Angiogenesis, the sprouting of new blood vessels from pre-existing ones, and the permeability of blood vessels are regulated by vascular endothelial growth factor (VEGF) via its two known receptors Flt1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2) The Flt4 receptor tyrosine kinase is related to the VEGF receptors, but does not bind VEGF and its expression becomes restricted mainly to lymphatic endothelia during development In this study, we have purified the Flt4 ligand, VEGF-C, and cloned its cDNA from human prostatic carcinoma cells While VEGF-C is homologous to other members of the VEGF/platelet derived growth factor (PDGF) family, its C-terminal half contains extra cysteine-rich motifs characteristic of a protein component of silk produced by the larval salivary glands of the midge, Chironomus tentans VEGF-C is proteolytically processed, binds Flt4, which we rename as VEGFR-3 and induces tyrosine autophosphorylation of VEGFR-3 and VEGFR-2 In addition, VEGF-C stimulated the migration of bovine capillary endothelial cells in collagen gel VEGF-C is thus a novel regulator of endothelia, and its effects may extend beyond the lymphatic system, where Flt4 is expressed

A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.

Spider silk has outstanding mechanical properties despite being spun at close to ambient temperatures and pressures using water as the solvent. The spider achieves this feat of benign fibre processing by judiciously controlling the folding and crystallization of the main protein constituents, and by adding auxiliary compounds, to create a composite material of defined hierarchical structure. Because the 'spinning dope' (the material from which silk is spun) is liquid crystalline, spiders can draw it during extrusion into a hardened fibre using minimal forces. This process involves an unusual internal drawdown within the spider's spinneret that is not seen in industrial fibre processing, followed by a conventional external drawdown after the dope has left the spinneret. Successful copying of the spider's internal processing and precise control over protein folding, combined with knowledge of the gene sequences of its spinning dopes, could permit industrial production of silk-based fibres with unique properties under benign conditions.

/pdf/liquid-crystalline-spinning-of-spider-silk-1li41hra2c.pdf

Liquid crystalline spinning of spider silk.

We have identified a member of the VEGF family by computer-based homology searching and have designated it VEGF-D. VEGF-D is most closely related to VEGF-C by virtue of the presence of N- and C-terminal extensions that are not found in other VEGF family members. In adult human tissues, VEGF-D mRNA is most abundant in heart, lung, skeletal muscle, colon, and small intestine. Analyses of VEGF-D receptor specificity revealed that VEGF-D is a ligand for both VEGF receptors (VEGFRs) VEGFR-2 (Flk1) and VEGFR-3 (Flt4) and can activate these receptors. However, VEGF-D does not bind to VEGFR-1. Expression of a truncated derivative of VEGF-D demonstrated that the receptor-binding capacities reside in the portion of the molecule that is most closely related in primary structure to other VEGF family members and that corresponds to the mature form of VEGF-C. In addition, VEGF-D is a mitogen for endothelial cells. The structural and functional similarities between VEGF-D and VEGF-C define a subfamily of the VEGFs.

https://www.pnas.org/content/pnas/95/2/548.full.pdf

Vascular endothelial growth factor D (VEGF-D) is a ligand for the tyrosine kinases VEGF receptor 2 (Flk1) and VEGF receptor 3 (Flt4)

Major nucleolar proteins shuttle between nucleus and cytoplasm

Successful implantation is the result of reciprocal interactions between the implantation-competent blastocyst and receptive uterus. Although various cellular aspects and molecular pathways of this dialogue have been identified, a comprehensive understanding of the implantation process is still missing. The receptive state of the uterus, which lasts for a limited period, is defined as the time when the uterine environment is conducive to blastocyst acceptance and implantation. A better understanding of the molecular signals that regulate uterine receptivity and implantation competency of the blastocyst is of clinical relevance because unraveling the nature of these signals may lead to strategies to correct implantation failure and improve pregnancy rates. Gene expression studies and genetically engineered mouse models have provided valuable clues to the implantation process with respect to specific growth factors, cytokines, lipid mediators, adhesion molecules, and transcription factors. However, a staggering amount of information from microarray experiments is also being generated at a rapid pace. If properly annotated and explored, this information will expand our knowledge regarding yet-to-be-identified unique, complementary, and/or redundant molecular pathways in implantation. It is hoped that the forthcoming information will generate new ideas and concepts for a process that is essential for maintaining procreation and solving major reproductive health issues in women.

Molecular cues to implantation

Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander mortalities in North America.

Protein C23, a predominant nucleolar phosphoprotein and a putative nucleolus organizer protein, was analyzed for its general DNA binding characteristics and for its selectivity in binding plasmid DNAs containing cloned fragments of the genes that code for ribosomal RNA (rDNA). By use of nitrocellulose filter disk assays, the protein bound saturably to nuclear DNA with a relatively high affinity. Binding was maximal at low ionic strength (0-0.1 M KCl) with progressively decreasing binding at or above 0.2 M. In competition assays protein C23 showed a marked preference for linear single-stranded vs. double-stranded DNA and little or no affinity for ribosomal RNA. The relative affinities of rDNA sequences for protein C23 were determined with cloned fragments spanning 15.8 kilobases (kb) of DNA starting approximately 3.7 kb upstream from the initiation site for 45S preribosomal RNA to near the 3' end of the sequence coding for 28S RNA. Of the five linearized plasmids tested, only one (pKW1) was an effective competitor for 32P-labeled nuclear DNA. As measured by the concentration of competing DNA required to achieve 50% competition, pKW1 was approximately 20-fold more effective than the second best competitor. The DNA insert in pKW1 is a 3.5-kb sequence which is located in the nontranscribed spacer region less than 0.5 kb upstream from the initiation site for 45S preribosomal RNA. These results suggest that protein C23 has a preference for binding DNA sequences in the nontranscribed spacer of rDNA.

Interaction of nucleolar phosphoprotein C23 with cloned segments of rat ribosomal deoxyribonucleic acid.

In 1998 viruses were isolated from tiger salamander larvae (Ambystoma tigrinum diaboli and A. tigrinum melanostictum) involved in North Dakota and Utah (USA) mortality events and spotted salamander (A. maculatum) larvae in a third event in Maine (USA). Although sympatric caudates and anurans were present at all three sites only ambystomid larvae appeared to be affected. Mortality at the North Dakota site was in the thousands while at the Utah and Maine sites mortality was in the hundreds. Sick larvae were lethargic and slow moving. They swam in circles with obvious buoyancy problems and were unable to remain upright. On the ventral surface, near the gills and hind limbs, red spots or swollen areas were noted. Necropsy findings included: hemorrhages and ulceration of the skin, subcutaneous and intramuscular edema, swollen and pale livers with multifocal hemorrhage, and distended fluid-filled intestines with areas of hemorrhage. Light microscopy revealed intracytoplasmic inclusions, suggestive of a viral infection, in a variety of organs. Electron microscopy of ultra thin sections of the same tissues revealed iridovirus-like particles within the inclusions. These viruses were isolated from a variety of organs, indicating a systemic infection. Representative viral isolates from the three mortality events were characterized using molecular assays. Characterization confirmed that the viral isolates were iridoviruses and that the two tiger salamander isolates were similar and could be distinguished from the spotted salamander isolate. The spotted salamander isolate was similar to frog virus 3, the type species of the genus Ranavirus, while the tiger salamander isolates were not. These data indicate that different species of salamanders can become infected and die in association with different iridoviruses. Challenge assays are required to determine the fish and amphibian host range of these isolates and to assess the susceptibility of tiger and spotted salamanders to heterologous virus isolates.

https://bioone.org/journals/journal-of-wildlife-diseases/volume-39/issue-3/0090-3558-39.3.556/DIAGNOSTIC-AND-MOLECULAR-EVALUATION-OF-THREE-IRIDOVIRUS-ASSOCIATED-SALAMANDER-MORTALITY/10.7589/0090-3558-39.3.556.pdf

Steven T. Case

Papers

Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander mortalities in North America.

Interaction of nucleolar phosphoprotein C23 with cloned segments of rat ribosomal deoxyribonucleic acid.

Diagnostic and molecular evaluation of three iridovirus-associated salamander mortality events.

Balbiani ring 3 in Chironomus tentans encodes a 185-kDa secretory protein which is synthesized throughout the fourth larval instar

A cell-specific glycosylated silk protein from Chironomus thummi salivary glands. Cloning, chromosomal localization, and characterization of cDNA.