LabVIEW-based control software for para-hydrogen induced polarization instrumentation.

The elucidation of cell metabolic mechanisms is the modern underpinning of the diagnosis, treatment, and in some cases the prevention of disease. Para-Hydrogen induced polarization (PHIP) enhances magnetic resonance imaging (MRI) signals over 10,000 fold, allowing for the MRI of cell metabolic mechanisms. This signal enhancement is the result of hyperpolarizing endogenous substances used as contrast agents during imaging. PHIP instrumentation hyperpolarizes Carbon-13 ((13)C) based substances using a process requiring control of a number of factors: chemical reaction timing, gas flow, monitoring of a static magnetic field (Bo), radio frequency (RF) irradiation timing, reaction temperature, and gas pressures. Current PHIP instruments manually control the hyperpolarization process resulting in the lack of the precise control of factors listed above, resulting in non-reproducible results. We discuss the design and implementation of a LabVIEW based computer program that automatically and precisely controls the delivery and manipulation of gases and samples, monitoring gas pressures, environmental temperature, and RF sample irradiation. We show that the automated control over the hyperpolarization process results in the hyperpolarization of hydroxyethylpropionate. The implementation of this software provides the fast prototyping of PHIP instrumentation for the evaluation of a myriad of (13)C based endogenous contrast agents used in molecular imaging.

Unifying electrostatic mechanism for receptor-ligand activity.

A prior article in skeletal form proposed an electrostatic mechanism for receptor-ligand activity. The present review provides an elaboration, including supporting evidence. The fundamental aspect entails the presence of molecular electrostatic potential associated with ions and dipoles in the ligand. The ligand can be regarded as an electrical link that joins prevalent electrostatic fields present in the surrounding protein matrix. The exact role of these fields is speculative. One possibility is to function as conduits for electrons and radicals in cell signaling. There is increasing support for important participation of these species in signal transduction. There might also be a favorable influence on energetics involving the electron transfer process. A summary of receptor biology is also provided, including receptors for acetylcholine (nicotinic and muscarinic), GABA, adrenergic, and glutamate.

Unifying electrostatic mechanism for phosphates and sulfates in cell signaling.

Prior proposals suggested the importance of electrochemistry in signal transduction and receptor-ligand activity. Electrostatic fields associated with ions and dipoles were assigned important roles. Little is known concerning the precise mode of action in cell signaling by widespread phosphorylation. According to the hypothetical framework, molecular electrostatic potential associated with phosphate anion is a key element as a link in the communication grid, possibly inducing favorable energetics in the electron transfer process. Similar involvement appears plausible for the sulfate anion. Supporting evidence for the electrostatic mechanism is presented. Representative literature on phosphorylation in the biological domain is reviewed with emphasis on cell signaling. The treatment includes phosphates from protein, lipids, and other molecules, plus the role of reactive oxygen species. Protein sulfation is also discussed.

Bioelectronome. Integrated approach to receptor chemistry, radicals, electrochemistry, cell signaling, and physiological effects based on electron transfer.

Bioelectronome refers to the host of electron transfer (ET) reactions that occur in living systems. This review presents an integrated approach to receptor chemistry based on electron transfer, radicals, electrochemistry, cell signaling, and end result. First, receptor activity is addressed from the unifying standpoint of redox transformations in which various receptors are discussed. After a listing of receptor-binding modes, receptor chemistry is treated with focus on generation of reactive oxygen species (ROS), activation by ROS, and subsequent cell signaling involving ROS. A general electrostatic mechanism is proposed for receptor-ligand action with supporting evidence. Cell-signaling processes appear to entail electron transfer, ROS, redox chains, and relays. The widespread involvement of phosphate from phosphorylation may be rationalized electrostatically by analogy with DNA phosphate. Extensive evidence supports important participation of ET functionalities in the mechanism of drugs and toxins. The integrated approach is applied to the main ET classes, namely, quinones, metal complexes, iminium species, and aromatic nitro compounds.

Effects of hypoxia on the onset of muscle deoxygenation and the lactate threshold.

Six subjects performed two trials of incremental cycling to exhaustion under normoxic and hypoxic conditions. The lactate threshold and onset of muscle deoxygenation were highly correlated under both conditions, and during the hypoxic condition both variables shifted leftward.

Ugandan Kaposi's sarcoma-associated herpesvirus phylogeny: evidence for cross-ethnic transmission of viral subtypes.

OBJECTIVE: The aim of this study was to test the relationship between Kaposi's sarcoma-associated herpesvirus (KSHV) phylogeny and host ethnicity at the within-country scale. METHODS: KSHV genomic DNA samples were isolated from 31 patients across eleven Ugandan ethnic groups. Amino acid sequences of the ORF-K1 gene were used to construct a neighbor-joining phylogenetic tree. RESULTS: A5 and B1 variants predominated with no evidence of distinct ethnic or geographic distribution. A new K1 subtype (F) was identified in a member of the Bantu Gisu tribe and a new subtype B variant (B3) among members of the Bantu Ganda tribe. CONCLUSIONS: The phylogeny may yet be structured by host ethnicity if members of Ugandan groups have convoluted biological origins, even as they identify with single tribes. An alternative possibility is that KSHV subtype evolution may have preceded major diversification of sub-Saharan Africans into ethnicities as we know them today, with ethnic groups beginning their histories already hosting multiple subtypes. A third alternative is that horizontal transmission of multiple KSHV subtypes may have broken up vertical lineages of the virus passed down within Ugandan populations.

Cell signaling (mechanism and reproductive toxicity): redox chains, radicals, electrons, relays, conduit, electrochemistry, and other medical implications.

This article deals with a novel, simple, integrated approach to cell signaling involving basic biochemical principles, and their relationship to reproductive toxicity. Initially, an overview of the biological aspects is presented. According to the hypothetical approach, cell signaling entails interaction of redox chains, involving initiation, propagation, and termination. The messengers are mainly radicals and electrons that are generated during electron transfer (ET) and hydrogen atom abstraction reactions. Termination and initiation processes in the chain occur at relay sites occupied by redox functionalities, including quinones, metal complexes, and imines, as well as redox amino acids. Conduits for the messengers, comprising species with nonbonding electrons, are omnipresent. Details are provided for the various electron transfer processes. In relation to the varying rates of cell communication, rationale is based on electrons and size of radicals. Another fit is similarly seen in inspection of endogenous precursors of reactive oxygen species (ROS); namely, proteins bearing redox moieties, lipid oxidation products, and carbohydrate radicals. A hypothesis is advanced in which electromagnetic fields associated with mobile radicals and electrons play a role. Although radicals have previously been investigated as messengers, the area occupies a minor part of the research, and it has not attracted broad consensus as an important component. For the first time, an integrated framework is presented composed of radicals, electrons, relays, conduits, and electrical fields. The approach is in keeping with the vast majority of experimental observations. Cell signaling also plays an important role in reproductive toxicity. The main classes that cause birth defects, including ROS, radiation, metal compounds, medicinals, abused drugs, and miscellaneous substances, are known to participate in the signaling process. A unifying basis exists, in that both signaling and reproductive toxicity are characterized by the electron transfer-reactive oxygen species-oxidative stress (ET-ROS-OS) scheme. This article also incorporates representative examples of the extensive investigations dealing with various medical implications. There is considerable literature pointing to a role for cell communication in a wide variety of illnesses.

Skin blood flow affects in vivo near-infrared spectroscopy measurements in human skeletal muscle.

Skin blood flow affects NIRS. Leg skin blood flow (SkBF) was increased and decreased following local heating and intradermal epinephrine injection. Epinephrine decreased muscle saturation (StO(2)), and heating the leg increased StO(2). The results suggest that changes in SkBF can significantly affect resting StO(2) as measured by near-infrared tissue spectroscopy.

Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships.

The biology of the mitochondrial electron transport chain is summarized. Our approach to the mechanism of uncouplers, inhibitors, and toxins is based on electron transfer (ET) and reactive oxygen species (ROS). Extensive supporting evidence, which is broadly applicable, is cited. ROS can be generated either endogenously or exogenously. Generally, the reactive entities arise via redox cycling by ET functionalities, such as, quinones (or precursors), metal compounds, imines (or iminiums), and aromatic nitro compounds (or reduced metabolites). In most cases, the ET functions are formed metabolically. The toxic substances belong to many categories, e.g., medicinals, industrial chemicals, abused drugs, and pesticides. Structure-activity relationships are presented from the ET-ROS perspective, and also quantitatively. Evidence for the theoretical framework is provided by the protective effect of antioxidants. Among other topics addressed are proton flux, membrane pores, and apoptosis. There is support for the thesis that mitochondrial insult may contribute to illnesses and aging.