bluuebunny/crossref_metadata_2025 huggingface dataset:
A trophic study of the sympatric Amazonian freshwater turtles Podocnemis unifilis and Podocnemis expansa (Testudines, Podocnemidae) using carbon and nitrogen stable isotope analyses
Authors: Lara N.R.F. , Marques T.S. , Montelo K.M. , de Ataídes Á.G. , Verdade L.M. , Malvásio A. , de Camargo P.B.
Published: November 2012

The Yellow-spotted River Turtle ( Podocnemis unifilis Troschel, 1848) and the South American River Turtle (Podocnemis expansa (Schweigger, 1812)) are two turtles species that are widely distributed and have ecological, economic, and cultural importance in the Amazon basin. Although sympatric regarding most of their distribution, few studies have addressed the coexistence of these two species. To examine this, we analyzed the trophic level and the primary carbon source from the diets of both species in Baixo Araguaia, Tocantins, Brazil, using stable isotope analyses of carbon (δ13C) and nitrogen (δ15N). We also verified possible intraspecific variations (related to sex and body mass) in the trophic levels and primary carbon sources of their diets. Podocnemis unifilis had higher values of δ15N than P. expansa, averaging 7.59‰ and 5.06‰, respectively, a difference which may indicate a possible trophic change owing to exploiting different food resources. No differences were found between the two species in relation to δ13C (mean values of –26.2‰ and –26.1‰, respectively). The similarity between δ13C values suggests that the sources of their basal feeding are the same, consisting mainly of C3 plants. There was no intraspecific variation in the values of δ13C and δ15N.
Red shiners (Cyprinella lutrensis) have larger eyes in turbid habitats
Authors: Dugas M.B. , Franssen N.R.
Published: November 2012

The costs and benefits of investing in expensive sensory systems are shaped by environments that vary in the ease with which sensory information can be accessed. Fish provide an excellent model system in which to address questions of sensory evolution; while fishes rely heavily on vision, their visual environment is far more diverse and challenging than that of terrestrial animals. Turbidity, for example, alters the quantity of ambient light, its color, and the ability of animals to resolve borders of objects. Several comparative studies suggest that turbidity is associated with a reduction in the resources devoted to vision. Using these as a guide, we tested the prediction that turbidity and eye size would be negatively associated in populations of red shiners ( Cyprinella lutrensis (Baird and Girard, 1853)), a small-bodied cyprinid that is common and abundant in habitats spanning nearly the entire range of turbidity found in the Great Plains of the United States. We found that eye size was positively associated with turbidity, perhaps surprising given previous comparative work, but consistent with the finding that red shiners from turbid habitats display more intense nuptial coloration. This result highlights the need for further investigations of among-population variation to fully understand the mechanisms underlying sensory system diversity in animals.
Identification of gene expression profile during fertilization in Brassica campestris subsp. chinensis
Authors: Jiang Jingjing , Jiang Jianxia , Qiu Lin , Miao Ying , Yao Lina , Cao Jiashu
Published: November 2012

Fertilization is controlled by a complex gene regulatory network. To study the fertilization mechanism, we determined time courses of the four developmental stages of fertilization in Chinese cabbage pak-choi (Brassica campestris subsp. chinensis) by cytological observation. We then used the Arabidopsis ATH1 microarray to characterize the gene expression profiles of pollinated and unpollinated pistils in B. campestris subsp. chinensis. The result showed 44 up-regulated genes and 33 down-regulated genes in pollinated pistils compared with unpollinated pistils. Gene ontology analysis identified 20% of the up-regulated genes as belonging to the category of cell wall metabolism. We compared the up-regulated genes in pollinated pistils with previously identified pollen development related genes. Ten genes were found to be in common, which were termed as continuously expressed genes, in the two processes in the present article. Their expression patterns during pollen development and fertilization processes were then verified by RT–PCR. One of the continuously expressed genes, the homologous gene of At3g01270 in B. campestris subsp. chinensis, was confirmed as specifically expressed in microspores and pollinated pistils by using in situ hybridization. The potential biological functions of the other continuously expressed genes were also discussed.
QUANTUM DISCORD IN THE GROUND STATE OF SPIN CHAINS
Authors: SARANDY MARCELO S. , DE OLIVEIRA THIAGO R. , AMICO LUIGI
Published: November 2012

The ground state of a quantum spin chain is a natural playground for investigating correlations. Nevertheless, not all correlations are genuinely of quantum nature. Here we review the recent progress to quantify the "quantumness" of the correlations throughout the phase diagram of quantum spin systems. Focusing to one spatial dimension, we discuss the behavior of quantum discord (QD) close to quantum phase transitions (QPT). In contrast to the two-spin entanglement, pairwise discord is effectively long-ranged in critical regimes. Besides the features of QPT, QD is especially feasible to explore the factorization phenomenon, giving rise to nontrivial ground classical states in quantum systems. The effects of spontaneous symmetry breaking are also discussed as well as the identification of quantum critical points through correlation witnesses.
ELECTROCARDIOGRAM ARRHYTHMIA PATTERN RECOGNITION BASED ON AN IMPROVED WAVELET NEURAL NETWORK
Authors: YANG GUANGYING
Published: November 2012

Electrocardiography (ECG) is a transthoracic interpretation of the electrical activity of the heart over a period of time, as detected by electrodes attached to the outer surface of the skin and recorded by a device external to the body. ECG signal classification is very important for the clinical detection of arrhythmia. This paper presents an application of an improved wavelet neural network structure to the classification of the ECG beats, because of the high precision and fast learning rate. Feature extraction method in this paper is wavelet transform. Our experimental data set is taken from the MIT-BIH arrhythmia database. The correct detection rate of QRS wave is 95% by testing the data of MIT-BIH database. The proposed methods are applied to a large number of ECG signals consisting of 600 training samples and 120 test samples from the MIT-BIH database. The samples equally represent six different ECG signal types, including normal beat, atrial premature beat, ventricular premature beat, left bundle branch block, right bundle branch block and paced beat. In comparison with pattern recognition methods of BP neural networks, RBF neural networks and Support Vector Machines (SVM), the results in this experiment prove that the wavelet neural network method has a better recognition rate when classifying electrocardiogram signals. The experimental results prove that supposed method in this paper is effective for arrhythmia pattern recognition field.
New high-precision U–Pb dates from western European Carboniferous tuffs; implications for time scale calibration, the periodicity of late Carboniferous cycles and stratigraphical correlation
Authors: Pointon Michael A. , Chew David M. , Ovtcharova Maria , Sevastopulo George D. , Crowley Quentin G.
Published: November 2012

We present three new high-precision U–Pb zircon chemical abrasion–isotope dilution–thermal ionization mass spectrometry (CA-ID-TIMS) dates from western European Carboniferous diagenetically altered volcanic ash layers (bentonites and tonsteins) that occur interbedded with cyclic siliciclastic sedimentary rocks. The dates constrain the average periodicity of western European late Carboniferous (Arnsbergian to early Langsettian) cyclic sedimentation to between 89 and 124 ka per cycle. This is consistent with the 100 ka ‘short’ eccentricity Milankovitch cycle and supports previous suggestions that the cycles are the product of glacio-eustasy. Cyclostratigraphic tuning of Namurian cycles to the 100 ka eccentricity cycle revises the timing of the global Mississippian–Pennsylvanian boundary to
c
. 323.9 Ma. CA-ID-TIMS dates also facilitate correlation between different facies belts where biostratigraphical correlations are difficult. Correlation between eastern and western European sequences confirms that the base of the Moscovian stage is located within the Duckmantian (Westphalian B) western European regional substage.

Supplementary materials:

Zircon separation and concentration procedures, U–Pb zircon CA-ID-TIMS methods and data table, average periodicity calculations for western and central European Namurian and Westphalian sedimentary cycles, and procedures for recalibrating legacy
40
Ar/
39
Ar dates are available at
www.geolsoc.org.uk/SUP18547
.
Crescent-like large-scale structures in the external zones of the western Gibraltar Arc (Betic–Rif orogenic wedge)
Authors: Crespo-Blanc Ana , Balanyá J. C. , Expósito I. , Luján M. , Suades E.
Published: November 2012

The external wedge of the Gibraltar Arc orogenic system (western Mediterranean) is a natural case of a fold-and-thrust salient. Although at the scale of the arc a swing of the structural trend can be observed, the presence of closed, crescent-like structures, some of them more than 25 km long and scattered over an area of 3500 km
2
, characterize the Gibraltar Arc external wedge. This feature makes it very different from a ‘classical’ arc-shaped fold-and-thrust belt. Detailed structural maps of representative crescent-like structures are presented. Synorogenic sediments reveal that they probably formed during a short time interval, most probably during a single shortening event. The crescent-like structures are localized in front of a recess formed by the internal zones that acted as backstop. This backstop shape and a viscous substrate (essentially Triassic evaporites below the fold-and-thrust external wedge) constrain the experimental setting of an analogue model in which we were able to reproduce structures that developed originally with a highly non-cylindrical shape during a single, straight convergence. Moreover, the tectonic transport directions along the thrusts are broadly comparable in the natural case and the model.
Clinopyroxene–rutile phyllonites from the East Tenda Shear Zone (Alpine Corsica, France): pressure–temperature–time constraints to the Alpine reworking of Variscan Corsica
Authors: Maggi Matteo , Rossetti Federico , Corfu Fernando , Theye Thomas , Andersen Torgeir B. , Faccenna Claudio
Published: November 2012

The East Tenda Shear Zone is the regional structure that marks the Alpine overthrusting of the Ligurian–Piedmontese ocean onto the Variscan Corsica. We present the first report of a Na-pyroxene (acmite)–rutile-bearing assemblage from a phyllonitic shear zone that occurs within the gneissic lithologies of the East Tenda Shear Zone. Acmite hosts inclusions of Na-amphibole and titanite, and is rimmed by retrogressive biotite. Forward modelling of the shear zone assemblages in the NCKFMASTHO chemical system indicates a cold burial–exhumation path (palaeogeothermal gradient <10 °C km
−1
) and a metamorphic climax with minimum pressure of 1.2 GPa and temperatures of 350–400 °C. U–Pb thermal ionization mass spectrometry analyses on synkinematic rutile yield a 3D array with an age of 48 ± 18 Ma (MSWD 7.3), whereas coexisting acmite–phengite and coatings of oxides or sulphides provide an intercept at 54 ± 8 Ma (MSWD = 48). The scatter of the arrays is considered to reflect secondary disturbances of the system and the age provided by acmite–phengite and the coatings at 54 ± 8 Ma is considered the most reliable estimate for shear zone formation. Implications of these new metamorphic and geochronological data are discussed in the regional framework of the Alpine geology and integrated in the plate-tectonic scenario of the central Mediterranean.
New evidence concerning the thermal history of Devonian and Carboniferous rocks in the South Portuguese Zone
Authors: Fernandes Paulo , Musgrave Jennifer A. , Clayton Geoff , Pereira Zélia , Oliveira José Tomás , Goodhue Robbie , Rodrigues Bruno
Published: November 2012

The Late Palaeozoic rocks of southern Portugal have a complex thermal history. Vitrinite reflectance determinations from 90 samples confirm that the organic maturity of Late Palaeozoic rocks in SW Portugal is very high, mainly corresponding to meta-anthracite coal rank. The optic fabric of vitrinite in oriented coal samples from the Brejeira Formation suggests maturation under simple, non-tectonic, burial conditions with peak temperatures being attained prior to Variscan deformation. The lack of any increase in vitrinite reflectance with depth through
c
. 1 km of section in borehole AC-1 is not consistent with conductive heat transfer and is interpreted as the result of late synorogenic to post-orogenic advective heating. This heating episode generated temperatures sufficiently high to produce levels of maturity corresponding to meta-anthracite coal rank through much of the terrane now exposed, but not high enough to result in overprinting of the pre-deformation optic fabric of vitrinite in the thin coals. The slightly lower maturity of older, platform-facies rocks in the Aljezur–Bordeira area may reflect either deposition on a basement high followed by less burial than adjacent parts of the basin, or the area being the site of a sink for descending relatively cool fluids.
Crustal evolution of the South Mayo Trough, western Ireland, based on U–Pb ages and Hf–O isotopes in detrital zircons
Authors: Yin Q.-Z. , Wimpenny J. , Tollstrup D. L. , Mange M. , Dewey J. F. , Zhou Q. , Li X.-H. , Wu F.-Y. , Li Q.-L. , Liu Y. , Tang G.-Q.
Published: November 2012

Ordovician strata of the South Mayo Trough in western Ireland contain clastic deposits that represent materials eroded from a large and diverse continental area over a time scale that spans much of the Earth’s history. Therefore, it is a useful region to use detrital zircons to construct a continental crustal growth model. Here, we report integrated U–Pb, Lu–Hf and O isotope measurements obtained from
in situ
analyses of 160 zircons from the South Mayo Trough. U–Pb zircon crystallization ages define three major magmatic episodes of crustal reworking in the Archaean (Lewisian), Mesoproterozoic (Grenville), and Ordovician (Grampian). These data, together with oxygen isotope data and Hf model ages, suggest that crustal growth, recorded in the strata of the South Mayo Trough, started at
c
. 4 Ga and continued until 1.4 Ga, with two major growth periods at 2.3–2.1 and 2.0–1.5 Ga. We find that the crustal incubation time is decoupled from the duration of supracrustal alteration processes; some zircons with very long crustal incubation times have pristine mantle δ
18
O signatures suggesting minimal low-temperature surface processing in their source regions. Identifying such zircons is the key for future studies in constructing realistic net continental crustal growth models unaffected by crustal recycling.

Supplementary materials:

Data tables for U–Pb, Lu–Hf and oxygen isotopes for detrital zircons from South Mayo Trough, as well as plots of values for zircon standards (δ
18
O for R33, U–Pb ages for 91500 and R33, and
176
Hf/
177
Hf for 91500, GJ-1, and Plešovice) and reverse concordia plots of zircon samples are available at
www.geolsoc.org.uk/SUP18543
.
Faulting in Banks Peninsula: tectonic setting and structural controls for late Miocene intraplate volcanism, New Zealand
Authors: Ring Uwe , Hampton Sam
Published: November 2012

An analysis of faulting in the late Miocene volcanic rocks of Banks Peninsula, South Island, New Zealand, shows that the formation of the volcanic edifice was largely controlled by NE–SW-striking dextral-oblique strike-slip faults. The data show a variable component of west–east- or NW–SE-oriented shortening and north–south or NE–SW extension. Synvolcanic faults reactivated Cretaceous normal faults and are interpreted to have formed a local pull-apart basin that controlled volcanism. Further east, the geometry of Akaroa Harbour is controlled by a north–south-striking oblique reverse fault. Limited fault-slip data collected from sub-recent loess deposits are not significantly different from the data collected in the volcanic rocks and appear to show that the kinematic field did not change significantly over the last
c
. 10 Ma. The overall kinematic field causing the recent series of earthquakes in the greater Christchurch region is also not fundamentally different from the one that controlled the eruption of the volcanic rocks. We conclude that the inherited Cretaceous faults controlled the development of the late Miocene volcanism on Banks Peninsula and largely provided a major anisotropy along which the recent faults ruptured.
Mapping crustal thickness and oceanic lithosphere distribution in the Eastern Mediterranean using gravity inversion
Authors: Cowie Leanne , Kusznir Nick
Published: November 2012

Oceanic and continental lithosphere distribution within the eastern Mediterranean is not well understood. A gravity inversion, incorporating a lithosphere thermal gravity anomaly correction, has been used to map Moho depth, crustal thickness and lithosphere thinning for the eastern Mediterranean, from which the distribution of oceanic and continental lithosphere, the structure of the ocean–continent transition (OCT) and the location of the continent–ocean boundary (COB) can be determined. The gravity inversion results show thin crust and high continental lithosphere thinning under the Ionian Sea and the Herodotus Basin, consistent with these basins being underlain by oceanic crust. Moho depths from gravity inversion are in agreement with seismic refraction estimates in these basins. Highly thinned continental crust is predicted under the offshore Sirte and Levant basins. The sharp decrease in crustal thickness predicted by gravity inversion off the Libyan and Egyptian coast gives an indication of COB location. Crustal thickness and continental lithosphere thinning determined from gravity inversion have also been used to explore the relationship between the Cretaceous West and Central African Rift System (WCARS: Benue Trough, Chad, Central African Shear Zone (CASZ) and Sudan basins) and the eastern Mediterranean basins; continuity between the Cretaceous WCARS and the eastern Mediterranean basins is not apparent in the gravity inversion results.
The development of the Nile drainage system: integration of onshore and offshore evidence
Authors: Macgregor Duncan S.
Published: November 2012

This paper reconstructs drainage systems with outlets close to the present-day Nile system, honouring both onshore and offshore evidence and attempts a source to sink quantification. A large river is evidenced to have extended the length of the Red Sea Hills from Eritrea to the current outlet since the Oligocene. The early route of the river is uncertain through Sudan but a more westerly course is proposed through Egypt. The largest contributor of clastic sediment was the Red Sea Hills, where average erosion of the order of 1200–1500 m is constrained by a combination of Apatite Fission Track Analysis, planation surface analysis, and Red Sea sink volumes. Nubia was a significant supplier of sand-rich sediment during wet periods. This sediment supply pattern contrasts with the present-day situation where the Ethiopian Highlands contribute the vast majority of sediments, this contrast being validated by available mineralogical data. This is a consequence of wetter climates in the past and of the younger Ethiopian topography. The interpretations presented here illustrate the importance of hinterland climate change on clastic supply and allow the reservoir fairways in the Nile Cone to be more precisely mapped out in time and space.
Heme modulates intestinal epithelial cell activation: involvement of NADPHox-derived ROS signaling
Authors: Barcellos-de-Souza Pedro , Moraes João Alfredo , de-Freitas-Junior Julio Cesar Madureira , Morgado-Díaz José Andrés , Barja-Fidalgo Christina , Arruda Maria Augusta
Published: November 2012

In many gut chronic inflammatory conditions, intestinal epithelium (IE) is deprived of the protection of the mucus secreted by IE-specialized cells. In these events, bleeding and subsequent lysis of erythrocytes are common. This may lead to the release of high amounts of heme in the intestinal lumen, which interacts with IE. Previous works from our group have shown that heme itself is a proinflammatory molecule, activating a number of phlogistic signaling events in a nicotinamide adenine dinucleotide phosphate oxidase (NADPHox)-dependent manner. In this study, we aim to evaluate the effects of heme upon a well-established nontransformed small intestine epithelial cell lineage (IEC 6). Our results show that free heme evokes intracellular reactive oxygen species (ROS) production by IEC 6 cells, which is inhibited both by pharmacological inhibition with diphenyleneiodonium (10 μM), a NADPHox inhibitor, and small interfering RNA-mediated suppression of NOX1, a constitutive NADPHox isoform present in intestinal epithelial cells. Focal adhesion kinase phosphorylation and actin cytoskeleton polymerization are also induced by heme in a NADPHox-dependent manner. Heme increases monolayer permeability and redistributes key modulators of cell-cell adhesion as zona occludens-1 and E-cadherin proteins via NADPHox signaling. Heme promotes IEC 6 cell migration and proliferation, phenomena also regulated by NADPHox-derived ROS. Heme, in NADPHox-activating concentrations, is able to induce mRNA expression of IL-6, a cytokine implicated in inflammatory and tumorigenic responses. These data indicate a prominent role for heme-derived signaling in the pathophysiology of intestinal mucosa dysfunction and address an important role of NADPHox activity on the pathogenesis of intestinal inflammatory conditions.
Hemodynamic shear stress characteristic of atherosclerosis-resistant regions promotes glycocalyx formation in cultured endothelial cells
Authors: Koo Andrew , Dewey C. Forbes , García-Cardeña Guillermo
Published: November 2012

The endothelial glycocalyx, a glycosaminoglycan layer located on the apical surface of vascular endothelial cells, has been shown to be important for several endothelial functions. Previous studies have documented that the glycocalyx is highly abundant in the mouse common carotid region, where the endothelium is exposed to laminar shear stress, and it is resistant to atherosclerosis. In contrast, the glycocalyx is scarce or absent in the mouse internal carotid sinus region, an area exposed to nonlaminar shear stress and highly susceptible to atherosclerosis. On the basis of these observations, we hypothesized that the expression of components of the endothelial glycocalyx is differentially regulated by distinct hemodynamic environments. To test this hypothesis, human endothelial cells were exposed to shear stress waveforms characteristic of atherosclerosis-resistant or atherosclerosis-susceptible regions of the human carotid, and the expression of several components of the glycocalyx was assessed. These experiments revealed that expression of several components of the endothelial glycocalyx is differentially regulated by distinct shear stress waveforms. Interestingly, we found that heparan sulfate expression is increased and evenly distributed on the apical surface of endothelial cells exposed to the atheroprotective waveform and is irregularly present in cells exposed to the atheroprone waveform. Furthermore, expression of a heparan sulfate proteoglycan, syndecan-1, is also differentially regulated by the two waveforms, and its suppression mutes the atheroprotective flow-induced cell surface expression of heparan sulfate. Collectively, these data link distinct hemodynamic environments to the differential expression of critical components of the endothelial glycocalyx.
Effects of ACE inhibition and ANG II stimulation on renal Na-Cl cotransporter distribution, phosphorylation, and membrane complex properties
Authors: Lee Donna H. , Maunsbach Arvid B. , Riquier-Brison Anne D. , Nguyen Mien T. X. , Fenton Robert A. , Bachmann Sebastian , Yu Alan S. , McDonough Alicia A.
Published: November 2012

The renal distal tubule Na-Cl cotransporter (NCC) reabsorbs <10% of the filtered Na+ but is a key control point for blood pressure regulation by angiotensin II (ANG II), angiotensin-converting enzyme inhibitors (ACEI), and thiazide diuretics. This study aimed to determine whether NCC phosphorylation (NCCp) was regulated by acute (20–30 min) treatment with the ACEI captopril (12 μg/min × 20 min) or by a sub-pressor dose of ANG II (20 ng·kg−1·min−1) in Inactin-anesthetized rats. By immuno-EM, NCCp was detected exclusively in or adjacent to apical plama membranes (APM) in controls and after ACEI or ANG II treatment, while NCC total was detected in both APM and subapical cytoplasmic vesicles (SCV) in all conditions. In renal homogenates, neither ACEI nor ANG II treatment altered NCCp abundance, assayed by immunoblot. However, by density gradient fractionation we identified a pool of low-density APM in which NCCp decreased 50% in response to captopril and was restored during ANG II infusion, and another pool of higher-density APM that responded reciprocally, indicative of regulated redistribution between two APM pools. In both pools, NCCp was preferentially localized to Triton-soluble membranes. Blue Native gel electrophoresis established that APM NCCp localized to ∼700 kDa complexes (containing γ-adducin) while unphosphorylated NCC in intracellular membranes primarily localized to ∼400 kDa complexes: there was no evidence for native monomeric or dimeric NCC or NCCp. In summary, this study demonstrates that phosphorylated NCC, localized to multimeric complexes in the APM, redistributes in a regulated manner within the APM in response to ACEI and ANG II.
CXCL17, an orphan chemokine, acts as a novel angiogenic and anti-inflammatory factor
Authors: Lee Wei-Yu , Wang Chun-Jen , Lin Ting-Yu , Hsiao Chih-Lun , Luo Ching-Wei
Published: November 2012

Chemokines play pivotal roles in the recruitment of various immune cells to diverse tissues in both physiological and pathological conditions. CXCL17 is an orphan chemokine preliminarily found to be involved in tumor angiogenesis. However, its protein nature, as well as its endogenous bioactivity, has not been well clarified. Using real-time PCR, immunohistochemical staining, and Western blotting, we found that CXCL17 is highly expressed in both a constitutive and inducible manner in the rat gastric mucosa, where it undergoes endoproteolysis during protein maturation. The mature CXCL17 exhibited strong chemoattractant abilities targeting monocytes and macrophages, potentially through ERK1/2 and p38 but not JNK signaling. CXCL17 also induced the production of proangiogenic factors such as vascular endothelial growth factor A from treated monocytes. Furthermore, in contrast to other CXC chemokines that accelerate inflammatory responses, CXCL17 showed novel anti-inflammatory effects on LPS-activated macrophages. Therefore, our data suggest that CXCL17 in the gastric lamina propria may play an important role in tissue repair and anti-inflammation, both of which help to maintain the integrity of the gastric mucosa.
Glucocorticoid mediates water avoidance stress-sensitized colon-bladder cross-talk via RSK2/PSD-95/NR2B in rats
Authors: Peng Hsien-Yu , Hsieh Ming-Chun , Lai Cheng-Yuan , Chen Gin-Den , Huang Yi-Ping , Lin Tzer-Bin
Published: November 2012

Unexpected environmental and social stimuli could trigger stress. Although coping with stress is essential for survival, long-term stress impacts visceral functions, and therefore, it plays a role in the development and exacerbation of symptoms of gastrointestinal/urogenital disorders. The aim of this study is to characterize the role of corticosterone in stress-sensitized colon-bladder cross-talk, a phenomenon presumed to underlie the comorbidity of functional bowel and bladder disorders. Cystometry and protein/mRNA expression in the lumbosacral dorsal horn (L6-S1) in response to intracolonic mustard oil (MO) instillation were analyzed in female Wistar-Kyoto rats subjected to water avoidance stress (WAS; 1 h/day for 10 days) or sham stress (WAsham). Whereas it had no effect on baseline-voiding function, chronic stress upregulated plasma corticosterone concentration and dorsal horn spinal p90 ribosomal S6 kinase 2 (RSK2) protein/mRNA levels, and RSK2 immunoreactivity colocalized with NeuN-positive neurons. Intracolonic MO dose-dependently decreased intrercontraction intervals and threshold pressure, provoked spinal RSK2 and NR2B phosphorylation, and enhanced PSD-95-RSK2 and PSD-95-NR2B coupling. Intrathecal kaempferol (a RSK2 activation antagonist; 30 min before MO instillation), bilateral adrenalectomy (7 days prior the stress paradigm), and subcutaneous RU-38486 (a glucocorticoid receptor antagonist; 30 min daily before stress sessions), but not RU-28318 (a mineralocorticoid receptor antagonist), attenuated MO-induced bladder hyperactivity, protein phosphorylation, and protein-protein interactions in the WAS group. Our results suggest that stress-associated glucocorticoid release mediates WAS-dependent sensitization of colon-bladder cross-talk via the spinal RSK2/PSD-95/NR2B cascade and offer a possibility for developing pharmacological strategies for the treatment of stress-related pelvic pain.
Decreased luteinizing hormone pulse frequency is associated with elevated 24-hour ghrelin after calorie restriction and exercise in premenopausal women
Authors: Scheid Jennifer L. , De Souza Mary Jane , Hill Brenna R. , Leidy Heather J. , Williams Nancy I.
Published: November 2012

Elevated ghrelin has been shown to be associated with reduced luteinizing hormone (LH) pulsatility in Rhesus monkeys, rats, men, and recently women. We previously reported that 24-h ghrelin concentrations are elevated in women following a 3-mo exercise and diet program leading to weight loss. We investigated whether the elevations in ghrelin following an ∼3-mo exercise and diet program leading to weight loss are associated with a decrease in LH pulsatility. The nonexercising control group (Control, n = 5) consumed a controlled diet that matched energy needs, whereas energy intake in the exercise group (Energy Deficit, n = 16) was reduced from baseline energy requirements and supervised exercise training occurred five times per a week. Significant decreases in body weight (−3.0 ± 0.6 kg), body fat (−2.9 ± 0.4 kg) and 24-h LH pulse frequency (−0.18 ± 0.08 pulses/h), and a significant increase in 24-h mean ghrelin were observed in only the Energy Deficit group. The pre-post change in LH pulse frequency was negatively correlated with the change in mean 24-h ghrelin ( R = −0.485, P = 0.030) and the change in peak ghrelin at lunch ( R = −0.518, P = 0.019). Interestingly, pre-post change in night LH pulse frequency was negatively correlated with the change in mean day ghrelin ( R = −0.704, P = 0.001). Elevated total ghrelin concentrations are associated with the suppression of LH pulsatility in premenopausal women and may play a role in the suppression of reproductive function following weight loss.
Muscle protein synthesis, mTORC1/MAPK/Hippo signaling, and capillary density are altered by blocking of myostatin and activins
Authors: Hulmi Juha J. , Oliveira Bernardo M. , Silvennoinen Mika , Hoogaars Willem M. H. , Ma Hongqiang , Pierre Philippe , Pasternack Arja , Kainulainen Heikki , Ritvos Olli
Published: November 2012

Loss of muscle mass and function occurs in various diseases. Myostatin blocking can attenuate muscle loss, but downstream signaling is not well known. Therefore, to elucidate associated signaling pathways, we used the soluble activin receptor IIb (sActRIIB-Fc) to block myostatin and activins in mice. Within 2 wk, the treatment rapidly increased muscle size as expected but decreased capillary density per area. sActRIIB-Fc increased muscle protein synthesis 1–2 days after the treatment correlating with enhanced mTORC1 signaling (phosphorylated rpS6 and S6K1, r = 0.8). Concurrently, increased REDD1 and eIF2Bε protein contents and phosphorylation of 4E-BP1 and AMPK was observed. In contrast, proangiogenic MAPK signaling and VEGF-A protein decreased. Hippo signaling has been characterized recently as a regulator of organ size and an important regulator of myogenesis in vitro. The phosphorylation of YAP (Yes-associated protein), a readout of activated Hippo signaling, increased after short- and longer-term myostatin and activin blocking and in exercised muscle. Moreover, dystrophic mdx mice had elevated phosphorylated and especially total YAP protein content. These results show that the blocking of myostatin and activins induce rapid skeletal muscle growth. This is associated with increased protein synthesis and mTORC1 signaling but decreased capillary density and proangiogenic signaling. It is also shown for the first time that Hippo signaling is activated in skeletal muscle after myostatin blocking and exercise and also in dystrophic muscle. This suggests that Hippo signaling may have a role in skeletal muscle in various circumstances.
Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene
Authors: Blevins James E. , Moralejo Daniel H. , Wolden-Hanson Tami H. , Thatcher Brendan S. , Ho Jacqueline M. , Kaiyala Karl J. , Matsumoto Kozo
Published: November 2012

CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a Fischer 344 background (Cck1r−/−) are lean and normophagic. In this study, the metabolic phenotype of this rat strain was further characterized. As expected, the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r−/− rats. Both Cck1r+/+ and Cck1r−/− rats became diet-induced obese (DIO) when maintained on a high-fat diet relative to chow-fed controls. Cck1r−/− rats consumed larger meals than controls during the dark cycle and smaller meals during the light cycle. These effects were accompanied by increased food intake, total spontaneous activity, and energy expenditure during the dark cycle and an apparent reduction in respiratory quotient during the light cycle. To assess whether enhanced responsiveness to anorexigenic factors may contribute to the lean phenotype, we examined the effects of melanotan II (MTII) on food intake and body weight. We found an enhanced effect of MTII in Cck1r−/− rats to suppress food intake and body weight following both central and peripheral administration. These results suggest that the lean phenotype is potentially driven by increases in total spontaneous activity and energy expenditure.
Neurotrophins regulate cholinergic synaptic transmission in cultured rat sympathetic neurons through a p75-dependent mechanism
Authors: Luther J. A. , Enes J. , Birren S. J.
Published: November 2012

The sympathetic nervous system regulates many essential physiological systems, and its dysfunction is implicated in cardiovascular diseases. Mechanisms that control the strength of sympathetic output are therefore potential targets for the management of these disorders. Here we show that neurotrophins rapidly potentiate cholinergic transmission between cultured rat sympathetic neurons. We found that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), acting at the p75 receptor, increased the amplitude of excitatory postsynaptic currents (EPSCs). We observed increased amplitude but not frequency of miniature synaptic currents after p75 activation, suggesting that p75 acts postsynaptically to modulate transmission at these synapses. This neurotrophic modulation enhances cholinergic EPSCs via sphingolipid signaling. Application of sphingolactone-24, an inhibitor of neutral sphingomyelinase, blocked the effect of BDNF, implicating a sphingolipid pathway. Furthermore, application of the p75-associated sphingolipid second messengers C2-ceramide and d- erythro-sphingosine restricted to the postsynaptic cell mimicked BDNF application. Postsynaptic blockade of ceramide production with fumonisin, a ceramide synthase inhibitor, blocked the effects of BDNF and d- erythro-sphingosine, implicating ceramide or ceramide phosphate as the active signal. Together these data suggest that neurotrophin signaling, which occurs in vivo via release from sympathetic neurons and target tissues such as the heart, acutely regulates the strength of the sympathetic postganglionic response to central cholinergic inputs. This pathway provides a potential mechanism for modulating the strength of sympathetic drive to target organs such as the heart and could play a role in the development of cardiovascular diseases.
Updating of the spatial reference frame of head direction cells in response to locomotion in the vertical plane
Authors: Taube Jeffrey S. , Wang Sarah S. , Kim Stanley Y. , Frohardt Russell J.
Published: November 2012

Many species navigate in three dimensions and are required to maintain accurate orientation while moving in an Earth vertical plane. Here we explored how head direction (HD) cells in the rat anterodorsal thalamus responded when rats locomoted along a 360° spiral track that was positioned vertically within the room at the N, S, E, or W location. Animals were introduced into the vertical plane either through passive placement ( experiment 1) or by allowing them to run up a 45° ramp from the floor to the vertically positioned platform ( experiment 2). In both experiments HD cells maintained direction-specific firing in the vertical plane with firing properties that were indistinguishable from those recorded in the horizontal plane. Interestingly, however, the cells' preferred directions were linked to different aspects of the animal's environment and depended on how the animal transitioned into the vertical plane. When animals were passively placed onto the vertical surface, the cells switched from using the room (global cues) as a reference frame to using the vertically positioned platform (local cues) as a reference frame, independent of where the platform was located. In contrast, when animals self-locomoted into the vertical plane, the cells' preferred directions remained anchored to the three-dimensional room coordinates and their activity could be accounted for by a simple 90° rotation of the floor's horizontal coordinate system to the vertical plane. These findings highlight the important role that active movement signals play for maintaining and updating spatial orientation when moving in three dimensions.
The response of NaV1.3 sodium channels to ramp stimuli: multiple components and mechanisms
Authors: Estacion Mark , Waxman Stephen G.
Published: November 2012

NaV1.3 voltage-gated sodium channels have been shown to be expressed at increased levels within axotomized dorsal root ganglion neurons and within injured axons within neuromas and have been implicated in neuropathic pain. Like a number of other sodium channel isoforms, NaV1.3 channels produce a robust response to slow ramplike stimuli. Here we show that the response of NaV1.3 to ramp stimuli consists of two components: an early component, dependent upon ramp rate, that corresponds to a window current that is dependent upon closed-state inactivation; and a second component at more depolarized potentials that is correlated with persistent current which is detected for many tens of milliseconds after the start of a depolarizing pulse. We also assessed the K354Q NaV1.3 epilepsy-associated mutant channel, which is known to display an enhanced persistent current and demonstrate a strong correlation with the second component of the ramp response. Our results show that a single sodium channel isoform can produce a ramp response with multiple components, reflecting multiple mechanisms, and suggest that the upregulated expression of NaV1.3 in axotomized dorsal root ganglion neurons and enhanced ramp current in K354Q mutant channels can contribute in several ways to hyperexcitability and abnormal spontaneous firing that contribute to hyperexcitability disorders, such as epilepsy and neuropathic pain.
Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations
Authors: Hawking Thomas G. , Gerdjikov Todor V.
Published: November 2012

Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45–90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.
Biophysical determinants of transcranial magnetic stimulation: effects of excitability and depth of targeted area
Authors: Stokes Mark G. , Barker Anthony T. , Dervinis Martynas , Verbruggen Frederick , Maizey Leah , Adams Rachel C. , Chambers Christopher D.
Published: November 2012

Safe and effective transcranial magnetic stimulation (TMS) requires accurate intensity calibration. Output is typically calibrated to individual motor cortex excitability and applied to nonmotor brain areas, assuming that it captures a site nonspecific factor of excitability. We tested this assumption by correlating the effect of TMS at motor and visual cortex. In 30 participants, we measured motor threshold (MT) and phosphene threshold (PT) at the scalp surface and at coil-scalp distances of 3.17, 5.63, and 9.03 mm. We also modeled the effect of TMS in a simple head model to test the effect of distance. Four independent tests confirmed a significant correlation between PT and MT. We also found similar effects of distance in motor and visual areas, which did not correlate across participants. Computational modeling suggests that the relationship between the effect of distance and the induced electric field is effectively linear within the range of distances that have been explored empirically. We conclude that MT-guided calibration is valid for nonmotor brain areas if coil-cortex distance is taken into account. For standard figure-of-eight TMS coils connected to biphasic stimulators, the effect of cortical distance should be adjusted using a general correction factor of 2.7% stimulator output per millimeter.
Recording EEG in immature rats with a novel miniature telemetry system
Authors: Zayachkivsky A. , Lehmkuhle M. J. , Fisher J. H. , Ekstrand J. J. , Dudek F. E.
Published: November 2012

Serial EEG recordings from immature rat pups are extremely difficult to obtain but important for analyzing animal models of neonatal seizures and other pediatric neurological conditions as well as normal physiology. In this report, we describe the features and applications of a novel miniature telemetry system designed to record EEG in rat pups as young as postnatal day 6 (P6). First, we have recorded electrographic seizure activity in two animal models of neonatal seizures, hypoxia- and kainate-induced seizures at P7. Second, we describe a viable approach for long-term continuous EEG monitoring of naturally reared rat pups implanted with EEG at P6. Third, we have used serial EEG recordings to record age-dependent changes in the background EEG signal as the animals matured from P7 to P11. The important advantages of using miniature wireless EEG technology are: 1) minimally invasive surgical implantation; 2) a device form-factor that is compatible with housing of rat pups with the dam and littermates; 3) serial recordings of EEG activity; and 4) low power consumption of the unit, theoretically allowing continuous monitoring for up to 2 yr without surgical reimplantation. The miniature EEG telemetry system provides a technical advance that allows researchers to record continuous and serial EEG recordings in neonatal rodent models of human neurological disorders, study the progression of the disease, and then assess possible therapies using quantitative EEG as an outcome measure. This new technical approach should improve animal models of human conditions that rely on EEG monitoring for diagnosis and therapy.
Firing rate and pattern heterogeneity in the globus pallidus arise from a single neuronal population
Authors: Deister Christopher A. , Dodla Ramana , Barraza David , Kita Hitoshi , Wilson Charles J.
Published: November 2012

Intrinsic heterogeneity in networks of interconnected cells has profound effects on synchrony and spike-time reliability of network responses. Projection neurons of the globus pallidus (GPe) are interconnected by GABAergic inhibitory synapses and in vivo fire continuously but display significant rate and firing pattern heterogeneity. Despite being deprived of most of their synaptic inputs, GPe neurons in slices also fire continuously and vary greatly in their firing rate (1–70 spikes/s) and in regularity of their firing. We asked if this rate and pattern heterogeneity arises from separate cell types differing in rate, local synaptic interconnections, or variability of intrinsic properties. We recorded the resting discharge of GPe neurons using extracellular methods both in vivo and in vitro. Spike-to-spike variability (jitter) was measured as the standard deviation of interspike intervals. Firing rate and jitter covaried continuously, with slow firing being associated with higher variability than faster firing, as would be expected from heterogeneity arising from a single physiologically distinct cell type. The relationship between rate and jitter was unaffected by blockade of GABA and glutamate receptors. When the firing rate of individual neurons was altered with constant current, jitter changed to maintain the rate-jitter relationship seen across neurons. Long duration (30–60 min) recordings showed slow and spontaneous bidirectional drift in rate similar to the across-cell heterogeneity. Paired recordings in vivo and in vitro showed that individual cells wandered in rate independently of each other. Input conductance and rate wandered together, in a manner suggestive that both were due to fluctuations of an inward current.