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Biomedical subjects

James C Liao

Publications and source records attributed to James C Liao.

9 recordsLinked to original sources
PubMed2003

Analysis of nitric oxide consumption by erythrocytes in blood vessels using a distributed multicellular model.

Multiple sets of experimental data have shown that the red blood cell (RBC) consumes nitric oxide (NO) about 600-1000-fold slower than the equivalent concentration of cell-free hemoglobin (Hb). Diffusion barriers of various sources have been suggested to explain this observation. In this work, a multicellular, spatially distributed, two-dimensional model, that describes the production, transport, and consumption of NO in blood vessels and the surrounding tissue, is developed. The model is used to assess the relative significance of NO transport barriers that reduce the rate of NO consumption in the blood. Unlike previous models of this system, the model developed here accounts explicitly for the presence of, and interactions among, a population of RBCs inside the lumen of the blood vessel and is, therefore, better suited to analyze, quantitatively, the contribution of each transport barrier as NO diffuses from its site of synthesis to the interior of the RBCs where it interacts with Hb. The model, which uses experimentally derived parameters, shows that extracellular unstirred boundary layer diffusion alone cannot account for the reduced NO consumption by RBC compared to an equivalent concentration of cell-free Hb. Since this result is reached using a two-dimensional representation of the RBCs, which overestimates the importance of the boundary layer diffusion resistance, it would be expected that in the real three-dimensional case, diffusion through the extracellular boundary layer would contribute even less to the overall mass transfer resistance. Consistent with recent experimental findings, the results of our model suggest that, under physiological conditions, transmembrane (membrane and its associated cytoskeleton layer) diffusion limitations in RBCs represent a key source of resistance for NO uptake by RBCs.

Animals↗
PubMed2003

The Kármán gait: novel body kinematics of rainbow trout swimming in a vortex street.

Most fishes commonly experience unsteady flows and hydrodynamic perturbations during their lifetime. In this study, we provide evidence that rainbow trout Oncorhynchus mykiss voluntarily alter their body kinematics when interacting with vortices present in the environment that are not self-generated. To demonstrate this, we measured axial swimming kinematics in response to changes in known hydrodynamic wake characteristics. We compared trout swimming in the Kármán street behind different diameter cylinders (2.5 and 5 cm) at two flow speeds (2.5 and 4.5 L s(-1), where L is total body length) to trout swimming in the free stream and in the cylinder bow wake. Trout swimming behind cylinders adopt a distinctive, previously undescribed pattern of movement in order to hold station, which we term the Kármán gait. During this gait, body amplitudes and curvatures are much larger than those of trout swimming at an equivalent flow velocity in the absence of a cylinder. Tail-beat frequency is not only lower than might be expected for a trout swimming in the reduced flow behind a cylinder, but also matches the vortex shedding frequency of the cylinder. Therefore, in addition to choosing to be in the slower flow velocity offered behind a cylinder (drafting), trout are also altering their body kinematics to synchronize with the shed vortices (tuning), using a mechanism that may not involve propulsive locomotion. This behavior is most distinctive when cylinder diameter is large relative to fish length. While tuning, trout have a longer body wavelength than the prescribed wake wavelength, indicating that only certain regions of the body may need to be oriented in a consistent manner to the oncoming vortices. Our results suggest that fish can capture energy from vortices generated by the environment to maintain station in downstream flow. Interestingly, trout swimming in front of a cylinder display lower tail-beat amplitudes and body wave speeds than trout subjected to any of the other treatments, implying that the bow wake may be the most energetically favorable region for a fish to hold station near a cylinder.

Animals↗
PubMed2002

A memorial review of Jay Bailey's contribution in prokaryotic metabolic engineering.

When mentioning prokaryotic metabolic engineering, most people will immediately think of Jay Bailey. Jay's contribution to this fast-growing field is evident and familiar to many. Therefore, instead of a detailed technical review, we attempt in this article to summarize his contribution and dissect reasons for his success in this area from a standpoint of one of his former students (VH) and of a colleague in the field (JCL). This short review is by no means complete and provides only a partial view of Jay's contribution to the metabolic engineering of prokaryotes.

Biochemistry↗
PubMed2002

Nitric oxide is consumed, rather than conserved, by reaction with oxyhemoglobin under physiological conditions.

Although irreversible reaction of NO with the oxyheme of hemoglobin (producing nitrate and methemoglobin) is extremely rapid, it has been proposed that, under normoxic conditions, NO binds preferentially to the minority deoxyheme to subsequently form S-nitrosohemoglobin (SNOHb). Thus, the primary reaction would be conservation, rather than consumption, of nitrogen oxide. Data supporting this conclusion were generated by using addition of a small volume of a concentrated aqueous solution of NO to a normoxic hemoglobin solution. Under these conditions, however, extremely rapid reactions can occur before mixing. We have thus compared bolus NO addition to NO generated homogeneously throughout solution by using NO donors, a more physiologically relevant condition. With bolus addition, multiple hemoglobin species are formed (as judged by visible spectroscopy) as well as both nitrite and nitrate. With donor, only nitrate and methemoglobin are formed, stoichiometric with the amount of NO liberated from the donor. Studies with increasing hemoglobin concentrations reveal that the nitrite-forming reaction (which may be NO autoxidation under these conditions) competes with reaction with hemoglobin. SNOHb formation is detectable with either bolus or donor; however, the amounts formed are much smaller than the amount of NO added (less than 1%). We conclude that the reaction of NO with hemoglobin under normoxic conditions results in consumption, rather than conservation, of NO.

Hemoglobins↗
PubMed2002

Co-expression pattern from DNA microarray experiments as a tool for operon prediction.

The prediction of operons, the smallest unit of transcription in prokaryotes, is the first step towards reconstruction of a regulatory network at the whole genome level. Sequence information, in particular the distance between open reading frames, has been used to predict if adjacent Escherichia coli genes are in an operon. While appreciably successful, these predictions need to be validated and refined experimentally. As a growing number of gene expression array experiments on E.coli became available, we investigated to what extent they could be used to improve and validate these predictions. To this end, we examined a large collection of published microarry data. The correlation between expression ratios of adjacent genes was used in a Bayesian classification scheme to predict whether the genes are in an operon or not. We found that for the genes whose expression levels change significantly across the experiments in the data set, the currently available gene expression data allowed a significant refinement of the sequenced-based predictions. We report these co-expression correlations in an E.coli genomic map. For a significant portion of gene pairs, however, the set of array experiments considered did not contain sufficient information to determine whether they are in the same transcriptional unit. This is not due to unreliability of the array data per se, but to the design of the experiments analyzed. In general, experiments that perturb a large number of genes offer more information for operon prediction than confined perturbations. These results provide a rationale for conducting expression studies comparing conditions that cause global changes in gene expression.

Chromosome Mapping↗
PubMed2002

Nitric oxide reaction with red blood cells and hemoglobin under heterogeneous conditions.

Understanding the interaction of nitric oxide (NO) with red blood cells (RBCs) is vital to elucidating the metabolic fate of NO in the vasculature. Because hemoglobin (Hb) is the most abundant intraerythrocytic protein and reacts rapidly with NO, the interaction of NO with Hb has been studied extensively. We and others have shown the NO reaction with RBCs is nearly 1,000-fold slower than the reaction with cell-free Hb. Because the reaction rate of NO with cell-free Hb and RBCs is quite different, we hypothesize that different reaction products evolve under locally high NO concentrations, which can be generated by bolus NO addition or NO inhalation. Here we use electron paramagnetic resonance to show that bolus NO addition to cell-free Hb solutions results in nitrosylhemoglobin [HbFe(II)NO] formation as a minor product through a MetHb-dependent pathway. Further, the RBC is shown to be more prone to form HbFe(II)NO under this heterogeneous condition compared with an equivalent free-Hb solution. In both cases, trapping MetHb with cyanide blocked the formation of HbFe(II)NO. We conclude that the formation of HbFe(II)NO is a heterogeneous phenomenon involving three successive reactions of NO with the same heme molecule. These results were supported further by mathematically modeling NO-Hb reactions and diffusion.

Animals↗
PubMed2002

Global expression profiling of acetate-grown Escherichia coli.

This study characterized the transcript profile of Escherichia coli in acetate cultures using DNA microarray on glass slides. Glucose-grown cultures were used as a reference. At the 95% confidence level, 354 genes were up-regulated in acetate, while 370 genes were down-regulated compared with the glucose-grown culture. Generally, more metabolic genes were up-regulated in acetate than other gene groups, while genes involved in cell replication, transcription, and translation machinery tended to be down-regulated. It appears that E. coli commits more resources to metabolism at the expense of growth when cultured in the poor carbon source. The expression profile confirms many known features in acetate metabolism such as the induction of the glyoxylate pathway, tricarboxylic acid cycle, and gluconeogenic genes. It also provided many previously unknown features, including induction of malic enzymes, ppsA, and the glycolate pathway and repression of glycolytic and glucose phosphotransferase genes in acetate. The carbon flux delivered from the malic enzymes and PpsA in acetate was further confirmed by deletion mutations. In general, the gene expression profiles qualitatively agree with the metabolic flux changes and may serve as a predictor for gene function and metabolic flux distribution.

Acetates↗
PubMed2002

Swimming in needlefish (Belonidae): anguilliform locomotion with fins.

The Atlantic needlefish (Strongylura marina) is a unique anguilliform swimmer in that it possesses prominent fins, lives in coastal surface-waters, and can propel itself across the surface of the water to escape predators. In a laboratory flow tank, steadily swimming needlefish perform a speed-dependent suite of behaviors while maintaining at least a half wavelength of undulation on the body at all times. To investigate the effects of discrete fins on anguilliform swimming, I used high-speed video to record body and fin kinematics at swimming speeds ranging from 0.25 to 2.0 L s(-1) (where L is the total body length). Analysis of axial kinematics indicates that needlefish are less efficient anguilliform swimmers than eels, indicated by their lower slip values. Body amplitudes increase with swimming speed, but unlike most fishes, tail-beat amplitude increases linearly and does not plateau at maximal swimming speeds. At 2.0 L s(-1), the propulsive wave shortens and decelerates as it travels posteriorly, owing to the prominence of the median fins in the caudal region of the body. Analyses of fin kinematics show that at 1.0 L s(-1) the dorsal and anal fins are slightly less than 180 degrees out of phase with the body and approximately 225 degrees out of phase with the caudal fin. Needlefish exhibit two gait transitions using their pectoral fins. At 0.25 L s(-1), the pectoral fins oscillate but do not produce thrust, at 1.0 L s(-1) they are held abducted from the body, forming a positive dihedral that may reduce rolling moments, and above 2.0 L s(-1) they remain completely adducted.

Animals↗