A species in decline: genetic diversity and conservation of the Victorian eastern barred bandicoot, Perameles gunnii

The eastern barred bandicoot, Perameles gunnii, has undergone a dramatic decline in distribution and abundance on the mainland of Australia during the twentieth century. In 1988 a captive breeding program was initiated to reduce the chance of extinction. With the extinction of the last wild mainland population in the early 1990s, reintroductions from captive-bred P. gunnii have met limited success, and currently only two extant populations persist in predator proof enclosures in the State of Victoria. With ~20 years of breeding, there are concerns that the genetic diversity within the breeding program has declined and may inhibit current and future success of the program. We have used ten nuclear microsatellite loci and sequencing of two partial mitochondrial genes (cytochrome oxidase I and ATPase 6) to determine genetic diversity within current Victorian P. gunnii. These diversity estimates are compared with historic samples from the captive breeding program dating back to 1995, historic samples from the last wild mainland population found at Hamilton in 1992 and contemporary Tasmanian wild populations. Results indicate that the captive P. gunnii population in the State of Victoria has lost significant genetic diversity through time. Genetic diversity is also reduced in populations at Hamilton Community Parklands and Mount Rothwell. Samples from the last wild population at Hamilton collected in 1992, along with samples from Tasmanian P. gunnii, had significantly greater genetic diversity than contemporary mainland populations. The results are discussed with reference to management options for maintaining genetic diversity within Victorian P. gunnii, including crossing Victorian and Tasmanian P. gunnii to increase genetic diversity, adaptability and evolutionary potential.     

The Assessment of Science: The Relative Merits of Post-Publication Review,the Impact Factor,and the Number of Citations

The assessment of scientific publications is an integral part of the scientific process. Here we investigate three methods of assessing the merit of a scientific paper: subjective post-publication peer review, the number of citations gained by a paper, and the impact factor of the journal in which the article was published. We investigate these methods using two datasets in which subjective post-publication assessments of scientific publications have been made by experts. We find that there are moderate, but statistically significant, correlations between assessor scores, when two assessors have rated the same paper, and between assessor score and the number of citations a paper accrues. However, we show that assessor score depends strongly on the journal in which the paper is published, and that assessors tend to over-rate papers published in journals with high impact factors. If we control for this bias, we find that the correlation between assessor scores and between assessor score and the number of citations is weak, suggesting that scientists have little ability to judge either the intrinsic merit of a paper or its likely impact. We also show that the number of citations a paper receives is an extremely error-prone measure of scientific merit. Finally, we argue that the impact factor is likely to be a poor measure of merit, since it depends on subjective assessment. We conclude that the three measures of scientific merit considered here are poor; in particular subjective assessments are an error-prone, biased, and expensive method by which to assess merit. We argue that the impact factor may be the most satisfactory of the methods we have considered, since it is a form of pre-publication review. However, we emphasise that it is likely to be a very error-prone measure of merit that is qualitative, not quantitative.

Author summary

Subjective assessments of the merit and likely impact of scientific publications are routinely made by scientists during their own research, and as part of promotion, appointment, and government committees. Using two large datasets in which scientists have made qualitative assessments of scientific merit, we show that scientists are poor at judging scientific merit and the likely impact of a paper, and that their judgment is strongly influenced by the journal in which the paper is published. We also demonstrate that the number of citations a paper accumulates is a poor measure of merit and we argue that although it is likely to be poor, the impact factor, of the journal in which a paper is published, may be the best measure of scientific merit currently available.     

Evidence for Finely-Regulated Asynchronous Growth of Toxoplasma gondii Cysts Based on Data-Driven Model Selection

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system. Analyzing these interactions is important for understanding the pathogenesis of this common infection. We developed a differential equation framework of cyst growth and employed Akaike Information Criteria (AIC) to determine the growth and removal functions that best describe the distribution of cyst sizes measured from the brains of chronically infected mice. The AIC strongly support models in which T. gondii cysts grow at a constant rate such that the per capita growth rate of the parasite is inversely proportional to the number of parasites within a cyst, suggesting finely-regulated asynchronous replication of the parasites. Our analyses were also able to reject the models where cyst removal rate increases linearly or quadratically in association with increase in cyst size. The modeling and analysis framework may provide a useful tool for understanding the pathogenesis of infections with other cyst producing parasites.     

Experimental Human Pneumococcal Carriage Augments IL-17A-dependent T-cell Defence of the Lung

Pneumococcal carriage is both immunising and a pre-requisite for mucosal and systemic disease. Murine models of pneumococcal colonisation show that IL-17A-secreting CD4⁺ T-cells (Th-17 cells) are essential for clearance of pneumococci from the nasopharynx. Pneumococcal-responding IL-17A-secreting CD4⁺ T-cells have not been described in the adult human lung and it is unknown whether they can be elicited by carriage and protect the lung from pneumococcal infection. We investigated the direct effect of experimental human pneumococcal nasal carriage (EHPC) on the frequency and phenotype of cognate CD4⁺ T-cells in broncho-alveolar lavage and blood using multi-parameter flow cytometry. We then examined whether they could augment ex vivo alveolar macrophage killing of pneumococci using an in vitro assay. We showed that human pneumococcal carriage leads to a 17.4-fold (p = 0.007) and 8-fold (p = 0.003) increase in the frequency of cognate IL-17A⁺ CD4⁺ T-cells in BAL and blood, respectively. The phenotype with the largest proportion were TNF⁺/IL-17A⁺ co-producing CD4⁺ memory T-cells (p<0.01); IFNγ⁺ CD4⁺ memory T-cells were not significantly increased following carriage. Pneumococci could stimulate large amounts of IL-17A protein from BAL cells in the absence of carriage but in the presence of cognate CD4⁺ memory T-cells, IL-17A protein levels were increased by a further 50%. Further to this we then show that alveolar macrophages, which express IL-17A receptors A and C, showed enhanced killing of opsonised pneumococci when stimulated with rhIL-17A (p = 0.013). Killing negatively correlated with RC (r = −0.9, p = 0.017) but not RA expression. We conclude that human pneumococcal carriage can increase the proportion of lung IL-17A-secreting CD4⁺ memory T-cells that may enhance innate cellular immunity against pathogenic challenge. These pathways may be utilised to enhance vaccine efficacy to protect the lung against pneumonia.     

Genetic Recombination Is Targeted towards Gene Promoter Regions in Dogs

The identification of the H3K4 trimethylase, PRDM9, as the gene responsible for recombination hotspot localization has provided considerable insight into the mechanisms by which recombination is initiated in mammals. However, uniquely amongst mammals, canids appear to lack a functional version of PRDM9 and may therefore provide a model for understanding recombination that occurs in the absence of PRDM9, and thus how PRDM9 functions to shape the recombination landscape. We have constructed a fine-scale genetic map from patterns of linkage disequilibrium assessed using high-throughput sequence data from 51 free-ranging dogs, Canis lupus familiaris. While broad-scale properties of recombination appear similar to other mammalian species, our fine-scale estimates indicate that canine highly elevated recombination rates are observed in the vicinity of CpG rich regions including gene promoter regions, but show little association with H3K4 trimethylation marks identified in spermatocytes. By comparison to genomic data from the Andean fox, Lycalopex culpaeus, we show that biased gene conversion is a plausible mechanism by which the high CpG content of the dog genome could have occurred.     

The timing of sexual maturation among boys and girls in eastern Poland, 1980–2000: A rural–urban comparison

The aim of this study was to determine secular changes in the sexual maturation of children and adolescents from Eastern regions of Poland between 1980 and 2000, with special attention paid to rural–urban differences. Our sample comprised 34,055 girls and 28,100 boys from 9 to 18 years of age. The age at which each gender reached each stage of sexual maturation was examined, along with menarcheal age in girls. An increase in the rate of sexual maturation was observed over the 20-year period of this study. Menarcheal age in girls decreased by 0.59 years. The length of sexual maturation decreased: from 6.58 years to 3.85 years in girls and from 5.84 years to 3.65 years in boys. A significantly faster rate of sexual maturation was observed between 1990 and 2000. Over the entire 20-year period, adolescents living in rural settings experienced a slower rate of sexual maturation than did their urban peers.     

Flavodoxin cofactor binding induces structural changes that are required for protein–protein interactions with NADP+ oxidoreductase and pyruvate formate-lyase activating enzyme

Flavodoxin (Fld) conformational changes, thermal stability, and cofactor binding were studied using circular dichroism (CD), isothermal titration calorimetry (ITC), and limited proteolysis. Thermodynamics of apo and holo-Fld folding were examined to discern the features of this important electron transfer protein and to provide data on apo-Fld. With the exception of fluorescence and UV–vis binding experiments with its cofactor flavin mononucleotide (FMN), apo-Fld is almost completely uncharacterized in Escherichia coli. Fld is more structured when the FMN cofactor is bound; the association is tight and driven by enthalpy of binding. Surface plasmon resonance binding experiments were carried out under anaerobic conditions for both apo- and holo-Fld and demonstrate the importance of structure and conformation for the interaction with binding partners. Holo-Fld is capable of associating with NADP⁺-dependent flavodoxin oxidoreductase (FNR) and pyruvate formate-lyase activating enzyme (PFL-AE) whereas there is no detectable interaction between apo-Fld and either protein. Limited proteolysis experiments were analyzed by LC-MS to identify the regions in Fld that are involved in conformation changes upon cofactor binding. Docking software was used to model the Fld/PFL-AE complex to understand the interactions between these two proteins and gain insight into electron transfer reactions from Fld to PFL-AE.