Evidence for reductive genome evolution and lateral acquisition of virulence functions in two Corynebacterium pseudotuberculosis strains

Background

Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity.

Methodology and Findings

We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer.

Conclusions

These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers {"type":"entrez-nucleotide","attrs":{"text":"CP001809","term_id":"340539261","term_text":"CP001809"}}CP001809 and {"type":"entrez-nucleotide","attrs":{"text":"CP001829","term_id":"302205157","term_text":"CP001829"}}CP001829.     

Visual perceptual difficulties and under-achievement at school in a large community-based sample of children

Introduction

Difficulties with visual perception (VP) are often described in children with neurological or developmental problems. However, there are few data regarding the range of visual perceptual abilities in populations of normal children, or on the impact of these abilities on children''s day-to-day functioning.

Methods

Data were obtained for 4512 participants in an ongoing birth cohort study (Avon Longitudinal Study of Parents and Children; ALSPAC). The children''s mothers responded to questions designed to elicit indications of visual perceptual difficulties or immaturity, when their children were aged 13 years. We examined associations with standardised school test results in reading and in mathematics at age 13–14 years (SATS-KS3), accounting for potential confounders including IQ.

Results

Three underlying factors explained half the variance in the VP question responses. These correlated best with questions on interpreting cluttered scenes; guidance of movement and face recognition. The adjusted parameter estimates (95% CI) for the cluttered-scenes factor (0.05; 0.02 to 0.08; p<0.001) suggested positive associations with the reading test results whilst that for the guidance-of-movement factor (0.03; 0.00 to 0.06; p = 0.026) suggested positive association with the mathematics results. The raw scores were associated with both test results.

Discussion

VP abilities were widely distributed in this sample of 13-year old children. Lower levels of VP function were associated with under-achievement in reading and in mathematics. Simple interventions can help children with VP difficulties, so research is needed into practicable, cost-effective strategies for identification and assessment, so that support can be targeted appropriately.     

Crocodiles in the Sahara desert: an update of distribution, habitats and population status for conservation planning in Mauritania

Background

Relict populations of Crocodylus niloticus persist in Chad, Egypt and Mauritania. Although crocodiles were widespread throughout the Sahara until the early 20^th century, increased aridity combined with human persecution led to local extinction. Knowledge on distribution, occupied habitats, population size and prey availability is scarce in most populations. This study evaluates the status of Saharan crocodiles and provides new data for Mauritania to assist conservation planning.

Methodology/Principal Findings

A series of surveys in Mauritania detected crocodile presence in 78 localities dispersed across 10 river basins and most tended to be isolated within river basins. Permanent gueltas and seasonal tâmoûrts were the most common occupied habitats. Crocodile encounters ranged from one to more than 20 individuals, but in most localities less than five crocodiles were observed. Larger numbers were observed after the rainy season and during night sampling. Crocodiles were found dead in between water points along dry river-beds suggesting the occurrence of dispersal.

Conclusion/Significance

Research priorities in Chad and Egypt should focus on quantifying population size and pressures exerted on habitats. The present study increased in by 35% the number of known crocodile localities in Mauritania. Gueltas are crucial for the persistence of mountain populations. Oscillations in water availability throughout the year and the small dimensions of gueltas affect biological traits, including activity and body size. Studies are needed to understand adaptation traits of desert populations. Molecular analyses are needed to quantify genetic variability, population sub-structuring and effective population size, and detect the occurrence of gene flow. Monitoring is needed to detect demographical and genetical trends in completely isolated populations. Crocodiles are apparently vulnerable during dispersal events. Awareness campaigns focusing on the vulnerability and relict value of crocodiles should be implemented. Classification of Mauritanian mountains as protected areas should be prioritised.     

Mode of effective connectivity within a putative neural network differentiates moral cognitions related to care and justice ethics

Background

Moral sensitivity refers to the interpretive awareness of moral conflict and can be justice or care oriented. Justice ethics is associated primarily with human rights and the application of moral rules, whereas care ethics is related to human needs and a situational approach involving social emotions. Among the core brain regions involved in moral issue processing are: medial prefrontal cortex, anterior (ACC) and posterior (PCC) cingulate cortex, posterior superior temporal sulcus (pSTS), insula and amygdala. This study sought to inform the long standing debate of whether care and justice moral ethics represent one or two different forms of cognition.

Methodology/Principal Findings

Model-free and model-based connectivity analysis were used to identify functional neural networks underlying care and justice ethics for a moral sensitivity task. In addition to modest differences in patterns of associated neural activity, distinct modes of functional and effective connectivity were observed for moral sensitivity for care and justice issues that were modulated by individual variation in moral ability.

Conclusions/Significance

These results support a neurobiological differentiation between care and justice ethics and suggest that human moral behavior reflects the outcome of integrating opposing rule-based, self-other perspectives, and emotional responses.     

FTO and MC4R gene variants are associated with obesity in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one offspring with PCOS were genotyped for 15 SNPs previously shown to be associated with obesity. Linkage and association with PCOS was assessed using the transmission/disequilibrium test (TDT). These SNPs were also analyzed in an independent case-control study involving 395 women with PCOS and 176 healthy women with regular menstrual cycles. Only one of these 15 SNPs (rs2815752 in NEGR1) was found to have a nominally significant association with PCOS (χ² = 6.11, P = 0.013), but this association failed to replicate in the case-control study. While not associated with PCOS itself, five SNPs in FTO and two in MC4R were associated with BMI as assessed with a quantitative-TDT analysis, several of which replicated association with BMI in the case-control cohort. These findings demonstrate that certain SNPs associated with obesity contribute to elevated BMI in PCOS, but do not appear to play a major role in PCOS per se. These findings support the notion that PCOS phenotypes are a consequence of an oligogenic/polygenic mechanism.     

Predicted impact of barriers to migration on the Serengeti wildebeest population

The Serengeti wildebeest migration is a rare and spectacular example of a once-common biological phenomenon. A proposed road project threatens to bisect the Serengeti ecosystem and its integrity. The precautionary principle dictates that we consider the possible consequences of a road completely disrupting the migration. We used an existing spatially-explicit simulation model of wildebeest movement and population dynamics to explore how placing a barrier to migration across the proposed route (thus creating two disjoint but mobile subpopulations) might affect the long-term size of the wildebeest population. Our simulation results suggest that a barrier to migration--even without causing habitat loss--could cause the wildebeest population to decline by about a third. The driver of this decline is the effect of habitat fragmentation (even without habitat loss) on the ability of wildebeest to effectively track temporal shifts in high-quality forage resources across the landscape. Given the important role of the wildebeest migration for a number of key ecological processes, these findings have potentially important ramifications for ecosystem biodiversity, structure, and function in the Serengeti.     

QAPgrid: a two level QAP-based approach for large-scale data analysis and visualization

Background

The visualization of large volumes of data is a computationally challenging task that often promises rewarding new insights. There is great potential in the application of new algorithms and models from combinatorial optimisation. Datasets often contain “hidden regularities” and a combined identification and visualization method should reveal these structures and present them in a way that helps analysis. While several methodologies exist, including those that use non-linear optimization algorithms, severe limitations exist even when working with only a few hundred objects.

Methodology/Principal Findings

We present a new data visualization approach (QAPgrid) that reveals patterns of similarities and differences in large datasets of objects for which a similarity measure can be computed. Objects are assigned to positions on an underlying square grid in a two-dimensional space. We use the Quadratic Assignment Problem (QAP) as a mathematical model to provide an objective function for assignment of objects to positions on the grid. We employ a Memetic Algorithm (a powerful metaheuristic) to tackle the large instances of this NP-hard combinatorial optimization problem, and we show its performance on the visualization of real data sets.

Conclusions/Significance

Overall, the results show that QAPgrid algorithm is able to produce a layout that represents the relationships between objects in the data set. Furthermore, it also represents the relationships between clusters that are feed into the algorithm. We apply the QAPgrid on the 84 Indo-European languages instance, producing a near-optimal layout. Next, we produce a layout of 470 world universities with an observed high degree of correlation with the score used by the Academic Ranking of World Universities compiled in the The Shanghai Jiao Tong University Academic Ranking of World Universities without the need of an ad hoc weighting of attributes. Finally, our Gene Ontology-based study on Saccharomyces cerevisiae fully demonstrates the scalability and precision of our method as a novel alternative tool for functional genomics.     

Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors

Background

Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively.

Principal Findings

The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity.

Conclusions

According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.     

Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity

Introduction

Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes.

Research Design and Methods

Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs.

Results

Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes.

Conclusions

Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and proliferation of new preadipocytes. This phenomenon may reflect the in vivo plasticity of adipose tissue in which ATMs play an additional role during inflammation and other disease states. Understanding this novel pathway could influence adipogenesis, leading to new treatments for obesity, inflammation, and type 2 diabetes.