A Period and a Prediction for the Of?p Spectrum Alternator HD 191612

The observational picture of the enigmatic O-type spectrum variable HD191612 has been sharpened substantially. A symmetrical, low-amplitude light curve with a period near 540 d has recently been reported from Hipparcos photometry. This period satisfies all of the spectroscopy since at least 1982, including extensive new observations during 2003 and 2004, and it has predicted the next transition during September--October 2004. Measurements of the H alpha equivalent width reveal a sharp emission peak in the phase diagram, in contrast to the apparently sinusoidal light curve. The He II absorption-line strength is essentially constant, while He I varies strongly, possibly filled in by emission in the O6 state, thus producing the apparent spectral-type variations. The O8 state appears to be the "normal" one. Two intermediate O7 observations have been obtained, which fall at the expected phases, but these are the only modern observations of the transitions so far. The period is too long for rotation or pulsation; although there is no direct evidence as yet for a companion, a model in which tidally induced oscillations drive an enhanced wind near periastron of an eccentric orbit appears promising. Further observations during the now predictable transitions may provide a critical test. Ultraviolet and X-ray observations during both states will likely also prove illuminating.Comment: 7 pages, 3 figures, 1 table; scheduled for the 2004 December 10 issue of ApJL, Vol. 617, No. 1. ApJ

Pegbelfermin (BMS-986036):an investigational PEGylated fibroblast growth factor 21 analogue for the treatment of nonalcoholic steatohepatitis

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin (BMS-986036) is a PEGylated fibroblast growth factor 21 (FGF21) analogue that is under investigation for the treatment of NASH. Areas covered: We reviewed the (pre)clinical pegbelfermin studies and compared these with other studies that assessed FGF21 and FGF21 analogues in the treatment of NASH. Expert opinion: With no FDA approved treatments available for NASH, there is an urgent need for novel therapies. Pegbelfermin is a systemic treatment with pleiotropic effects on various tissues. Short-term adverse effects are limited, but more research is required to study potential long-term safety issues. In a phase 2a trial, pegbelfermin has shown promising improvements in several NASH related outcomes. However, clinical trials demonstrating long-term benefits on hard outcomes such as liver histology, cirrhosis development, or survival are required for further validation

Sorting living mesenchymal stem cells using a TWIST1 RNA-based probe depends on incubation time and uptake capacity

Bone marrow derived mesenchymal stromal cells (BMSCs) are multipotent progenitors of particular interest for cell-based tissue engineering therapies. However, one disadvantage that limit their clinical use is their heterogeneity. In the last decades a great effort was made to select BMSC subpopulations based on cell surface markers, however there is still no general consensus on which markers to use to obtain the best BMSCs for tissue regeneration. Looking for alternatives we decided to focus on a probe-based method to detect intracellular mRNA in living cells, the SmartFlare technology. This technology does not require fixation of the cells and allows us to sort living cells based on gene expression into functionally different populations. However, since the technology is available it is debated whether the probes specifically recognize their target mRNAs. We validated the TWIST1 probe and demonstrated that it specifically recognizes TWIST1 in BMSCs. However, differences in probe concentration, incubation time and cellular uptake can strongly influence signal specificity. In addition we found that TWIST1high expressing cells have an increased expansion rate compared to TWIST1low expressing cells derivedfrom the same initial population of BMSCs. The SmartFlare probes recognize their target gene, however for each probe and cell type validation of the protocol is necessary