bluuebunny/crossref_metadata_2025 huggingface dataset:
In VivoDiffusion Tensor Imaging and Histopathology of the Fimbria-Fornix in Temporal Lobe Epilepsy
Authors: Concha Luis , Livy Daniel J. , Beaulieu Christian , Wheatley B. Matt , Gross Donald W.
Published: January 2010

While diffusion tensor imaging (DTI) has been extensively used to infer micro-structural characteristics of cerebral white matter in human conditions, correlations between humanin vivoDTI and histology have not been performed. Temporal lobe epilepsy (TLE) patients with mesial temporal sclerosis (MTS) have abnormal DTI parameters of the fimbria-fornix (relative to TLE patients without MTS) which are presumed to represent differences in axonal/myelin integrity. Medically intractable TLE patients who undergo temporal lobe resection including the fimbria-fornix provide a unique opportunity to study the anatomical correlates of water diffusion abnormalities in freshly excised tissue. Eleven patients with medically intractable TLE were recruited (six with and five without MTS) for presurgical DTI followed by surgical excision of a small specimen of the fimbria-fornix which was processed for electron microscopy. Blinded quantitative analysis of the microphotographs included axonal diameter, density and area, cumulative axon membrane circumference, and myelin thickness and area. As predicted by DTI the fimbria-fornix of TLE patients with MTS had increased extra-axonal fraction, and reduced cumulative axonal membrane circumference and myelin area. Consistent with the animal literature, water diffusion anisotropy over the crus of the fimbria-fornix was strongly correlated with axonal membranes (cumulative membrane circumference) within the surgical specimen (∼15% of what was analyzed with DTI). The demonstration of a correlation between histology and humanin vivoDTI, in combination with the observation thatin vivoDTI accurately predicted white matter abnormalities in a human disease condition, provides strong validation of the application of DTI as a noninvasive marker of white matter pathology.
From Comparison to Classification: A Cortical Tool for Boosting Perception
Authors: Nahum Mor , Daikhin Luba , Lubin Yedida , Cohen Yamit , Ahissar Merav
Published: January 2010

Humans are much better in relative than in absolute judgments. This common assertion is based on findings that discrimination thresholds are much lower when measured with methods that allow interstimuli comparisons than when measured with methods that require classification of one stimulus at a time and are hence sensitive to memory load. We now challenged this notion by measuring discrimination thresholds and evoked potentials while listeners performed a two-tone frequency discrimination task. We tested various protocols that differed in the pattern of cross-trial tone repetition. We found that best performance was achieved only when listeners effectively used cross-trial repetition to avoid interstimulus comparisons with the repeated reference tone. Instead, they classified one tone, the nonreference tone, as either high or low by comparing it with a recently formed internal reference. Listeners were not aware of the switch from interstimulus comparison to classification. Its successful use was revealed by the conjunction of improved behavioral performance and an event-related potential component (P3), indicating an implicit perceptual decision, which followed the nonreference tone in each trial. Interestingly, tone repetition itself did not suffice for the switch, implying that the bottleneck to discrimination does not reside at the lower, sensory stage. Rather, the temporal consistency of repetition was important, suggesting the involvement of higher-level mechanisms with longer time constants. These findings suggest that classification is based on more automatic and accurate mechanisms than interstimulus comparisons and that the ability to effectively use them depends on a dynamic interplay between higher- and lower-level cortical mechanisms.
α2-Adrenoceptor Blockade Accelerates the Neurogenic, Neurotrophic, and Behavioral Effects of Chronic Antidepressant Treatment
Authors: Yanpallewar Sudhirkumar U. , Fernandes Kimberly , Marathe Swananda V. , Vadodaria Krishna C. , Jhaveri Dhanisha , Rommelfanger Karen , Ladiwala Uma , Jha Shanker , Muthig Verena , Hein Lutz , Bartlett Perry , Weinshenker David , Vaidya Vidita A.
Published: January 2010

Slow-onset adaptive changes that arise from sustained antidepressant treatment, such as enhanced adult hippocampal neurogenesis and increased trophic factor expression, play a key role in the behavioral effects of antidepressants. α2-Adrenoceptors contribute to the modulation of mood and are potential targets for the development of faster acting antidepressants. We investigated the influence of α2-adrenoceptors on adult hippocampal neurogenesis. Our results indicate that α2-adrenoceptor agonists, clonidine and guanabenz, decrease adult hippocampal neurogenesis through a selective effect on the proliferation, but not the survival or differentiation, of progenitors. These effects persist in dopamine β-hydroxylase knock-out (Dbh−/−) mice lacking norepinephrine, supporting a role for α2-heteroceptors on progenitor cells, rather than α2-autoreceptors on noradrenergic neurons that inhibit norepinephrine release. Adult hippocampal progenitorsin vitroexpress all the α2-adrenoceptor subtypes, and decreased neurosphere frequency and BrdU incorporation indicate direct effects of α2-adrenoceptor stimulation on progenitors. Furthermore, coadministration of the α2-adrenoceptor antagonist yohimbine with the antidepressant imipramine significantly accelerates effects on hippocampal progenitor proliferation, the morphological maturation of newborn neurons, and the increase in expression of brain derived neurotrophic factor and vascular endothelial growth factor implicated in the neurogenic and behavioral effects of antidepressants. Finally, short-duration (7 d) yohimbine and imipramine treatment results in robust behavioral responses in the novelty suppressed feeding test, which normally requires 3 weeks of treatment with classical antidepressants. Our results demonstrate that α2-adrenoceptors, expressed by progenitor cells, decrease adult hippocampal neurogenesis, while their blockade speeds up antidepressant action, highlighting their importance as targets for faster acting antidepressants.
Rapid, Learning-Induced Inhibitory Synaptogenesis in Murine Barrel Field
Authors: Jasinska Malgorzata , Siucinska Ewa , Cybulska-Klosowicz Anita , Pyza Elzbieta , Furness David N. , Kossut Malgorzata , Glazewski Stanislaw
Published: January 2010

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse. Here, we show using quantitative transmission electron microscopy that a simple form of learning involving mystacial vibrissae results in ∼70% increase in the density of inhibitory synapses on spines of neurons located in layer IV barrels that represent the stimulated vibrissae. The spines contain one asymmetrical (excitatory) and one symmetrical (inhibitory) synapse (double-synapse spines), and their density increases threefold as a result of learning with no apparent change in the density of asymmetrical synapses. This effect seems to be specific for learning because pseudoconditioning (in which the conditioned and unconditioned stimuli are delivered at random) does not lead to the enhancement of symmetrical synapses but instead results in an upregulation of asymmetrical synapses on spines. Symmetrical synapses of cells located in barrels receiving the conditioned stimulus also show a greater concentration of GABA in their presynaptic terminals. These results indicate that the immediate effect of classical conditioning in the “conditioned” barrels is rapid, pronounced, and inhibitory.
In the Adult Hippocampus, Chronic Nerve Growth Factor Deprivation Shifts GABAergic Signaling from the Hyperpolarizing to the Depolarizing Direction
Authors: Lagostena Laura , Rosato-Siri Marcelo , D'Onofrio Mara , Brandi Rossella , Arisi Ivan , Capsoni Simona , Franzot Jessica , Cattaneo Antonino , Cherubini Enrico
Published: January 2010

GABA, the main inhibitory transmitter in adulthood, early in postnatal development exerts a depolarizing and excitatory action. This effect, which results from a high intracellular chloride concentration ([Cl−]i), promotes neuronal growth and synaptogenesis. During the second postnatal week, the developmental regulated expression of the cation-chloride cotransporter KCC2 accounts for the shift of GABA from the depolarizing to the hyperpolarizing direction. Changes in chloride homeostasis associated with high [Cl−]ihave been found in several neurological disorders, including temporal lobe epilepsy. Here, we report that, in adult transgenic mice engineered to express recombinant neutralizing anti-nerve growth factor antibodies (AD11 mice), GABA became depolarizing and excitatory. AD11 mice exhibit a severe deficit of the cholinergic function associated with an age-dependent progressive neurodegenerative pathology resembling that observed in Alzheimer patients. Thus, in hippocampal slices obtained from 6-month-old AD11 (but not wild-type) mice, the GABAAagonist isoguvacine significantly increased the firing of CA1 principal cells and, at the network level, the frequency of multiunit activity recorded with extracellular electrodes. In addition, in AD11 mice, the reversal of GABAA-mediated postsynaptic currents and of GABA-evoked single-channel currents were positive with respect to the resting membrane potential as estimated in perforated patch and cell attached recordings, respectively. Real-time quantitative reverse transcription-PCR and immunocytochemical experiments revealed a reduced expression of mRNA encoding for Kcc2 and of the respective protein. This novel mechanism may represent a homeostatic response that counterbalances within the hippocampal network the Alzheimer-like neurodegenerative pathology found in AD11 mice.
A Basal Ganglia Pathway Drives Selective Auditory Responses in Songbird Dopaminergic Neurons via Disinhibition
Authors: Gale Samuel D. , Perkel David J.
Published: January 2010

Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to the bird's own song (BOS) than to other sounds, and area X is critical for these responses. Direct pharmacological modulation of area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song control regions to dopaminergic neurons involves a projection from area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that area X disinhibits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning.
The Type I Interferon-α Mediates a More Severe Neurological Disease in the Absence of the Canonical Signaling Molecule Interferon Regulatory Factor 9
Authors: Hofer Markus J. , Li Wen , Lim Sue Ling , Campbell Iain L.
Published: January 2010

Type I interferons (IFN) are crucial in host defense but also are implicated as causative factors for neurological disease. Interferon regulatory factor (IRF9) is involved in type I IFN-regulated gene expression where it associates with STAT1:STAT2 heterodimers to form the transcriptional complex ISGF3. The role of IRF9 in cellular responses to type I IFN is poorly definedin vivoand hence was examined here. While transgenic mice (termedGIFN) with chronic production of low levels of IFN-α in the CNS were relatively unaffected, the same animals lacking IRF9 [GIFNxIRF9 knock-out(KO)] had cataracts, became moribund, and died prematurely. The brain ofGIFNxIRF9 KOmice showed calcification with pronounced inflammation and neurodegeneration whereas inflammation and retinal degeneration affected the eyes. In addition, IFN-γ-like gene expression in the CNS in association with IFN-γ mRNA and increased phosphotyrosine-STAT1 suggested a role for IFN-γ. However,GIFNxIRF9 KOmice deficient for IFN-γ signaling developed an even more severe and accelerated disease, indicating that IFN-γ was protective. In IRF9-deficient cultured mixed glial cells, IFN-α induced prolonged activation of STAT1 and STAT2 and induced the expression of IFN-γ-like genes. We conclude that (1) type I IFN signaling and cellular responses can occurin vivoin the absence of IRF9, (2) IRF9 protects against the pathophysiological actions of type I IFN in the CNS, and (3) STAT1 and possibly STAT2 participate in alternative IRF9-independent signaling pathways activated by IFN-α in glial cells resulting in enhanced IFN-γ-like responses.
Assembly and Stoichiometry of the AMPA Receptor and Transmembrane AMPA Receptor Regulatory Protein Complex
Authors: Kim Kwang S. , Yan Dan , Tomita Susumu
Published: January 2010

Glutamate is a major excitatory neurotransmitter in the vertebrate brain. AMPA-type glutamate receptors mediate fast excitatory transmission. AMPA receptors assemble with transmembrane AMPA receptor regulatory protein (TARP) auxiliary subunits and function as native ion channels. However, the assembly and stoichiometry of AMPA receptor and TARP complexes remain unclear. Here, we developed a novel strategy to determine the assembly and stoichiometry of this protein complex and found that functional AMPA receptors indeed assembled as a tetramer in a dimer-of-dimers structure. Furthermore, we found that the AMPA receptor auxiliary subunit, TARP, had a variable stoichiometry (1–4 TARP units) on AMPA receptors and that 1 TARP unit was sufficient to modulate AMPA receptor activity. In neurons, TARP had fixed and minimum stoichiometry on AMPA receptors. This fundamental composition of the AMPA receptor/TARP complex is important for the elucidation of the molecular machinery that underlies synaptic transmission.
Rapamycin Protects against Neuron Death inIn VitroandIn VivoModels of Parkinson's Disease
Authors: Malagelada Cristina , Jin Zong Hao , Jackson-Lewis Vernice , Przedborski Serge , Greene Lloyd A.
Published: January 2010

We report that rapamycin, an allosteric inhibitor of certain but not all actions of the key cellular kinase mammalian target of rapamycin (mTOR), protects neurons from death in both cellular and animal toxin models of Parkinson's disease (PD). This protective action appears to be attributable to blocked translation of RTP801/REDD1/Ddit4, a protein that is induced in cell and animal models of PD and in affected neurons of PD patients and that causes neuron death by leading to dephosphorylation of the survival kinase Akt. In support of this mechanism, in PD models, rapamycin spares phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity. The capacity of rapamycin to provide neuroprotection in PD models appears to arise from its selective suppression of some but not all actions of mTOR, as indicated by the contrasting finding that Torin1, a full catalytic mTOR inhibitor, is not protective and induces Akt dephosphorylation and neuron death.
Enhancement of Spatial Reversal Learning by 5-HT2CReceptor Antagonism Is Neuroanatomically Specific
Authors: Boulougouris Vasileios , Robbins Trevor W.
Published: January 2010

We have recently demonstrated that systemic administration of 5-HT2Cand 5-HT2Areceptor antagonists significantly enhanced and impaired spatial reversal learning, respectively. In this study, the role of 5-HT2Cand 5-HT2Areceptor subtypes in the mediation of these opposing effects was further investigated with respect to neuroanatomical specificity. The roles of 5-HT2Cand 5-HT2Areceptors were examined within some of the brain regions implicated in cognitive flexibility, namely the orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), by means of targeted infusions of selective 5-HT2Cand 5-HT2Areceptor antagonists (SB 242084 and M100907, respectively). Intra-OFC 5-HT2Creceptor antagonism produced dose-dependent effects similar to those of systemic administration, i.e., improved spatial reversal learning by reducing the number of trials (all doses: 0.1, 0.3, and 1.0 μg) and perseverative errors to criterion (0.3 and 1.0 μg) compared with controls. However, the highest dose (1.0 μg) showed a nonselective effect, as it also affected retention preceding the reversal phase and decreased learning errors. Intracerebral infusions of SB 242084 into the mPFC or NAc produced no significant effects on any behavioral measures. Similarly, no significant differences were observed with intra-OFC, -mPFC, or -NAc infusions of M100907. These data suggest that the improved performance in reversal learning observed after 5-HT2Creceptor antagonism is mediated within the OFC. These data also bear on the issue of whether 5-HT2Creceptor antagonism within the OFC might help elucidate the biological substrate of obsessive-compulsive disorder, offering the potential for therapeutic application.
ADAM22, A Kv1 Channel-Interacting Protein, Recruits Membrane-Associated Guanylate Kinases to Juxtaparanodes of Myelinated Axons
Authors: Ogawa Yasuhiro , Oses-Prieto Juan , Kim Moon Young , Horresh Ido , Peles Elior , Burlingame Alma L. , Trimmer James S. , Meijer Dies , Rasband Matthew N.
Published: January 2010

Clustered Kv1 K+channels regulate neuronal excitability at juxtaparanodes of myelinated axons, axon initial segments, and cerebellar basket cell terminals (BCTs). These channels are part of a larger protein complex that includes cell adhesion molecules and scaffolding proteins. To identify proteins that regulate assembly, clustering, and/or maintenance of axonal Kv1 channel protein complexes, we immunoprecipitated Kv1.2 α subunits, and then used mass spectrometry to identify interacting proteins. We found that a disintegrin and metalloproteinase 22 (ADAM22) is a component of the Kv1 channel complex and that ADAM22 coimmunoprecipitates Kv1.2 and the membrane-associated guanylate kinases (MAGUKs) PSD-93 and PSD-95. When coexpressed with MAGUKs in heterologous cells, ADAM22 and Kv1 channels are recruited into membrane surface clusters. However, coexpression of Kv1.2 with ADAM22 and MAGUKs does not alter channel properties. Among all the known Kv1 channel-interacting proteins, only ADAM22 is found at every site where Kv1 channels are clustered. Analysis ofCaspr-null mice showed that, like other previously described juxtaparanodal proteins, disruption of the paranodal junction resulted in redistribution of ADAM22 into paranodal zones. Analysis ofCaspr2-,PSD-93-,PSD-95-, and doublePSD-93/PSD-95-null mice showed ADAM22 clustering at BCTs requires PSD-95, but ADAM22 clustering at juxtaparanodes requires neither PSD-93 nor PSD-95. In direct contrast, analysis ofADAM22-null mice demonstrated juxtaparanodal clustering of PSD-93 and PSD-95 requires ADAM22, whereas Kv1.2 and Caspr2 clustering is normal inADAM22-null mice. Thus, ADAM22 is an axonal component of the Kv1 K+channel complex that recruits MAGUKs to juxtaparanodes.
Bilateral Postsynaptic Actions of Pyramidal Tract and Reticulospinal Neurons on Feline Erector Spinae Motoneurons
Authors: Galea Mary Pauline , Hammar Ingela , Nilsson Elin , Jankowska Elzbieta
Published: January 2010

Trunk muscles are important for postural adjustments associated with voluntary movements but little has been done to analyze mechanisms of supraspinal control of these muscles at a cellular level. The present study therefore aimed to investigate the input from pyramidal tract (PT) neurons to motoneurons of the musculus longissimus lumborum of the erector spinae and to analyze to what extent it is relayed by reticulospinal (RS) neurons. Intracellular records from motoneurons were used to evaluate effects of electrical stimulation of medullary pyramids and of axons of RS neurons descending in the medial longitudinal fasciculus (MLF). The results revealed that similar synaptic actions were evoked from the ipsilateral and contralateral PTs, including disynaptic and trisynaptic EPSPs and trisynaptic IPSPs. Stimulation of the MLF-evoked monosynaptic and disynaptic EPSPs and disynaptic or trisynaptic IPSPs in the same motoneurons. All short-latency PSPs of PT origin were abolished by transection of the MLF, while they remained after transection of PT fibers at a spinal level. Hence, RS neurons might serve as the main relay neurons of the most direct PT actions on musculus (m.) longissimus. However, longer-latency IPSPs remaining after MLF or PT spinal lesions and after ipsilateral or contralateral hemisection of spinal cord indicate that PT actions are also mediated by ipsilaterally and/or contralaterally located spinal interneurons. The bilateral effects of PT stimulation thereby provide an explanation why trunk movements after unilateral injuries of PT neurons (e.g., stroke) are impaired to a lesser degree than movements of the extremities.
Somatostatin Contributes toIn VivoGamma Oscillation Modulation and Odor Discrimination in the Olfactory Bulb
Authors: Lepousez Gabriel , Mouret Aurélie , Loudes Catherine , Epelbaum Jacques , Viollet Cécile
Published: January 2010

Neuropeptides are systematically encountered in local interneurons, but their functional contribution in neural networks is poorly documented. In the mouse main olfactory bulb (MOB), somatostatin is mainly concentrated in local GABAergic interneurons restricted to the external plexiform layer (EPL). Immunohistochemical experiments revealed that the sst2 receptor, the major somatostatin receptor subtype in the telencephalon, is expressed by mitral cells, the MOB principal cells. As odor-activated mitral cells synchronize and generate gamma oscillations of the local field potentials, we investigated whether pharmacological manipulations of sst2 receptors could influence these oscillations in freely behaving mice. In wild-type, but not in sst2 knock-out mice, gamma oscillation power decreased lastingly after intrabulbar injection of an sst2-selective antagonist (BIM-23627), while sst2-selective agonists (octreotide and L-779976) durably increased it. Sst2-mediated oscillation changes were correlated with modifications of the dendrodendritic synaptic transmission between mitral and granule cells. Finally, bilateral injections of BIM-23627 and octreotide respectively decreased and increased odor discrimination performances. Together, these results suggest that endogenous somatostatin, presumably released from EPL interneurons, affects gamma oscillations through the dendrodendritic reciprocal synapse and contributes to olfactory processing. This provides the first direct correlation between synaptic, oscillatory, and perceptual effects induced by an intrinsic neuromodulator.
Brain-Derived Neurotrophic Factor and Epidermal Growth Factor Activate Neuronal m-Calpain via Mitogen-Activated Protein Kinase-Dependent Phosphorylation
Authors: Zadran Sohila , Jourdi Hussam , Rostamiani Karoline , Qin Qingyu , Bi Xiaoning , Baudry Michel
Published: January 2010

Calpain is a calcium-dependent protease that plays a significant role in synaptic plasticity, cell motility, and neurodegeneration. Two major calpain isoforms are present in brain, with μ-calpain (calpain1) requiring micromolar calcium concentrations for activation and m-calpain (calpain2) needing millimolar concentrations. Recent studies in fibroblasts indicate that epidermal growth factor (EGF) can activate m-calpain independently of calcium via mitogen-activated protein kinase (MAPK)-mediated phosphorylation. In neurons, MAPK is activated by both brain-derived neurotrophic factor (BDNF) and EGF. We therefore examined whether these growth factors could activate m-calpain by MAPK-dependent phosphorylation using cultured primary neurons and HEK–TrkB cells, both of which express BDNF and EGF receptors. Calpain activation was monitored by quantitative analysis of spectrin degradation and by a fluorescence resonance energy transfer (FRET)-based assay, which assessed the truncation of a calpain-specific peptide flanked by the FRET fluorophore pair DABCYL and EDANS. In both cell types, BDNF and EGF rapidly elicited calpain activation, which was completely blocked by MAPK and calpain inhibitors. BDNF stimulated m-calpain but not μ-calpain serine phosphorylation, an effect also blocked by MAPK inhibitors. Remarkably, BDNF- and EGF-induced calpain activation was preferentially localized in dendrites and dendritic spines of hippocampal neurons and was associated with actin polymerization, which was prevented by calpain inhibition. Our results indicate that, in cultured neurons, both BDNF and EGF activate m-calpain by MAPK-mediated phosphorylation. These results strongly support a role for calpain in synaptic plasticity and may explain why m-calpain, although widely expressed in CNS, requires nonphysiological calcium levels for activation.
Neuroblastoma Phox2b Variants Stimulate Proliferation and Dedifferentiation of Immature Sympathetic Neurons
Authors: Reiff Tobias , Tsarovina Konstantina , Majdazari Afsaneh , Schmidt Mirko , del Pino Isabel , Rohrer Hermann
Published: January 2010

Neuroblastoma is a pediatric tumor that is thought to arise from autonomic precursors in the neural crest. Mutations in thePHOX2Bgene have been observed in familial and sporadic forms of neuroblastoma and represent the first defined genetic predisposition for neuroblastoma. Here, we address the mechanisms that may underlie this predisposition, comparing the function of wild-type and mutant Phox2b proteins ectopically expressed in proliferating, embryonic sympathetic neurons. Phox2b displays a strong antiproliferative effect, which is lost in all Phox2b neuroblastoma variants analyzed. In contrast, an increase in sympathetic neuron proliferation is elicited by Phox2b variants with mutations in the homeodomain when endogenous Phox2b levels are lowered by siRNA-mediated knockdown to mimic the situation of heterozygousPHOX2Bmutations in neuroblastoma. The increased proliferation is blocked by Hand2 knockdown and the antiproliferative Phox2b effects are rescued by Hand2 overexpression, implying Hand2 in Phox2b-mediated proliferation control. A Phox2b variant with a nonsense mutation in the homeodomain elicits, in addition, a decreased expression of characteristic marker genes. Together, these results suggest thatPHOX2Bmutations predispose to neuroblastoma by increasing proliferation and promoting dedifferentiation of cells in the sympathoadrenergic lineage.
Medication information leaflets for patients: The further validation of an analytic linguistic framework
Authors: Clerehan Rosemary , Hirsh Di , Buchbinder Rachelle
Published: January 2010

While clinicians may routinely use patient information leaflets about drug therapy, a poorly conceived leaflet has the potential to do harm. We previously developed a novel approach to analysing leaflets about a rheumatoid arthritis drug, using an analytic approach based on systemic functional linguistics. The aim of the present study was to verify the validity of the linguistic framework by applying it to two further arthritis drug leaflets. The findings confirmed the applicability of the framework and were used to refine it. A new stage or ‘move’ in the genre was identified. While the function of many of the moves appeared to be ‘to instruct’ the patient, the instruction was often unclear. The role relationships expressed in the text were critical to the meaning. As with our previous study, judged on their lexical density, the leaflets resembled academic text. The framework can provide specific tools to assess and produce medication information leaflets to support readers in taking medication. Future work could utilize the framework to evaluate information on other treatments and procedures or on healthcare information more widely.
Marked bodies and selves: A literary-semiotic perspective on breast cancer and identity
Authors: Henriksen Nina , Hansen Helle Ploug
Published: January 2010

A diagnosis of breast cancer is not just life-threatening but often also disfiguring. Breast cancer research has pointedly focused on the connection between bodily loss and loss of self. We will examine the narratives of two Danish women who have been treated for breast cancer and are dealing with the consequences of their treatment. Drawing upon theories of phenomenology and literary-semiotics we demonstrate how the women are negotiating their identities. In narratives of breast cancer bodily practices play a prominent role in helping or hindering the re-construction of identity. We will focus on breast reconstruction as a bodily practice and seek to understand how and why breast cancer survivors either accept or reject the possibility of reconstructing their identity through breast reconstruction. We suggest that the literary semiotic concept of marking can lead to a broader understanding of the connection between illness, body and identity. Breast reconstruction and the refusal of breast reconstruction can be viewed as part of a semiotic monitoring and marking of the body that can take place in the aftermath of treatment for breast cancer.
Misunderstandings in multilingual counselling settings involving school nurses and obese/overweight pupils
Authors: Magnusson Maria Birgitta , Hulthén Lena , Kjellgren Karin I
Published: January 2010

School nurses’ counselling is pivotal in stemming the obesity epidemic. Barriers for good counselling such as nurses’ misunderstandings and ambiguities when relating to overweight and obesity need to be addressed. In this study, we explored misunderstandings in school nurses’ counselling of overweight pupils in multilingual settings, together with how school nurses talk about the condition. Counselling sessions involving eight nurses and 20 pupils (aged 8–16 years) were audio-recorded and analysed using theme-oriented discourse analysis. Statistical methods were used as a complement. The focal themes were misunderstandings and nurses’ talk about overweight and obesity. Analytical themes were framing, footing and facework. Data analyses revealed three main origins of misunderstandings occurring in school nurses’ counselling of obese and overweight pupils: (1) nurses’ illusion that they know what advice the pupils need; (2) nurses’ insensitivity to the pupils’ and parents’ concerns; and (3) lack of lingual understanding. School nurses’ apparent difficulties to talk about overweight and obesity suggest a need to reflect on how to name these issues during counselling. School nurses’ dominance and pupils’ passivity were obvious. We suggest that counselling should be regarded as learning contexts and be subjected to possible quality assurance in the future.
Accounting for medical communication: Parents’ perceptions of communicative roles and responsibilities in the pediatric intensive care unit
Authors: Gordon Cynthia , Barton Ellen , Meert Kathleen L. , Eggly Susan , Pollack Murray , Zimmerman Jerry , Anand K. J.S. , Carcillo Joseph , Newth Christopher J.L. , Dean J. Michael , Willson Douglas F. , Nicholson Carol
Published: January 2010

Through discourse analysis of transcribed interviews conducted over the phone with parents whose child died in the Pediatric Intensive Care Unit (PICU) (n = 51), this study uncovers parents’ perceptions of clinicians’ and their own communicative roles and responsibilities in the context of team-based care. We examine parents’ descriptions and narratives of communicative experiences they had with PICU clinicians, focusing on how parents use accounts to evaluate the communicative behaviors they report (n = 47). Findings indicate that parental perceptions of communicative responsibilities are more nuanced than assumed in previous research: Parents identified their own responsibilities as participating as part of the team of care, gathering information, interacting with appropriate affect, and working to understand complex and uncertain medical information. Complementarily, parents identified clinician responsibilities as communicating professionally, providing medical information clearly, managing parents’ hope responsibly, and communicating with appropriate affect. Through the accounts they provide, parents evaluate both parental and clinician role-responsibilities as fulfilled and unfulfilled. Clinicians’ management of prognostic uncertainty and parents’ struggles to understand that uncertainty emerged as key, complementary themes with practical implications for incorporating parents into the PICU care team. The study also highlights insights retrospective interview data bring to the examination of medical communication.
Chinese mental illness narratives: Controlling the spirit
Authors: Ramsay Guy
Published: January 2010

Through analysis of local level narrative themes and linguistic features and their attendant narrative ‘domains’ and emotive content, this study explicates the discursive forms of Chinese personal narratives about mental illness published in a psychoeducational volume in mainland China. The cultural phenomena underpinning the explicated discursive forms are considered. The study finds that the Chinese mental illness narratives emphasize the problematic nature of the illness experience for the individual concerned, as well as the importance of gaining control over the personal and social disembodiment that mental illness brings about. The language of medicine presents as a dominant linguistic feature of the texts. Narrative authors appear to respond to their illness experience by negotiating and utilizing social relationships and support structures and through active medical intercession. As such, their narratives appear deeply culturally marked despite their psychoeducational intent and institutional context of publication. The study findings bear out the call for more attention to be given to the cultural dimension when analysing illness narratives.
Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective
Authors: Ludwig Heinz , Beksac Meral , Bladé Joan , Boccadoro Mario , Cavenagh Jamie , Cavo Michele , Dimopoulos Meletios , Drach Johannes , Einsele Hermann , Facon Thierry , Goldschmidt Hartmut , Harousseau Jean-Luc , Hess Urs , Ketterer Nicolas , Kropff Martin , Mendeleeva Larisa , Morgan Gareth , Palumbo Antonio , Plesner Torben , San Miguel Jesús , Shpilberg Ofer , Sondergeld Pia , Sonneveld Pieter , Zweegman Sonja
Published: January 2010

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.
In-Situ Combustion : Opportunities and Anxieties
Authors: Dayal Har Sharad , Bhushan B. V. , Mitra Sujit , Sinha S. K. , Sur Sidhartha
Published: January 2010

To enhance production and improve recovery, normal wet In Situ Combustion (ISC) process has been applied by ONGC in the heavy oil field of Balol situated in the state of Gujarat, India. Injection of air @ 0.7 MMSm3/d resulted in increasing oil production from the field from 350m3/d to about 700 m3/d with corresponding reduction in average water cut from 80% to 55%. The field results indicate that the process is not archaic and has the strength to arrest strong edge water encroachment. It can significantly increase production and recovery, if applied in right perspective. The process needs to be looked upon as a displacement process also rather than a conventional thermal technique only. The process presents significant opportunities in conventional and heavy oil reservoirs to add reserves. The air compressors and well completions are the anxieties that can be mitigated by adopting good engineering based on an informed understanding of the process. The ISC process never looses spark, provided it is designed and operated in high temperature oxidation mode.
Management of Change, Key Component of an Effective HSE Management System
Authors: Julaihi Saiee , Jaafar Ahmad Tarmizi , Abu Bakar Nur Atikah
Published: January 2010

Management of Change System is an essential component of HSE management. Whilst the typical risk management framework is aimed at ensuring a safe system of work, the somewhat complementary management of change system is crucial in sustaining that safe system of work.

In the execution of work activities, changes or deviation from defined processes/procedures is inevitable; and this is not necessarily a problem provided such changes are adequately controlled. The key consideration in managing changes is ensuring that risk posed by proposed changes, if any, remains ALARP.

In PETRONAS Carigali, the management of change system clearly defines the required change governance, spanning the entire value chain of the company business; it caters for:

▪ Geophysical (survey and seismic) activities ▪ drilling activities ▪ facility design, fabrication and installation ▪ production and maintenance activities ▪ facility abandonment and decommissioning

Key considerations in the management of change system include the followings:

▪ Types of changes requiring control are clearly defined; including changes to plant design, operating philosophy, plant equipment, operating parameters, standard operating procedures, personnel, bypass of safety critical equipment, etc. ▪ For temporary changes, the maximum duration and criteria for approval of such changes clearly defined. ▪ Types of risk assessment that need to be carried out for the various proposed changes; including aspect of risk screening and acceptance criteria. ▪ Approval process, including review by multi-disciplines technical authorities. ▪ Key performance indicators and target; the critical success factors of the management of change system.

Specific examples of changes, selected from amongst the different types of changes representing the entire business value chain, will be discussed. This is aimed at sharing PETRONAS Carigali experience on how changes are managed in the organization, including a perspective of the key challenges.
Process Wastewater Treatment and Management in Gas-to-Liquids Industries
Authors: Pon Saravanan N. , Van Vuuren Marlene J.
Published: January 2010

Gas to Liquids, or GTL, is a technology breakthrough to convert natural gas into high-performing, ultra-clean liquid fuels by means of Fischer-Tropsch (FT) reaction. A by-product of the FT reaction is process wastewater, generated in large volumes, 25% more than hydrocarbon products, on a weight basis. The process wastewater generated from GTL industries needs to be treated to comply with the standards set by Regulatory Agencies for effective reuse as well as for safe discharge into the sea or other water bodies. The treatment and management of wastewater for reuse and disposal is particularly important for Gulf countries, since they occupy one of the most arid regions in the world. This paper addresses treatment methodology for GTL process wastewater and the management of treated wastewater, including approaches to their reuse and alternate disposal options.

The first part of this paper identifies source of wastewater from the GTL industries and briefly describes typical contaminants found in process wastewater and extensively illustrates treatment technology. Process wastewater mainly contains dissolved hydrocarbons and acidic contaminants, such as, alcohols, acids, ketones, aldehydes, acetates and other oxygenates. The second part discusses the management of treated water for various applications and how they are reused or alternatively disposed off. In addition a number of recommendations, emphasizing in particular that more efforts are needed in GTL industries for the improvement of water reuse through an integrated, multi-disciplinary water management strategy.
Hydraulic Fracturing in Low Temperature Horizontal Wells
Authors: Wenjun Wang , Lin Wang , Xingfu Zhang , Sun Qingyou , Tang Pengfei , Haitao Wang , Zhongsheng Wu , Qingtiao Zhang
Published: January 2010

For shallow burying, the temperature is less than 30°C and low pressure in Putaohua formations in Chaoyanggou area in Daqing oilfield. Eight horizontal wells have been drilled in the area and need hydraulic fracturing to improve the oil production. Two challenges have to be faced. One is how to rapidly completely breaking for gel at the low temperature and improve the flow-back ratio of fracturing fluid after the fracturing, to reduce the formation damage. It is difficult to gel breaking quickly with conventional breaker in the conventional hydraulic fluid system under the super low temperature. Another one is how to improve the production of fracturing in the horizontal wells. According to the characteristic of the horizontal wells in the low temperature, low pressure reservoir, some new technologies have been used in the 8 wells fracturing jobs, such as a new type low temperature breaker, a new type of cleanup, mechanical isolation staged fracturing. In this paper, we provide details about these new hydraulic fracturing techniques applied in the horizontal wells. The Application in eight wells just as the following aspects: According to the study in the lab, a new type of fracturing fluid system has been used to suit the low temperature. At 30°C, after 4h later, the fracturing fluid was broken, and the viscosity of fracturing fluid is 3.5mPa.s. Mechanical isolation and staged fracturing with two packers is used in the horizontal wells with high efficient treatment about 4 to 6 stages per day to improve the oil production. Base on above all, we get the good result of oil production on the 8 horizontal wells, about 5.2 times higher than that on vertical fracturing wells at the same area. In this paper, we provide details about these new hydraulic fracturing techniques applied in the horizontal wells. These new technologies of fracturing provide an effective method for the horizontal wells in low temperature reservoirs in Daqing oil field.
A New Method to Discriminate Effectively the Influence of Water Injection and Natural Water Influx upon Reservoir Pressure System: A Case History from Cainan Oilfield
Authors: Nie Renshi , Jia Yonglu , Shen Nan , Qin Xusheng , Luo Xingwang , Zhang Wu , Liu Shun
Published: January 2010

Cainan oilfield is located in northwest China. The Jurassic sandstone reservoir with huge natural edge water and bottom edge water energy began to put into production in 1992 and injection in 1995. The volume of natural water is about 35 times the volume of reservoir. The reservoir production rate began to decline in 1999, at present, the production rate decline is very rapid, the average water cut is 79.83% and the recovery is 44.04%. There is a most pressing problems needed to address, which is that the water injection and the natural water influx how to influence the reservoir pressure system respectively, including the pressure maintenance level and the pressure exhaustion level, etc.

No reservoir engineering method is found to discriminate effectively the influence of water injection and natural water influx upon reservoir pressure system. A new method based on material balance principle is presented to resolve the above practical problem. Study is taken on from two aspects that fluids flow in and out of the reservoir. In terms of "in", the injection water and the influx water are divided into two parts according to their function in the reservoir: one part plays the role of maintaining the reservoir energy, the other plays the role of driving fluids. In terms of "out", the production fluids are produced due to two factors: one is the driving of the injection water and the influx water, the other is the reservoir energy depletion. After a series of deriving and deduction of complex formulas, the contributions of the water injection and the natural water influx to the reservoir pressure system respectively are calculated by use of the actual history production data. The results available can be used in guidance and reference to the next development adjustment for stabilizing production.
SGS Versus Collocated Cokriging Petrophysical Modeling: A Comparative Study in a Heterogeneous Gas Condensate Carbonate Reservoir
Authors: Tavakkoli Meyssam , Kharrat Riyaz , Inaloo Sahar
Published: January 2010

Building an accurate static model for entire field was the primary objective in the reservoir characterization and simulation. The goal was to develop a model with sufficient detail to represent reservoir discontinuity and petrophysical properties in field scale. There are different geostatistical methods for petrophysical modeling. Sequential Gaussian simulation (SGS) is a kriging based algorithm which simulates nodes after each other sequentially, subsequently using simulated values as a conditioning data. It is necessary to use standard Gaussian values in SGS method. Collocated Cokriging (C.C) is a reduced form of Cokriging, which requires knowledge of only the hard data covariance model, the correlation coefficient between the hard and soft (auxiliary) data, and the variances of the two attributes. In this study, porosity and permeability of a heterogeneous gas condensate carbonate reservoir are modeled first by SGS method. Than seismic attributes with high distribution density but low resolution are used as an auxiliary variable for porosity modeling from well logs data (limited distribution but high resolution).Determining which seismic attributes are meaningful to assist in the modeling and estimation process requires statistical analysis. In second step the modeled porosity by C.C is used as an auxiliary variable for permeability modeling. So in this method, seismic attributes have an indirect role in permeability modeling as well. A common practice usually involves the use of a cross validation scheme, where each well is removed sequentially, and its property is predicted using information from the remaining wells.