bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrazioni spurie: letteratura della realtà nell'Italia contemporanea
Authors: Palumbo Raffaello
Published: May 2011

L'enorme successo di Gomorra di Saviano ha richiamato l'attenzione su un fenomeno, quello del "ritorno al reale" (Angelo Guglielmi) della narrativa italiana recente. Il terminus a quo di un tale fenomeno, infatti, può essere fissato nei primi anni Novanta, e il libro di Saviano rappresenta piuttosto la punta dell'iceberg degli autori italiani di nuova generazione a produrre narrazioni ibride che oscillano tra i due poli della fiction e della non fiction. Attraverso il riferimento ad alcuni testi esemplari il saggio rintraccia innanzi tutto alcuni intertesti fondamentali. In secondo luogo, il saggio mette a fuoco il legame tra tali forme ibride di narrazione ed una nuova stagione dell'impegno.
Uno sguardo dalla periferia: appunti per una storia novecentesca della poesia in dialetto nel Triveneto
Authors: Benvegnù Damiano
Published: May 2011

The so-called Triveneto is--for economical, anthropological, sociolinguistic, and literary reasons--a particular case within the Italian survey. In the twentieth century alone this macroregion has seen a unique and uneven development that has changed sometimes destroyed its previous anthropological and linguistic (i.e. dialect) continuity. This paper explores the consequences and relationships between this particular "sviluppo disuguale" and the literary production of several poets from this area during the past century. It outlines the dialectics among different sociolinguistic oppositions in order to sketch a model helpful in understanding the special tension between national language and dialect(s) in Italian contemporary poetry.
"Io so": A Reading of Roberto Saviano's Gomorra
Authors: Pocci Luca
Published: May 2011

This article addresses the debate on Gomorra discussing, in particular, the textual hybridity of Saviano's book. Drawing on J. L. Austin's philosophy of language, the author argues that this controversial characteristic is due not so much to the blending of different genres as to the presence of two distinct pragmatic dimensions, a constative and a performative dimension. The constative effectiveness and the performative efficacy of the text are crucial aspects of Gomorra and, as it is shown, both aspects derive from the beneficial indiscipline that Saviano exhibits in mixing together discursive activities and purposes which are usually kept separate.
Potential role of multidrug resistant proteins in refractory epilepsy and antiepileptic drugs interactions
Authors: Lazarowski Alberto , Czornyj Liliana
Published: May 2011

Epilepsy is a common neurological disorder. About one-third of epilepsy patients have a multidrug resistance (MDR) phenotype and develop refractory epilepsy (RE). Changes in the properties of the antiepileptic drugs (AEDs) targets resulting in reduced drug sensitivity, can’t explain the MDR phenotype. This particular refractoriness is now attributed to overexpression of multidrug transporters in brain, leading to impaired access of AEDs to CNS targets, and it was documented in both human as well as in experimental models of RE. Single nucleotide polymorphism (SNP) identified in the MDR1-ABCB1gene (C3435T/CC-genotype) is associated with increased intestinal expression of P-glycoprotein (P-gp) that affects levels of AEDs in plasma. The functional studies of P-gp using P-gp inhibitors could show the still unclear clinical impact of ABCB1 polymorphisms on AEDs resistance. Some drug-drug interactions previously believed to be cytochrome P450 (CYP) mediated are now also considered to be due to the modulation of multidrug-transporters. Because in certain cases pharmacoresistance can be overcome by add-on therapy, co-administered P-gp inhibitors could contribute to the effectiveness of AEDs treatment in RE. And in this regard, perhaps we can postulate to P-gp as a new clinical therapeutic target in multidrug-refractory epilepsy.
The Polymodal Ion Channel Transient Receptor Potential Vanilloid 4 Modulates Calcium Flux, Spiking Rate, and Apoptosis of Mouse Retinal Ganglion Cells
Authors: Ryskamp Daniel A. , Witkovsky Paul , Barabas Peter , Huang Wei , Koehler Christopher , Akimov Nikolay P. , Lee Suk Hee , Chauhan Shiwani , Xing Wei , Rentería René C. , Liedtke Wolfgang , Križaj David
Published: May 2011

Sustained increase in intraocular pressure represents a major risk factor for eye disease, yet the cellular mechanisms of pressure transduction in the posterior eye are essentially unknown. Here we show that the mouse retina expresses mRNA and protein for the polymodal transient receptor potential vanilloid 4 (TRPV4) cation channel known to mediate osmotransduction and mechanotransduction. TRPV4 antibodies labeled perikarya, axons, and dendrites of retinal ganglion cells (RGCs) and intensely immunostained the optic nerve head. Müller glial cells, but not retinal astrocytes or microglia, also expressed TRPV4 immunoreactivity. The selective TRPV4 agonists 4α-PDD and GSK1016790A elevated [Ca2+]iin dissociated RGCs in a dose-dependent manner, whereas the TRPV1 agonist capsaicin had no effect on [Ca2+]RGC. Exposure to hypotonic stimulation evoked robust increases in [Ca2+]RGC. RGC responses to TRPV4-selective agonists and hypotonic stimulation were absent in Ca2+-free saline and were antagonized by the nonselective TRP channel antagonists Ruthenium Red and gadolinium, but were unaffected by the TRPV1 antagonist capsazepine. TRPV4-selective agonists increased the spiking frequency recorded from intact retinas recorded with multielectrode arrays. Sustained exposure to TRPV4 agonists evoked dose-dependent apoptosis of RGCs. Our results demonstrate functional TRPV4 expression in RGCs and suggest that its activation mediates response to membrane stretch leading to elevated [Ca2+]iand augmented excitability. Excessive Ca2+influx through TRPV4 predisposes RGCs to activation of Ca2+-dependent proapoptotic signaling pathways, indicating that TRPV4 is a component of the response mechanism to pathological elevations of intraocular pressure.
Spinster Controls Dpp Signaling during Glial Migration in theDrosophilaEye
Authors: Yuva-Aydemir Yeliz , Bauke Ann-Christin , Klämbt Christian
Published: May 2011

The development of multicellular organisms requires the well balanced and coordinated migration of many cell types. This is of particular importance within the developing nervous system, where glial cells often move long distances to reach their targets. The majority of glial cells in the peripheral nervous system of theDrosophilaembryo is derived from the CNS and migrates along motor axons toward their targets. In the developingDrosophilaeye, CNS-derived glial cells move outward toward the nascent photoreceptor cells, but the molecular mechanisms coupling the migration of glial cells with the growth of the eye imaginal disc are mostly unknown. Here, we used an enhancer trap approach to identify the genespinster, which encodes a multipass transmembrane protein involved in endosome–lysosome trafficking, as being expressed in many glial cells.spinstermutants are characterized by glial overmigration. Genetic experiments demonstrate that Spinster modulates the activity of several signaling cascades. Within the migrating perineurial glial cells, Spinster is required to downregulate Dpp (Decapentaplegic) signaling activity, which ceases migratory abilities. In addition, Spinster affects the growth of the carpet cell, which indirectly modulates glial migration.
The Parkinsonian Mimetic, MPP+, Specifically Impairs Mitochondrial Transport in Dopamine Axons
Authors: Kim-Han Jeong Sook , Antenor-Dorsey Jo Ann , O'Malley Karen L.
Published: May 2011

Impaired axonal transport may play a key role in Parkinson's disease. To test this notion, a microchamber system was adapted to segregate axons from cell bodies using green fluorescent protein-labeled mouse dopamine (DA) neurons. Transport was examined in axons challenged with the DA neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+). MPP+rapidly reduced overall mitochondrial motility in DA axons; among motile mitochondria, anterograde transport was slower yet retrograde transport was increased. Transport effects were specific for DA mitochondria, which were smaller and transported more slowly than their non-DA counterparts. MPP+did not affect synaptophysin-tagged vesicles or any other measureable moving particle. Toxin effects on DA mitochondria were not dependent upon ATP, calcium, free radical species, JNK, or caspase3/PKC pathways but were completely blocked by the thiol-anti-oxidantN-acetyl-cysteine or membrane-permeable glutathione. Since these drugs also rescued processes from degeneration, these findings emphasize the need to develop therapeutics aimed at axons as well as cell bodies to preserve “normal” circuitry and function as long as possible.
The Activity-Regulated Cytoskeletal-Associated Protein (Arc/Arg3.1) Is Required for Reconsolidation of a Pavlovian Fear Memory
Authors: Maddox Stephanie A. , Schafe Glenn E.
Published: May 2011

The activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is an immediate-early gene that has been widely implicated in synaptic plasticity and in the consolidation of a variety of hippocampal- and amygdala-dependent memory tasks. The functional role of Arc/Arg3.1 in memory reconsolidation processes, however, has not been systematically studied. In the present study, we examined the role of Arc/Arg3.1 in the reconsolidation of an amygdala-dependent auditory pavlovian fear memory. We show that Arc/Arg3.1 protein is regulated in the lateral nucleus of the amygdala (LA) by retrieval of an auditory fear memory. Next, we show that antisense knockdown of Arc/Arg3.1 in the LA impairs fear memory reconsolidation of both a recent (1-d-old) as well as a well-consolidated (2-week-old) fear memory; that is, post-retrieval short-term memory, tested at 3 h after retrieval, is intact, whereas post-retrieval long-term memory, tested ∼24 h after retrieval, is significantly impaired. The effect of Arc/Arg3.1 knockdown was observed to be time limited and specific to an actively reactivated fear memory. Moreover, the reconsolidation deficit induced by Arc/Arg3.1 knockdown was not found to be sensitive to spontaneous recovery, reinstatement, or a shift in the testing context, suggesting that our behavioral effects are not attributable to facilitated extinction. Collectively, our findings provide the first comprehensive look at the functional role of Arc/Arg3.1 in memory reconsolidation processes in the mammalian brain.
Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) EnantiomersIn Vitroand in the MPTP-Lesioned Primate:R-MDMA Reduces Severity of Dyskinesia, WhereasS-MDMA Extends Duration of ON-Time
Authors: Huot Philippe , Johnston Tom H. , Lewis Katie D. , Koprich James B. , Reyes M. Gabriela , Fox Susan H. , Piggott Matthew J. , Brotchie Jonathan M.
Published: May 2011

l-3,4-Dihydroxyphenylalanine (l-DOPA) is the most effective treatment for Parkinson's disease, but long-terml-DOPA administration is marred by the emergence of motor complications, namely, dyskinesia and a shortening of antiparkinsonian benefit (wearing-OFF). 3,4-Methylenedioxymethamphetamine (MDMA) is unique in that it exerts antidyskinetic effects and may enhance antiparkinsonian actions ofl-DOPA. MDMA is composed of two enantiomers with different pharmacological profiles; here, we describe a novel enantiospecific synthesis of the two enantiomers and expand on the previous characterization of their pharmacology.R-MDMA (rectus-MDMA) is relatively selective for 5-HT2Areceptors, whereasS-MDMA (sinister-MDMA) inhibits both serotonin (SERT) and dopamine transporters (DAT; SERT/DAT ratio of 10 to 1).R- orS-MDMA (1, 3, and 10 mg/kg, s.c.) was administered in combination withl-DOPA (15 mg/kg, s.c.) to six female common marmosets (Callithrix jacchus) rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration. Motor disability, including parkinsonism and dyskinesia, and duration of antiparkinsonian benefit (ON-time) were evaluated. After the administration ofR-MDMA (3 and 10 mg/kg), the severity of peak-dose dyskinesia was decreased (by 33 and 46%, respectively;p< 0.05); although total ON-time was unchanged (∼220 min), the duration of ON-time with disabling dyskinesia was decreased by 90 min when compared tol-DOPA alone (69% reduction;p< 0.05).S-MDMA (1 mg/kg) increased the total ON-time by 88 min compared tol-DOPA alone (34% increase;p< 0.05), though dyskinesia were exacerbated. These data suggest that racemic MDMA exerts simultaneous effects, reducing dyskinesia and extending ON-time, by 5-HT2Aantagonism and SERT-selective mixed monoamine uptake inhibition, which arise from itsRandSenantiomers, respectively.
Same or Different? A Neural Circuit Mechanism of Similarity-Based Pattern Match Decision Making
Authors: Engel Tatiana A. , Wang Xiao-Jing
Published: May 2011

The ability to judge whether sensory stimuli match an internally represented pattern is central to many brain functions. To elucidate the underlying mechanism, we developed a neural circuit model for match/nonmatch decision making. At the core of this model is a “comparison circuit” consisting of two distinct neural populations: match enhancement cells show higher firing response for a match than a nonmatch to the target pattern, and match suppression cells exhibit the opposite trend. We propose that these two neural pools emerge from inhibition-dominated recurrent dynamics and heterogeneous top–down excitation from a working memory circuit. A downstream system learns, through plastic synapses, to extract the necessary information to make match/nonmatch decisions. The model accounts for key physiological observations from behaving monkeys in delayed match-to-sample experiments, including tasks that require more than simple feature match (e.g., when BB in ABBA sequence must be ignored). A testable prediction is that magnitudes of match enhancement and suppression neural signals are parametrically tuned to the similarity between compared patterns. Furthermore, the same neural signals from the comparison circuit can be used differently in the decision process for different stimulus statistics or tasks; reward-dependent synaptic plasticity enables decision neurons to flexibly adjust the readout scheme to task demands, whereby the most informative neural signals have the highest impact on the decision.
Hippocampal Theta-Phase Modulation of Replay Correlates with Configural-Relational Short-Term Memory Performance: Figure 1.
Authors: Poch Claudia , Fuentemilla Lluis , Barnes Gareth R. , Düzel Emrah
Published: May 2011

There is now growing evidence that the hippocampus generates theta rhythms that can phase bias fast neural oscillations in the neocortex, allowing coordination of widespread fast oscillatory populations outside limbic areas. A recent magnetoencephalographic study showed that maintenance of configural-relational scene information in a delayed match-to-sample (DMS) task was associated with replay of that information during the delay period. The periodicity of the replay was coordinated by the phase of the ongoing theta rhythm, and the degree of theta coordination during the delay period was positively correlated with DMS performance. Here, we reanalyzed these data to investigate which brain regions were involved in generating the theta oscillations that coordinated the periodic replay of configural–relational information. We used a beamformer algorithm to produce estimates of regional theta rhythms and constructed volumetric images of the phase-locking between the local theta cycle and the instances of replay (in the 13–80 Hz band). We found that individual differences in DMS performance for configural-relational associations were related to the degree of phase coupling of instances of cortical reactivations to theta oscillations generated in the right posterior hippocampus and the right inferior frontal gyrus. This demonstrates that the timing of memory reactivations in humans is biased toward hippocampal theta phase.
Tactile Spatial Acuity Enhancement in Blindness: Evidence for Experience-Dependent Mechanisms
Authors: Wong Michael , Gnanakumaran Vishi , Goldreich Daniel
Published: May 2011

Tactile spatial acuity is enhanced in blindness, according to several studies, but the cause of this enhancement has been controversial. Two competing hypotheses are the tactile experience hypothesis (reliance on the sense of touch drives tactile-acuity enhancement) and the visual deprivation hypothesis (the absence of vision itself drives tactile-acuity enhancement). Here, we performed experiments to distinguish between these two hypotheses. We used force-controlled grating orientation tasks to compare the passive (finger stationary) tactile spatial acuity of 28 profoundly blind and 55 normally sighted humans on the index, middle, and ring fingers of each hand, and on the lips. The tactile experience hypothesis predicted that blind participants would outperform the sighted on the fingers, and that Braille reading would correlate with tactile acuity. The visual deprivation hypothesis predicted that blind participants would outperform the sighted on fingers and lips. Consistent with the tactile experience hypothesis, the blind significantly outperformed the sighted on all fingers, but not on the lips. Additionally, among blind participants, proficient Braille readers on their preferred reading index finger outperformed nonreaders. Finally, proficient Braille readers performed better with their preferred reading index finger than with the opposite index finger, and their acuity on the preferred reading finger correlated with their weekly reading time. These results clearly implicate reliance on the sense of touch as the trigger for tactile spatial acuity enhancement in the blind, and suggest the action of underlying experience-dependent neural mechanisms such as somatosensory and/or cross-modal cortical plasticity.
Critical Role of Astroglial Apolipoprotein E and Liver X Receptor-α Expression for Microglial Aβ Phagocytosis
Authors: Terwel Dick , Steffensen Knut R. , Verghese Philip B. , Kummer Markus P. , Gustafsson Jan-Åke , Holtzman David M. , Heneka Michael T.
Published: May 2011

Liver X receptors (LXRs) regulate immune cell function and cholesterol metabolism, both factors that are critically involved in Alzheimer's disease (AD). To investigate the therapeutic potential of long-term LXR activation in amyloid-β (Aβ) peptide deposition in an AD model, 13-month-old, amyloid plaque-bearing APP23 mice were treated with the LXR agonist TO901317. Postmortem analysis demonstrated that TO901317 efficiently crossed the blood–brain barrier. Insoluble and soluble Aβ levels in the treated APP23 mice were reduced by 80% and 40%, respectively, compared with untreated animals. Amyloid precursor protein (APP) processing, however, was hardly changed by the compound, suggesting that the observed effects were instead mediated by Aβ disposal. Despite the profound effect on Aβ levels, spatial learning in the Morris water maze was only slightly improved by the treatment. ABCA1 (ATP-binding cassette transporter 1) and apolipoprotein E (ApoE) protein levels were increased and found to be primarily localized in astrocytes. Experiments using primary microglia demonstrated that medium derived from primary astrocytes exposed to TO901317 stimulated phagocytosis of fibrillar Aβ. Conditioned medium from TO901317-treated ApoE−/−or LXRα−/−astrocytes did not increase phagocytosis of Aβ. In APP23 mice, long-term treatment with TO901317 strongly increased the association of microglia and Aβ plaques. Short-term treatment of APP/PS1 mice with TO901317 also increased this association, which was dependent on the presence of LXRα and was accompanied by increased ApoE lipidation. Together, these data suggest that astrocytic LXRα activation and subsequent release of ApoE by astrocytes is critical for the ability of microglia to remove fibrillar Aβ in response to treatment with TO901317.
A Novel Nonoperative Technique in the Initial Management and Treatment of Congenital Microstomia
Authors: Rezak Kristen M. , Bouvier Amy , Olack Brian , Larumbe Jose C. , Stelnicki Eric
Published: May 2011

Congenital microstomia in the newborn can result in poor functional and aesthetic outcomes. In the past, treatment options have included surgical methods such as commissurotomies and z-plasties as well as nonsurgical treatments using oral splints. In severe microstomia, a surgical release may be required to permit splint placement. Because of the small diameter of the stoma, such surgical releases are not optimal and frequently must be repeated. We devised a nonoperative technique for the initial treatment of congenital microstomia that will slowly enlarge the stomal diameter without the need for surgical release.

The patient is a newborn male born with multiple congenital anomalies including severe mandibular hypoplasia and retrusion, microstomia, and microglossia. The size of his oral cavity was less than 1 cm at birth with no clinical signs of a tongue. After initial dilation in the operating room with Hagar dilators, the oral stoma was serially dilated using Boston Scientific esophageal balloons. Once full dilation was achieved, we fabricated oral splints to continue the dilation process while maintaining oral competence with no surgical intervention.
Investigations on Inhibitors of Hedgehog Signal Pathway: A Quantitative Structure-Activity Relationship Study
Authors: Zhu Ruixin , Liu Qi , Tang Jian , Li Huiliang , Cao Zhiwei
Published: May 2011

The hedgehog signal pathway is an essential agent in developmental patterning, wherein the local concentration of the Hedgehog morphogens directs cellular differentiation and expansion. Furthermore, the Hedgehog pathway has been implicated in tumor/stromal interaction and cancer stem cell. Nowadays searching novel inhibitors for Hedgehog Signal Pathway is drawing much more attention by biological, chemical and pharmological scientists. In our study, a solid computational model is proposed which incorporates various statistical analysis methods to perform a Quantitative Structure-Activity Relationship (QSAR) study on the inhibitors of Hedgehog signaling. The whole QSAR data contain 93 cyclopamine derivatives as well as their activities against four different cell lines (NCI-H446, BxPC-3, SW1990 and NCI-H157). Our extensive testing indicated that the binary classification model is a better choice for building the QSAR model of inhibitors of Hedgehog signaling compared with other statistical methods and the corresponding in silico analysis provides three possible ways to improve the activity of inhibitors by demethylation, methylation and hydroxylation at specific positions of the compound scaffold respectively. From these, demethylation is the best choice for inhibitor structure modifications. Our investigation also revealed that NCI-H466 served as the best cell line for testing the activities of inhibitors of Hedgehog signal pathway among others.
Immobilization of Glucose Oxidase in Alginate-Chitosan Microcapsules
Authors: Wang Xia , Zhu Ke-Xue , Zhou Hui-Ming
Published: May 2011

In order to improve its stability and catalytic rate in flour, the immobilization of glucose oxidase (GOX) was investigated in this work. The enzyme was encapsulated in calcium alginate-chitosan microspheres (CACM) using an emulsification-internal gelation-GOX adsorption‑chitosan coating method. The interaction between alginate and chitosan was confirmed by infrared spectroscopy (IR). The resultant CACM in wet state, whose morphology was investigated by scanning electron microscopy (SEM), was spherical with a mean diameter of about 26 μm. The GOX load, encapsulation efficiency and activity of the CACM-GOX were influenced by concentration of chitosan, encapsulation time and encapsulation pH. The highest total enzymatic activity and encapsulation efficiency was achieved when the pH of the adsorption medium was near the isoelectric point (pI) of GOX, approximately pH 4.0. In addition, the molecular weight of chitosan also evidently influenced the encapsulation efficiency. Storage stabilities of GOX samples were investigated continuously over two months and the retained activity of CACM-GOX was 70.4%, markedly higher than the 7.5% of free enzyme. The results reveal the great potential of CACM-GOX as a flour improver.
2-(Benzoylamino)-3-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)acrylic acid
Authors: Kaushik Darpan , Verma Tarawanti , Madaan Kapish
Published: May 2011

A novel acrylic acid derivative was synthesized via acid hydrolysis of 4-((5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)-2-phenyloxazol-5(4H)-one in gl. acetic acid. The structure of the title compound was established on the basis of IR, 1H NMR, 13C-NMR and mass spectral data.
Consecutive Low Doses of Cyclosporine A Induce Pro-Inflammatory Cytokines and Accelerate Allograft Skin Rejection
Authors: López-Flores Roberto , Bojalil Rafael , Benítez José C. , Ledesma-Soto Yadira , Terrazas César A. , Rodríguez-Sosa Miriam , Terrazas Luis I.
Published: May 2011

Cyclosporine A (CsA) is a fungus-derived molecule with potent immunosuppressive activity that has been largely used to downregulate cell-mediated immune responses during transplantation. However, previous data have indicated that CsA shows immunomodulatory activity that relays on the antigen concentration and the dose of CsA used. To test the hypothesis that minimal doses of CsA may show different outcomes on grafts, we used an experimental model for skin transplants in mice. ICR outbred mice received skin allografts and were either treated daily with different doses of CsA or left untreated. Untreated mice showed allograft rejection within 14 days, with graft necrosis, infiltration of neutrophils and macrophages and displayed high percentages of CD8+ T cells in the spleens, which were associated with high serum levels of IL-12, IFN-g and TNF-α. As expected, mice treated with therapeutic doses of CsA (15 mg/kg) did not show allograft rejection within the follow-up period of 30 days and displayed the lowest levels of IL-12, IFN-g and TNF-α as well as a reduction in CD8+ lymphocytes. In contrast, mice treated with consecutive minimal doses of CsA (5 × 10−55 mg/kg) displayed an acute graft rejection as early as one to five days after skin allograft; they also displayed necrosis and strong inflammatory infiltration that was associated with high levels of IL-12, IFN-g and TNF-α. Moreover, the CD4+ CD25hiFoxP3+ subpopulation of cells in the spleens of these mice was significantly inhibited compared with animals that received the therapeutic treatment of CsA and those treated with placebo. Our data suggest that consecutive, minimal doses of CsA may affect Treg cells and may stimulate innate immunity.
Extended X-ray absorption fine structure of bimetallic nanoparticles
Authors: Antoniak Carolin
Published: May 2011

Electronic and magnetic properties strongly depend on the structure of the material, especially on the crystal symmetry and chemical environment. In nanoparticles, the break of symmetry at the surface may yield different physical properties with respect to the corresponding bulk material. A useful tool to investigate the electronic structure, magnetic behaviour and local crystallographic structure is X-ray absorption spectroscopy. In this review, recent developments in the field of extended X-ray absorption fine structure measurements and in the analysis methods for structural investigations of bimetallic nanoparticles are highlighted. The standard analysis based on Fourier transforms is compared to the relatively new field of wavelet transforms that have the potential to outperform traditional analysis, especially in bimetallic alloys. As an example, the lattice expansion and inhomogeneous alloying found in FePt nanoparticles is presented, and this is discussed below in terms of the influence of employed density functional theory calculations on the magnetic properties.
Sleep Duration and “on” Time during Different Periods of the Day and Night in Patients with Advanced Parkinson's Disease Receiving Adjunctive Ropinirole Prolonged Release
Authors: Reichmann Heinz , Cooper James , Rolfe Katie , Martinez-Martin Pablo
Published: May 2011

Patients undergoing long-term therapy for PD often experience motor fluctuations and nocturnal disturbances. In apost-hocanalysis, we explored effects of ropinirole prolonged release on sleep, night-time awakenings, and “on” time over 24 hours. Patients with advanced PD suboptimally controlled with L-dopa were randomized to adjunctive ropinirole prolonged release (2–24 mg/day) or placebo for 24 weeks. Awake/asleep and, if awake, “on”/“off” status was recorded via diary cards. At week 24 last observation carried forward, changes in nighttime or daytime sleep duration were not significantly different between treatments. Of patients with baseline awakenings, a significantly higher proportion in the ropinirole prolonged release group had a reduction in awakenings versus placebo. Patients receiving ropinirole prolonged release had a significantly greater increase in amount/percentage of awake time “on”/“on” without troublesome dyskinesia during all periods assessed (including night-time and early morning), versus placebo, and higher odds for being “on” on waking. Adjunctive once-daily ropinirole prolonged release may help provide 24-hour symptom control in patients with advanced PD not optimally controlled with L-dopa.
Enantioselective Potentiometric Membrane Electrodes Based on Antibiotics for the Determination of L- and D-Glyceric Acids
Authors: Stefan-van Staden Raluca-Ioana , Nejem R'afat M. , van Staden Jacobus Frederick , Aboul-Enein Hassan Y.
Published: May 2011

Glyceric acid (GA) is a human metabolite existing in L- and D-configurations, which are considered the markers for the diseases L- and D-glyceric aciduria/academia, respectively. Enantioselective, potentiometric membrane electrodes based on carbon paste modified with antibiotics as chiral selectors, vancomycin, and teicoplanin were designed for the assay of L- and D-GA, respectively, in the concentration ranges of 10−9–10−7and 10−4–10−2 moL/L with very low detection limits (1.5 × 10−10 moL/L for L-GA and 1.6 × 10−4  moL/L for D-GA, resp.). The surface of the electrodes can be regenerated simply by polishing in order to obtain a fresh surface ready to be used in a new assay. The proposed electrodes can be successfully applied for the enantioanalysis of L- and D-glyceric acids in serum samples.
Clinical Evaluation of Xylazine-Butorphanol-Guaifenesin-Ketamine as Short-Term TIVA in Equines
Authors: Thakur Bhanu Partap Singh , Sharma Sandeep Kumar , Sharma Arvind , Kumar Adarsh
Published: May 2011

Xylazine (1.1 mg/kg), butorphanol (0.02 mg/kg), guaifenesin 5% (20 mg/kg), and ketamine (2.2 mg/kg) combinations were able to induce short-term surgical anaesthesia for 23.33 ± 2.57 min in Spiti ponies with excellent to good muscle relaxation and analgesia. Urination and neighing was a constant feature during recovery period. Biphasic P wave, biphasic T wave, and depressed PR segment were common electrocardiographic findings. Biochemical attributes were within physiological limits except a significant increase in ALT values during anaesthesia. The values returned to normal during recovery ruling out any renal or hepatic toxicity. Occasionally, negative T wave, notched P wave, and sinus block were noticed. It is recommended that the anaesthetic combinations xylazine-butorphanol-guaifenesin-ketamine can be safely used for short-term total intravenous anaesthesia (TIVA) in equines under field conditions.
Acute Kidney Injury: Controversies Revisited
Authors: Yong Kenneth , Dogra Gursharan , Boudville Neil , Pinder Mary , Lim Wai
Published: May 2011

This paper addresses the epidemiology of AKI specifically in relation to recent changes in AKI classification and revisits the controversies regarding the timing of initiation of dialysis and the use of peritoneal dialysis as a renal replacement therapy for AKI. In summary, the new RIFLE/AKIN classifications of AKI have facilitated more uniform diagnosis of AKI and clinically significant risk stratification. Regardless, the issue of timing of dialysis initiation still remains unanswered and warrants further examination. Furthermore, peritoneal dialysis as a treatment modality for AKI remains underutilised in spite of potential beneficial effects. Future research should be directed at identifying early reliable biomarkers of AKI, which in conjunction with RIFLE/AKIN classifications of AKI could facilitate well-designed large randomised controlled trials of early versus late initiation of dialysis in AKI. In addition, further studies of peritoneal dialysis in AKI addressing dialysis dose and associated complications are required for this therapy to be accepted more widely by clinicians.
Regulation of Cell Survival Mechanisms in Alzheimer′s Disease by Glycogen Synthase Kinase‐3
Authors: Mines Marjelo A. , Beurel Eleonore , Jope Richard S.
Published: May 2011

A pivotal role has emerged for glycogen synthase kinase‐3 (GSK3) as an important contributor to Alzheimer′s disease pathology. Evidence for the involvement of GSK3 in Alzheimer′s disease pathology and neuronal loss comes from studies of GSK3 overexpression, GSK3 localization studies, multiple relationships between GSK3 and amyloid β‐peptide (Aβ), interactions between GSK3 and the microtubule‐associated tau protein, and GSK3‐mediated apoptotic cell death. Apoptotic signaling proceeds by either an intrinsic pathway or an extrinsic pathway. GSK3 is well established to promote intrinsic apoptotic signaling induced by many insults, several of which may contribute to neuronal loss in Alzheimer′s disease. Particularly important is evidence that GSK3 promotes intrinsic apoptotic signaling induced by Aβ. GSK3 appears to promote intrinsic apoptotic signaling by modulating proteins in the apoptosis signaling pathway and by modulating transcription factors that regulate the expression of proteins involved in apoptosis. Thus, GSK3 appears to contribute to several neuropathological mechanisms in Alzheimer′s disease, including apoptosis‐mediated neuronal loss.
The Registry and Follow-Up of Complex Pediatric Therapies Program of Western Canada: A Mechanism for Service, Audit, and Research after Life-Saving Therapies for Young Children
Authors: Robertson Charlene M. T. , Sauve Reg S. , Joffe Ari R. , Alton Gwen Y. , Moddemann Diane M. , Blakley Patricia M. , Synnes Anne R. , Dinu Irina A. , Harder Joyce R. , Soni Reeni , Bodani Jaya P. , Kakadekar Ashok P. , Dyck John D. , Human Derek G. , Ross David B. , Rebeyka Ivan M.
Published: May 2011

Newly emerging health technologies are being developed to care for children with complex cardiac defects. Neurodevelopmental and childhood school-related outcomes are of great interest to parents of children receiving this care, care providers, and healthcare administrators. Since the 1970s, neonatal follow-up clinics have provided service, audit, and research for preterm infants as care for these at-risk children evolved. We have chosen to present for this issue the mechanism for longitudinal follow-up of survivors that we have developed for western Canada patterned after neonatal follow-up. Our program provides registration for young children receiving complex cardiac surgery, heart transplantation, ventricular assist device support, and extracorporeal life support among others. The program includes multidisciplinary assessments with appropriate neurodevelopmental intervention, active quality improvement evaluations, and outcomes research. Through this mechanism, consistently high (96%) follow-up over two years is maintained.
GENT: Gene Expression Database of Normal and Tumor Tissues
Authors: Shin Gwangsik , Kang Tae-Wook , Yang Sungjin , Baek Su-Jin , Jeong Yong-Su , Kim Seon-Young
Published: May 2011

Background

Some oncogenes such as ERBB2 and EGFR are over-expressed in only a subset of patients. Cancer outlier profile analysis is one of computational approaches to identify outliers in gene expression data. A database with a large sample size would be a great advantage when searching for genes over-expressed in only a subset of patients.

Description

GENT (Gene Expression database of Normal and Tumor tissues) is a web-accessible database that provides gene expression patterns across diverse human cancer and normal tissues. More than 40000 samples, profiled by Affymetrix U133A or U133plus2 platforms in many different laboratories across the world, were collected from public resources and combined into two large data sets, helping the identification of cancer outliers that are over-expressed in only a subset of patients. Gene expression patterns in nearly 1000 human cancer cell lines are also provided. In each tissue, users can retrieve gene expression patterns classified by more detailed clinical information.

Conclusions

The large samples size (>24300 for U133plus2 and >16400 for U133A) of GENT provides an advantage in identifying cancer outliers. A cancer cell line gene expression database is useful for target validation by in vitro experiment. We hope GENT will be a useful resource for cancer researchers in many stages from target discovery to target validation. GENT is available at http://medicalgenome.kribb.re.kr/GENT/ or http://genome.kobic.re.kr/GENT/ .
Dapagliflozin: A Once-Daily Oral Therapy Sodium-Glucose Cotransporter-2 Inhibitor for the Treatment of Adult Patients with Type 2 Diabetes
Authors: Jadoon Khalid , Idris Iskandar
Published: May 2011

The induction of glycosuria using phlorizin, a nonselective inhibitor of renal and intestinal transport was well recognised to lower glucose levels and induce calorie loss in animal models of diabetes. Phlorizin and other similar molecules however were not suitable for clinical use due to adverse effects of non selective inhibition of extra-renal glucose transport system. More recent understanding of the physiology of renal glucose transport system and increased knowledge of rare genetic syndromes of renal glycosuria has resulted in the development of drugs that selectively inhibit the Sodium Glucose Transporter-2 (SGLT2). Among the various agents currently being developed within this drug class, dapagliflozin is the most advanced in clinical development. This article discusses the basic physiology of the SGLT2 transporter system, pharmacokinetics and pharmacodynamic information of dapagliflozin, its efficacy in lowering HbA1c and weight as well as its safety and adverse effects profile. This is discussed based on evidence derived from clinical trials involving a spectrum of patients with diabetes, from drug naïve to individuals already on insulin therapy.
Meclizine: Safety and Efficacy in the Treatment and Prevention of Motion Sickness
Authors: Patel Priti N. , Ambizas Emily M.
Published: May 2011

Motion sickness is a self-limiting but uncomfortable phenomenon experienced by many people. It is common during civilian travel and also among professionals during travel or military manoeuvres. Meclizine is a piperzine antihistamine that is effective for the prevention and treatment of motion sickness, particularly during mild civilian travel. It is well tolerated with few adverse effects and its oral dosage form is convenient for patients to take prior to exposure to motion as a preventative measure.
Effects of Kynurenine Pathway Inhibition on NAD+ Metabolism and Cell Viability in Human Primary Astrocytes and Neurons
Authors: Braidy Nady , Guillemin Gilles J. , Grant Ross
Published: May 2011

The kynurenine pathway (KP) is the principle route of L-Tryptophan (TRP) metabolism, producing several neurotoxic and neuroprotective metabolic precursors before complete oxidation to the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+). KP inhibition may prove therapeutic in central nervous system (CNS) inflammation by reducing the production of excitotoxins such as quinolinic acid (QUIN). However, KP metabolism may also be cytoprotective through the de novo synthesis of intracellular NAD+. We tested the hypothesis that the KP is directly involved in the maintenance of intracellular NAD+ levels and SIRT1 function in primary astrocytes and neurons through regulation of NAD+ synthesis. Competitive inhibition of indoleamine 2,3 dioxygenase (IDO), and quinolinic acid phosphoribosyltransferase (QPRT) activities with 1-methyl-L-Tryptophan (1-MT), and phthalic acid (PA) respectively, resulted in a dose-dependent decrease in intracellular NAD+ levels and sirtuin deacetylase-1 (SIRT1) activity, and correlated directly with reduced cell viability. These results support the hypothesis that the primary role of KP activation during neuroinflammation is to maintain NAD+ levels through de novo synthesis from TRP. Inhibition of KP metabolism under these conditions can compromise cell viability, NAD-dependent SIRT1 activity and CNS function, unless alternative precursors for NAD+ synthesis are made available.
Alzheimers Disease: Review of Emerging Treatment Role for Intravenous Immunoglobulins
Authors: Kayed Rakez , Jackson George R. , Estes D. Mark , Barrett Alan D.T.
Published: May 2011

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Currently available therapies are symptomatic but do not alter underlying disease progression. Immunotherapeutic approaches such as anti Aβ peptide active vaccination trials have had limited success to date. Intravenous immunoblobulin (IVIg) is widely used in immune-mediated neurological disorders such myasthenia gravis and Guillain-Barre syndrome. These preparations have been obtained from the pooled plasma of healthy human donors and contain natural anti-amyloid antibodies and are well tolerated. A small pilot study of passive immunotherapy using IVIg has suggested cognitive improvement. A multicenter phase III trial is ongoing and will determine whether or not this treatment can ameliorate cognitive deficits in mild-to-moderate AD. Here, we briefly review the pathogenic role of amyloid and tau in AD, as well as immunotherapeutic efforts to date. We also summarize what is known about naturally occurring anti-Aβ and tau antibodies in IVIg with a view toward explaining potential mechanisms underlying their therapeutic effects.
Analysis of the Membrane proteins of an Antarctic Bacterium Pseudomonas Syringae
Authors: Jagannadham M.V. , Saranya S.
Published: May 2011

The proteins of an Antarctic bacterium Pseudomonas syringae Lz4W, identified earlier by different membrane protein preparation methods, were combined together and the redundant identities removed. In total, 1479 proteins including 148 outer membrane proteins from this bacterium were predicted by the algorithm PSORTb3.0. A detailed analysis on their subcellular localization was undertaken which was determined using TMHMM, TMB-hunt and BOMP. A comparison of PSORTb predicted outer membrane proteins with BOMP, revealed that most of the proteins predicted by the former, contained β–barrels in the outer membranes. A comparative analysis of PSORTb, TMHMM and TMB-hunt reveals that most of the outer membranes proteins of this bacterium could be identified using this approach. Thus, by using a combination of biochemical and different bioinformatics algorithms, the membrane proteins of P. syringae are analyzed. In particular, PSORTb results are compared and supported by other algorithms, to improve the strength of OM proteins prediction. Several proteins, having an important role in cold adaptation of the organism, could also be identified.
Characteristics of pollutants and their correlation to meteorological conditions at a suburban site in the North China Plain
Authors: Xu W. Y. , Zhao C. S. , Ran L. , Deng Z. Z. , Liu P. F. , Ma N. , Lin W. L. , Xu X. B. , Yan P. , He X. , Yu J. , Liang W. D. , Chen L. L.
Published: May 2011

Abstract. North China Plain (NCP) is one of the most densely populated regions in China and has experienced enormous economic growth in the past decades. Its regional trace gas pollution has also become one of the top environmental concerns in China. Measurements of surface trace gases, including O3, NOx, SO2 and CO were carried out within the HaChi (Haze in China) project at Wuqing Meteorology Station, located between 2 mega-cities (Beijing and Tianjin) in the NCP, from 9 July 2009 to 21 January 2010. Detailed statistical analyses were made in order to provide information on the levels of the measured air pollutants and their characteristics. Gaseous air pollutant concentrations were also studied together with meteorological data and satellite data to help us better understand the causes of the observed variations in the trace gases during the field campaign. In comparison to measurements from other rural and background stations in the NCP, relatively high concentrations were detected in Wuqing, presumably due to regional mixing and transport of pollutants. Local meteorology had deterministic impacts on air pollution levels, which have to be accounted for when evaluating other effects on pollutant concentrations. Trace gas concentrations showed strong dependence on wind, providing information on regional pollution characteristics. O3 mixing ratio also showed clear dependencies on temperature and relative humidity.
Distribution of hydrogen peroxide and formaldehyde over Central Europe during the HOOVER project
Authors: Klippel T. , Fischer H. , Bozem H. , Lawrence M. G. , Butler T. , Jöckel P. , Tost H. , Martinez M. , Harder H. , Regelin E. , Sander R. , Schiller C. L. , Stickler A. , Lelieveld J.
Published: May 2011

Abstract. In this study we report measurements of hydrogen peroxide (H2O2), methyl hydroperoxide* (MHP* as a proxy of MHP based on an unspecific measurement of total organic peroxides) and formaldehyde (HCHO) from the HOx OVer EuRope (HOOVER) project (HOx = OH+HO2). HOOVER included two airborne field campaigns, in October 2006 and July 2007. Measurement flights were conducted from the base of operation Hohn (Germany, 54° N, 9° E) towards the Mediterranean and to the subpolar regions over Norway. We find negative concentration gradients with increasing latitude throughout the troposphere for H2O2 and CH3OOH*. In contrast, observed HCHO is almost homogeneously distributed over central and northern Europe and is elevated over the Mediterranean. In general, the measured gradients tend to be steepest entering the Mediterranean region, where we also find the highest abundances of the 3 species. Mixing ratios of these tracers generally decrease with altitude. H2O2 and CH3OOH* show maxima above the boundary layer at 2–5 km, being more distinct over southern than over northern Europe. We also present a comparison of our data with simulations by two global 3-D-models, MATCH-MPIC and EMAC, and with the box model CAABA. The models realistically represent altitude and latitude gradients for both HCHO and hydroperoxides (ROOH). In contrast, the models have problems reproducing the absolute mixing ratios, in particular of H2O2. Large uncertainties about retention coefficients and cloud microphysical parameters suggest that cloud scavenging might be a large source of error for the simulation of H2O2. A sensitivity study with EMAC shows a strong influence of cloud and precipitation scavenging on the budget of H2O2 as simulations improve significantly with this effect switched off.