VEGF links hippocampal activity with neurogenesis, learning and memory

An enriched environment is associated with hippocampal plasticity, including improved cognitive performance and increased neurogenesis. Here, we show that hippocampal expression of vascular endothelial growth factor (VEGF) is increased by both an enriched environment and performance in a spatial maze. Hippocampal gene transfer of VEGF in adult rats resulted in approximately 2 times more neurogenesis associated with improved cognition. In contrast, overexpression of placental growth factor, which signals through Flt1 but not kinase insert domain protein receptors (KDRs), had negative effects on neurogenesis and inhibited learning, although it similarly increased endothelial cell proliferation. Expression of a dominant-negative mutant KDR inhibited basal neurogenesis and impaired learning. Coexpression of mutant KDR antagonized VEGF-enhanced neurogenesis and learning without inhibiting endothelial cell proliferation. Furthermore, inhibition of VEGF expression by RNA interference completely blocked the environmental induction of neurogenesis. These data support a model in which VEGF, acting through KDR, mediates the effect of the environment on neurogenesis and cognition.     

The knockout mouse project

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.     

A tiling resolution DNA microarray with complete coverage of the human genome

We constructed a tiling resolution array consisting of 32,433 overlapping BAC clones covering the entire human genome. This increases our ability to identify genetic alterations and their boundaries throughout the genome in a single comparative genomic hybridization (CGH) experiment. At this tiling resolution, we identified minute DNA alterations not previously reported. These alterations include microamplifications and deletions containing oncogenes, tumor-suppressor genes and new genes that may be associated with multiple tumor types. Our findings show the need to move beyond conventional marker-based genome comparison approaches, that rely on inference of continuity between interval markers. Our submegabase resolution tiling set for array CGH (SMRT array) allows comprehensive assessment of genomic integrity and thereby the identification of new genes associated with disease.     

Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.     

Immunochemical identification of vitellogenin in the serum of the newtTriturus cristatus

Summary The hematic yolk precursor — vitellogenin — has been identified immunochemically in the serum of estrogenized females of the newtTriturus cristatus by employing an antiserum prepared against yolk proteins.     

Effect of pylorus ligation on gastric mucosal mast cell population in normal and adrenalectomised albino rats

Summary Pylorus ligation in normal albino rats acts like a stressor leading to degranulation of mast cells in gastric mucosa, thereby decreasing their number. This decrease is less pronounced when pylorus ligation is done in adrenalectomized rats. This implies that action of a stressor on gastric function involves the adrenal steroids which liberate the powerful gastric stimulant histamine from gastric mucosal mast cells.     

Population dynamics of soil inhabiting mites in cucumber treated with granular insect growth regulatirs (IGRs)

Summary In small field trials, certain granular insect growth regulators (IGRs) induced significant reduction in soil inhabiting mites of cucumber plantation at a rate as low as 0.25 kg. a.i./acre. However, suborders speciificity relationship could easily be detected.     

Permeability of cellophane membranes to parotid proteins during dialysis

Summary Pooled parotid saliva was dialyzed in cellophane membranes against water for periods of up to 1 week and loss of proteins was monitored by acrylamide gel-electrophoresis. A gradual loss of cationic proteins was observed whereas anionic proteins were not appreciably affected. Loss of the cationic proteins could be greatly reduced by performing dialyses against dilute electrolyte solutions rather than water. These effects were attributed primarily to electrostatic charges associated with the dialysis membranes.The assistance of Mr E. Pederson and Dr G. Clark is gratefully acknowledged. Supported by Naval Medical Research and Development Command Project MR005.19 6048, Bethesda, Maryland. The opinions expressed herein are those of the authors and are not be construed as reflecting the views of the Navy Department or the Naval Service at large. The use of commercially available products does not imply endorsement of these products or preference to other similar products on the market.Deceased.