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U P Fringeli,H J Apell,M Fringeli,P Läuger Na+/K+-ATPase can be isolated from the outer medulla of mammalian kidney in the form of flat membrane fragments containing the enzyme in a density of 10(3)-10(4) protein molecules per microm2 (Deguchi et al. (1977) J. Cell. Biol. 75, 619-634). In this paper we show that these membrane fragments can... ( view more ) be bound to a germanium plate coated with a phospholipid bilayer. With this system infrared spectroscopic studies of the enzyme have been carried out using the technique of attenuated total reflection (ATR). At a coverage of the lipid surface corresponding to 30-40% of a monolayer of membrane fragments, characteristic infrared bands of the protein such as the amide I and II bands can be resolved. About 24% of the NH-groups of the peptide backbone are found to be resistant to proton/deuterium exchange within a time period of several days. Evidence for orientation of the protein with respect to the supporting lipid layer is obtained from experiments with polarized light, the largest polarization effects being associated with the -COO- band at 1400 cm-1. Experiments with aqueous media of different ionic composition indicate that the average orientation of transition moments changes when K+ in the medium is replaced by Tris+ or Na+. ( view less ) U P Fringeli,P Leutert,H Thurnhofer,M Fringeli,M M Burger Surfacing and membrane-penetrating ability of vinculin and bovine serum albumin have been studied on a macroscopic level by means of a Langmuir film balance and on a molecular level by means of infrared attenuated total reflection spectroscopy. It is suggested that the driving force of the nonspont... ( view more )aneous process of membrane penetration by native vinculin is the spontaneous formation of rigid vinculin monolayers in the membrane. Lateral adhesion of vinculin molecules results from the formation of intermolecular pleated-sheet structures. Vinculin surface activity was found to result from an alpha-helical segment oriented approximately perpendicular to plane of the membrane. There is a conformational equilibrium between this helix and random structure. High ionic strength (110 mM) favors helix formation that leads to the greater than 100-fold enhancement of surfacing velocity relative to the velocity observed at a lower ionic strength (10 mM). Vinculin has a second helical segment oriented parallel to the plane of the membrane that is in a conformational equilibrium with the pleated-sheet structure. ( view less ) U P Fringeli,M Fringeli The conformation of the linear peptide antibiotic alamethicin in dipalmitoyl phosphatidylcholine multilayers was investigated in the absence of an electric field by means of infrared attenuated total reflection spectroscopy. Alamethicin was found to be incorporated into the lipid membrane not only ... ( view more )in the dry state but also in an aqueous environment. Its molecular conformation, however, changed from a helix when dry to an extended chain when aqueous. The extended chain aggregated to di- and multimers spanning the lipid bilayer. The equilibrium concentration of alamethicin in the surrounding water was 90 nM, which is in the range of concentrations used in black film experiments. The corresponding molar ratio of lipid to peptide was 80:1. Concerning the molecular mechanism of electric field-induced pore formation, one has to conclude that the dipole model proposed by several authors is very unlikely because it is based on the assumption that the major part of alamethicin is adsorbed on the membrane surface, from which small amounts flip into the membrane under the influence of an electric field. An alternative mechanism is proposed, based on a field-induced conformational change of the peptide from the extended state to a helix. This transition is favored by the resulting dipole moment of the alamethicin helix. ( view less ) Christian Frings,Dirk WenturaIn this paper, we yield evidence for the dependence of affective priming on the congruency of the previous trial. Affective priming refers to the finding that valence categorizations of targets are facilitated when the preceding prime is of the same valence. In two experiments, affective priming wa... ( view more )s diminished after incongruent trials (i.e., prime and target were of different valence), whereas, significant affective priming was observed after congruent trials (i.e., prime and target were of same valence). We compare this pattern to the known sequential dependencies in Stroop- and Eriksen-type tasks. Furthermore, our results can help to improve the statistical power of studies in which the affective priming task is used as a measure for automatic evaluations of attitude-objects. ( view less ) M Gerwig,A C Esser,H Guberina,M Frings,F P Kolb,M Forsting,V Aurich,A Beck,D Timmann To elucidate whether the cerebellar cortex may contribute to trace eyeblink conditioning in humans, eight patients with degenerative cerebellar disorders (four with sporadic adult onset ataxia, three with autosomal dominant cerebellar ataxia type III and one with spinocerebellar ataxia type 6) and ... ( view more )eight age- and sex-matched healthy control subjects were investigated. Individual high resolution three-dimensional MRI data sets were acquired. As revealed by volumetric measurements of the cerebellum using ECCET software, patients showed cerebellar atrophy to various degrees. No abnormalities were observed in the control subjects. Eyeblink conditioning was performed twice using a tone of 40 ms as conditioned stimulus, followed by a short (400 ms) and a long (1,000 ms) trace interval and an air-puff of 100 ms as unconditioned stimulus. Using the short trace interval, eyeblink conditioning was significantly impaired in cerebellar patients compared to controls, even in those who fulfilled criteria of awareness. Using the long trace interval no significant group differences could be observed. The present findings of impaired trace eyeblink acquisition in patients with cortical cerebellar degeneration suggest that the cerebellar cortex in humans, in addition to the interposed nucleus, is involved in trace eyeblink conditioning, if the trace interval is relatively short. Using a long trace interval, the cerebellum appears to be less important. ( view less ) Christian Frings,Regine Bader,Charles Spence Abundant experimental evidence has demonstrated attentional selection within the visual modality. Furthermore, the consensus view is currently that two processes contribute to selection: the amplification of the target stimuli and the ignoring (or suppression) of any distractor information. However... ( view more ), at present it is less clear how selection is achieved within the tactile modality. In the present study, we analyze the aftereffects of ignoring tactile distractors, in a novel tactile variant of the negative priming paradigm. In the typical negative priming paradigm, repeating an ignored distractor stimulus as the target on the following trial usually leads to a cost in terms of reaction times (RTs) or error rates, thereby indicating that selection is achieved in part by the ignoring of distractors. In two experiments, we observed significant RT costs when a previously ignored vibrotactile stimulus constituted the target in the next trial. This result shows that tactile selection is in part achieved by active ignoring of distractor representations, as has been shown previously in both the visual and auditory modalities. ( view less ) Kathrin Wagner,Lars Frings,Joachim Spreer,Anne Buller,Regula Everts,Ulrike Halsband,Andreas Schulze-Bonhage The encoding of verbal stimuli elicits left-lateralized activation patterns within the medial temporal lobes in healthy adults. In our study, patients with left- and right-sided temporal lobe epilepsy (LTLE, RTLE) were investigated during the encoding and retrieval of word-pair associates using fun... ( view more )ctional magnetic resonance imaging. Functional asymmetry of activation patterns in hippocampal, inferior frontal, and temporolateral neocortical areas associated with language functions was analyzed. Hippocampal activation patterns in patients with LTLE were more right-lateralized than those in patients with RTLE (P<0.05). There were no group differences with respect to lateralization in frontal or temporolateral regions of interest (ROIs). For both groups, frontal cortical activation patterns were significantly more left-lateralized than hippocampal patterns (P<0.05). For patients with LTLE, there was a strong trend toward a difference in functional asymmetry between the temporolateral and hippocampal ROIs (P=0.059). A graded effect of epileptic activity on laterality of the different regional activation patterns is discussed. ( view less ) Jasmina Matijasevi?,Norbert Hassler,Gerald Reiter,Urs Peter Fringeli The development and optimization of biomimetic surfaces required for biosensors and medical assays are made more efficient by quantitatively monitoring the surface chemical reactions in situ by means of attenuated total reflection (ATR) FTIR spectroscopy. single-beam-sample-reference (SBSR) ATR, as... ( view more ) well as modulated excitation (ME), techniques have been applied to get physicochemical information on growth and structure of the surface layer. SBSR and ME methods result in optimum background compensation and signal-to-noise ratio. Surface modification was performed on a germanium multiple internal reflection element (Ge-MIRE). Activation of the surface resulted in free Ge-OH groups used for a spontaneous chemical reaction with 7-octenyltrichlorosilane (7-OTCS) in toluene. Formation of Ge-O-Si bonds was enabled by hydrolization of Si-Cl3 after partial elimination of a tightly bound thin water layer covering the MIRE. Unwanted side-reaction by hydrolization of Si-Cl3 in solution followed by polymerization paralleled this process. Steady growing of the silane layer to multilayer thickness with increasing time was observed in all experiments. Most unexpectedly, in some experiments the end-standing double bond of the silane layer was found to be partly oxidized even after being exposed only to toluene, probably because of catalysis by molecular sieve nanoparticles remaining in toluene after drying. Finally, theoretical means are presented enabling the calculation of the spectrum of dissolved 7-OTCS in toluene, a prerequisite for background compensation during in situ studies of the growing layer. ( view less ) C Detlefs,F Duc,Z A Kaze?,J Vanacken,P Frings,W Bras,J E Lorenzo,P C Canfield,G L J A RikkenWe report the first direct observation of the influence of high magnetic fields on the Jahn-Teller (JT) transition in TbVO(4). Contrary to spectroscopic and magnetic methods, x-ray diffraction directly measures the JT distortion; the splitting between the (311)/(131) and (202)/(022) pairs of Bragg ... ( view more )reflections is proportional to the order parameter. Our experimental results are compared to mean-field calculations, taking into account all possible orientations of the grains relative to the applied field, and qualitative agreement is obtained. ( view less ) D Klimmeck,U Mayer,N Ungerer,U Warnken,M Schnölzer,S Frings,F Möhrlen The olfactory neuroepithelium represents a unique interface between the brain and the external environment. Olfactory function comprises a distinct set of molecular tasks: sensory signal transduction, cytoprotection and adult neurogenesis. A multitude of biochemical studies has revealed the central... ( view more ) role of Ca(2+) signaling in the function of olfactory receptor neurons (ORNs). We set out to establish Ca(2+)-dependent signaling networks in ORN cilia by proteomic analysis. We subjected a ciliary membrane preparation to Ca(2+)/calmodulin-affinity chromatography using mild detergent conditions in order to maintain functional protein complexes involved in olfactory Ca(2+) signaling. Thus, calmodulin serves as a valuable tool to gain access to novel Ca(2+)-regulated protein complexes. Tandem mass spectrometry (nanoscale liquid-chromatography-electrospray injection) identified 123 distinct proteins. Ninety-seven proteins (79%) could be assigned to specific olfactory functions, including 32 to sensory signal transduction and 40 to cytoprotection. We point out novel perspectives for research on the Ca(2+)-signaling networks in the olfactory system of the rat. ( view less ) Ulrich Mayer,Nicole Ungerer,Daniel Klimmeck,Uwe Warnken,Martina Schnölzer,Stephan Frings,Frank Möhrlen The cilia of mammalian olfactory receptor neurons (ORNs) represent the sensory interface that is exposed to the air within the nasal cavity. The cilia are the site where odorants bind to specific receptors and initiate olfactory transduction that leads to excitation of the neuron. This process invo... ( view more )lves a multitude of ciliary proteins that mediate chemoelectrical transduction, amplification, and adaptation of the primary sensory signal. Many of these proteins were initially identified by their enzymatic activities using a membrane protein preparation from olfactory cilia. This so-called "calcium-shock" preparation is a versatile tool for the exploration of protein expression, enzyme kinetics, regulatory mechanisms, and ciliary development. To support such studies, we present a first proteomic analysis of this membrane preparation. We subjected the cilia preparation to liquid chromatography-electrospray ionisation (LC-ESI-MS/MS) tandem mass spectrometry and identified 268 proteins, of which 49% are membrane proteins. A detailed analysis of their cellular and subcellular localization showed that the cilia preparation obtained by calcium shock not only is highly enriched in ORN proteins but also contains a significant amount of nonciliary material. Although our proteomic study does not identify the entire set of ciliary and nonciliary proteins, it provides the first estimate of the purity of the calcium-shock preparation and provides valuable biochemical information for further research. ( view less ) Lars Frings,Kathrin Wagner,Ulrike Halsband,Ralf Schwarzwald,Josef Zentner,Andreas Schulze-Bonhage We addressed the question whether lateralization of memory-related medial temporal lobe (MTL) activity in medial temporal lobe epilepsy (MTLE) patients is determined by pathology or sex, differentiating between two MTL subregions implicated in visuospatial memory as regions-of-interest (ROI) - the ... ( view more )hippocampus (Hc) and the parahippocampal place area (PPA). We further assessed the relation between lateralization of hippocampal activation and postsurgical memory decline regarding performance in standardized neuropsychological tests of verbal and visuospatial learning. Functional magnetic resonance imaging (fMRI) data were acquired from unilateral MTLE patients performing an object location memory task in a virtual environment. Individual lateralization indices (LI) based on memory-related brain activation patterns were calculated for each subject and ROI. Correlational analyses were computed between pre- to postsurgical changes in learning and asymmetry in hippocampal activation. Results revealed that lateralization of hippocampal, memory-related activity in patients with MTLE was determined by the side of seizure focus, not sex. Laterality of activation in the PPA was neither influenced by side of pathology nor sex. Lateralization of hippocampal activation was significantly correlated with decline in verbal learning after surgery. We were able to demonstrate that asymmetry of hippocampal fMRI-activation in unilateral MTLE patients is determined by the side of seizure focus, thus indicating the relative functional integrity of the hippocampi. This is corroborated by the finding that greater activation of the to-be-resected hippocampus leads to stronger verbal memory decline after surgery. ( view less ) Peter Wühr,Christian Frings The present study investigated the ability to inhibit the processing of an irrelevant visual object while processing a relevant one. Participants were presented with 2 overlapping shapes (e.g., circle and square) in different colors. The task was to name the color of the relevant object designated ... ( view more )by shape. Congruent or incongruent color words appeared in the relevant object, in the irrelevant object, or in the background. Stroop effects indicated how strong the respective area of the display was processed. The results of 4 experiments showed that words in the relevant object produced larger Stroop effects than words in the background, indicating amplification of relevant objects. In addition, words in the irrelevant object consistently produced smaller Stroop effects than words in the background, indicating inhibition of irrelevant objects. Control experiments replicated these findings with brief display durations (250 ms) and ruled out perceptual factors as a possible explanation. In summary, results support the notion of an inhibitory mechanism of object-based attention, which can be applied in addition to the amplification of relevant objects. ( view less ) Beate Schoch,Jens Peter Regel,Markus Frings,Marcus Gerwig,Matthias Maschke,Markus Neuhäuser,Dagmar Timmann To evaluate the therapies for cerebellar diseases appropriate neurological assessment methods to measure severity of ataxia are required. Reliability and validity of the semiquantitative International Cooperative Ataxia Rating Scale (ICARS) has recently been examined in patients with degenerative a... ( view more )taxias. We evaluated reliability (internal consistency), criterion-related validity and internal construct validity of ICARS for the first time in patients with focal cerebellar lesions (68 patients with surgical lesions and 68 patients with ischemic lesions). For comparison 45 patients with degenerative cerebellar ataxia were included. We found an excellent Cronbach's alpha as a measurement for internal consistency which was independent from underlying disease. Criterion-related validity was high. Total ICARS score mirrored clearly the immediate postsurgical worsening and the improvement during the first 3 months after focal surgical and ischemic lesions, whereas in chronic state of focal and degenerative cerebellar disorders ICARS score remained nearly unchanged. Principal component analysis in patients with focal lesions revealed five distinct and clinically meaningful factors which corresponded to the four ICARS subscores and reflected the laterality of kinetic functions. In degenerative disorders, however, the items for the subscore "kinetic function" loaded to more than one factor. Total ICARS score seems to be a useful and valid measurement to describe the time course of ataxia in patients with focal and degenerative disorders affecting primarily the cerebellum. Validity of subscores however is good in focal, but not in degenerative disorders. ( view less ) Daniel Gilbert,Christina Franjic-Würtz,Katharina Funk,Thomas Gensch,Stephan Frings,Frank Möhrlen Recent research into the generation of hyperalgesia has revealed that both the excitability of peripheral nociceptors and the transmission of their afferent signals in the spinal cord are subject to modulation by Cl(-) currents. The underlying Cl(-) homeostasis of nociceptive neurons, in particular... ( view more ) its postnatal maturation, is, however, poorly understood. Here we measure the intracellular Cl(-) concentration, [Cl(-)]i, of somatosensory neurons in intact dorsal root ganglia of mice. Using two-photon fluorescence-lifetime imaging microscopy, we determined [Cl(-)]i in newborn and adult animals. We found that the somatosensory neurons undergo a transition of Cl(-) homeostasis during the first three postnatal weeks that leads to a decline of [Cl(-)]i in most neurons. Immunohistochemistry showed that a major fraction of neurons in the dorsal root ganglia express the cation-chloride co-transporters NKCC1 and KCC2, indicating that the molecular equipment for Cl(-) accumulation and extrusion is present. RT-PCR analysis showed that the transcription pattern of electroneutral Cl(-) co-transporters does not change during the maturation process. These findings demonstrate that dorsal root ganglion neurons undergo a developmental transition of chloride homeostasis during the first three postnatal weeks. This process parallels the developmental "chloride switch" in the central nervous system. However, while most CNS neurons achieve homogeneously low [Cl(-)]i levels - which is the basis of GABAergic and glycinergic inhibition - somatosensory neurons maintain a heterogeneous pattern of [Cl(-)]i values. This suggests that Cl(-) currents are excitatory in some somatosensory neurons, but inhibitory in others. Our results are consistent with the hypothesis that Cl(-) homeostasis in somatosensory neurons is regulated through posttranslational modification of cation-chloride co-transporters. ( view less ) Kathrin Wagner,Lars Frings,Ulrike Halsband,Regula Everts,Anne Buller,Joachim Spreer,Josef Zentner,Andreas Schulze-Bonhage Using functional magnetic resonance imaging during a verbal memory task, we investigated correlations of signal fluctuations within the hippocampus and ipsilateral frontal as well as temporal areas in temporal lobe epilepsy patients. Declarative memory abilities were additionally examined before an... ( view more )d after temporal lobe epilepsy surgery. A significant difference exists in functional connectivity between patients whose mnemonic functions deteriorated and those who remained stable or improved. Univariate analyses showed significantly higher preoperative coupling between the hippocampus and Brodmann area 22 for the group that decreased in verbal learning. We suggest greater coupling to reflect higher functional network integrity. Postoperatively reduced learning ability in patients with higher preoperative coupling underlines the importance of hippocampal interaction with cortical areas for successful memory formation. ( view less ) Christian Frings,Christian Groh-BordinNegative priming (NP) refers to the finding that the processing of stimuli previously ignored is usually impaired in terms of reaction times and error rates. Although a robust empirical phenomenon, behavioral experiments were not able to ultimately distinguish between retrieval- and inhibition-base... ( view more )d accounts of NP. Electrophysiological measures may help improve our understanding of this phenomenon. In this paper, we report an ERP correlate of identity NP with visual stimuli. In particular, we observed an enhanced N200 component when a distractor from the previous trial became the target in the next trial. This N200 modulation is explained in terms of a stronger response conflict when a previously ignored target must be selected against incompatible, and not previously ignored distractors; this interpretation is discussed as evidence for an inhibition view of NP. ( view less ) Christian Frings,Klaus Rothermund,Dirk WenturaResponse retrieval theories assume that stimuli and responses become integrated into "event files" (Hommel, 1998) in memory so that a second encounter with a specific stimulus automatically retrieves the response that was previously associated with this stimulus. In this article, we tested a specif... ( view more )ic prediction of a recent variant of stimulus retrieval theories as introduced by Rothermund, Wentura, and De Houwer (2005): In selection tasks where target stimuli are accompanied by distractors, responses to target stimuli are automatically bound to distractor stimuli as well; repeating the distractor should retrieve the response to the target that formerly accompanied the distractor. In three experiments we confirmed this prediction: Distractor repetition facilitated responding in the probe in the case of response repetition whereas repeating the distractor delayed responding in the case of response change. ( view less ) Christian Frings,Silke Feix,Ulrike Röthig,Charlotte Brüser,Miriam Junge Reactions to stimuli that were shortly before presented as distractors are usually slowed down; this phenomenon is known as negative priming. Negative priming is an accepted index for tapping into selective control mechanisms. Although this effect is well established for adults, it has been claimed... ( view more ) that children do not show negative priming. Recently, however, V. E. Pritchard and E. Neumann challenged this view and concluded that selective control mechanisms are already fully developed in young children. The authors of the present study analyzed differences between older studies, in which no negative priming had been observed, and the Pritchard and Neumann (2004) study. In sum, the present study yielded further evidence for an intact selective control mechanism in young children. The authors also linked this empirical finding to the broader literature on negative priming by a direct comparison with an adult sample. ( view less ) Anja Weyer,Michael Abele,Tanja Schmitz-Hübsch,Beate Schoch,Markus Frings,Dagmar Timmann,Thomas Klockgether The objective of this study was to test the reliability and validity of the Scale for the Assessment and Rating of Ataxia (SARA) in ataxia patients not suffering from autosomal dominant spinocerebellar ataxia (SCA). To this end, 64 patients with various ataxia disorders or stable cerebellar lesions... ( view more ) were rated independently by two investigators. In addition to SARA, the following assessment instruments were applied: ataxia disease stage, Barthel index and part IV (functional assessment) of the Unified Huntington's Disease Rating scale (UHDRS-IV). Eighteen patients were rated twice. Inter-rater and intrarater reliability were very high with ICCs of 0.98 and 0.99. Internal consistency was high indicated by Cronbach's alpha of 0.97. Factorial analysis revealed that the rating results were mainly determined by one major factor with an eigenvalue of 6.34 which explained 52.8% of the variance. SARA score increased with disease stage (P<0.0001) and was closely correlated with Barthel index (r=-0.63, P<0.0001) and UHDRS-IV (r=-0.62, P<0.0001), but only weakly correlated with disease duration (r=0.44, P<0.001). The results suggest that SARA is a reliable and valid measure of ataxia in non-SCA ataxia patients. ( view less ) Timothy Hopthrow,Dominic Abrams,Daniel Frings,Lorne G HulbertAlcohol is often consumed in group settings. The present article examines the effect of alcohol on intergroup competitiveness through the use of a prisoner's dilemma game. One hundred fifty-eight college students participated in the study, either individually or as a member of a 4-person experiment... ( view more )al single-sex group. Participants consumed either alcohol (1.13 g ethanol/kg body weight) or a placebo. Results show no effect of alcohol on cooperative choice within individuals. However, groups were significantly less cooperative after consuming alcohol than they were after consuming a placebo. In addition, after consuming alcohol, groups were less cooperative than were individuals. Results are discussed in terms of the way alcohol may affect focus of attention on group-level cues. ( view less ) Bettina Gomer,Kathrin Wagner,Lars Frings,Josef Saar,Astrid Carius,Markus Härle,Bernhard J Steinhoff,Andreas Schulze-Bonhage Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of focal epilepsies. To explore potential side effects, this study investigated their influence on cognitive functions comparatively by means of a standardized neuropsychologic... ( view more )al test battery assessing several cognitive domains. In this observational study, cognitive changes were explored in 30 consecutively recruited patients with focal epilepsy treated with LEV and in 21 patients treated with TPM, comparing functions assessed prior to gradual initiation and after reaching steady state of the individual target dosage. Before titration, patient groups did not differ significantly with respect to cognitive performance. Whereas the LEV group manifested no change in cognitive performance after AED titration, the TPM group worsened in the cognitive domains of cognitive speed and verbal fluency, as well as short-term memory. These findings suggest that TPM, unlike LEV, may impair frontal lobe functions. The lack of cognitive side effects related to LEV treatment may be relevant for treatment decisions. ( view less ) Christian Frings,Peter Wühr Responses to probe targets that have been distractors in a prime display are slower than responses to new targets, a finding called negative priming (NP). The selective attention model, which attributes NP to lingering inhibition of the prime distractor, predicts that NP should occur only when the ... ( view more )prime display has disappeared before the probe display is processed. The present study tested this prediction both in easy- and in difficult selection tasks. In Experiments 1, 2, and 3A, target selection was easy, and NP was observed only after prime display offset, regardless of whether offset was manipulated between or within participants. In Experiment 3B, target selection was difficult, and NP was found with and without prime display offset. Experiment 4 replicated the finding of NP without prime display offset in a difficult-selection task. A modified version of the selective attention model can explain the results of the present study. However, we also discuss the results in light of episodic retrieval theory and temporal discrimination theory. ( view less ) A Quiske,J Unterrainer,K Wagner,L Frings,T Breyer,U Halsband,C Ostertag,C E Elger,A Ebner,I Tuxhorn,J-P Ernst,B J Steinhoff,T Mayer,A Schulze-Bonhage We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of (125)I-seed and 3 months after seed explantation. Performance was compared ... ( view more )with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of (125)I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects. ( view less ) Daniel Gilbert,Katharina Funk,Brigitte Dekowski,Ralf Lechler,Sandro Keller,Frank Möhrlen,Stephan Frings,Volker Hagen The vanilloid capsaicin, N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide, is the pungent ingredient of chili peppers and is used in pain research as an activating ligand of heat-sensitive transduction channels in nociceptive neurons. Here we describe the synthesis and application of two capsaic... ( view more )in derivatives modified at the hydroxy function of the vanillyl motif: alpha-carboxy-4,5-dimethoxy-2-nitrobenzyl-caged (CDMNB-caged) capsaicin and {7-[bis(carboxymethyl)amino]coumarin-4-yl}methoxycarbonyl-caged (BCMACMOC-caged) capsaicin. These compounds show dramatically reduced pungency, but release active capsaicin upon irradiation with UV light. CDMNB-caged capsaicin can be used to perform concentration-jump experiments, while BCMACMOC-caged capsaicin is membrane-impermeant and can be applied selectively to the intracellular or extracellular sides of a plasma membrane. Both compounds can serve as valuable research tools in pain physiology. ( view less )
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