Angiogenesis during human extraembryonic development involves the spatiotemporal control of PDGF ligand and receptor gene expression.

We have examined the role of platelet-derived growth factor (PDGF) ligand and receptor genes in the angiogenic process of the developing human placenta. In situ hybridization analysis of first trimester placentae showed that most microcapillary endothelial cells coexpress the PDGF-B and PDGF beta-receptor genes. This observation indicates that PDGF-B may participate in placental angiogenesis by forming autostimulatory loops in capillary endothelial cells to promote cell proliferation. Endothelial cells of macro blood vessels maintained high PDGF-B expression, whereas PDGF beta-receptor mRNA was not detectable. In contrast, PDGF beta-receptor mRNA was readily detectable in fibroblast-like cells and smooth muscle cells in the surrounding intima of intermediate and macro blood vessels. Taken together, these data suggest that the PDGF-B signalling pathway appears to switch from an autocrine to a paracrine mechanism to stimulate growth of surrounding PDGF beta-receptor-positive mesenchymal stromal cells. Smooth muscle cells of the blood vessel intima also expressed the PDGF-A gene, the protein product of which is presumably targeted to the fibroblast-like cells of the mesenchymal stroma as these cells were the only ones expressing the PDGF alpha-receptor. PDGF-A expression was also detected in columnar cytotrophoblasts where it may have a potential role in stimulating mesenchymal cell growth at the base of the growing placental villi. We discuss the possibility that the regulation of the PDGF-B and beta-receptor gene expression might represent the potential targets for primary angiogenic factors.     

Developing a Social Autopsy Tool for Dengue Mortality: A Pilot Study

BackgroundDengue fever is a public health problem in the tropical and sub-tropical world. Dengue cases have grown dramatically in recent years as well as dengue mortality. Colombia has experienced periodic dengue outbreaks with numerous dengue related-deaths, where the Santander department has been particularly affected. Although social determinants of health (SDH) shape health outcomes, including mortality, it is not yet understood how these affect dengue mortality. The aim of this pilot study was to develop and pre-test a social autopsy (SA) tool for dengue mortality.ConclusionsThe SA tool is based on the scientific literature, a validated conceptual framework, researchers’ and health professionals’ expertise, and a pilot study. It is the first time that a SA tool has been created for the dengue mortality context. Our work furthers the study on SDH and how these are applied to neglected tropical diseases, like dengue. This tool could be integrated in surveillance systems to provide complementary information on the modifiable and avoidable death-related factors and therefore, be able to formulate interventions for dengue mortality reduction.     

A Dynamic Study of Protein Secretion and Aggregation in the Secretory Pathway

Precise coordination of protein biogenesis, traffic and homeostasis within the early secretory compartment (ESC) is key for cell physiology. As a consequence, disturbances in these processes underlie many genetic and chronic diseases. Dynamic imaging methods are needed to follow the fate of cargo proteins and their interactions with resident enzymes and folding assistants. Here we applied the Halotag labelling system to study the behavior of proteins with different fates and roles in ESC: a chaperone, an ERAD substrate and an aggregation-prone molecule. Exploiting the Halo property of binding covalently ligands labelled with different fluorochromes, we developed and performed non-radioactive pulse and chase assays to follow sequential waves of proteins in ESC, discriminating between young and old molecules at the single cell level. In this way, we could monitor secretion and degradation of ER proteins in living cells. We can also follow the biogenesis, growth, accumulation and movements of protein aggregates in the ESC. Our data show that protein deposits within ESC grow by sequential apposition of molecules up to a given size, after which novel seeds are detected. The possibility of using ligands with distinct optical and physical properties offers a novel possibility to dynamically follow the fate of proteins in the ESC.     

Changes of 3,4-dihydroxybenzoic and 4-hydroxybenzoic acids inNicotiana tabacum cell suspension culture

The optimum conditions for cell suspension culture experiments have been characterized by respiration,p-Phenylenediamine oxidase and growth of cell suspension ofNicotiana tabacum for 15 days in stationary culture. Change of 3,4-Dihydroxybenzoic and 4-Hydroxybenzoic acids both present at 10⁻⁴ M in culture medium were studied in short term experiments. An oxidation product of 3,4-Dihydroxybenzoic acid characterized by an absorption maximum at 280 nm was isolated after 1 h of incubation. The 4-Hydroxybenzoic acid did not change when incubated for 4 h under the same conditions.     

A new variety of Draba oreibata (Brassicaceae) from Nevada,U.S.A.

A new variety ofDraba oreibata, var.serpentina, is described, illustrated, and discussed.     

Cortactin Controls Surface Expression of the Voltage-gated Potassium Channel KV10.1

K_V10.1 is a voltage-gated potassium channel aberrantly expressed in many cases of cancer, and participates in cancer initiation and tumor progression. Its action as an oncoprotein can be inhibited by a functional monoclonal antibody, indicating a role for channels located at the plasma membrane, accessible to the antibody. Cortactin is an actin-interacting protein implicated in cytoskeletal architecture and often amplified in several types of cancer. In this study, we describe a physical and functional interaction between cortactin and K_V10.1. Binding of these two proteins occurs between the C terminus of K_V10.1 and the proline-rich domain of cortactin, regions targeted by many post-translational modifications. This interaction is specific for K_V10.1 and does not occur with K_V10.2. Cortactin controls the abundance of K_V10.1 at the plasma membrane and is required for functional expression of K_V10.1 channels.