Assessment of the Impact of Climate Shifts on Malaria Transmission in the Sahel

Climate affects malaria transmission through a complex network of causative pathways. We seek to evaluate the impact of hypothetical climate change scenarios on malaria transmission in the Sahel by using a novel mechanistic, high spatial- and temporal-resolution coupled hydrology and agent-based entomology model. The hydrology model component resolves individual precipitation events and individual breeding pools. The impact of future potential climate shifts on the representative Sahel village of Banizoumbou, Niger, is estimated by forcing the model of Banizoumbou environment with meteorological data from two locations along the north–south climatological gradient observed in the Sahel—both for warmer, drier scenarios from the north and cooler, wetter scenarios from the south. These shifts in climate represent hypothetical but historically realistic climate change scenarios. For Banizoumbou climatic conditions (latitude 13.54 N), a shift toward cooler, wetter conditions may dramatically increase mosquito abundance; however, our modeling results indicate that the increased malaria transmissibility is not simply proportional to the precipitation increase. The cooler, wetter conditions increase the length of the sporogonic cycle, dampening a large vectorial capacity increase otherwise brought about by increased mosquito survival and greater overall abundance. Furthermore, simulations varying rainfall event frequency demonstrate the importance of precipitation patterns, rather than simply average or time-integrated precipitation, as a controlling factor of these dynamics. Modeling results suggest that in addition to changes in temperature and total precipitation, changes in rainfall patterns are very important to predict changes in disease susceptibility resulting from climate shifts. The combined effect of these climate-shift–induced perturbations can be represented with the aid of a detailed mechanistic model.     

Preface for the Vittorio Gallo Honorary Issue of Neurochemical Research

Neurochemical Research -     

Ebsulfur Is a Benzisothiazolone Cytocidal Inhibitor Targeting the Trypanothione Reductase of Trypanosoma brucei

Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured parasites. The inhibition of TryR by EbS was irreversible and NADPH-dependent. EbS formed a complex with TryR and caused oxidation and inactivation of the enzyme. EbS was more toxic for T. brucei than for Trypanosoma cruzi, probably due to lower levels of TryR and trypanothione in T. brucei. Furthermore, inhibition of TryR produced high intracellular reactive oxygen species. Hydrogen peroxide, known to be constitutively high in T. brucei, enhanced the EbS inhibition of TryR. The elevation of reactive oxygen species production in parasites caused by EbS induced a programmed cell death. Soluble EbS analogues were synthesized and cured T. brucei brucei infection in mice when used together with nifurtimox. Altogether, EbS and EbS analogues disrupt the trypanothione system, hampering the defense against oxidative stress. Thus, EbS is a promising lead for development of drugs against African trypanosomiasis.     

Differential Water Mite Parasitism,Phenoloxidase Activity,and Resistance to Mites Are Unrelated across Pairs of Related Damselfly Species

Related host species often demonstrate differences in prevalence and/or intensity of infection by particular parasite species, as well as different levels of resistance to those parasites. The mechanisms underlying this interspecific variation in parasitism and resistance expression are not well understood. Surprisingly, few researchers have assessed relations between actual levels of parasitism and resistance to parasites seen in nature across multiple host species. The main goal of this study was to determine whether interspecific variation in resistance against ectoparasitic larval water mites either was predictive of interspecific variation in parasitism for ten closely related species of damselflies (grouped into five “species pairs”), or was predicted by interspecific variation in a commonly used measure of innate immunity (total Phenoloxidase or potential PO activity). Two of five species pairs had interspecific differences in proportions of individuals resisting larval Arrenurus water mites, only one of five species pairs had species differences in prevalence of larval Arrenurus water mites, and another two of five species pairs showed species differences in mean PO activity. Within the two species pairs where species differed in proportion of individuals resisting mites the species with the higher proportion did not have correspondingly higher PO activity levels. Furthermore, the proportion of individuals resisting mites mirrored prevalence of parasitism in only one species pair. There was no interspecific variation in median intensity of mite infestation within any species pair. We conclude that a species’ relative ability to resist particular parasites does not explain interspecific variation in parasitism within species pairs and that neither resistance nor parasitism is reflected by interspecific variation in total PO or potential PO activity.     

The effect of population structure on the rate of evolution

Ecological factors exert a range of effects on the dynamics of the evolutionary process. A particularly marked effect comes from population structure, which can affect the probability that new mutations reach fixation. Our interest is in population structures, such as those depicted by ‘star graphs’, that amplify the effects of selection by further increasing the fixation probability of advantageous mutants and decreasing the fixation probability of disadvantageous mutants. The fact that star graphs increase the fixation probability of beneficial mutations has lead to the conclusion that evolution proceeds more rapidly in star-structured populations, compared with mixed (unstructured) populations. Here, we show that the effects of population structure on the rate of evolution are more complex and subtle than previously recognized and draw attention to the importance of fixation time. By comparing population structures that amplify selection with other population structures, both analytically and numerically, we show that evolution can slow down substantially even in populations where selection is amplified.     

The moose throat bot fly <Emphasis Type="Italic">Cephenemyia ulrichii</Emphasis> larvae (Diptera: Oestridae) found developing in roe deer (<Emphasis Type="Italic">Capreolus capreolus</Emphasis>) for the first time

About fifty larvae of Cephenemyia ulrichii Brauer (Diptera: Oestridae), some of them nearly full-grown third instars, were found in the throat of a roe deer (Capreolus capreolus) in June 2007 near Helsinki in Finland. The parasite is considered to be host specific, occurring only in the moose (Alces alces), and this paper is apparently the first report of a successful infestation in an aberrant host.     

ALKBH4 Depletion in Mice Leads to Spermatogenic Defects

ALKBH4, an AlkB homologue in the 2-oxoglutarate and Fe²⁺ dependent hydroxylase family, has previously been shown to regulate the level of monomethylated lysine-84 in actin and thereby indirectly influences the ability of non-muscular myosin II to bind actin filaments. ALKBH4 modulates fundamental processes including cytokinesis and cell motility, and its depletion is lethal during early preimplantation embryo stage. The aim of this study was to investigate the effect of ALKBH4 deficiency in a physiological context, using inducible Alkbh4 knockout mice. Here, we report that ALKBH4 is essential for the development of spermatocytes during the prophase of meiosis, and that ALKBH4 depletion leads to insufficient establishment of the synaptonemal complex. We also show that ALKBH4 is localized in nucleolar structures of Sertoli cells, spermatogonia and primary spermatocytes.     

Effect of Acute Exercise on Prostate Cancer Cell Growth

Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among the candidates are modifications of endogenous hormone levels. Long-term exercise is known to reduce serum levels of growth stimulating hormones. In contrast, the endocrine effects of acute endurance exercise include increased levels of mitogenic factors such as GH and IGF-1. It can be speculated that the elevation of serum growth factors may be detrimental to prostate cancer progression into malignancy. The incentive of the current study is to evaluate the effect of acute exercise serum on prostate cancer cell growth. We designed an exercise intervention where 10 male individuals performed 60 minutes of bicycle exercise at increasing intensity. Serum samples were obtained before (rest serum) and after completed exercise (exercise serum). The established prostate cancer cell line LNCaP was exposed to exercise or rest serum. Exercise serum from 9 out of 10 individuals had a growth inhibitory effect on LNCaP cells. Incubation with pooled exercise serum resulted in a 31% inhibition of LNCaP growth and pre-incubation before subcutaneous injection into SCID mice caused a delay in tumor formation. Serum analyses indicated two possible candidates for the effect; increased levels of IGFBP-1 and reduced levels of EGF. In conclusion, despite the fear of possible detrimental effects of acute exercise serum on tumor cell growth, we show that even the short-term effects seem to add to the overall beneficial influence of exercise on neoplasia.