bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxytocinergic and serotonergic systems involvement in sodium intake regulation: satiety or hypertonicity markers?
Authors: Godino Andrea , De Luca Laurival Antonio , Antunes-Rodrigues José , Vivas Laura
Published: June 2007

Previous studies demonstrated the inhibitory participation of serotonergic (5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD-induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD-induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5-HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and nondepleted animals. The OT plasma levels significantly increased only in the PD-induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.
Nonuniformity in the von Bezold-Jarisch reflex
Authors: Salo Lauren M. , Woods Robyn L. , Anderson Colin R. , McAllen Robin M.
Published: June 2007

The von Bezold-Jarisch reflex (BJR) is a vagally mediated chemoreflex from the heart and lungs, causing hypopnea, bradycardia, and inhibition of sympathetic vasomotor tone. However, cardiac sympathetic nerve activity (CSNA) has not been systematically compared with vasomotor activity during the BJR. In 11 urethane-anesthetized (1–1.5 g/kg iv), artificially ventilated rats, we measured CSNA simultaneously with lumbar sympathetic activity (LSNA) while the BJR was evoked by right atrial bolus injections of phenylbiguanide (0.5, 1.0, 1.5, and 2 μg). Nerve and heartbeat responses were analyzed by calculating normalized cumulative sums. LSNA and heartbeats were always reduced by the BJR. An excitatory “rebound” component often followed the inhibition of LSNA but never outweighed it. For CSNA, however, excitation usually (in 7 of 11 rats) outweighed any initial inhibition, such that the net response to phenylbiguanide was excitatory. The differences in net response between LSNA, CSNA, and heartbeats were all significant ( P < 0.01). A second experimental series on seven rats showed that methyl atropine (1 mg/kg iv) abolished the bradycardia of the BJR, whereas subsequent bilateral vagotomy substantially reduced LSNA and CSNA responses, both excitatory and inhibitory. These findings show that, during the BJR, 1) CSNA is often excited, 2) there may be coactivation of sympathetic and parasympathetic drives to the heart, 3) divergent responses may be evoked simultaneously in cardiac vagal, cardiac sympathetic, and vasomotor nervous pathways, and 4) those divergent responses are mediated primarily by the vagi.
The urokinase-type plasminogen activator receptor is not required for skeletal muscle inflammation or regeneration
Authors: Bryer Scott C. , Koh Timothy J.
Published: June 2007

The hypothesis of this study was the urokinase-type plasminogen activator receptor (uPAR) is required for accumulation of inflammatory cells in injured skeletal muscle and for efficient muscle regeneration. Expression of uPAR was elevated at 1 and 3 days after cardiotoxin-induced muscle injury in wild-type mice before returning to baseline levels. Neutrophil accumulation peaked 1 day postinjury in muscle from both wild-type (WT) and uPAR null mice, while macrophage accumulation peaked between 3 and 5 days postinjury, with no differences between strains. Histological analyses confirmed efficient muscle regeneration in both wild-type and uPAR null mice, with no difference between strains in the formation or growth of regenerating fibers, or recovery of normal morphology. Furthermore, in vitro experiments demonstrated that chemotaxis is not different between WT and uPAR null macrophages. Finally, fusion of cultured satellite cells into multinucleated myotubes was not different between cells isolated from WT and uPAR null mice. These results demonstrate that uPAR is not required for the accumulation of inflammatory cells or the regeneration of skeletal muscle following injury, suggesting uPA can act independently of uPAR to regulate events critical for muscle regeneration.
Thyroid hormone replacement normalizes renal renin and angiotensin receptor expression in thyroidectomized fetal sheep
Authors: Chen Kai , Carey Luke C. , Valego Nancy K. , Rose James C.
Published: June 2007

Previous studies have suggested that thyroid hormone influences maturation of the renin-angiotensin system (RAS) and cardiovascular function in the late-gestation fetal sheep. To further examine the importance of thyroid hormone in this regard, we used the technique of thyroidectomy (TX) to remove endogenous thyroid hormone from the circulation and then replaced it with physiological amounts of exogenous thyroxine. We hypothesized that the previously observed changes in RAS activity and cardiovascular function associated with TX would be normalized. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. After 3 days of recovery, TX fetuses were continuously intravenously infused with thyroxine until delivery by cesarean section close to term (around 138 dGA). Immediately before necropsy, fetuses were infused with isoproterenol, and the hemodynamic responses were noted. Thyroid hormone replacement normalized not only plasma triiodothyronine (T3) and thyroxine (T4) levels but also the TX-induced decreases in renal renin mRNA and renal renin content. Renal ANG II subtype receptor expression levels were also normalized for both mRNA and protein. Decreased basal heat rate and systolic blood pressure associated with TX returned to normal following replacement; however, changes in mean blood pressure and isoproterenol-induced changes in mean blood pressure were not altered. These findings demonstrate that replacement of thyroid hormone in hypothyroid sheep fetuses can restore renal ANG II receptor and renin expression and secretion to normal.
Evidence that neurotensin mediates postprandial intestinal hyperemia in the python,Python regius
Authors: Skovgaard Nini , Conlon J. Michael , Wang Tobias
Published: June 2007

Digestion of large meals in pythons produces substantial increases in heart rate and cardiac output, as well as a dilation of the mesenteric vascular bed leading to intestinal hyperemia, but the mediators of these effects are unknown. Bolus intra-arterial injections of python neurotensin ([His3, Val4, Ala7]NT) (1 − 1,000 pmol/kg) into the anesthetized ball python Python regius ( n = 7) produced a dose-dependent vasodilation that was associated with a decrease in systemic pressure (Psys) and increase in systemic blood flow (Qsys). There was no effect on pulmonary pressure and conductance. A significant ( P < 0.05) increase in heart rate ( fH) and total cardiac output (Qtot) was seen only at high doses (>30 pmol/kg). The systemic vasodilation and increase in Qtotpersisted after β-adrenergic blockade with propranolol, but the rise in fHwas abolished. Also, the systemic vasodilation persisted after histamine H2-receptor blockade. In unanesthetized pythons ( n = 4), bolus injection of python NT in a dose as low as 1 pmol/kg produced a significant increase in blood flow to the mesenteric artery (177% ± 54%; mean ± SE) and mesenteric conductance (219% ± 74%) without any increase in Qsys, systemic conductance, Psys, and fH. The data provide evidence that NT is an important hormonal mediator of postprandial intestinal hyperemia in the python, but its involvement in mediating the cardiac responses to digestion may be relatively minor.
Artificial sweeteners and salts producing a metallic taste sensation activate TRPV1 receptors
Authors: Riera Céline E. , Vogel Horst , Simon Sidney A. , Coutre Johannes le
Published: June 2007

Throughout the world many people use artificial sweeteners (AS) for the purpose of reducing caloric intake. The most prominently used of these molecules include saccharin, aspartame (Nutrasweet), acesulfame-K, and cyclamate. Despite the caloric advantage they provide, one key concern in their use is their aversive aftertaste that has been characterized on a sensory level as bitter and/or metallic. Recently, it has been shown that the activation of particular T2R bitter taste receptors is partially involved with the bitter aftertaste sensation of saccharin and acesulfame-K. To more fully understand the biology behind these phenomena we have addressed the question of whether AS could stimulate transient receptor potential vanilloid-1 (TRPV1) receptors, as these receptors are activated by a large range of structurally different chemicals. Moreover, TRPV1 receptors and/or their variants are found in taste receptor cells and in nerve terminals throughout the oral cavity. Hence, TRPV1 activation could be involved in the AS aftertaste or even contribute to the poorly understood metallic taste sensation. Using Ca2+imaging on TRPV1 receptors heterologously expressed in the human embryonic kidney (HEK) 293 cells and on dissociated primary sensory neurons, we find that in both systems, AS activate TRPV1 receptors, and, moreover, they sensitize these channels to acid and heat. We also found that TRPV1 receptors are activated by CuSO4, ZnSO4, and FeSO4, three salts known to produce a metallic taste sensation. In summary, our results identify a novel group of compounds that activate TRPV1 and, consequently, provide a molecular mechanism that may account for off tastes of sweeteners and metallic tasting salts.
The farnesoid X receptor FXRα/NR1H4 acquired ligand specificity for bile salts late in vertebrate evolution
Authors: Cai Shi-Ying , Xiong Liangshi , Wray Charles G. , Ballatori Nazzareno , Boyer James L.
Published: June 2007

The nuclear receptor FXRα (NR1H4) plays a pivotal role in maintaining bile salt and lipid homeostasis by functioning as a bile salt sensor in mammals. In contrast, FXRβ (NR1H5) from mouse is activated by lanosterol and does not share common ligands with FXRα. To further elucidate FXR ligand/receptor and structure/function relationships, we characterized a FXR gene from the marine skate, Leucoraja erinacea, representing a vertebrate lineage that diverged over 400 million years ago. Phylogenetic analysis of sequence data indicated that skate Fxr (sFxr) is a FXRβ. There is an extra sequence in the middle of the sFxr ligand binding domain (LBD) compared with the LBD of FXRα. Luciferase reporter assays demonstrated that sFxr responds weakly to scymnol sulfate, bile salts, and synthetic FXRα ligands, in striking difference from human FXRα (hFXRα). Interestingly, all-trans retinoic acid was capable of transactivating both hFXRα and sFxr. When the extra amino acids in the sFxr LBD were deleted and replaced with the corresponding sequence from hFXRα, the mutant sFxr gained responsiveness to ursodeoxycholic acid, GW4064, and fexaramine. Surprisingly, chenodeoxycholic acid antagonized this activation. Together, these results indicate that FXR is an ancient nuclear receptor and suggest that FXRα may have acquired ligand specificity for bile acids later in evolution by deletion of a sequence from its LBD. Acquisition of this property may be an example of molecular exploitation, where an older molecule is recruited for a new functional role.
Met-RANTES reduces endothelial progenitor cell homing to activated (glomerular) endothelium in vitro and in vivo
Authors: Rookmaaker Maarten B. , Verhaar Marianne C. , de Boer Hetty C. , Goldschmeding Roel , Joles Jaap A. , Koomans Hein A. , Gröne Hermann-Josef , Rabelink Ton J.
Published: June 2007

The chemokine RANTES (regulated upon activation normal T-cell expressed and secreted) is involved in the formation of an inflammatory infiltrate during glomerulonephritis. However, RANTES receptor inhibition, although reducing glomerular leukocyte infiltration, can also increase damage. We hypothesized that RANTES does not only promote the influx and activation of inflammatory leukocytes but also mediates glomerular microvascular repair by stimulating the homing of bone marrow (BM)-derived endothelial progenitor cells. To investigate the role of RANTES in the participation of BM-derived cells in glomerular vascular repair, we used a rat BM transplantation model in combination with reversible anti-Thy-1.1 glomerulonephritis. Twenty-four hours after the induction of glomerulonephritis, BM-transplanted rats were treated for 7 days with either the RANTES receptor antagonist Met-RANTES or saline. The participation of BM-derived endothelial cells in glomerular repair, glomerular monocyte infiltration, and proteinuria was evaluated at days 7 and 28. Furthermore, we used an in vitro perfusion chamber assay to study the role of RANTES receptors in shear-resistant adhesion of the CD34+ stem cells to activated endothelium under flow. In our reversible glomerulonephritis model, RANTES receptor inhibition specifically reduced the participation of BM-derived cells in glomerular vascular repair by more than 40% at day 7 without impairing monocyte influx. However, no obvious change in recovery from proteinuria or morphological damage was observed. Blockade of RANTES receptors on CD34+ cells in vitro partially inhibited platelet-enhanced, shear-resistant firm adhesion of the CD34+ cells to activated endothelium. In conclusion, our data suggest that RANTES is involved in the homing and participation of BM-derived endothelial cells in glomerular repair.
Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-β1 in renal epithelial cells
Authors: Traylor Amie , Hock Thomas , Hill-Kapturczak Nathalie
Published: June 2007

Excess transforming growth factor-β1 (TGF-β1) in the kidney leads to increased cell proliferation and deposition of extracellular matrix, resulting in progressive kidney fibrosis. TGF-β1, however, stabilizes and attenuates tissue injury through the activation of cytoprotective proteins, including heme oxygenase-1 (HO-1). HO-1 catabolizes pro-oxidant heme into substances with anti-oxidant, anti-apoptotic, anti-fibrogenic, vasodilatory and immune modulatory properties. Little is known regarding the molecular regulation of human HO-1 induction by TGF-β1 except that it is dependent on de novo RNA synthesis and requires a group of structurally related proteins called Smads. It is not known whether other DNA binding proteins are required to initiate transcription of HO-1 and, furthermore, the promoter region(s) involved in TGF-β1-mediated induction of HO-1 has not been identified. The purpose of this study was to further delineate the molecular regulation of HO-1 by TGF-β1 in human renal proximal tubular cells. Actinomycin D and nuclear run-on studies demonstrate that TGF-β1 augments HO-1 expression by increased gene transcription and does not involve increased mRNA stability. Using transient transfection, mithramycin A, small interfering RNA, electrophoretic mobility shift assays, and decoy oligonucleotide experiments, a TGF-β1-responsive region is identified between 9.1 and 9.4 kb of the human HO-1 promoter. This ∼280-bp TGF-β1-responsive region contains a putative Smad binding element and specificity protein 1 binding sites, both of which are required for human HO-1 induction by TGF-β1.
The influence of physical training on the angiopoietin and VEGF-A systems in human skeletal muscle
Authors: Gustafsson T. , Rundqvist H. , Norrbom J. , Rullman E. , Jansson E. , Sundberg C. J.
Published: June 2007

Eleven subjects performed one-legged exercise four times per week for 5 wk. The subjects exercised one leg for 45 min with restricted blood flow (R leg), followed by exercise with the other leg at the same absolute workload with unrestricted blood flow (UR leg). mRNA and protein expression were measured in biopsies from the vastus lateralis muscle obtained at rest before the training period, after 10 days, and after 5 wk of training, as well as 120 min after the first and last exercise bouts. Basal Ang-2 and Tie-1 mRNA levels increased in both legs with training. The Ang-2-to-Ang-1 ratio increased to a greater extent in the R leg. The changes in Ang-2 mRNA were followed by similar changes at the protein level. In the R leg, VEGF-A mRNA expression responded transiently after acute exercise both before and after the 5-wk training program. Over the course of the exercise program, there was a concurrent increase in basal VEGF-A protein and VEGFR-2 mRNA in the R leg. Ki-67 mRNA showed a greater increase in the R leg and the protein was localized to the endothelial cells. In summary, the increased translation of VEGF-A is suggested to be caused by the short mRNA burst induced by each exercise bout. The concurrent increase in the Ang-2-to-Ang-1 ratio and the VEGF-expression combined with the higher level of Ki-67 mRNA in the R leg indicate that changes in these systems are of importance also in nonpathological angiogenic condition such as voluntary exercise in humans. It further establish that hypoxia/ischemia-related metabolic perturbation is likely to be involved as stimuli in this process in human skeletal muscle.
Role of Individual Basal Ganglia Nuclei in Force Amplitude Generation
Authors: Spraker Matthew B. , Yu Hong , Corcos Daniel M. , Vaillancourt David E.
Published: June 2007

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.
What Delay Fields Tell Us About Striate Cortex
Authors: Tehovnik Edward J. , Slocum Warren M.
Published: June 2007

It is well known that electrical activation of striate cortex (area V1) can disrupt visual behavior. Based on this knowledge, we discovered that electrical microstimulation of V1 in macaque monkeys delays saccadic eye movements when made to visual targets located in the receptive field of the stimulated neurons. This review discusses the following issues. First, the parameters that affect the delay of saccades by microstimulation of V1 are reviewed. Second, the excitability properties of the V1 elements mediating the delay are discussed. Third, the properties that determine the size and shape of the region of visual space affected by stimulation of V1 are described. This region is called a delay field. Fourth, whether the delay effect is mainly due to a disruption of the visual signal transmitted through V1 or whether it is a disturbance of the motor signal transmitted between V1 and the brain stem saccade generator is investigated. Fifth, the properties of delay fields are used to estimate the number of elements activated directly by electrical microstimulation of macaque V1. Sixth, these properties are used to make inferences about the characteristics of visual percepts induced by such stimulation. Seventh, the disruptive effects of V1 stimulation in monkeys and humans are compared. Eighth, a cortical mechanism to account for the disruptive effects of V1 stimulation is proposed. Finally, these effects are related to normal vision.
Contribution of Persistent Sodium Current to Locomotor Pattern Generation in Neonatal Rats
Authors: Tazerart Sabrina , Viemari Jean-Charles , Darbon Pascal , Vinay Laurent , Brocard Frédéric
Published: June 2007

The persistent sodium current ( INaP) is known to play a role in rhythm generation in different systems. Here, we investigated its contribution to locomotor pattern generation in the neonatal rat spinal cord. The locomotor network is mainly located in the ventromedial gray matter of upper lumbar segments. By means of whole cell recordings in slices, we characterized membrane and INaPbiophysical properties of interneurons located in this area. Compared with motoneurons, interneurons were more excitable, because of higher input resistance and membrane time constant, and displayed lower firing frequency arising from broader spikes and longer AHPs. Ramp voltage-clamp protocols revealed a riluzole- or TTX-sensitive inward current, presumably INaP, three times smaller in interneurons than in motoneurons. However, in contrast to motoneurons, INaPmediated a prolonged plateau potential in interneurons after reducing K+and Ca2+currents. We further used in vitro isolated spinal cord preparations to investigate the contribution of INaPto locomotor pattern. Application of riluzole (10 μM) to the whole spinal cord or to the upper lumbar segments disturbed fictive locomotion, whereas application of riluzole over the caudal lumbar segments had no effect. The effects of riluzole appeared to arise from a specific blockade of INaPbecause action potential waveform, dorsal root–evoked potentials, and miniature excitatory postsynaptic currents were not affected. This study provides new functional features of ventromedial interneurons, with the first description of INaP-mediated plateau potentials, and new insights into the operation of the locomotor network with a critical implication of INaPin stabilizing the locomotor pattern.
Moving From an Averaged to Specific View of Spinal Cord Pain Processing Circuits
Authors: Graham B. A. , Brichta A. M. , Callister R. J.
Published: June 2007

Neurons in the superficial dorsal horn (SDH) of the spinal cord play a critical role in processing potentially painful or noxious signals from skin, muscle, and viscera. Many acute pain therapies are based on the notion that altering the excitability of SDH neurons can block or gate these signals and reduce pain. This same notion also underlies treatments for certain chronic pain states. Basic scientists are now beginning to identify a number of potential molecular targets for spinal cord–based pain therapies with a focus on ion channels and receptors that can alter neuronal excitability. The current challenge in pain research is to identify which are the most promising targets and how their manipulation alters pain processing. In this review, we propose that our understanding of spinal pain processing mechanisms and translation of these discoveries into pain therapies could be improved by 1) better appreciating and understanding neuronal heterogeneity in the SDH; 2) establishing connectivity patterns among SDH neuron types; and 3) testing and extending findings made in vitro to intact (in vivo) animal models. As this information becomes available, it will be possible to determine the precise distribution of potential therapeutic targets on various SDH neuron types within specific circuits known to be functionally important in spinal pain processing.
Cardiac mass and cardiomyocyte size are governed by different genetic loci on either autosomes or chromosome Y in recombinant inbred mice
Authors: Llamas Bastien , Bélanger Sonia , Picard Sylvie , Deschepper Christian F.
Published: June 2007

Left ventricular hypertrophy is one of the main risk factors for cardiovascular mortality and morbidity. It has been proposed that hypertrophic stimuli act in great part by increasing the size of cardiomyocytes, and that the latter characteristic is a necessary condition to differentiate left ventricular hypertrophy from other benign forms of cardiac enlargement. To test whether the same genetic loci control the size of cardiomyocytes and left ventricular mass, we performed whole genome linkage analyses in a panel of 24 recombinant inbred AXB/BXA mouse strains. Whereas one major locus was linked to left ventricular mass in both males and females, loci linked to the size of cardiomyocytes were clearly distinct and showed sex-specific linkage. Moreover, the parental origin of chromosome Y had strong effects on the size of cardiomyocytes in male mice but did not affect left ventricular mass. In addition to showing that genetic loci that increase the size of cardiomyocytes are not necessarily linked to increased left ventricular mass, our findings have important consequences in evaluating cardiac phenotypes when performing genetic manipulations in mice, and in determining the cause of sex-specific differences when using models derived from C57BL/6J mice.
Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A upregulates ACE and AT1 receptor gene expression and signaling: role in cardiac hypertrophy
Authors: Vellaichamy Elangovan , Zhao Di , Somanna Naveen , Pandey Kailash N.
Published: June 2007

Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signaling antagonizes the physiological effects mediated by the renin-angiotensin system (RAS). The objective of this study was to determine whether the targeted-disruption of Npr1 gene (coding for GC-A/NPRA) leads to the activation of cardiac RAS genes involved on the hypertrophic remodeling process. The Npr1 gene-knockout ( Npr1−/−) mice showed 30–35 mmHg higher systolic blood pressure (SBP) and a 63% greater heart weight-to-body weight (HW/BW) ratio compared with wild-type ( Npr1+/+) mice. The mRNA levels of both angiotensin-converting enzyme and angiotensin II type 1a receptor were increased by three- and fourfold, respectively, in Npr1−/−null mutant mice hearts compared with the wild-type Npr1+/+mice hearts. In parallel, the expression levels of interleukin-6 and tumor necrosis factor-α were increased by four- to fivefold, in Npr1−/−mice hearts compared with control animals. The NF-κB binding activity in nuclear extracts of Npr1−/−mice hearts was increased by fourfold compared with wild-type Npr1+/+mice hearts. Treatments with captopril or hydralazine equally attenuated SBP; however, only captopril significantly decreased the HW/BW ratio and suppressed cytokine gene expression in Npr1−/−mice hearts. The ventricular cGMP level was reduced by almost sixfold in Npr1−/−mice compared with wild-type control mice. The results of the present study indicate that disruption of NPRA/cGMP signaling leads to the augmented expression of cardiac RAS pathways that promote the development of cardiac hypertrophy and remodeling.
TNF-α interferes with lipid homeostasis and activates acute and proatherogenic processes
Authors: Tacer Klementina Fon , Kuzman Drago , Seliškar Matej , Pompon Denis , Rozman Damjana
Published: June 2007

The interaction between disrupted lipid homeostasis and immune response is implicated in the pathogenesis of several diseases, but the molecular bridges between the major players are still a matter of controversy. Our systemic study of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α) in the livers of mice exposed to 20-h cytokine/fasting for the first time shows that TNF-α interferes with adaptation to fasting and activates harmful proatherogenic pathways, partially through interaction with the insulin-Insig-sterol regulatory element binding protein (Srebp) signaling pathway. In addition to the increased expression of acute-phase inflammatory genes, the most prominent alterations represent modified lipid homeostasis observed on the gene expression and metabolite levels. These include reduction of HDL-cholesterol, increase of LDL-cholesterol, and elevated expression of cholesterogenic genes, accompanied by increase of potentially harmful precholesterol metabolites and suppression of cholesterol elimination through bile acids, likely by farnesoid X receptor-independent mechanisms. On the transcriptional level, a shift from fatty oxidation toward fatty acid synthesis is observed. The concept of the influence of TNF-α on the Srebp regulatory network, followed by downstream effects on sterol metabolism, is novel. Observed acute alterations in lipid metabolism are in agreement with chronic disturbances found in patients.
Evolution of Birdsong Syntax by Interjection Communication
Authors: Sasahara Kazutoshi , Ikegami Takashi
Published: June 2007

Animals use diverse forms of communication, from sound signals to body postures. Recent ethological studies have reported a unique syntactic communication of a songbird, the Bengalese finch (Lonchura striata var. domestica). Male Bengalese finches sing complex courtship songs, which can be reconstructed by finite automata, and female Bengalese finches prefer complex songs, as opposed to monotonous or random ones. These facts suggest that the song syntaxes of male birds may have evolved as a result of sexual selection by female birds. Inspired by this hypothesis, we developed a communication model that is a system coupling different types of automaton, one for song production by males and another for song evaluation by females. We applied this model to study the evolution of syntactic animal communication in terms of the self-organization of coevolving automata. Three types of courting strategies as well as a relationship between the song syntax and female preference emerged. We argue that despite the simple communication involved, the complexity and diversity of song syntaxes can evolve via diverse female preferences.
Genetic Exchange Leading to Self-Assembling RNA Species upon Encapsulation in Artificial Protocells
Authors: Zenisek Sergio-Francis M. , Hayden Eric J. , Lehman Niles
Published: June 2007

The encapsulation of information-bearing macromolecules inside protocells is a critical step in scenarios for the origins of life on the Earth as well as for the construction of artificial living systems. For these protocells to emulate life, they must be able to transmit genetic information to other cells. We have used a water-in-oil emulsion system to simulate the compartmentalization of catalytic RNA molecules. By exploiting RNA-directed recombination reactions previously developed in our laboratory, including a ribozyme self-assembly pathway, we demonstrate that it is possible for information to be exchanged among protocells. This can happen either indirectly by the passage of divalent cations through the inter-protocellular medium (oil), or by the direct interaction of two or more protocells that allows RNA molecules to be exchanged. The degree of agitation affects the ability of such exchange. The consequences of these results include the implications that prototypical living systems can transmit information among compartments, and that the environment can regulate the extent of this crosstalk.
Interpreting Rosen
Authors: Wolkenhauer Olaf
Published: June 2007

Some reflections on Robert Rosen, Chu and Ho, and Louie.
A Living System Must Have Noncomputable Models
Authors: Louie A. H.
Published: June 2007

Chu and Ho's recent article in Artificial Life is riddled with errors. In particular, they use a wrong definition of Robert Rosen's mechanism. This renders their “critical assessment” of Rosen's central proof null and void.
Dependency-Based Construction of Semantic Space Models
Authors: Padó Sebastian , Lapata Mirella
Published: June 2007

Traditionally, vector-based semantic space models use word co-occurrence counts from large corpora to represent lexical meaning. In this article we present a novel framework for constructing semantic spaces that takes syntactic relations into account. We introduce a formalization for this class of models, which allows linguistic knowledge to guide the construction process. We evaluate our framework on a range of tasks relevant for cognitive science and natural language processing: semantic priming, synonymy detection, and word sense disambiguation. In all cases, our framework obtains results that are comparable or superior to the state of the art.
Hierarchical Phrase-Based Translation
Authors: Chiang David
Published: June 2007

We present a statistical machine translation model that uses hierarchical phrases—phrases that contain subphrases. The model is formally a synchronous context-free grammar but is learned from a parallel text without any syntactic annotations. Thus it can be seen as combining fundamental ideas from both syntax-based translation and phrase-based translation. We describe our system's training and decoding methods in detail, and evaluate it for translation speed and translation accuracy. Using BLEU as a metric of translation accuracy, we find that our system performs significantly better than the Alignment Template System, a state-of-the-art phrase-based system.
Candanbala's Tears: Recovering the Emotional Life of Jainism
Authors: Kelting M. Whitney
Published: June 2007

In the oft-told narrative of the Jain sati Candanbala, we see her standing at the door in chains, making an offering of lentils to Mahavir with tears in her eyes. Candanbala's tears, which arise after Mahavir passes by without taking alms, resonate with the Jain experience of worshipping an unresponsive Jina. Jain theology has been presented as anti-emotion and yet, within the most normative strata of the tradition, we find emotions and bhakti devotionalism as key first causes of moral actions of ideal persons. This essay examines the representations of Candanbala's tears in Shvetambar narrative and hymn literature alongside contemporary performances of the Candanbala Fast, the end of which is marked by a reenactment of this narrative. Analysis (informed by field research) of textual materials illuminates the potential for beneficial emotions within the Jain tradition alongside the argument that Candanbala's popularity arises from an identification with her moment of despair.
Hermetic Histories: Divine Providence and Conspiracy Theory
Authors: Bennett Brian
Published: June 2007

In the ancient world, the writing of history was closely connected with divination. In this essay I argue that two types of historiography, the providential and the conspiratorial, have a distinct divinatory dimension. Divination purports to uncover occult influences behind the gritty flux of human affairs. Providentialism looks for the "hand of God" in historical events both great and small. Conspiracism is concerned not with the "hand of God" but the "hidden hand." Providentialism and conspiracism are hermetic histories. Like divination they concern themselves with tracking and interpreting signs. History is deciphered via sacred/secret texts, such as the Bible or The Protocols of the Elders of Zion. In this mode historiography is akin to cryptography. Providentialism and conspiracism are hermetic also in the sense that they present "airtight," all-encompassing explanations of past events. They are totalizing histories. The purpose of this essay is to highlight connections between the discourses of divination, divine providence, and conspiracy theory. By way of illustration, I discuss the Primary Chronicle of Kievan Rus' and two articles written in the post-Soviet period by the late Metropolitan Ioann. The approach taken in this essay foreshortens textual detail and historical depth in favor of a kind of Wittgensteinian perspicuous presentation. Hence the value of formal links: the vaulting phrases of providentialism resound in the Primary Chronicle, yet the text seems grounded in the Lebenswelt of divination; in the articles of Ioann, providentialism passes into conspiracism, demonstrating a link between the two hermetic discourses.
Actuality, Potentiality and De Anima II.5
Authors: Heinaman Robert
Published: June 2007

Myles Burnyeat has argued that in De Anima II.5 Aristotle marks out a refined kind of alteration which is to be distinguished from ordinary alteration, change of quality as defined in Physics III.1-3. Aristotle's aim, he says, is to make it clear that perception is an alteration of this refined sort and not an ordinary alteration. Thus, it both supports his own interpretation of Aristotle's view of perception, and refutes the Sorabji interpretation according to which perception is a composite of form and matter where the matter is a material alteration in the body. I argue that Burnyeat's interpretation of II.5 should be rejected for a number of reasons, and offer a new interpretation of the distinctions drawn in the chapter, and the relations between them. I conclude that the chapter provides no evidence against the Sorabji view or for Burnyeat's view. Aristotle's assertion that perception is a refined kind of alteration means that it is the kind of alteration that preserves and is good for the subject of that alteration. There is no inconsistency in the thought that perception is a refined alteration of this sort while it, or its matter, is an ordinary alteration.
Anselm's Argumentum and the Early Medieval Theory of Argument
Authors: Holopainen Toivo
Published: June 2007

The article aims at elucidating the argumentation in Anselm's Proslogion by relating some aspects of it to the early medieval theory of argument. The focus of the analysis is on the "single argument" (unum argumentum), the discovery of which Anselm announces in the Preface to the Proslogion. Part 1 of the article offers a preliminary description of the single argument by describing the reductio ad absurdum technique based on the notion "that than which a greater cannot be thought". Part 2 discusses the ideas about arguments and argumentation that Boethius presents in Book One of his In Ciceronis Topica. Part 3 draws attention to some early medieval sources (Abelard, Lanfranc, Anselm) that are witness to the importance of the Boethian ideas in Anselm's time. Finally, Part 4 argues that Anselm looked at his single argument in the Boethian framework and that the term "that than which a greater cannot be thought" should be identified as his single argument.
Francesco Patrizi da Cherso's Criticism of Aristotle's Logic Francesco Patrizi da Cherso's Criticism of Aristotle's Logic
Authors: Deitz Luc
Published: June 2007

Francesco Patrizi da Cherso's Discussiones peripateticae (1581) are one of the most comprehensive analyses of the whole of Aristotelian philosophy to be published before Werner Jaeger's Aristoteles. The main thrust of the argument in the Discussiones is that whatever Aristotle had said that was true was not new, and that whatever he had said that was new was not true. The article shows how Patrizi proves this with respect to the Organon, and deals with the implications for the history af ancient philosophy in general implied by his stance.
Foundations and Mass Movements: The Case of the World Social Forum1
Authors:   Research Unit for Political Economy
Published: June 2007

Foundation funding flows to very diverse activities, including welfare programs, the arts, academia, and the media. It has been argued that all such funding, no matter how apparently non-political the activity, has political significance, strengthening the hegemony of the ruling classes. By their very nature, foundation interventions in social movements play a political role.

This includes their involvement with apparently “grassroots” protests such as the World Social Forum, where the individuals, organizations, and institutions assisted by foundations span a wide range, some even espousing radical views. This flexibility and range in fact increase the reach and influence of foundations, allowing them to intervene in rapidly changing social developments. Since foundations are largely created and sustained by the ruling classes and state powers of the imperialist countries, foundation intervention in social movements in the imperialist countries as well as in the third world should be seen as part of imperialism's efforts to prevent the emergence of systemic challenges to its rule at home and its sway abroad.
Divining the Past: The Linguistic Reconstruction of 'African' Roots in Diasporic Ritual Registers and Songs
Authors: Wirtz Kristina
Published: June 2007

I examine the assumptions underlying scholars' use of etymological reconstruction to connect ritual registers in African diasporic religions with African 'sources', and to thereby reclaim African diasporic history by recovering 'lost' or hidden meanings. I compare these efforts to the interpretive practices of practitioners of Cuban Santería, who engage in textual and performative 'divinations' of hidden or lost meanings in Lucumí and in ritual modes of 'temporal telescoping' through which an African past becomes transcendent and ritually immanent. I suggest that religiously informed modes of historical subjectivity can illuminate the efforts of linguists and other scholars of the African diaspora who are engaged in seeking 'lost' or hidden memories and meanings and in 'temporal telescoping'. I argue that scholars of African diasporic religion and language must attend more carefully to issues of time, historical consciousness and historicity, especially as they are embedded in our own language ideologies and historiographic interpretive practices.
Ecué's Atlantic: An Essay in Methodology
Authors: Palmié Stephan
Published: June 2007

Arguing from an exposition of the principal epistemological and methodological problems that have plagued African-Americanist research since its inception as a properly disciplined anthropological pursuit, this essay focuses on an ostensibly 'clear' case of 'transatlantic continuities' to question linear construction of historical relations between 'African' and 'African-American' cultural forms. Detailing the social history of an African male initiatory sodality and its supposed Cuban equivalent within their wider political economic contexts, I argue that the apparent dispersion of Cross-River-type secret societies ought not to be seen as a pattern of diffusion from a (temporally prior) point of inception to (temporally later) sites of recreation, but as a total pattern of simultaneous 'Atlantic' eventuation and cultural production.
Modal and Nonmodal Symmetric Perturbations. Part I: Completeness of Normal Modes and Constructions of Nonmodal Solutions
Authors: Xu Qin
Published: June 2007

It is shown that the classic normal modes for symmetric perturbations in a layer of vertically sheared basic flow can be classified into three types: paired growing and decaying modes, paired slowly propagating modes, and paired fast propagating modes. In the limit of vanishing growth rate (or frequency), the paired growing and decaying (or slowly propagating) modes degenerate into paired stationary and linearly growing modes. Degeneracies occur only on a discrete set (which is infinite but has zero measure) in the wavenumber space when the Richardson number is smaller than one. A nonmodal solution is not affected by the degenerate modes unless the solution is horizontally periodic and contains wavenumbers at which the degeneracy occurs. The classic modes and degenerate modes form a complete set in the sense that they contain all the wavenumbers and thus can construct any admissible nonmodal solutions.

The mode structures are analyzed by considering the slopes of their slantwise circulations relative to the absolute-momentum surface and isentropic surface of the basic state in the vertical cross section perpendicular to the circulation bands. The cross-band streamfunction component modes are shown to be orthogonal between different pairs (measured by the subspace inner product associated with the cross-band kinetic energy). The full-component modes, however, are nonorthogonal (measured by the full-space inner product associated with the total perturbation energy), and two paired modes have exactly opposite polarization relationships between the cross-band motion and its driving inertial–buoyancy force (associated with the along-band velocity and buoyancy perturbations). These properties have important implications for the nonmodal growths examined in Part II.

In association with the complete set of normal modes, a complete set of adjoint modes is derived along with the biorthogonal relationships between the normal modes and adjoint modes. By using the biorthogonality, nonmodal solutions can be conveniently constructed from the normal modes for the initial value problem.
A Seasonal Climatology of Rossby Wave Breaking in the 320–2000-K Layer
Authors: Hitchman Matthew H. , Huesmann Amihan S.
Published: June 2007

Differential advection in Rossby waves can lead to potential vorticity (PV; P) contours on isentropic surfaces folding over in latitude (Py < 0) in a process called Rossby wave breaking (RWB). Exploring the properties of RWB may shed light on underlying dynamics and enable quantification of irreversible transport. A seasonal climatology of Py and RWB statistics is presented for the 320–850-K layer using NCEP reanalysis data during 1979–2005 and for the 320–2000-K layer using the Met Office (UKMO) data during 1991–2003. A primary goal is to depict the spatial extent and seasonality of RWB maxima. This analysis shows seven distinct RWB regimes: poleward and equatorward of the subtropical westerly jets, poleward and equatorward of the stratospheric polar night jets, flanking the equator in the stratosphere and mesosphere, equatorward of subtropical monsoon anticyclones, and the summertime polar stratosphere.

A striking PV gradient maximum exists at the equator throughout the layer 360–2000 K, flanked by subtropical RWB maxima, integral components of the Lagrangian cross-equatorial flow. Strong RWB occurs in the polar night vortex where β is small. Over the summer pole, strong poleward RWB associated with synoptic waves decays into small amplitude motions in the upper stratosphere, where heating gradients cause Py < 0. The seven spatial regimes are linked to three different dynamical causes of reversals: wave breaking associated with westerly jets, a combined barotropic/inertial instability in cross-equatorial flow, and on the periphery of monsoon anticyclones.