Impairment of rat postnatal lung alveolar development by glucocorticoids: involvement of the p21CIP1 and p27KIP1 cyclin-dependent kinase inhibitors

It has been shown that glucocorticoids accelerate lung development by limiting alveolar formation resulting from a premature maturation of the alveolar septa. Based on these data, the aim of the present work was to analyze the influence of dexamethasone on cell cycle control mechanisms during postnatal lung development. Cell proliferation is regulated by a network of signaling pathways that converge to the key regulator of cell cycle machinery: the cyclin-dependent kinase (CDK) system. The activity of the various cyclin/CDK complexes can be modulated by the levels of the cyclins and their CDKs, and by expression of specific CDK inhibitors (CKIs). In the present study, newborn rats were given a 4-d treatment with dexamethasone (0.1-0.01 microg/g body weight dexamethasone sodium phosphate daily on d 1-4), or saline. Morphologically, the treatment caused a significant thinning of the septa and an acceleration of lung maturation on d 4. Study of cyclin/CDK system at d 1-36 documented a transient down-regulation of cyclin/CDK complex activities at d 4 in the dexamethasone-treated animals. Analysis of the mechanisms involved suggested a role for the CKIs p21CIP1 and p27KIP1. Indeed, we observed an increase in p21CIP1 and p27KIP1 protein levels on d 4 in the dexamethasone-treated animals. By contrast, no variations in either cyclin and CDK expression, or cyclin/CDK complex formation could be documented. We conclude that glucocorticoids may accelerate lung maturation by influencing cell cycle control mechanisms, mainly through impairment of G1 cyclin/CDK complex activation.

The 1452 or 1453 A.D. Kuwae Eruption Signal Derived from Multiple Ice Core Records: Greatest Volcanic Sulfate Event of the Past 700 Years

We combined 33 ice core records, 13 from the Northern Hemisphere and 20 from the Southern Hemisphere, to determine the timing and magnitude of the great Kuwae eruption in the mid-15th century. We extracted volcanic deposition signals by applying a high-pass loess filter to the time series and examining peaks that exceed twice the 31 year running median absolute deviation. By accounting for the dating uncertainties associated with each record, these ice core records together reveal a large volcanogenic acid deposition event during 1453 - 1457 A. D. The results suggest only one major stratospheric injection from the Kuwae eruption and confirm previous findings that the Kuwae eruption took place in late 1452 or early 1453, which may serve as a reference to evaluate and improve the dating of ice core records. The average total sulfate deposition from the Kuwae eruption was 93 kg SO4/km(2) in Antarctica and 25 kg SO4/km(2) in Greenland. The deposition in Greenland was probably underestimated since it was the average value of only two northern Greenland sites with very low accumulation rates. After taking the spatial variation into consideration, the average Kuwae deposition in Greenland was estimated to be 45 kg SO4/km(2). By applying the same technique to the other major eruptions of the past 700 years our result suggests that the Kuwae eruption was the largest stratospheric sulfate event of that period, probably surpassing the total sulfate deposition of the Tambora eruption of 1815, which produced 59 kg SO4/km(2) in Antarctica and 50 kg SO4/km(2) in Greenland.

Implementation of the Convention on the Protection and Promotion of the Diversity of Cultural Expressions in the Digital Age: Challenges, Priority Actions and Recommendations

Report presented to the Intergovernmental Committee of the Convention on the Protection and Promotion of the Diversity of Cultural Expressions Seventh Ordinary Session, Paris, December 10-­‐13, 2013

Unravelling the multiple roles of FUS in RNA processing and on ALS pathogenesis

Two genes with related functions in RNA biogenesis were recently reported in patients with familial ALS: the FUS/TLS gene at the ALS6 locus and the TARDBP/TDP-43 gene at the ALS10 locus [1, 2]. FUS has been implicated to function in several steps of gene expression, including transcription regulation [3], RNA splicing [4, 5], mRNA transport in neurons [6] and, interestingly, in microRNA (miRNA) processing [7]. The goal of this project is to identify the molecular mechanisms leading to the development of FUS mutations-associated ALS. Specifically, we want to test the hypothesis that these FUS mutations misregulate miRNA levels that in turn affect the expression of genes critical for motor neuron survival. In addition we want to test whether misregulation of the miRNA profile is a common feature in ALS. We have performed immunoprecipitations from total extracts of 293T cells expressing FLAG-tagged FUS to characterize its interactome by mass spectrometry. This proteomic study not only revealed a strong interaction of FUS with splicing factors, but shows that FUS might be involved in many, quite different pathways. To map which parts of the FUS protein contribute to the interaction with splicing factors, we have performed a set of experiments with a series of missense and deletion mutants. With this approach, we will not only gain information on the binding partners of FUS along with a map of the required domains for the interactions, but it will also help to unravel whether certain ALS-associated FUS mutations lead to a loss or gain of function due to gain or loss of interactors. Additionally, we have performed quantitative interactomics using SILAC to identify interactome differences of ALS-associated FUS mutants. To this end we have performed immunoprecipitations of total extract from 293T cells, stably transduced with constructs expressing wild-type FUS-FLAG as well as three different ALS-associated mutants (G156E, R244C, P525L). First results indicate striking differences in the interactome with certain RNA binding proteins. We are now validating these candidates in order to reveal the importance of these differential interactions in the context of ALS.

A Process Model of the Formation of Spatial Presence Experiences

In order to bridge interdisciplinary differences in Presence research and to establish connections between Presence and “older” concepts of psychology and communication, a theoretical model of the formation of Spatial Presence is proposed. It is applicable to the exposure to different media and intended to unify the existing efforts to develop a theory of Presence. The model includes assumptions about attention allocation, mental models, and involvement, and considers the role of media factors and user characteristics as well, thus incorporating much previous work. It is argued that a commonly accepted model of Spatial Presence is the only solution to secure further progress within the international, interdisciplinary and multiple-paradigm community of Presence research.

Systemic light-chain amyloidosis revealed by progressive nail involvement, diffuse alopecia and sicca syndrome: report of an unusual case with a review of the literature.

Immunoglobulin light-chain (AL) amyloidosis is a form of systemic amyloidosis in which the fibrils are derived from monoclonal light chains. We report a case of a 66-year-old woman presenting with nail changes, parchment-like hand changes, progressive alopecia and sicca syndrome. Histopathological studies of biopsy specimens of the scalp, the nail, minor labial salivary glands and abdominal skin revealed deposits of AL κ-type amyloid. Urine protein electrophoresis exhibited a weak band of κ-type light chains. Based on this striking case, we here review the characteristic nail and hair manifestations associated with systemic amyloidosis. Knowledge of these signs is important for an early diagnosis of systemic amyloidosis, identification of the underlying disease and patient management.

Multiple myeloma-associated amyloidoma of the sacrum: case report and review of the literature.

Study Design Case report. Objectives With only two previously reported cases, localized amyloidosis of the sacrum is extremely rare. Here we report a 64-year-old woman with a large osteolytic lesion accompanied by weakness and paresthesia of the right leg and difficulties in bladder control. Methods Fine needle biopsy and standard staging procedures revealed a primary solitary amyloidoma that was treated with intralesional resection, lumbopelvic stabilization, and consolidation radiotherapy. Results Clinical follow-up revealed the diagnosis of multiple myeloma 9 months after initial treatment. At 12 months, no local recurrence has occurred, the neurologic symptoms have resolved, and the systemic disease is in remission. Conclusions Intralesional resection with adjuvant radiotherapy of the amyloidoma achieved good local tumor control with limited morbidity.

The 10-year anniversary of the European Association for Cardiovascular Prevention and Rehabilitation: achievements and challenges

On the occasion of the 2014 European Society of Cardiology annual congress in Barcelona the European Association for Cardiovascular Prevention and Rehabilitation (EACPR) will celebrate its 10-year anniversary, having been initiated in Munich in 2004. In this article each EACPR president gives their personal recollections and views on the main achievements under their leadership and discusses the challenges for preventive cardiology that still lay ahead.

Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria.

BACKGROUND Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. OBJECTIVE An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials. METHODS A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place. RESULTS The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed. CONCLUSION Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.

Improvement of the processes around the radiology workplace : avoidance of time delays

Radiologists have been confronted with multiple new challenges in recent years. While there has been a steady increase in the number of radiological examinations and imaging material per examination, examination protocols have become more complex and highly time-consuming whereas case-based remuneration is on the decline. The identification of inefficient components in examination processes and reporting is therefore essential. Where and why do time delays occur? How can they be avoided? The following article provides a brief overview and is designed to stimulate discussion.