Spatial structure,host heterogeneity and parasite virulence: implications for vaccine‐driven evolution

Natural host‐parasite interactions exhibit considerable variation in host quality, with profound consequences for disease ecology and evolution. For instance, treatments (such as vaccination) may select for more transmissible or virulent strains. Previous theory has addressed the ecological and evolutionary impact of host heterogeneity under the assumption that hosts and parasites disperse globally. Here, we investigate the joint effects of host heterogeneity and local dispersal on the evolution of parasite life‐history traits. We first formalise a general theoretical framework combining variation in host quality and spatial structure. We then apply this model to the specific problem of parasite evolution following vaccination. We show that, depending on the type of vaccine, spatial structure may select for higher or lower virulence compared to the predictions of non‐spatial theory. We discuss the implications of our results for disease management, and their broader fundamental relevance for other causes of host heterogeneity in nature.     

Chromium Differentially Affects Hydrogen Peroxide Distribution in Primary and Adventitious Roots of <i>Arabidopsis thaliana</i> L.

The post-embryonic growth of the Arabidopsis thaliana root system can be modified by different types of stress, such as sublethal concentrations of metals, which may induce the production of reactive oxygen species (ROS). In this study, the effects of different concentrations of potassium chromate (K_₂CrO₄) on the distribution and relative quantity of hydrogen peroxide (H₂O₂) were determined in primary and adventitious roots in A. thaliana HyPer line seedlings. This line has a biosensor that specifically reports H₂O₂ levels within tissues as fluorescence. Primary root growth was inhibited at 100 μM Cr (VI); in contrast, adventitious root formation was induced over the main root growth axis. These structures proliferated from 100-160 μM Cr (VI), and much higher concentrations (180-200 μM) of K_₂CrO₄ were required to affect their growth. The H₂O₂ distributions were observed in the columella and lateral root cap of primary roots of plants grown in medium lacking dichromate, but following the development of toxicity symptoms, H₂O₂ changed its distribution to the meristem and differentiation zones. Conversely, adventitious roots had comparable H₂O₂ distribution patterns in untreated plants and those exposed to Cr (VI) supplementation. Thus, differential H₂O₂ distribution correlates with the resistance of adventitious roots, but not primary roots, to dichromate and underlies cell reorganization at the apex to support growth.     

Activity of steroid 4 and derivatives 4a–4f as inhibitors of the enzyme 5α-reductase 1

It is known that the growth of prostate metastatic bone tumor depends on androgens, and tumor formation can start from migratory malignant cells produced in that organ. These cells exhibit grater type 1 5α-reductase (5α-R1) activity than type 2 5α-reductase. Noteworthy, both isozymes convert testosterone (T) to the more active androgen dihydrotestosterone (DHT) in the target tissues.Thus, in order to potentially improve the prognosis of this disease, in this work, seven derivatives of 17-(1H-benzimidazol-1-yl)-16-formillandrosta-5,16-dien-3β-yl benzoate (4a–f) and 17-(1H-benzimidazol-1-yl)-3-hydroxy-16-formylandrost-5,16-diene (4) were synthesized, characterized and identified as inhibitors of type 1 5α-reductase (5αR1). These derivatives having the advantage of improved plasma half-life.The inhibitory activity of the compounds towards 5α-R1 isoenzyme was determined by conversion of T into DHT in the presence or absence of compounds 4, 4a–f. Further, in vivo experiments were also carried out, treating gonadectomized hamsters with T and/or 4, 4a–f and evaluating their effect on the diameter of hamster flank organs and on the weight of the prostatic and seminal vesicles. Results indicated that compounds 4, 4b, 4c, served as in vitro inhibitors of the enzyme 5α-R1 and pharmacological experiments showed that 4 and derivatives 4a–f decreased the diameter of the flank glands, the weight of the prostate and seminal vesicles of treated hamsters without any appreciable toxicity during observation. Noteworthy the fact that compound 4 is the product, in all cases, of the hydrolysis of the series of esters 4a–f, thus they can serve as precursors (prodrugs) of the active form 4.     

Bathymetric distribution and diversity of deep water polychaetous annelids in the Sigsbee Basin, northwestern Gulf of Mexico

The deep water polychaete fauna is analyzed in this study particularly regarding its composition and variations with depth in the Sigsbee Basin, northwestern region of the Gulf of Mexico. Samples were taken at 10 stations along a bathymetric gradient with depth ranges from 200 to 3760 m with a USNEL (0.25 m²) corer. A total of 287 individuals were identified, from 21 families and 65 species. The most important families, both in terms of abundance and species richness, were: Paraonidae (65.4 ind./0.25 m², 9 spp.), Cirratulidae (28.93 ind./0.25 m², 7 spp.) and Spionidae (18.07 ind./0.25 m², 7 spp.). In general, density tended to decrease with depth with minima at around 2000 m, although two abundance peaks were detected at 3700 and 3760 m, making the pattern seem an inverted parabolic curve. The Shannon-Wiener diversity values varied from 0.54–0.92 at around 2000 m to 3.39 at 3620 m and 3.34 at 3760 m. These results contrast with what is already reported from the North Atlantic and the Tropical Pacific deep benthic communities, where highest diversities are found at 2000 m. Faunal changes evaluated through Beta Diversity (0.08–0.1) and the low similarity found between the stations, emphasized the high variability in the composition of the fauna in the Sigsee Basin, meaning that the faunal composition is practically different at all the sampling stations. Ten species are newly recorded for the Mexican fauna.     

Phosphate relieves chromium toxicity in Arabidopsis thaliana plants by interfering with chromate uptake

Soil contamination by hexavalent chromium [Cr(VI) or chromate] due to anthropogenic activities has become an increasingly important environmental problem. Mineral nutrients such as phosphate (Pi), sulfate and nitrate have been reported to attenuate Cr(VI) toxicity, but the underlying mechanisms remain to be clarified. Here, we show that chromate activates the expression of low-Pi inducible reporter genes AtPT1 and AtPT2 in Arabidopsis thaliana transgenic seedlings. Primary-root growth was inhibited by 60 % in AtPT2::uidA-expressing seedlings upon exposure to 140-μM Cr(VI). However, increasing the Pi and sulfate supply to the seedlings that were experiencing Cr(VI) toxicity completely and partially restored the root growth, respectively. This effect correlated with the Cr(VI)-induced AtPT2::uidA expression being completely reversed by addition of Pi. To evaluate whether the nutrient supply may affect the endogenous level of Cr in plants grown under toxic Cr(VI) levels, the contents of Cr were measured (by ICP-MS analyses) in seedlings treated with Cr and with or without Pi, sulfate or nitrate. It was found that Cr accumulation increases tenfold in plants treated with 140-μM Cr(VI) without modifying the phosphorus concentration in the plant. In contrast, the supply of Pi specifically decreased the Cr content to levels similar to those found in seedlings grown in medium without chromate. Taken together, these results show that in A. thaliana seedlings the uptake of Cr(VI) is reduced by Pi. Moreover, our data indicate that Pi and sulfate supplements may be useful in strategies for handling Cr-contaminated soils.     

Novel dehydroepiandrosterone benzimidazolyl derivatives as 5α-reductase isozymes inhibitors

5α-R isozymes (types 1 and 2) play an important role in prostate gland development because they are responsible for intraprostatic dihydrotestosterone (DHT) levels when the physiological serum testosterone (T) concentration is low. In this study, we synthesized seven novel dehydroepiandrosterone derivatives with benzimidazol moiety at C-17, and determined their effect on the activity of 5α-reductase types 1 and 2. The derivatives with an aliphatic ester at C-3 of the dehydroepiandrosterone scaffold induced specific inhibition of 5α-R1 activity, whereas those with a cycloaliphatic ester (cyclopropyl, cyclobutyl, or cyclopentyl ring) or an alcohol group at C-3 inhibited the activity of both isozymes. Derivatives with a cyclohexyl or cycloheptyl ester at C-3 showed no inhibitory activity. In pharmacological experiments, derivatives with esters having an alcohol or the aliphatic group or one of the three smaller cycloaliphatic rings at C-3 decreased the diameter of male hamster flank organs, with the cyclobutyl and cyclopentyl esters exhibiting higher effect. With exception of the cyclobutyl and cyclopentyl esters, these compounds reduced the weight of the prostate and seminal vesicles.     

Little to no genetic structure in the ectomycorrhizal basidiomycete Suillus spraguei (Syn. S. pictus) across parts of the northeastern USA

Population genetic studies of ectomycorrhizal fungi at scales larger than 100 km are still relatively rare with highly variable results. In this study, we determined the population genetic structure of the ectomycorrhizal basidiomycete Suillus spraguei over distances up to 600 km in northeastern USA forests. S. spraguei associates exclusively with five-needled pines and only with white pine (Pinus strobus) in the eastern USA. We used six microsatellite loci to assess the genetic structure between eight sites sampled in the Adirondack Park of New York and seven sites sampled in other forests of New York, Pennsylvania, and Massachusetts. Except for one site, little to no genetic differentiation was detected in pairwise comparisons of the sites (F _ST?=?0 to 0.05). Only one site was moderately differentiated from most other sites (F _ST?=?0.02 to 0.15). The Mantel test showed no significant correlation between genetic and geographic distances (isolation by distance; R ²?=?0.003, P?=?0.3). The STRUCTURE analysis also supported the presence of a single cluster (K?=?1).     

Patterns of spatio-temporal variation in the survival rates of a viviparous lizard: the interacting effects of sex,reproductive trade-offs,aridity, and human-induced disturbance

Examination of the spatial and temporal variation in survival rates provides insight on how the action of natural selection varies among populations of single species. In this study, we used mark-recapture data from seven populations of the viviparous lizard Sceloporus grammicus in Central Mexico and a multi-model inference framework to examine interpopulation variation in the survival of adult males and females. We aimed to analyze the potential effects of aridity, human-induced disturbance, and reproductive costs on the survival rates of these lizards. For females in particular, we also searched for a negative relationship between litter size (adjusted for female size) and female survival. Our results demonstrate seasonal changes in survival for males and females. In three out of our seven study sites female survival decreased during the birthing season. In contrast, male survival did not appear to decrease during the mating season. We found an interaction between site-specific aridity and reproductive season affecting female survival. A decrease in female survival during the birthing season was observed in relatively arid sites. In one of these arid sites we found a negative effect of size-adjusted litter size on female survival: females producing more offspring than those expected for their size were more likely to die. This result represents evidence of a physiological trade-off for gravid females occurring in at least one of the studied populations. Interpopulation variation in the degree of human-induced disturbance could not explain the observed patterns of spatial variation in survival rates. Our results demonstrate wide variation in sex-specific survival patterns of this viviparous lizard and provide evidence that negative associations between reproduction and survival are highly dependent on the local environmental conditions.     

Synthesis and biological evaluation of esters of 16-formyl-17-methoxy-dehydroepiandrosterone derivatives as inhibitors of 5α-reductase type 2

In this study, we investigated the in vitro effect of 16-formyl-17-methoxy dehydroepiandrosterone derivatives on the activity of 5α-reductase type 2 (5α-R2) obtained from human prostate. The activity of different concentrations of these derivatives was determined for the conversion of labelled testosterone to dihydrotestosterone. The results indicated that an aliphatic ester moiety at the C-3 position of these derivatives increases their in vitro potency as inhibitors of 5α-R2 activity compared to finasteride®, which is considered to be a potent inhibitor of 5α-R2. In this case, the augmentation of the lipophilicity of these dehydroepiandrosterone derivatives increased their potency as inhibitors of 5α-R2. However, the presence of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl rings as the cycloaliphatic ester moiety at C-3 of the formyl methoxy dehydroepiandrosterone scaffold did not inhibit the activity of this enzyme. This may be due to the presence of steric factors between the enzyme and the spatial structure of these derivatives.