BMP-2/6 Heterodimer Is More Effective than BMP-2 or BMP-6 Homodimers as Inductor of Differentiation of Human Embryonic Stem Cells

Bone Morphogenetic Protein (BMP) signaling pathways are involved in differentiation of stem cells into diverse cell types, and thus BMPs can be used as main guidance molecules for in vitro differentiation of human stem cells.We have analyzed the ability for inducing differentiation of the heterodimer BMP-2/BMP-6 (BMP-2/6) compared to the homodimers BMP-2 or BMP-6, using human embryonic stem (hES) cells H9 as model system. When incubated in a medium with high concentration of basic fibroblastic growth factor (FGF2), 100 ng/ml of human recombinant BMPs induced morphological changes and differentiation of hES cells in 24 to 48 hours. After 5 days, expression of differentiation markers was induced and quantified by quantitative PCR (qPCR) and flow cytometry. BMP-2/6 exhibited stronger activity for the induction of the expression of trophectodermal (CDX2) and endodermal (SOX17, GATA4, AFP) markers than BMP-2 or BMP-6 homodimers. BMP-2/6 also induced the expression of BMPR2 gene more effectively than BMP-2 or BMP-6 when used at the same concentration and time. Moreover, the percentage of cells expressing the surface endodermal marker CXCR4 was also increased for the heterodimer when compared to both homodimers. BMP-2/6 was a more potent activator of Smad-dependent (SMAD1/5) and Smad-independent signaling (mitogen-activated protein kinases ERK and p38) than BMP-2 and BMP-6, and the activation of these pathways might play a role in its increased potency for inducing hES cell differentiation.Therefore, we conclude that BMP-2/6 is more potent than BMP-2 or BMP-6 for inducing differentiation of hES cells, and it can be used as a more powerful substitute of these BMPs in in vitro differentiation guidance

Variation of BMP3 Contributes to Dog Breed Skull Diversity

Since the beginnings of domestication, the craniofacial architecture of the domestic dog has morphed and radiated to human whims. By beginning to define the genetic underpinnings of breed skull shapes, we can elucidate mechanisms of morphological diversification while presenting a framework for understanding human cephalic disorders. Using intrabreed association mapping with museum specimen measurements, we show that skull shape is regulated by at least five quantitative trait loci (QTLs). Our detailed analysis using whole-genome sequencing uncovers a missense mutation in BMP3. Validation studies in zebrafish show that Bmp3 function in cranial development is ancient. Our study reveals the causal variant for a canine QTL contributing to a major morphologic trait

The safety and efficacy of ERCP in the pediatric population with standard scopes: Does size really matter?

Experience with endoscopic retrograde cholangiopancreatography in the pediatric population is limited. The aim of this study was to evaluate the outcomes of ERCP in the pediatric population performed by adult gastroenterologists with standard duodenoscopes. This study is a structured retrospective review of endoscopic reports, computerized and paper medical records, and radiographic images of patients under the age of 18 who underwent ERCP for any indication at a tertiary referral centre. Data regarding demographic characteristics and medical history of patients, indications, technical success rate, final clinical diagnosis, and complications were analyzed. Forty-eight children with a mean age of 13 years (range 2-17) underwent a total of 65 ERCPs. The indications of ERCP were as follows; suspected choledocholithiasis (55 %), post-liver transplantation anastomotic biliary strictures (21 %), post-surgical bile duct injury (10 %), choledochal cyst (2 %), recurrent or chronic pancreatitis (10 %), and trauma (2 %). The cannulation success rate in the overall procedure was 93.8 %. Therapeutic interventions were performed in 70.7 % of patients. Post ERCP pancreatitis was the most common complication occurring in 9.2 % of patients, and no procedure related mortality occurred. When performed by well-trained adult gastroenterologists, the use of endoscopic retrograde cholangiopancreatography with standard duodenoscopes is safe in pediatric population