christian Spirituality, Church History and Missiolog

Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma

Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrine loop or by stromal cells as paracrine cross talk. Suppression of GLI1, by silencing or drug-mediated, inhibits LAC cells proliferation, attenuates their stemness and increases their susceptibility to apoptosis in vitro and in vivo. These findings provide insight into the growth of LACs and point to GLI1 as a downstream effector for oncogenic pathways. Thus, strategies involving direct inhibition of GLI1 may be useful in the treatment of LACs

Safety, tolerability, pharmacokinetics and pharmacodynamics of the oral cyclin-dependent kinase inhibitor AZD5438 when administered at intermittent and continuous dosing schedules in patients with advanced solid tumours.

BACKGROUND: AZD5438 is an orally bioavailable inhibitor of cyclin E-cdk2, cyclin A-cdk2 and cyclin B-cdk1 complexes. Three phase I studies assessed the clinical safety, tolerability, pharmacokinetics and pharmacodynamics of AZD5438 when administered in different dosing schedules. PATIENTS AND METHODS: AZD5438 was administered four times daily, once every 7 days (study 1), for 14 consecutive days followed by 7 days of rest (study 2), or continuously (study 3), to patients with advanced solid tumours. Dose escalation proceeded until the emergence of dose-limiting toxic effects. RESULTS: Sixty-four patients were included across the three studies (19, 17 and 28, respectively). Nausea and vomiting were the most common adverse events. When dosed continuously, 40 mg four times daily was considered intolerable, and due to safety issues, all studies were terminated prematurely. Consequently, no intolerable dose was identified during the weekly schedule. Pharmacokinetics demonstrated dose-proportional exposure, high interpatient variability and accumulation after multiple doses. Skin biopsies indicated reduced retinoblastoma protein phosphorylation at cdk2 phospho-sites; other pharmacodynamic assessments did not reveal consistent trends. CONCLUSIONS: AZD5438 was generally well tolerated in a weekly dosing schedule, but not in continuous schedules. The clinical development programme for AZD5438 was discontinued owing to tolerability and exposure data from these studies