HEMATOLOGY, BIOCHEMISTRY, AND METAL CONTAMINANT LEVELS IN WILD-CAUGHT CLAPPER RAIL (RALLUS CREPITANS) IN NORTHEASTERN FLORIDA.

The clapper rail (Rallus crepitans) is native to salt marshes along the eastern United States. Populations are likely stable, but may be at risk due to the degradation of wetland habitat by contaminants. Contaminants can cause adverse effects in birds such as alteration of immune and reproductive function, and previous studies have used this species as a sentinel for estuarine health. Blood samples were collected from clapper rails in Florida and hematology counts, plasma biochemistry panels, and metal assessments using inductively coupled plasma-mass spectrometry were performed. Biochemical and hematology data were too limited to determine if contaminants were adversely affecting clapper rails in this study, but cadmium, lead, and zinc were increased for several birds. Although contaminant levels were not consistently elevated for all birds, additional research is needed to assess if clapper rails in this region are at risk of contaminant exposure due to increasing urbanization and development pressures.

Miniscrew biomechanics: Guidelines for the use of rigid indirect anchorage mechanics.

Indirect anchorage is an established form of anchorage provided by orthodontic miniscrews. Although there are different ways to set up the mechanics, rigid indirect anchorage offers the greatest biomechanical versatility but is more difficult to install than conventional, nonrigid indirect anchorage or direct anchorage. The purpose of this article was to introduce readers to the concept of rigid indirect anchorage and provide guidelines as to its use.

Emergence of Resistance to MTI-101 Selects for a MET Genotype and Phenotype in EGFR Driven PC-9 and PTEN Deleted H446 Lung Cancer Cell Lines.

MTI-101 is a first-in-class cyclic peptide that kills cells via calcium overload in a caspase-independent manner. Understanding biomarkers of response is critical for positioning a novel therapeutic toward clinical development. Isogenic MTI-101-acquired drug-resistant lung cancer cell line systems (PC-9 and H446) coupled with differential RNA-SEQ analysis indicated that downregulated genes were enriched in the hallmark gene set for epithelial-to-mesenchymal transition (EMT) in both MTI-101-acquired resistant cell lines. The RNA-SEQ results were consistent with changes in the phenotype, including a decreased invasion in Matrigel and expression changes in EMT markers (E-cadherin, vimentin and Twist) at the protein level. Furthermore, in the EGFR-driven PC-9 cell line, selection for resistance towards MTI-101 resulted in collateral sensitivity toward EGFR inhibitors. MTI-101 treatment showed synergistic activity with the standard of care agents erlotinib, osimertinib and cisplatin when used in combination in PC-9 and H446 cells, respectively. Finally, in vivo data indicate that MTI-101 treatment selects for increased E-cadherin and decreased vimentin in H446, along with a decreased incident of bone metastasis in the PC-9 in vivo model. Together, these data indicate that chronic MTI-101 treatment can lead to a change in cell state that could potentially be leveraged therapeutically to reduce metastatic disease.

Role of Calcium Homeostasis in Modulating EMT in Cancer.

Calcium is essential for cells to perform numerous physiological processes. In cancer, the augmentation of calcium signaling supports the more proliferative and migratory cells, which is a characteristic of the epithelial-to-mesenchymal transition (EMT). By genetically and epigenetically modifying genes, channels, and entire signaling pathways, cancer cells have adapted to survive with an extreme imbalance of calcium that allows them to grow and metastasize in an abnormal manner. This cellular remodeling also allows for the evasion of immune surveillance and the development of drug resistance, which lead to poor prognosis in patients. Understanding the role calcium flux plays in driving the phenotypes associated with invasion, immune suppression, metastasis, and drug resistance remains critical for determining treatments to optimize clinical outcomes and future drug discovery.

Drosophila Enhancer of zeste protein interacts with dSAP18.

The Drosophila Enhancer of zeste [E(z)] gene encodes a member of the Polycomb group of transcriptional repressors. Here we report evidence for direct physical interaction between E(Z) and dSAP18, which previously has been shown to interact with Drosophila GAGA factor and BICOID proteins. dSAP18 shares extensive sequence similarity with a human polypeptide originally identified as a subunit of the SIN3A-HDAC (switch-independent 3-histone deacetylase) co-repressor complex. Yeast two-hybrid and in vitro binding assays demonstrate direct E(Z)-dSAP18 interaction and show that dSAP18 is capable of interacting with itself. Co-immunoprecipitation experiments provide evidence for in vivo association of E(Z) and dSAP18. Gel filtration analysis of embryo nuclear extracts shows that dSAP18 is present in native protein complexes ranging from approximately 1100 to approximately 450 kDa in molecular mass. These studies provide support for a model in which dSAP18 contributes to the activities of multiple protein complexes, and potentially may mediate interactions between distinct proteins and/or protein complexes.