Proceedings of the XIth International Symposium on Fossil Cnidaria and Porifera, Liege, Belgium, August 19-29, 2011: Preface

peer reviewe

Regulation and Innovation: Approaching Market Failure from Both Sides

Regulation is often claimed to be the enemy of socially desirable in-novation because of factors including innovation’s unpredictability and regulation’s compliance costs. In this essay, we bring two intellectual property scholars’ perspectives to bear on the question of regulation’s impact on innovation. We offer a novel, yet intuitive, analytical frame-work that takes both market demand failures, and failures of supplier appropriability into account. Traditionally, regulation seeks to mitigate market failures that create deviations between the demand portfolio perceived by suppliers and the socially optimal demand portfolio. Studies of the interplay between regulation and innovation have mostly taken this perspective, considering the impact of various regulatory transaction and compliance costs on innovation. Intellectual property law and competition law target a different sort of problem, where markets fail to supply products and services at competitive prices or to undertake innovative activities because of supplier appropriability issues

New insights into the phosphorylation of the threonine motif of the β1 integrin cytoplasmic domain

Integrins require an activation step before ligand binding and signaling that is mediated by talin and kindlin binding to the beta integrin cytosolic domain (beta-tail). Conflicting reports exist about the contribution of phosphorylation of a conserved threonine motif in the beta 1-tail (beta 1-pT788/pT789) to integrin activation. We show that widely used and commercially available antibodies against beta 1-pT788/pT789 integrin do not detect specific beta 1-pT788/ pT789 integrin signals in immunoblots of several human and mouse cell lysates but bind bi-phosphorylated threonine resi-dues in numerous proteins, which were identified by mass spectrometry experiments. Furthermore, we found that fibro-blasts and epithelial cells expressing the phospho-mimicking beta 1-TT788/789DD integrin failed to activate beta 1 integrins and displayed reduced integrin ligand binding, adhesion initiation and cell spreading. These cellular defects are specifically caused by the inability of kindlin to bind beta 1-tail polypeptides carrying a phosphorylated threonine motif or phospho-mimicking TT788/789DD substitutions. Our findings indicate that the double-threonine motif in beta 1-class integrins is not a major phosphory-lation site but if phosphorylated would curb integrin function

Edouard Poty: a bio- and bibliography

peer reviewe

Survival of MUTYH-Associated Polyposis Patients With Colorectal Cancer and Matched Control Colorectal Cancer Patients

Background: MUTYH-associated polyposis is a recessively inherited disorder characterized by a lifetime risk of colorectal cancer that is up to 100%. Because specific histological and molecular genetic features of MUTYH-associated polyposis colorectal cancers might influence tumor behavior and patient survival, we compared survival between patients with MUTYH-associated polyposis colorectal cancer and matched control patients with colorectal cancer from the general population. Method:s In this retrospective multicenter cohort study from Europe, 147 patients with MUTYH-associated polyposis colorectal cancer were compared with 272 population-based control patients with colorectal cancer who were matched for country, age at diagnosis, year of diagnosis, stage, and subsite of colorectal cancer. Kaplan–Meier survival and Cox regression analyses were used to compare survival between patients with MUTYH-associated polyposis colorectal cancer and control patients with colorectal cancer. All statistical tests were two-sided. Results: Five-year survival for patients with MUTYH-associated polyposis colorectal cancer was 78% (95% confidence interval [CI] = 70% to 84%) and for control patients was 63% (95% CI = 56% to 69%) (log-rank test, P = .002). After adjustment for differences in age, stage, sex, subsite, country, and year of diagnosis, survival remained better for MUTYH-associated polyposis colorectal cancer patients than for control patients (hazard ratio of death = 0.48, 95% CI = 0.32 to 0.72). Conclusions: In a European study cohort, we found statistically significantly better survival for patients with MUTYH-associated polyposis colorectal cancer than for matched control patients with colorectal cancer

Low pressure radiofrequency balloon angioplasty: Evaluation in porcine peripheral arteries

AbstractObjectives. The purpose of this study was to evaluate the efficacy of radiofrequency-powered thermal balloon angioplasty in an in vivo porcine model.Background. Various modes of thermal energy used adjunctively during balloon angioplasty have demonstrated the potential to enhance the results of acute lumen dilation.Methods. In normal pigs, 75 peripheral arteries were dilated with a newly designed, radiofrequency-powered, thermal angioplasty balloon. All inflations were performed at 2-atm pressure for 85 s. Dilations were performed either with (hot) or without (cold) the application of heat. Lumen dimensions and vessel morphology were assessed with intravascular ultrasonography. At the end of each study, dilated arterial segments were harvested for histologic examination.Results. Single cold balloon inflations resulted in a 12.7% increase in arterial cross-sectional area whereas single hot inflations resulted in a 22.9% increase (p < 0.03). Similarly, when multiple cold inflations were compared with multiple hot inflations, two, three and four sequential hot inflations resulted in a significantly greater increase in cross-sectional area than an equivalent number of cold inflations (p < 0.03).Histologic examination demonstrated a temperaturedependent effect on the depth of medial necrosis and extent of arterial wall thinning (p < 0.001) as well as evidence for uniform alteration of elastic tissue fibers at temperatures of ≥60 °C (p < 0.03).Conclusions. Low pressure radiofrequency thermal balloon angioplasty results in a greater increase in cross-sectional area in porcine peripheral arteries than does nonheated conventional balloon angioplasty. The pathologic basis for this enhanced dilation may be a temperature-dependent effect on medial necrosis, thinning of the arterial wall or alteration of vascular elastic fibers, alone or in combination

The longest delay: Re-emergence of coral reef ecosystems after the Late Devonian extinctions

Reefs are an excellent tool for tracking marine-ecosystem changes, especially through mass extinction transitions. Although metazoan reefs proliferated during the Phanerozoic, prolonged metazoan reef-recovery intervals often occurred after extinction events. Here, we document and review the reef-recovery interval following the Late Devonian Frasnian-Famennian (Kellwasser) and end-Famennian (Hangenberg) mass extinctions, which eliminated the largest area of metazoan (stromatoporoid-coral) reefs of the Phanerozoic. Previous reports of the late Visean coral bioconstructions from western Palaeotethys Ocean, may mark the first metazoan reef proliferation after the Hangenberg extinction. In this study, abundant coral reefs, coral frameworks and coral biostromes were described in detail for the first time from the late Visean strata on the South China Block (eastern Palaeotethys Ocean). The occurrence of these coral bioconstructions further suggests that the late Visean coral reef recovery may have been a widespread phenomenon. Based on the high-resolution reef database constructed in this study, three sub-intervals of the Mississippian metazoan reef recovery were distinguished, which are (1) metazoan “reef gap” phase (MRG) without metazoan reefs during the Tournaisian; (2) metazoan reef re-establishment phase (MRR) containing a few metazoan reefs from early Visean to early part of the late Visean; and (3) metazoan reef proliferation phase (MRP) with global coral reef flourishment during the middle part of the late Visean (late Asbian to early Brigantian substages). Hence, coral reef ecosystems proliferated and became dominant in marine ecosystems during the late Asbian to early Brigantian, indicating a prolonged metazoan reef recovery of about 12 Ma and 23 Ma until the MRR and MRP, respectively. Coral reef proliferation at this time shows that the Mississippian was not solely a period dominated by microbial reefs. Late Visean coral reef development coincided with increased nektonic and benthic diversity, showing that metazoan reef recovery closely tracked overall marine ecosystem evolution. Even compared with other slow reef-recovery intervals, such as the middle-late Cambrian and Early-Middle Triassic with the intervals until the MRR and MRP of 5 Ma and 2 Ma, and 15 Ma and 9 Ma respectively, the Mississippian metazoan reef recovery was the longest in reef history. Harsh climatic and oceanic conditions were present during the Mississippian, mainly including the widespread marine anoxia during the middle part of Tournaisian and the following recurrent glacial and interglacial climatic episodes with frequent changes in sea level, sedimentary facies and sea-water surface temperature, which may have stymied metazoan reef recovery during this time. During the late Visean, marine communities flourished during a phase of relative warm conditions and high sea level, and coincided with the long-delayed re-emergence of coral reef ecosystems after the Late Devonian extinctions

The correlation potential of magnetic susceptibility and outcrop gamma-ray logs at Tournaisian-Viséan boundary sections in western Europe

We have measured five deep-water carbonate and carbonate-siliciclastic sections at the Tournaisian-Visean (Tn/V) boundary in western Europe, using petrophysical outcrop logging techniques (gamma-ray spectrometry /GRS/ and magnetic susceptibility /MS/). The aim was to trace correlatable log patterns across the flanks of the London-Brabant Massif from eastern Ireland to western Germany. Both GRS and MS logging proved useful for long-distance (up to similar to 1000 km) correlation. The log patterns can be interpreted in terms of sea-level fluctuations. A late Tournaisian regression, a sequence boundary at the Tn/V boundary, early Visean lowstand systems tract and an overlying transgressive to regressive succession can be identified from the GRS and MS logs. The Tn/V sequence boundary can be correlated with exposure features and karstic surfaces in the up-dip shallow-water settings at the boundary between sequence 4 and 5 of Hance et al. (2001, 2002). This indicates that sea-level fluctuations around the Tn/V boundary were synchronous and traceable on the flanks of the London-Brabant Massif. The GRS-based logging has a greater correlation potential than MS as it can be applied in a broad spectrum of facies and depositional settings. In certain sections, the MS signal shows an increasing trend during transgression and a decreasing during regression, which is opposite to the MS paradigm from shallow-water carbonate platform settings. These trends are assumed to result from landward/basinward facies shifts of low-productivity carbonate ramp systems. Lowstand shedding of carbonate tempestites and turbidites results in low MS values while during sea-level rise the ramp systems backstep, developing retrograding facies successions in their distal parts, which are associated with upward-increasing MS values

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group