Selection on plant optical traits and floral scent: Effects via seed development and antagonistic interactions

Evolutionary explanations of plant reproductive traits have usually emphasized optical characteristics of plants and selection mediated by pollinators. In recent years, studies have been broadened by incorporating also interactions with antagonists and by studying plant fragrant cues. Here, we examined if optical and fragrance traits of the perennial herb Primula veris correlated with reproductive success, in terms of fruit and seed set, and with avoidance of seed predators. Selection path analysis showed that both optical and fragrance traits influenced total seed production, and effects occurred both via fruit and seed set and via predator avoidance. In one case the same trait, inflorescence height, influenced total seed production both positively and negatively through effects on different components of fitness. Our results lend support to the notion that selection by mutualists and antagonists simultaneously acts on optical and fragrance traits.     

CD4+ and CD8+ T Cells Can Act Separately in Tumour Rejection after Immunization with Murine Pneumotropic Virus Chimeric Her2/neu Virus-Like Particles

Background

Immunization with murine pneumotropic virus virus-like particles carrying Her2/neu (Her2MPtVLPs) prevents tumour outgrowth in mice when given prophylactically, and therapeutically if combined with the adjuvant CpG. We investigated which components of the immune system are involved in tumour rejection, and whether long-term immunological memory can be obtained.

Methodology and Results

During the effector phase in BALB/c mice, only depletion of CD4⁺ and CD8⁺ in combination, with or without NK cells, completely abrogated tumour protection. Depletion of single CD4⁺, CD8⁺ or NK cell populations only had minor effects. During the immunization/induction phase, combined depletion of CD4⁺ and CD8⁺ cells abolished protection, while depletion of each individual subset had no or negligible effect. When tumour rejection was studied in knock-out mice with a C57Bl/6 background, protection was lost in CD4^−/−CD8^−/− and CD4^−/−, but not in CD8^−/− mice. In contrast, when normal C57Bl/6 mice were depleted of different cell types, protection was lost irrespective of whether only CD4⁺, only CD8⁺, or CD4⁺ and CD8⁺ cells in combination were eradicated. No anti-Her2/neu antibodies were detected but a Her2/neu-specific IFNγ response was seen. Studies of long-term memory showed that BALB/c mice could be protected against tumour development when immunized together with CpG as long as ten weeks before challenge.

Conclusion

Her2MPtVLP immunization is efficient in stimulating several compartments of the immune system, and induces an efficient immune response including long-term memory. In addition, when depleting mice of isolated cellular compartments, tumour protection is not as efficiently abolished as when depleting several immune compartments together.     

Hypertension, diabetes and overweight: looming legacies of the Biafran famine

Background

Sub-Saharan Africa is facing rapidly increasing prevalences of cardiovascular disease, obesity, diabetes and hypertension. Previous and ongoing undernutrition among pregnant women may contribute to this development as suggested by epidemiological studies from high income countries linking undernutrition in fetal life with increased burden of non-communicable diseases in later life. We undertook to study the risks for hypertension, glucose intolerance and overweight forty years after fetal exposure to famine afflicted Biafra during the Nigerian civil war (1967–1970).

Methods and Findings

Cohort study performed in June 27–July 31, 2009 in Enugu, Nigeria. Adults (n = 1,339) born before (1965–67), during (1968–January 1970), or after (1971–73) the years of famine were included. Blood pressure (BP), random plasma glucose (p-glucose) and anthropometrics, as well as prevalence of hypertension (BP>140/90 mmHg), impaired glucose tolerance (IGT; p-glucose 7.8–11.0 mmol/l), diabetes (DM; p-glucose ≥11.1 mmol/l), or overweight (BMI>25 kg/m²) were compared between the three groups. Fetal-infant exposure to famine was associated with elevated systolic (+7 mmHg; p<0.001) and diastolic (+5 mmHg; p<0.001) BP, increased p-glucose (+0.3 mmol/L; p<0.05) and waist circumference (+3cm, p<0.001), increased risk of systolic hypertension (adjusted OR 2.87; 95% CI 1.90–4.34), IGT (OR 1.65; 95% CI 1.02–2.69) and overweight (OR 1.41; 95% CI 1.03–1.93) as compared to people born after the famine. Limitations of this study include the lack of birth weight data and the inability to separate effects of fetal and infant famine.

Conclusions

Fetal and infant undernutrition is associated with significantly increased risk of hypertension and impaired glucose tolerance in 40-year-old Nigerians. Prevention of undernutrition during pregnancy and in infancy should therefore be given high priority in health, education, and economic agendas.     

Mice with experimental colitis show an altered metabolism with decreased metabolic rate

Patients with inflammatory bowel disease (IBD) suffer from body weight loss, malnutrition, and several other metabolic alterations affecting their quality of life. The aim of this study was to investigate the metabolic changes that may occur during acute and chronic colonic inflammation induced by dextran sulfate sodium (DSS) in mice. Clinical symptoms and inflammatory markers revealed the presence of an ongoing inflammatory response in the DSS-treated mice. Mice with acute inflammation had decreased body weight, respiratory exchange ratios (RER), food intake, and body fat content. Mice with chronic inflammation had decreased nutrient uptake, body fat content, locomotor activity, metabolic rates, and bone mineral density. Despite this, the body weight, food and water intake, lean mass, and RER of these mice returned to values similar to those in healthy controls. Thus, murine experimental colitis is associated with significant metabolic alterations similar to IBD patients. Our data show that the metabolic responses during acute and chronic inflammation are different, although the metabolic rate is reduced in both phases. These observations suggest compensatory metabolic alterations in chronic colitis resulting in a healthy appearance despite gross colon pathology.     

HLA Class I and II Expression in Oropharyngeal Squamous Cell Carcinoma in Relation to Tumor HPV Status and Clinical Outcome

HPV-DNA positive (HPV_DNA+) oropharyngeal squamous cell carcinoma (OSCC) has better clinical outcome than HPV-DNA negative (HPV_DNA-) OSCC. Current treatment may be unnecessarily extensive for most HPV+ OSCC, but before de-escalation, additional markers are needed together with HPV status to better predict treatment response. Here the influence of HLA class I/HLA class II expression was explored. Pre-treatment biopsies, from 439/484 OSCC patients diagnosed 2000-2009 and treated curatively, were analyzed for HLA I and II expression, p16^INK4a and HPV DNA. Absent/weak as compared to high HLA class I intensity correlated to a very favorable disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) in HPV_DNA+ OSCC, both in univariate and multivariate analysis, while HLA class II had no impact. Notably, HPV_DNA+ OSCC with absent/weak HLA class I responded equally well when treated with induction-chemo-radiotherapy (CRT) or radiotherapy (RT) alone. In patients with HPV_DNA- OSCC, high HLA class I/class II expression correlated in general to a better clinical outcome. p16^INK4a overexpression correlated to a better clinical outcome in HPV_DNA+ OSCC. Absence of HLA class I intensity in HPV_DNA+ OSCC suggests a very high survival independent of treatment and could possibly be used clinically to select patients for randomized trials de-escalating therapy.     

VEGF receptor signalling - in control of vascular function

Vascular endothelial growth-factor receptors (VEGFRs) regulate the cardiovascular system. VEGFR1 is required for the recruitment of haematopoietic precursors and migration of monocytes and macrophages, whereas VEGFR2 and VEGFR3 are essential for the functions of vascular endothelial and lymphendothelial cells, respectively. Recent insights have shed light onto VEGFR signal transduction and the interplay between different VEGFRs and VEGF co-receptors in development, adult physiology and disease.     

Genotypic diversity and migration patterns of Phytophthora infestans in the Nordic countries

In this study we investigated the genotypic diversity and the migration patterns of Phytophthora infestans in the Nordic countries. Isolates of P. infestans from outbreaks in 43 fields sampled in 2008 were collected using stratified sampling with country, field, and disease foci as the different strata. Microsatellites were used as markers to determine the genotypic variation in the sampled material. The results show a high genotypic variation of P. infestans in the Nordic countries with most of the genotypes found only once among the collected isolates. The major part of the genotypic variation was observed within the fields, with low differentiation between the fields. The observed low association of alleles among loci is consistent with frequent sexual reproduction of P. infestans in the Nordic countries. Coalescence analyses did not support a single common population for the four countries, thus indicating some degree of geographic differentiation. The analyses of migration patterns showed differing levels of gene flow among the Nordic countries. No correlation between migration rates and geographical distance could be seen. This could be explained by different degrees of genetic similarity between the pathogen populations in the different countries.     

Identification of a third human polyomavirus

We have previously reported on a system for large-scale molecular virus screening of clinical samples. As part of an effort to systematically search for unrecognized human pathogens, the technology was applied for virus screening of human respiratory tract samples. This resulted in the identification of a previously unknown polyomavirus provisionally named KI polyomavirus. The virus is phylogenetically related to other primate polyomaviruses in the early region of the genome but has very little homology (<30% amino acid identity) to known polyomaviruses in the late region. The virus was found by PCR in 6 (1%) of 637 nasopharyngeal aspirates and in 1 (0.5%) of 192 fecal samples but was not detected in sets of urine and blood samples. Since polyomaviruses have oncogenic potential and may produce severe disease in immunosuppressed individuals, continued searching for the virus in different medical contexts is important. This finding further illustrates how unbiased screening of respiratory tract samples can be used for the discovery of diverse virus types.     

Sex-specific mutation rates in salmonid fish

If germline mutations arise because of replication errors, the mutation rate may differ between males and females given that they differ in their number of germ cell divisions. As males of many higher organisms produce more gametes than females, this has led to the idea of "male-driven evolution." The extent of such male bias to the mutation rate is currently debated. For human some recent data suggest a very low bias, at a factor 1.7 only, while other approaches have given values of alpha(m) (the male-to-female mutation rate ratio) of 5, which is more close to what might be expected from male and female germ cell biology. Comparative analyses of sex-specific mutation rates in other organisms may be necessary for understanding the generality of an effect of sex and the number of germline DNA replications on the mutation rate. In this study we estimate for the first time sex-specific mutation rates in fish. Comparing the intronic substitution rates of the autosomal GH- 2 gene and its duplicated Y-linked and male-specific copy GH- 2Y (447-468 bp of each gene), we estimate alpha(m) to be 5.35-6.60 in salmonid fish of the genus Oncorhynchus. To the observations previously made among mammals and birds, this adds evidence from another class of vertebrates showing that a majority of mutations are of paternal origin. This would suggest that replication errors play a major role for the generation of new mutations.