Molecular characterization of a recently identified circovirus in zebra finches (Taeniopygia guttata) associated with immunosuppression and opportunistic infections

A recently identified circovirus (family Circoviridae) was detected in 14 zebra finches (Taeniopygia guttata) from seven aviaries and hobbyist breeders using polymerase chain reaction followed by sequencing. Full genome sequences of virus strains from six zebra finches consistently revealed characteristic circoviral genomic features such as a stem-loop structure and two major open reading frames (ORFs) encoding the replication-associated protein and the putative capsid protein. One further ORF encoding a protein of unknown function was additionally identified in all six genomes. Based on full genome nucleotide comparison, zebra finch circovirus was most similar to Finch circovirus originating from a Gouldian finch (Chloebia gouldiae) sharing 78% nucleotide identity. High genetic diversity was detected in the circoviruses from individual zebra finches. Comparison of the six full genome sequences revealed two genetic subgroups, which shared pairwise nucleotide identities between 91.4% and 92.7%. Analyses including partial sequences of the replication-associated protein gene of the zebra finch circovirus strains from all 14 birds supported the existence of two main clusters. Clinical diseases associated with circovirus infection were found in nestlings, fledglings and adult birds and varied from mild to severe with high mortality caused by secondary infections. Macrorhabdus ornithogaster was the most frequently detected opportunistic pathogen. Feathering disorders were seen in two birds. Lymphocytic depletion of the spleen and leukocytopaenia were detected in individual birds, suggesting immunosuppression and a pathogenesis common to circovirus infections in other birds.     

Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers

HIV quasispecies was analysed in plasma and proviral genomes hosted by duodenal mucosa and peripheral blood cells (PBMC) from patients with early or chronic infection, with respect to viral heterogeneity, tropism compartmentalization and extent of immune activation. Seventeen HIV-1-infected combined antiretroviral therapy naive patients were enrolled (11 early infection and six chronic infection). V3 and nef genomic regions were analysed by ultra-deep pyrosequencing. Sequences were used to infer co-receptor usage and to construct phylogenetic trees. As markers of immune activation, plasma sCD14 and soluble tumour necrosis factor receptor II (sTNFRII) levels were measured. Median diversity of HIV RNA was lower in patients with early infection versus chronic infection patients. Overall, direct correlation was observed between V3 diversity and X4 frequency; V3 diversity of HIV RNA was inversely correlated with CD4 T-cell count; median sCD14 and sTNFRII values were similar in early and chronic patients, but X4 frequency of HIV RNA was directly correlated with plasma sCD14. The proportion of patients harbouring X4 variants and median intra-patient X4 frequency of proviral genomes tended to be higher in chronic infection than early infection patients. More pronounced compartmentalization of proviral quasispecies in gut compared with PBMC samples was observed in patients with early infection compared with chronic patients. The loss of gut/PBMC compartmentalization in more advanced stages of HIV infection was confirmed by longitudinal observation. More studies are needed to understand the pathogenetic significance of early HIV quasispecies compartmentalization and progressive intermixing of viral variants in subsequent phases of the infection, as well as the role of immune activation in tropism switch.     

Perceptual and acoustic analysis of lexical stress in Greek speakers with dysarthria

The study reported in this paper investigated the abilities of Greek speakers with dysarthria to signal lexical stress at the single word level. Three speakers with dysarthria and two unimpaired control participants were recorded completing a repetition task of a list of words consisting of minimal pairs of Greek disyllabic words contrasted by lexical stress location only. Fourteen listeners were asked to determine the attempted stress location for each word pair. Acoustic analyses of duration and intensity ratios, both within and across words, were undertaken to identify possible acoustic correlates of the listeners’ judgments concerning stress location. Acoustic and perceptual data indicate that while each participant with dysarthria in this study had some difficulty in signaling stress unambiguously, the pattern of difficulty was different for each speaker. Further, it was found that the relationship between the listeners’ judgments of stress location and the acoustic data was not conclusive.     

Demonstration of a lexical access deficit in relapsing-remitting and secondary progressive forms of multiple sclerosis

The commonly used test to evaluate naming ability in multiple sclerosis (MS) is the Boston Naming Test (BNT). In previous studies the BNP has not shown any specific deficit in MS patients. The BNT score is obtained by adding spontaneously correct answers to correct answers obtained after semantic and phonological clues are given. Our hypothesis was that due to a lexical access deficit based on executive dysfunction, MS patients would need more clues than control subjects to normalize their performances,. Fifteen relapsing-remitting (RR) and 17 secondary progressive (SP) MS patients, and 32 controls matched for sex, age, and educational level, took the BNT. The 32 MS patients also took the BCCog (Short French battery used in MS to evaluate cognitive functions) in order to evaluate their executive functions. MS patients needed significantly more clues than matched controls to normalize their performances (P < 0.001). This lexical access deficit was more frequent in the SP than in the RR group (P < 0.05). A lexical access deficit inducing a denomination problem has thus been shown in MS patients. Further research should aim to better evaluate the executive functions of patients with a lexical access deficit.     

Update on the Human Immunodeficiency Virus

At the end of 2011, UNAIDS estimated that 34 million (31.4 to 35.9) individuals were infected by HIV worldwide and that 2.5 million were newly infected during the year. Since 2001, we have observed an increased number of HIV-infected patients in the world, due to an expanded access to antiretroviral drugs. More than 23,5 million (22.1 to 24.8) HIV-infected patients live in Sub-Saharan Africa. The number of HIV-infected patients in France is estimated at 152,000. Two types of HIV cause AIDS: HIV-1 and HIV-2 that are subdivided in groups (M, N, O, P for HIV-1; A to H for HIV-2), subtypes (A-D, F-H, J-K for HIV-1 group M), sub-subtype (A1-A4 for subtype A, F1 and F2 for subtype F in HIV-1 group M), circulating recombinant forms (CRF), and unique recombinant forms in a small number of patients. Virological diagnostic and monitoring techniques have been constantly upgraded since HIV-1 was isolated in 1983 and the first serological tests became available in 1985. This is especially true for HIV-1, the most prevalent worldwide.     

湖北钉螺数量性状研究Ⅰ.遗传变异信息的可靠性与样本量的关系

目的　探讨湖北钉螺数量性状遗传变异信息的可靠性与样本量的关系。方法　从云南大理和湖南岳阳两地区随机抽取钉螺各6 0只,分别对钉螺壳形态数量性状进行测量,计算各数量性状指标的变异系数(CV)、组间变异百分比和多样性指数。结果　CV以外唇缘厚度变异最大,肋壳钉螺达到了2 0 .5 7% ,光壳钉螺为14 .14 % ,其次是次螺层长度,分别12 .98%和11.4 9% ;肋壳钉螺有近四分之三的性状指标CV大于光壳钉螺的,且平均CV9.35 %也大于光壳钉螺的7.83% ;肋壳钉螺的平均多样性指数为1.5 4 1,高于光壳钉螺的1.2 2 0 ;当样本量<30 ,所得到的遗传变异的结果极不可靠,随着样本量的增加遗传变异信息的可靠性也增加,当样本量>5 5时,所得到的遗传变异的结果趋于稳定。结论　在湖北钉螺形态数量性状的遗传变异研究中,每个钉螺种群以分析不少于5 5个钉螺标本为好。     

Tailoring Interventions: Understanding Medical Practice Culture

This article describes the results of a study that used intensive direct observations of eight medical practices to assess the factors affecting the barriers and facilitators to adult immunization for influenza and pneumonia. The study aimed to describe the culture of these practices by identifying key features that facilitate or deter the immunization process. The article presents profiles of six of the eight practices describing their cultural and organizational frameworks. Six features that are critical to an understanding of the cultures of these practices, particularly as they relate to receptivity to influenza immunization for diverse practices and patient populations, are highlighted. These include policies and procedures, funding source, physician philosophy, patient receptivity to provider recommendation, and physical environment and social environment. The article also discusses strategies for applying knowledge about the culture of each practice to introduce appropriate and feasible interventions aimed at increasing immunization rates.     

From the Cover: The decline of mammal functional and evolutionary diversity worldwide

Biodiversity is declining worldwide. Because species interact with one another and with their environment, losses of particular organisms alter the function of ecosystems. Our understanding of the global rates and specific causes of functional decline remains limited, however. Species losses also reduce the cumulative amount of extant evolutionary history (“phylogenetic diversity” [PD]) in communities—our biodiversity heritage. Here we provide a global assessment of how each known anthropogenic threat is driving declines in functional diversity (FD) and PD, using terrestrial mammals as a case study. We find that habitat loss and harvest (e.g., legal hunting, poaching, snaring) are by far the biggest drivers of ongoing FD and PD loss. Declines in FD in high-biodiversity countries, particularly in Southeast Asia and South America, are greater than would be expected if species losses were random with respect to ecological function. Among functional guilds, herbivores are disproportionately likely to be declining from harvest, with important implications for plant communities and nutrient cycling. Frugivores are particularly likely to be declining from both harvest and habitat loss, with potential ramifications for seed dispersal and even forest carbon storage. Globally, phylogenetically unique species do not have an elevated risk of decline, but in areas such as Australia and parts of Southeast Asia, both habitat loss and harvest are biased toward phylogenetically unique species. Enhanced conservation efforts, including a renewed focus on harvest sustainability, are urgently needed to prevent the deterioration of ecosystem function, especially in the South American and equatorial Asian tropics.

Earth is likely entering its sixth mass extinction event (1–3), this one attributable to the actions of a single species: humans. The current loss of vertebrate species is estimated to be ∼1,000 times faster than the background rate of extinctions from the fossil record (4). Recent work suggests that we may even be underestimating the scale of the problem because a focus on extinctions (i.e., complete loss of species) ignores the even more dramatic decline and loss of populations (3). For each actual species extinction, there are ∼10 serious declines in abundance in extant populations, leading to “biotic annihilation” across the planet (3). For example, abundance has declined by an average of 60% in ∼17,000 monitored vertebrate populations over the last few decades (2).These losses can have major ripple effects. Organisms interact with others around them and with their environment, such that each species can affect the function of its ecosystem (5–8). For example, predators might regulate the abundance of herbivores and thereby indirectly influence plant productivity, including human agricultural output (9). Assessments of human-induced extinctions have largely focused on the loss of species (1, 10) and how those losses result in declines in the diversity of taxonomic forms (often measured as “species richness” (SR)— the number of unique species in an area). How these declines in the diversity of species affect the diversity of ecological functions has been much less explored (11), despite the fact that many ecological functions are important to the maintenance of intact ecosystems and also support human economies. For example, ∼15% of humanity depends on protein from wild-caught vertebrates (12).Moreover, the decline and loss of species reduces the cumulative evolutionary history present in any community (7, 13, 14). This evolutionary history is often represented by phylogenetic diversity (PD), or the diversity of lineages present within an assemblage of species, measured as the cumulative length of the branches on the evolutionary tree (phylogeny) linking the species. In some cases, PD may be a proxy for species interactions or functional diversity (FD) (15). Much more importantly (in our opinion), PD has immense intrinsic value because it is a fundamental measure of biodiversity—arguably the best such measure (16, 17). As such, the protection of PD is a prime conservation objective.Whether a given level of decline in SR leads to small versus large declines in FD and PD is difficult to predict. SR is often highly correlated with, and thus may be a strong proxy for, both FD and PD (18), but this is by no means the case in all systems or with all taxa (e.g., ref. 16). On the one hand, if many threatened species in a given area are functionally similar or redundant (6), then substantial taxonomic losses could occur with minimal impact on FD. On the other hand, if taxonomic diversity were to decline only slightly but the species that were lost had played unique ecological roles, then declines in FD could be severe (19). Likewise, the loss of many closely related species would have less impact on PD than would the loss of the same number of distantly related species (13, 20). Some simulation analyses have suggested that large numbers of species could be lost with relatively little impact on PD (14) or at least without a proportionally greater loss of PD (21). In contrast, empirical studies suggest that extinction risk is often disproportionately high in evolutionarily unique clades (22, 23).Research over the last decade has begun to elucidate patterns in regional and global FD and PD (e.g., refs. 24–26). Indeed, mapping standing levels of FD and PD across the globe has provided guidance as to where additional conservation measures are needed to safeguard these facets of biodiversity (27, 28). Because species differ greatly in both their likelihood of near-term extinction and their contributions to FD and PD (20), maps of different aspects of extant biodiversity might not show where diversity is actually at the greatest risk.Extinction risk across species can be driven by numerous factors (29), but we still lack a general understanding of which of these anthropogenic threats are driving declines in FD and PD. Moreover, we have little knowledge about whether ongoing losses of species and populations are biased toward functionally and phylogenetically unique taxa versus redundant taxa, either globally or in particular regions (30). Such information could help inform global assessments for conservation policy. For example, one of the nine “planetary boundaries” monitored by the Stockholm Resilience Centre (SRC) in its assessment of humanity’s impacts on Earth’s life support systems is biosphere integrity, comprising two components: genetic diversity and FD (11). We have a growing understanding of global changes in genetic diversity (31), but for FD, the SRC displays only a question mark (11).Here we provide a detailed assessment of how FD and PD are changing across the globe due to ongoing declines of populations from known major anthropogenic threats. For each threat, and for all threats combined, we determined the spatial variation in impacts on FD and PD and assessed whether ongoing declines in these facets of biodiversity are greater or less than what would be expected if declines in SR were random with respect to ecological function and evolutionary relatedness. We focus on mammals (terrestrial and freshwater aquatic species, excluding marine taxa) because many of these species have important ecological roles, trait and phylogenetic data are available for nearly all species (32, 33), and the taxon as a whole (along with other vertebrate groups) is highly threatened by human activities (1). We generated a database categorizing the degree to which each of the terrestrial and freshwater mammal species on the International Union for the Conservation of Nature (IUCN) Red List (34) is affected by anthropogenic threats (SI Appendix, Table S1). This was analyzed in conjunction with a recent phylogeny of mammals (33), a dataset of mammal functional traits (32), and global range maps for mammal species (34). We assessed how ongoing declines in SR associated with different anthropogenic threats influence FD and PD across the world’s landmasses, assuming that currently declining species are lost (3).The sampling units in our analysis are nations. Using this approach rather than, for example, a grid of points across the Earth was intended to help circumvent some of the fine-scale inaccuracies in the species-level range maps. In other words, it was less likely that a species would be erroneously listed as present or absent in an entire country than at a particular finer-scale grid cell. Moreover, arguably the most important conservation policies are at the national level, so using countries as sampling units means that our analysis is conducted at a scale potentially useful for informing biodiversity policy.     

Cytidine deamination induced HIV-1 drug resistance

The HIV-1 Vif protein is essential for overcoming the antiviral activity of DNA-editing apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) cytidine deaminases. We show that naturally occurring HIV-1 Vif point mutants with suboptimal anti-APOBEC3G activity induce the appearance of proviruses with lamivudine (3TC) drug resistance-associated mutations before any drug exposure. These mutations, ensuing from cytidine deamination events, were detected in >40% of proviruses with partially defective Vif mutants. Transfer of drug resistance from hypermutated proviruses via recombination allowed for 3TC escape under culture conditions prohibitive for any WT viral growth. These results demonstrate that defective hypermutated genomes can shape the phenotype of the circulating viral population. Partially active Vif alleles resulting in incomplete neutralization of cytoplasmic APOBEC3 molecules are directly responsible for the generation of a highly diverse, yet G-to-A biased, proviral reservoir, which can be exploited by HIV-1 to generate viable and drug-resistant progenies.