Population dynamics in a cyclic environment: consequences of cyclic food abundance on tawny owl reproduction and survival

1. Understanding which factors regulate population dynamics may help us to understand how a population would respond to environmental change, and why some populations are declining.
2. In southern Finland, vole abundance shows a three-phased cycle of low, increase and decrease phases, but these have been fading out in recent years. During five such cycles (1981–1995), all tawny owls Strix aluco were censused in a 250-km² study area, and their reproduction and survival were monitored.
3. Males and females showed similar dynamics, but experienced breeders recruited more offspring and had higher survival than first breeders. Offspring recruitment, but not survival of breeding individuals varied in accordance with vole abundance.
4. The population's numerical response to prey abundance was primarily due to first-breeding individuals entering the population in the increase phase when immigration was the highest. First-breeding birds were younger, but experienced breeders were older in more favourable vole years.
5. A stage-specific matrix population model integrating survival and fecundity showed that, despite obvious variation in fecundity between vole cycle phases, this variation had limited importance for overall tawny owl population dynamics, but that the survival of experienced breeders during the low phase is most important for population growth.
6. Model and data agreed that the vole cycle drives the dynamics of this avian predator by limiting the recruitment of new breeders during the low phase. Population dynamics hence differ not only from the classic example of the species in a more temperate region in the UK where the number of territories is stable across years, but also from the dynamics of other avian vole predators in Fennoscandia where the recurring crash in vole abundance drastically lowers adult survival thereby creating vacancies.     

Analysis of diversity and linkage disequilibrium along chromosome 3B of bread wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

A highly polymorphic core collection of bread wheat and a more narrow-based breeding material, gathered from pedigrees of seven modern cultivars, was analysed in order to compare genetic diversity indices and linkage disequilibrium (LD) patterns along the chromosome 3B with microsatellite (SSR) and Diversity Arrays Technology markers. Five ancestral gene pools could be identified within the core collection, indicating a strong geographical structure (Northwest Europe, Southeast Europe, CIMMYT–ICARDA group, Asia, Nepal). The breeding material showed a temporal structure, corresponding to different periods of breeding programmes [old varieties (from old landraces to 1919), semi-modern varieties (1920–1959), modern varieties (1960–2006)]. Basic statistics showed a higher genetic diversity in the core collection than in the breeding material, indicating a stronger selection pressure in this latter material. More generally, the chromosome 3B had a lower diversity than the whole B-genome. LD was weak in all studied materials. Amongst geographical groups, the CIMMYT–ICARDA pool presented the longest ranged LD in contrast to Asian accessions. In the breeding material, LD increased from old cultivars to modern varieties. Genitors of seven modern cultivars were found to be different; most marker pairs in significant LD were observed amongst genitors of Alexandre and Koreli varieties, indicating an important inbreeding effect. At low genetic distances (0–5 cM), the breeding material had higher LD than the core collection, but globally the two materials had similar values in all classes. Marker pairs in significant LD are generally observed around the centromere in both arms and at distal position on the short arm of the chromosome 3B.     

NMR structure of the viral peptide linked to the genome (VPg) of poliovirus

VPgs are essential for replication of picornaviruses, which cause diseases such as poliomyelitis, foot and mouth disease, and the common cold. VPg in infected cells is covalently linked to the 5' end of the viral RNA, or, in a uridylylated form, free in the cytoplasm. We show here the first solution structure for a picornaviral VPg, that of the 22-residue peptide from poliovirus serotype 1. VPg in buffer is inherently flexible, but a single conformer was obtained by adding trimethylamine N-oxide (TMAO). TMAO had only minor effects on the TOCSY spectrum. However, it increased the amount of structured peptide, as indicated by more peaks in the NOESY spectrum and an up to 300% increase in the ratio of normalized NOE cross peak intensities to that in buffer. The data for VPg in TMAO yielded a well defined structure bundle with 0.6 A RMSD (versus 6.6 A in buffer alone), with 10-30 unambiguous constraints per residue. The structure consists of a large loop region from residues 1 to 14, from which the reactive tyrosinate projects outward, and a C-terminal helix from residues 18 to 21 that aligns the sidechains of conserved residues on one face. The structure has a stable docking position at an area on the poliovirus polymerase crystal structure identified as a VPg binding site by mutagenesis studies. Further, UTP and ATP dock in a base-specific manner to the reactive face of VPg, held in place by residues conserved in all picornavirus VPgs.     

Glucose Metabolism, Hyperosmotic Stress, and Reprogramming of Somatic Cells

The availability of glucose and oxygen are important regulatory elements that help directing stem cell fate. In the undifferentiated state, stem cells, and their artificially reprogrammed equivalent-induced pluripotent stem cells (iPS) are characterized by limited oxidative capacity and active anaerobic glycolysis. Recent studies have shown that pluripotency—a characteristic of staminality—is associated with a poorly developed mitochondrial patrimony, while differentiation is accompanied by an activation of mitochondrial biogenesis. Besides being an important energy source in hypoxia, high glucose level results in hyperosmotic stress. The identification of specific metabolic pathways and biophysical factors that regulate stem cell fate, including high glucose in the extracellular medium, may therefore facilitate reprogramming efficiency and control the differentiation and fate of iPS cells, which are increasingly being explored as therapeutic tools. In this article, we review recent knowledge of the role of glucose metabolism and high glucose level as major anaerobic energy source, and a determinant of osmolarity as possible tools for reprogramming therapies in clinical applications. As in the diabetic setting hyperglycemia negatively affect the stem/progenitor cell fate and likely somatic reprogramming, we also discuss the in vivo potential transferability of the available in vitro findings.     

Optimizing the concentration and bolus of a drug delivered by continuous infusion

We consider treatment regimes in which an agent is administered continuously at a specified concentration until either a response is achieved or a predetermined maximum infusion time is reached. Response is an event defined to characterize therapeutic efficacy. A portion of the maximum planned total amount administered is given as an initial bolus. For such regimes, the amount of the agent received by the patient depends on the time to response. An additional complication when response is evaluated periodically rather than continuously is that the response time is interval censored. We address the problem of designing a clinical trial in which such response time data and a binary indicator of toxicity are used together to jointly optimize the concentration and the size of the bolus. We propose a sequentially adaptive Bayesian design that chooses the optimal treatment for successive patients by maximizing the posterior mean utility of the joint efficacy-toxicity outcome. The methodology is illustrated by a trial in which tissue plasminogen activator is infused intraarterially as rapid treatment for acute ischemic stroke.     

Rap1 promotes endothelial mechanosensing complex formation,NO release and normal endothelial function

Decreased nitric oxide (NO) bioavailability underlies a number of cardiovascular pathologies, including hypertension. The shear stress exerted by flowing blood is the main determinant of NO release. Rap1 promotes integrin‐ and cadherin‐mediated signaling. Here, we show that Rap1 is a critical regulator of NO production and endothelial function. Rap1 deficiency in murine endothelium attenuates NO production and diminishes NO‐dependent vasodilation, leading to endothelial dysfunction and hypertension, without deleterious effects on vessel integrity. Mechanistically, Rap1 is activated by shear stress, promotes the formation of the endothelial mechanosensing complex—comprised of PECAM‐1, VE‐cadherin and VEGFR2‐ and downstream signaling to NO production. Our study establishes a novel paradigm for Rap1 as a regulator of mechanotransduction.     

PCR detection of nearly any dengue virus strain using a highly sensitive primer 'cocktail'

PCR detection of viral pathogens is extremely useful, but suffers from the challenge of detecting the many variant strains of a given virus that arise over time. Here, we report the computational derivation and initial experimental testing of a combination of 10 PCR primers to be used in a single high-sensitivity mixed PCR reaction for the detection of dengue virus. Primer sequences were computed such that their probability of mispriming with human DNA is extremely low. A 'cocktail' of 10 primers was shown experimentally to be able to detect cDNA clones representing the four serotypes and dengue virus RNA spiked into total human whole blood RNA. Computationally, the primers are predicted to detect 95% of the 1688 dengue strains analyzed (with perfect primer match). Allowing up to one mismatch and one insertion per primer, the primer set detects 99% of strains. Primer sets from three previous studies have been compared with the present set of primers and their relative sensitivity for dengue virus is discussed. These results provide the formulation and demonstration of a mixed primer PCR reagent that may enable the detection of nearly any dengue strain irrespective of serotype, in a single PCR reaction, and illustrate an approach to the broad problem of detecting highly mutable RNA viruses.     

Inducible kidney-specific Sgk1 knockout mice show a salt-losing phenotype

The expression of the serum- and glucocorticoid-regulated kinase 1 (Sgk1) is induced by mineralocorticoids and, in turn, upregulates the renal epithelial Na(+) channel (ENaC). Total inactivation of Sgk1 has been associated with transient urinary Na(+) wasting with a low-Na(+) diet, while the aldosterone-mediated ENaC channel activation was unchanged in the collecting duct. Since Sgk1 is ubiquitously expressed, we aimed to study the role of renal Sgk1 and generated an inducible kidney-specific knockout (KO) mouse. We took advantage of the previously described TetOn/CreLoxP system, in which rtTA is under the control of the Pax8 promotor, allowing inducible inactivation of the floxed Sgk1 allele in the renal tubules (Sgk1fl/fl/Pax8/LC1 mice). We found that under a standard Na(+) diet, renal water and Na(+)/K(+) excretion had a tendency to be higher in doxycycline-treated Sgk1 KO mice compared with control mice. The impaired ability of Sgk1 KO mice to retain Na(+) increased significantly with a low-salt diet despite higher plasma aldosterone levels. On a low-Na(+) diet, the Sgk1 KO mice were also hyperkaliuric and lost body weight. This phenotype was accompanied by a decrease in systolic and diastolic blood pressure. At the protein level, we observed a reduction in phosphorylation of the ubiquitin protein-ligase Nedd4-2 and a decrease in the expression of the Na(+)-Cl(-)-cotransporter (NCC) and to a lesser extent of ENaC.