Charting a New Frontier Integrating Mathematical Modeling in Complex Biological Systems from Molecules to Ecosystems.

Advances in quantitative biology data collection and analysis across scales (molecular, cellular, organismal, and ecological) have transformed how we understand, categorize, and predict complex biological systems. This surge of quantitative data creates an opportunity to apply, develop, and evaluate mathematical models of biological systems and explore novel methods of analysis. Simultaneously, thanks to increased computational power, mathematicians, engineers and physical scientists have developed sophisticated models of biological systems at different scales.

Understanding Drivers of Variation and Predicting Variability Across Levels of Biological Organization.

Differences within a biological system are ubiquitous, creating variation in nature. Variation underlies all evolutionary processes and allows persistence and resilience in changing environments; thus, uncovering the drivers of variation is critical. The growing recognition that variation is central to biology presents a timely opportunity for determining unifying principles that drive variation across biological levels of organization.

Movement, demographics, and occupancy dynamics of a federally-threatened salamander: evaluating the adequacy of critical habitat.

Critical habitat for many species is often limited to occupied localities. For rare and cryptic species, or those lacking sufficient data, occupied habitats may go unrecognized, potentially hindering species recovery. Proposed critical habitat for the aquatic Jollyville Plateau salamander (Eurycea tonkawae) and two sister species were delineated based on the assumption that surface habitat is restricted to springs and excludes intervening stream reaches.

Identification and characterization of a rat hepatic oncofetal membrane glycoprotein.

A major interest of our laboratory is to delineate the pathways leading to experimentally induced liver cancer in the rat. Although the cellular progenitors of primary hepatocellular carcinoma remain controversial, current findings suggest that proliferation of chemically initiated liver epithelial cells gives rise to hepatic nodules, a rare population of which eventually progress to carcinoma. Presently, the availability of cell surface markers that are closely associated with malignant progression is needed for the identification, isolation, and further characterization of these rare malignant cells.

Comparison of the structural characteristics of cell-CAM 105 from hepatocytes with those of an altered form expressed by rat transplantable hepatocellular carcinomas.

The structural features of the adult rat hepatocyte (ARH) forms of cell-CAM 105, a Mr 105,000 cell adhesion molecule, were compared using a variety of immunochemical and biochemical techniques with altered forms of more basic pI present on two transplantable hepatocellular carcinomas (THC 1682c and THC AS-30D). Immunoprecipitation analysis with polyclonal (anti-gp 105-2) and monoclonal (MAb) antibodies specific for cell-CAM 105 (MAb 362.50) demonstrated that ARH and THC cell-CAM 105 were indistinguishable in several respects including: (a) binding to wheat germ agglutinin; (b) labeling with NaIO4/NaB3H4; (c) susceptibility to digestion with endoglycosidases (endoglycosidase H and F and peptide N-glycosidase F N-glycanase); (d) rate of turnover on the cell surface; and (e) differential resistance of upper and lower forms to trypsin digestion in the presence or absence of calcium.

Detection of an altered form of cell-CAM 105 on rat transplantable and primary hepatocellular carcinomas.

Monoclonal (MAb 362.50) and polyclonal (anti-gp 105-2) antibodies have been used to examine the expression by transplantable (THC) and primary (PHC) hepatocellular carcinomas of a 105 kd rat hepatocyte cell adhesion molecule designated cell-CAM 105. Two-dimensional gel analysis of components immunoprecipitated with MAb 362.

Alterations in the expression of a hepatocyte cell adhesion molecule by transplantable rat hepatocellular carcinomas.

Alterations in the expression of normal cell surface components on 13 transplantable hepatocellular carcinomas were examined using a heteroantiserum [anti-Mr 105,000 glycoprotein (gp 105)] reactive with a family of nine wheat germ agglutinin binding components from normal rat hepatocytes with an average molecular weight of 105,000. Analysis by two-dimensional polyacrylamide gel electrophoresis of components immunoprecipitated by anti-gp105 antiserum from detergent extracts of transplantable hepatocellular carcinoma cells surface labeled with 125I revealed qualitative and quantitative changes in the expression of anti-gp105-reactive components with the most consistent change being the apparent loss of a pair of acidic (pl 4.1 to 4.

Identification of dipeptidyl peptidase IV as a protein shared by the plasma membrane of hepatocytes and liver biomatrix.

The histotypic organization of liver parenchyma involves specific intercellular contacts and interaction of hepatocytes with supporting biomatrix. Evidence from this laboratory identified a peptide (Hep105, apparent Mr 105 000) that is shared by the plasma membrane of rat hepatocytes and rat liver biomatrix. This report identifies Hep105 as a peptide component of dipeptidyl peptidase IV (DPPIV; EC 3.

Structural differences in envelope glycoproteins associated with rat leukaemia virus produced by Novikoff hepatocellular carcinoma and spontaneously transformed Wistar rat embryo cells.

Immunochemical and immunocytochemical techniques have been used to characterize viral glycoproteins and endogenous rat leukaemia viruses (RaLV) produced both by Novikoff hepatocellular carcinoma cells and spontaneously transformed Wistar rat embryo cells (WRC). Results from immunocytochemical analysis demonstrated that RaLV produced by Novikoff and WRC cells could be distinguished by their unique patterns of reactivity with xenoantisera raised against virus particles or viral glycoproteins. This differential labelling was unexpected since all the antisera tested had been shown by immunoprecipitation and immunodepletion analysis to be reactive with viral glycoproteins expressed on the cell surface.

Phytochrome induces photoreversible calcium fluxes in a purified mitochondrial fraction from oats.

Previous studies have indicated that phytochrome regulates Ca(2+) fluxes across the plasma membrane of plant cells. In this study we investigated whether phytochrome can also regulate such fluxes across mitochondrial membranes, using the Ca(2+)-sensitive dye murexide to monitor the uptake and release of Ca(2+) by mitochondria. The results showed that Ca(2+) fluxes in these organelles could be photoreversibly altered, red light diminishing the net uptake rate and far-red light restoring this rate to its dark control level.