bluuebunny/crossref_metadata_2025 huggingface dataset:
Separate episodes of eclogite and blueschist facies metamorphism in the Aegean metamorphic core complex of Ios, Cyclades, Greece
Authors: Forster M. A. , Lister G. S.
Published: September 2007

Blueschists and eclogites outcrop together throughout the Cyclades, Aegean Sea, Greece. Their coexistence has been explained by compositional variation between different lithologies and a single metamorphic episode under transitional eclogite—blueschist facies conditions has been proposed. However, a detailed study of the fabrics and microstructures in an exceptionally well-preserved eclogite boudin reveals a distinct sequence of several different mineral growth events, all under conditions of high-pressure metamorphism. The earliest metamorphic mineral paragenesis recognized is a blueschist facies, glaucophane-bearing assemblage. Eclogite facies metamorphism followed, which is suggested here as being pervasive throughout the rock mass. This period of metamorphic mineral growth was overprinted by widespread blueschist facies retrogression, with hydration ± metasomatism of earlier formed (eclogite facies) assemblages. These hydration reactions were responsible for a period of porphyroblastic mineral growth in the blueschist facies (prior toc.40 Ma) which largely obliterated the earlier formed eclogite facies assemblages. Omphacite + garnet assemblages relict from the eclogite facies event are preserved only within the cores of the mafic boudins because fluid was not able to penetrate them. Evidence for the early blueschist assemblage is now preserved only as inclusions within the eclogitic garnets in the core of the boudin. This pattern of metamorphic mineral growth may have significant tectonic implications, as it is consistent with the pattern of metamorphic evolution across the high-pressure metamorphic belt of the Aegean region.
The Northern Sacramento Mountains, southwest United States. Part II: Exhumation history and detachment faulting
Authors: Pease V. , Foster D. , Wooden J. , O’Sullivan P. , Argent J. , Fanning C.
Published: September 2007

Thermochronologic and thermobarometric data reveal the timing, distribution and intensity of thermal events associated with detachment faulting in the Sacramento Mountains metamorphic core complex. In the northwest Sacramento Mountains, cooling rates ofc.100°C Ma−1are associated with Late Cretaceous plutonism followed by cooling of the crust by thermal conduction. Post-Late Cretaceous cooling slowed toc.1–6°C Ma−1. Finally, the region records average cooling rates of 38–53°C Ma−1betweenc.20 and 15 Ma. In contrast, the thermal profile of the northeast Sacramento Mountains is dominated by syntectonic Tertiary plutonism followed by very rapid cooling. A granodioritic suite intruded atc.680°C andc.3 kbar atc.20 Ma, records cooling to <100°C byc.15 Ma. Such rapid cooling and exhumation suggests that unroofing by tectonic denudation was the driving mechanism for the final cooling. The similarity of the miocene cooling profiles between these two areas clearly suggests that the Sacramento Mountains experienced a regional cooling event associated with tectonic unroofing driven by regional Miocene crustal extension. Estimates of the initial angle of the Sacramento Mountains detachment fault using palaeothermal gradients suggest that it was active at a dip of 25°.
Evolution and development of the Levant (Dead Sea Rift) Transform System: A historical-chronological review of a structural controversy
Authors: Beydoun Z. R.
Published: September 2007

The Levant Fracture System is a transform plate boundary that connects the extensional Red Sea spreading centre, in the south, with the collisional Tauride region, in the north, across the Levant. The debate regarding its origin, evolution and development is reviewed, with proposed models ranging from a primordial geosuture, along which only vertical movements have occurred, to a Neogene transform, along which the Arabian Plate has moved 107 km left-laterally northwards in two stages, 62 km in the Miocene and 45 km in the Pliocene-Recent. Overwhelming field evidence supports this degree of motion south of Lebanon but in Lebanon, where the system branches into a braided fault system generally trending north-northeast, evidence for such motion is lacking. Proponents of the transform model have explained away this lack of evidence by invoking division of the total horizontal motion to the south amongst the main fault strands across Lebanon and ascribing the uplift/ depression of the Lebano-Palmyride structural units to transpressional-transtensional deformation by this horizontal motion. The inversion of the Lebano-Palmyride belts had, in fact, been largely achieved by the Late Oligocene as a consequence of oblique collision between the Eurasian-Arabian Plates during closure of the Neo-Tethys. The Neogene initiation of the Levant Fracture System, resulting from the opening of the Gulf of Aden-Red Sea, could only, therefore, have modified existing structures, not been responsible for them. Pliocene bypassing of the principal Lebanese Yammouneh Fault requires that active motion in the south be transmitted through other faults. The currently active north-south Roum Fault has been proposed as the principal candidate and its trace northwards appears identifiable on satellite images. Field checks suggest it has broken into short left-stepping segments and it probably cuts the coast obliquely just south of Beirut. Current research to establish the geometry and magnitude of horizontal motion on this fault is discussed.
The lithospheric structure of the Kenya Rift as revealed by wide-angle seismic measurements
Authors: Khan M. A. , Mechie J. , Birt C. , Byrne G. , Gaciri S. , Jacob B. , Keller G. R. , Maguire P. K. H. , Novak O. , Nyambok I. O. , Patel J. P. , Prodehl C. , Riaroh D. , Simiyu S. , Thybo H.
Published: September 2007

The Kenya Rift International Seismic Project (KRISP) seismic refraction-wideangle reflection experiments carried out between 1985 and 1994 show abrupt changes in Moho depths and P
n
phase velocities as the rift boundaries are crossed. Beneath the rift flanks, normal P
n
phase velocities of 8.0–8.3 km s
−1
are observed, except for the Chyulu Hills volcanic field, east of the rift, where it is 7.9–8.0 km s
−1
. Also to the east, some of the thickest crust (38–44km) encountered so far beneath Kenya has been observed over a distance of
c.
300km. However, beneath the surface expression of the rift itself, the uppermost mantle velocity of the P
n
phase is anomalously low at 7.5-7.8 km s
−1
throughout its length.

Beneath the rift itself, there are major differences in crustal thickness, extension and upper mantle velocity structure between the north and the south. Beneath the section from the centre of the Kenya Dome southwards, where the extension is estimated to be 5–10km, the crust is thinned by
c.
10 km to a thickness of 35 km, and the narrow low-velocity zone in the mantle extends to a depth of at least 65 km. However, in the north beneath Turkana, where the extension is 35–40km, the crust is only
c.
20km thick and two layers with velocities of 8.1 and 8.3 km s
−1
are embedded in the low velocity mantle material at depths of 40–45 km and 60–65 km. This mantle velocity structure indicates that the depth to the onset of melting is at least 65 km beneath the northern part of the rift and is thus not shallower than the corresponding depth (45–50 km) in the south. These results, taken together with those from teleseismic studies, petrology and surface geology, have been used to deduce that anomalously hot mantle material appeared below the present site of the Kenya Rift
c.
20–30 Ma ago. This led to widespread volcanism along the whole length of the rift and modification of the underlying crust by mafic igneous underplating and intrusion.
Role of protein kinase C-δ in the age-dependent secretagogue action of bile acids in mammalian colon
Authors: Kanchanapoo Jainuch , Ao Mei , Prasad Roli , Moore Christopher , Kay Cynthia , Piyachaturawat Pawinee , Rao Mrinalini C.
Published: September 2007

The role of specific PKC isoforms in the regulation of epithelial Cl− secretion by Ca2+-dependent secretagogues remains controversial. In the developing rabbit distal colon, the bile acid taurodeoxycholate (TDC) acts via intracellular calcium to stimulate Cl− transport in adult, but not in young, animals, whereas the PKC activator phorbol dibutyrate (PDB) stimulates Cl− transport at all ages. We tested the hypothesis that specific PKC isoforms account for the age-specific effects of TDC. The effects of conventional (cPKC) and novel (nPKC) PKC-specific inhibitors on TDC- and PDB-stimulated Cl− transport in adult and weanling colonocytes were assessed by using 6-methoxy-quinolyl acetoethyl ester. In adult colonocytes, the cPKC inhibitor Gö-6976 inhibited PDB action but not TDC action, whereas the cPKC and nPKC inhibitor Gö-6850 blocked both TDC and PDB actions. Additionally, rottlerin and the PKC-δ-specific inhibitor peptide (δV1-1) inhibited TDC- and PDB-stimulated Cl− transport in adult colonocytes. Rottlerin also decreased TDC-stimulated short-circuit current in intact colonic epithelia. Only Gö-6976, but neither rottlerin nor δV1-1, inhibited PDB-stimulated transport in weanling colonocytes. Colonic lysates express PKC-α, -λ, and -ι protein equally at all ages, but they do not express PKC-γ or -θ at any age. Expression of PKC-β and PKC-ε protein was newborn>adult>weanling, whereas PKC-δ was expressed in adult but not in weanling or newborn colonocytes. TDC (1.6-fold) and PDB (2.0-fold) stimulated PKC-δ enzymatic activity in adult colonocytes but failed to do so in weanling colonocytes. PKC-δ mRNA expression showed age dependence. Thus PKC-δ appears critical for the action of TDC in the adult colon, and its low expression in young animals may account for their inability to secrete in response to bile acids.
Intracellular calcium regulation of connexin43
Authors: Lurtz Monica M. , Louis Charles F.
Published: September 2007

The mechanism by which intracellular Ca2+ concentration ([Ca2+]i) regulates the permeability of gap junctions composed of connexin43 (Cx43) was investigated in HeLa cells stably transfected with this connexin. Extracellular addition of Ca2+ in the presence of the Ca2+ ionophore ionomycin produced a sustained elevation in [Ca2+]i that resulted in an inhibition of the cell-to-cell transfer of the fluorescent dye Alexa fluor 594 (IC50 of 360 nM Ca2+). The Ca2+ dependency of this inhibition of Cx43 gap junctional permeability is very similar to that described in sheep lens epithelial cell cultures that express the three sheep lens connexins (Cx43, Cx44, and Cx49). The intracellular Ca2+-mediated decrease in cell-to-cell dye transfer was prevented by an inhibitor of calmodulin action but not by inhibitors of Ca2+/calmodulin-dependent protein kinase II or protein kinase C. In experiments that used HeLa cells transfected with a Cx43 COOH-terminus truncation mutant (Cx43Δ257), cell-to-cell coupling was similarly decreased by an elevation of [Ca2+]i (IC50 of 310 nM Ca2+) and similarly prevented by the addition of an inhibitor of calmodulin. These data indicate that physiological concentrations of [Ca2+]i regulate the permeability of Cx43 in a calmodulin-dependent manner that does not require the major portion of the COOH terminus of Cx43.
Endothelin stimulates vascular hydroxyl radical formation: effect of obesity
Authors: Mundy Alexa L. , Haas Elvira , Bhattacharya Indranil , Widmer Corinne C. , Kretz Martin , Baumann Karin , Barton Matthias
Published: September 2007

Reactive oxygen species (ROS) and endothelin-1 (ET-1) contribute to vascular pathophysiology in obesity. In this context, whether ET-1 modulates hydroxyl radical (•OH) formation and the function of ROS/•OH in obesity is not known. In the present study, formation and function of ROS, including •OH, were investigated in the aorta of lean and leptin-deficient obese ob/ob mice. Hydroxyl radical formation was detected ex vivo using terephthalic acid in intact aortic rings and the involvement of ROS in ET-1-mediated vasoreactivity was analyzed using the antioxidant EPC-K1, a combination of α-tocopherol and ascorbic acid. Generation of either •OH, •O2−, and H2O2was strongly inhibited by EPC-K1 (all P < 0.05). In obese mice, basal vascular •OH formation and ROS activity were reduced by 3-fold and 5-fold, respectively ( P < 0.05 vs. lean). ET-1 markedly enhanced •OH formation in lean (6-fold, P < 0.05 vs. untreated) but not in obese mice. Obesity increased ET-1-induced contractions ( P < 0.05 vs. lean), and ROS scavenging further enhanced the response ( P < 0.05 vs. untreated). Exogenous ROS, including •OH caused stronger vasodilation in obese animals ( P < 0.05 vs. lean), whereas endothelium-dependent relaxation was similar between lean and obese animals. In conclusion, we present a sensitive method allowing ex vivo measurement of vascular •OH generation and provide evidence that ET-1 regulates vascular •OH formation. The data indicate that in obesity, vascular formation of ROS, including •OH is lower, whereas the sensitivity to ROS is increased, suggesting a novel and important role of ROS, including •OH in the regulation of vascular tone in disease status associated with increased body weight.
Adenosine enhances long term the contractile response to angiotensin II in afferent arterioles
Authors: Patzak Andreas , Lai En Yin , Fähling Michael , Sendeski Mauricio , Martinka Peter , Persson Pontus B. , Persson A. Erik G.
Published: September 2007

Adenosine (Ado) enhances ANG II-induced constrictions of afferent arterioles (Af) by receptor-dependent and -independent pathways. Here, we test the hypothesis that transient Ado treatment has a sustained effect on Af contractility, resulting in increased ANG II responses after longer absence of Ado. Treatment with Ado (cumulative from 10−11to 10−4mol/l) and consecutive washout for 10 or 30 min increased constrictions on ANG II in isolated, perfused Af. Cytosolic calcium transients on ANG II were not enhanced in Ado-treated vessels. Selective or global inhibition of A1- and A2-adenosine receptors did not inhibit the Ado effect. Nitrobenzylthioinosine (an Ado transport inhibitor) clearly reduced the Ado-mediated responses. Selective inhibition of p38 MAPK with SB-203580 also prevented the Ado effect. Inosine treatment did not influence arteriolar reactivity to ANG II. Contractile responses of Af on norepinephrine and endothelin-1 were not influenced by Ado. Phosphorylation of the p38 MAPK and of the regulatory unit of 20-kDa myosin light chain was enhanced after Ado treatment and ANG II in Af. However, phosphorylation of p38 MAPK induced by norepinephrine or endothelin-1 was reduced in vessels treated with Ado, whereas 20-kDa myosin light chain was unchanged. The results suggest an intracellular, long-lasting mechanism including p38 MAPK activation responsible for the increase of ANG II-induced contractions by Ado. The effect is not calcium dependent and specific for ANG II. The prolonged enhancement of the ANG II sensitivity of Af may be important for tubuloglomerular feedback.
Synergistic impacts of heat shock and spawning on the physiology and immune health ofCrassostrea gigas: an explanation for summer mortality in Pacific oysters
Authors: Li Yan , Qin Jian G. , Abbott Catherine A. , Li Xiaoxu , Benkendorff Kirsten
Published: September 2007

Mass mortality is often observed in cultured oysters during the period following spawning in the summer season. To examine the underlying causes leading to this phenomenon, thermotolerance of the Pacific oyster Crassostrea gigas was assessed using pre- and postspawning oysters that were sequentially treated with sublethal (37°C) and lethal heat shocks (44°C). The effects were examined on a range of immune and metabolic parameters in addition to mortality rate. A preventative 37°C significantly reduced oyster mortality after exposure to a second heat shock of 44°C, but in postspawning oysters mortality remained at 80%, compared with < 10% in prespawning oysters. Levels of the 72 kDa and 69 kDa heat shock proteins were low in the gill tissue from postspawning oysters stimulated by heat shock, indicating spawning reduced heat shock protein synthesis. The postspawning oysters had depleted glycogen stores in the mantle tissue and reduced adenylate energy charge after heat shock, indicative of lower energy for metabolic activity. A cumulative effect of spawning and heat shock was observed on the immunocompetence of oysters, demonstrated by reduced hemocyte phagocytosis and hemolymph antimicrobial activity. These results support the hypothesis that the energy expended during reproduction compromises the thermotolerance and immune status of oysters, leaving them easily subject to mortality if heat stress occurs in postspawning stage. This study improves our understanding of oyster summer mortality and has implications for the long-term persistence of mollusks under the influence of global warming.
Molecular mechanisms underlying the development of endothermy in birds (Gallus gallus): a new role of PGC-1α?
Authors: Walter Isabel , Seebacher Frank
Published: September 2007

In endotherms, plasticity of internal heat production in response to environmental variability is an important component of thermoregulation. During embryogenesis endotherms cannot regulate their body temperature metabolically and are therefore similar to ectotherms. The transition from ectothermy to endothermy occurs by the development of metabolic capacity during embryogenesis. Here we test the hypothesis that the development of metabolism during embryogenesis in birds is under transcriptional control and that metabolic capacity is upregulated in colder environments. The peroxisome proliferator-activated receptor-γ (PPARγ) coactivator-1α (PGC-1α) is the major metabolic regulator in mammals. PGC-1α and its target PPARγ were significantly elevated during development in pectoral muscle and liver of chickens ( Gallus gallus) compared with adults. However, the timing of upregulation of PGC-1α and PPARγ was not in synchrony. In cool incubation temperatures (35°C) both PGC-1α and PPARγ gene expression was increased in liver but not in skeletal muscle, compared with a 38°C incubation treatment. Cytochrome c oxidase and citrate synthase enzyme activities and ATP synthase gene expression increased during embryonic development in liver and muscle, and there was a significant effect of incubation temperature on these parameters. Our findings suggest that PGC-1α might be important for establishing endothermic metabolic capacity during embryogenesis in birds.
Acute angiotensin-converting enzyme inhibition evokes bradykinin-induced sympathetic activation in diabetic rats
Authors: Augustyniak Robert A. , Maliszewska-Scislo Maria , Chen Haiping , Fallucca John , Rossi Noreen F.
Published: September 2007

We have previously shown that acute intravenous injection of the angiotensin-converting enzyme (ACE) inhibitor enalapril in diabetic rats evokes a baroreflex-independent sympathoexcitatory effect that does not occur with angiotensin receptor blockade alone. As ACE inhibition also blocks bradykinin degradation, we sought to determine whether bradykinin mediated this effect. Experiments were performed in conscious male Sprague-Dawley rats, chronically instrumented to measure mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA), 2 wk after streptozotocin (55 mg/kg iv, diabetic, n = 11) or citrate vehicle (normal, n = 10). Enalapril (2.5 mg/kg iv) decreased MAP in normal rats (−15 ± 3 mmHg), while a smaller response (−4 ± 1 mmHg) occurred in diabetic rats. Despite these different depressor responses to enalapril, HR (+44 ± 8 vs. +26 ± 7 bpm) and RSNA (+90 ± 21 vs +71 ± 8% baseline) increased similarly between the groups ( P ≥ 0.22 for both). Pretreatment with the bradykinin B2 receptor antagonist Hoe 140 (10 μg/kg bolus followed by 0.8·μg−1kg·min−1 infusion) attenuated the decrease in MAP observed with enalapril in normal rats but had no effect in diabetic rats. Moreover, the normal group had smaller HR and RSNA responses (HR: +13 ± 8 bpm; RSNA: +32 ± 13% baseline) that were abolished in the diabetic group (HR: −4 ± 5 bpm; RSNA: −5 ± 9% baseline; P < 0.05 vs. preenalapril values). Additionally, bradykinin (20 μg/kg iv) evoked a larger, more prolonged sympathoexcitatory effect in diabetic compared with normal rats that was further potentiated after treatment with enalapril. We conclude that enhanced bradykinin signaling mediates the baroreflex-independent sympathoexcitatory effect of enalapril in diabetic rats.
Fasting and postprandial concentrations of GLP-1 in intestinal lymph and portal plasma: evidence for selective release of GLP-1 in the lymph system
Authors: D'Alessio David , Lu Wendell , Sun William , Zheng Shuqin , Yang Qing , Seeley Randy , Woods Stephen C. , Tso Patrick
Published: September 2007

Glucagon like peptide 1 (GLP-1) is an intestinal hormone that plays an important role in glucose metabolism. GLP-1 is released from mucosal L cells following nutrient ingestion and contributes to the incretin effect, with the enhancement of insulin secretion occurring with enteral compared with intravenous glucose administration. The mechanisms linking nutrient absorption and GLP-1 secretion are unknown, and studies addressing this topic, particularly in small animal models, have been hampered by the relatively low concentrations of GLP-1 in the circulation. We hypothesized that GLP-1 levels would be higher in samples of intestinal lymph compared with plasma and could provide a novel system in which to study meal-induced hormone secretion. We addressed this hypothesis in conscious rats with indwelling catheters in the portal vein and distal intestinal lymph duct. These animals had plasma and lymph sampled before and for 240 min after instillation of a liquid meal in the gastrointestinal tract. Lymph contained detectable concentrations of glucose, insulin, and GLP-1 that were reliably measured using our assays. Before and after the Ensure feeding, plasma insulin levels were approximately two times as high in portal plasma as intestinal lymph. In marked contrast, GLP-1 levels were five to six times higher in lymph relative to portal plasma following nutrient administration. This relative difference in GLP-1 levels was even greater when lymph was compared with peripheral plasma and dramatically exceeded the ratio of lymph to plasma peptide tyrosine-tyrosine concentrations. This is the first observation of a gastrointestinal hormone being disproportionately transported in lymph. The remarkable levels of GLP-1 in intestinal lymph demonstrate the potential for lymphatic sampling as a more sensitive means of studying the secretory physiology of this hormone in vivo. In addition, these data raise the possibility that intestinal lymph may serve as a specialized signaling conduit for regulatory peptides secreted by gastrointestinal endocrine cells.
JAK kinases promote invasiveness in VHL-mediated renal cell carcinoma by a suppressor of cytokine signaling-regulated, HIF-independent mechanism
Authors: Wu Karen L. , Miao Hui , Khan Shenaz
Published: September 2007

von Hippel-Lindau (VHL) disease is a cancer syndrome, which includes renal cell carcinoma (RCC), and is caused by VHL mutations. Most, but not all VHL phenotypes are due to failure of mutant VHL to regulate constitutive proteolysis of hypoxia-inducible factors (HIFs). Janus kinases (JAK1, 2, 3, and TYK2) promote cell survival and proliferation, processes tightly controlled by SOCS proteins, which have sequence and structural homology to VHL. We hypothesized that in VHL disease, RCC pathogenesis results from enhanced SOCS1 degradation, leading to upregulated JAK activity. We find that baseline JAK2, JAK3, and TYK2 activities are increased in RCC cell lines, even after serum deprivation or coincubation with cytokine inhibitors. Furthermore, JAK activity is sustained in RCC stably expressing HIF2α shRNA. Invasion through Matrigel and migration in wound-healing assays, in vitro correlates of metastasis, are significantly greater in VHL mutant RCC compared with wild-type cells, and blocked by dominant-negative JAK expression or JAK inhibitors. Finally, we observe enhanced SOCS2/SOCS1 coprecipitation and reduced SOCS1 expression due to proteasomal degradation in VHL-null RCC compared with wild-type cells. The data support a new HIF-independent mechanism of RCC metastasis, whereby SOCS2 recruits SOCS1 for ubiquitination and proteasome degradation, which lead to unrestricted JAK-dependent RCC invasion. In addition to commonly proposed RCC treatment strategies that target HIFs, our data suggest that JAK inhibition represents an alternative therapeutic approach.
Delay Activity and Sensory-Motor Translation During Planned Eye or Hand Movements to Visual or Tactile Targets
Authors: Macaluso E. , Frith C. D. , Driver J.
Published: September 2007

To perform eye or hand movements toward a relevant location, the brain must translate sensory input into motor output. Recent studies revealed segregation between circuits for translating visual information into saccadic or manual movements, but less is known about translation of tactile information into such movements. Using human functional magnetic resonance imaging (fMRI) in a delay paradigm, we factorially crossed sensory modality (vision or touch) and motor effector (eyes or hands) for lateralized movements (gaze shifts to left or right or pressing a left or right button with the corresponding left or right hand located there). We investigated activity in the delay-period between stimulation and response, asking whether the currently relevant side (left or right) during the delay was encoded according to sensory modality, upcoming motor response, or some interactive combination of these. Delay activity mainly reflected the motor response subsequently required. Irrespective of visual or tactile input, we found sustained activity in posterior partial cortex, frontal-eye field, and contralateral visual cortex when subjects would later make an eye movement. For delays prior to manual button-press response, activity increased in contralateral precentral regions, again regardless of stimulated modality. Posterior superior temporal sulcus showed sustained delay activity, irrespective of sensory modality, side, and response type. We conclude that the delay activations reflect translation of sensory signals into effector-specific motor circuits in parietal and frontal cortex (plus an impact on contralateral visual cortex for planned saccades), regardless of cue modality, whereas posterior STS provides a representation that generalizes across both sensory modality and motor effector.
Concurrent Encoding of Frequency and Amplitude Modulation in Human Auditory Cortex: Encoding Transition
Authors: Luo Huan , Wang Yadong , Poeppel David , Simon Jonathan Z.
Published: September 2007

Complex natural sounds (e.g., animal vocalizations or speech) can be characterized by specific spectrotemporal patterns the components of which change in both frequency (FM) and amplitude (AM). The neural coding of AM and FM has been widely studied in humans and animals but typically with either pure AM or pure FM stimuli. The neural mechanisms employed to perceptually unify AM and FM acoustic features remain unclear. Using stimuli with simultaneous sinusoidal AM (at rate fAM = 37 Hz) and FM (with varying rates ƒFM), magnetoencephalography (MEG) is used to investigate the elicited auditory steady-state response (aSSR) at relevant frequencies (ƒAM, ƒFM, ƒAM + fFM). Previous work demonstrated that for sounds with slower FM dynamics ( fFM < 5 Hz), the phase of the aSSR at ƒAM tracked the FM; in other words, AM and FM features were co-tracked and co-represented by “phase modulation” encoding. This study explores the neural coding mechanism for stimuli with faster FM dynamics (≤30 Hz), demonstrating that at faster rates ( fFM > 5 Hz), there is a transition from pure phase modulation encoding to a single-upper-sideband (SSB) response (at frequency fAM + fFM) pattern. We propose that this unexpected SSB response can be explained by the additional involvement of subsidiary AM encoding responses simultaneously to, and in quadrature with, the ongoing phase modulation. These results, using MEG to reveal a possible neural encoding of specific acoustic properties, demonstrate more generally that physiological tests of encoding hypotheses can be performed noninvasively on human subjects, complementing invasive, single-unit recordings in animals.
Rotation Axes of the Head During Positioning, Head Shaking, and Locomotion
Authors: Kunin Mikhail , Osaki Yasuhiro , Cohen Bernard , Raphan Theodore
Published: September 2007

Static head orientations obey Donders’ law and are postulated to be rotations constrained by a Fick gimbal. Head oscillations can be voluntary or generated during natural locomotion. Whether the rotation axes of the voluntary oscillations or during locomotion are constrained by the same gimbal is unknown and is the subject of this study. Head orientation was monitored with an Optotrak (Northern Digital). Human subjects viewed visual targets wearing pin-hole goggles to achieve static head positions with the eyes centered in the orbit. Incremental rotation axes were determined for pitch and yaw by computing the velocity vectors during head oscillation and during locomotion at 1.5 m/s on a treadmill. Static head orientation could be described by a generalization of the Fick gimbal by having the axis of the second rotation rotate by a fraction, k, of the angle of the first rotation without a third rotation. We have designated this as a k-gimbal system. Incremental rotation axes for both pitch and yaw oscillations were functions of the pitch but not the yaw head positions. The pivot point for head oscillations was close to the midpoint of the interaural line. During locomotion, however, the pivot point was considerably lower. These findings are well explained by an implementation of the k-gimbal model, which has a rotation axis superimposed on a Fick-gimbal system. This could be realized physiologically by the head interface with the dens and occipital condyles during head oscillation with a contribution of the lower spine to pitch during locomotion.
Applying Double Magnetic Induction to Measure Two-Dimensional Head-Unrestrained Gaze Shifts in Human Subjects
Authors: Bremen Peter , Van der Willigen Robert F. , Van Opstal A. John
Published: September 2007

This study compares the performance of a newly developed gaze (eye-in-space) measurement technique based on double magnetic induction (DMI) by a custom-made gold-plated copper ring on the eye with the classical scleral search coil (SSC) technique to record two-dimensional (2D) head-unrestrained gaze shifts. We tested both systems simultaneously during head-free saccades toward light-emitting diodes (LEDs) within the entire oculomotor range (±35 deg). The absence of irritating lead wires in the case of the DMI method leads to a higher guarantee of success (no coil breakage) and to less irritation on the subject's eye, which results in a longer and more comfortable measurement time. Correlations between DMI and SSC signals for horizontal and vertical eye position, velocity, and acceleration were close to 1.0. The difference between the SSC signal and the DMI signal remains within a few degrees. In our current setup the resolution was about 0.3 deg for the DMI method versus 0.2 deg for the SSC technique. The DMI method is an especially good alternative in the case of patient and laboratory animal gaze control studies where breakage of the SSC lead wires is particularly cumbersome.
Temporal Gene Expression Profiling of the Wheat Leaf Rust Pathosystem Using cDNA Microarray Reveals Differences in Compatible and Incompatible Defence Pathways
Authors: Fofana Bourlaye , Banks Travis W. , McCallum Brent , Strelkov Stephen E. , Cloutier Sylvie
Published: September 2007

In this study, we detail the construction of a custom cDNA spotted microarray containing 7728 wheat ESTs and the use of the array to identify host genes that are differentially expressed upon challenges with leaf rust fungal pathogens. Wheat cultivar RL6003 (Thatcher Lr1) was inoculated with Puccinia triticina virulence phenotypes BBB (incompatible) or TJB (7-2) (compatible) and sampled at four different time points (3, 6, 12, and 24 hours) after inoculation. Transcript expression levels relative to a mock treatment were measured. One hundred ninety two genes were found to have significantly altered expression between the compatible and incompatible reactions. Among those were genes involved in photosynthesis, the production of reactive oxygen species, ubiquitination, signal transduction, as well as in the shikimate/phenylpropanoid pathway. These data indicate that various metabolic pathways are affected, some of which might be used by RL6003 to mount a coordinated defense against an incompatible fungal pathogen.
Ozonation of Human Blood Induces a Remarkable Upregulation of Heme Oxygenase-1 and Heat Stress Protein-70
Authors: Bocci Velio , Aldinucci Carlo , Mosci Francesca , Carraro Fabio , Valacchi Giuseppe
Published: September 2007

Heme oxygenase-I (HO-1) has emerged as one of the most protective enzymes and its pleiotropic activities have been demonstrated in a variety of human pathologies. Unpublished observations have shown that HO-1 is induced after the infusion of ozonated blood into the respective donors, and many other experimental observations have demonstrated the efficacy of oxidizing agents. It appeared worthwhile to evaluate whether we could better define the activity of potential inducers such as hydrogen peroxide and ozonated human plasma. Human vascular endothelial cells at confluence were challenged with different concentrations of these inducers and the simultaneous production of nitric oxide (NO); and HO-1 was measured by either measuring nitrite, or bilirubin formation, or/and the immune reactivity of the protein by Western blot using a rabbit antihuman HO-1 and Hsp-70. The results show that production of both NO and HO-1 is fairly dose dependent but is particularly elevated using human plasma after transient exposure to a medium ozone concentration. At this concentration, there is also induction of Hsp-70. The results clarify another positive effect achievable by the use of ozone therapy.
Influence of Phase Composition on Sintered Microstructure of Combustion Synthesized Oxides
Authors: Ganesh Ibram , Ferreira J. M. F.
Published: September 2007

The effects of powders synthesis methods (urea-combustion synthesis (CS) and conventional solid-state (SS) reaction) on the sintering ability, microstructural features, and mechanical properties ofAl2O3,MgAl2O4spinel, and 20 wt.% ZrO2–MgAl2O4upon sintering at 1625C∘were investigated. X-ray diffraction (XRD), scanning electron microscopy (SEM), relative density (RD), apparent porosity and water absorption capacity, hardness, fracture toughness, and three-point bend test studies revealed the superior sintering ability of CS ZrO2-MgAl2O4composite powder as compared with one prepared by SS reaction. In contrast, single-phase powders obtained by SS reaction exhibit superior sintering ability over CS synthesized ones. The reasons for differences observed are discussed along this paper.
Association of Ultrasound Findings with Decision to Continue Down Syndrome Pregnancies
Authors: Perry Sandy , Woodall Angela L. , Pressman Eva K.
Published: September 2007

Objective: To evaluate the association of ultrasound findings and other factors with the decision to terminate trisomy-21-affected pregnancies. Methods: We performed a retrospective analysis of trisomy-21-affected pregnancies diagnosed prior to 24 weeks’ gestation. Data were collected on maternal age, indications for prenatal diagnosis, gestational age at diagnosis, marital status, race, parity and ultrasound findings. Logistic regression, χ2, t test and Fishers exact test were used for statistical analysis. Results: Fifty-nine pregnancies were identified with a termination rate of 72.9%. Termination rates were significantly lower in patients with major (50%) or minor (64%) ultrasound abnormalities than in patients with normal ultrasound exams (92%), p = 0.026 and 0.022, respectively. Patients who chose terminations were older (36.1 vs. 32.3), but this did not reach statistical significance (p = 0.059). Conclusion: Patients with abnormal ultrasound results were more likely to continue a trisomy 21 pregnancy.
The Diffusion of Innovation: Factors Influencing the Uptake of Pharmacogenetics
Authors: Fuks Nielsen Louise , Moldrup Claus
Published: September 2007

Background: Inspired by diffusion research, this paper examines how perceived need, health status, experiences with medicine and testing, consumption of mass media and sociodemography influence the public’s familiarity, knowledge, attitudes and intentions regarding pharmacogenetics. The objective is to identify factors affecting the adoption pattern of pharmacogenetics in the public. Method: The paper is based on an Internet-based questionnaire survey conducted in March 2005. A total of 3,000 representative Danes aged 18–70 years were included in the survey, representing a response rate of 58.9%. Results/Conclusion: Knowledge of pharmacogenetics, and thus the diffusion of the technology, is influenced by medicine consumption, experienced lack of effect and side effects, use of medical testing and perception of societal need. Increased knowledge is seen in all cases. The general perception of and attitude to pharmacogenetics is related to prior use of medical tests and perception of societal need for pharmacogenetics, which in both cases indicates an increased positive approach.
The ICTUS Study: A Prospective Longitudinal Observational Study of 1,380 AD Patients in Europe
Authors: Reynish E. , Cortes F. , Andrieu S. , Cantet C. , Olde Rikkert M. , Melis R. , Froelich L. , Frisoni G.B. , Jönsson L. , Visser P.J. , Ousset P.J. , Vellas B.
Published: September 2007

The long-term objective of the ICTUS study is to identify milestones in Alzheimer’s disease (AD) progression and to develop a model to predict disease course in individual AD patients in Europe. The secondary objectives are to describe the patterns of prescribing, and the socioeconomic impact of AD in Europe. Between 2003 and 2005 1,380 patients with probable AD were recruited in specialised (secondary care) clinics in 12 European countries. Their mean age was 76 years and they had a mean of 8.0 ± (SD) 4.6 years of education. Thirty-five percent were male. The mean MMSE score was 20.4 ± (SD) 4.0. Forty-three percent had very mild dementia (CDR 0.5) and 44% had mild dementia (CDR 1). All patients completed baseline evaluation and biannual follow-up is ongoing. The goals of the current study are to describe the specific methods for recruitment in this crosscultural setting and the characteristics of the inception ICTUS cohort, including clinical features, co-morbidity, neuropsychological performance, neuropsychiatric symptoms, functional impairment and social burden.
Breaking Loops in Large Complex Pedigrees
Authors: Axenovich Tatiana I. , Zorkoltseva Irina V. , Liu Fan , Kirichenko Anatoly V. , Aulchenko Yurii S.
Published: September 2007

For pedigrees with multiple loops, exact likelihoods could not be computed in an acceptable time frame and thus, approximate methods are used. Some of these methods are based on breaking loops and approximations of complex pedigree likelihoods using the exact likelihood of the corresponding zero-loop pedigree. Due to ignoring loops, this method results in a loss of genetic information and a decrease in the power to detect linkage. To minimize this loss, an optimal set of loop breakers has to be selected. In this paper, we present a graph theory based algorithm for automatic selection of an optimal set of loop breakers. We propose using a total relationship between measured pedigree members as a proxy to power. To minimize the loss of genetic information, we suggest selection of such breakers whose duplication in a pedigree would be accompanied by a minimal loss of total relationship between measured pedigree members. We show that our algorithm compares favorably with other existing loop-breaker selection algorithms in terms of conservation of genetic information, statistical power and CPU time of subsequent linkage analysis. We implemented our method in a software package LOOP_EDGE, which is available at http://mga.bionet.nsc.ru/nlru/.
DNA Repair Polymorphisms Modify Bladder Cancer Risk: A Multi-factor Analytic Strategy
Authors: Andrew Angeline S. , Karagas Margaret R. , Nelson Heather H. , Guarrera Simonetta , Polidoro Silvia , Gamberini Sara , Sacerdote Carlotta , Moore Jason H. , Kelsey Karl T. , Demidenko Eugene , Vineis Paolo , Matullo Giuseppe
Published: September 2007

Objectives: A number of common non-synonymous single nucleotide polymorphisms (SNPs) in DNA repair genes have been reported to modify bladder cancer risk. These include: APE1-Asn148Gln, XRCC1-Arg399Gln and XRCC1-Arg194Trp in the BER pathway, XPD-Gln751Lys in the NER pathway and XRCC3-Thr241Met in the DSB repair pathway. Methods: To examine the independent and interacting effects of these SNPs in a large study group, we analyzed these genotypes in 1,029 cases and 1,281 controls enrolled in two case-control studies of incident bladder cancer, one conducted in New Hampshire, USA and the other in Turin, Italy. Results: The odds ratio among current smokers with the variant XRCC3-241 (TT) genotype was 1.7 (95% CI 1.0–2.7) compared to wild-type. We evaluated gene-environment and gene-gene interactions using four analytic approaches: logistic regression, Multifactor Dimensionality Reduction (MDR), hierarchical interaction graphs, classification and regression trees (CART), and logic regression analyses. All five methods supported a gene-gene interaction between XRCC1-399/XRCC3-241 (p = 0.001) (adjusted OR for XRCC1-399 GG, XRCC3-241 TT vs. wild-type 2.0 (95% CI 1.4–3.0)). Three methods predicted an interaction between XRCC1-399/XPD-751 (p = 0.008) (adjusted OR for XRCC1-399 GA or AA, XRCC3-241 AA vs. wild-type 1.4 (95% CI 1.1–2.0)). Conclusions: These results support the hypothesis that common polymorphisms in DNA repair genes modify bladder cancer risk and highlight the value of using multiple complementary analytic approaches to identify multi-factor interactions.
Small Artery Remodeling and Erythrocyte Deformability in L-NAME-Induced Hypertension: Role of Transglutaminases
Authors: Pistea Adrian , Bakker Erik N.T.P. , Spaan Jos A.E. , Hardeman Max R. , van Rooijen Nico , VanBavel Ed
Published: September 2007

Background: Hypertension is associated with inward remodeling of small arteries and decreased erythrocyte deformability, both impairing proper tissue perfusion. We hypothesized that these alterations depend on transglutaminases, cross-linking enzymes present in the vascular wall, monocytes/macrophages and erythrocytes. Methods and Results: Wild-type (WT) mice and tissue-type transglutaminase (tTG) knockout (KO) mice received the nitric oxide inhibitor Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) to induce hypertension. After 1 week, mesenteric arteries from hypertensive WT mice showed a smaller lumen diameter (–6.9 ± 2.0%, p = 0.024) and a larger wall-to-lumen ratio (11.8 ± 3.5%, p = 0.012) than controls, whereas inward remodeling was absent in hypertensive tTG KO mice. After 3 weeks, the wall-to-lumen ratio was increased in WT (20.8 ± 4.8%, p = 0.005) but less so in tTG KO mice (11.7 ± 4.6%, p = 0.026), and wall stress was normalized in WT but not in tTG KO mice. L-NAME did not influence expression of tTG or an alternative transglutaminase, coagulation factor XIII (FXIII). Suppression of FXIII by macrophage depletion was associated with increased tTG in the presence of L-NAME. L-NAME treatment decreased erythrocyte deformability in the WT mice (–15.3% at 30 dynes/cm2, p = 0.014) but not in the tTG KO mice. Conclusion: Transglutaminases are involved in small artery inward remodeling and erythrocyte stiffening associated with nitric oxide inhibition-related hypertension.
The Influence of Exogenous Tissue Factor on the Regulators of Proliferation and Apoptosis in Endothelial Cells
Authors: Pradier Amandine , Ettelaie Camille
Published: September 2007

Background: The exposure of tissue factor (TF) at the site of injury or trauma is a rapid process that leads to the initiation of blood coagulation as well as homeostatic processes giving rise to vascular repair. Aims and Methods: By exposing human endothelial cells to combinations of exogenous TF and factor VIIa (FVIIa) in serum-free medium, the influence of TF concentrations on cellular proliferation and apoptosis was investigated. Results: Lower concentrations of TF resulted in increased cellular proliferation as well as upregulation of cyclin D1, downregulation of p21 and p27 and induction of tube formation in vitro. Conversely, incubation with higher concentrations of TF resulted in the activation of caspase-3, expression of p53 and Bax, translocation of p53 into the nucleus and induction of DNA fragmentation. Incubation of the cells with TF/FVIIa led to a lower proliferation rate with additional upregulation in p27. Conclusions: TF seems to have a bifunctional role in determining the fate of endothelial cells, depending on the concentration and the interactions of this protein. The release of TF in the locality of the injured tissue makes this protein an ideal factor for ascertaining the level of injury and determining the fate of the cells.
Cyclic AMP-Independent CGRP8–37-Sensitive Receptors Mediate Adrenomedullin-Induced Decrease of CaCl2-Contraction in Pregnant Rat Mesenteric Artery
Authors: Ross Gracious R. , Yallampalli Uma , Yallampalli Chandra
Published: September 2007

Objectives: We tested the hypothesis that adrenomedullin reduces calcium influx independent of potassium channels in depolarized endothelium-denuded mesenteric artery from pregnant rats. Results: Adrenomedullin reduced the CaCl2-induced contraction, while the receptor antagonist calcitonin gene-related peptide (CGRP)8–37, but not adrenomedullin22–52, reversed these effects. Adenylate cyclase inhibition by SQ22536 did not prevent adrenomedullin effects on CaCl2-induced contraction. Adrenomedullin did not inhibit depolarization-induced calcium entry to isolated vascular smooth muscle. Inhibition of myosin light-chain (MLC) phosphatase by calyculin A reversed the effects of adrenomedullin on contraction caused by submillimolar concentrations of CaCl2, while adrenomedullin still inhibited contraction caused by higher concentrations of CaCl2. However, the ratio of phosphorylated to total myosin phosphatase target 1, the regulatory subunit of MLC phosphatase, did not change with adrenomedullin, indicating a lack of MLC phosphatase activation. Interestingly, sodium fluoride, a nonspecific protein phosphatase inhibitor, completely blocked the effect of adrenomedullin on CaCl2-induced contraction. Adrenomedullin inhibited calcium mobilization from intracellular stores induced by thapsigargin. Conclusion: Adrenomedullin inhibits CaCl2-induced contraction, without affecting calcium influx, through a CGRP8–37-sensitive receptor, but not using the cyclic adenosine monophosphate pathway, probably through activation of protein phosphatases. Inhibition of intracellular calcium release is an additional role played by adrenomedullin in calcium homeostasis in vascular smooth muscle.