Engineering excellence in breakthrough biomedical technologies: bioengineering at the University of California, Riverside

The Department of Bioengineering at the University of California, Riverside (UCR), was established in 2006 and is the youngest department in the Bourns College of Engineering. It is an interdisciplinary research engine that builds strength from highly recognized experts in biochemistry, biophysics, biology, and engineering, focusing on common critical themes. The range of faculty research interests is notable for its diversity, from the basic cell biology through cell function to the physiology of the whole organism, each directed at breakthroughs in biomedical devices for measurement and therapy. The department forges future leaders in bioengineering, mirroring the field in being energetic, interdisciplinary, and fast moving at the frontiers of biomedical discoveries. Our educational programs combine a solid foundation in bio logical sciences and engineering, diverse communication skills, and training in the most advanced quantitative bioengineering research. Bioengineering at UCR also includes the Bioengineering Interdepartmental Graduate (BIG) program. With its slogan Start-Grow-Be-BIG, it is already recognized for its many accomplishments, including being third in the nation in 2011 for bioengineering students receiving National Science Foundation graduate research fellowships as well as being one of the most ethnically inclusive programs in the nation.     

Renal cyclic GMP and cholinergic mechanisms in erythropoietin production.

Cobalt treatment in rats produced sequential elevations in both renal cyclic GMP concentration and lysosomal enzyme activity in plasma. These effects of cobalt were significantly inhibited by atropine pretreatment, as was cobalt-mediated erythropoietin (ESF) production. Physostigmine, an inhibitor of acetylcholinesterase, potentiated the erythropoietic effect of cobalt. These data are consistent with the hypothesis that the erythropoietic effect of cobalt is associated with a cholinergic mechanism involving cyclic GMP-mediated lysosomal enzyme release. These cholinergic events may precede a previously described cyclic AMP activation of a renal erythropoietic factor.     

Do small and large luteal cells of the sheep interact in the production of progesterone?

Corpora lutea from cyclic ewes were dissociated by collagenase and trypsin/EGTA treatments, and enriched fractions of small and large luteal cells were prepared on gradients of Ficoll. These fractions were incubated separately or remixed before incubation. Colchicine, cytochalasin B and the calcium channel-blocker verapamil significantly reduced progesterone production by both small and large luteal cell fractions, while isoprenaline stimulated an increase in progesterone production by large luteal cell fractions only. When fractions of small and large luteal cells were remixed, no more and no less progesterone was produced than would have been predicted from equivalent fractions incubated separately. There was therefore no evidence of synergism between small and large luteal cells in the production of progesterone. Prostaglandin F-2 alpha, which can inhibit LH-stimulated progesterone production by ovine luteal tissue in vitro, had no effect on LH-stimulated progesterone production by small luteal cell fractions, but significantly inhibited that by enriched fractions of large luteal cells. Since large luteal cell fractions were contaminated with small luteal cells, which are probably responsible for the progesterone-secretory response of these fractions to LH, it was concluded that the inhibition of LH-stimulated progesterone production by small luteal cells is dependent on the presence of large luteal cells. Oxytocin added to large and small luteal cell fractions did not affect progesterone production by either fraction. It was therefore concluded that the inhibitory action of PGF-2 alpha on LH-stimulated progesterone production may require the interaction of large and small luteal cells, but that oxytocin is not likely to be an intermediary in this interaction.     

Depressor effect of diabetes in spontaneously hypertensive rat: role of vascular reactivity and prolyl hydroxylase and lysyl oxidase activities

Streptozotocin (STZ)-induced diabetes (8 weeks) produced a marked depressor effect in the spontaneously hypertensive rat (SHR), confirming earlier studies, but had no effect on arterial pressure of normotensive controls (WKY). We investigated the phenomenon further by examining the effects of diabetes on the activities of aortic prolyl hydroxylase (PH) and lysyl oxidase (LO), marker enzymes for collagen biosynthesis, and on the reactivity of isolated mesenteric arteries to vasoactive agents. PH and LO activities of nondiabetic SHR were greater than those of the WKY controls. Diabetes markedly reduced PH and LO activities of SHR aortae, but had no significant effect on PH and LO activities of the WKY strain. The effects of diabetes on vascular collagen biosynthetic enzymes of SHR were not associated with reductions in mesenteric arterial responsiveness or sensitivity to norepinephrine, methoxamine, serotonin or KC1. These results suggest that the depressor effect of diabetes in SHR is associated with a reduction in vascular collagen biosynthesis but not a reduction in vascular reactivity.     

Seasonality of first coitus in the United States.

Recent attention to causes of seasonality of births leads to an interest in seasonality patterns in the antecedents to birth, including gestational length, conception, and coital activity. In this paper we study the beginning of the process: first intercourse among adolescents and young adults. Analysis of a small and local dataset is suggestive that loss of virginity is particularly likely during the summer. A test of this "Summer Vacation Theory" using a large national dataset supports the generality of the phenomenon. Further, a prediction that seasonality patterns will change during the transition from high school to work and college is tested and supported. The existence of both biological and psycho-social mechanisms is suggested. Policy implications are reviewed.     

The role of bovine lipoproteins in the regulation of steroidogenesis and HMG-CoA reductase in bovine adrenocortical cells.

The sources of cholesterol for steroid hormone production were examined using bovine adrenocortical (BAC) cells in primary culture. The experiments were designed to determine the effects of lipoproteins on cortisol production and the level of BAC cell 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Most studies on BAC cell lipoprotein requirements have been conducted using human low-density lipoprotein (hHDL); none have used the homologous bovine lipoproteins. BAC cells treated with corticotropin (ACTH) in a medium devoid of lipoproteins increased and maintained cortisol production 7- to 20-fold above basal levels. Under such conditions ACTH also increased the rate of HMG-CoA reductase activity. Inhibition of HMG-CoA reductase with mevinolin inhibited cortisol production by 85%, indicating that the cells were using cholesterol synthesized de novo for steroid production. Cortisol production was increased almost 40-fold above basal levels if hLDL (100 micrograms/ml) was included in the incubation medium. Human LDL also suppressed the levels of HMG-CoA reductase in a concentration-dependent fashion. Human HDL was without effect on either BAC cell steroidogenesis of HMG-CoA reductase. Addition of bovine LDL (bLDL) to the incubation medium also caused an increase in cortisol production and inhibited cholesterol synthesis. By contrast to hHDL, bHDL (100 micrograms/ml) increased the ability of BAC cells to produce cortisol production. Bovine HDL (bHDL) also was able to decrease HMG-CoA reductase, but not to the extent caused by hLDL or bLDL. These data demonstrate that bovine adrenal cells can use bHDL as a source of cholesterol for steroid hormone production. These findings may be of particular importance when one considers that in vivo, the bHDL content of bovine serum greatly surpasses the level of bLDL.     

On the feasibility of electron transfer to singlet oxygen from mitochondrial components

The incorporation of [¹⁴C]mannose from GDP-[¹⁴C]mannose into dolichyl mannosyl phosphate in rat liver microsomes showed a biphasic time-course; an initial rapid incorporation of mannose which ceased within 2 min and a much slower incorporation which continued for 30 min. In the presence of 0.18 mM (250 μg/ml) bacitracin, the rapid incorporation proceeded normally whereas the slow incorporation was inhibited by about 70%. Upon addition of dolichyl pyrophosphate, the microsomes catalyzed the dephosphorylation of the added compound which was also inhibited by bacitracin. The results, coupled with several other observations, suggest that the rapid reaction represents the transfer of mannose to endogenous dolichyl phosphate whereas the bacitracin-sensitive, slow reaction represents a more complex process in which the enzymatic dephosphorylation of dolichyl pyrophosphate is involved as a rate-limiting step.     

Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method.

We developed a method for immunoaffinity purification of Saccharomyces cerevisiae adenylyl cyclase based on creating a fusion with a small peptide epitope. Using oligonucleotide technology to encode the peptide epitope we constructed a plasmid that expressed the fusion protein from the S. cerevisiae alcohol dehydrogenase promoter ADH1. A monoclonal antibody previously raised against the peptide was used to purify adenylyl cyclase by affinity chromatography. The purified enzyme appeared to be a multisubunit complex consisting of the 200-kilodalton adenylyl cyclase fusion protein and an unidentified 70-kilodalton protein. The purified protein could be activated by RAS proteins. Activation had an absolute requirement for a guanine nucleoside triphosphate.