bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting the characteristics of coal seams from chemical, physical and petrographic studies of peat deposits
Authors: Cohen Arthur D. , Spackman William , Raymond Robert
Published: October 2007

The purpose of this paper is to illustrate some of the kinds of information about coals that are at present being generated from studies of peat deposits and also to point out some possible new areas of research that might be undertaken in the future.

Some notable examples of new ideas about coal seam composition or formation that have been generated from studies of modern peat deposits include: (1) discovery of the probable progenitors of certain coal macerals and elucidation of the processes by which they may have formed; (2) evidence that some types of mineral matter may be dissolved out of peat deposits; (3) verification of the role of marine waters in emplacement of sulphur in peat; (4) discovery of the importance of ‘doming’ in peat deposit development; (5) discovery of a new way to form a split in a coal seam, i.e. development of a ‘fire splay’; (6) elucidation of the mechanisms responsible for producing stratification in coal seams; (7) recognition of the world-wide importance of ‘back-barrier’ coal-forming environments.

These kinds of discoveries are important in themselves; however, they can also be shown to have many additional practical applications, especially if woven into models to predict the economic characteristics of coal seams.
Recent advances in coalification studies and their application to geology
Authors: Teichmüller Marlies
Published: October 2007

Recent advances in coalification studies since 1970 are reported, concerning microscopic methods, causes of coalification, the coalification process as such and application to geology. The degree of coalification (‘rank’) is mostly determined on the basis of vitrinite reflectance measured on finely dispersed material in rocks. For rocks bare of vitrinite other microscopic methods are used, such as fluorescence properties of liptinites and graptolite reflectance under incident light or coloration of microfossils like palynomorphs and conodonts in transmitted light. The validity of the various methods is discussed.

Maximum rock temperature and its duration are the main causes of chemical coalification reactions. Heating rates during subsidence influence the attainment of rank equilibrium. Contact-metamorphic coals and natural cokes formed from bituminous coals are characterized by a relatively high reflectance and anisotropy. Strong frictional heat may cause local increase of rank adjacent to thrust planes. Graphitization is thermodynamically not possible in nature without pressure and shearing. Confining pressure retards the chemical coalification reactions. Tectonic stress, especially shearing, promotes the increase of maximum reflectance and of anisotropy. It commonly leads to bi-axial optical properties instead of the more typical uni-axial negative geometry of vitrinite in undisturbed coal seams. Bi-axial optical properties are common for vitrinite inclusions in clastic rocks.

On the basis of combined fluorescence microscopical and geochemical studies, ‘bituminization’ has been recognized as
the
characteristic part of coalification in the range between sub-bituminous and bituminous coal. It is characterized by the generation of petroleum-like substances which enable the coal to soften and to agglomerate during carbonization. Hydrogenation properties are favoured by the bituminization process. The different liptinite macerals behave differently during coalification and pass coalification ‘jumps’ at different rank stages. A considerable part of total inertinites is formed during early coalification (brown coal to sub-bituminous coal stage) as ‘rank inertinite’. This new knowledge appears to become important in relation to hydrocarbon exploration (‘diagenetic methane’).

Some examples for the application of coalification studies to geology refer to vitrinite reflectance as an indicator of rock diagenesis and metamorphism, palaeogeographical and structural history, palaeogeothermics and hydrocarbon exploration. Large-scale areal coalification studies in foredeeps and backdeeps of ancient and recent orogens suggest estimations of crustal thicknesses and relations to plate tectonics.
Oil-prone coals of the Walloon Coal Measures, Surat Basin, Australia
Authors: Khorasani Ganjavar Khavari
Published: October 2007

Studies of autochthonous coals from the Walloon Coal Measures, Surat Basin, Australia, suggest that the process of liptinite enrichment and the formation of perhydrous vitrinites have given rise to oil-prone coals. These processes were essentially controlled by the type of flora contributing to the peat accumulation and the biochemical transformation of the flora under dysaerobic conditions. These processes lead to the coals being hydrogen-rich and oil prone, and contrast with the process described by other authors for Indonesian source rocks. The mature phase of oil generation from hydrogen-rich coals such as those of the Walloon Coal Measures may be preceded by several earlier phases, during which hydrocarbons are likely to be generated from subereous components and terpene resinites in low rank lignites and sub-bituminous coals.
On computing all abductive explanations from a propositional Horn theory
Authors: Eiter Thomas , Makino Kazuhisa
Published: October 2007

Abduction is a fundamental mode of reasoning with applications in many areas of AI and Computer Science. The computation of abductive explanations is an important computational problem, which is at the core of early systems such as the ATMS and Clause Management Systems and is intimately related to prime implicate generation in propositional logic. Many algorithms have been devised for computing some abductive explanation, and the complexity of the problem has been well studied. However, little attention has been paid to the problem of computing multiple explanations, and in particular all explanations for an abductive query. We fill this gap and consider the computation of all explanations of an abductive query from a propositional Horn theory, or of a polynomial subset of them. Our study pays particular attention to the form of the query, ranging from a literal to a compound formula, to whether explanations are based on a set of abducible literals and to the representation of the Horn theory, either by a Horn conjunctive normal form (CNF) or model-based in terms of its characteristic models. For these combinations, we present either tractability results in terms of polynomial total-time algorithms, intractability results in terms of nonexistence of such algorithms (unless P = NP), or semi-tractability results in terms of solvability in quasi-polynomial time, established by polynomial-time equivalence to the problem of dualizing a monotone CNF expression. Our results complement previous results in the literature, and refute a longstanding conjecture by Selman and Levesque. They elucidate the complexity of generating all abductive explanations and shed light on related problems such as generating sets of restricted prime implicates of a Horn theory. The algorithms for tractable cases can be readily applied for generating a polynomial subset of explanations in polynomial time.
Performance of various computers using standard linear equations software in a Fortran environment
Authors: Dongarra Jack J.
Published: October 2007

This note compares the performance of different computer systems while solving dense systems of linear equations using the LINPACK software in a Fortran environment. About 100 computers, ranging from a CRAY X-MP to the 68000 based systems such as the Apollo and SUN Workstations to IBM PC's, are compared.
A new index mode for the VAX-11
Authors: De Prycker Martin L.
Published: October 2007

One advantage of most high level languages over machine languages consists of the availability of concepts which are frequently used by most programmers. One of these concepts is the array mechanism, where the high level language generally provides three operations associated with array manipulations: type-checking, bounds-checking and address calculation.
The Phoenix Project
Authors: Stevenson David
Published: October 2007

The Phoenix Project was an exploration of the issues surrounding large scale scientific computing. It was conducted at the Institute for Advanced Computation, NASA-Ames Research Center at Moffett Field, California from 1975 to 1979. The primary results of the project were a sizing of the likely needs of large scale scientific computing during the 1980s, what computing technology could be available to meet those needs, a conceptual design of a processor that could meet those needs, and a programming, language suitable for use by this community on a parallel processor such as the one proposed.
Cache memory for microprocessors
Authors: Lindsay Donald C.
Published: October 2007

A growth path for current microprocessors is suggested which includes bus enhancements and cache memories. The implications are examined, and several differences from the mainframe world are pointed out.
Cilia and Developmental Signaling
Authors: Eggenschwiler Jonathan T. , Anderson Kathryn V.
Published: October 2007

Recent studies have revealed unexpected connections between the mammalian Hedgehog (Hh) signal transduction pathway and the primary cilium, a microtubule-based organelle that protrudes from the surface of most vertebrate cells. Intraflagellar transport proteins, which are required for the construction of cilia, are essential for all responses to mammalian Hh proteins, and proteins required for Hh signal transduction are enriched in primary cilia. The phenotypes of different mouse mutants that affect ciliary proteins suggest that cilia may act as processive machines that organize sequential steps in the Hh signal transduction pathway. Cilia on vertebrate cells are likely to be important in additional developmental signaling pathways and are required for PDGF receptor α signaling in cultured fibroblasts. Cilia are not essential for either canonical or noncanonical Wnt signaling, although cell-type-specific modulation of cilia components may link cilia and Wnt signaling in some tissues. Because ciliogenesis in invertebrates is limited to a very small number of specialized cell types, the role of cilia in developmental signaling pathways is likely a uniquely vertebrate phenomenon.
Following the Chromosome Path to the Garden of the Genome
Authors: Pardue Mary-Lou
Published: October 2007

I have been fascinated by chromosomes for longer than I care to mention; their beautiful structure, cell-type-specific changes in morphology, and elegant movements delight me. Shortly before I began graduate study, the development of nucleic acid hybridization made it possible to compare two nucleic acids whether or not their sequences were known. From this stemmed a progression of development in tools and techniques that continues to enhance our understanding of how chromosomes function. As my PhD project I contributed to this progression by developing in situ hybridization, a technique for hybridization to nucleic acids within their cellular context. Early studies with this technique initiated several lines of research, two of which I describe here, that I have pursued to this day. First, analysis of RNA populations by hybridization to polytene chromosomes (a proto-microarray-type experiment) led us to characterize levels of regulation during heat shock beyond those recognizable by puffing studies. We found also that one still-undeciphered major heat shock puff encodes a novel set of RNAs for which we propose a regulatory role. Second, localization of various multicopy DNA sequences has suggested roles for them in chromosome structure: Most recently we have found that Drosophila telomeres consist of and are maintained by special non-LTR (long terminal repeat) retrotransposons.
Expression of functional Toll-like receptors 2 and 4 in human aortic valve interstitial cells: potential roles in aortic valve inflammation and stenosis
Authors: Meng Xianzhong , Ao Lihua , Song Yong , Babu Ashok , Yang Xiaoping , Wang Maorong , Weyant Michael J. , Dinarello Charles A. , Cleveland Joseph C. , Fullerton David A.
Published: October 2007

Calcific aortic valve stenosis is the most common indication for surgical valve replacement. Inflammation appears to be one of the mechanisms involved in aortic valve calcification, and valve interstitial cells seem to contribute to that process. Although Toll-like receptors (TLRs) play an important role in the cellular inflammatory response, it is unknown whether human aortic valve interstitial cells (HAVICs) express functional TLRs. We examined the expression of TLR2 and TLR4 in human aortic valve leaflets and in isolated HAVICs and analyzed the response of cultured HAVICs to the TLR2 and TLR4 agonists peptidoglycan (PGN) and LPS. Abundant TLR2 and TLR4 proteins were found in human aortic valve leaflets and in isolated HAVICs, and both receptors were detected in the membrane and cytoplasm of cultured HAVICs. Stimulation by either PGN or LPS resulted in the activation of the NF-κB signaling pathway and the production of multiple proinflammatory mediators, including IL-6, IL-8, and ICAM-1. In addition, stimulation by either PGN or LPS upregulated the expression of bone morphogenetic protein-2 (BMP-2) and Runx2, factors associated with osteogenesis. This study demonstrates for the first time that HAVICs express TLR2 and TLR4 and that stimulation of HAVICs by PGN or LPS induces the expression of proinflammatory mediators and the upregulation of osteogenesis-associated factors. These results suggest that TLR2 and TLR4 may play a role in aortic valve inflammation and stenosis.
Hypoxia effects on cell volume and ion uptake of cerebral microvascular endothelial cells
Authors: Brillault Julien , Lam Tina I. , Rutkowsky Jennifer M. , Foroutan Shahin , O'Donnell Martha E.
Published: October 2007

Increased transport of Na across an intact blood-brain barrier (BBB) contributes to cerebral edema formation in ischemic stroke. Our previous studies have shown that ischemic factors stimulate activity of a luminal BBB Na-K-Cl cotransporter, and we have hypothesized that during ischemia, the cotransporter together with the abluminal Na/K pump mediates increased transport of Na from blood into the brain. However, it is possible that elevated Na-K-Cl cotransporter activity could also cause cell swelling if it outpaces ion efflux pathways. The present study was conducted to evaluate the effects of hypoxia on intracellular volume of BBB cells. Cerebral microvascular endothelial cell (CMEC) monolayers were exposed to varying levels of hypoxia for 1 to 5 h in an O2-controlled glove box, and cell volume was assessed using 3- O-methyl-d-[3H]glucose and [14C]sucrose as markers of total and extracellular water space, respectively. Cells exposed to either 7.5%, 3%, or 1% O2showed gradual increases in volume (compared with 19% O2normoxic controls) that became significant after 3 or more hours. By ion chromatography methods, we also found that a 30-min exposure to 7.5% O2caused an increase in bumetanide-sensitive net Na uptake by the cells without increasing cell Na content. CMEC Na content was significantly increased, however, following 3 or more hours of exposure to 7.5% O2. These findings are consistent with the hypothesis that during cerebral ischemia, the BBB Na-K-Cl cotransporter is stimulated to mediate transendothelial uptake of Na into the brain and that increased cotransporter activity also contributes to gradual swelling of the cells.
Regulation of fibroblast growth factor-2 expression in pulmonary arterial smooth muscle cells involves increased reactive oxygen species generation
Authors: Black Stephen M. , DeVol Jennifer M. , Wedgwood Stephen
Published: October 2007

We have previously demonstrated increased fibroblast growth factor-2 (FGF-2) expression in a lamb model of increased pulmonary blood flow secondary to congenital heart disease, which may contribute to the associated increases in pulmonary arterial muscularization. However, the mechanisms underlying these increases in FGF-2 expression remain to be identified. Initially, we found that exogenous FGF-2 increased endogenous FGF-2 promoter activity and protein levels in ovine pulmonary arterial smooth muscle cells (PASMC). Furthermore, we found that these increases in FGF-2 expression were mediated by increases in superoxide levels via NADPH oxidase activation. In addition, FGF-2-mediated increases in FGF-2 expression and PASMC proliferation were attenuated by inhibition of phosphatidylinositol 3-kinase, Akt, and NADPH oxidase. Increases in FGF-2 expression could be stimulated by other factors known to increase reactive oxygen species (ROS) signaling in PASMC (endothelin-1 and transforming growth factor-β1), whereas antioxidants attenuated these increases. Deletion constructs localized the growth factor- and ROS-sensitive region within the proximal 103 bp of the FGF-2 promoter, and sequence analysis identified a putative hypoxia response element (HRE), a DNA binding site for the ROS-sensitive transcription factor hypoxia-inducible factor-1α (HIF-1α). Stabilization of HIF-1α increased FGF-2 promoter activity, whereas mutation of the putative HRE attenuated FGF-2-induced FGF-2 promoter activity. Furthermore, FGF-2 increased HIF-1α protein levels and consensus HRE promoter activity in PASMC via antioxidant-sensitive mechanisms. Thus we conclude that FGF-2 can stimulate its own expression in PASMC via NADPH oxidase-mediated activation of ROS-sensitive transcription factors, including HIF-1α. This positive feedback mechanism may contribute to pulmonary vascular remodeling associated with increased pulmonary blood flow.
Roles of PKA, PI3K, and cPLA2in the NO-mediated negative inotropic effect of β2-adrenoceptor agonists in guinea pig right papillary muscles
Authors: Faucher Fabien A. , Gannier François E. , Lignon Jacques M. , Cosnay Pierre , Malécot Claire O.
Published: October 2007

Although β2-adrenoceptors represent 15–25% of β-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of β2-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, −5% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 μM) due to activation of β1-adrenoceptors. In the presence of 4 μM atenolol, the concentration-dependent NIE (−12% at 6 μM) was biphasic, best described by a double logistic equation with respective EC50values of 3 and ∼420 nM, and was insensitive to SR59230A. In muscles from pertussis toxin-treated guinea pigs, the salbutamol-induced positive inotropic effect was sensitive to low concentrations of ICI-118551 in an unusual manner. Experiments in reserpinized animals revealed the importance of the phosphorylation-dephosphorylation processes. PKA inhibition reduced and suppressed the effects obtained at low and high concentrations, respectively, indicating that its activation was a prerequisite to the NIE. The effect occurring at nanomolar concentrations depended upon PKA/phosphatidylinositol 3-kinase/cytosolic phospholipase A2(cPLA2) activations leading to nitric oxide (NO) release via the arachidonic acid/cyclooxygenase pathway. NO release via PKA-dependent phosphorylation of the receptor was responsible for the inotropic effect observed at submicromolar concentrations, which is negatively controlled by cPLA2. The possibility that these effects are due to an equilibrium between different affinity states of the receptor (Gs/Gicoupled and Giindependent with different signaling pathways) that can be displaced by ICI-118551 is discussed. We conclude that β2-adrenoceptors are functional in guinea pig heart and can modulate the inotropic state.
Enhancement of lymphocyte migration and cytokine production by ephrinB1 system in rheumatoid arthritis
Authors: Kitamura Takuya , Kabuyama Yukihito , Kamataki Akihisa , Homma Miwako K. , Kobayashi Hideo , Aota Shigeo , Kikuchi Shin-ichi , Homma Yoshimi
Published: October 2007

Although the etiology of early events in rheumatoid arthritis (RA) remains undefined, an anomaly in T cell homeostasis and hyperproliferation of synovial-lining cells are involved in the disease process. Since it has been reported that the ephrin/Eph receptor system plays important signaling roles in inflammation processes, we attempted to examine ephrinB molecules in T cells and synovial cells derived from RA in this study. The expression level of ephrinB1 was significantly high in synovial fibroblasts and CD3-positive exudate lymphocytes in synovial tissues derived from patients with RA compared with those in osteoarthritis (OA). Protein and mRNA levels of ephrinB1 were also higher in peripheral blood lymphocytes (PBLs) prepared from patients with RA than those from normal controls. Similar results were obtained from an animal model of human RA, collagen antibody-induced arthritis mice. Moreover, a recombinant ephrinB1/Fc fusion protein stimulated normal PBLs to exhibit enhanced migration and production of TNF-α. EphrinB1/Fc also activated synovial cells established from patients with RA to produce IL-6. Tyrosine phosphorylation of EphB1 was induced in these cells by ephrinB1/Fc. The CpG islands in the 5′ upstream regulatory region of the ephrinB1 gene were hypomethylated in RA patients compared with those of normal donors. These results suggest that ephrinB1 and EphB1 receptors play an important role in the inflammatory states of RA, especially by affecting the population and function of T cells. Inhibition of the ephrinB/EphB system might be a novel target for the treatment of RA.
Topology of the selectivity filter of a TRPV channel: rapid accessibility of contiguous residues from the external medium
Authors: Dodier Yolaine , Dionne François , Raybaud Alexandra , Sauvé Rémy , Parent Lucie
Published: October 2007

The transient receptor potential type V5 (TRPV5) channel is a six-transmembrane domain ion channel that is highly selective to Ca2+. To study the topology of the selectivity filter using the substituted cysteine accessibility method (SCAM), cysteine mutants at positions 541–547 were studied as heterotetramers using dimeric constructs that couple the control channel in tandem with a cysteine-bearing subunit. Whole cell currents of dimeric constructs D542C, G543C, P544C, A545C, and Y547C were rapidly inhibited by positively charged 2-(trimethyl ammonium)methyl methane thiosulfonate bromide (MTSMT), 2-(aminoethyl)methane thiosulfonate bromide (MTSEA), and 2-(trimethyl ammonium)ethyl methane thiosulfonate bromide (MTSET) reagents, whereas D542C, P544C, and A545C were inhibited only by negatively charged sodium 2-(sulfonatoethyl)methane thiosulfonate (MTSES). In contrast, the I541C dimer remained insensitive to positive and negative reagents. However, I541C/D542G and I541C/D542N dimeric constructs were rapidly (<30 s) and strongly inhibited by positively and negatively charged methane thiosulfonate reagents, suggesting that removing two of the four carboxylate residues at position 542 disrupts a constriction point in the selectivity filter. Taken together, these results establish that the side chains of contiguous amino acids in the selectivity filter of TRPV5 are rapidly accessible from the external medium, in contrast to the three-dimensional structure of the selectivity filter in K+ channels, where main chain carbonyls were shown to project toward a narrow permeation pathway. The I541C data further suggest that the selectivity filter of the TRPV5 channel espouses a specific conformation that restrains accessibility in the presence of four carboxylate residues at position 542.
Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3
Authors: Heidemann Jan , Rüther Christoph , Kebschull Moritz , Domschke Wolfram , Brüwer Matthias , Koch Stefan , Kucharzik Torsten , Maaser Christian
Published: October 2007

Members of the interleukin (IL)-12 family constitute subunits of IL-12, -23, and -27. These ILs represent pivotal mediators in the regulation of cell-mediated immune responses and in animal models of human inflammatory bowel disease. Recent work has suggested that intestinal endothelial cells might serve as a second line of defense in bacterial sensing of invading pathogens. The purpose of this study was to examine the production of IL-12 family members in intestinal endothelial cells (HIMEC). HIMEC were stimulated with proinflammatory agents (TNF-α, IFN-γ, IL-1β) and microbial antigens [LPS, lipoteichoic acid, peptidoglycan, CpG-DNA, flagellin, poly(I:C)]. Expression of IL-12 family members and of Toll-like receptor (TLR)3 in HIMEC was assessed by real-time RT-PCR, immunostaining, flow cytometry, and immunoblot analysis. HIMEC display an induction of Epstein-Barr virus-induced gene 3 (EBI3), IL-12p35, and IL-23p19, whereas no expression of IL-12p40 and IL-27p28 was detectable. The strongest induction was induced by proinflammatory factors known to utilize the NF-κB pathway, and expression of EBI3 and IL-23p19 was diminished by an NF-κB inhibitor. HIMEC display regulated expression of TLR3. Adhesion and transmigration assays showed proinflammatory responses after HIMEC stimulation. HIMEC are capable of producing IL-12 family members as a response to microbial stimuli. The TLR3 agonist, poly(I:C), was shown to enhance leukocyte adhesion in vitro in HIMEC. Our data suggest that the intestinal microvasculature is responsive to ligands of TLR3 expressed on intestinal endothelial cells, thereby adding to the regulation of adaptive immunity and leukocyte recruitment.
Gastric mucosal protection against ethanol by EP2and EP4signaling through the inhibition of leukotriene C4production
Authors: Hattori Youichiro , Ohno Takashi , Ae Takako , Saeki Takeo , Arai Katsuharu , Mizuguchi Sumito , Saigenji Katsunori , Majima Masataka
Published: October 2007

Prostaglandin (PG)E derivatives are widely used for treating gastric mucosal injury. PGE receptors are classified into four subtypes, EP1, EP2, EP3, and EP4. We have tested which EP receptor subtypes participate in gastric mucosal protection against ethanol-induced gastric mucosal injury and clarified the mechanisms of such protection. The gastric mucosa of anesthetized rats was perfused at 2 ml/min with physiological saline, agonists for EP1, EP2, EP3, and EP4, or 50% ethanol, using a constant-rate pump connected to a cannula placed in the esophagus. The gastric microcirculation of the mucosal base of anesthetized rats was observed by transillumination through a window made by removal of the adventitia and muscularis externa. PGE2and subtype-specific EP agonists were applied to the muscularis mucosae at the window. Application of 50% ethanol dilated the mucosal arterioles and constricted the collecting venules. Collecting venule constriction by ethanol was completely inhibited by PGE2and by EP2and EP4agonists (100 nM) but not by an EP1or an EP3agonist. Ethanol-induced mucosal injury was also inhibited by EP2and EP4agonists. When leukotriene (LT)C4levels in the perfusate of the gastric mucosa were determined by ELISA, intragastric ethanol administration elevated the LTC4levels sixfold from the basal levels. These elevated levels were significantly (60%) reduced by both EP2and EP4agonists but not by other EP agonists. Since LTC4application at the window constricted collecting venules strongly, and an LTC antagonist reduced ethanol-induced mucosal injury, reductions in LTC4generation in response to EP2and EP4receptor signaling may be relevant to the protective action of PGE2. The present results indicate that EP2and EP4receptor signaling inhibits ethanol-induced gastric mucosal injury through cancellation of collecting venule constriction by reducing LTC4production.
Endometriosis as a neurovascular condition: estrous variations in innervation, vascularization, and growth factor content of ectopic endometrial cysts in the rat
Authors: Zhang Guohua , Dmitrieva Natalia , Liu Yan , McGinty Kristina A. , Berkley Karen J.
Published: October 2007

Endometriosis is a poorly understood, estradiol-dependent condition associated with severe pelvic pains and defined by vascularized endometrial growths outside the uterus. Endometriosis is produced in cycling rats by autotransplanting pieces of uterus onto abdominal arteries where they develop into cysts. The surgery induces vaginal and abdominal muscle hyperalgesia, whose severity is greatest in proestrus and nearly absent in estrus. The cysts contain growth factors and cytokines and develop their own sympathetic and sensory C- and Aδ-fiber innervation. Here, we used quantitative immunostaining and protein array analyses to test the hypothesis that the innervation and growth factor/cytokine content of the cysts, but not uterine horn, contribute to proestrous-to-estrous changes in hyperalgesic severity. If so, these characteristics in the cysts, but not the uterine horn, should change with estrous stage. In cysts, the density of sympathetic (but not sensory) neurites and amounts of NGF and VEGF proteins (but not cytokines IL-1, IL-6, IL-10, or TNF-α) were greater in proestrus than estrus. These changes were accompanied by vascular changes. Both sympathetic and sensory fibers in both stages colabeled with TrkA, indicating that changes in NGF could act on both afferent and efferent fibers. In contrast with the cysts, no changes occurred in the uterine horn between proestrus and estrus. Together, these results suggest that coordinated proestrous-to-estrous changes in innervation and vascularization of the cysts contribute to similar changes in hyperalgesic severity. The findings also encourage consideration of endometriosis as a neurovascular condition.
Altered TP receptor function in isolated, perfused kidneys of nondiabetic and diabetic ApoE-deficient mice
Authors: Michel Frédéric , Simonet Serge , Vayssettes-Courchay Christine , Bertin Florence , Sansilvestri-Morel Patricia , Bernhardt Fabienne , Paysant Jérôme , Silvestre Jean-Sébastien , Levy Bernard I. , Félétou Michel , Verbeuren Tony J.
Published: October 2007

Early manifestations of kidney disease occur in atherosclerosis and activation of TP (thromboxane A2) receptors is implicated in atherosclerotic, diabetes, and renal diseases. The purpose of the present study was to analyze, in isolated, perfused mouse kidneys, the participation of TP receptors in renal vasoconstrictions and vasodilatations. In kidneys, taken from wild-type C57BL6, apolipoprotein E-deficient (ApoE-KO) and diabetic ApoE-KO mice, changes in perfusion pressure were recorded. Constrictions to TP receptor ligands U 46619, arachidonic acid, PGH2, and 8-iso-PGF2α, but not those to angiotensin II, endothelin, or norepinephrine, were inhibited by the selective TP receptor antagonist Triplion (S 18886; 10 nM). Acetylcholine and prostacyclin evoked biphasic responses during methoxamine constrictions; the constrictor part was blocked by Triplion. In ApoE-KO mouse kidneys, compared with C57BL6, a specific decrease in norepinephrine response and no modification in dilator responses were observed. In diabetic ApoE-KO mouse kidneys, constrictions to U 46619 and those to 8-iso-PGF2α were significantly and selectively augmented, without modification in the expression of the TP receptor, and again without any significant change in vasodilator activity. Thus TP receptors are functional, and their activation is not involved in norepinephrine, endothelin, and angiotensin II vasoconstrictions but is implicated in the unusual vasoconstrictions to acetylcholine and prostacyclin. Increased responsiveness of TP receptors occurs in diabetic ApoE-KO mouse kidneys. Thus early changes in TP receptor-mediated vasoconstrictor activity may participate in the development of kidney disease in atherosclerosis and diabetes.
Renal interstitial adenosine is increased in angiotensin II-induced hypertensive rats
Authors: Franco Martha , Bautista Rocio , Pérez-Méndez Oscar , González Lidia , Pacheco Ursino , Sánchez-Lozada L. G. , Santamaría José , Tapia Edilia , Monreal Rogelio , Martínez Flavio
Published: October 2007

Since marked renal vasoconstriction is observed in angiotensin II (ANG II)-mediated hypertensive rats, we studied the possible interaction between ANG II and adenosine in this model. ANG II was infused into male Wistar rats through osmotic minipumps (435 ng·kg−1·min−1) for 14 days. In sham and ANG II groups, renal tissue and interstitial adenosine were measured; both increased to a similar twofold extent in the ANG II-treated rats (31.40 ± 4 vs. 62.0 ± 8.4 nM, sham vs. ANG II, interstitial adenosine; P< 0.001). The latter decreased by 47% with the specific blockade of 5′-nucleotidase. Glomerular hemodynamics demonstrated marked renal vasoconstriction in the angiotensin-treated group, which was reverted by an adenosine A1-receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 10 μg·kg−1·min−1). 5′-Nucleotidase and adenosine deaminase (ADA) activities were measured in the cytosolic and membrane fractions. Only the membrane ADA activity decreased from 1,202 ± 80 to 900 ± 50 mU/mg protein in the ANG II-treated rats ( P< 0.05), as well as in their protein and mRNA expression. Despite the adenosine elevation, A1and A2breceptor protein did not change; in contrast, downregulation was observed in A2areceptor and upregulation in A3receptor. A similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A3receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the ANG II-induced hypertension and that it is mediated by a decrease in the activity and expression of ADA, increased production of adenosine, and an induced imbalance in adenosine receptors.
Maleate nephrotoxicity: mechanisms of injury and correlates with ischemic/hypoxic tubular cell death
Authors: Zager Richard A. , Johnson Ali C. M. , Naito Masayo , Bomsztyk Karol
Published: October 2007

Maleate injection causes dose-dependent injury in proximal tubular cells. This study sought to better define underlying pathogenic mechanisms and to test whether maleate toxicity recapitulates critical components of the hypoxic/ischemic renal injury cascade. CD-1 mice were injected with maleate or used as a source for proximal tubule segments (PTS) for in vitro studies. Maleate induced dose-dependent PTS injury [lactate deydrogenase (LDH) release, ATP reductions, nonesterified fatty acid (NEFA) accumulation]. These changes were partially dependent on maleate metabolism (protection conferred by metabolic inhibitors: succinate, acetoacetate). Maleate toxicity reproduced critical characteristics of the hypoxia/ATP depletion-induced injury cascade: 1) glutathione (GSH) conferred protection, but due to its glycine, not cysteine (antioxidant), content; 2) ATP reductions reflected decreased production, not Na-K-ATPase-driven increased consumption; 3) cell death was completely blocked by extracellular acidosis (pH 6.6); 4) intracellular Ca2+chelation (BAPTA) mitigated cell death; 5) maleate and hypoxia each caused plasma membrane cholesterol shedding and in both instances, this was completely glycine suppressible; 6) maleate + hypoxia caused neither additive NEFA accumulation nor LDH release, implying shared pathogenic pathways; and 7) maleate, like ischemia, induced renal cortical cholesterol loading; increased HMG CoA reductase (HMGCR) activity (statin inhibitable), increased HMGCR mRNA levels, and increased RNA polymerase II recruitment to the HMGCR locus (chromatin immunoprecipitation, ChIP, assay) were involved. These results further define critical determinants of maleate nephrotoxicity and suggest that it can serve as a useful adjunct for studies of ischemia/ATP depletion-induced, proximal tubule-specific, cell death.
Lower body negative pressure exercise plus brief postexercise lower body negative pressure improve post-bed rest orthostatic tolerance
Authors: Watenpaugh Donald E. , O'Leary Deborah D. , Schneider Suzanne M. , Lee Stuart M. C. , Macias Brandon R. , Tanaka Kunihiko , Hughson Richard L. , Hargens Alan R.
Published: October 2007

Orthostatic intolerance follows actual weightlessness and weightlessness simulated by bed rest. Orthostasis immediately after acute exercise imposes greater cardiovascular stress than orthostasis without prior exercise. We hypothesized that 5 min/day of simulated orthostasis [supine lower body negative pressure (LBNP)] immediately following LBNP exercise maintains orthostatic tolerance during bed rest. Identical twins (14 women, 16 men) underwent 30 days of 6° head-down tilt bed rest. One of each pair was randomly selected as a control, and their sibling performed 40 min/day of treadmill exercise while supine in 53 mmHg (SD 4) [7.05 kPa (SD 0.50)] LBNP. LBNP continued for 5 min after exercise stopped. Head-up tilt at 60° plus graded LBNP assessed orthostatic tolerance before and after bed rest. Hemodynamic measurements accompanied these tests. Bed rest decreased orthostatic tolerance time to a greater extent in control [34% (SD 10)] than in countermeasure subjects [13% (SD 20); P < 0.004]. Controls exhibited cardiac stroke volume reduction and relative cardioacceleration typically seen after bed rest, yet no such changes occurred in the countermeasure group. These findings demonstrate that 40 min/day of supine LBNP treadmill exercise followed immediately by 5 min of resting LBNP attenuates, but does not fully prevent, the orthostatic intolerance associated with 30 days of bed rest. We speculate that longer postexercise LBNP may improve results. Together with our earlier related studies, these ground-based results support spaceflight evaluation of postexercise orthostatic stress as a time-efficient countermeasure against postflight orthostatic intolerance.
Apparent latent heat of evaporation from clothing: attenuation and “heat pipe” effects
Authors: Havenith George , Richards Mark G. , Wang Xiaoxin , Bröde Peter , Candas Victor , den Hartog Emiel , Holmér Ingvar , Kuklane Kalev , Meinander Harriet , Nocker Wolfgang
Published: October 2007

Investigating claims that a clothed person's mass loss does not always represent their evaporative heat loss (EVAP), a thermal manikin study was performed measuring heat balance components in more detail than human studies would permit. Using clothing with different levels of vapor permeability and measuring heat losses from skin controlled at 34°C in ambient temperatures of 10, 20, and 34°C with constant vapor pressure (1 kPa), additional heat losses from wet skin compared with dry skin were analyzed. EVAP based on mass loss ( Emass) measurement and direct measurement of the extra heat loss by the manikin due to wet skin ( Eapp) were compared. A clear discrepancy was observed. Emass overestimated Eapp in warm environments, and both under and overestimations were observed in cool environments, depending on the clothing vapor permeability. At 34°C, apparent latent heat (λapp) of pure evaporative cooling was lower than the physical value (λ; 2,430 J/g) and reduced with increasing vapor resistance up to 45%. At lower temperatures, λapp increases due to additional skin heat loss via evaporation of moisture that condenses inside the clothing, analogous to a heat pipe. For impermeable clothing, λapp even exceeds λ by four times that value at 10°C. These findings demonstrate that the traditional way of calculating evaporative heat loss of a clothed person can lead to substantial errors, especially for clothing with low permeability, which can be positive or negative, depending on the climate and clothing type. The model presented explains human subject data on EVAP that previously seemed contradictive.
Recording Chronically From the Same Neurons in Awake, Behaving Primates
Authors: Tolias Andreas S. , Ecker Alexander S. , Siapas Athanassios G. , Hoenselaar Andreas , Keliris Georgios A. , Logothetis Nikos K.
Published: October 2007

Understanding the mechanisms of learning requires characterizing how the response properties of individual neurons and interactions across populations of neurons change over time. To study learning in vivo, we need the ability to track an electrophysiological signature that uniquely identifies each recorded neuron for extended periods of time. We have identified such an extracellular signature using a statistical framework that allows quantification of the accuracy by which stable neurons can be identified across successive recording sessions. Our statistical framework uses spike waveform information recorded on a tetrode's four channels to define a measure of similarity between neurons recorded across time. We use this framework to quantitatively demonstrate for the first time the ability to record from the same neurons across multiple consecutive days and weeks. The chronic recording techniques and methods of analyses we report can be used to characterize the changes in brain circuits due to learning.
Differences in Response to Muscarinic Activation Between First and Higher Order Thalamic Relays
Authors: Varela C. , Sherman S. Murray
Published: October 2007

The mammalian thalamus is composed of two types of thalamocortical relay. First order relays receive information from subcortical sources and relay it to cortex, whereas higher order relays receive information from layer 5 of one cortical area and relay it to another. Recent reports suggest that modulatory inputs to first and higher order relays may differ. We used rat thalamic brain slices and whole cell recordings from relay cells in various first order (the lateral geniculate nucleus, the ventral posterior nucleus, and the ventral portion of the medial geniculate body) and higher order (the lateral posterior, the posterior medial nucleus, and the dorsal portion of the medial geniculate body) relays to explore their responses to activation of muscarinic receptors. We found that, whereas all first order relay cells show a depolarizing response to muscarinic activation, ∼20% of higher order relay cells respond with hyperpolarization. The depolarization is accompanied by an overall increase in input resistance, whereas the hyperpolarization correlates with a decrease in resistance. Because activation of cholinergic brain stem afferents to thalamus increases with increasing behavioral vigilance, the findings suggest that increased vigilance will depolarize all first order and most higher order relay cells but will hyperpolarize a significant subset of higher order relay cells. Such hyperpolarization is expected to bias these relay cells to the burst firing mode, and so these results are consistent with evidence of more bursting among higher order than first order relay cells.
Differential Modulation by Nicotine of Substantia Nigra Versus Ventral Tegmental Area Dopamine Neurons
Authors: Keath J. Russel , Iacoviello Michael P. , Barrett Lindy E. , Mansvelder Huibert D. , McGehee Daniel S.
Published: October 2007

Midbrain dopamine (DA) neurons are found in two nuclei, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). The SNc dopaminergic projections to the dorsal striatum are involved in voluntary movement and habit learning, whereas the VTA projections to the ventral striatum contribute to reward and motivation. Nicotine induces profound DA release from VTA dopamine neurons but substantially less from the SNc. Nicotinic acetylcholine receptor (nAChR) expression differs between these nuclei, but it is unknown whether there are differences in nAChR expression on the afferent projections to these nuclei. Here we have compared the nicotinic modulation of excitatory and inhibitory synaptic inputs to VTA and SNc dopamine neurons. Although nicotine enhances both the excitatory and inhibitory drive to SNc DA cells with response magnitudes similar to those seen in the VTA, the prevalence of these responses in SNc is much lower. We also found that a mixture of nAChR subtypes underlies the synaptic modulation in SNc, further distinguishing this nucleus from the VTA, where α7 nAChRs enhance glutamate inputs and non-α7 receptors enhance GABA inputs. Finally, we compared the nicotine sensitivity of DA neurons in these two nuclei and found larger response magnitudes in VTA relative to SNc. Thus the observed differences in nicotine-induced DA release from VTA and SNc are likely due to differences in nAChR expression on the afferent inputs as well as on the DA neurons themselves. This may explain why nicotine has a greater effect on behaviors associated with the VTA than the SNc.
Discharge of the Readily Releasable Pool With Action Potentials at Hippocampal Synapses
Authors: Stevens Charles F. , Williams James H.
Published: October 2007

A readily releasable pool (RRP) of synaptic vesicles has been identified at hippocampal synapses with application of hypertonic solution. RRP size correlates with important properties of synaptic function such as release probability. However, a discrepancy in RRP size has been reported depending on the method used to evoke synaptic release. This study was undertaken to determine quantitative relationships between the RRP defined with hypertonic solution and that released with trains of action potentials. We find that asynchronous release at cell culture synapses contributes significantly to the discharge of the RRP with trains of action potentials and that RRP size is the same when elicited by either nerve stimuli or hypertonic challenge.
Sensory Transduction and Adaptation in Inner and Outer Hair Cells of the Mouse Auditory System
Authors: Stauffer Eric A. , Holt Jeffrey R.
Published: October 2007

Auditory function in the mammalian inner ear is optimized by collaboration of two classes of sensory cells known as inner and outer hair cells. Outer hair cells amplify and tune sound stimuli that are transduced and transmitted by inner hair cells. Although they subserve distinct functions, they share a number of common properties. Here we compare the properties of mechanotransduction and adaptation recorded from inner and outer hair cells of the postnatal mouse cochlea. Rapid outer hair bundle deflections of about 0.5 micron evoked average maximal transduction currents of about 325 pA, whereas inner hair bundle deflections of about 0.9 micron were required to evoke average maximal currents of about 310 pA. The similar amplitude was surprising given the difference in the number of stereocilia, 81 for outer hair cells and 48 for inner hair cells, but may be reconciled by the difference in single-channel conductance. Step deflections of inner and outer hair bundles evoked adaptation that had two components: a fast component that consisted of about 60% of the response occurred over the first few milliseconds and a slow component that consisted of about 40% of the response followed over the subsequent 20–50 ms. The rate of the slow component in both inner and outer hair cells was similar to the rate of slow adaptation in vestibular hair cells. The rate of the fast component was similar to that of auditory hair cells in other organisms and several properties were consistent with a model that proposes calcium-dependent release of tension allows transduction channel closure.