bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle
Authors: Carroll Chad C. , O'Connor Devin T. , Steinmeyer Robert , Del Mundo Jonathon D. , McMullan David R. , Whitt Jamie A. , Ramos Jahir E. , Gonzales Rayna J.
Published: May 2013

This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h ( P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein−1·min−1). COX-2 activity was elevated at 4 and 24 h after RE ( P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein−1·min−1). The protein level of COX-1 was not altered ( P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater ( P > 0.05) at 4 h and 5-fold greater ( P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.
Cortical distal nephron Cl−transport in volume homeostasis and blood pressure regulation
Authors: Wall Susan M. , Weinstein Alan M.
Published: May 2013

Renal intercalated cells mediate the secretion or absorption of Cl−and OH−/H+equivalents in the connecting segment (CNT) and cortical collecting duct (CCD). In so doing, they regulate acid-base balance, vascular volume, and blood pressure. Cl−absorption is either electrogenic and amiloride-sensitive or electroneutral and thiazide-sensitive. However, which Cl−transporter(s) are targeted by these diuretics is debated. While epithelial Na+channel (ENaC) does not transport Cl−, it modulates Cl−transport probably by generating a lumen-negative voltage, which drives Cl−flux across tight junctions. In addition, recent evidence indicates that ENaC inhibition increases electrogenic Cl−secretion via a type A intercalated cells. During ENaC blockade, Cl−is taken up across the basolateral membrane through the Na+-K+−2Cl−cotransporter (NKCC1) and then secreted across the apical membrane through a conductive pathway (a Cl−channel or an electrogenic exchanger). The mechanism of this apical Cl−secretion is unresolved. In contrast, thiazide diuretics inhibit electroneutral Cl−absorption mediated by a Na+-dependent Cl−/HCO3−exchanger. The relative contribution of the thiazide and the amiloride-sensitive components of Cl−absorption varies between studies and probably depends on the treatment model employed. Cl−absorption increases markedly with angiotensin and aldosterone administration, largely by upregulating the Na+-independent Cl−/HCO3−exchanger pendrin. In the absence of pendrin [ Slc26a4(−/−)or pendrin null mice], aldosterone-stimulated Cl−absorption is significantly reduced, which attenuates the pressor response to this steroid hormone. Pendrin also modulates aldosterone-induced changes in ENaC abundance and function through a kidney-specific mechanism that does not involve changes in the concentration of a circulating hormone. Instead, pendrin changes ENaC abundance and function, at least in part, by altering luminal HCO3−. This review summarizes mechanisms of Cl−transport in CNT and CCD and how these transporters contribute to the regulation of extracellular volume and blood pressure.
Progression of microalbuminuria in SHR is associated with lower expression of critical components of the apical endocytic machinery in the renal proximal tubule
Authors: Inoue Bruna H. , Arruda-Junior Daniel F. , Campos Luciene C. G. , Barreto Ana Luiza T. , Rodrigues Mariliza V. , Krieger José Eduardo , Girardi Adriana C. C.
Published: May 2013

Cumulative epidemiological evidence indicates that the presence of microalbuminuria predicts a higher frequency of cardiovascular events, peripheral disease, and mortality in essential hypertension. Microalbuminuria may arise from increased glomerular permeability and/or reduced proximal tubular reabsorption of albumin by receptor-mediated endocytosis. This study aimed to evaluate the temporal pattern of urinary protein excretion and to test the hypothesis that progression of microalbuminuria is associated with decreased protein expression of critical components of the endocytic apparatus in the renal proximal tubule of spontaneously hypertensive rats (SHR). We found that urinary albumin excretion increased progressively with blood pressure in SHR from 6 to 21 wk of age. In addition, SDS-PAGE analysis of urinary proteins showed that microalbuminuric SHR virtually excreted proteins of the size of albumin or smaller (<70 kDa), typical of tubular proteinuria. Moreover, the protein abundance of the endocytic receptors megalin and cubilin as well as of the chloride channel ClC-5 progressively decreased in the renal cortex of SHR from 6 to 21 wk of age. Expression of the vacuolar H+-ATPase B2 subunit was also reduced in the renal cortex of 21-wk-old compared with both 6- and 14-wk-old SHR. Collectively, our study suggests that enhanced urinary protein excretion, especially of albumin, may be due, at least in part, to lower expression of key components of the apical endocytic apparatus in the renal proximal tubule. Finally, one may speculate that dysfunction of the apical endocytic pathway in the renal proximal tubule may contribute to the development of microalbuminuria in essential hypertension.
Impaired EphA4 signaling leads to congenital hydronephrosis, renal injury, and hypertension
Authors: Sällström Johan , Peuckert Christiane , Gao Xiang , Larsson Erik , Nilsson Anders , Jensen Boye L. , Onozato Maristela L. , Persson A. Erik G. , Kullander Klas , Carlström Mattias
Published: May 2013

Experimental hydronephrosis induced by partial ureteral obstruction at 3 wk of age causes hypertension and renal impairment in adult rats and mice. Signaling by Ephrin receptors (Eph) and their ligands (ephrins) importantly regulates embryonic development. Genetically modified mice, where the cytoplasmic domain of the EphA4 receptor has been substituted by enhanced green fluorescent protein ( EphA4 gf/gf), develop spontaneous hydronephrosis and provide a model for further studies of the disorder. The present study aimed to determine if animals with congenital hydronephrosis develop hypertension and renal injuries, similar to that of experimental hydronephrosis. Ultrasound and Doppler techniques were used to visualize renal impairment in the adult mice. Telemetric blood pressure measurements were performed in EphA4 gf/gf mice and littermate controls ( EphA4 +/+) during normal (0.7% NaCl)- and high (4% NaCl)-sodium conditions. Renal excretion, renal plasma flow, and glomerular filtration were studied, and histology and morphology of the kidneys and ureters were performed. EphA4 gf/gf mice developed variable degrees of hydronephrosis that correlated with their blood pressure level. In contrast to EphA4 +/+, the EphA4 gf/gf mice displayed salt-sensitive hypertension, reduced urine concentrating ability, reduced renal plasma flow, and lower glomerular filtration rate. Kidneys from EphA4 gf/gf mice showed increased renal injuries, as evidenced by fibrosis, inflammation, and glomerular and tubular changes. In conclusion, congenital hydronephrosis causes hypertension and renal damage, similar to that observed in experimentally induced hydronephrosis. This study further reinforces the supposed causal link between hydronephrosis and later development of hypertension in humans.
The effect of diaphragm contraction on upper airway collapsibility
Authors: Hillman David R. , Walsh Jennifer H. , Maddison Kathleen J. , Platt Peter R. , Schwartz Alan R. , Eastwood Peter R.
Published: May 2013

Increasing lung volume increases upper airway patency and decreases airway resistance and collapsibility. The role of diaphragm contraction in producing these changes remains unclear. This study was undertaken to determine the effect of selective diaphragm contraction, induced by phrenic nerve stimulation, on upper airway collapsibility and the extent to which any observed change was attributable to lung volume-related changes in pressure gradients or to diaphragm descent-related mediastinal traction. Continuous bilateral transcutaneous cervical phrenic nerve stimulation (30 Hz) was applied to nine supine, anesthetized human subjects during transient decreases in airway pressure to levels sufficient to produce flow limitation when unstimulated. Stimulation was applied at two intensities (low and high) and its effects on lung volume and airflow quantified relative to unstimulated conditions. Lung volume increased by 386 ± 269 ml (means ± SD) and 761 ± 556 ml during low and high stimulation, respectively ( P < 0.05 for the difference between these values), which was associated with peak inspiratory flow increases of 69 ± 57 and 137 ± 108 ml/s, respectively ( P < 0.05 for the difference). Stimulation-induced change in lung volume correlated with change in peak flow ( r = 0.65, P < 0.01). Diaphragm descent-related outward displacement of the abdominal wall produced no change in airflow unless accompanied by lung volume change. We conclude that phrenic nerve stimulation-induced diaphragm contraction increases lung volume and reduces airway collapsibility in a dose-dependent manner. The effect appears primarily mediated by changes in lung volume rather than mediastinal traction from diaphragm descent. The study provides a rationale for use of continuous phrenic stimulation to treat obstructive sleep apnea.
Method for stationarity-segmentation of spike train data with application to the Pearson cross-correlation
Authors: Quiroga-Lombard Claudio S. , Hass Joachim , Durstewitz Daniel
Published: May 2013

Correlations among neurons are supposed to play an important role in computation and information coding in the nervous system. Empirically, functional interactions between neurons are most commonly assessed by cross-correlation functions. Recent studies have suggested that pairwise correlations may indeed be sufficient to capture most of the information present in neural interactions. Many applications of correlation functions, however, implicitly tend to assume that the underlying processes are stationary. This assumption will usually fail for real neurons recorded in vivo since their activity during behavioral tasks is heavily influenced by stimulus-, movement-, or cognition-related processes as well as by more general processes like slow oscillations or changes in state of alertness. To address the problem of nonstationarity, we introduce a method for assessing stationarity empirically and then “slicing” spike trains into stationary segments according to the statistical definition of weak-sense stationarity. We examine pairwise Pearson cross-correlations (PCCs) under both stationary and nonstationary conditions and identify another source of covariance that can be differentiated from the covariance of the spike times and emerges as a consequence of residual nonstationarities after the slicing process: the covariance of the firing rates defined on each segment. Based on this, a correction of the PCC is introduced that accounts for the effect of segmentation. We probe these methods both on simulated data sets and on in vivo recordings from the prefrontal cortex of behaving rats. Rather than for removing nonstationarities, the present method may also be used for detecting significant events in spike trains.
Bilateral tremor responses to unilateral loading and fatiguing muscle contractions
Authors: Kavanagh Justin J. , Cresswell Andrew G. , Sabapathy Surendran , Carroll Timothy J.
Published: May 2013

Although physiological tremor has been extensively studied within a single limb, tremor relationships between limbs are not well understood. Early investigations proposed that tremor in each limb is driven by CNS oscillators operating in parallel. However, recent evidence suggests that tremor in both limbs arises from shared neural inputs and is more likely to be observed under perturbed conditions. In the present study, postural tremor about the elbow joint and elbow flexor EMG activity were examined on both sides of the body in response to unilateral loading and fatiguing muscle contractions. Applying loads of 0.5, 1.0, 1.5, and 3.0 kg to a single limb increased tremor and muscle activity in the loaded limb but did not affect the unloaded limb, indicating that manipulating the inertial characteristics of a limb does not evoke bilateral tremor responses. In contrast, maximal-effort unilateral isometric contractions resulted in increased tremor and muscle activity in both the active limb and the nonactive limb without any changes in between-limb tremor or muscle coupling. When unilateral contractions were repeated intermittently, to the extent that maximum torque generation about the elbow joint declined by 50%, different tremor profiles were observed in each limb. Specifically, unilateral fatigue altered coupling between limbs and generated a bilateral response such that tremor and brachioradialis EMG decreased for the fatigued limb and increased in the contralateral nonfatigued limb. Our results demonstrate that activity in the nonactive limb may be due to a “spillover” effect rather than directly coupled neural output to both arms and that between-limb coupling for tremor and muscle activity is only altered under considerably perturbed conditions, such as fatigue-inducing contractions.
Fixational saccades reflect volitional action preparation
Authors: Watanabe Masayuki , Matsuo Yuka , Zha Ling , Munoz Douglas P. , Kobayashi Yasushi
Published: May 2013

Human volitional actions are preceded by preparatory processes, a critical mental process of cognitive control for future behavior. Volitional action preparation is regulated by large-scale neural circuits including the cerebral cortex and the basal ganglia. Because volitional action preparation is a covert process, the network dynamics of such neural circuits have been examined by neuroimaging and recording event-related potentials. Here, we examined whether such covert processes can be measured by the overt responses of fixational saccades (including microsaccades), the largest miniature eye movements that occur during eye fixation. We analyzed fixational saccades while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade in response to peripheral stimulus appearance. We used the antisaccade paradigm, in which subjects generate a saccade toward the opposite direction of a peripheral stimulus. Appropriate antisaccade performance requires the following two aspects of volitional control: 1) facilitation of saccades away from the stimulus and 2) suppression of inappropriate saccades toward the stimulus. We found that fixational saccades that occurred before stimulus appearance reflected the dual preparatory states of saccade facilitation and suppression and correlated with behavioral outcome (i.e., whether subjects succeeded or failed to cancel inappropriate saccades toward the stimulus). Moreover, fixational saccades explained a large proportion of individual differences in behavioral performance (poor/excellent) across subjects. These results suggest that fixational saccades predict the outcome of future volitional actions and may be used as a potential biomarker to detect people with difficulties in volitional action preparation.
cAMP and Mitochondria
Authors: Valsecchi Federica , Ramos-Espiritu Lavoisier S. , Buck Jochen , Levin Lonny R. , Manfredi Giovanni
Published: May 2013

Phosphorylation of mitochondrial proteins has emerged as a major regulatory mechanism for metabolic adaptation. cAMP signaling and PKA phosphorylation of mitochondrial proteins have just started to be investigated, and the presence of cAMP-generating enzymes and PKA inside mitochondria is still controversial. Here, we discuss the role of cAMP in regulating mitochondrial bioenergetics through protein phosphorylation and the evidence for soluble adenylyl cyclase as the source of cAMP inside mitochondria.
Nogo-A Represses Anatomical and Synaptic Plasticity in the Central Nervous System
Authors: Kempf Anissa , Schwab Martin E.
Published: May 2013

Nogo-A was initially discovered as a myelin-associated growth inhibitory protein limiting axonal regeneration after central nervous system (CNS) injury. This review summarizes current knowledge on how myelin and neuronal Nogo-A and its receptors exert physiological functions ranging from the regulation of growth suppression to synaptic plasticity in the developing and adult intact CNS.
Transduction of Voltage and Ca2+Signals by Slo1 BK Channels
Authors: Hoshi T. , Pantazis A. , Olcese R.
Published: May 2013

Large-conductance Ca2+- and voltage-gated K+channels are activated by an increase in intracellular Ca2+concentration and/or depolarization. The channel activation mechanism is well described by an allosteric model encompassing the gate, voltage sensors, and Ca2+sensors, and the model is an excellent framework to understand the influences of auxiliary β and γ subunits and regulatory factors such as Mg2+. Recent advances permit elucidation of structural correlates of the biophysical mechanism.
Membrane-Tethered Ligands: Tools for Cell-Autonomous Pharmacological Manipulation of Biological Circuits
Authors: Choi Charles , Nitabach Michael N.
Published: May 2013

Detection of secreted signaling molecules by cognate cell surface receptors is a major intercellular communication pathway in cellular circuits that control biological processes. Understanding the biological significance of these connections would allow us to understand how cellular circuits operate as a whole. Membrane-tethered ligands are recombinant transgenes with structural modules that allow them to act on cell-surface receptors and ion channel subtypes with pharmacological specificity in a cell-autonomous manner. Membrane-tethered ligands have been successful in the specific manipulation of ion channels as well as G-protein-coupled receptors, and, in combination with cell-specific promoters, such manipulations have been restricted to genetically defined subpopulations within cellular circuits in vivo to induce specific phenotypes controlled by those circuits. These studies establish the membrane-tethering approach as a generally applicable method for dissecting neural and physiological circuits.
Gap Junction Remodeling in Skin Repair Following Wounding and Disease
Authors: Churko Jared M. , Laird Dale W.
Published: May 2013

In the present review, we provide an overview of connexin expression during skin development and remodeling in wound healing, and reflect on how loss- or gain-of-function connexin mutations may change cellular phenotypes and lead to diseases of the skin. We also consider the therapeutic value of targeting connexins in wound healing.
Hairy Sensation
Authors: Lechner Stefan G. , Lewin Gary R.
Published: May 2013

The hairs of the skin not only function to prevent heat loss but also have important sensory functions. Recent work has now established that each hair of the skin is innervated by one or more of three types of mechanoreceptor ending. Each of these three mechanoreceptor types possesses distinct molecular features and detects distinctive information about skin touch, which is relayed to specific brain locations in a somatotopic fashion.
Cluster analysis reveals differential transcript profiles associated with resistance training-induced human skeletal muscle hypertrophy
Authors: Thalacker-Mercer Anna , Stec Michael , Cui Xiangqin , Cross James , Windham Samuel , Bamman Marcas
Published: May 2013

Using genomic microarray analysis, we sought to identify and annotate differences in the pretraining skeletal muscle transcriptomes among human subjects clustered as nonresponders (Non), modest responders (Mod), and extreme responders (Xtr) based on differential magnitudes of myofiber hypertrophy in response to progressive resistance training (RT) (Non −16 μm2, Mod 1,111 μm2, or Xtr 2,475 μm2). In prior work, we noted differences among clusters in the prevalence of myogenic stem cells prior to and during RT ( 35 ), and in the translational signaling responses to the first bout of resistance exercise ( 30 ). Here we identified remarkable differences in the pretraining transcript profiles among clusters (8,026 gene transcripts differentially expressed between Xtr and Non, 2,463 between Xtr and Mod, and 1,294 between Mod and Non). Annotated functions and networks of differentially expressed genes suggest Xtr were “primed” to respond to RT through transcriptional regulation, along with a uniquely expressed network of genes involved in skeletal muscle development, while the failed response in Non may have been driven by excessive proinflammatory signaling. Protein follow-up analysis revealed higher basal levels of acetylated histone H3 (K36) in the two responder clusters (Mod, Xtr) compared with Non, and only the responders experienced alterations in the muscle content of select proteins (e.g., α-tubulin, p27kip) in response to the first resistance exercise stimulus. Overall, the widely disparate transcriptomes identified prior to RT among the three clusters support the notion that at least some of the interindividual heterogeneity in propensity for RT-induced myofiber hypertrophy is likely predetermined.
Effect of Lutein and Antioxidant Supplementation on VEGF Expression, MMP-2 Activity, and Ultrastructural Alterations in Apolipoprotein E-Deficient Mouse
Authors: Fernández-Robredo Patricia , Sádaba Luis M. , Salinas-Alamán Angel , Recalde Sergio , Rodríguez José A. , García-Layana Alfredo
Published: May 2013

Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE−/−) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE−/−mice (n=40, 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV (two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice (n=10) were also used as control (WT-C). ApoE−/−mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE−/−mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE−/−mice. Moreover, these changes could be prevented by efficient antioxidant treatments.
A Memory/Immunology-Based Control Approach with Applications to Multiple Spacecraft Formation Flying
Authors: Weng Liguo , Xia Min , Hu Kai , Qiao Zhuhan
Published: May 2013

This paper addresses the problem of formation control for multiple spacecrafts in Planetary Orbital Environment (POE). Due to the presence of diverse interferences and uncertainties in the outer space, such as the changing spacecraft mass, unavailable space parameters, and varying gravity forces, traditional control methods encounter great difficulties in this area. A new control approach inspired by human memory and immune system is proposed, and this approach is shown to be capable of learning from past control experience and current behavior to improve its performance. It demands much less system dynamic information as compared with traditional controls. Both theoretic analysis and computer simulation verify its effectiveness.
A Mixed Problem with an Integral Two-Space-Variables Condition for Parabolic Equation with The Bessel Operator
Authors: Abdelfatah Bouziani , Taki-Eddine Oussaeif , Leila Ben Aoua
Published: May 2013

We study a mixed problem with an integral two-space-variables condition for parabolic equation with the Bessel operator. The existence and uniqueness of the solution in functional weighted Sobolev space are proved. The proof is based on a priori estimate “energy inequality” and the density of the range of the operator generated by the problem considered.
What Makes an Act a Pretense One? Young Children’s Pretend-Real Judgments and Explanations
Authors: Ma Lili , Lillard Angeline S.
Published: May 2013

The present study examined what makes an act a pretense one for adults and preschoolers. Participants watched pretense versus real acts, judged whether each act was pretend or real, and justified their judgment by citing the cues they used. These reported cues are presumed to reflect viewers’ conception of what makes an act a pretense one. The results suggested that like adults, 5-year-olds represented pretense behavior in the form of contrasts between pretense and its real counterpart. However, children placed greater weight on deviant content than on behavioral cues, whereas adults used behavioral cues, especially movement, when content information was not available. These results are discussed in terms of how children’s intuitive theories of pretense might differ from those of adults.
Approximate Fixed Point Theorems in Fuzzy Norm Spaces for an Operator
Authors: Mohsenalhosseini S. A. M. , Mazaheri H.
Published: May 2013

We define approximate fixed point and fuzzy diameter in fuzzy norm spaces. We prove theorems for various types of well-known generalized contractions on fuzzy norm spaces with the use of two general lemmas that are given regarding approximate fixed points of operators on fuzzy norm spaces.
Recent Progress of Propolis for Its Biological and Chemical Compositions and Its Botanical Origin
Authors: Toreti Viviane Cristina , Sato Helia Harumi , Pastore Glaucia Maria , Park Yong Kun
Published: May 2013

Propolis is the generic name given to the product obtained from resinous substances, which is gummy and balsamic and which is collected by bees from flowers, buds, and exudates of plants. It is a popular folk medicine possessing a broad spectrum of biological activities. These biological properties are related to its chemical composition and more specifically to the phenolic compounds that vary in their structure and concentration depending on the region of production, availability of sources to collect plant resins, genetic variability of the queen bee, the technique used for production, and the season in which propolis is produced. Many scientific articles are published every year in different international journal, and several groups of researchers have focused their attention on the chemical compounds and biological activity of propolis. This paper presents a review on the publications on propolis and patents of applications and biological constituents of propolis.
Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity
Authors: Guo Tianruo , Al Abed Amr , Lovell Nigel H. , Dokos Socrates
Published: May 2013

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation.
A Rare Case of Nasopharyngeal Pleomorphic Adenoma
Authors: Berrettini S. , Fortunato S. , De Vito A. , Bruschini L.
Published: May 2013

Salivary gland tumors are rare. The majority of these tumors are benign and about 70% are pleomorphic adenomas (PA). Nasopharynx is an unusual site for the PA tumor. Only six cases are presented in the literature from 1990 to 2011. The diagnosis of this disease is linked to the sum of imaging tests, clinical and histological study of the mass of the above. The radiologic features of noninvasion of surrounding structures give the first clue to the benign lesion. From the review of the literature and our experience is identified as the gold standard in surgical treatment for this condition. Thanks to the endoscopic surgery, we can perform a complete resection of the lesion without damaging adjacent structures. We presented a case of pleomorphic adenoma of nasopharynx with literature review.
Injection Moulded Biocomposites from Oat Hull and Polypropylene/Polylactide Blend: Fabrication and Performance Evaluation
Authors: Reddy Jeevan Prasad , Misra Manjusri , Mohanty Amar
Published: May 2013

Oat hull fibre reinforced polypropylene- (PP-)/polylactide- (PLA-) based biocomposites were fabricated and their process engineering and performances were evaluated. The effect of ethylene propylene-g-maleic anhydride (EP-g-Ma) compatibilizer on mechanical properties of 30 wt% oat hull reinforced PP/PLA (90/10) blend composites was investigated. Thermal degradation parameters of the oat hull fibre were determined using thermogravimetric analysis. The effect of fibre reinforcement on crystallinity of oat hull fibre reinforced PP/PLA composites was studied by differential scanning calorimetry (DSC). Thermomechanical properties of the composites were analyzed by dynamic mechanical analyzer (DMA). The interfacial bonding between the fibre and the matrix was examined using scanning electron microscope (SEM). Significant improvement in tensile strength (40%) and flexural strength (46%) was observed with the addition of EP-g-Ma compatibilizer. DSC analysis of oat hull fibre reinforced composites showed an increase in the crystallization temperature ( Tc) due to the nucleation effect of oat hull fibre. DMA results revealed that the storage modulus of PP/PLA/Oat hull fibre composites was higher compared to PP/PLA blend throughout the investigated range of temperature.
Anxiolytic‐Like Actions of Fatty Acids Identified in Human Amniotic Fluid
Authors: García-Ríos Rosa Isela , Rodríguez-Landa Juan Francisco , Contreras Carlos M.
Published: May 2013

Eight fatty acids (C12–C18) were previously identified in human amniotic fluid, colostrum, and milk in similar proportions but different amounts. Amniotic fluid is well known to be the natural environment for development in mammals. Interestingly, amniotic fluid and an artificial mixture of fatty acids contained in amniotic fluid produce similar anxiolytic‐like actions in Wistar rats. We explored whether the lowest amount of fatty acids contained in amniotic fluid with respect to colostrum and milk produces such anxiolytic‐like effects. Although a trend toward a dose‐response effect was observed, only an amount of fatty acids that was similar to amniotic fluid fully mimicked the effect of diazepam (2 mg/kg, i.p.) in the defensive burying test, an action devoid of effects on locomotor activity and motor coordination. Our results confirm that the amount of fatty acids contained in amniotic fluid is sufficient to produce anxiolytic‐like effects, suggesting similar actions during intrauterine development.
Overcoming Barriers to Family Planning through Integration: Perspectives of HIV-Positive Men in Nyanza Province, Kenya
Authors: Steinfeld Rachel L. , Newmann Sara J. , Onono Maricianah , Cohen Craig R. , Bukusi Elizabeth A. , Grossman Daniel
Published: May 2013

This study explored barriers to and facilitators of using family planning services among HIV-positive men in Nyanza Province, Kenya. From May to June 2010, in-depth interviews were conducted with 30 men receiving care at 15 HIV clinics. The key barriers to the use of family planning included concerns about side effects of contraceptives, lack of knowledge about contraceptive methods, myths and misconceptions including fear of infertility, structural barriers such as staffing shortages at HIV clinics, and a lack of male focus in family planning methods and service delivery. The integration of family planning into HIV clinics including family planning counseling and education was cited as an important strategy to improve family planning receptivity among men. Integrating family planning into HIV services is a promising strategy to facilitate male involvement in family planning. Integration needs to be rigorously evaluated in order to measure its impact on unmet need for contraception among HIV-positive women and their partners and assure that it is implemented in a manner that engages both men and women.
An Analytical Approximation for Continuous Flow Microwave Heating of Liquids
Authors: Cuccurullo G. , Giordano L. , Viccione G.
Published: May 2013

Both a numerical and an analytical models were developed to simulate temperature profiles in continuous laminar pipe flow during microwave heating. Fully developed velocity and thermally developing conditions were assumed. The numerical solution was obtained by first solving Maxwell equations and then by coupling them with the energy balance for the flowing fluid. On the other hand, the same problem was solved analytically under the simplifying assumption foreseeing uniform heat generation inside the pipe. With the aim of reducing computational efforts, numerical and analytical results were compared in order to investigate conditions for which the two models allowed to recover the same temperature patterns. Thus, it has been shown that suitable conditions can be found for which the simplified analytical model can lead to an easy way to predict the heat transfer through the pipe.
Noninvasive Detection of HER2 Amplification with Plasma DNA Digital PCR
Authors: Gevensleben Heidrun , Garcia-Murillas Isaac , Graeser Monika K. , Schiavon Gaia , Osin Peter , Parton Marina , Smith Ian E. , Ashworth Alan , Turner Nicholas C.
Published: May 2013

Purpose: Digital PCR is a highly accurate method of determining DNA concentration. We adapted digital PCR to determine the presence of oncogenic amplification through noninvasive analysis of circulating free plasma DNA and exemplify this approach by developing a plasma DNA digital PCR assay for HER2 copy number.

Experimental Design: The reference gene for copy number assessment was assessed experimentally and bioinformatically. Chromosome 17 pericentromeric probes were shown to be suboptimal, and EFTUD2 at chromosome position 17q21.31 was selected for analysis. Digital PCR assay parameters were determined on plasma samples from a development cohort of 65 patients and assessed in an independent validation cohort of plasma samples from 58 patients with metastatic breast cancer. The sequential probability ratio test was used to assign the plasma DNA digital PCR test as being HER2-positive or -negative in the validation cohort.

Results: In the development cohort, the HER2:EFTUD2 plasma DNA copy number ratio had a receiver operator area under the curve (AUC) = 0.92 [95% confidence interval (CI), 0.86–0.99, P = 0.0003]. In the independent validation cohort, 64% (7 of 11) of patients with HER2-amplified cancers were classified as plasma digital PCR HER2–positive and 94% (44 of 47) of patients with HER2-nonamplified cancers were classified as digital PCR HER2–negative, with a positive and negative predictive value of 70% and 92%, respectively.

Conclusion: Analysis of plasma DNA with digital PCR has the potential to screen for the acquisition of HER2 amplification in metastatic breast cancer. This approach could potentially be adapted to the analysis of any locus amplified in cancer. Clin Cancer Res; 19(12); 3276–84. ©2013 AACR.
Systems Analysis of the NCI-60 Cancer Cell Lines by Alignment of Protein Pathway Activation Modules with “-OMIC” Data Fields and Therapeutic Response Signatures
Authors: Federici Giulia , Gao Xi , Slawek Janusz , Arodz Tomasz , Shitaye Amanuel , Wulfkuhle Julia D. , De Maria Ruggero , Liotta Lance A. , Petricoin Emanuel F.
Published: May 2013

The NCI-60 cell line set is likely the most molecularly profiled set of human tumor cell lines in the world. However, a critical missing component of previous analyses has been the inability to place the massive amounts of “-omic” data in the context of functional protein signaling networks, which often contain many of the drug targets for new targeted therapeutics. We used reverse-phase protein array (RPPA) analysis to measure the activation/phosphorylation state of 135 proteins, with a total analysis of nearly 200 key protein isoforms involved in cell proliferation, survival, migration, adhesion, etc., in all 60 cell lines. We aggregated the signaling data into biochemical modules of interconnected kinase substrates for 6 key cancer signaling pathways: AKT, mTOR, EGF receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), integrin, and apoptosis signaling. The net activation state of these protein network modules was correlated to available individual protein, phosphoprotein, mutational, metabolomic, miRNA, transcriptional, and drug sensitivity data. Pathway activation mapping identified reproducible and distinct signaling cohorts that transcended organ-type distinctions. Direct correlations with the protein network modules involved largely protein phosphorylation data but we also identified direct correlations of signaling networks with metabolites, miRNA, and DNA data. The integration of protein activation measurements into biochemically interconnected modules provided a novel means to align the functional protein architecture with multiple “-omic” data sets and therapeutic response correlations. This approach may provide a deeper understanding of how cellular biochemistry defines therapeutic response. Such “-omic” portraits could inform rational anticancer agent screenings and drive personalized therapeutic approaches. Mol Cancer Res; 11(6); 676–85. ©2013 AACR.
Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case–Cohort Study of Postmenopausal Women
Authors: Kim Sangmi , Taylor Jack A. , Milne Ginger L. , Sandler Dale P.
Published: May 2013

Overweight or obese women are at increased risk of developing and dying from breast cancer. Obesity-driven inflammation may stimulate prostaglandin E2 (PGE2)-mediated aromatase activation and estrogen biosynthesis in breast tissues. We hypothesized that increased production of PGE2 would contribute to elevated breast cancer risk in postmenopausal women. We carried out a case–cohort study with 307 incident breast cancer cases and 300 subcohort members from the Sister Study cohort. HRs and 95% confidence intervals (CI) were estimated for the association between urinary levels of a major PGE2 metabolite (PGE-M) and breast cancer risk using Prentice's pseudo-likelihood approach. Several lifestyle factors were associated with urinary levels of PGE-M: smoking, high-saturated fat diet, and obesity increased urinary PGE-M, and use of nonsteroidal antiinflammatory drugs (NSAID) decreased urinary PGE-M. Although there was no association between urinary PGE-M and postmenopausal breast cancer risk in the overall analysis or among regular users of NSAIDs, there was a positive association among postmenopausal women who did not regularly use NSAIDs with HRs of 2.1 [95% confidence interval (CI): 1.0–4.3]; 2.0 (95% CI: 1.0–3.9); and 2.2 (95% CI: 1.1–4.3) for the second, third, and highest quartiles of PGE-M. Our findings suggest a link between systemic PGE2 formation and postmenopausal breast cancer, and a possible modification of the association by lifestyle and pharmacologic interventions. If confirmed in larger studies, these results may have useful implications for the development of preventive strategies. Cancer Prev Res; 6(6); 511–8. ©2013 AACR.
Incidence of antibodies to protamine sulfate/heparin complexes in cardiac surgery patients and impact on platelet activation and clinical outcome
Authors: Leroux Dorothée , Rollin Jérome , Amiral Jean , May Marc-Antoine , Pouplard Claire , Gruel Yves
Published: May 2013

A new ELISA (Zymutest HIA®), based on incubation of diluted plasma with protamine/heparin (PRT/H) complexes without and with platelet factor 4 (PF4) provided by a platelet lysate, was used to detect heparindependent antibodies in a cohort of 232 cardiac surgery (CS) patients and in 47 patients with heparin-induced thrombocytopenia (HIT). Significant binding of IgG/A/M to PRT/H complexes was demonstrated in 59 CS patients (25.4%), with similar absorbances whether platelet lysate was added to the plasma or not, and significant reactivity to PF4/H in 29 of them. Antibodies to PRT or heparin alone were present in 15 and two of these patients, respectively. Importantly, antibodies to PRT/H were detected in only three of the 47 HIT patients, who had also undergone recent CS. The Zymutest HIA® was positive in another 41 CS patients (17%), but only or mainly when their plasma was tested with platelet lysate, with significant levels of antibodies to PF4/H in 40 of them without detectable reactivity to PRT or heparin alone. Slight antibody binding to PRT/H complexes was also measured in six of these 41 patients. Therefore, a total of 35 CS patients exhibited dual antibody reactivity towards PRT/H and PF4/H complexes. Serotonin release assay performed with PRT alone was positive in 17 CS patients with antibodies to PRT/H, but all had normal platelet count evolution without thrombosis postoperatively. In conclusion, antibodies to PRT/H are frequently present in CS patients postoperatively (25.4%), and can activate platelets in vitro, but their clinical impact remains questionable.
Coagulation potential of immobilised factor VIII in flow-dependent fibrin generation on platelet surfaces
Authors: Doi Masaaki , Matsui Hideto , Matsunari Yasunori , Shima Midori , Sugimoto Mitsuhiko
Published: May 2013

Coagulation factor VIII (FVIII) plays an essential role in haemostasis. To date, physiologic activity of FVIII circulating in the bloodstream (S-FVIII) is evaluated by classic coagulation assays. However, the functional relevance of FVIII (-von Willebrand factor complex) immobilised on thrombogenic surfaces (I-FVIII) remains unclear. We used an in vitro perfusion chamber system to evaluate the function of I-FVIII in the process of mural thrombus formation under whole blood flow conditions. In perfusion of either control or synthetic haemophilic blood, the intra-thrombus fibrin generation on platelet surfaces significantly increased as a function of I-FVIII, independent of S-FVIII, under high shear rate conditions. This I-FVIII effect was unvarying regardless of anti-FVIII inhibitor levels in synthetic haemophilic blood. Thus, our results illustrate coagulation potentials of immobilised clotting factors, distinct from those in the bloodstream, under physiologic flow conditions and may give a clue for novel therapeutic approaches for haemophilic patients with anti-FVIII inhibitors.
Mortality and Sudden Death in Pediatric Left Ventricular Noncompaction in a Tertiary Referral Center
Authors: Brescia Samuel T. , Rossano Joseph W. , Pignatelli Ricardo , Jefferies John L. , Price Jack F. , Decker Jamie A. , Denfield Susan W. , Dreyer W. Jeffrey , Smith O’Brian , Towbin Jeffrey A. , Kim Jeffrey J.
Published: May 2013

Background—

Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death.

Methods and Results—

We retrospectively reviewed all children diagnosed with left ventricular noncompaction at Texas Children’s Hospital from January 1990 to January 2009. Patients with congenital cardiac lesions were excluded. Two hundred forty-two children were diagnosed with isolated left ventricular noncompaction over the study period. Thirty-one (12.8%) died, and 13 (5.4%) were received a transplant. One hundred fifty (62%) presented with or developed cardiac dysfunction. The presence of cardiac dysfunction was strongly associated with mortality (hazard ratio, 11;
P
<0.001). ECG abnormalities were present in 87%, with ventricular hypertrophy and repolarization abnormalities occurring most commonly. Repolarization abnormalities were associated with increased mortality (hazard ratio, 2.1;
P
=0.02). Eighty children (33.1%) had an arrhythmia, and those with arrhythmias had increased mortality (hazard ratio, 2.8;
P
=0.002). Forty-two (17.4%) had ventricular tachycardia, with 5 presenting with resuscitated sudden cardiac death. In total, there were 15 cases of sudden cardiac death in the cohort (6.2%). Nearly all patients with sudden death (14 of 15) had abnormal cardiac dimensions or cardiac dysfunction. No patient with normal cardiac dimensions and function without preceding arrhythmias died.

Conclusions—

Left ventricular noncompaction has a high mortality rate and is strongly associated with arrhythmias in children. Preceding cardiac dysfunction or ventricular arrhythmias are associated with increased mortality. Children with normal cardiac dimensions and normal function are at low risk for sudden death.
A revision of the endemic Chinese genus Cornopsylla (Hemiptera: Psyllidae), with potential pests on Zanthoxylum (Rutaceae)
Authors: LUO XINYU
Published: May 2013

The endemic Chinese psyllid genus Cornopsylla Li is reviewed with a revised generic diagnosis. Cornopsylla zanthoxylae Li and C. trichotoma Li are redescribed, and Cornopsylla magna sp. nov. and C. rotundiconis sp. nov. are described. Keys to adults and nymphs of this genus are given, and the systematic position of Cornopsylla is reviewed. The potential of Cornopsylla spp. as major pests on cultivated Zanthoxylum is discussed. Psylla sarcospermae (Li) comb. nov. is proposed for this species that does not share the generic characters of Cornopsylla.
An index to new genera and species of Nematoda in Zootaxa from 2007 to 2012
Authors: XU YU MEI , ZHAO ZENG QI , WANG JIAN MING
Published: May 2013

Of 104 papers on nematodes published in Zootaxa from 2007 to 2012, seventy five, by 136 authors from 27 countries, described eight new genera and 155 new species. A bibliographic analysis of these papers and a list of new genera and species are presented in this paper.
Endothelium and Regulatory Inflammatory Mechanisms During Organ Rejection
Authors: Taccone Fabio Silvio , Crimi Ettore , Anstey James , Infante Teresa , Donadello Katia , Scolletta Sabino , Al-Omran Mohammed , Napoli Claudio
Published: May 2013

Endothelial integrity is mandatory for physiologic organ function; however, endothelium dysfunction can be caused by systemic inflammation, occurring during sepsis or organ rejection after transplantation. This article will address our current understanding of endothelial involvement in organ transplantation and rejection. Overall, more detailed studies focusing on the endothelial modulation after organ transplantation would be necessary to investigate the role of endothelium activation during organ rejection.