The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

Current use of cardiac magnetic resonance in tertiary referral centres for the diagnosis of cardiomyopathy: the ESC EORP Cardiomyopathy/Myocarditis Registry.

ims: Cardiac magnetic resonance (CMR) is recommended in the diagnosis of cardiomyopathies, but it is time-consuming, expensive, and limited in availability in some European regions. The aim of this study was to determine the use of CMR in cardiomyopathy patients enrolled into the European Society of Cardiology (ESC) cardiomyopathy registry [part of the EURObservational Research Programme (EORP)]. Methods and results: Three thousand, two hundred, and eight consecutive adult patients (34.6% female; median age: 53.0 ± 15 years) with cardiomyopathy were studied: 1260 with dilated (DCM), 1739 with hypertrophic (HCM), 66 with restrictive (RCM), and 143 with arrhythmogenic right ventricular cardiomyopathy (ARVC). CMR scans were performed at baseline in only 29.4% of patients. CMR utilization was variable according to cardiomyopathy subtypes: from 51.1% in ARVC to 36.4% in RCM, 33.8% in HCM, and 20.6% in DCM (P < 0.001). CMR use in tertiary referral centres located in different European countries varied from 1% to 63.2%. Patients undergoing CMR were younger, less symptomatic, less frequently had implantable cardioverter-defibrillator (ICD)/pacemaker implanted, had fewer cardiovascular risk factors and comorbidities (P < 0.001). In 28.6% of patients, CMR was used along with transthoracic echocardiography (TTE); 67.6% patients underwent TTE alone, and 0.9% only CMR. Conclusion: Less than one-third of patients enrolled in the registry underwent CMR and the use varied greatly between cardiomyopathy subtypes, clinical profiles of patients, and European tertiary referral centres. This gap with current guidelines needs to be considered carefully by scientific societies to promote wider availability and use of CMR in patients with cardiomyopathies

Prospective follow-up in various subtypes of cardiomyopathies: Insights from the ESC EORP Cardiomyopathy Registry

Aims: The European Society of Cardiology (ESC) European Observational Research Programme (EORP) Cardiomyopathy Registry is a prospective multinational registry of consecutive patients with cardiomyopathies. The objective of this report is to describe the short-term outcomes of adult patients (≥18 years old). Methods and results: Out of 3208 patients recruited, follow-up data at 1 year were obtained in 2713 patients (84.6%) [1420 with hypertrophic (HCM); 1105 dilated (DCM); 128 arrhythmogenic right ventricular (ARVC); and 60 restrictive (RCM) cardiomyopathies]. Improvement of symptoms (dyspnoea, chest pain, and palpitations) was globally observed over time (P < 0.05 for each). Additional invasive procedures were performed: prophylactic implantation of implantable cardioverter-defibrillator (ICD) (5.2%), pacemaker (1.2%), heart transplant (1.1%), ablation for atrial or ventricular arrhythmia (0.5% and 0.1%). Patients with atrial fibrillation increased from 28.7% to 32.2% of the cohort. Ventricular arrhythmias (VF/ventricular tachycardias) in ICD carriers (primary prevention) at 1 year were more frequent in ARVC, then in DCM, HCM, and RCM (10.3%, 8.2%, 7.5%, and 0%, respectively). Major cardiovascular events (MACE) occurred in 29.3% of RCM, 10.5% of DCM, 5.3% of HCM, and 3.9% of ARVC (P < 0.001). MACE were more frequent in index patients compared to relatives (10.8% vs. 4.4%, P < 0.001), more frequent in East Europe centres (13.1%) and least common in South Europe (5.3%) (P < 0.001). Subtype of cardiomyopathy, geographical region, and proband were predictors of MACE on multivariable analysis. Conclusions: Despite symptomatic improvement, patients with cardiomyopathies remain prone to major clinical events in the short term. Outcomes were different not only according to cardiomyopathy subtypes but also in relatives vs. index patients, and according to European regions

IRE1-Independent Gain Control of the Unfolded Protein Response

Nonconventional splicing of the gene encoding the Hac1p transcription activator regulates the unfolded protein response (UPR) in Saccharomyces cerevisiae. This simple on/off switch contrasts with a more complex circuitry in higher eukaryotes. Here we show that a heretofore unrecognized pathway operates in yeast to regulate the transcription of HAC1. The resulting increase in Hac1p production, combined with the production or activation of a putative UPR modulatory factor, is necessary to qualitatively modify the cellular response in order to survive the inducing conditions. This parallel endoplasmic reticulum–to–nucleus signaling pathway thereby serves to modify the UPR-driven transcriptional program. The results suggest a surprising conservation among all eukaryotes of the ways by which the elements of the UPR signaling circuit are connected. We show that by adding an additional signaling element to the basic UPR circuit, a simple switch is transformed into a complex response

The ocean sampling day consortium.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

Doubling of marine dinitrogen-fixation rates based on direct measurements

Biological dinitrogen fixation provides the largest input of nitrogen to the oceans, therefore exerting important control on the ocean’s nitrogen inventory and primary productivity. Nitrogen-isotope data fromocean sediments suggest that the marine-nitrogen inventory has been balanced for the past 3,000 years (ref. 4). Producing a balanced marine-nitrogenbudget based on direct measurements has proved difficult, however, with nitrogen loss exceeding the gain from dinitrogen fixation by approximately 200 TgNyr-1 (refs 5, 6). Here we present data from the Atlantic Ocean and show that the most widely used method of measuring oceanic N2-fixation rates underestimates the contribution of N2-fixing microorganisms (diazotrophs) relative to a newly developed method. Using molecular techniques to quantify the abundance of specific clades of diazotrophs in parallel with rates of 15N2 incorporation into particulate organic matter, we suggest that the difference between N2-fixation rates measured with the established method and those measured with the new method8 can be related to the composition of the diazotrophic community. Our data show that in areas dominated by Trichodesmium, the established method underestimatesN2-fixation rates by an averageof 62%. We also find that the newly developed method yields N2-fixation rates more than six times higher than those from the established method when unicellular, symbiotic cyanobacteria and c-proteobacteria dominate the diazotrophic community. On the basis of average areal rates measured over the Atlantic Ocean, we calculated basin-wide N2-fixation rates of 14+/-1TgNyr-1 and 24+/-1TgNyr-1 for the established and new methods, respectively. If our findings can be extrapolated to other ocean basins, this suggests that the global marine N2-fixation rate derived from direct measurements may increase from 103+/-8TgNyr-1 to 177+/-8TgNyr-1, and that the contribution of N2 fixers other than Trichodesmium is much more significant than was previously thought

Murine 5T multiple myeloma cells induce angiogenesis in vitro and in vivo

Multiple myeloma is a B cell malignancy. Recently, it has been demonstrated that bone marrow samples of patients with multiple myeloma display an enhanced angiogenesis. The mechanisms involved seem to be multiple and complex. We here demonstrate that the murine 5T multiple myeloma models are able to induce angiogenesis in vitro by using a rat aortic ring assay and in vivo by determining the microvessel density. The rat aortic rings cultured in 5T multiple myeloma conditioned medium exhibit a higher number of longer and more branched microvessels than the rings cultured in control medium. In bone marrow samples from 5T multiple myeloma diseased mice, a statistically significant increase of the microvessel density was observed when compared to bone marrow samples from age-matched controls. The angiogenic phenotype of both 5T multiple myeloma cells could be related, at least in part, to their capacity to produce vascular endothelial growth factor. These data clearly demonstrate that the 5T multiple myeloma models are good models to study angiogenesis in multiple myeloma and will allow to unravel the mechanisms of neovascularisation, as well as to test new putative inhibitors of angiogenesis

Seasonal and Long-Term Changes in Relative Abundance of Bull Sharks from a Tourist Shark Feeding Site in Fiji

Shark tourism has become increasingly popular, but remains controversial because of major concerns originating from the need of tour operators to use bait or chum to reliably attract sharks. We used direct underwater sampling to document changes in bull shark Carcharhinus leucas relative abundance at the Shark Reef Marine Reserve, a shark feeding site in Fiji, and the reproductive cycle of the species in Fijian waters. Between 2003 and 2009, the total number of C. leucas counted on each day ranged from 0 to 40. Whereas the number of C. leucas counted at the feeding site increased over the years, shark numbers decreased over the course of a calendar year with fewest animals counted in November. Externally visible reproductive status information indicates that the species' seasonal departure from the feeding site may be related to reproductive activity

Phylogenetic groups, virulence genes and quinolone resistance of integron-bearing Escherichia coli strains isolated from a wastewater treatment plant

We investigated phylogenetic affiliation, occurrence of virulence genes and quinolone resistance in 109 integron-containing strains of Escherichia coli isolated from a wastewater treatment plant. Selection for integron-bearing strains caused a shift toward phylogroup D, which was most numerous, followed by A, B1 and B2. Phylogroups D and B2, both of which are reported to include virulent extraintestinal pathotypes, made up 50.5% of all isolates and were present in every stage of wastewater treatment, including final effluent. Diarrheagenic pathotypes made up 21% of the strains. The average virulence factor genes score was low (1.40) and the range was from 0 to 5. Quinolone and fluoroquinolone resistance was observed in 56.0% and 50.4% of the strains, respectively; however, it was not associated with virulence factor score. Although the average virulence factor score was low, 17.4% of strains had three and more virulence genes. They were isolated mostly from raw sewage, but 30% of them were cultured from final effluent. Release of multiresistant integron-bearing E. coli strains with virulence traits into the environment may create potential threat and be of public health concern