bluuebunny/crossref_metadata_2025 huggingface dataset:
μ-Opioid modulation in the rostral solitary nucleus and reticular formation alters taste reactivity: evidence for a suppressive effect on consummatory behavior
Authors: Kinzeler Nicole R. , Travers Susan P.
Published: June 2011

The neural control of feeding involves many neuromodulators, including the endogenous opioids that bind μ-opioid receptors (MORs). Injections of the MOR agonist, Damgo, into limbic and hypothalamic forebrain sites increase intake, particularly of palatable foods. Indeed, forebrain Damgo injections increase sucrose-elicited licking but reduce aversive responding (gaping) to quinine, suggesting that MOR activation may enhance taste palatability. A μ-opioid influence on taste reactivity has not been assessed in the brain stem. However, MORs are present in the first-order taste relay, the rostral nucleus of the solitary tract (rNST), and in the immediately subjacent reticular formation (RF), a region known to be essential for consummatory responses. Thus, to evaluate the consequences of rNST/dorsal RF Damgo in this region, we implanted rats with intraoral cannulas, electromyographic electrodes, and brain cannulas aimed at the ventral border of the rNST. Licking and gaping elicited with sucrose, water, and quinine were assessed before and after intramedullary Damgo and saline infusions. Damgo slowed the rate, increased the amplitude, and decreased the size of fluid-induced lick and gape bouts. In addition, the neutral stimulus water, which typically elicits licks, began to evoke gapes. Thus, the current results demonstrate that μ-opioid activation in the rNST/dorsal RF exerts complex effects on oromotor responding that contrast with forebrain effects and are more indicative of a suppressive, rather than a facilitatory effect on ingestion.
Neurokinin 3 receptor forms a complex with acetylated histone H3 and H4 in hypothalamic neurons following hyperosmotic challenge
Authors: Flynn Francis W. , Jensen Dane D. , Thakar Amit , Xu Xihui , Flynn Steven W. , Zhang Zhaojie
Published: June 2011

The neurokinin 3 receptor (NK3R) is a G protein-coupled receptor that is expressed in brain and is highly expressed by magnocellular vasopressinergic neurons in both the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus. Hyperosmolarity causes a ligand-mediated internalization of NK3Rs to the cytoplasm and to the nuclei of vasopressinergic PVN neurons. This receptor activation-dependent pathway is presumed to be a means to directly transmit synaptic signals from the cell membrane to the nucleus. The present study evaluated in vivo the subnuclear domains that associate with NK3R. Rats were administered 2 M NaCl (intragastric) or no intragastric load, and 40 min later, the PVN was dissected and nuclei were isolated. Using double-immuno-transmission electron microscopy (TEM), we show that, compared with controls, hyperosmolarity causes a significant increase in NK3R Immunogold beads in the nucleus of PVN neurons. Furthermore, NK3R spatially colocalized with histone H4 and with highly acetylated H4 in nuclei isolated from the PVN of rats administered 2 M NaCl, but not in nuclei from control rats. Next, coimmunoprecipitation experiments showed that acetylated H4, as well as acetylated H3, were pulled down with NK3R in the PVN nuclear enriched fraction from rats treated with 2 M NaCl, but not from control rats. In response to hyperosmolarity, NK3R is transported to the nucleus of PVN neurons and associates with transcriptionally active chromatin, where it may influence the transcription of genes.
Attenuated renal vascular responses to acute angiotensin II infusion in smooth muscle-specific Na+/Ca2+exchanger knockout mice
Authors: Zhao Di , Zhang Jin , Blaustein Mordecai P. , Navar L. Gabriel
Published: June 2011

Recent studies in smooth muscle-specific Na+/Ca2+exchanger-1 knockout (NCX1sm−/−) mice reveal reduced arterial pressure and impaired myogenic responses compared with heterozygous littermates. In this study, we determined renal function in male anesthetized NCX1sm−/−mice and NCX1 heterozygous (NCX1+/−) littermates before and during acute ANG II infusions. Systolic blood pressure in awake mice was lower in NCX1sm−/−mice compared with NCX1+/−mice (119 ± 4 vs. 131 ± 3 mmHg, P < 0.05). Acute ANG II infusions (5 ng·min−1·g−1body wt) increased mean arterial pressure in anesthetized NCX1+/−(109 ± 2 to 134 ± 3 mmHg, P < 0.001, n = 8) and NCX1sm−/−(101 ± 8 to 129 ± 8 mmHg, P < 0.01, n = 6) mice to a similar extent (Δ25 ± 1 vs. Δ28 ± 4 mmHg, P > 0.05). In response to ANG II infusions, PAH clearance (CPAH) decreased from 1.39 ± 0.27 to 0.98 ± 0.22 ml·min−1·g−1( P < 0.05) and glomerular filtration rate (GFR) was reduced from 0.50 ± 0.09 to 0.32 ± 0.06 ml·min−1·g−1( P < 0.05) in NCX1+/−mice. In contrast, the NCX1sm−/−did not exhibit significant reductions in either CPAH(1.16 ± 0.30 to 1.22 ± 0.34 ml·min−1·g−1, P > 0.05) or GFR (0.48 ± 0.08 to 0.41 ± 0.05 ml·min−1·g−1, P > 0.05) during acute ANG II infusions. Using flometry to measure renal blood flow continuously, NCX1sm−/−mice had significantly attenuated responses to ANG II infusions (−34.2 ± 3.9%, P < 0.05) compared with those in NCX1+/−mice (−48 ± 2%) or in wild-type mice (−69 ± 7%). These data indicate that renal vascular responses to ANG II are attenuated in NCX1sm−/−mice compared with NCX1+/−mice and that NCX1 contributes to the renal vasoconstriction response to acute ANG II infusions.
Mesenteric lymph from rats with trauma-hemorrhagic shock causes abnormal cardiac myocyte function and induces myocardial contractile dysfunction
Authors: Sambol Justin T. , Lee Marlon A. , Jiang Mingshan , Dosi Garima , Dong Wei , Deitch Edwin A. , Yatani Atsuko
Published: June 2011

Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30–35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1–2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca2+ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/d tmax) were decreased and inotropic response to Ca2+ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction.
Bronchoconstriction in nonhuman primates: a species comparison
Authors: Seehase S. , Schlepütz M. , Switalla S. , Mätz-Rensing K. , Kaup F. J. , Zöller M. , Schlumbohm C. , Fuchs E. , Lauenstein H.-D. , Winkler C. , Kuehl A. R. , Uhlig S. , Braun A. , Sewald K. , Martin C.
Published: June 2011

Bronchoconstriction is a characteristic symptom of various chronic obstructive respiratory diseases such as chronic obstructive pulmonary disease and asthma. Precision-cut lung slices (PCLS) are a suitable ex vivo model to study physiological mechanisms of bronchoconstriction in different species. In the present study, we established an ex vivo model of bronchoconstriction in nonhuman primates (NHPs). PCLS prepared from common marmosets, cynomolgus macaques, rhesus macaques, and anubis baboons were stimulated with increasing concentrations of representative bronchoconstrictors: methacholine, histamine, serotonin, leukotriene D4 (LTD4), U46619, and endothelin-1. Alterations in the airway caliber were measured and compared with previously published data from rodents, guinea pigs, and humans. Methacholine induced maximal airway constriction, varying between 74 and 88% in all NHP species, whereas serotonin was ineffective. Histamine induced maximal bronchoconstriction of 77 to 90% in rhesus macaques, cynomolgus macaques, and baboons and a lesser constriction of 53% in marmosets. LTD4 was ineffective in marmosets and rhesus macaques but induced a maximum constriction of 44 to 49% in cynomolgus macaques and baboons. U46619 and endothelin-1 caused airway constriction in all NHP species, with maximum constrictions of 65 to 91% and 70 to 81%, respectively. In conclusion, PCLS from NHPs represent a valuable ex vivo model for studying bronchoconstriction. All NHPs respond to mediators relevant to human airway disorders such as methacholine, histamine, U46619, and endothelin-1 and are insensitive to the rodent mast cell product serotonin. Only PCLS from cynomolgus macaques and baboons, however, responded also to leukotrienes, suggesting that among all compared species, these two NHPs resemble the human airway mechanisms best.
Nucleus accumbens shell, but not core, tracks motivational value of salt
Authors: Loriaux Amy L. , Roitman Jamie D. , Roitman Mitchell F.
Published: June 2011

To appropriately respond to an affective stimulus, we must be able to track its value across changes in both the external and internal environment. The nucleus accumbens (NAc) is a critical component of reward circuitry, but recent work suggests that the NAc encodes aversion as well as reward. It remains unknown whether differential NAc activity reflects flexible changes in stimulus value when it is altered due to a change in physiological state. We measured the activity of individual NAc neurons when rats were given intraoral infusions of a hypertonic salt solution (0.45 M NaCl) across multiple sessions in which motivational state was manipulated. This normally nonpreferred taste was made rewarding via sodium depletion, which resulted in a strong motivation to seek out and consume salt. Recordings were made in three conditions: while sodium replete (REP), during acute sodium depletion (DEP), and following replenishment of salt to normal sodium balance (POST). We found that NAc neurons in the shell and core subregions responded differently across the three conditions. In the shell, we observed overall increases in NAc activity when the salt solution was nonpreferred (REP) but decreases when the salt solution was preferred (DEP). In the core, overall activity was significantly altered only after sodium balance was restored (POST). The results lend further support to the selective encoding of affective stimuli by the NAc and suggest that NAc shell is particularly involved in flexibly encoding stimulus value based on motivational state.
Smooth changes in the EMG patterns during gait transitions under body weight unloading
Authors: Labini Francesca Sylos , Ivanenko Yuri P. , Cappellini Germana , Gravano Silvio , Lacquaniti Francesco
Published: June 2011

During gradual speed changes, humans exhibit a sudden discontinuous switch from walking to running at a specific speed, and it has been suggested that different gaits may be associated with different functioning of neuronal networks. In this study we recorded the EMG activity of leg muscles at slow increments and decrements in treadmill belt speed and at different levels of body weight unloading. In contrast to normal walking at 1 g, at lower levels of simulated gravity (<0.4 g) the transition between walking and running was generally gradual, without systematic abrupt changes in either intensity or timing of EMG patterns. This phenomenon depended to a limited extent on the gravity simulation technique, although the exact level of the appearance of smooth transitions (0.4–0.6 g) tended to be lower for the vertical than for the tilted body weight support system. Furthermore, simulations performed with a half-center oscillator neuromechanical model showed that the abruptness of motor patterns at gait transitions at 1 g could be predicted from the distinct parameters anchored already in the normal range of walking and running speeds, whereas at low gravity levels the parameters of the model were similar for the two human gaits. A lack of discontinuous changes in the pattern of speed-dependent locomotor characteristics in a hypogravity environment is consistent with the idea of a continuous shift in the state of a given set of central pattern generators, rather than the activation of a separate set of central pattern generators for each distinct gait.
Effects of persistent inward currents, accommodation, and adaptation on motor unit behavior: a simulation study
Authors: Revill Ann L. , Fuglevand Andrew J.
Published: June 2011

Motor neurons are often assumed to generate spikes in proportion to the excitatory synaptic input received. There are, however, many intrinsic properties of motor neurons that might affect this relationship, such as persistent inward currents (PICs), spike-threshold accommodation, or spike-frequency adaptation. These nonlinear properties have been investigated in reduced animal preparation but have not been well studied during natural motor behaviors because of the difficulty in characterizing synaptic input in intact animals. Therefore, we studied the influence of each of these intrinsic properties on spiking responses and muscle force using a population model of motor units that simulates voluntary contractions in human subjects. In particular, we focused on the difference in firing rate of low-threshold motor units when higher threshold motor units were recruited and subsequently derecruited, referred to as ΔF. Others have used ΔF to evaluate the extent of PIC activation during voluntary behavior. Our results showed that positive ΔF values could arise when any one of these nonlinear properties was included in the simulations. Therefore, a positive ΔF should not be considered as exclusive evidence for PIC activation. Furthermore, by systematically varying contraction duration and speed in our simulations, we identified a means that might be used experimentally to distinguish among PICs, accommodation, and adaptation as contributors to ΔF.
Slow oscillating population activity in developing cortical networks: models and experimental results
Authors: Baltz Thomas , Herzog Andreas , Voigt Thomas
Published: June 2011

During early development neuronal networks express slow oscillating synchronized activity. The activity can be driven by several, not necessarily mutually exclusive, mechanisms. Each mechanism might have distinctive consequences for the phenomenology, formation, or sustainment of the early activity pattern. Here we study the emergence of the oscillatory activity in three computational models and multisite extracellular recordings that we obtained from developing cortical networks in vitro. The modeled networks consist of leaky integrate-and-fire neurons with adaptation coupled via depressing synapses, which were driven by neurons that are intrinsically bursting, intrinsically random spiking, or driven by spontaneous synaptic activity. The activity of model networks driven by intrinsically bursting cells best matched the phenomenology of 1-wk-old cultures, in which early oscillatory activity has just begun. Intrinsically bursting neurons were present in cortical cultures, but we found them only in those cultures that were younger than 3 wk in vitro. On the other hand, synaptically dependent random spiking was highest after 3 wk in vitro. In conclusion, model networks driven by intrinsically bursting cells show a good approximation of the emergent recurrent population activity in young networks, whereas the activity of more mature networks seems to be better explained by spontaneous synaptic activity. Moreover, similar to previous experimental observations, distributed stimulation in the model was more effective in suppressing population bursts than repeated stimulation of the same neurons. This observation can be explained by an effective depression of a larger fraction of synapses by distributed stimulation.
Comparative posthearing development of inhibitory inputs to the lateral superior olive in gerbils and mice
Authors: Walcher Jan , Hassfurth Benjamin , Grothe Benedikt , Koch Ursula
Published: June 2011

Interaural intensity differences are analyzed in neurons of the lateral superior olive (LSO) by integration of an inhibitory input from the medial nucleus of the trapezoid body (MNTB), activated by sound from the contralateral ear, with an excitatory input from the ipsilateral cochlear nucleus. The early postnatal refinement of this inhibitory MNTB-LSO projection along the tonotopic axis of the LSO has been extensively studied. However, little is known to what extent physiological changes at these inputs also occur after the onset of sound-evoked activity. Using whole-cell patch-clamp recordings of LSO neurons in acute brain stem slices, we analyzed the developmental changes of inhibitory synaptic currents evoked by MNTB fiber stimulation occurring after hearing onset. We compared these results in gerbils and mice, two species frequently used in auditory research. Our data show that neither the number of presumed input fibers nor the conductance of single fibers significantly changed after hearing onset. Also the amplitude of miniature inhibitory currents remained constant during this developmental period. In contrast, the kinetics of inhibitory synaptic currents greatly accelerated after hearing onset. We conclude that tonotopic refinement of inhibitory projections to the LSO is largely completed before the onset of hearing, whereas acceleration of synaptic kinetics occurs to a large part after hearing onset and might thus be dependent on proper auditory experience. Surprisingly, inhibitory input characteristics, as well as basic membrane properties of LSO neurons, were rather similar in gerbils and mice.
Global Stability of a Virus Infection Model with Time Delay and Absorption
Authors: Tian Xiaohong , Xu Rui
Published: June 2011

In this paper, a virus infection model with time delay and absorption is studied. By analyzing the corresponding characteristic equations, the local stability of each of feasible equilibria of the model is established. By using comparison arguments, it is shown that the infection free equilibrium is globally asymptotically stable when the basic reproduction ratio is less than unity. When the basic reproduction ratio is greater than unity, sufficient conditions are derived for the global stability of the virus‐infected equilibrium. Numerical simulations are carried out to illustrate the theoretical results.
Weingarten and Linear Weingarten Type Tubular Surfaces in E3
Authors: Tunçer Yılmaz , Yoon Dae Won , Karacan Murat Kemal
Published: June 2011

We study tubular surfaces in Euclidean 3‐space satisfying some equations in terms of the Gaussian curvature, the mean curvature, the second Gaussian curvature, and the second mean curvature. This paper is a completion of Weingarten and linear Weingarten tubular surfaces in Euclidean 3‐space.
A Phase IIIb, Multicentre, Randomised, Parallel-Group, Placebo-Controlled, Double-Blind Study to Investigate the Efficacy and Safety of OROS Hydromorphone in Subjects with Moderate-to-Severe Chronic Pain Induced by Osteoarthritis of the Hip or the Knee
Authors: Vojtaššák Jozef , Vojtaššák Jozef , Jacobs Adam , Rynn Leonie , Waechter Sandra , Richarz Ute
Published: June 2011

Background. Opioid analgesics are included in treatment guidelines for the symptomatic management of osteoarthritis (OA). Starting with a low dose of opioid and slowly titrating to a higher dose may help avoid intolerable side effects. Methods. Subjects aged ≥40 years, with moderate to severe pain induced by OA of the hip or knee not adequately controlled by previous non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol treatment, were enrolled. Subjects received OROS hydromorphone 4 mg or placebo once-daily. The dose was titrated every 3-4 days in case of unsatisfactory pain control during the 4-week titration phase. A 12 week maintenance phase followed. The primary efficacy endpoint was the change in “pain on average” measured on the Brief Pain Inventory (BPI) scale from baseline to the end of the maintenance phase. Results. 139 subjects received OROS hydromorphone and 149 subjects received placebo. All efficacy endpoints showed similar improvements from baseline to end of study in the 2 groups. The safety results were consistent with the safety profile of OROS hydromorphone. Conclusion.The study did not meet the primary endpoint; although many subjects' pain was not adequately controlled at inclusion, their pain may have improved with continued paracetamol or NSAID treatment.
Assessment of Protective Effect of Some Modern Agrochemicals against Ozone-Induced Stress in Sensitive Clover and Tobacco Cultivars
Authors: Blum Oleg , Didyk Nataliya , Pavluchenko Nataliya , Godzik Barbara
Published: June 2011

Some modern agrochemicals with antioxidant potential were tested for their protective effect against ozone injury using clover and tobacco ozone-sensitive cultivars as model plants subjected to ambient ozone at two sites (Kyiv city in Ukraine and Szarów village in Poland). All used agrochemicals showed partial protective effects against ozone injury on clover and tobacco. Conducted studies confirmed the effectiveness of modern fungicides belonging to strobilurin group as protectants of sensitive crops against ozone damage. The effectiveness of new growth regulators “Emistym C” and “Agrostymulin” was showed for the first time. Out of the studied agrochemicals, fungicide “Strobi” and natural growth regulator “Emistym C” demonstrated the best protective effects. These agrochemicals present promise for further studies of their possible utilization for enhancement of ozone tolerance of sensitive crops.
Primary Meningeal Rhabdomyosarcoma
Authors: Palta Manisha , Riedel Richard F. , Vredenburgh James J. , Cummings Thomas J. , Green Scott , Chang Zheng , Kirkpatrick John P.
Published: June 2011

Primary meningeal rhabdomyosarcoma is a rare primary brain malignancy, with scant case reports. While most reports of primary intracranial rhabdomyosarcoma occur in pediatric patients, a handful of cases in adult patients have been reported in the medical literature. We report the case of a 44-year-old male who developed primary meningeal rhabdomyosarcoma. After developing episodes of right lower extremity weakness, word finding difficulty, and headaches, a brain magnetic resonance imaging (MRI) demonstrated a vertex lesion with radiographic appearance of a meningeal-derived tumor. Subtotal surgical resection was performed due to sagittal sinus invasion and initial pathology was interpreted as an anaplastic meningioma. Re-review of pathology demonstrated rhabdomyosarcoma negative for alveolar translocation t(2;13). Staging studies revealed no evidence of disseminated disease. He was treated with stereotactic radiotherapy with concurrent temozolamide to be followed by vincristine, actinomycin-D, and cyclophosphamide (VAC) systemic therapy.
Multiclass Sparse Bayesian Regression for fMRI-Based Prediction
Authors: Michel Vincent , Eger Evelyn , Keribin Christine , Thirion Bertrand
Published: June 2011

Inverse inferencehas recently become a popular approach for analyzing neuroimaging data, by quantifying the amount of information contained in brain images on perceptual, cognitive, and behavioral parameters. As it outlines brain regions that convey information for an accurate prediction of the parameter of interest, it allows to understand how the corresponding information is encoded in the brain. However, it relies on a prediction function that is plagued by the curse of dimensionality, as there are far more features (voxels) than samples (images), and dimension reduction is thus a mandatory step. We introduce in this paper a new model, calledMulticlass Sparse Bayesian Regression(MCBR), that, unlike classical alternatives, automatically adapts the amount of regularization to the available data. MCBR consists in grouping features into several classes and then regularizing each class differently in order to apply an adaptive and efficient regularization. We detail these framework and validate our algorithm on simulated and real neuroimaging data sets, showing that it performs better than reference methods while yielding interpretable clusters of features.
Evaluation of Biomarkers of NAFLD in a Cohort of Morbidly Obese Patients
Authors: Kälsch Julia , Bechmann Lars P. , Kälsch Hagen , Schlattjan Martin , Erhard Jochen , Gerken Guido , Canbay Ali
Published: June 2011

Hepatocyte apoptosis is a key event in nonalcoholic fatty liver disease (NAFLD), and serum apoptotic markers are emerging as surrogate markers for NAFLD. We studied the role of caspase-cleaved cytokeratin18 in the diagnosis of fibrosis in a cohort of 127 morbidly obese patients and also performed a review of the literature biomarkers of NAFLD and fibrosis. Here, we found that cleaved caspase 18 correlated with liver steatosis and liver injury as assessed by serum transaminase levels. Furthermore, hepatocyte apoptosis as assessed by cleaved CK18 and TUNEL staining correlated with the extent of fibrosis as assessed by Sirius Red staining and serum hyaluronic acid. These results underscore the important role of hepatocyte apoptosis in the pathogenesis of fibrosis in NAFLD, which led to the utilization of surrogate markers for apoptosis in the noninvasive diagnosis of NAFLD. We furthermore reviewed current literature of biomarkers of NAFLD and fibrosis.
Proteomic Characterization of Cerebrospinal Fluid from Ataxia-Telangiectasia (A-T) Patients Using a LC/MS-Based Label-Free Protein Quantification Technology
Authors: Dzieciatkowska Monika , Qi Guihong , You Jinsam , Bemis Kerry G. , Sahm Heather , Lederman Howard M. , Crawford Thomas O. , Gelbert Lawrence M. , Rothblum-Oviatt Cynthia , Wang Mu
Published: June 2011

Cerebrospinal fluid (CSF) has been used for biomarker discovery of neurodegenerative diseases in humans since biological changes in the brain can be seen in this biofluid. Inactivation of A-T-mutated protein (ATM), a multifunctional protein kinase, is responsible for A-T, yet biochemical studies have not succeeded in conclusively identifying the molecular mechanism(s) underlying the neurodegeneration seen in A-T patients or the proteins that can be used as biomarkers for neurologic assessment of A-T or as potential therapeutic targets. In this study, we applied a high-throughput LC/MS-based label-free protein quantification technology to quantitatively characterize the proteins in CSF samples in order to identify differentially expressed proteins that can serve as potential biomarker candidates for A-T. Among 204 identified CSF proteins with high peptide-identification confidence, thirteen showed significant protein expression changes. Bioinformatic analysis revealed that these 13 proteins are either involved in neurodegenerative disorders or cancer. Future molecular and functional characterization of these proteins would provide more insights into the potential therapeutic targets for the treatment of A-T and the biomarkers that can be used to monitor or predict A-T disease progression. Clinical validation studies are required before any of these proteins can be developed into clinically useful biomarkers.
Frontal Analysis Continuous Capillary Electrophoresis Study on the Interaction of an Amphiphilic Alternating Copolymer with Triton X-100
Authors: Hashidzume Akihito , Shimomachi Takuya , Sato Takahiro
Published: June 2011

The interaction of amphiphilic alternating copolymers of sodium maleate and dodecyl vinyl ether (Mal/C12) with a nonionic surfactant, Triton X-100 (TX), was investigated by frontal analysis continuous capillary electrophoresis (FACCE). The binding isotherms obtained from FACCE data were indicative of weak cooperative interaction for all the polymers examined. The cooperative interaction was also analyzed by the Hill model, and the results were compared with the previous results on the interaction of statistical copolymers of sodium 2-acrylamido-2-methylpropanesulfonate andN-dodecylmethacrylamide with TX.
Dynamic Analysis of a Nonlinear Timoshenko Equation
Authors: Esquivel-Avila Jorge Alfredo
Published: June 2011

We characterize the global and nonglobal solutions of the Timoshenko equation in a bounded
domain. We consider nonlinear dissipation and a nonlinear source term. We prove blowup of
solutions as well as convergence to the zero and nonzero equilibria, and we give rates of decay to the
zero equilibrium. In particular, we prove instability of the ground state. We show existence of global
solutions without a uniform bound in time for the equation with nonlinear damping. We define and
use a potential well and positive invariant sets.
Isolated Transverse Sacrum Fracture: A Case Report
Authors: Kavalci Cemil , Akdur Gökhan , Sayhan Mustafa Burak , Sogut Ozgur , Gökdemir Mehmet Tahir
Published: June 2011

Sacral fracture commonly results from high-energy trauma. Most insufficiency fractures of the sacrum are seen in women after the age of 70. Fractures of the sacrum are rare and generally combined with a concomitant pelvic fracture. Transverse sacral fractures are even less frequent which constitute only 3–5% of all sacral fractures. This type of fractures provide a diagnostic challenge. We report a unique case of isolated transverse fracture of sacrum in a young man sustained low-energy trauma. The patient presented to our emergency department after several hours of injury, and diagnosed by clinical features and roentgenogram findings.
Effect of Microwave Power on the Physical Properties of Carboxylic Acid-Coated Manganese-Ion-Doped Zinc Sulfide Nanoparticles
Authors: Bhattacharjee Baibaswata , Lu Chung-Hsin
Published: June 2011

Bright ZnS : Mn2+nanoparticles have been synthesized employing microwave irradiation technique and using zinc 2-ethylhexanoate as a novel zinc precursor. A series of samples is obtained by changing the microwave power (from 150 W to 500 W) to study its effect on the physical properties of the ZnS : Mn2+nanoparticles. The particle size increases with increasing microwave power for the samples synthesized in the microwave range of 150 W to 300 W. The decrease in particle size for higher microwave power (400 W and 500 W) can be described as an onset of the secondary nucleation due to the excess energy associated with the higher microwave power. The sample synthesized with microwave power of 300 W shows highest luminescence intensity suggesting increase in Mn2+luminescence center for the sample synthesized at 300 W, as supported by the quantity analysis results.
Asymptotic Formula for Oscillatory Solutions of Some Singular Nonlinear Differential Equation
Authors: Rachůnková Irena , Rachůnek Lukáš
Published: June 2011

Singular differential equation (p(t)u′) ′ = p(t)f(u) is investigated. Here
f
is Lipschitz continuous on ℝ and has at least two zeros 0 and L > 0
. The
function p
is continuous on [0,∞) and has a positive continuous derivative on
(0,∞) and p(0) = 0. An asymptotic formula for oscillatory solutions is
derived.
ADP-Ribosylarginine Hydrolase Regulates Cell Proliferation and Tumorigenesis
Authors: Kato Jiro , Zhu Jianfeng , Liu Chengyu , Stylianou Mario , Hoffmann Victoria , Lizak Martin J. , Glasgow Connie G. , Moss Joel
Published: June 2011

Protein ADP-ribosylation is a reversible posttranslational modification of uncertain significance in cancer. In this study, we evaluated the consequences for cancer susceptibility in the mouse of a genetic deletion of the enzyme responsible for removing mono-ADP–ribose moieties from arginines in cellular proteins. Specifically, we analyzed cancer susceptibility in animals lacking the ADP-ribosylarginine hydrolase (ARH1) that cleaves the ADP ribose–protein bond. ARH1−/− cells or ARH1−/− cells overexpressing an inactive mutant ARH1 protein (ARH1−/−+dm) had higher proliferation rates than either wild-type ARH1+/+ cells or ARH1−/− cells engineered to express the wild-type ARH1 enzyme. More significantly, ARH1−/− and ARH1+/− mice spontaneously developed lymphomas, adenocarcinomas, and metastases more frequently than wild-type ARH1+/+ mice. In ARH1+/− mice, we documented in all arising tumors mutation of the remaining wild-type allele (or loss of heterozygosity), illustrating the strict correlation that existed between tumor formation and absence of ARH1 gene function. Our findings show that proper control of protein ADP-ribosylation levels affected by ARH1 is essential for cancer suppression. Cancer Res; 71(15); 5327–35. ©2011 AACR.
Api6/AIM/Spα/CD5L Overexpression in Alveolar Type II Epithelial Cells Induces Spontaneous Lung Adenocarcinoma
Authors: Li Yuan , Qu Peng , Wu Lingyan , Li Beilin , Du Hong , Yan Cong
Published: June 2011

Chronic inflammation is an important contributor to the development of lung cancers, one of the most common malignancies worldwide, but the underlying molecular mechanisms of inflammation that specifically cue cancer risk remain poorly understood. Apoptosis inhibitor 6 (Api6, also known as AIM, Sp-α, and CD5L) is a downstream target gene of neutral lipids and peroxisome proliferator–activated receptor gamma in lung alveolar type II (AT II) epithelial cells. An association among increased expression of Api6 in certain settings of pathogenic lung inflammation in mice prompted us to hypothesize a possible role in cancer. Here, we report that Api6 promotes malignant transformation by limiting lung epithelial cell apoptosis and promoting immune escape. The specific function of Api6 in AT II cells was determined by using a doxycycline-inducible Api6 mouse model. Api6 overexpression inhibited apoptosis and activated oncogenic signaling in AT II lung epithelial cells, inducing emphysema and adenocarcinoma. In addition, Api6 overexpression in AT II cells increased the concentrations of proinflammatory cytokines/chemokines in bronchoalveolar lavage fluid and serum, promoting expansion of myeloid-derived suppressor cells (MDSC) in lung and blood but not in bone marrow or spleen. Lung MDSCs suppressed T-cell proliferation and activity in vitro and reduced levels of T cells in vivo following doxycycline treatment to activate Api6. Together, our findings establish that Api6 promotes lung tumorigenesis by blocking a mechanism of epithelial apoptosis that would normally support immunosurveillance. Cancer Res; 71(16); 5488–99. ©2011 AACR.
Discovery of a Small Molecule Targeting IRA2 Deletion in Budding Yeast and Neurofibromin Loss in Malignant Peripheral Nerve Sheath Tumor Cells
Authors: Wood Matthew , Rawe Melissa , Johansson Gunnar , Pang Shu , Soderquist Ryan S. , Patel Ami V. , Nelson Sandra , Seibel William , Ratner Nancy , Sanchez Yolanda
Published: June 2011

Malignant peripheral nerve sheath tumor (MPNST) is a life-threatening complication of neurofibromatosis type 1 (NF1). NF1 is caused by mutation in the gene encoding neurofibromin, a negative regulator of Ras signaling. There are no effective pharmacologic therapies for MPNST. To identify new therapeutic approaches targeting this dangerous malignancy, we developed assays in NF1+/+ and NF1−/− MPNST cell lines and in budding yeast lacking the NF1 homologue IRA2 (ira2Δ). Here, we describe UC1, a small molecule that targets NF1−/− cell lines and ira2Δ budding yeast. By using yeast genetics, we identified NAB3 as a high-copy suppressor of UC1 sensitivity. NAB3 encodes an RNA binding protein that associates with the C-terminal domain of RNA Pol II and plays a role in the termination of nonpolyadenylated RNA transcripts. Strains with deletion of IRA2 are sensitive to genetic inactivation of NAB3, suggesting an interaction between Ras signaling and Nab3-dependent transcript termination. This work identifies a lead compound and a possible target pathway for NF1-associated MPNST, and shows a novel model system approach to identify and validate target pathways for cancer cells in which NF1 loss drives tumor formation. Mol Cancer Ther; 10(9); 1740–50. ©2011 AACR.
EZH2 Promotes Malignant Phenotypes and Is a Predictor of Oral Cancer Development in Patients with Oral Leukoplakia
Authors: Cao Wei , Younis Rania H. , Li Jiang , Chen Haiyan , Xia Ronghui , Mao Li , Chen Wantao , Ren Hening
Published: June 2011

Oral leukoplakia (OL) is the most common premalignancy in the oral cavity. A small proportion of OLs progresses to oral squamous cell carcinoma (OSCC). To assess OSCC risk of OLs, we investigated the role of the transcriptional repressor enhancer of zeste homolog 2 (EZH2) in oral tumorigenesis and its clinical implication as an OSCC risk predictor. Immunohistochemistry was used to measure EZH2 expression in OLs from 76 patients, including 37 who later developed OSCC and 39 who did not. EZH2 expression was associated with clinicopathologic parameters and clinical outcomes. To determine the biological role of EZH2 in OL, EZH2 level was reduced using EZH2 siRNAs in Leuk-1 cells, its impact on cell cycle, anchorage-dependent/independent growth, and invasion was assessed. We observed strong EZH2 expression in 34 (45%), moderate expression in 26 (34%), and weak/no expression in 16 (21%) of the OLs. The higher EZH2 levels were strongly associated with dysplasia (P < 0.001) and OSCC development (P < 0.0001). Multivariate analysis indicated that EZH2 expression was the only independent factor for OSCC development (P < 0.0001). At 5 years after diagnosis, 80% of patients whose OLs expressed strong EZH2 developed OSCC whereas only 24% patients with moderate and none with weak/no EZH2 expression did so (P < 0.0001). In Leuk-1 cells, EZH2 downregulation resulted in G1 arrest; decreased invasion capability, decreased anchorage-independent growth; downregulation of cyclin D1 and upregulation of p15INK4B. Our data suggest that EZH2 plays an important role in OL malignant transformation and may be a biomarker in predicting OSCC development in patients with OLs. Cancer Prev Res; 4(11); 1816–24. ©2011 AACR.
Metabolic Syndrome and Risks of Colon and Rectal Cancer: The European Prospective Investigation into Cancer and Nutrition Study
Authors: Aleksandrova Krasimira , Boeing Heiner , Jenab Mazda , Bas Bueno-de-Mesquita H. , Jansen Eugene , van Duijnhoven Fränzel J.B. , Fedirko Veronika , Rinaldi Sabina , Romieu Isabelle , Riboli Elio , Romaguera Dora , Overvad Kim , Østergaard Jane Nautrup , Olsen Anja , Tjønneland Anne , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Morois Sophie , Masala Giovanna , Agnoli Claudia , Panico Salvatore , Tumino Rosario , Vineis Paolo , Kaaks Rudolf , Lukanova Annekatrin , Trichopoulou Antonia , Naska Androniki , Bamia Christina , Peeters Petra H. , Rodríguez Laudina , Buckland Genevieve , Sánchez María-José , Dorronsoro Miren , Huerta Jose-María , Barricarte Aurelio , Hallmans Göran , Palmqvist Richard , Khaw Kay-Tee , Wareham Nicholas , Allen Naomi E. , Tsilidis Konstantinos K , Pischon Tobias
Published: June 2011

Metabolic syndrome (MetS) is purportedly related to risk of developing colorectal cancer; however, the association of MetS, as defined according to recent international criteria, and colorectal cancer has not been yet evaluated. In particular, it remains unclear to what extent the MetS components individually account for such an association. We addressed these issues in a nested case–control study that included 1,093 incident cases matched (1:1) to controls by using incidence density sampling. Conditional logistic regression was used to estimate relative risks (RR) and 95% CIs. MetS was defined according to the criteria of the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATPIII), the International Diabetes Federation (IDF), and the 2009 harmonized definition. Among individual components, abdominal obesity (RR = 1.51; 95% CI: 1.16–1.96) was associated with colon cancer, whereas abnormal glucose metabolism was associated with both colon (RR = 2.05; 95% CI: 1.57–2.68) and rectal cancer (RR = 2.07; 95% CI: 1.45–2.96). MetS, as defined by each of the definitions, was similarly associated with colon cancer (e.g., RR = 1.91; 95% CI: 1.47–2.42 for MetS by NCEP/ATPIII), whereas MetS by NCEP/ATPIII, but not IDF or harmonized definition, was associated with rectal cancer (RR = 1.45; 95% CI: 1.02–2.06). Overall, these associations were stronger in women than in men. However, the association between MetS and colorectal

cancer was accounted for by abdominal obesity and abnormal glucose metabolism such that MetS did not provide risk information beyond these components (likelihood ratio test P = 0.10 for MetS by NCEP/ATPIII). These data suggest that simple assessment of abnormal glucose metabolism and/or abdominal obesity to identify individuals at colorectal cancer risk may have higher clinical utility than applying more complex MetS definitions. Cancer Prev Res; 4(11); 1873–83. ©2011 AACR.
Occurrence of Overactive Bladder in Patients with Benign Prostatic Hyperplasia in the Czech Republic
Authors: Hanuš T. , Zámečník L. , Doležal T. , Karmazínová Z.
Published: June 2011

Introduction: Bladder outlet obstruction (BOO) due to prostatic hyperplasia is often accompanied by overactive bladder (OAB) symptoms, which often disappear after specific BOO pharmacotherapy. The aim of this study was to map out the spectrum in BOO pharmacotherapy to find out the occurrence of OAB in this population and to find its treatment. Materials and Methods: Follow-up consists of a retrospective and a prospective part, which includes all the patient’s data related to the lower urinary tract symptoms in BOO and OAB. In all, 654 data record forms were distributed during the study and 98% of those were validated. Results: According to our observations, alpha-blockers were used most frequently at the beginning of BOO treatment (73%), followed by phytopharmaca (19.9%) and finally finasteride (5.5%). If the treatment is changed, the proportion of finasteride increases. Only a small number of patients with BOO and OAB are treated in combination with antimuscarinics. Conclusions: A combined therapy (alpha-blocker + antimuscarinics) is effective in a majority of men with infravesical obstruction and symptoms of OAB. However, OAB in our study was primarily underdiagnosed in almost 50% of all patients treated for LUTS.
Meeting the Nutritional Needs of the Low-Birth-Weight Infant
Authors: Ziegler Ekhard E.
Published: June 2011

Delivering adequate amounts of nutrients to premature infants at all times is challenging because the infant’s immature gastrointestinal tract is initially unable to accept feedings, necessitating the use of parenteral nutrition. In the past, inadequate amounts of nutrients have commonly been given to premature infants because the administration of nutrients was thought to be hazardous. Inadequate nutrient intakes have resulted in widespread postnatal growth restriction. Now that it is known that postnatal growth restriction is associated with poor neurocognitive development, efforts are made to increase nutrient intakes. In this review, nutrient requirements of premature infants that have been determined by the factorial and empirical methods are reviewed. Current good practices regarding parenteral nutrition are discussed, as are guidelines for the introduction and advancement of enteral feedings. Because of its trophic effects on the gastrointestinal tract and its anti-infectious effects, human milk is strongly preferred as the early feeding of choice for premature infants. Human milk also protects infants against necrotizing enterocolitis. Once full feeding is achieved, the challenge is to provide nutrients in amounts that support the infant’s growth like that of the fetus. In the case of the infant fed his/her mother’s milk or banked donor milk, nutrient fortification is necessary and is generally practiced. However, adequate intakes of protein are seldom achieved with routine fortification and methods of providing additional fortification are discussed.
Feeding Very-Low-Birth-Weight Infants: Our Aspirations versus the Reality in Practice
Authors: Corpeleijn Willemijn E. , Vermeulen Marijn J. , van den Akker Chris H. , van Goudoever Johannes B.
Published: June 2011

Recently, new guidelines for enteral feedings in premature infants were issued by the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition. Nevertheless, practice proves difficult to attain suggested intakes at all times, and occurrence of significant potential cumulative nutritional deficits ‘lies in wait’ in the neonatal intensive care unit. This review describes several aspects that are mandatory for optimizing nutritional intake in these vulnerable infants. These aspects range from optimal infrastructure to the initiation of parenteral nutrition with proper transition to enteral breast or formula feedings. Proper monitoring of nutritional tolerance includes serum biochemistry although proper specific markers are unknown and safety reference values are lacking. Although a lot of progress has been made through research during the last few decades, numerous questions still remain unanswered as to what would be the optimal quantity and quality of the various macronutrients. The inevitable suboptimal intake may, however, contribute significantly to the incidence of neonatal diseases, including impaired neurodevelopment. Therefore, it is pivotal that all hospital staff acknowledges that preterm birth is a nutritional emergency and that all must be done, both in clinical practice as well as in research, to reduce nutritional deficits.
Is Early Nutrition Related to Short-Term Health and Long-Term Outcome
Authors: Szajewska Hania , Makrides Maria
Published: June 2011

This paper summarizes the literature concerning the effects of administering (1) long-chain polyunsaturated fatty acids (LCPUFA), (2) probiotics and/or (3) prebiotics to preterm infants. Clinically relevant, short- and long-term efficacy outcomes, such as those related to a reduced risk of disease, as well as outcomes related to safety, were sought. MEDLINE and the Cochrane Library literature searches performed in September 2010 were limited to randomized controlled trials, their systematic reviews or meta-analyses. LCPUFA supplementation, particularly docosahexaenoic acid (DHA), of infant formula for preterm infants has consistently demonstrated better visual development of preterm infants compared with unsupplemented formulas. There is increasing evidence to suggest that LCPUFA supplementation for preterm infants is also related to improvements in more global measures of development, without any adverse effects. It is, however, important to note that the DHA doses tested in the infant formula interventions for preterm infants have been rather conservative. Newer studies comparing dietary DHA concentrations that match in utero accumulation rates with dietary DHA concentrations typical in the milk of women consuming little fish or in supplemented infant formulas demonstrate that these higher DHA doses are related to improvements in domains of cognitive development. Although further work is needed to better understand the optimal DHA requirements of preterm infants, it is clear that a dietary source of DHA is important to support neurodevelopment. To date, the most promising application of probiotics in preterm infants is the prevention of necrotizing enterocolitis by the administration of certain probiotics. Many other benefits of administering probiotics and/or prebiotics to preterm infants are, however, largely unproven. Efficacy and safety should be established for each probiotic and/or prebiotic product. Further research should specify strain-specific outcomes and determine optimal dosing schedules. Safety and long-term follow-up studies are of particular interest.