RNA viruses as complex adaptive systems

RNA viruses have high mutation rates and so their populations exist as dynamic and complex mutant distributions. It has been consistently observed that when challenged with a new environment, viral populations adapt following hyperbolic-like kinetics: adaptation is initially very rapid, but then slows down as fitness reaches an asymptotic value. These adaptive dynamics have been explained in terms of populations moving towards the top of peaks on rugged fitness landscapes. Fitness fluctuations of varying magnitude are observed during adaptation. Often the presence of fluctuations in the evolution of physical systems indicates some form of self-organization, or where many components of the system are simultaneously involved. Here we analyze data from several in vitro evolution experiments carried out with vesicular stomatitis virus (VSV) looking for the signature of criticality and scaling. Long-range fitness correlations have been detected during the adaptive process. We also found that the magnitude of fitness fluctuations, far from being trivial, conform to a Weibull probability distribution function, suggesting that viral adaptation belongs to a broad category of phenomena previously documented in other fields and related with emergence.     

Tracing the origin of the compensasome: evolutionary history of DEAH helicase and MYST acetyltransferase gene families

Dosage compensation in Drosophila is mediated by a complex of proteins and RNAs called the "compensasome." Two of the genes that encode proteins of the complex, maleless (mle) and males-absent-on-the-first (mof), respectively, belong to the DEAH helicase and MYST acetyltransferase gene families. We performed comprehensive phylogenetic and structural analyses to determine the evolutionary histories of these two gene families and thus to better understand the origin of the compensasome. All of the members of the DEAH and MYST families of the completely sequenced Saccharomyces cerevisiae and Caenorhabditis elegans genomes, as well as those so far (June 2000) found in Drosophila melanogaster (for which the euchromatic part of the genome has also been fully sequenced) and Homo sapiens, were analyzed. We describe a total of 39 DEAH helicases in these four species. Almost all of them can be grouped in just three main branches. The first branch includes the yeast PRP2, PRP16, PRP22, and PRP43 splicing factors and their orthologs in animal species. Each PRP gene has a single ortholog in metazoans. The second branch includes just four genes, found in yeast (Ecm16) and Drosophila (kurz) and their orthologs in humans and Caenorhabditis. The third branch includes (1) a single yeast gene (YLR419w); (2) six Drosophila genes, including maleless and spindle-E/homeless; (3) four human genes, among them the ortholog of maleless, which encodes RNA helicase A; and (4) three C. elegans genes, including orthologs of maleless and spindle-E. Thus, this branch has largely expanded in metazoans. We also show that, for the whole DEAH family, only MLE and its metazoan orthologs have acquired new protein domains since the fungi/animals split. We found a total of 17 MYST family proteins in the four analyzed species. We determined putative orthologs of mof in both C. elegans and H. sapiens, and we show that the most likely ortholog in yeast is the Sas2 gene. Moreover, a paralog of mof exists in Drosophila. All of these results, together with those found for a third member of the compensasome, msl-3, suggest that this complex emerged after the fungi/animals split and that it may be present in mammalian species. Both gene duplication and the acquisition of new protein modules may have played important roles in the origin of the compensasome.     

Glucose Metabolism Disorders,HIV and Antiretroviral Therapy among Tanzanian Adults

Introduction

Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.

Methods

In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.

Results

HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.

Conclusions

HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.     

Global patterns of arthropod herbivory on an invasive plant,the physic nut (Jatropha curcas L.)

The physic nut (Jatropha curcas L.) is a multipurpose and oil‐producing shrub of Central and South American origin. Since the 15th century, this shrub has existed across tropical regions. Despite its presumed resistance to herbivores, reports show that arthropod herbivores infest it. However, no comprehensive account of arthropod herbivores, which consume the physic nut, exists. Here, we conducted a literature review that provides a comprehensive account of arthropod herbivores of the physic nut. Based on the co‐evolutionary hypothesis, we expected to find a higher herbivore of species richness and a larger proportion of native herbivores within the native range than elsewhere. As physic nut is a well‐defended plant chemically, we expected to find evidence for highest herbivory levels in plant parts that are the least defended. By the literatures review, we compiled 78 arthropod herbivores representing nine orders and from 31 families that feed on physic nut across the globe. As expected, the highest numbers of herbivores (34 species) were documented within the native range of the J. curcas and the lowest species number (21 species) in Africa. Of the 34 species in Central and South America, 94% were of native origin. Nine species were found feeding on J. curcas on more than one continent. Origins of 49% of species were from the native range of J. curcas. The highest percentage (54%) of species belonged to Hemiptera. With regard to feeding guilds, 59% of the herbivores belonged to sucking and 41% to chewing species. Forty‐one per cent of species were flower or fruit feeders, and 36% foliage feeders. We conclude that J. curcas is, despite its toxicity, vulnerable to herbivory, mainly to foliage, flower and fruit feeders.     

Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1

The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4⁺ helper T lymphocytes (T_H cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when T_H cell infection is concomitant to epitope recognition (trans-infection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved T_H epitopes may be counterproductive.     

Livestock vehicle accidents in Spain: causes, consequences, and effects on animal welfare

Livestock vehicle accidents are rare but involve significant economic, human, and nonhuman farm animal losses. This study obtained information on the characteristics of accidents, the animals involved, and injuries to humans from newspaper reports about livestock vehicle accidents in Spain from January 2000 to December 2008. Most accidents involved pig transport (57%), followed by bovine (30%), poultry (8%), and sheep (5%). Driver mortality was not high (6%), and most accidents (76%) involved only the livestock vehicle, which often was overturned (64%) on a straight road transect (51%). Multivariate analysis of the data suggests 2 types of accidents, depending on the species transported. In the first cluster, 95.3% of the cases involved pig transport with articulated vehicles (60.5%). In the second cluster, 94.4% of the accidents involved small vehicles used for cattle transport (44.4%). The results of this study indicate that the characteristics of livestock vehicle accidents vary according to species. One of the main causes of accidents appears to be driver fatigue, which may be due to several factors such as intense workdays, poorly designed route plans, or high levels of pressure from companies.     

Inferred kinship patterns reveal low levels of extra-pair paternity in the endangered Neotropical Jabiru Stork (Jabiru mycteria, Aves: Ciconiiformes)

The present study inferred the genetic mating system in a natural breeding population of the Jabiru Stork (Jabiru mycteria), a Neotropical wading bird considered endangered in part of its distribution range. Based on data from eight microsatellite loci, maximum-likelihood kinship reconstruction techniques, parentage assignment analyses and effective population size (Ne) estimates were applied to samples collected in the Brazilian Pantanal wetland (N = 45 nestlings from 20 nests; N = 17 shed adult feathers from 11 nests). The relationship diagnosis was determined for most of the complete clutches (86.66 %): 92.31 % were full siblings and 7.69 % were half siblings. Shed feathers collected from the nests matched the genetic parents of the offspring in 80 % of cases. Feathers collected from the ground below the nests were compatible with the putative parents in 41.67 % of cases. A mean Ne of 35 reproductive individuals was inferred, corresponding to an Ne/Nc ratio of 0.09, which is similar to the ratio found in populations of a number of different wild animals. The higher proportion of full siblings identified in the broods suggests that genetic monogamy is the prevalent mating system in the Jabiru Stork, while the detection of half siblings suggests some degree of extra-pair paternity. The present findings are in agreement with previous ecological observations of social monogamy in this species, despite the isolated evidence of extra-pair copulation events. This study also demonstrates the usefulness of a noninvasive approach to sampling adults and performing parentage and relatedness analyses in an elusive, threatened species.     

Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms

Insulin-like growth factor binding proteins (IGFBPs) play important physiological functions through the modulation of IGF signaling as well as IGF-independent mechanisms. Despite the established role of IGFs in development, a similar role for the seven known IGFBPs has not been established in humans. Here, we show that an autosomal-recessive syndrome that consists of progressive retinal arterial macroaneurysms and supravalvular pulmonic stenosis is caused by mutation of IGFBP7. Consistent with the recently established inhibitory role of IGFBP7 on BRAF signaling, the BRAF/MEK/ERK pathway is upregulated in these patients, which may explain why the cardiac phenotype overlaps with other disorders characterized by germline mutations in this pathway. The retinal phenotype appears to be mediated by a role in vascular endothelium, where IGFBP7 is highly expressed.