Retinoic acid inhibits the growth of bone marrow mesenchymal stem cells and induces p27Kip1 and p16INK4A up-regulation

The importance of bone marrow mesenchymal stem cells in hemopoiesis has been definitely demonstrated. Thus, their impairment might cause profound alteration on production and maturation of blood cells. In the present paper, we investigated, for the first time, the effect of retinoic acid, an important antileukemic molecule, on the proliferation of primary cultures of human bone marrow mesenchymal stem cells. We demonstrated that retinoic acid, at a pharmacological concentration, hampers strongly the growth of the cells, without inducing osteoblastic differentiation. The analysis of cell division cycle machinery showed that the antiproliferative effect is associated with (i) the up-regulation of two cyclin-dependent kinase inhibitors, namely p27^Kip1 and p16^INK4A, and (ii) the down-regulation of cyclin-dependent kinase 2 activity and pRB phosphorylation. The reported findings represent novel insights into the antileukemic effects of the drug and contribute in clarifying the molecular mechanism of its pharmacological activity.     

Docking and small angle X-ray scattering studies of purine nucleoside phosphorylase

Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed.     

Structure of the ovary in Steingelia (Sternorrhyncha: Coccinea), and its phylogenetic implications

The paired ovaries of Steingelia gorodetskia are composed of about 100 telotrophic ovarioles devoid of terminal filaments (scale insect autapomorphy). In structure they resemble those of other scale insects, but differ in the following details: (a) all ovarioles develop synchronously, (b) they are suspended to the lateral oviducts by means of long stalks, (c) the tropharium is tubular (unique in scale insects) and (d) consists of 15-35, trophocytes, 2-4 previtellogenic oocytes that further develop, and numerous somatic prefollicular cells, (e) the vitellarium houses 2-4 linearly arranged vitellarial oocytes (versus one in most scale insects). Most of these features must be considered as plesiomorphic corresponding with the conditions in the most primitive Heteroptera. Bacterial endosymbionts have been found in some somatic cells, trophocytes, oocytes and in the nutritive cord. Present results support the opinion, based on external morphology, that the Steingeliidae are closely related to the Ortheziidae, Xylococcidae and Matsucoccidae.     

Presenilin-1 is located in rat mitochondria

Presenilins are mutated in most cases of autosomal dominant inherited forms of early onset Alzheimer's disease and such mutations are known to sensitize cells to apoptotic stimuli in vitro. Previous studies show that presenilins are primarily located in the endoplasmatic reticulum and cell membranes. Here we report, based on immunoblot analysis and immunoelectron microscopy studies, that PS1 is also located in mitochondrial membranes. For these studies we used tissue sections and subcellular fractions of rat brain and liver. Immunogold labeling of sections show that PS1 is predominantly located in the inner membrane of mitochondria. The function of PS1 in mitochondrial membranes is presently unknown. PS1 mutations may make cells more vulnerable to apoptotic stimuli due to dysfunction of this protein at the mitochondrial level.     

Sphingosine-1-phosphate receptors and the development of the vascular system

Extracellular sphingolipid signaling has been implicated as an essential event in vascular development. Sphingosine-1-phosphate (S1P), through interactions with G protein-coupled receptors, regulates functions of endothelial and smooth muscle cells (SMCs)-the major cell types of the vasculature. The knockout of the gene encoding the S1P1 receptor (formally known as Edg-1) in mice blocks vascular maturation, the process where SMCs and pericytes envelop nascent endothelial tubes. The question that remains is how stimulation of S1P receptors controls this critical event in the developmental sequence leading to the formation of functional blood vessels.     

A new species of Campomanesia (Myrtaceae) from southeastern Brazil

Campomanesia simulans, a new species from the states of São Paulo and Minas Gerais, Brazil, is described and illustrated.