Geothermal resource assessment for the state of Texas: status of progress, November 1980. Final report

Data pertaining to wells and thermal aquifers and data interpretation methods are presented. Findings from a program of field measurements of water temperatures (mainly in South-Central Texas) and an assessment of hydrologic properties of three Cretaceous aquifers (in North-Central Texas) are included. Landsat lineaments and their pertinance to the localization of low-temperature geothermal resources are emphasized. Lineament data were compared to structural and stratigraphic features along the Balcones/Ouachita trend in Central Texas to test for correlations. (MHR

Simultaneous quantification of 12 different nucleotides and nucleosides released from renal epithelium and in human urine samples using ion-pair reversed-phase HPLC

Nucleotides and nucleosides are not only involved in cellular metabolism but also act extracellularly via P1 and P2 receptors, to elicit a wide variety of physiological and pathophysiological responses through paracrine and autocrine signalling pathways. For the first time, we have used an ion-pair reversed-phase high-performance liquid chromatography ultraviolet (UV)-coupled method to rapidly and simultaneously quantify 12 different nucleotides and nucleosides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, adenosine, uridine triphosphate, uridine diphosphate, uridine monophosphate, uridine, guanosine triphosphate, guanosine diphosphate, guanosine monophosphate, guanosine): (1) released from a mouse renal cell line (M1 cortical collecting duct) and (2) in human biological samples (i.e., urine). To facilitate analysis of urine samples, a solid-phase extraction step was incorporated (overall recovery rate ? 98 %). All samples were analyzed following injection (100 ?l) into a Synergi Polar-RP 80 Å (250 × 4.6 mm) reversed-phase column with a particle size of 10 ?m, protected with a guard column. A gradient elution profile was run with a mobile phase (phosphate buffer plus ion-pairing agent tetrabutylammonium hydrogen sulfate; pH 6) in 2-30 % acetonitrile (v/v) for 35 min (including equilibration time) at 1 ml min(-1) flow rate. Eluted compounds were detected by UV absorbance at 254 nm and quantified using standard curves for nucleotide and nucleoside mixtures of known concentration. Following validation (specificity, linearity, limits of detection and quantitation, system precision, accuracy, and intermediate precision parameters), this protocol was successfully and reproducibly used to quantify picomolar to nanomolar concentrations of nucleosides and nucleotides in isotonic and hypotonic cell buffers that transiently bathed M1 cells, and urine samples from normal subjects and overactive bladder patients

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

The P2X7 receptor (P2X7-R) is expressed in the retina and brain and has been implicated in neurodegenerative diseases. However, whether it is expressed by neurons and plays a role as a neurotransmitter receptor has been the subject of controversy. In this study, we first show that the novel vesicular transporter for ATP, VNUT, is expressed in the retina, verifying the presence of the molecular machinery for ATP to act as neurotransmitter at P2X7-Rs. Secondly we show the presence of P2X7-R mRNA and protein in the retina and cortex and absence of the full length variant 1 of the receptor in the P2X7-R knock out (P2X7-KO) mouse. The role of the P2X7-R in neuronal function of the retina was assessed by comparing the electroretinogram response of P2X7-KO with WT mice. The rod photoreceptor response was found to be similar, while both rod and cone pathway post-photoreceptor responses were significantly larger in P2X7-KO mice. This suggests that activation of P2X7-Rs modulates output of second order retinal neurons. In line with this finding, P2X7-Rs were found in the outer plexiform layer and on inner retinal cell classes, including horizontal, amacrine and ganglion cells. The receptor co-localized with conventional synapses in the IPL and was expressed on amacrine cells post-synaptic to rod bipolar ribbon synapses. In view of the changes in visual function in the P2X7-KO mouse and the immunocytochemical location of the receptor in the normal retina, it is likely the P2X7-R provides excitatory input to photoreceptor terminals or to inhibitory cells that shape both the rod and cone pathway response

In pursuit of P2X3 antagonists: novel therapeutics for chronic pain and afferent sensitization

Treating pain by inhibiting ATP activation of P2X3-containing receptors heralds an exciting new approach to pain management, and Afferent's program marks the vanguard in a new class of drugs poised to explore this approach to meet the significant unmet needs in pain management. P2X3 receptor subunits are expressed predominately and selectively in so-called C- and Aδ-fiber primary afferent neurons in most tissues and organ systems, including skin, joints, and hollow organs, suggesting a high degree of specificity to the pain sensing system in the human body. P2X3 antagonists block the activation of these fibers by ATP and stand to offer an alternative approach to the management of pain and discomfort. In addition, P2X3 is expressed pre-synaptically at central terminals of C-fiber afferent neurons, where ATP further sensitizes transmission of painful signals. As a result of the selectivity of the expression of P2X3, there is a lower likelihood of adverse effects in the brain, gastrointestinal, or cardiovascular tissues, effects which remain limiting factors for many existing pain therapeutics. In the periphery, ATP (the factor that triggers P2X3 receptor activation) can be released from various cells as a result of tissue inflammation, injury or stress, as well as visceral organ distension, and stimulate these local nociceptors. The P2X3 receptor rationale has aroused a formidable level of investigation producing many reports that clarify the potential role of ATP as a pain mediator, in chronic sensitized states in particular, and has piqued the interest of pharmaceutical companies. P2X receptor-mediated afferent activation has been implicated in inflammatory, visceral, and neuropathic pain states, as well as in airways hyperreactivity, migraine, itch, and cancer pain. It is well appreciated that oftentimes new mechanisms translate poorly from models into clinical efficacy and effectiveness; however, the breadth of activity seen from P2X3 inhibition in models offers a realistic chance that this novel mechanism to inhibit afferent nerve sensitization may find its place in the sun and bring some merciful relief to the torment of persistent discomfort and pain. The development philosophy at Afferent is to conduct proof of concept patient studies and best identify target patient groups that may benefit from this new intervention

P2 receptor-mediated modulation of neurotransmitter release—an update

Presynaptic nerve terminals are equipped with a number of presynaptic auto- and heteroreceptors, including ionotropic P2X and metabotropic P2Y receptors. P2 receptors serve as modulation sites of transmitter release by ATP and other nucleotides released by neuronal activity and pathological signals. A wide variety of P2X and P2Y receptors expressed at pre- and postsynaptic sites as well as in glial cells are involved directly or indirectly in the modulation of neurotransmitter release. Nucleotides are released from synaptic and nonsynaptic sites throughout the nervous system and might reach concentrations high enough to activate these receptors. By providing a fine-tuning mechanism these receptors also offer attractive sites for pharmacotherapy in nervous system diseases. Here we review the rapidly emerging data on the modulation of transmitter release by facilitatory and inhibitory P2 receptors and the receptor subtypes involved in these interactions

ATP-Evoked Intracellular Ca Signaling of Different Supporting Cells in the Hearing Mouse Hemicochlea

Hearing and its protection is regulated by ATP-evoked Ca2+ signaling in the supporting cells of the organ of Corti, however, the unique anatomy of the cochlea hampers observing these mechanisms. For the first time, we have performed functional ratiometric Ca2+ imaging (fura-2) in three different supporting cell types in the hemicochlea preparation of hearing mice to measure purinergic receptor-mediated Ca2+ signaling in pillar, Deiters' and Hensen's cells. Their resting [Ca2+]i was determined and compared in the same type of preparation. ATP evoked reversible, repeatable and dose-dependent Ca2+ transients in all three cell types, showing desensitization. Inhibiting the Ca2+ signaling of the ionotropic P2X (omission of extracellular Ca2+) and metabotropic P2Y purinergic receptors (depletion of intracellular Ca2+ stores) revealed the involvement of both receptor types. Detection of P2X2,3,4,6,7 and P2Y1,2,6,12,14 receptor mRNAs by RT-PCR supported this finding and antagonism by PPADS suggested different functional purinergic receptor population in pillar versus Deiters' and Hensen's cells. The sum of the extra- and intracellular Ca2+-dependent components of the response was about equal with the control ATP response (linear additivity) in pillar cells, and showed supralinearity in Deiters' and Hensen's cells. Calcium-induced calcium release might explain this synergistic interaction. The more pronounced Ca2+ leak from the endoplasmic reticulum in Deiters' and Hensen's cells, unmasked by cyclopiazonic acid, may also suggests the higher activity of the internal stores in Ca2+ signaling in these cells. Differences in Ca2+ homeostasis and ATP-induced Ca2+ signaling might reflect the distinct roles these cells play in cochlear function and pathophysiology

Geothermal Gradient Map of Texas (and Generalized Tectonic Features)

Geothermal gradient contours are commonly used to show presumed variations in the earth's internal heat. Many researchers apply the heat-flow equation literally (see inset table 1), assuming that geothermal gradients change as a function of heat flow. But the underlying premise of the heat-flow equation is that radiogenic heat flows from high to low-potential areas by means of solid-state conduction. Rarely do such conditions occur in nature owing to the interaction of hydrodynamics. Moreover, thermal conductivity is a factor in the heat flow equation. Thermal conductivity varies inversely with geothermal gradient. Clearly, for any correlation between geothermal gradient and heat flow to be meaningful, one must allow for the thermal conductivity of rock in which the geothermal gradient is measured. It is also important for users of this map to be aware that many of the apparent areal perturbations of geothermal gradient may be due to subsurface water flow; thus, Darcy's Law, as discussed below and as shown in table 1, is important. Within these constraints, this map shows geothermal gradients contoured for a few specific geologic horizons across Texas. Uniformity of rock type was the main criterion used in choosing the horizons presented here. This ensures a more or less constant thermal conductivity, thus avoiding perturbations of geothermal gradients owing to areal variations in thermal conductivities. It would have been desirable to depict statewide geothermal gradients as a single set of contours representing a single rock type and, preferably, a single rock unit. The best possible situation would be a statewide sampling of, for example, granitic basement, because a crystalline basement complex would yield gradient values that (theoretically) indicate thermal conditions in the crust. In fact, this ideal case (readings confined to granitic rock) cannot be attained because of (1) geologic realities—granitic basement probably does not occur throughout Texas; and (2) data constraints—the paucity of wells penetrating basement across the state. Given these geologic and data constraints, we collected readings on bottom-hole temperature (BHT) and depth for a uniform rock type within as few geologic units as possible but allowing for adequate well control over a broad area. Sedimentary carbonate rocks (limestone and dolomite units) are the best compromise on the basis of these criteria. Carbonate rock units are generally thick and widespread and have little internal lithic variation. Moreover, many limestone and dolomite units are petroleum reservoirs, and thus there is widespread electric log control for use in computing geothermal gradients. Four carbonate rock units provide data for contouring geothermal gradients for most of Texas inland of the Stuart City/Sligo Reef Trend (Lower Cretaceous Shelf Edge). These include three Mesozoic formations beneath the inner Gulf Coastal Plain: the Jurassic Smackover Formation and the Sligo/Pettet and Edwards Formations, both of Cretaceous age. For the remainder of the state west of the Balcones/Ouachita Trend, we employed data mostly from the Ellenburger Group of Ordovician age. Coastward of the Lower Cretaceous Shelf Edge, however, fundamental geologic changes occur. There, few wells are completed in carbonate rocks owing to radical facies changes and excessive depths to correlative Mesozoic units. Most of the BHT/depth (bottom-hole temperature) data exist for Tertiary and Quaternary clastic rock units, and within these units, there is no assurance of lateral or vertical lithic continuity. Hence, for this region (the Tertiary Gulf Coast Basin), we present a separate set of contours based on a moving average of the gradient data derived from the 1:1,000,000-scale version of the Geothermal Gradient Map of North America (American Association of Petroleum Geologists and US Geological Survey, 1976). In this way, we were able to smooth contours that otherwise would suggest geothermal anomalies but that may in fact merely be due to penetration of sandstone and mudstone in adjacent wells. In short, five sets of data are contoured on this map: the moving-average contours for the Tertiary Gulf Coast Basin and separate contours for each of the four discrete geologic units. The carbonate rock units are depicted as separate sets of contours so that each set will be internally consistent while still being broadly comparable to one another. The local overlapping of contours for different units indicates local, apparent geothermal perturbations that probably result from hydrodynamic conditions within the rock unit and not from variations in heat flow. This mosaic of contours thus allows better resolution of certain controls on local anomalies and allows direct comparison of geothermal gradients to subsurface structures mapped on key horizons (namely the Ellenburger and the Edwards, compare this map to that by Sellards and Hendricks, 1948; also an updated depiction of statewide structures is forthcoming [Ewing and others, in progress]). However, the segregation of the gradient map by rock unit promotes a fragmented view of statewide geothermal trends: because of uneven well control there are significant blank areas on this map; compare this depiction to the inset figure 1. Gaps in contouring occur along the Balcones/Ouachita Trend, along the Llano Uplift, in parts of Trans-Pecos Texas west of the Delaware Basin, and in West Texas along parts of the Amarillo Uplift and the Matador Arch. These gaps appear where there are no wells penetrating the designated horizons or correlative strata, or, as occurs along parts of the Balcones trend, the target horizons do not lie within the proper depth range. We attempted to obtain all readings from points deeper than 2,000 ft (to avoid near-surface hydrologic perturbations) but shallower than the range of geopressured conditions (because of the abrupt discontinuities of geothermal gradients in that zone).Bureau of Economic Geolog

Integration of geothermal data along the Balcones/Ouachita trend, central Texas. Final report

This report presents data that address possible controls on warm-water resources. Data are presented on a series of maps, and interpretations appear in the brief text accompanying the maps. It is thought that structural controls provided by the Balcones Fault Zone on the west and by the Luling-Mexia-Talco Fault Zone on the east localize the warm waters. The ultimate controlling attribute is the foundered Ouachita structural belt, which, in turn, has controlled the orientation and magnitude of displacement of the superjacent normal fault systems. This thesis is supported by maps (in pocket) showing the following: distribution of thermal waters measured in wells along the Balcones/Ouachita structural trend showing water temperature in /sup 0/F, total depth of the well measured, water salinity in parts per million, and the geologic formation producing the water; structural contours on the base of the Cretaceous System showing the configuration of the Paleozoic Ouachita basement; structural configuration of the Balcones and Luling Fault Zone, Mexia and Talco Fault Zone, and foreland areas adjacent to the Ouachita Orogen using data from the Buda Limestone, Sligo Formation, and Ellenburger Group; Landsat lineaments and Bouguer gravity contours; and geothermal gradient contours of the Balcones/Ouachita trend based on thermal values from Paleozoic and selected Mesozoic formations