bluuebunny/crossref_metadata_2025 huggingface dataset:
Scattering and Pairing in Cuprate Superconductors
Authors: Taillefer Louis
Published: July 2010

The origin of the exceptionally strong superconductivity of cuprates remains a subject of debate after more than two decades of investigation. Here we follow a new lead: The onset temperature for superconductivity scales with the strength of the anomalous normal-state scattering that makes the resistivity linear in temperature. The same correlation between linear resistivity and Tc is found in organic superconductors, for which pairing is known to come from fluctuations of a nearby antiferromagnetic phase, and in pnictide superconductors, for which an antiferromagnetic scenario is also likely. In the cuprates, the question is whether the pseudogap phase plays the corresponding role, with its fluctuations responsible for pairing and scattering. We review recent studies that shed light on this phase—its boundary, its quantum critical point, and its broken symmetries. The emerging picture is that of a phase with spin-density-wave order and fluctuations, in broad analogy with organic, pnictide, and heavy-fermion superconductors.
Adrenergic receptor activation involves ATP release and feedback through purinergic receptors
Authors: Sumi Yuka , Woehrle Tobias , Chen Yu , Yao Yongli , Li Andrew , Junger Wolfgang G.
Published: July 2010

Formyl peptide receptor-induced chemotaxis of neutrophils depends on the release of ATP and autocrine feedback through purinergic receptors. Here, we show that adrenergic receptor signaling requires similar purinergic feedback mechanisms. Real-time RT-PCR analysis revealed that human embryonic kidney (HEK)-293 cells express several subtypes of adrenergic (α1-, α2-, and β-receptors), adenosine (P1), and nucleotide receptors (P2). Stimulation of Gq-coupled α1-receptors caused release of cellular ATP and MAPK activation, which was blocked by inhibiting P2 receptors with suramin. Stimulation of Gi-coupled α2-receptors induced weak ATP release, while Gs-coupled β-receptors caused accumulation of extracellular ADP and adenosine. β-Receptors triggered intracellular cAMP signaling, which was blocked by scavenging extracellular adenosine with adenosine deaminase or by inhibiting A2a adenosine receptors with SCH58261. These findings suggest that adrenergic receptors require purinergic receptors to elicit downstream signaling responses in HEK-293 cells. We evaluated the physiological relevance of these findings using mouse aorta tissue rings. Stimulation of α1-receptors induced ATP release and tissue contraction, which was reduced by removing extracellular ATP with apyrase or in the absence of P2Y2receptors in aorta rings from P2Y2receptor knockout mice. We conclude that, like formyl peptide receptors, adrenergic receptors require purinergic feedback mechanisms to control complex physiological processes such as smooth muscle contraction and regulation of vascular tone.
Comparison of in vivo postexercise phosphocreatine recovery and resting ATP synthesis flux for the assessment of skeletal muscle mitochondrial function
Authors: van den Broek N. M. A. , Ciapaite J. , Nicolay K. , Prompers J. J.
Published: July 2010

31P magnetic resonance spectroscopy (MRS) has been used to assess skeletal muscle mitochondrial function in vivo by measuring 1) phosphocreatine (PCr) recovery after exercise or 2) resting ATP synthesis flux with saturation transfer (ST). In this study, we compared both parameters in a rat model of mitochondrial dysfunction with the aim of establishing the most appropriate method for the assessment of in vivo muscle mitochondrial function. Mitochondrial dysfunction was induced in adult Wistar rats by daily subcutaneous injections with the complex I inhibitor diphenyleneiodonium (DPI) for 2 wk. In vivo31P MRS measurements were supplemented by in vitro measurements of oxygen consumption in isolated mitochondria. Two weeks of DPI treatment induced mitochondrial dysfunction, as evidenced by a 20% lower maximal ADP-stimulated oxygen consumption rate in isolated mitochondria from DPI-treated rats oxidizing pyruvate plus malate. This was paralleled by a 46% decrease in in vivo oxidative capacity, determined from postexercise PCr recovery. Interestingly, no significant difference in resting, ST-based ATP synthesis flux was observed between DPI-treated rats and controls. These results show that PCr recovery after exercise has a more direct relationship with skeletal muscle mitochondrial function than the ATP synthesis flux measured with31P ST MRS in the resting state.
Moderate hyperbilirubinemia improves renal hemodynamics in ANG II-dependent hypertension
Authors: Vera Trinity , Stec David E.
Published: July 2010

We have previously demonstrated that moderate hyperbilirubinemia decreases blood pressure in ANG II-dependent hypertension through mechanisms that decrease oxidative stress and increase nitric oxide levels. Since decreases in renal hemodynamics play an important role in mediating the hypertensive actions of ANG II, the goal of the present study was to examine the effect of moderate hyperbilirubinemia on glomerular filtration rate (GFR) and renal blood flow (RBF) in a mouse model of ANG II hypertension. Mice were made moderately hyperbilirubinemic by two methods: indinavir or specific morpholino antisense oligonucleotides against UGT1A1, which is the enzyme responsible for the conjugation of bilirubin in the liver. GFR and RBF were measured in mice after implantation of an osmotic minipump delivering ANG II at a rate of 1 μg·kg−1·min−1. GFR was measured by continuous infusion of I125-labeled iothalamate on days 5 and 6 of ANG II infusion in conscious mice. RBF was measured on day 7 of ANG II infusion in anesthetized mice. Blood levels of unconjugated bilirubin were significantly increased in mice treated with indinavir or anti-UGT1A1 ( P = 0.002). ANG II decreased GFR by 33% of control ( n = 9, P = 0.004), and this was normalized by moderate hyperbilirubinemia ( n = 6). Next, we examined the effect of moderate hyperbilirubinemia on RBF in ANG II-infused mice. ANG II infusion significantly decreased RBF by 22% ( P = 0.037) of control, and this decrease was normalized by moderate hyperbilirubinemia ( n = 6). These results indicate that improvement of renal hemodynamics may be one mechanism by which moderate hyperbilirubinemia lowers blood pressure in this model.
Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to a nitric oxide donor in the pregnant rat
Authors: Sasser Jennifer M. , Ni Xi-Ping , Humphreys Michael H. , Baylis Chris
Published: July 2010

Pregnancy is characterized by plasma volume expansion and renal sodium retention with loss of natriuretic response to atrial natriuretic peptide due to increased medullary phosphodiesterase-5 (PDE5). Here, we determined whether natriuretic responses to nitric oxide (NO) are also blunted in pregnancy due to increased PDE5. Anesthetized 16-day pregnant and virgin rats were studied at baseline and during intrarenal infusion of the NO donor spermine NONOate (2.5 nmol/min), the PDE5 inhibitor sildenafil (SILD; 0.5 μg/min), or a combination. The right (noninfused) kidney served as a control. Intrarenal NONOate had no effect on mean arterial pressure (MAP); however, SILD reduced MAP in virgin rats, and the combination of NONOate+SILD reduced MAP in both virgin and pregnant rats. Neither NONOate nor SILD altered glomerular filtration rate. NONOate and SILD each stimulated sodium excretion (UNaV) and fractional excretion of sodium (FENa) in virgin rats, but the combination did not result in an additional natriuretic response. However, NONOate infusion did not increase UNaV or FENain pregnant rats, but the natriuretic response to NONOate was restored with SILD, and SILD alone produced a natriuresis during pregnancy. Sodium nitroprusside (10−4mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10−7mol/l). Therefore, increased intrarenal PDE5 mediates the blunted natriuretic response to NO, and loss of responsiveness to the cGMP-dependent, natriuretic agents may contribute to volume expansion during pregnancy.
Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids
Authors: Sieber Jonas , Lindenmeyer Maja Tamara , Kampe Kapil , Campbell Kirk Nicholas , Cohen Clemens David , Hopfer Helmut , Mundel Peter , Jehle Andreas Werner
Published: July 2010

Apoptosis of podocytes is considered critical in the pathogenesis of diabetic nephropathy (DN). Free fatty acids (FFAs) are critically involved in the pathogenesis of diabetes mellitus type 2, in particular the regulation of pancreatic β cell survival. The objectives of this study were to elucidate the role of palmitic acid, palmitoleic, and oleic acid in the regulation of podocyte cell death and endoplasmic reticulum (ER) stress. We show that palmitic acid increases podocyte cell death, both apoptosis and necrosis of podocytes, in a dose and time-dependent fashion. Palmitic acid induces podocyte ER stress, leading to an unfolded protein response as reflected by the induction of the ER chaperone immunoglobulin heavy chain binding protein (BiP) and proapoptotic C/EBP homologous protein (CHOP) transcription factor. Of note, the monounsaturated palmitoleic and oleic acid can attenuate the palmitic acid-induced upregulation of CHOP, thereby preventing cell death. Similarly, gene silencing of CHOP protects against palmitic acid-induced podocyte apoptosis. Our results offer a rationale for interventional studies aimed at testing whether dietary shifting of the FFA balance toward unsaturated FFAs can delay the progression of DN.
Inhibition of NAD(P)H oxidase potentiates AT2 receptor agonist-induced natriuresis in Sprague-Dawley rats
Authors: Sabuhi Rifat , Asghar Mohammad , Hussain Tahir
Published: July 2010

A positive association between renin-angiotensin system, especially AT1 receptor, and oxidative stress in the pathogenesis of hypertension and cardiovascular/renal diseases has been suggested. However, the role of oxidative stress, especially superoxide radicals in renal sodium handling in response to AT1 and AT2 receptors, is not known. Therefore, the present study was designed to investigate the role of NAD(P)H oxidase (NOX), a major superoxide radical producing enzyme, in AT1 and AT2 receptor function on natriuresis/diuresis in Sprague-Dawley rats. The rats under anesthesia were intravenously infused with NOX inhibitor apocynin (3.5 μg·kg−1·min−1), the AT1 receptor antagonist candesartan (100 μg/kg; bolus), and the AT2 receptor agonist CGP-42112A (1 μg·kg−1·min−1) alone and in combinations. Candesartan alone significantly increased urinary flow (UF; μl/30 min) by 53 and urinary Na excretion (UNaV; μmol/min) by 0.4 over basal. Preinfusion of apocynin had no effect on the net increase in UF or UNaV in response to candesartan. On the other hand, apocynin preinfusion caused profound increases in CGP-42112A-induced UF by 72, UNaV by 1.14, and fractional excretion of Na by 7.8. Apocynin and CGP-42112A alone did not cause significant increase in UF or UNaV over the basal. CGP-42112A infusion in the presence of apocynin increased urinary nitrite/nitrates and cGMP over basal. The infusion of candesartan, apocynin, and CGP-42112A alone or in combinations had no effect on the blood pressure or the glomerular filtration rate, suggesting tubular effects on natriuresis/diuresis. The data suggest that NOX may have an antagonistic role in AT2 receptor-mediated natriuresis/diuresis possibly via neutralizing nitric oxide and thereby influence fluid-Na homeostasis.
Augmented cyclooxygenase-2 effects on renal function during varying states of angiotensin II
Authors: Green Torrance , Rodriguez Jorge , Navar L. Gabriel
Published: July 2010

Nonsteroidal anti-inflammatory drug usage has long revealed renoprotective prostaglandin actions on the renal microvasculature during increased pressor hormone influence, but whether increased cyclooxygenase (COX)-2 expression supports prostaglandin vasodilatory influence by interfering with the actions of ANG II remains unresolved. Therefore, we tested the hypothesis that COX-2 inhibition causes hemodynamic and excretory effects that are increased in proportion to ANG II activity. In anesthetized Sprague-Dawley rats having augmented cortical COX-2 expression but different ANG II activity, we conducted renal clearance experiments during acute inhibition of COX-2 with nimesulide (NMSLD) and inhibition of COX-1 with SC-560. In one series of experiments, acute captopril [acute angiotensin-converting enzyme (ACE) inhibitor (aACEi)] was administered alone ( n = 13) or in combination with chronic captopril [chronic ACEi (cACEi)] pretreatment ( n = 19). In another series of experiments, rats were fed a normal-sodium [0.4% (NS), n = 12] or a low-sodium [0.03% (LS), n = 18] diet. NMSLD did not alter mean arterial blood pressure in any group but, in the LS and cACEi groups, decreased renal plasma flow (from 3.99 ± 0.33 to 2.85 ± 0.26 and from 4.30 ± 0.19 to 3.22 ± 0.21 ml·min−1·g−1), cortical blood flow (−12 ± 8% and −13 ± 4%), and glomerular filtration rate (from 0.88 ± 0.04 to 0.65 ± 0.05 and from 0.95 ± 0.07 to 0.70 ± 0.05 ml·min−1·g−1). In contrast, medullary blood flow (MBF) was significantly decreased by COX-2 inhibition in NS (−24 ± 5%), LS (−27 ± 8%), aACEi (−16 ± 3.8%), and cACEi (−24 ± 4.2%) groups. Absolute and fractional sodium excretion rates were unchanged by NMSLD, except in the LS group (0.75 ± 0.05 μeq/min and 0.43 ± 0.15% and 0.51 ± 0.06 μeq/min and 0.26 ± 0.10%). SC-560 did not augment the effects of NMSLD. These results demonstrate an augmented COX-2-mediated vasodilation that is not contingent on ANG II, in contrast to COX-2-mediated augmented sodium excretion, where ANG II activity is requisite. Furthermore, the COX-2 effects on MBF are not contingent on ANG II or changes in cortical microvascular responses. These results reflect COX-2 continual regulation of MBF and adaptive opposition to ANG II prohypertensinogenic effects on renal plasma flow, cortical blood flow, glomerular filtration rate, and absolute and fractional sodium excretion.
Vasopressin increases expression of UT-A1, UT-A3, and ER chaperone GRP78 in the renal medulla of mice with a urinary concentrating defect
Authors: Cai Qi , Nelson Sarah K. , McReynolds Matthew R. , Diamond-Stanic Maggie Keck , Elliott David , Brooks Heddwen L.
Published: July 2010

Activation of V2 receptors (V2R) during antidiuresis increases the permeability of the inner medullary collecting duct to urea and water. Extracellular osmolality is elevated as the concentrating capacity of the kidney increases. Osmolality is known to contribute to the regulation of collecting duct water (aquaporin-2; AQP2) and urea transporter (UT-A1, UT-A3) regulation. AQP1KO mice are a concentrating mechanism knockout, a defect attributed to the loss of high interstitial osmolality. A V2R-specific agonist, deamino-8-d-arginine vasopressin (dDAVP), was infused into wild-type and AQP1KO mice for 7 days. UT-A1 mRNA and protein abundance were significantly increased in the medullas of wild-type and AQP1KO mice following dDAVP infusion. The mRNA and protein abundance of UT-A3, the basolateral urea transporter, was significantly increased by dDAVP in both wild-type and AQP1KO mice. Semiquantitative immunoblots revealed that dDAVP infusion induced a significant increase in the medullary expression of the endoplasmic reticulum (ER) chaperone GRP78. Immunofluorescence studies demonstrated that GRP78 expression colocalized with AQP2 in principal cells of the papillary tip of the renal medulla. Using immunohistochemistry and immunogold electron microscopy, we demonstrate that vasopressin induced a marked apical targeting of GRP78 in medullary principal cells. Urea-sensitive genes, GADD153 and ATF4 (components of the ER stress pathway), were significantly increased in AQP1KO mice by dDAVP infusion. These findings strongly support an important role of vasopressin in the activation of an ER stress response in renal collecting duct cells, in addition to its role in activating an increase in UT-A1 and UT-A3 abundance.
Important role of muscle carnosine in rowing performance
Authors: Baguet Audrey , Bourgois Jan , Vanhee Lander , Achten Eric , Derave Wim
Published: July 2010

The role of the presence of carnosine (β-alanyl-l-histidine) in millimolar concentrations in human skeletal muscle is poorly understood. Chronic oral β-alanine supplementation is shown to elevate muscle carnosine content and improve anaerobic exercise performance during some laboratory tests, mainly in the untrained. It remains to be determined whether carnosine loading can improve single competition-like events in elite athletes. The aims of the present study were to investigate if performance is related to the muscle carnosine content and if β-alanine supplementation improves performance in highly trained rowers. Eighteen Belgian elite rowers were supplemented for 7 wk with either placebo or β-alanine (5 g/day). Before and following supplementation, muscle carnosine content in soleus and gastrocnemius medialis was measured by proton magnetic resonance spectroscopy (1H-MRS) and the performance was evaluated in a 2,000-m ergometer test. At baseline, there was a strong positive correlation between 100-, 500-, 2,000-, and 6,000-m speed and muscle carnosine content. After β-alanine supplementation, the carnosine content increased by 45.3% in soleus and 28.2% in gastrocnemius. Following supplementation, the β-alanine group was 4.3 s faster than the placebo group, whereas before supplementation they were 0.3 s slower ( P = 0.07). Muscle carnosine elevation was positively correlated to 2,000-m performance enhancement ( P = 0.042 and r = 0.498). It can be concluded that the positive correlation between baseline muscle carnosine levels and rowing performance and the positive correlation between changes in muscle carnosine and performance improvement suggest that muscle carnosine is a new determinant of rowing performance.
Activity Patterns and Timing of Muscle Activity in the Forward Walking and Backward Walking Stick InsectCarausius morosus
Authors: Rosenbaum Philipp , Wosnitza Anne , Büschges Ansgar , Gruhn Matthias
Published: July 2010

Understanding how animals control locomotion in different behaviors requires understanding both the kinematics of leg movements and the neural activity underlying these movements. Stick insect leg kinematics differ in forward and backward walking. Describing leg muscle activity in these behaviors is a first step toward understanding the neuronal basis for these differences. We report here the phasing of EMG activities and latencies of first spikes relative to precise electrical measurements of middle leg tarsus touchdown and liftoff of three pairs ( protractor/retractor coxae, levator/depressor trochanteris, extensor/flexor tibiae) of stick insect middle leg antagonistic muscles that play central roles in generating leg movements during forward and backward straight walking. Forward walking stance phase muscle (depressor, flexor, and retractor) activities were tightly coupled to touchdown, beginning on average 93 ms prior to and 9 and 35 ms after touchdown, respectively. Forward walking swing phase muscle (levator, extensor, and protractor) activities were less tightly coupled to liftoff, beginning on average 100, 67, and 37 ms before liftoff, respectively. In backward walking the protractor/retractor muscles reversed their phasing compared with forward walking, with the retractor being active during swing and the protractor during stance. Comparison of intact animal and reduced two- and one-middle-leg preparations during forward straight walking showed only small alterations in overall EMG activity but changes in first spike latencies in most muscles. Changing body height, most likely due to changes in leg joint loading, altered the intensity, but not the timing, of depressor muscle activity.
Development of Glutamatergic Synaptic Transmission in Binaural Auditory Neurons
Authors: Tait Sanchez Jason , Wang Yuan , Rubel Edwin W , Barria Andres
Published: July 2010

Glutamatergic synaptic transmission is essential for binaural auditory processing in birds and mammals. Using whole cell voltage clamp recordings, we characterized the development of synaptic ionotropic glutamate receptor (iGluR) function from auditory neurons in the chick nucleus laminaris (NL), the first nucleus responsible for binaural processing. We show that synaptic transmission is mediated by AMPA- and N-methyl-d-aspartate (NMDA)-type glutamate receptors (AMPA-R and NMDA-R, respectively) when hearing is first emerging and dendritic morphology is being established across different sound frequency regions. Puff application of glutamate agonists at embryonic day 9 (E9) revealed that both iGluRs are functionally present prior to synapse formation (E10). Between E11 and E19, the amplitude of isolated AMPA-R currents from high-frequency (HF) neurons increased 14-fold. A significant increase in the frequency of spontaneous events is also observed. Additionally, AMPA-R currents become faster and more rectifying, suggesting developmental changes in subunit composition. These developmental changes were similar in all tonotopic regions examined. However, mid- and low-frequency neurons exhibit fewer spontaneous events and evoked AMPA-R currents are smaller, slower, and less rectifying than currents from age-matched HF neurons. The amplitude of isolated NMDA-R currents from HF neurons also increased, reaching a peak at E17 and declining sharply by E19, a trend consistent across tonotopic regions. With age, NMDA-R kinetics become significantly faster, indicating a developmental switch in receptor subunit composition. Dramatic increases in the amplitude and speed of glutamatergic synaptic transmission occurs in NL during embryonic development. These changes are first seen in HF neurons suggesting regulation by peripheral inputs and may be necessary to enhance coincidence detection of binaural auditory information.
Brain Activations in Response to Vibrotactile Tooth Stimulation: a Psychophysical and fMRI Study
Authors: Trulsson Mats , Francis Susan T. , Bowtell Richard , McGlone Francis
Published: July 2010

The tactile sensitivity of the teeth, and associated periodontium, serves important sensory and motor functions. Microneurographic recordings from human periodontal ligament mechanoreceptor (PDLM) nerves, in response to tooth loading, reveal discharge patterns with sole slowly adapting (SA) II-type characteristics, highlighting the unique role of PDLMs in oral sensory processes. Here we investigate these receptors' properties, psychophysically and with neuroimaging (fMRI), in response to varying frequencies of dynamic (vibrotactile) stimulation. The finding of increased activity in primary (SI) and secondary (SII) somatosensory cortices (SI and SII) at low frequencies of stimulation (20 Hz) as compared with higher frequencies (50 and 100 Hz), shows an increased entrainment of the PDLMs at this lower frequency in line with expected SA II-type response properties. At the highest frequency (100 Hz), no significant activity was found in SI or SII, suggesting this frequency is outside the range of activity of PDLMs. An activation matrix is mapped that includes SI, SII, insular, inferior frontal gyrus, inferior parietal lobe and supplementary motor area as well as middle frontal gyrus and cerebellum. We compared the responses to tooth stimulation with those produced by identical vibrotactile stimulation of the finger. The results strongly suggest that the PDLMs play a significant role in the specification of the forces used to hold and manipulate food between teeth, and in these respects, the masticatory system appears analogous to fine finger-control mechanisms used during precision manipulation of small objects. Because fMRI reveals activations in posterior insular cortex, we also speculate that PDLMs, and SA II-type receptors in general, may be involved in one aspect of the feeling of body ownership.
Maternal Diabetes Increases Small Conductance Ca2+-Activated K+(SK) Currents That Alter Action Potential Properties and Excitability of Cardiac Motoneurons in the Nucleus Ambiguus
Authors: Lin Min , Chen Qing-Hui , Wurster Robert D. , Hatcher Jeff T. , Liu Ye-Qi , Li Lihua , Harden Scott W. , Cheng Zixi (Jack)
Published: July 2010

Parasympathetic cardiac motoneurons (PCMNs) in the nucleus ambiguus (NA) play a key role in regulating cardiac functions. In this study, we examined the effects of maternal diabetes on excitability, action potential (AP) properties, and small conductance Ca2+-activated K+(SK) currents of PCMNs. Neonatal mice from diabetic (OVE26 female, NMDM) and normal (FVB female, control) mothers that had been mated with nondiabetic fathers (FVB male) were used. Tracer XRITC was injected into the pericardial sac at P7-9 to retrogradely label PCMNs. Two days later, XRITC-labeled PCMNs were identified in brain stem slices. The responses of spike frequency, AP repolarization (half-width) and afterhyperpolarization (AHP) of PCMNs to current injections were studied using whole cell current clamp. Outward and afterhyperpolarization currents ( IAHP) in response to voltage steps were measured using whole cell voltage clamp. In examining the effects of maternal diabetes on excitability and AP properties, we found that in NMDM spike frequency decreased, the half-width and AHP peak amplitude increased, and the peak amplitude of outward transient currents and IAHPincreased compared with those measured in control. In examining the effects of maternal diabetes on SK channels, we found that after blockage of SK channels with a specific SK channel blocker apamin, maternal diabetes significantly increased apamin-sensitive outward transient currents and IAHP, and suppressed AHP amplitude in NMDM more than those in control. Further, apamin application increased the firing rate to current injections and completely abolished the difference of the firing rate between control and NMDM. We suggest that the augmented SK-mediated currents may contribute to the increased AHP amplitude and the attenuated excitability of PCMNs in NMDM.
Cortical Organization in the Etruscan Shrew (Suncus etruscus)
Authors: Roth-Alpermann Claudia , Anjum Farzana , Naumann Robert , Brecht Michael
Published: July 2010

Cortical organization in the Etruscan shrew is of comparative interest because of its small size and because the Etruscan shrew is an amazing tactile hunter. Here we investigated cortical organization in Etruscan shrews by electrophysiological mapping. We developed an anesthesia protocol for this very small mammal in which we combined massive application of local anesthesia, very slow induction of general anesthesia, and passive cooling. Under this anesthesia regime, we characterized auditory, visual, and somatosensory cortical responses. We found that large parts of shrew cortex respond to such stimuli. Of the responsive sites, a small fraction (∼14%) responded to visual stimuli in a caudally located region. Another small fraction of sites (∼11%) responded to auditory stimuli in a centrally located region. The majority of sites (∼75%) responded to tactile stimuli. We identified two topographically organized somatosensory areas with small receptive fields referred to as putative primary somatosensory cortex and putative secondary somatosensory cortex. In a posterior-lateral region that partially overlaps with piriform cortex, we observed large somatosensory receptive fields and often polysensory responses. In an anterior-lateral region that partially overlaps with piriform cortex, we observed large unimodal somatosensory receptive fields. Our findings demonstrate a remarkable degree of tactile specialization in Etruscan shrew cortex.
Grids for Applications in High-Temperature High-Resolution Transmission Electron Microscopy
Authors: Lan Yucheng , Wang Hui , Wang Dezhi , Chen Gang , Ren Zhifeng
Published: July 2010

New TEM grids coated with ultrathin amorphous films have been developed using atomic layer deposition technique. The amorphous films can withstand temperatures over in air and in vacuum when the thickness of the film is 2 nm, and up to in air when the thickness is 25 nm, which makes heating TEM grids with nanoparticles up to in air and immediate TEM observation without interrupting the nanoparticles possible. Such coated TEM grids are very much desired for applications in high-temperature high-resolution transmission electron microscopy.
Review onTrypanosoma cruzi: Host Cell Interaction
Authors: de Souza Wanderley , de Carvalho Tecia Maria Ulisses , Barrias Emile Santos
Published: July 2010

Trypanosoma cruzi, the causative agent of Chagas' disease, which affects a large number of individuals in Central and South America, is transmitted to vertebrate hosts by blood-sucking insects. This protozoan is an obligate intracellular parasite. The infective forms of the parasite are metacyclic and bloodstream trypomastigote and amastigote. Metacyclic trypomastigotes are released with the feces of the insect while amastigotes and bloodstream trypomastigotes are released from the infected host cells of the vertebrate host after a complex intracellular life cycle. The recognition between parasite and mammalian host cell involves numerous molecules present in both cell types. Here, we present a brief review of the interaction betweenTrypanosoma cruziand its host cells, mainly emphasizing the mechanisms and molecules that participate in theT. cruziinvasion process of the mammalian cells.
Intelligent Wireless Sensors with Application to the Identification of Structural Modal Parameters and Steel Cable Forces: From the Lab to the Field
Authors: Lei Y. , Shen W. A. , Song Y. , Wang Y.
Published: July 2010

Wireless sensing systems have been proposed for structural heath monitoring in recent years. While wireless sensors are cost-competitive compared to tethered monitoring systems, their significant merit also lies in their embedded computational capabilities. In this paper, performance of the two embedded engineering algorithms, namely the fast Fourier transform and peak-picking algorithm implemented in the wireless sensing nodes codeveloped at Stanford University and the University of Michigan is investigated through laboratory and field experimental studies. Furthermore, the wireless sensor network embedded with the engineering algorithms is adopted for the identification of structural modal parameters and forces in steel bridge cables. Identification results by the embedded algorithms in the intelligent wireless sensors are compared with those obtained by conventional offline analysis of the measured time-history data. Such a comparison serves to validate the effectiveness of the intelligent wireless sensor network. In addition, it is shown that self-interrogation of measurement data based upon the two embedded algorithms in wireless sensor nodes greatly reduces the amount of data to be transmitted by the wireless sensing network. Thus, the intelligent wireless sensors offer scalable network solutions that are power-efficient for the health monitoring of civil infrastructures.
Comparative Study of Spermatogenesis and Nucleolar Behavior in Testicular Lobes ofEuschistus heros(Heteroptera: Pentatomidae)
Authors: de Souza Hederson Vinicius , Itoyama Mary Massumi
Published: July 2010

In some testicular lobes of the Pentatomidae there may be occurrence of atypical spermatogenesis or polymegaly, leading to the production of nonfertile sperm. The comparative analysis of spermatogenesis and nucleolar behavior in testicular lobes ofEuschistus herosshowed cells with polymegaly in lobes 4 and 6. Generally, when these lobes are present in the same individual, there is also the formation of atypical cells in the flanking lobe. Such characteristic was not seen inE. heros. However, differences regarding the concentration of heteropyknotic chromatin and silver-positive bodies in this lobe deserve attention. This study explored the literature and demonstrated the prevalence of some lobes in the formation of differentiated cells. It was also found in the literature that there is an association of the chromocenter with the nucleolus in several species of Pentatomidae, but inE. herosthis association does not appear to occur.
Scleroderma Renal Crisis: A Pathology Perspective
Authors: Batal Ibrahim , Domsic Robyn T. , Medsger Thomas A. , Bastacky Sheldon
Published: July 2010

Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is associated with increased vascular permeability, activation of coagulation cascade, and renin secretion, which may lead to the acute renal failure typically associated with accelerated hypertension. The histologic picture of SRC is that of a thrombotic microangiopathy process with prominent small vessel involvement manifesting as myxoid intimal changes, thrombi, onion skin lesions, and/or fibrointimal sclerosis. Renal biopsies play an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in SSc patients, helping to predict the clinical outcome and optimizing patient management. Kidney transplantation may be the only treatment option available for a subset of SRC patients who develop end-stage renal failure despite aggressive angiotensin-converting enzyme inhibitor therapy. However, the posttransplant outcome for SSc patients is currently suboptimal compared to the general renal transplant population.
The Species Richness of Vascular Plants and Amphibia in Major Plant Communities in Temperate to Tropical Australia: Relationship with Annual Biomass Production
Authors: Specht R. L. , Tyler M. J.
Published: July 2010

Aerodynamic fluxes (frictional, thermal, evaporative) in the atmosphere as it flows over and through a plant community determine the Foliage Projective Covers and eco-morphological attributes of new leaves developed annually in overstorey and understorey strata. The number of leaves produced on vertical foliage shoots depends on available soil water and nutrients, also ambient temperature, during this short growth season. Stem density (number of stems per hectare) and species richness (number of species per hectare) in the overstorey of major Floristic Groups are correlated with annual shoot growth (ASG, t ) in that stratum. Species richness in the overstorey increases in the climatic gradient from the arid to the humid zone as well as with increasing air temperatures (about C) from temperate to tropical Australia. Species richness in the understorey is highest in plant communities in temperate Australia, decreasing in the temperature gradient towards the tropics. As with other major plant and animal groups within an ecosystem, the species richness of Amphibia is correlated with the amount of solar energy fixed (per annum) by the major plant formation in the region—a photosynthetic potential determined by the foliage shoots (ASG, t ) produced annually in the overstorey.
A New Algorithm for the Available Transfer Capability Determination
Authors: Busan Stendley , Othman Muhammad Murtadha , Musirin Ismail , Mohamed Azah , Hussain Aini
Published: July 2010

This paper presents a fast and accurate method to determine the available transfer capability. Ralston′s method is used to predict the two trajectory points of voltage magnitude, power flow, and maximum generator rotor angle difference. Then, the cubic spline interpolation technique is used to accurately trace theP-V, P-S,orP-Δδcurves between two points of trajectory. TheP-V, P-SandP-Δδcurves represent as the variations of voltage magnitude, power, flow and maximum generator rotor angle difference due to the increase of power transfer. The actual available transfer capability value is determined at the intersection point between the curve and the constraints limit. The effectiveness of the proposed method is verified by referring to the results of ATC for a case study of 2737‐Polish system and 39‐New England bus system. The proposed method gives satisfactorily accurate and fast computation of ATC as compared to recursive AC power flow method.
Coupling among Electroencephalogram Gamma Signals on a Short Time Scale
Authors: McAssey Michael P. , Hsieh Fushing , Smith Anne C.
Published: July 2010

An important goal in neuroscience is to identify instances when EEG signals are coupled. We employ a method to measure the coupling strength between gamma signals (40–100 Hz) on a short time scale as the maximum cross-correlation over a range of time lags within a sliding variable-width window. Instances of coupling states among several signals are also identified, using a mixed multivariate beta distribution to model coupling strength across multiple gamma signals with reference to a common base signal. We first apply our variable-window method to simulated signals and compare its performance to a fixed-window approach. We then focus on gamma signals recorded in two regions of the rat hippocampus. Our results indicate that this may be a useful method for mapping coupling patterns among signals in EEG datasets.
Phase I/II Study of Oncolytic HSVGM-CSF in Combination with Radiotherapy and Cisplatin in Untreated Stage III/IV Squamous Cell Cancer of the Head and Neck
Authors: Harrington Kevin J. , Hingorani Mohan , Tanay Mary Anne , Hickey Jennifer , Bhide Shreerang A. , Clarke Peter M. , Renouf Louise C. , Thway Khin , Sibtain Amen , McNeish Iain A. , Newbold Kate L. , Goldsweig Howard , Coffin Robert , Nutting Christopher M.
Published: July 2010

Purpose: This study sought to define the recommended dose of JS1/34.5-/47-/GM-CSF, an oncolytic herpes simplex type-1 virus (HSV-1) encoding human granulocyte-macrophage colony-stimulating factor (GM-CSF), for future studies in combination with chemoradiotherapy in patients with squamous cell cancer of the head and neck (SCCHN).

Experimental Design: Patients with stage III/IVA/IVB SCCHN received chemoradiotherapy (70 Gy/35 fractions with concomitant cisplatin 100 mg/m2 on days 1, 22, and 43) and dose-escalating (106, 106, 106, 106 pfu/mL for cohort 1; 106, 107, 107, 107 for cohort 2; 106, 108, 108, 108 for cohort 3) JS1/34.5-/47-/GM-CSF by intratumoral injection on days 1, 22, 43, and 64. Patients underwent neck dissection 6 to 10 weeks later. Primary end points were safety and recommended dose/schedule for future study. Secondary end points included antitumor activity (radiologic, pathologic). Relapse rates and survival were also monitored.

Results: Seventeen patients were treated without delays to chemoradiotherapy or dose-limiting toxicity. Fourteen patients (82.3%) showed tumor response by Response Evaluation Criteria in Solid Tumors, and pathologic complete remission was confirmed in 93% of patients at neck dissection. HSV was detected in injected and adjacent uninjected tumors at levels higher than the input dose, indicating viral replication. All patients were seropositive at the end of treatment. No patient developed locoregional recurrence, and disease-specific survival was 82.4% at a median follow-up of 29 months (range, 19-40 months).

Conclusions: JS1/34.5-/47-/GM-CSF combined with cisplatin-based chemoradiotherapy is well tolerated in patients with SCCHN. The recommended phase II dose is 106, 108, 108, 108. Locoregional control was achieved in all patients, with a 76.5% relapse-free rate so far. Further study of this approach is warranted in locally advanced SCCHN. Clin Cancer Res; 16(15); 4005–15. ©2010 AACR.
Epithelial Membrane Protein-2 Is a Novel Therapeutic Target in Ovarian Cancer
Authors: Fu Maoyong , Maresh Erin L. , Soslow Robert A. , Alavi Mohammad , Mah Vei , Zhou Qin , Iasonos Alexia , Goodglick Lee , Gordon Lynn K. , Braun Jonathan , Wadehra Madhuri
Published: July 2010

Purpose: The tetraspan protein epithelial membrane protein-2 (EMP2) has been shown to regulate the surface display and signaling from select integrin pairs, and it was recently identified as a prognostic biomarker in human endometrial cancer. In this study, we assessed the role of EMP2 in human ovarian cancer.

Experimental Design: We examined the expression of EMP2 within a population of women with ovarian cancer using tissue microarray assay technology. We evaluated the efficacy of EMP2-directed antibody therapy using a fully human recombinant bivalent antibody fragment (diabody) in vitro and ovarian cancer xenograft models in vivo.

Results: EMP2 was found to be highly expressed in >70% of serous and endometrioid ovarian tumors compared with nonmalignant ovarian epithelium using a human ovarian cancer tissue microarray. Using anti-EMP2 diabody, we evaluated the in vitro response of nine human ovarian cancer cell lines with detectable EMP2 expression. Treatment of human ovarian cancer cell lines with anti-EMP2 diabodies induced cell death and retarded cell growth, and these response rates correlated with cellular EMP2 expression. We next assessed the effects of anti-EMP2 diabodies in mice bearing xenografts from the ovarian endometrioid carcinoma cell line OVCAR5. Anti-EMP2 diabodies significantly suppressed tumor growth and induced cell death in OVCAR5 xenografts.

Conclusions: These findings indicate that EMP2 is expressed in the majority of ovarian tumors and may be a feasible target in vivo. Clin Cancer Res; 16(15); 3954–63. ©2010 AACR.
White Tea Extract Induces Apoptosis in Non–Small Cell Lung Cancer Cells: the Role of Peroxisome Proliferator-Activated Receptor-γ and 15-Lipoxygenases
Authors: Mao Jenny T. , Nie Wen-Xian , Tsu I-Hsien , Jin Yu-Sheng , Rao Jian Yu , Lu Qing-Yi , Zhang Zuo-Feng , Go Vay Liang W. , Serio Kenneth J.
Published: July 2010

Emerging preclinical data suggests that tea possess anticarcinogenic and antimutagenic properties. We therefore hypothesize that white tea extract (WTE) is capable of favorably modulating apoptosis, a mechanism associated with lung tumorigenesis. We examined the effects of physiologically relevant doses of WTE on the induction of apoptosis in non–small cell lung cancer cell lines A549 (adenocarcinoma) and H520 (squamous cell carcinoma) cells. We further characterized the molecular mechanisms responsible for WTE-induced apoptosis, including the induction of peroxisome proliferator-activated receptor-γ (PPAR-γ) and the 15-lipoxygenase (15-LOX) signaling pathways. We found that WTE was effective in inducing apoptosis in both A549 and H520 cells, and inhibition of PPAR-γ with GW9662 partially reversed WTE-induced apoptosis. We further show that WTE increased PPAR-γ activation and mRNA expression, concomitantly increased 15(S)-hydroxy-eicosatetraenoic acid release, and upregulated 15-LOX-1 and 15-LOX-2 mRNA expression by A549 cells. Inhibition of 15-LOX with nordihydroguaiaretic acid (NGDA), as well as caffeic acid, abrogated WTE-induced PPAR-γ activation and upregulation of PPAR-γ mRNA expression in A549 cells. WTE also induced cyclin-dependent kinase inhibitor 1A mRNA expression and activated caspase-3. Inhibition of caspase-3 abrogated WTE-induced apoptosis. Our findings indicate that WTE is capable of inducing apoptosis in non–small cell lung cancer cell lines. The induction of apoptosis seems to be mediated, in part, through the upregulation of the PPAR-γ and 15-LOX signaling pathways, with enhanced activation of caspase-3. Our findings support the future investigation of WTE as an antineoplastic and chemopreventive agent for lung cancer. Cancer Prev Res; 3(9); 1132–40. ©2010 AACR.
Suppression of S-Phase Kinase-Associated Protein 2 Induces Apoptosis and Inhibits Tumor Growth in Human Laryngeal Cancer
Authors: Liu Jiangtao , Tan Lijun , Li Huijun , Wang Qiwei , Ji Wenyue
Published: July 2010

S-phase kinase-associated protein 2 (Skp2) is related to cellular proliferation and differentiation in laryngeal carcinoma. This study aimed to investigate the effect of Skp-2 suppression on p27 expression, cellular proliferation, apoptosis, and tumor growth in laryngeal squamous cell carcinoma. Skp2 was stably suppressed in Hep2 laryngeal carcinoma cells by lentivirus siRNA technology and Hep2-siRNA was then inoculated into nude mice. The siRNA-induced suppression of Skp2 increased p27 expression, decreased cellular proliferation, and increased apoptosis in human laryngeal carcinoma cells and tumors, indicating that Skp2 is a viable target in the gene therapy treatment of human laryngeal carcinoma.
Pre-Operative Intravenous Dexamethasone Prevents Auditory Threshold Shift in a Guinea Pig Model of Cochlear Implantation
Authors: Connolly Timothy M. , Eastwood Hayden , Kel Gordana , Lisnichuk Halina , Richardson Rachael , O’Leary Stephen
Published: July 2010

Aim: To protect hearing during cochlear implantation with systemic administration of dexamethasone. Methods: Seventeen normal-hearing guinea pigs were randomly allocated to receive an intravenous injection of either normal saline (control), low- (0.2 mg/kg) or high- (2 mg/kg) dose dexamethasone 60 min prior to cochlear implantation. Auditory brainstem response (ABR) threshold shifts (2–32 kHz) were estimated between pre- and 4-week-postoperative levels. Results: ABR threshold shifts (8–32 kHz) observed in control and low-dose steroid groups were significantly reduced in the high-dose steroid group. Conclusions: A single, high-dose injection of intravenous dexamethasone protected hearing during cochlear implantation.
The Actions of Dopamine Receptors in the Guinea Pig Cochlea
Authors: Garrett Andrew R. , Robertson Donald , Sellick Peter M. , Mulders Wilhelmina H.A.M.
Published: July 2010

Dopamine, a major lateral olivocochlear efferent neurotransmitter, exerts both excitatory and inhibitory effects on the central nervous system depending on the receptor involved. We investigated the effects of different dopamine receptors on the cochlea by perilymphatic perfusion with D1/5, D2 and D3 receptor agonists and antagonists and recording neural and hair cell responses (compound action potential – CAP; summating potential – SP) before, during and after perfusions. The D1/5 agonist resulted in marked suppression of CAP amplitudes whilst leaving SP amplitudes unchanged, suggesting an inhibitory action of these receptors on afferent dendrites. The D1/5 antagonist had little or no effect, suggesting that there is no influence of tonic dopamine release on these receptors. In contrast, perfusing a D2 receptor antagonist resulted in marked suppression of CAP suggesting an excitatory action of the receptors and a strong influence of tonic dopamine release on the D2 receptors. The D2 agonist had little effect, implying that tonic dopamine release is maximally activating this class of dopamine receptors. D2 antagonists resulted in reduction of SP, cochlear microphonic and distortion product otoacoustic emission amplitudes, suggesting that D2 receptor action is not confined to afferent dendrites. Perfusion with D3 agonists and antagonists had no effect.
The Effect of Radial Velocity Gridding Artifacts on Variationally Retrieved Vertical Velocities
Authors: Collis Scott , Protat Alain , Chung Kao-Shen
Published: July 2010

This article investigates the source and impact of artifacts produced by ordered linear interpolation techniques on variationally retrieved updraft intensities. Qualitative reasoning for the generation of periodic perturbations in gridded products is presented, and a simple analytical investigation into the impact of gridding artifacts on updraft retrieval is carried out. By projecting a nonconvergent flow typical of Darwin, Australia, onto the viewing geometry of a scanning radar, a numerical assessment of the impact of gridding artifacts is carried out. A simple enhancement to ordered linear interpolation, mixed-order linear interpolation, is proposed to reduce gridding artifacts. Radial velocity grids produced using both techniques are used to investigate the generation of spurious updrafts, with the simple ordered linear interpolation technique producing erroneous updrafts on the order of 2 m s−1. To investigate the impact on vertical velocities retrieved from a real weather event, radar-derived measurements taken during the active monsoon phase of Tropical Warm Pool International Cloud Experiment are gridded using both techniques, and vertical velocities are retrieved and contrasted.