Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The fine structure of an algal mat from a freshwater maritime antarctic lake

The three-dimensional microstructure of Tolypothrix mats from the bottom of a maritime antarctic lake of Signy Island, South Orkneys, was examined. Samples from mats at two depths, 4 and 6 m, within the lake were taken by scuba divers and frozen (−80 °C) in March 1987. The samples were freeze-fractured and examined by ambient and low temperature scanning electron microscopy (LTSEM). The mats shared a similar structure consisting of a compact lower zone of prostrate filaments and an upper zone of loose vertical filaments. An outer layer of extremely loose spreading filaments was only found by LTSEM, leading to the conclusion that some collapse of the mat structure occurred during dehydration for ambient SEM. Fine detail of the mat matrix such as the attachment of epiphytes and associated microfauna to the filaments was often obscured by mucilage. Fast-particle etching was used to remove this mucilage and also the organic coat that covers uncleaned diatoms, thereby allowing the identification of attached cells in situ. A variety of attachment strategies were observed although sessile forms were most common. Further fast-particle etching of the epiphytic diatom assemblages revealed that many of the attached diatoms were devoid of cell contents. Together with the epiphytic diatoms a variety of microfauna were identified, both incorporated within the mat and on the mat surface. The implications of these observations are discussed

Depth-related changes in benthic diatom assemblages of a maritime Antarctic lake

The epiphytic diatoms of filamentous matforming algae in Sombre Lake, Signy Island, South Orkneys, Antarctica were examined in a field study from January to March 1987. Results reveal 1) a shallow shelf assemblage, dominated by Fragilaria spp, with high percentages of empty frustules, and low numbers of viable cells and, 2) a mid-depth zone containing the most luxuriant epiphytic growth dominated by Achnanthes minutisima Kütz., Synedra rumpens var. familiaris (Kütz) Hust., and Cymbella minuta Hilse ex Rabenh., and 3) a deep water assemblage with low numbers of actively growing cells, dominated by Stauroneis anceps var. hyalina M. Perag. et Brun. in Hérib. The comparison of methods and their impact on ecological interpretation is discussed together with a consideration of the principal factors potentially influencing community structure