Human bone chips release of sclerostin and FGF-23 into the culture medium: an in vitro pilot study

Abstract OBJECTIVE: Signaling molecules derived from osteocytes have been proposed as a mechanism by which autografts contribute to bone regeneration. However, there have been no studies that determined the role of osteocytes in bone grafts. MATERIAL AND METHOD: Herein, it was examined whether bone chips and demineralized bone matrix release sclerostin and FGF-23, both of which are highly expressed by osteocytes. RESULTS: Bone grafts from seven donors were placed in culture medium. Immunoassay showed that bone chips released sclerostin (median 1.0 ng/ml) and FGF-23 (median 9.8 relative units/ml) within the first day, with declining levels overtime. Demineralized bone matrix also released detectable amounts of sclerostin into culture medium, while FGF-23 remained close to the detection limit. In vitro expanded isolated bone cells failed to release detectable amounts of sclerostin and FGF-23. CONCLUSION: These results suggest that autografts but also demineralized bone matrix can release signaling molecules that are characteristically produced by osteocytes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. KEYWORDS: FGF-23; autologous bone; bone grafts; demineralized bone matrix; osteocytes; sclerostin

Regularity conditions in the realisability problem in applications to point processes and random closed sets

We study existence of random elements with partially specified distributions. The technique relies on the existence of a positive ex-tension for linear functionals accompanied by additional conditions that ensure the regularity of the extension needed for interpreting it as a probability measure. It is shown in which case the extens ion can be chosen to possess some invariance properties. The results are applied to the existence of point processes with given correlation measure and random closed sets with given two-point covering function or contact distribution function. It is shown that the regularity condition can be efficiently checked in many cases in order to ensure that the obtained point processes are indeed locally finite and random sets have closed realisations.

Fire ecology north and south of the Alps since the last ice age

Wildfires are very rare in central Europe, which is probably why fire effects on vegetation have been neglected by most central European ecologists and palaeoecologists. Presently, reconstructions of fire history and fire ecology are almost absent. We analysed sediment cores from lakes on the Swiss Plateau (Lobsigensee and Soppensee) for pollen and charcoal to investigate the relationship between vegetation and fire. Microscopic charcoal evidence suggests increasing regional fire frequencies during the Neolithic (7350-4150 cal. BP, 5400-2200 BC) and the subsequent prehistoric epochs at Lobsigensee, whereas at Soppensee burnings remained rather rare until modern times. Neolithic peaks of charcoal at 6200 and 5500 cal. BP (4250 and 3550 BC) coincided with declines of pollen of fire-sensitive taxa at both sites (e.g., Ulmus, Tilia, Hedera, Fagus), suggesting synchronous vegetational responses to fire at regional scales. However, correlation analysis between charcoal and pollen for the period 6600-4400 cal. BP (4650-2650 BC) revealed no significant link between fire and vegetation at Soppensee, whereas at Lobsigensee increases of Corylus and decreases of Fagus were related to fire events. Fire impact on vegetation increased during the subsequent epochs at both sites. Correlation analyses of charcoal and pollen data for the period 4250-1150 cal. BP (2300 BC -AD 800) suggest that fires were intentionally set to disrupt forests and to provide open areas for arable and pastoral farming (e.g., significant positive correlations between charcoal and Cerealia, Plantago lanceolata, Asteroideae). These results are compared with southern European records (Lago di Origlio, Lago di Muzzano), which are situated in particularly fire-prone environments. After the Mesolithic period (I1 200-7350 cal. BP, 9250-5400 BC), charcoal influx was higher by an order of magnitude in the south, suggesting more frequent fires. Neolithic fires caused similar though more pronounced responses of vegetation in the south (e.g., expansions of Corylus). Post-Neolithic land-use practices involving (controlled) burning culminated in both regions at about 2550 cal. BP (c. 600 BC). However, fire-caused disappearances of entire forest communities were confined to the southern sites. Such differences in fire effects among the sites are explained by the dissimilar importance of fire as a result of different climatic conditions and cultural activities. Our results imply that the remaining (fire-sensitive) fragments of central European vegetation north of the Alps are especially endangered by increasing fire frequencies resulting from predicted climatic change.

CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.

Metabolic syndrome after transplantation is a major concern following solid organ transplantation (SOT). The CREB-regulated transcription co-activator 2 (CRTC2) regulates glucose metabolism. The effect of CRTC2 polymorphisms on new-onset diabetes after transplantation (NODAT) was investigated in a discovery sample of SOT recipients (n1=197). Positive results were tested for replication in two samples from the Swiss Transplant Cohort Study (STCS, n2=1294 and n3=759). Obesity and other metabolic traits were also tested. Associations with metabolic traits in population-based samples (n4=46'186, n5=123'865, n6>100,000) were finally analyzed. In the discovery sample, CRTC2 rs8450-AA genotype was associated with NODAT, fasting blood glucose and body mass index (Pcorrected<0.05). CRTC2 rs8450-AA genotype was associated with NODAT in the second STCS replication sample (odd ratio (OR)=2.01, P=0.04). In the combined STCS replication samples, the effect of rs8450-AA genotype on NODAT was observed in patients having received SOT from a deceased donor and treated with tacrolimus (n=395, OR=2.08, P=0.02) and in non-kidney transplant recipients (OR=2.09, P=0.02). Moreover, rs8450-AA genotype was associated with overweight or obesity (n=1215, OR=1.56, P=0.02), new-onset hyperlipidemia (n=1007, OR=1.76, P=0.007), and lower high-density lipoprotein-cholesterol (n=1214, β=-0.08, P=0.001). In the population-based samples, a proxy of rs8450G>A was significantly associated with several metabolic abnormalities. CRTC2 rs8450G>A appears to have an important role in the high prevalence of metabolic traits observed in patients with SOT. A weak association with metabolic traits was also observed in the population-based samples.The Pharmacogenomics Journal advance online publication, 8 December 2015; doi:10.1038/tpj.2015.82.

Disease evolution and outcomes in familial AML with germline CEBPA mutations

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.

Contractual Difficulties in Environmental Management and the Protection of Biodiversity: The Case of Conservation and Mitigation Banking

This paper offers a principal-agent model of feasible private contracting in mitigation and conservation banking aimed at the protection of natural habitat and bio-diversity of US wetlands and uplands. It is shown that while it is straightforward to design an incentive contract, such a contract may not achieve the federally mandated objective of no net loss of habitat. This is because the minimum payment required as an economic incentive to private agents may be greater than what they should receive for the habitat values that they actually created in the field. This possible problem is shown to derive from nonconvexity in the production possibility set between the biological value of land as natural habitat and in non-habitat uses such as in urban development. The paper concludes with a consideration of several institutional devises that may promote the convergence of private contracting and the attainment of no net loss. These include the payment of subsidies, greater accuracy in the identification of actual quality by the principal, and the use of several incentive alignment devises.

Bericht über den Alpengarten bei der Lindauer Hütte im Gauertal

erstattet von Rektor Hoock

Memoria y construcción del yo en Angélica Gorodischer

Fil: Varela, Fabiana Inés. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras

Horizontal profiles of longwave and shortwave radiation components over sea ice near Barrow, Alaska during the 2011 melt

An integrated instrument package for measuring and understanding the surface radiation budget of sea ice is presented, along with results from its first deployment. The setup simultaneously measures broadband fluxes of upwelling and downwelling terrestrial and solar radiation (four components separately), spectral fluxes of incident and reflected solar radiation, and supporting data such as air temperature and humidity, surface temperature, and location (GPS), in addition to photographing the sky and observed surface during each measurement. The instruments are mounted on a small sled, allowing measurements of the radiation budget to be made at many locations in the study area to see the effect of small-scale surface processes on the large-scale radiation budget. Such observations have many applications, from calibration and validation of remote sensing products to improving our understanding of surface processes that affect atmosphere-snow-ice interactions and drive feedbacks, ultimately leading to the potential to improve climate modelling of ice-covered regions of the ocean. The photographs, spectral data, and other observations allow for improved analysis of the broadband data. An example of this is shown by using the observations made during a partly cloudy day, which show erratic variations due to passing clouds, and creating a careful estimate of what the radiation budget along the observed line would have been under uniform sky conditions, clear or overcast. Other data from the setup's first deployment, in June 2011 on fast ice near Point Barrow, Alaska, are also shown; these illustrate the rapid changes of the radiation budget during a cold period that led to refreezing and new snow well into the melt season.