Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors

Interaction between endothelial cells and mural cells (pericytes and vascular smooth muscle) is essential for vascular development and maintenance. Endothelial cells arise from Flk1-expressing (Flk1+) mesoderm cells, whereas mural cells are believed to derive from mesoderm, neural crest or epicardial cells and migrate to form the vessel wall. Difficulty in preparing pure populations of these lineages has hampered dissection of the mechanisms underlying vascular formation. Here we show that Flk1+ cells derived from embryonic stem cells can differentiate into both endothelial and mural cells and can reproduce the vascular organization process. Vascular endothelial growth factor promotes endothelial cell differentiation, whereas mural cells are induced by platelet-derived growth factor-BB. Vascular cells derived from Flk1+ cells can organize into vessel-like structures consisting of endothelial tubes supported by mural cells in three-dimensional culture. Injection of Flk1+ cells into chick embryos showed that they can incorporate as endothelial and mural cells and contribute to the developing vasculature in vivo. Our findings indicate that Flk1+ cells can act as 'vascular progenitor cells' to form mature vessels and thus offer potential for tissue engineering of the vascular system.     

Evidence of Hydrogen Bonding in Chloroform and Polyacrylates from NMR Measurements

IntroductionHydrogen bonding in polymer solutions hasattracted particular attention in recent yearsbecause of its importance in the understanding ofintermolecular interactions,which often affectphysical properties of polymer mixtures[17] .Studies have indicated that hydrogen bondingaffects the phase equilibrium behavior[8] ,e.g.,chloroform shows abnormal thermodynamicproperties in its vapor pressure,as well as in theheat and the volume of mixing with poly( propylene glycol dimethyl ether) [9] …     

Membrane fractions of rabbit granulocytes. 1. The presence of ouabain-sensitive ATPase and the electrophoretic patterns.

In one or two membrane fractions isolated from the homogenate of casein-induced rabbit granulocytes ouabain-sensitive ATPase activity was found definitely. Electrophoretic patterns of these membrane fractions showed no significant differences in staining for carbohydrate and protein.     

Atypical mitochondrial morphology of the intestinal absorptive cells of the germfree rat

Zusammenfassung Die Mitochondrien der Dünndarm-Epithelzellen 3 Monate alter keimfreier Ratten zeigten elektronenmikroskopisch auffallende Formunterschiede im Gegensatz zu Vergleichstieren desselben Wurfes, die mit Coecum-Inhalt gewöhnlicher Ratten kontaminiert wurden.

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This work was supported in part by Grant No. 5 POI AM05664-05 AMP and Grant No. 5-K6-GM-14,208-05 to the Albert Einstein College of Medicine by the National Institutes of Health.     

Periostin in vitreoretinal diseases

Proliferative vitreoretinal diseases such as diabetic retinopathy, proliferative vitreoretinopathy (PVR), and age-related macular degeneration are a leading cause of decreased vision and blindness in developed countries. In these diseases, retinal fibro(vascular) membrane (FVM) formation above and beneath the retina plays an important role. Gene expression profiling of human FVMs revealed significant upregulation of periostin. Subsequent analyses demonstrated increased periostin expression in the vitreous of patients with both proliferative diabetic retinopathy and PVR. Immunohistochemical analysis showed co-localization of periostin with α-SMA and M2 macrophage markers in FVMs. In vitro, periostin blockade inhibited migration and adhesion induced by PVR vitreous and transforming growth factor-β2 (TGF-β2). In vivo, a novel single-stranded RNAi agent targeting periostin showed the inhibitory effect on experimental retinal and choroidal FVM formation without affecting the viability of retinal cells. These results indicated that periostin is a pivotal molecule for FVM formation and a promising therapeutic target for these proliferative vitreoretinal diseases.     

Reversible shape change of Triton-treated erythrocyte ghosts induced by Ca2+ and Mg-ATP

The shape of the human erythrocyte depends on intracellular ATP content and echinocytic erythrocyte ghosts obtained in the presence of Mg-ATP acquire a diskocytic shape after incubation at 37 degrees C; however, agreement is lacking about the molecular basis of the shape changes. The suggestion that phosphorylation of cytoskeletal structures underlying the membrane is involved has been disputed and alternative explanations based on lipid bilayer theory and metabolism of phospholipid have been proposed. Recently, we re-examined the effect of ATP on the shape of ghosts and found that it consists of two distinct steps. We have, therefore, now examined the effect of physiological concentrations of Ca2+ and ATP on the cytoskeleton of the erythrocyte membrane directly using Triton-treated ghosts which had lost this permeability barrier. Our findings suggest that a noncovalent effect of ATP on the cytoskeleton is a prerequisite for shape change.     

Binding of a non-beta-lactam antibiotic to penicillin-binding proteins

In the search for new beta-lactam antibiotics of natural origin, the discoveries of cephamycins and sulfazecins (monobactams) were important turning points in that they accelerated many screening efforts aimed at other new compounds. In our target-directed screening for beta-lactam antibiotics using beta-lactam hypersensitive mutants, we have examined Gram-negative bacteria isolated from natural habitats and have recently reported several types of beta-lactam antibiotics such as cephabacins and formadicins. Here we report a novel antibiotic, lactivicin, found using this system. Although lactivicin has various biological activities commonly observed in beta-lactam antibiotics, it does not possess a beta-lactam ring in its molecule, but has the unique structure of a dicyclic dipeptide.     

Thyrotrophin in the pars tuberalis triggers photoperiodic response

Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.