Effects of serum and serum heat-inactivation on human bone derived osteoblast progenitor cells

Generally, heat inactivated foetal calf serum (FCS) containing media are used for the cultivation of animal and human cells. The role of serum source and serum treatment on the behaviour of cells has long been neglected. The present study was performed to investigate the effects of serum heat inactivation and serum source on trabecular bone derived progenitor cells (HBC). Furthermore, it was investigated in how far these reactions differed from those seen in bone marrow derived mesenchymal progenitor cells (HBMC) cultures. We found that HBC cultures performed differently in the presence of FCS and HS with or without heat inactivation. The reactions similar to some degree those observed in HBMC cultures. The implications of the results on cell-implant surface interaction studies are discusse

Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum.

BACKGROUND: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy. METHODS: We describe the clinical, biochemical and molecular features of 2 siblings with a novel homozygous mutation in RARS2. Both patients presented neonatally with lactic acidosis. While the older sibling had severe neurological symptoms with microcephaly, seizures and developmental delay, the younger patient was still neurologically asymptomatic at the age of 2 months. RESULTS: MRI studies in both children lacked pontocerebellar involvement. The expression of the OXPHOS complex proteins was decreased in both patients, whereas oxygen consumption was increased. CONCLUSIONS: Characteristic neuroradiological abnormalities of PCH6 such as vermis and cerebellar hypoplasia and progressive pontocerebellar atrophy may be missing in patients with RARS2 mutations. RARS2 testing should therefore also be performed in patients without pontocerebellar hypoplasia but otherwise typical clinical symptoms

A Search for Variations of Fundamental Constants using Atomic Fountain Clocks

Over five years we have compared the hyperfine frequencies of 133Cs and 87Rb atoms in their electronic ground state using several laser cooled 133Cs and 87Rb atomic fountains with an accuracy of ~10^{-15}. These measurements set a stringent upper bound to a possible fractional time variation of the ratio between the two frequencies : (d/dt)ln(nu_Rb/nu_Cs)=(0.2 +/- 7.0)*10^{-16} yr^{-1} (1 sigma uncertainty). The same limit applies to a possible variation of the quantity (mu_Rb/mu_Cs)*alpha^{-0.44}, which involves the ratio of nuclear magnetic moments and the fine structure constant.Comment: 4 pages, 3 figures, 1 table submitted to Phys. Rev. Let

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Cross-sectional observational study of 208 patients with non-classical urea cycle disorders.

Urea cycle disorders (UCDs) are inherited disorders of ammonia detoxification often regarded as mainly of relevance to pediatricians. Based on an increasing number of case studies it has become obvious that a significant number of UCD patients are affected by their disease in a non-classical way: presenting outside the newborn period, following a mild course, presenting with unusual clinical features, or asymptomatic patients with only biochemical signs of a UCD. These patients are surviving into adolescence and adulthood, rendering this group of diseases clinically relevant to adult physicians as well as pediatricians. In preparation for an international workshop we collected data on all patients with non-classical UCDs treated by the participants in 20 European metabolic centres. Information was collected on a cohort of 208 patients 50% of which were ≥ 16 years old. The largest subgroup (121 patients) had X-linked ornithine transcarbamylase deficiency (OTCD) of whom 83 were female and 29% of these were asymptomatic. In index patients, there was a mean delay from first symptoms to diagnosis of 1.6 years. Cognitive impairment was present in 36% of all patients including female OTCD patients (in 31%) and those 41 patients identified presymptomatically following positive newborn screening (in 12%). In conclusion, UCD patients with non-classical clinical presentations require the interest and care of adult physicians and have a high risk of neurological complications. To improve the outcome of UCDs, a greater awareness by health professionals of the importance of hyperammonemia and UCDs, and ultimately avoidance of the still long delay to correctly diagnose the patients, is crucial

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance:A retrospective, single-center study and the generation of www.emergencyprotocol.net

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long‐term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single‐center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in‐hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium‐chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD

Cold atom Clocks and Applications

This paper describes advances in microwave frequency standards using laser-cooled atoms at BNM-SYRTE. First, recent improvements of the $^{133}$Cs and $^{87}$Rb atomic fountains are described. Thanks to the routine use of a cryogenic sapphire oscillator as an ultra-stable local frequency reference, a fountain frequency instability of $1.6\times 10^{-14}\tau^{-1/2}$ where $\tau$ is the measurement time in seconds is measured. The second advance is a powerful method to control the frequency shift due to cold collisions. These two advances lead to a frequency stability of $2\times 10^{-16}$ at $50,000s for the first time for primary standards. In addition, these clocks realize the SI second with an accuracy of$7\times 10^{-16}$, one order of magnitude below that of uncooled devices. In a second part, we describe tests of possible variations of fundamental constants using$^{87}$Rb and$^{133}$Cs fountains. Finally we give an update on the cold atom space clock PHARAO developed in collaboration with CNES. This clock is one of the main instruments of the ACES/ESA mission which is scheduled to fly on board the International Space Station in 2008, enabling a new generation of relativity tests.Comment: 30 pages, 11 figure

Commissioning of a photoelectron spectrometer for soft X ray photon diagnostics at the European XFEL

Commissioning and first operation of an angle-resolved photoelectron spectrometer for non-invasive shot-to-shot diagnostics at the European XFEL soft X-ray beamline are described. The objective with the instrument is to provide the users and operators with reliable pulse-resolved information regarding photon energy and polarization that opens up a variety of applications for novel experiments but also hardware optimization