Reconstruction of the Evolutionary Dynamics of A(H3N2) Influenza Viruses Circulating in Italy from 2004 to 2012

Background

Influenza A viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (HA) domain causes seasonal epidemics. The A(H3N2) virus has higher mutation rate than the A(H1N1) virus. The aim of this study was to reconstruct the evolutionary dynamics of the A(H3N2) viruses circulating in Italy between 2004 and 2012 in the light of the forces driving viral evolution.

Methods

Phylodinamic analyses were made using a Bayesian method, and codon-specific positive selection acting on the HA coding sequence was evaluated.

Results

Global and local phylogenetic analyses showed that the Italian strains collected between 2004 and 2012 grouped into five significant Italian clades that included viral sequences circulating in different epidemic seasons. The time of the most recent common ancestor (tMRCA) of the tree root was between May and December 2003. The tMRCA estimates of the major clades suggest that the origin of a new viral strain precedes the effective circulation of the strain in the Italian population by 6–31 months, thus supporting a central role of global migration in seeding the epidemics in Italy. The study of selection pressure showed that four codons were under positive selection, three of which were located in antigenic sites. Analysis of population dynamics showed the alternation of periods of exponential growth followed by a decrease in the effective number of infections corresponding to epidemic and inter-epidemic seasons.

Conclusions

Our analyses suggest that a complex interaction between the immune status of the population, migrations, and a few selective sweeps drive the influenza A(H3N2) virus evolution. Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.     

Medium chain fatty acids in intrauterine growth restricted and small for gestational age pregnancies

Introduction

Low birth weight is associated with an increased risk of heart disease, high blood pressure and diabetes in adult life. Fetal growth is determined by nutrient availability, which is related to placenta nutrient transport. Medium chain fatty acids (MCFAs) are a particular class of nutrients, known to be a readily available energy source. Until now no data are reported on these MCFAs in low birth weight fetus.

Aim

This is a prospective study conducted in a tertiary center of prenatal diagnosis to investigate the maternal and fetal MCFAs levels in appropriate for gestational age (AGA), intrauterine growth restricted (IUGR), and small for gestational age (SGA) pregnancies.

Method

The plasmatic levels of MCFAs in AGA, IUGR and SGA mother–infant pairs were quantified by gas chromatography–mass spectrometry. The analytical method had a linearity range of 0.1–50 mg/L and a limit of quantification of 0.03 mg/L. Reduced fetal growth was defined as an estimated fetal weight below the 3rd–10th percentile for gestational age, with (IUGR) or without (SGA) fetal Doppler abnormalities.

Result

Maternal and fetal MCFAs plasma levels were significantly different among SGA, IUGR and AGA groups. Additionally, the observed MCFAs fetal to maternal ratio is >1 for IUGR group, whilst for SGA and AGA the fetal to maternal ratio is less than one.

Conclusion

Changes in MCFAs levels in fetal and maternal plasma are not related to placental functionality or nutrients availability, suggesting the presence of a de novo biosynthesis.

     

Heterostyly accelerates diversification via reduced extinction in primroses

The exceptional species diversity of flowering plants, exceeding that of their sister group more than 250-fold, is especially evident in floral innovations, interactions with pollinators and sexual systems. Multiple theories, emphasizing flower–pollinator interactions, genetic effects of mating systems or high evolvability, predict that floral evolution profoundly affects angiosperm diversification. However, consequences for speciation and extinction dynamics remain poorly understood. Here, we investigate trajectories of species diversification focusing on heterostyly, a remarkable floral syndrome where outcrossing is enforced via cross-compatible floral morphs differing in placement of their respective sexual organs. Heterostyly evolved at least 20 times independently in angiosperms. Using Darwin''s model for heterostyly, the primrose family, we show that heterostyly accelerates species diversification via decreasing extinction rates rather than increasing speciation rates, probably owing to avoidance of the negative genetic effects of selfing. However, impact of heterostyly appears to differ over short and long evolutionary time-scales: the accelerating effect of heterostyly on lineage diversification is manifest only over long evolutionary time-scales, whereas recent losses of heterostyly may prompt ephemeral bursts of speciation. Our results suggest that temporal or clade-specific conditions may ultimately determine the net effects of specific traits on patterns of species diversification.     

Sialylation in protostomes: a perspective from <Emphasis Type="Italic">Drosophila</Emphasis> genetics and biochemistry

Numerous studies have revealed important functions for sialylation in both prokaryotes and higher animals. However, the genetic and biochemical potential for sialylation in Drosophila has only been confirmed recently. Recent studies suggest significant similarities between the sialylation pathways of vertebrates and insects and provide evidence for their common evolutionary origin. These new data support the hypothesis that sialylation in insects is a specialized and developmentally regulated process which likely plays a prominent role in the nervous system. Yet several key issues remain to be addressed in Drosophila, including the initiation of sialic acid de novo biosynthesis and understanding the structure and function of sialylated glycoconjugates. This review discusses our current knowledge of the Drosophila sialylation pathway, as compared to the pathway in bacteria and vertebrates. We arrive at the conclusion that Drosophila is emerging as a useful model organism that is poised to shed new light on the function of sialylation not only in protostomes, but also in a larger evolutionary context. K. Koles and E. Repnikova contributed equally to this work.     

High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus

Background  

In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef.     

Archaeal and bacterial diversity in five different hydrothermal ponds in the Copahue region in Argentina

Copahue is an acidic geothermal volcanic region in the northwest corner of Neuquén Province, Argentina. In the area, there are various ponds, pools and hot springs with different temperatures, pH values and levels of anthropogenic influence. In this study, the prokaryotic biodiversity of five representative ponds was studied by using two complementary molecular ecology techniques: phylogenetic analysis of 16S rRNA bacterial and archaeal genes and FISH (or CARD-FISH) for quantitative estimation of biodiversity. The results, supported by multivariate statistical analysis, showed that the biodiversity in Copahue ponds seemed to be determined by temperature. High temperature ponds were dominated by archaea, mainly apparently novel representatives from the orders Sulfolobales and Thermoplasmatales that had no close cultivated relatives. By contrast, moderate temperature ponds were colonised by well-characterised sulphur-oxidising bacteria related to acidic environments, such as other geothermal sites or acid mine drainage, and archaea were absent. By combining the biodiversity results from this study and the reported physicochemical features of Copahue, a preliminary model of the possible biogeochemical interaction was outlined for moderate and high temperature ponds.     

An overview of cell renewal in the testis throughout the reproductive cycle of a seasonal breeding teleost, the gilthead seabream (Sparus aurata L)

The gilthead seabream is a protandrous hermaphrodite seasonal breeding teleost with a bisexual gonad that offers an interesting model for studying the testicular regression process that occurs in both seasonal testicular involution and sex change. Insofar as fish reproduction is concerned, little is known about cell renewal and elimination during the reproductive cycle of seasonal breeding teleosts with asynchronous spermatogenesis. We have previously described how acidophilic granulocytes infiltrate the testis during postspawning where, surprisingly, they produce interleukin-1beta, a known growth factor for mammalian spermatogonia, rather than being directly involved in the elimination of degenerative germ cells. In this study, we are able to discriminate between spermatogonia stem cells and primary spermatogonia according to their nuclear and cytoplasmic diameters and location in the germinal epithelium, finding that these two cell types, together with Sertoli cells, proliferate throughout the reproductive cycle with a rate that depends on the reproductive stage. Thus, during spermatogenesis the spermatogonia stem cells, the Sertoli cells, and the developing germ cells (primary spermatogonia, A and B spermatogonia, and spermatocytes) in the germinal compartment, and cells with fibroblast-shaped nuclei in the interstitial tissue proliferate. However, during spawning, the testis shows few proliferating cells. During postspawning, the resumption of proliferation, the occurrence of apoptotic spermatogonia, and the phagocytosis of nonshed spermatozoa by Sertoli cells lead to a reorganization of both the germinal compartment and the interstitial tissue. Finally, the proliferation of spermatogonia increases during resting when, unexpectedly, both oogonia and oocytes also proliferate. This proliferative pattern was correlated with the gonadosomatic index, testicular morphology, and testicular and gonad areas, suggesting that complex mechanisms operate in the regulation of gonocyte proliferation in hermaphrodite fish.     

Co-localization of susceptibility loci for psoriasis (PSORS4) and atopic dermatitis (ATOD2) on human chromosome 1q21

Psoriasis (PS) is a chronic inflammatory skin disorder characterized by keratinocyte hyperproliferation and altered differentiation. Atopic dermatitis (ATOD) is a chronic inflammatory, pruritic and eczematous disease frequently associated with respiratory atopy. These diseases are associated with distinct immunologic abnormalities and represent typical examples of complex diseases triggered by both genetic and environmental factors, as demonstrated by independent twin studies. Genome wide linkage studies have mapped susceptibility loci on several chromosomes (PSORS1-9; ATOD1-5). Four of them overlap on chromosomes 1q21, 3q21, 17q25 and 20p although ATOD is quite distinct from PS and these two diseases rarely occur together in the same patient. An association fine-mapping study has been performed to refine PSORS4 and ATOD2 susceptibility loci on chromosome 1q21 analyzing two independently collected cohorts of 128 PS and 120 ATOD trios. Genotype and haplotype analysis of PSORS4 and ATOD2 led us to detect significant p value for haplotypes defined by MIDDLE and ENDAL16 markers in both PS (p = 0.0000036) and ATOD (p = 0.0276), suggesting a strict co-localization within an interval of 42 kb. This genomic interval contains a single gene, LOR, encoding for loricrin. Polymorphic markers mapping in regulatory and coding regions did not show evidence of association in neither of the two diseases. However, expression profiles of LOR in skin biopsies have shown reduced levels in PS and increased levels in ATOD, suggesting the existence of a specific misregulation in LOR mRNA production.