bluuebunny/crossref_metadata_2025 huggingface dataset:
Nicotinic α7Receptors as a New Target for Treatment of Cannabis Abuse
Authors: Solinas Marcello , Scherma Maria , Fattore Liana , Stroik Jessica , Wertheim Carrie , Tanda Gianluigi , Fratta Walter , Goldberg Steven R.
Published: May 2007

Increasing use of cannabis makes the search for medications to reduce cannabis abuse extremely important. Here, we show that homomeric α7nicotinic receptors are novel molecular entities that could be targeted in the development of new drugs for the treatment of cannabis dependence. In rats, systemic administration of the selective α7nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA), but not the selective heteromeric non-α7nicotinic acetylcholine receptor antagonist dihydrobetaerythroidine, (1) antagonized the discriminative effects of δ-9-tetrahydrocannabinol (THC), the main active ingredient in cannabis, (2) reduced intravenous self-administration of the synthetic cannabinoid CB1 receptor agonist WIN55,212-2 [(R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone, mesylate salt], and (3) decreased THC-induced dopamine elevations in the shell of the nucleus accumbens. Altogether, our results indicate that blockade of α7nicotinic receptors reverses abuse-related behavioral and neurochemical effects of cannabinoids. Importantly, MLA reversed the effects of cannabinoids at doses that did not produce depressant or toxic effects, further pointing to α7nicotinic antagonists as potentially useful agents in the treatment of cannabis abuse in humans.
Translocation of Gqα Mediates Long-Term Adaptation inDrosophilaPhotoreceptors
Authors: Frechter Shahar , Elia Natalie , Tzarfaty Vered , Selinger Zvi , Minke Baruch
Published: May 2007

Light adaptation is a process that enables photoreceptor cells to operate over a wide range of light intensities without saturation. In invertebrate photoreceptors, fast adaptation is mediated by a Ca2+-dependent negative-feedback mechanism, which mainly affects the terminal steps of the cascade. Therefore, the response to each photon is smaller as light intensity increases, accommodating both high sensitivity and a vast dynamic range. Here, we describe a novel type of adaptation, which is mediated by one of the first steps in the phototransduction cascade affecting the sensitivity to absorbed photons. Long exposure to light resulted in dramatic reduction in the probability of each absorbed photon to elicit a response, whereas the size and shape of each single photon response did not change. To dissect the molecular mechanism underlying this form of adaptation we used a series ofDrosophilamutants. Genetic dissection showed a pivotal role for light-induced translocation of Gqα between the signaling membrane and the cytosol. Biochemical studies revealed that the sensitivity to light depends on membrane Gqα concentration, which was modulated either by light or by mutations that impaired its targeting to the membrane. We conclude that long-term adaptation is mediated by the movement of Gqα from the signaling membrane to the cytosol, thereby reducing the probability of each photon to elicit a response. The slow time scale of this adaptation fits well with day/night light intensity changes, because there is no need to maintain single photon sensitivity during daytime.
Recurrent Dendrodendritic Inhibition of Accessory Olfactory Bulb Mitral Cells Requires Activation of Group I Metabotropic Glutamate Receptors
Authors: Castro Jason B. , Hovis Kenneth R. , Urban Nathaniel N.
Published: May 2007

Metabotropic glutamate receptors (mGluRs) modulate neural excitability and network tone in many brain regions. Expression of mGluRs is particularly high in the accessory olfactory bulb (AOB), a CNS structure critical for detecting chemicals that identify kin and conspecifics. Because of its relative simplicity and its direct projection to the hypothalamus, the AOB provides a model system for studying how mGluRs affect the flow of encoded sensory information to downstream areas. We investigated the role of group I mGluRs in synaptic processing in AOB slices and found that under control conditions, recurrent inhibition of principal neurons (mitral cells) was completely eliminated by the mGluR1 antagonist LY367385 [(S)-(+)-α-amino-4-carboxy-2 methylbenzeneacetic acid]. In addition, the group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine; 20 μm] induced a dramatic increase in the rate of spontaneous IPSCs. This increase was dependent on voltage-gated calcium channels but persisted even after blockade of ionotropic glutamatergic transmission and sodium channels. Together, these results indicate that mGluR1 plays a critical role in controlling information flow through the AOB and suggest that mGluR1 may be an important locus for experience-dependent changes in synaptic function.
Characterization of Ligands for Fish Taste Receptors
Authors: Oike Hideaki , Nagai Toshitada , Furuyama Akira , Okada Shinji , Aihara Yoshiko , Ishimaru Yoshiro , Marui Takayuki , Matsumoto Ichiro , Misaka Takumi , Abe Keiko
Published: May 2007

Recent progress in the molecular biology of taste reception has revealed that in mammals, the heteromeric receptors T1R1/3 and T1R2/3 respond to amino acids and sweeteners, respectively, whereas T2Rs are receptors for bitter tastants. Similar taste receptors have also been characterized in fish, but their ligands have not been identified yet. In the present study, we conducted a series of experiments to identify the fish taste receptor ligands. Facial nerve recordings in zebrafish (Danio rerio) demonstrated that the fish perceived amino acids and even denatonium, which is a representative of aversive bitter compounds for mammals andDrosophila. Calcium imaging analysis of T1Rs in zebrafish and medaka fish (Oryzias latipes) using an HEK293T heterologous expression system revealed that both T1R1/3 and a series of T1R2/3 responded to amino acids but not to sugars. A triple-labeling,in situhybridization analysis demonstrated that cells expressing T1R1/3 and T1R2/3s exist in PLCβ2-expressing taste bud cells of medaka fish. Functional analysis using T2Rs showed that zfT2R5 and mfT2R1 responded to denatonium. Behavior observations confirmed that zebrafish prefer amino acids and avoid denatonium. These results suggest that, although there may be some fish-specific way of discriminating ligands, vertebrates could have a conserved gustatory mechanism by which T1Rs and T2Rs respond to attractive and aversive tastants, respectively.
Cytoplasmic Dynein and LIS1 Are Required for Microtubule Advance during Growth Cone Remodeling and Fast Axonal Outgrowth
Authors: Grabham Peter W. , Seale Garrett E. , Bennecib Malika , Goldberg Daniel J. , Vallee Richard B.
Published: May 2007

Recent evidence has implicated dynein and its regulatory factors dynactin and LIS1 in neuronal and non-neuronal cell migration. In the current study we sought to test whether effects on neuronal cell motility might reflect, in part, a role for these proteins in the growth cone. In chick sensory neurons subjected to acute laminin treatment dynein, dynactin, and LIS1 were mobilized strikingly and rapidly to the leading edge of the growth cone, where they were seen to be associated with microtubules converging into the laminin-induced axonal outgrowths. To interfere acutely with LIS1 and dynein function and to minimize secondary phenotypic effects, we injected antibodies to these proteins just before axon initiation. Antibody to both proteins produced an almost complete block of laminin-induced growth cone remodeling and the underlying reorganization of microtubules. Penetration of microtubules into the peripheral zone of differentiating axonal growth cones was decreased dramatically by antibody injection, as judged by live analysis of enhanced green fluorescent protein-tubulin and the microtubule tip-associated EB3 (end-binding protein 3). Dynein and LIS1 inhibition had no detectable effect on microtubule assembly but reduced the ability of microtubules to resist retrograde actin flow. In hippocampal neurons dynein, dynactin, and LIS1 were enriched in axonal growth cones at stage 3, and both growth cone organization and axon elongation were altered by LIS1 RNA interference. Together, our data indicate that dynein and LIS1 play a surprisingly prominent role in microtubule advance during growth cone remodeling associated with axonogenesis. These data may explain, in part, the role of these proteins in brain developmental disease and support an important role in diverse aspects of neuronal differentiation and nervous system development.
Cholinergic Axons Modulate GABAergic Signaling among Hippocampal Interneurons via Postsynaptic α7 Nicotinic Receptors
Authors: Wanaverbecq Nicolas , Semyanov Alexey , Pavlov Ivan , Walker Matthew C. , Kullmann Dimitri M.
Published: May 2007

Homopentameric α7 nicotinic receptors have a high affinity for acetylcholine (ACh), are permeable to Ca2+ions, and are abundant in hippocampal interneurons. Although nicotinic agonists evoke inward currents and Ca2+transients in stratum radiatum interneurons, the role of endogenous ACh in modulating synaptic integration by interneurons is incompletely understood. Many cholinergic axonal varicosities do not have postsynaptic specializations, but α7 receptors frequently occur close to synaptic GABAAreceptors. These observations raise the possibility that α7 nicotinic receptors activated by ACh released from cholinergic axons modulate GABAergic transmission in interneurons. We show that agonists of α7 receptors profoundly depress GABAergic IPSCs recorded in stratum radiatum interneurons in the CA1 region of the hippocampus. This depression is accompanied by a small increase in GABA release. α7 nicotinic receptor agonists also depress GABA- or muscimol-evoked currents in interneurons, indicating that the major effect is a postsynaptic modulation of GABAAreceptors. The depression of GABA-evoked currents is abolished by chelating Ca2+in the recorded interneuron and attenuated by inhibitors of PKC. We also show that stimuli designed to release endogenous ACh from cholinergic axons evoke an α7 receptor-dependent heterosynaptic depression of GABAergic IPSCs in interneurons. This heterosynaptic modulation is amplified by blocking cholinesterases. These results reveal a novel mechanism by which cholinergic neurons modulate information processing in the hippocampus.
Optimal Sensorimotor Integration in Recurrent Cortical Networks: A Neural Implementation of Kalman Filters
Authors: Denève Sophie , Duhamel Jean-René , Pouget Alexandre
Published: May 2007

Several behavioral experiments suggest that the nervous system uses an internal model of the dynamics of the body to implement a close approximation to a Kalman filter. This filter can be used to perform a variety of tasks nearly optimally, such as predicting the sensory consequence of motor action, integrating sensory and body posture signals, and computing motor commands. We propose that the neural implementation of this Kalman filter involves recurrent basis function networks with attractor dynamics, a kind of architecture that can be readily mapped onto cortical circuits. In such networks, the tuning curves to variables such as arm velocity are remarkably noninvariant in the sense that the amplitude and width of the tuning curves of a given neuron can vary greatly depending on other variables such as the position of the arm or the reliability of the sensory feedback. This property could explain some puzzling properties of tuning curves in the motor and premotor cortex, and it leads to several new predictions.
Time Discounting for Primary Rewards
Authors: McClure Samuel M. , Ericson Keith M. , Laibson David I. , Loewenstein George , Cohen Jonathan D.
Published: May 2007

Previous research, involving monetary rewards, found that limbic reward-related areas show greater activity when an intertemporal choice includes an immediate reward than when the options include only delayed rewards. In contrast, the lateral prefrontal and parietal cortex (areas commonly associated with deliberative cognitive processes, including future planning) respond to intertemporal choices in general but do not exhibit sensitivity to immediacy (McClure et al., 2004). The current experiments extend these findings to primary rewards (fruit juice or water) and time delays of minutes instead of weeks. Thirsty subjects choose between small volumes of drinks delivered at precise times during the experiment (e.g., 2 ml now vs 3 ml in 5 min). Consistent with previous findings, limbic activation was greater for choices between an immediate reward and a delayed reward than for choices between two delayed rewards, whereas the lateral prefrontal cortex and posterior parietal cortex responded similarly whether choices were between an immediate and a delayed reward or between two delayed rewards. Moreover, relative activation of the two sets of brain regions predicts actual choice behavior. A second experiment finds that when the delivery of all rewards is offset by 10 min (so that the earliest available juice reward in any choice is 10 min), no differential activity is observed in limbic reward-related areas for choices involving the earliest versus only more delayed rewards. We discuss implications of this finding for differences between primary and secondary rewards.
Multiple Modes of Synaptic Excitation of Olfactory Bulb Granule Cells
Authors: Balu Ramani , Pressler R. Todd , Strowbridge Ben W.
Published: May 2007

Inhibition generated by granule cells, the most common GABAergic cell type in the olfactory bulb, plays a critical role in shaping the output of the olfactory bulb. However, relatively little is known about the synaptic mechanisms responsible for activating these interneurons in addition to the specialized dendrodendritic synapses located on distal dendrites. Using two-photon guided minimal stimulation in acute rat brain slices, we found that distal and proximal excitatory synapses onto granule cells are functionally distinct. Proximal synapses arise from piriform cortical neurons and facilitate with paired-pulse stimulation, whereas distal dendrodendritic synapses generate EPSCs with slower kinetics that depress with paired stimulation. Proximal cortical feedback inputs can relieve the tonic Mg block of NMDA receptors (NMDARs) at distal synapses and gate dendrodendritic inhibition onto mitral cells. Most excitatory synapses we examined onto granule cells activated both NMDARs and AMPA receptors, whereas a subpopulation appeared to be NMDAR silent. The convergence of two types of excitatory inputs onto GABAergic granule cells provides a novel mechanism for regulating the degree of interglomerular processing of sensory input in the olfactory bulb through piriform cortex/olfactory bulb synaptic interactions.
Functional Characterization of Intrinsic Cholinergic Interneurons in the Cortex
Authors: von Engelhardt Jakob , Eliava Marina , Meyer Axel H. , Rozov Andrei , Monyer Hannah
Published: May 2007

Acetylcholine is a major neurotransmitter that modulates cortical functions. In addition to basal forebrain neurons that give rise to the principal cholinergic input into the cortex, a second source constituted by intrinsic cholinergic interneurons has been identified. Although these cells have been characterized anatomically, little is known about their functional role in cortical microcircuits. The paucity of this cell population has been a major hindrance for detailed electrophysiological investigations. To facilitate functional studies, we generated transgenic mice that express enhanced green fluorescent protein (EGFP) in choline acetyltransferase (ChAT)-positive neurons. Aided by the transgene expression, the characterization of distinct cholinergic interneurons was possible. These cells were located in layer 2–3, had a bipolar morphology, were calretinin- and vasoactive intestinal peptide positive, but had a non-GABAergic phenotype. Paired recordings showed that EGFP/ChAT-positive neurons receive excitatory and inhibitory input from adjacent principal cells and various types of interneurons. However, EGFP/ChAT-positive neurons do not exert direct postsynaptic responses in neighboring neurons. Interestingly, prolonged activation of EGFP-labeled cholinergic neurons induces an increase in spontaneous EPSCs in adjacent pyramidal neurons. This indirect effect is mediated by nicotinic receptors that are presumably presynaptically localized. Thus, intrinsic bipolar cholinergic neurons can modulate cortical function locally.
The Transduction Channel TRPM5 Is Gated by Intracellular Calcium in Taste Cells
Authors: Zhang Zheng , Zhao Zhen , Margolskee Robert , Liman Emily
Published: May 2007

Bitter, sweet, and umami tastants are detected by G-protein-coupled receptors that signal through a common second-messenger cascade involving gustducin, phospholipase C β2, and the transient receptor potential M5 (TRPM5) ion channel. The mechanism by which phosphoinositide signaling activates TRPM5 has been studied in heterologous cell types with contradictory results. To resolve this issue and understand the role of TRPM5 in taste signaling, we took advantage of mice in which the TRPM5 promoter drives expression of green fluorescent protein and mice that carry a targeted deletion of the TRPM5 gene to unequivocally identify TRPM5-dependent currents in taste receptor cells. Our results show that brief elevation of intracellular inositol trisphosphate or Ca2+is sufficient to gate TRPM5-dependent currents in intact taste cells, but only intracellular Ca2+is able to activate TRPM5-dependent currents in excised patches. Detailed study in excised patches showed that TRPM5 forms a nonselective cation channel that is half-activated by 8 μmCa2+and that desensitizes in response to prolonged exposure to intracellular Ca2+. In addition to channels encoded by the TRPM5 gene, we found that taste cells have a second type of Ca2+-activated nonselective cation channel that is less sensitive to intracellular Ca2+. These data constrain proposed models for taste transduction and suggest a link between receptor signaling and membrane potential in taste cells.
Linking Synaptic Plasticity and Spike Output at Excitatory and Inhibitory Synapses onto Cerebellar Purkinje Cells
Authors: Mittmann Wolfgang , Häusser Michael
Published: May 2007

Understanding the relationship between synaptic plasticity and neuronal output is essential if we are to understand how plasticity is encoded in neural circuits. In the cerebellar cortex, motor learning is thought to be implemented by long-term depression (LTD) of excitatory parallel fiber (PF) to Purkinje cell synapses triggered by climbing fiber (CF) input. However, theories of motor learning generally neglect the contribution of plasticity of inhibitory inputs to Purkinje cells. Here we describe how CF-induced plasticity of both excitatory and inhibitory inputs is reflected in Purkinje cell spike output. We show that coactivation of the CF with PF input and interneuron input leads not only to LTD of PF synapses but also to comparable, “balanced” LTD of evoked inhibitory inputs. These two forms of plasticity have opposite effects on the spike output of Purkinje cells, with the number and timing of spikes sensitively reflecting the degree of plasticity. We used dynamic clamp to evaluate plasticity-induced changes in spike responses to sequences of excitation and feedforward inhibition of varied relative and absolute amplitude. Balanced LTD of both excitatory and inhibitory components decreased the net spike output of Purkinje cells only for inputs with small inhibitory components, whereas for inputs with a larger proportion of feedforward inhibition CF-triggered LTD resulted in an increase in the net spike output. Thus, the net effect of CF-triggered plasticity on Purkinje cell output depends on the balance of excitation and feedforward inhibition and can paradoxically increase cerebellar output, contrary to current theories of cerebellar motor learning.
Primate Reaching Cued by Multichannel Spatiotemporal Cortical Microstimulation
Authors: Fitzsimmons N. A. , Drake W. , Hanson T. L. , Lebedev M. A. , Nicolelis M. A. L.
Published: May 2007

Both humans and animals can discriminate signals delivered to sensory areas of their brains using electrical microstimulation. This opens the possibility of creating an artificial sensory channel that could be implemented in neuroprosthetic devices. Although microstimulation delivered through multiple implanted electrodes could be beneficial for this purpose, appropriate microstimulation protocols have not been developed. Here, we report a series of experiments in which owl monkeys performed reaching movements guided by spatiotemporal patterns of cortical microstimulation delivered to primary somatosensory cortex through chronically implanted multielectrode arrays. The monkeys learned to discriminate microstimulation patterns, and their ability to learn new patterns and new behavioral rules improved during several months of testing. Significantly, information was conveyed to the brain through the interplay of microstimulation patterns delivered to multiple electrodes and the temporal order in which these electrodes were stimulated. This suggests multichannel microstimulation as a viable means of sensorizing neural prostheses.
A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival
Authors: Meikle Lynsey , Talos Delia M. , Onda Hiroaki , Pollizzi Kristen , Rotenberg Alexander , Sahin Mustafa , Jensen Frances E. , Kwiatkowski David J.
Published: May 2007

Tuberous sclerosis (TSC) is a hamartoma syndrome caused by mutations inTSC1orTSC2in which cerebral cortical tubers and seizures are major clinical issues. We have engineered mice in which most cortical neurons lose Tsc1 expression during embryonic development. These Tsc1 mutant mice display several neurological abnormalities beginning at postnatal day 5 with subsequent failure to thrive and median survival of 35 d. The mice also display clinical and electrographic seizures both spontaneously and with physical stimulation, and some seizures end in a fatal tonic phase. Many cortical and hippocampal neurons are enlarged and/or dysplastic in the Tsc1 mutant mice, strongly express phospho-S6, and are ectopic in multiple sites in the cortex and hippocampus. There is a striking delay in myelination in the mutant mice, which appears to be caused by an inductive neuronal defect. This new TSC brain model replicates several features of human TSC brain lesions and implicates an important function of Tsc1/Tsc2 in neuronal development.
The Erlangen Slot Machine – A Platform for Interdisciplinary Research in Dynamically Reconfigurable Computing (ESM - Eine Hardware-Plattform für interdisziplinäre Forschung im Bereich des dynamischen rekonfigurierbaren Rechnens)
Authors: Angermeier Josef , Göhringer Diana , Majer Mateusz , Teich Jürgen , Fekete Sándor P. , Veen Jan C. van der
Published: May 2007

We introduce a hardware platform called Erlangen Slot Machine (ESM) that has been built in Erlangen within the project ReCoNodes for enabling interdisciplinary research on reconfigurable computing. For this dynamically reconfigurable computer, the cooperation partner in Braunschweig provides algorithmic solutions, in particular for the optimization of module placements and inter-module communication.
Exploration, Partitioning and Simulation of Reconfigurable Systems (Exploration, Partitionierung und Simulation rekonfigurierbarer Systeme)
Authors: Dittmann Florian , Rammig Franz J. , Streubühr Martin , Haubelt Christian , Schallenberg Andreas , Nebel Wolfgang
Published: May 2007

Reconfigurable devices in large complex systems allow the reduction of the amount of required resources. They serve as run-time re-usable devices for performance critical data-oriented processes. However, the use of reconfigurable devices within large systems greatly increases the design complexity. The designer´s task gets even harder when the goal is a resource efficient solution. Constructing a good design requires the consideration of many design alternatives. With today´s complex systems and the resulting degrees of freedom the designer should be assisted by sophisticated design space exploration tools. However, all known system-level design space exploration tools do not exploit the potentials dynamic hardware reconfiguration exposes. Moreover, the implementation of selected solutions poses an additional challenge and also requires a cycle-level simulation. This paper presents a novel design methodology which is able to overcome these drawbacks by integrating state-of-the-art temporal partitioning approaches for dynamic hardware reconfiguration into system-level design space exploration.
New Adaptive Multi-grained Hardware Architecture for Processing of Dynamic Function Patterns (Neue adaptive multi-granulare Hardwarearchitektur)
Authors: Thomas Alexander , Becker Jürgen
Published: May 2007

A new dynamic reconfigurable hardware architecture, the HoneyComb, will be introduced that has been developed within the project AMURHA. New integrated features enhance the flexibility and usability of future array-based systems by exploring the new approach.
Collaborative Research Center 516: Design and Manufacturing of Active Micro Systems (Sonderforschungsbereich 516: Konstruktion und Fertigung aktiver Mikrosysteme)
Authors: Büttgenbach Stephanus
Published: May 2007

The objective of the Collaborative Research Center “Design and manufacturing of active micro systems“ is the development of new technologies for the design and the production of electromagnetic micro drives. These technologies concern new design approaches, novel processes for fabrication and assembly, and new concepts for guides and measuring methods. The feasibility of the developed technologies is demonstrated by the use of prototype micro motors.
Heavenly Khao Chae——Aromatic Soaked Rice
Authors: yu su-mei
Published: May 2007

Khao chae--aromatic soaked rice--is served only during the hot summer months in Thailand. Its exquisite taste and laborious preparation beckoned the author, Su-Mei Yu, back to her birthplace. Skilled elderly cooks recruited by friends abruptly changed their minds about sharing their methods. These refusals led to an understanding of their superstitious beliefs.

With those who believe otherwise, the author not only learned how to make several versions of khao chae, but their shared memories taught her the dish's history and its influence on the people who make and eat it. Its ancient tradition binds together the people of a displaced nation, the Mon, among whom khao chae originated. Their ancient New Year custom, adopted by the Thais, became a summer food tradition in the Royal court of King Chulalongkhorn (1868-1910), one of the most celebrated times for Thai culinary art. The court turned the cooking of khao chae into a competitive feat. Although more than a century has passed, and despite climatic change and westernization of Thai culture, the remembrances of magical feasts of khao chae floated back as the summer heat stirred the minds of elderly folks.
Lactose Intolerance and Evolution: No Use Crying Over Undigested Milk
Authors: scheindlin benjamin
Published: May 2007

Lactose intolerance is an inability to digest milk sugar, characterized by abdominal cramps, nausea, and diarrhea after ingesting milk products. It develops in adolescence or adulthood among those whose bodies naturally stop producing the lactose-digesting enzyme lactase after childhood. Although uncommon in the United States, lactose intolerance actually occurs in the majority of people around the world. The ability to continue producing lactase, and thus to digest milk products, is a relatively recent evolutionary development.

After presentation of an illustrative clinical example, the biology of lactase production and lactose intolerance is reviewed. The "culture-historical" hypothesis of Simoons in the 1970's held that persistent lactase production developed in a dairy herding population in Northern Europe during a time of food scarcity, when the ability to digest milk would have provided a survival advantage. Simoons demonstrated that low prevalence of lactose intolerance was associated with pastoral practices among early populations around the world.

Hirschhorn recently provided strong genetic evidence for the culture-historical hypothesis using contemporary techniques of genomics and single nucleotide polymorphisms. His research group found that European derived persistent lactase production is due to a mutation near the lactase gene that occurred only about 10 million years ago and rapidly increased in prevalence.
The Myth of Apicius
Authors: grainger sally
Published: May 2007

Numerous stories are attached to that notorious Roman gourmand Marcus Gavius Apicius: his greed was legendary and so apparently was his skill - but skill in what exactly? This article will attempt to disentangle the evidence for Apicius the man (or men) from the text that bears his name: the recipe collection known as de re coquinaria that we often, almost for convenience sake, attribute to one or other of the Apicii. In doing so we will look at the nature of cooks and cooking in the Roman world, particularly in relation to the food texts. I will argue that the recipe collection was in fact written entirely by slave cooks rather then anyone from the elite and as such is a remarkable survival.
Whole body hypothermia for the treatment of hypoxic-ischaemic encephalopathy in term infants – a safety study in Hungary
Authors: Róka Anikó , Bodrogi Eszter , Szabó Miklós , Machay Tamás
Published: May 2007

Az asphyxiát elszenvedett újszülöttek kezelésében ígéretes lehetőség a mérsékelt, teljestest-hypothermia, amely több támadásponton képes csökkenteni a hypoxia-ischaemia által beindított biokémiai kaszkádot, valamint a maradandó szervkárosodást.
Célkitűzés:
A vizsgálat célja az volt, hogy egy nagy esetszámú hatékonysági vizsgálatot megelőzően felmérje a mérsékelt teljestest-hypothermia biztonságosságát és technikai kivitelezhetőségét Magyarországon.
Módszer:
Nyitott, prospektív „esetsorozat” klinikai vizsgálat keretében 2003 októberétől 2005 januárjáig a Semmelweis Egyetem I. Gyermekgyógyászati Klinika NIC osztályán 28 érett asphyxiás újszülöttnél alkalmaztak hypothermiás kezelést, melyhez 23, korábban (1996 és 2002 közötti időszakban) kezelt, klinikai paramétereikben hasonló újszülöttet választottak történelmi kontrollként. Beválasztási kritériumok: 5 perces Apgar-érték: ≤5, emellett felvételkor BE: ≤ –15 mmol/l és hypoxiás-ischaemiás encephalopathiára jellemző neurológiai tünetek jelenléte egyidejűleg. A mérsékelt, egésztest-hypothermiát (maghő: 33,0–34,0 °C) folyamatos morfin analgézia mellett 72 órán keresztül tartották fenn. Az intenzív kezelés alatt laboratóriumi vizsgálatok, szeriális koponya-UH, valamint standard intenzív terápiás monitorozás történt. A vizsgálat során összehasonlították a mortalitást, durva neurológiai maradványtünetek előfordulását, és az előre meghatározott klinikai paramétereket.
Eredmények:
A két csoport antropometriai adatai és iniciális klinikai állapota (Apgar, pH, BE, encephalopathia tünetei) szignifikánsan nem különbözött. A hypothermiás (10/28) és a kontrollcsoport (10/21) mortalitásában nem találtak különbséget. A vizsgált klinikai paraméterekben (laboratóriumi paraméterek, ultrahang-eltérések, hypoglykaemia, vérzékenység, súlyos hipotenzió előfordulása, katecholamin-igény, oliguria) és a 1,5–2 éves utánkövetés során észlelt idegrendszeri károsodás arányaiban szignifikáns különbség nem igazolódott. A hypothermiával oki összefüggésbe hozható mellékhatást nem észleltek.
Következtetés:
A mérsékelt, egésztest-hypothermia a vizsgálat szerint biztonsággal alkalmazható, nem fokozza a súlyos perinatalis asphyxiát elszenvedett újszülöttek mortalitását és morbiditását. A hatásosság megítélésére további, széles nemzetközi összefogáson alapuló nagy esetszámú randomizált klinikai vizsgálatra van szükség.
Fast track colo-rectal surgery
Authors: Sipos Péter , Ondrejka Pál
Published: May 2007

A vastagbélműtéteket követő gyors felépüléshez sok tényező járul hozzá. A műtéthez kapcsolódó folyamatok optimálissá tételéhez nemcsak az operációs technika, hanem ezen túl a műtét előtti és utáni tényezők is nagyban hozzájárulnak. A Medline elektronikus adatbázisból kulcsszavakra való kereséssel gyűjtöttük ki a megfelelő cikkeket, majd az oxfordi Evidence Based Medicine beosztása alapján rangsoroltuk őket és a legrelevánsabbakat használtuk fel. Randomizált, multicentrikus tanulmányok igazolták, hogy a vastagbélműtéteket megelőző hashajtás nem csökkenti az anastomosis insufficientiák és sebszövődmények számát; a hasi drének rutinszerű használata nem szükséges; a körültekintő, korai táplálás a vastagbélsebészetben is biztonságos és jól tolerálható, és a laparoszkópos vastagbélműtétek a nyílt műtétekkel egyenértékűek. A kapott evidenciákat jelenleg nem teljes mértékben alkalmazzuk. A laparoszkópos műtéti technika előnyeit a fast track perioperatív ellátás nagyban fokozza. Ahhoz, hogy a vastagbélsebészet perioperatív folyamataiban szerepet játszó faktorok előnyeit a legjobban kihasználhassuk, ezek kellő ismerete szükséges.
Multi-Institutional Phase II Study of S-1 Monotherapy in Advanced Gastric Cancer with Pharmacokinetic and Pharmacogenomic Evaluations
Authors: Jeung Hei-Cheul , Rha Sun Young , Kim Hoon Kyo , Lim Ho Young , Kim Samyong , Kim Si Young , Gong Soo Jeong , Park Chan Hee , Ahn Joong Bae , Noh Sung Hoon , Chung Hyun Cheol
Published: May 2007

This study describes the first phase II study of S-1, a novel oral fluoropyrimidine, in a non-Japanese Asian population with advanced gastric cancer. S-1 was administered twice daily for 28 days every 6 weeks. A pharmacokinetic study was performed on day 28 of cycles 1 and 3. Genomic DNA from peripheral mononuclear cells was analyzed using a cDNA microarray-based comparative genomic hybridization (CGH) method. Thirty-one patients were initially given a dose of 35 mg/m2 twice daily (bid) (group 1); then, the protocol was amended by increasing the dose to 40 mg/m2 bid for an additional 31 patients (group 2) because of good tolerability to S-1. The overall response rate was 19.3% (95% confidence interval, 9.2%–29.5%). Over a median follow-up duration of 265 days, the median time to progression and overall survival time were 126 and 264 days, respectively. The 1-year survival rate was 34%. There was no grade 4 toxicity and the major adverse event was anemia. Pharmacokinetic parameters were similar to those of the previous Japanese reports. Microarray CGH identified 18 genes with copy number changes that were associated with hemoglobin reduction with S-1 treatment. A logistic regression analysis, integrating one clinical parameter (initial hemoglobin level) combined with three genetic copy number variations (HIST1H2BL, C10orf127, and XPNPEP2), provided a predictive model for the development of severe hemoglobin reduction. In conclusion, this study showed the feasibility of using S-1 at 35 mg/m2 bid in gastric cancer. We suggest that the pharmacogenomic markers identified in this study may be potential candidates for predicting anemia after S-1 treatment.
Intensity-Modulated Radiation Therapy for Head and Neck Carcinoma
Authors: Grégoire Vincent , De Neve Wilfried , Eisbruch Avraham , Lee Nancy , Van den Weyngaert Danielle , Van Gestel Dirk
Published: May 2007

Learning Objectives

After completing this course, the reader will be able to: Outline innovations related to targeted radiation therapy.Describe trials proving an advantage using IMRT.Assess treatment planning modalities and how IMRT fields are designed.Evaluate when there is a toxicity advantage for IMRT.Discern when conventional radiotherapy should be used instead of IMRT.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Primary Effusion Lymphoma
Authors: Chen Yi-Bin , Rahemtullah Aliyah , Hochberg Ephraim
Published: May 2007

Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma (NHL) that accounts for approximately 4% of all HIV-associated NHL. PEL has a unique clinical presentation in having a predilection for arising in body cavities such as the pleural space, pericardium, and peritoneum. PEL cells are morphologically variable with a null lymphocyte immunophenotype and evidence of human herpesvirus (HHV)-8 infection. The exact oncogenic mechanisms of HHV-8 have not been clearly defined. Treatment is usually with combination CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy and antiretroviral therapy (if HIV positive). The prognosis for PEL is poor, with a median survival time of around 6 months. As the exact molecular steps in HHV-8–driven oncogenesis are unraveled, it is hoped that more specific therapeutic targets will be revealed.
The Effectiveness of Darbepoetin Alfa Administered Every 3 Weeks on Hematologic Outcomes and Quality of Life in Older Patients With Chemotherapy-Induced Anemia
Authors: Boccia Ralph , Lillie Tom , Tomita Dianne , Balducci Lodovico
Published: May 2007

Chemotherapy-induced anemia (CIA) may substantially impact the health-related quality of life (HRQoL) of older cancer patients. This exploratory analysis evaluated the effect of darbepoetin alfa administered as a fixed dose (300 μg) every 3 weeks (Q3W) on hematologic outcomes, HRQoL, and safety in older (≥65 years old) versus younger (<65 years old) patients with CIA (hemoglobin <11g/dl). Patients were categorized by age at screening: <65, ≥65 to <70, ≥70 to <75, ≥75 to <80, and ≥80 years old. Patients who received at least one dose of darbepoetin alfa were included in the analysis; of 1,493 patients, 724 were ≥65 years old. Age did not appear to influence hematologic outcomes after treatment with darbepoetin alfa; in all age categories, similar percentages of patients (78%–80%) achieved the target hemoglobin in approximately the same time (4–5 weeks). Also, the percentage of patients in each age category who received RBC transfusions was reduced from 10%–13% in month 1 to 2%–4% in month 4. Although younger patients reported the greatest improvement in HRQoL scores, approximately one half in each older age category reported clinically significant improvement in fatigue, and improvement in the Energy and Overall Health Assessment and Work Productivity and Activity Impairment scales. There were no treatment-related deaths. Treatment-related thromboembolic events were reported by <1% of patients <65 years old and <1% of patients ≥65 to <70 and ≥70 to <75 years old. Darbepoetin alfa Q3W appeared well tolerated and effective for treating older patients with CIA.
Management and Preparedness for Infusion and Hypersensitivity Reactions
Authors: Lenz Heinz-Josef
Published: May 2007

Learning Objectives

After completing this course, the reader will be able to: Discuss the physiology of the different clinical hypersensitivity and infusion reactions to monoclonal antibodies and chemotherapy.Select appropriate prevention and treatment strategies for hypersensitivity reactions.Describe the differences between acquired and acute hypersensitivity reactions.

CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com
Are we making a difference?
Authors: Clyne Michael
Published: May 2007

Language is crucial in our lives and to all disciplines. It affects our well-being individually and collectively and touches important sociopolitical issues. Linguists/applied linguists have exciting opportunities for interdisciplinary research and to work in contexts personally meaningful to them. While language is the concern of all people, professionals have special responsibilities to provide leadership in understanding how it works and responsible insights into the uses and abuses of language in society.

Australian language specialists can offer the rest of the world experience with language policy, typological and language contact studies, and bilingual language acquisition. Some Australians have advanced linguistic knowledge through studies of indigenous languages. Many have worked with indigenous, ethnic and other communities and professional groups, providing evidence in court or advice to teachers and families. Some broadcast regularly or occasionally. But have we succeeded in contesting the monolingual mindset of the mainstream? The Australian authors represented in language sections of most general bookshops are not linguists.

Far more collaboration and coordination of initiatives through the professional societies is needed to put languages back on the national agenda and make Australia more language-aware. This should lead to recognizing, valuing, fostering and transmitting, supporting and sharing our linguistic diversity. Australia’s rich language potential has only been partly realized.
Classroom discourse in problem-based learning classrooms in the health sciences
Authors: Woodward-Kron Robyn , Remedios Louisa
Published: May 2007

Classroom discourse analysis has contributed to understandings of the nature of student-teacher interactions, and how learning takes place in the classroom; however, much of this work has been undertaken in teacher-directed learning contexts. Student-centred classrooms such as problem-based learning (PBL) approaches are increasingly common in professional disciplines such as the health sciences and medicine. With the globalisation of education, health science and medical education, PBL classrooms are often sites of considerable linguistic and cultural diversity, yet little is known from a classroom discourse perspective about the language demands of PBL. This paper examines the ways in which the students and tutor negotiate and construct meanings through language in one first year physiotherapy PBL tutorial at an Australian university, with a particular focus on the ways in which the discourse is regulated in a student-centred learning environment. The analysis of the classroom discourse is underpinned by Halliday’s systemic functional linguistics. The findings provide a description of the linguistic resources students draw on to co-construct and negotiate knowledge, as well as show how the tutor, with minimal strategic interventions, scaffolds the students’ learning. The findings also suggest that the PBL environment can be a challenging one for students whose cultural and language backgrounds are different from that of the classroom.
Malposition of Unerupted Mandibular Second Premolar in Children with Cleft Lip and Palate
Authors: Shalish Miri , Will Leslie A. , Shustermann Stephen
Published: May 2007

Objective: To determine whether distoangular malposition of the unerupted mandibular second premolar (MnP2) is more frequent in children with unilateral clefts of the lip and palate.

Materials and Methods: This retrospective study examined panoramic radiographs from 45 patients with unilateral clefts of the lip and/or palate who had no previous orthodontics. A control sample consisted of age- and sex-matched patients. The distal angle formed between the long axis of MnP2 and the tangent to the inferior border was measured. The mean, standard deviation, and range were calculated for the angles measured in the cleft and the control groups. The significance of the differences between the means was evaluated by the paired t-test. The angles of the cleft and noncleft sides were also measured and compared.

Results: The mean inclination of the MnP2 on the cleft side was 73.6°, compared with 84.6° in the control group. This difference was highly significant statistically (P < .0001). The difference in angles from the cleft and noncleft sides was 0.7°, not statistically significant. A significant association was found between clefting and distoangular malposition of the developing MnP2, suggesting a shared genetic etiology. This association is independent of the clefting side, ruling out possible local mechanical effects.

Conclusion: Clinicians should be aware of the potential for anomalous development of MnP2 in children with clefts.
The Perception of Children's Computer-Imaged Facial Profiles by Patients, Mothers and Clinicians
Authors: Miner Robert M. , Anderson Nina K. , Evans Carla A. , Giddon Donald B.
Published: May 2007

Objective: To demonstrate the usefulness of a new imaging system for comparing the morphometric bases of children's self-perception of their facial profile with the perceptions of their mothers and treating clinicians.

Materials and Methods: Rather than choosing among a series of static images, a computer imaging program was developed to elicit a range of acceptable responses or tolerance for change from which a midpoint of acceptability was derived. Using the method of Giddon et al, three profile features (upper and lower lips and mandible) from standardized images of 24 patients aged 8– 15 years were distorted and presented to patients, parents, and clinicians in random order as slowly moving images (four frames per second) from retrusive and protrusive extremes. Subjects clicked the mouse when the image became acceptable and released it when it was no longer acceptable. Subjects responded similarly to a neutral facial profile.

Results: Patients and their mothers overestimated the protrusiveness of the mandible of the actual pretreatment profile. Consistent with related studies, mothers had a smaller tolerance for change in the soft tissue profile than the children or clinicians. The magnitudes of the children's self-preference and preferred change in a neutral face were also significantly correlated. Both patients and mothers preferred a more protrusive profile than that of the actual or neutral face for the patient and neutral face.

Conclusion: Imaging software can be used with children to compare their preferences with those of parents and clinicians to facilitate treatment planning and patient satisfaction.
Excess Adhesive Flash Upon Bracket Placement
Authors: Armstrong David , Shen Gang , Petocz Peter , Darendeliler M. Ali
Published: May 2007

Objective: To determine if there is any significant difference in excess adhesive flash (EAF) with the use of APC PLUS adhesive coated appliance system and Transbond XT and if other variables such as side of the mouth, time taken to bond the brackets, the age of the orthodontic specialist, or the years of clinical experience affected the amount of EAF.

Materials and Methods: Twenty orthodontic specialists bonded 20 preadjusted straight wire brackets (Victory, 3M Unitek) on a typodont with a Class I crowded malocclusion in a split-mouth design, with one-half of the brackets bonded with APC PLUS adhesive system and the other half with Transbond XT. The teeth were sputter coated with gold and an image was taken at 32× magnification in a scanning electron microscope (Philips XL30). The resultant tagged image file (TIF) was opened in AnalySIS Pro 3.1 (Soft Imaging System, Munich, Germany) and the area of EAF was measured.

Results: t-Tests demonstrated that: (1) there was no statistically significant difference in EAF between two adhesives when bonding in different quadrants of dentition; and (2) there was no statistically significant difference in EAF between two adhesives overall. Analysis of variance models demonstrated there were no statistically significant differences found regarding the age of the orthodontic specialists, years of clinical experience, and time in performing the bonding.

Conclusions: The addition of a coloring agent to assist in the visualization of the excess adhesive does not reduce the amount of excessive adhesive around orthodontic brackets.