Recent divergences and size decreases of eastern gorilla populations

Compared with other African apes, eastern gorillas (Gorilla beringei) have been little studied genetically. We used analysis of autosomal DNA genotypes obtained from non-invasively collected faecal samples to estimate the evolutionary histories of the two extant mountain gorilla populations and the closely related eastern lowland gorillas. Our results suggest that eastern lowland gorillas and mountain gorillas split beginning some 10 000 years ago, followed 5000 years ago by the split of the two mountain gorilla populations of Bwindi Impenetrable National Park and the Virungas Massif. All three populations have decreased in effective population size, with particularly substantial 10-fold decreases for the mountain gorillas. These dynamics probably reflect responses to habitat changes resulting from climate fluctuations over the past 20 000 years as well as increasing human influence in this densely populated region in the last several thousand years.     

The double-stranded RNA-binding protein,Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation

Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.     

Remarkably Low KIR and HLA Diversity in Amerindians Reveals Signatures of Strong Purifying Selection Shaping the Centromeric KIR Region

The killer-cell immunoglobulin-like receptors (KIR) recognize human leukocyte antigen (HLA) molecules to regulate the cytotoxic and inflammatory responses of natural killer cells. KIR genes are encoded by a rapidly evolving gene family on chromosome 19 and present an unusual variation of presence and absence of genes and high allelic diversity. Although many studies have associated KIR polymorphism with susceptibility to several diseases over the last decades, the high-resolution allele-level haplotypes have only recently started to be described in populations. Here, we use a highly innovative custom next-generation sequencing method that provides a state-of-art characterization of KIR and HLA diversity in 706 individuals from eight unique South American populations: five Amerindian populations from Brazil (three Guarani and two Kaingang); one Amerindian population from Paraguay (Aché); and two urban populations from Southern Brazil (European and Japanese descendants from Curitiba). For the first time, we describe complete high-resolution KIR haplotypes in South American populations, exploring copy number, linkage disequilibrium, and KIR–HLA interactions. We show that all Amerindians analyzed to date exhibit the lowest numbers of KIR–HLA interactions among all described worldwide populations, and that 83–97% of their KIR–HLA interactions rely on a few HLA-C molecules. Using multiple approaches, we found signatures of strong purifying selection on the KIR centromeric region, which codes for the strongest NK cell educator receptors, possibly driven by the limited HLA diversity in these populations. Our study expands the current knowledge of KIR genetic diversity in populations to understand KIR–HLA coevolution and its impact on human health and survival.     

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine

Background

This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV) for 2010–2011.

Methodology/Principal Findings

Health care workers (HCW) vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK) or HCW vaccinated in 2010 with the 2010–2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE) was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7%) reported 468 events compared to 328 of the 7645 HCW (4.3%) who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010–2011 seasonal vaccine (1% vs. 0.03%, p<0.001). Paresthesia was reported by 7 HCW (0.1%) after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.

Conclusion

The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010–2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01289418","term_id":"NCT01289418"}}NCT01289418, {"type":"clinical-trial","attrs":{"text":"NCT01318876","term_id":"NCT01318876"}}NCT01318876     

Legumes mitigate ecological consequences of a topographic gradient in a northern Mongolian steppe

Topography should create spatial variation in water and nutrients and play an especially important role in the ecology of water-limited systems. We use stable isotopes to discern how plants respond both to ecological gradients associated with elevation and to neighboring legumes on a south-facing slope in the semi-arid, historically grazed steppe of northern Mongolia. Out of three target species, Potentilla acaulis, Potentilla sericea, and Festuca lenensis, when >30 cm from a legume, all showed a decrease in leaf δ¹⁵N with increasing elevation. This, together with measures of soil δ¹⁵N, suggests greater N processing at the moister, more productive, lower elevation, and more N fixation at the upper elevation, where cover of legumes and lichens and plant-available nitrate were greater. Total soil N was greater at the lower elevation, but not lichen biomass or root colonization by AMF. Leaf δ¹³C values for P. acaulis and F. lenensis are consistent with increasing water stress with elevation; δ¹³C values indicated the greatest intrinsic water use efficiency for P. sericea, which is more abundant at the upper elevation. Nearby legumes (<10 cm) moderate the effect of elevation on leaf δ¹⁵N, confirming legumes’ meaningful input of N, and affect leaf δ¹³C for two species, suggesting an influence on the efficiency of carbon fixation. Variation in leaf %N and %C as a function of elevation and proximity to a legume differs among species. Apparently, most N input is at upper elevations, pointing to the possible importance of grazers, in addition to hydrological processes, as transporters of N throughout this landscape.     

Phylogeny and taxonomy of species in the Grosmannia serpens complex

Grosmannia serpens was first described from pine in Italy in 1936 and it has been recorded subsequently from many countries in both the northern and southern hemispheres. The fungus is vectored primarily by root-infesting bark beetles and has been reported to contribute to pine-root diseases in Italy and South Africa. The objective of this study was to consider the identity of a global collection of isolates not previously available and using DNA sequence-based comparisons not previously applied to most of these isolates. Phylogenetic analyses of the ITS2-LSU, actin, beta-tubulin, calmodulin and translation elongation factor-1 alpha sequences revealed that these morphologically similar isolates represent a complex of five cryptic species. Grosmannia serpens sensu stricto thus is redefined and comprises only isolates from Italy including the ex-type isolate. The ex-type isolate of Verticicladiella alacris was shown to be distinct from G. serpens, and a new holomorphic species, G. alacris, is described. The teleomorph state of G. alacris was obtained through mating studies in the laboratory, confirming that this species is heterothallic. Most of the available isolates, including those from South Africa, USA, France, Portugal and some from Spain, represent G. alacris. The remaining three taxa, known only in their anamorph states, are described as the new species Leptographium gibbsii for isolates from the UK, L. yamaokae for isolates from Japan and L. castellanum for isolates from Spain and the Dominican Republic.     

Enhanced expression of lipogenic genes may contribute to hyperglycemia and alterations in plasma lipids in response to dietary iron deficiency

Iron deficiency (ID) remains a public health concern affecting ~25% of the world’s population. Metabolic consequences of ID include elevated plasma glucose concentrations consistent with increased reliance on glucose as a metabolic substrate, though the mechanisms controlling these responses remain unclear. To further characterize the metabolic response to ID, weanling male Sprague–Dawley rats were fed either a control (C; 40 mg Fe/kg diet) or iron-deficient (ID; 3 mg Fe/kg diet) diet or were pair-fed (PF) the C diet to the level of intake of the ID group for 21 days. In addition to reductions in hemoglobin, hematocrit, and plasma iron, the ID group also exhibited higher percent body fat and plasma triglycerides compared to the PF group. Steady-state levels of both plasma glucose and insulin increased 40 and 45%, respectively, in the ID group compared to the PF group. Plasma cortisol levels were decreased 67% in the ID group compared to the PF diet group. The systematic evaluation of the expression of genes involved in insulin signaling, glucose metabolism, and fatty acid metabolism in the liver and skeletal muscle revealed significant alterations in the expression of 48 and 52 genes in these tissues, respectively. A significant concurrent increase in lipogenic gene expression and decrease in gene expression related to β-oxidation in both the liver and skeletal muscle, in combination with differential tissue expression of genes involved in glucose metabolism, provides novel insight into the adaptive metabolic response in rodent models of severe iron deficiency anemia.     

Physiographic and climatic events in the Chihuahuan Desert lead to the speciation and distinct demographic patterns of two sister Sceloporus lizards

The biogeographic history of the Chihuahuan Desert is known to be complex, and there is evidence of the effects of physiographic and climatic events in species diversification and demographic population changes in many taxa. Here, using DNA sequence data, we studied the influence of the physiographic and climatic events that occurred in the Chihuahuan Desert during the Pliocene–Pleistocene transition on the speciation and evolutionary history of the sister lizard species Sceloporus cyanostictus and S. gadsdeni. First, based on mtDNA and nDNA sequences, we estimated the divergence times of the sister species. Then, based on mtDNA sequences, we investigated the demographic history of both species within a phylogeographic framework. The divergence time was inferred to be 1.48 Mya, date that corresponds to the existence of a large lake in the Mapimian subprovince, between the current geographic locations of S. cyanostictus and S. gadsdeni. This lake could have acted as a barrier, leading to the speciation of both species. For the demographic history of the two species, we identified two distinct patterns: the population expansion of S. gadsdeni within the Last Glacial Maximum and the potential population decline of S. cyanostictus. Our results can be used as a guide for the study of other aspects that could be critical to developing conservation actions that ensure the survival of not only S. gadsdeni and S. cyanostictus, but also other co‐occurring lizard species.     

The neuronal voltage-dependent sodium channel type II IQ motif lowers the calcium affinity of the C-domain of calmodulin

Calmodulin (CaM) is the primary calcium sensor in eukaryotes. Calcium binds cooperatively to pairs of EF-hand motifs in each domain (N and C). This allows CaM to regulate cellular processes via calcium-dependent interactions with a variety of proteins, including ion channels. One neuronal target is NaV1.2, voltage-dependent sodium channel type II, to which CaM binds via an IQ motif within the NaV1.2 C-terminal tail (residues 1901-1938) [Mori, M., et al. (2000) Biochemistry 39, 1316-1323]. Here we report on the use of circular dichroism, fluorescein emission, and fluorescence anisotropy to study the interaction between CaM and NaV1.2 at varying calcium concentrations. At 1 mM MgCl2, both full-length CaM (CaM1-148) and a C-domain fragment (CaM76-148) exhibit tight (nanomolar) calcium-independent binding to the NaV1.2 IQ motif, whereas an N-domain fragment of CaM (CaM1-80) binds weakly, regardless of calcium concentration. Equilibrium calcium titrations of CaM at several concentrations of the NaV1.2 IQ peptide showed that the peptide reduced the calcium affinity of the CaM C-domain sites (III and IV) without affecting the N-domain sites (I and II) significantly. This leads us to propose that the CaM C-domain mediates constitutive binding to the NaV1.2 peptide, but that interaction then distorts calcium-binding sites III and IV, thereby reducing their affinity for calcium. This contrasts with the CaM-binding domains of voltage-dependent Ca2+ channels, kinases, and phosphatases, which increase the calcium binding affinity of the C-domain of CaM.