Mechanisms of species coexistence: a field test of theoretical models using intertidal snails

Competitor coexistence is often facilitated by spatial segregation. Traditionally, spatial segregation is predicted to occur when species differ in the habitat in which they are either superior at competing for resources or less susceptible to predation. However, predictions from a behavioural model demonstrate that spatial segregation and coexistence can also occur in the absence of such interspecific trade‐offs in competitive ability and vulnerability to predation. Unlike other models of competitor coexistence this model predicts that when species rank both habitat productivity and ‘riskinesses’ similarly, but differ slightly in their habitat‐specific vulnerabilities to predators, they will tend to segregate across habitats, with the species experiencing the higher ratio of mortality risk across the habitats occurring primarily in the safer habitat. Here, we investigate the hypothesis that intraspecific trade‐offs between resource availability and mortality risk can lead to spatial segregation of competing species by (1) documenting the spatial (i.e. intertidal) distribution of two marine snails, Littorina sitkana and L. subrotundata and (2) performing field experiments to quantify growth and mortality rates of each species at ‘low’ and ‘high’ intertidal heights. Our results indicate that both species agree on the rankings of habitat riskiness and productivity, experiencing higher predation and higher growth in low‐ than in high‐intertidal habitats. However, L. sitkana and L. subrotundata experienced differences in their habitat‐specific mortality risks and growth rates. Despite both species being similarly at risk of predation in high‐intertidal habitats (where mortality was lower), L. subrotundata was subject to significantly higher mortality than L. sitkana at the low‐intertidal height. In contrast, growth rate differences between habitats were greater for L. sitkana than for L. subrotundata. Whereas both species grew at the same rate at the high‐intertidal level (where growth was lower), L. sitkana individuals grew more rapidly than L. subrotundata snails at the low‐intertidal level. As predicted by the behavioural model, the species that experienced the higher ratio of mortality across habitats (i.e. L. subrotundata) occurred exclusively in the safer, high‐intertidal habitat. Taken together, these results provide support for the hypothesis that spatial segregation, and potentially competitor coexistence, can occur in the absence of interspecific trade‐offs in resource acquisition ability or vulnerability to predation.     

Angiovision: Aortic stent-graft placement by augmented angionavigation

The endovascular treatment of abdominal aortic aneurysm (EVAR - EndoVascular Aneurism Repair) has become an alternative therapy to conventional open surgery. The objective of Angiovision project was to contribute to the improvement of EVAR procedures in terms of accuracy and customization of the interventional strategy. Our approach was mainly based on the use of patient-specific data, computer-aided endovascular navigation and numerical simulation. We proposed a new FEM-based patient-specific simulation solution to estimate the deformations caused by the introduction of stiff endovascular devices. We developed and implemented an original endovascular navigation system to augment the intraoperative fluoroscopy with the visualization of deformed preoperative aorto-iliac structure, and related information concerning vessel wall (calcifications), as well as stent-graft virtual deployment. The proposed solution, that requires only lightweight computer equipment, can be used in a standard operating room in order to optimize device placement (from a single angle of incidence). Evaluation is currently under way.     

High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction

Objectives

Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.

Approach and Results

Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = −0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = −0.265, p<0.001), but not when HDL levels were higher (r = −0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48–10.53), p<0.001), beyond traditional confounding factors.

Conclusions

Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.     

Microtubule alteration is an early cellular reaction to the metabolic challenge in ischemic cardiomyocytes

Cytoskeleton damage, particularly microtubule (MT) alterations, may play an important role in the pathogenesis of ischemia-induced myocardial injury. However, this disorganization has been scarcely confirmed in the cellular context. We evaluated MT network disassembly in myoblast cell line H9c2 and in neonatal rat cardiomyocytes in an in vitro substrate-free hypoxia model of simulated ischemia (SI). After different duration of SI from 30 up to 180 min, the cells were fixed and the microtubule network was revealed by immunocytochemistry. The microtubule alterations were quantified using a house-developed image analysis program. Additionally, the tubulin fraction were extracted and quantified by Western blotting. The cell respiration, the release of cellular LDH and the cell viability were evaluated at the same periods. An early MT disassembly was observed after 60 min of SI. The decrease in MT fluorescence intensity at 60 and 90 min was correlated with a microtubule disassembly. Conversely, SI-induced significant LDH release (35%) and decrease in cell viability (34%) occurred after 120 min only. These results suggest that the simulated ischemia-induced changes in MT network should not be considered as an ultrastructural hallmark of the cell injury and could rather be an early ultrastructural correlate of the cellular reaction to the metabolic challenge.     

UVA-induced cyclobutane pyrimidine dimers form predominantly at thymine-thymine dipyrimidines and correlate with the mutation spectrum in rodent cells

Ligation-mediated PCR was employed to quantify cyclobutane pyrimidine dimer (CPD) formation at nucleotide resolution along exon 2 of the adenine phosphoribosyltransferase (aprt) locus in Chinese hamster ovary (CHO) cells following irradiation with either UVA (340–400 nm), UVB (295–320 nm), UVC (254 nm) or simulated sunlight (SSL; λ > 295 nm). The resulting DNA damage spectrum for each wavelength region was then aligned with the corresponding mutational spectrum generated previously in the same genetic target. The DNA sequence specificities of CPD formation induced by UVC, UVB or SSL were very similar, i.e., in each case the overall relative proportion of this photoproduct forming at TT, TC, CT and CC sites was ~28, ~26, ~16 and ~30%, respectively. Furthermore, a clear correspondence was noted between the precise locations of CPD damage hotspots, and of ‘UV signature’ mutational hotspots consisting primarily of C→T and CC→TT transitions within pyrimidine runs. However, following UVA exposure, in strong contrast to the above situation for UVC, UVB or SSL, CPDs were generated much more frequently at TT sites than at TC, CT or CC sites (57% versus 18, 11 and 14%, respectively). This CPD deposition pattern correlates well with the strikingly high proportion of mutations recovered opposite TT dipyrimidines in UVA- irradiated CHO cells. Our results directly implicate the CPD as a major promutagenic DNA photoproduct induced specifically by UVA in rodent cells.     

Identification and quantification of free radicals during myocardial ischemia and reperfusion using electron paramagnetic resonance spectroscopy

There is general agreement that free radicals are involved in reperfusion injury. Electron paramagnetic resonance (EPR) spectroscopy can be considered as the more suitable technique to directly measure and characterize free radical generation during myocardial ischemia and reperfusion. There are essentially two approaches used in the detection of unstable reactive species: freezing technique and spin traps. The detection of secondary free radicals or ascorbyl free radicals during reperfusion might provide an index of oxidative stress. Spin trapping can also characterize nitric oxide. EPR spectroscopy can provide important data regarding redox state and free radical metabolism but ideally, the spin traps must not interfere with cell or organism function.     

Structure-activity relationship of biaryl acylsulfonamide analogues on the human EP(3) prostanoid receptor

Potent and selective ligands for the human EP3 prostanoid receptor are described. Biaryl compounds bearing a tethered ortho substituted acidic moiety were identified as potent EP3 antagonists based on the SAR described herein. The binding affinity of key compounds on all eight human prostanoid receptors is reported.     

Gamma-secretase: substrates and inhibitors

The amyloid β-protein (Aβ) deposited in Alzheimer’s disease (AD), the most common form of dementia in the elderly, is a secreted proteolytic product of the amyloid β-protein precursor (APP). Generation of Aβ from the APP requires two sequential proteolytic events, β-secretase cleavage to generate the amino terminus, followed by γ-secretase cleavage to generate the carboxyl terminus. Because this process is a central event in the pathogenesis of AD, γ-secretase is believed to be an excellent therapeutic target. γ-Secretase activity has been demonstrated to be membrane-associated, with the cleavage site primarily determined by the location of the substrate with respect to the membrane. It has also been shown that this unusual proteolytic activity not only occurs for APP, but also for proteins involved in morphogenic processes or cell proliferation and differentiation such as Notch and ErbB4. Thus far, all γ-secretase substrates are involved in some form of nuclear signaling. These recent findings have important implications for the development of pharmacological interventions that target γ-secretase.     

Synthesis and NMR solution structure of an alpha-helical hairpin stapled with two disulfide bridges

Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of alpha-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, alpha2p8, encompassing the alpha-helical hairpin present in the structure of p8MTCP1, as an alpha-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of alpha2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65+/-0.25 and 1.51+/-0.21 A, respectively. Excised from its protein context, the alpha-hairpin keeps its native structure: an alpha-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25-36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This alpha-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries.