bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression
Authors: Reineke Lucas C. , Merrick William C.
Published: October 2009

Cap-independent initiation of translation is thought to promote protein synthesis on some mRNAs during times when cap-dependent initiation is down-regulated. However, the mechanism of cap-independent initiation is poorly understood. We have previously reported the secondary structure within the yeast minimal URE2 IRES element. In this study, we sought to investigate the mechanism of internal initiation in yeast by assessing the functional role of nucleotides within the minimal URE2 IRES element, and delineating the cis-sequences that modulate levels of internal initiation using a monocistronic reporter vector. Furthermore, we compared the eIF2A sensitivity of the URE2 IRES element with some of the invasive growth IRES elements using ΔeIF2A yeast. We found that the stability of the stem–loop structure within the minimal URE2 IRES element is not a critical determinant of optimal IRES activity, and the downstream sequences that modulate URE2 IRES-mediated translation can be defined to discrete regions within the URE2 coding region. Repression of internal initiation on the URE2 minimal IRES element by eIF2A is not dependent on the stability of the secondary structure within the URE2 IRES element. Our data also indicate that eIF2A-mediated repression is not specific to the URE2 IRES element, as both the GIC1 and PAB1 IRES elements are repressed by eIF2A. These data provide valuable insights into the mRNA requirements for internal initiation in yeast, and insights into the mechanism of eIF2A-mediated suppression.
Free energy calculation of modified base-pair formation in explicit solvent: A predictive model
Authors: Vendeix Franck A.P. , Munoz Antonio M. , Agris Paul F.
Published: October 2009

The maturation of RNAs includes site-specific post-transcriptional modifications that contribute significantly to hydrogen bond formation within RNA and between different RNAs, especially in formation of mismatch base pairs. Thus, an understanding of the geometry and strength of the base-pairing of modified ribonucleoside 5′-monophosphates, previously not defined, is applicable to investigations of RNA structure and function and of the design of novel RNAs. The geometry and free energies of base-pairings were calculated in aqueous solution under neutral conditions with AMBER force fields and molecular dynamics simulations (MDSs). For example, unmodified uridines were observed to bind to uridine and cytidine with significant stability, but the ribose C1′–C1′ distances were far short (∼8.9 Å) of distances observed for canonical A-form RNA helices. In contrast, 5-oxyacetic acid uridine, known to bind adenosine, wobble to guanosine, and form mismatch base pairs with uridine and cytidine, bound adenosine and guanosine with geometries and energies comparable to an unmodified uridine. However, the 5-oxyacetic acid uridine base paired to uridine and cytidine with a C1′–C1′ distance comparable to that of an A-form helix, ∼11 Å, when a H2O molecule migrated between and stably hydrogen bonded to both bases. Even in formation of canonical base pairs, intermediate structures with a second energy minimum consisted of transient H2O molecules forming hydrogen bonded bridges between the two bases. Thus, MDS is predictive of the effects of modifications, H2O molecule intervention in the formation of base-pair geometry, and energies that are important for native RNA structure and function.
Green approaches to colorimetric monitoring of calcium in water
Authors: Savvin Sergey B. , Kuznetsov Vladimir V. , Ermolenko Yulia V. , Chernikova Irina Yu. , Mikhailova Alla V.
Published: October 2009

Simple, ecologically harmless chemical reactions have always been a point of interest for chemists and analysts as fit to be applied to work in or out of laboratories. A new concept of chemical analysis is exemplified in the article by means of selective determination of calcium ions with the organic reagent arsenazo III (2,2'-[1,8-dihydroxy-3,6-disulfonaphthylene-2,7-bisazo]-bisbenzenearsonic acid disodium salt) with no application of toxic solvents during the seasonal analysis of water in the Yauza River (the city of Moscow).
The sense of the interface: Applying semiotics to HCI research
Authors: Scolari Carlos
Published: October 2009

The objective of this article is to reflect on the application of Semiotics to Human-Computer Interaction (HCI) and interface analysis. To accomplish the objective the article presents an example of semiotic analysis of a blog interface but the methodology proposed, conveniently adapted, may be applied to any kind of digital interactive environment. The analysis reconstructs the interface sense production device (including the surface of the page and the link architecture), identifies implied users and exchange scenes of the blog and concludes with some reflections on interface evolution and hybridation. Finally, the article proposes future trends for a Semiotics of HCI.
1950 Supplement to the Metal Cleaning Bibliographical Abstracts
Authors: Harris Jay C.
Published: October 2009

This 1950 Supplement to the A.S.T.M. special technical publicatio No. 90 on “Metal Cleaning, Bibliographical Abstracts” is intended to bring up to date the coverage by this bibliography of the published data on metal cleaning. The 1949 edition of this publication covers the years 1893 to 1949 with the references being arranged by year, and secondarily by author, or by the journal in which the article appeared if anonymous. The same system has been followed in this supplement. Since it is planned to combine this supplement with the main bibliography when it is next printed, references falling within the dates of the 1949 edition have been assigned the same number as the reference in the 1949 edition that will precede them in the combined bibliography, with the addition of a letter of the alphabet (for example, 57A). In order to facilitate reference to the abstracts they have been thoroughly indexed in the following four ways: Subject Index Author Index Specification Index Patent Index
Classical Major Histocompatibility Complex Class I Molecules in Motoneurons: New Actors at the Neuromuscular Junction
Authors: Thams Sebastian , Brodin Petter , Plantman Stefan , Saxelin Robert , Kärre Klas , Cullheim Staffan
Published: October 2009

Major histocompatibility complex (MHC) class I molecules have fundamental functions in the immune system. Recent studies have suggested that these molecules may also have non-immune functions in the nervous system, in particular related to synaptic function and plasticity. Because adult motoneurons express mRNAs for MHC class I molecules, we have examined their subcellular expression patternin vivoand their role for the synaptic connectivity of these neurons. We observed immunoreactivity for classical MHC class I (Ia) protein in motoneuron somata, but the predominant expression was found in axons and presynaptically at neuromuscular junctions (NMJs). Peripheral nerve lesion induced a strong increase of motoneuron MHC class Ia (H2-Kb/Db) mRNA, indicating a role for MHC class Ia molecules during regeneration. Accordingly, there was an accumulation of MHC class Ia proteins at the cut ends and in growth cones of motor axons after lesion. InKb−/−Db−/−mice (lacking MHC class Ia molecules), the time course for recovery of grip ability in reinnervated muscles was significantly delayed. Muscles fromKb−/−Db−/−mice displayed an increased density and a disturbed distribution of NMJs and fewer terminal Schwann cells/NMJ compared with wild-type mice. A population of Schwann cells in sciatic nerves expressed the paired Ig receptor B, which binds to MHC class I molecules. These results provide the first evidence that neuronal MHC class Ia molecules are present in motor axons, that they are important for organization of NMJs and motor recovery after nerve lesion, and that their actions may be mediated via Schwann cells.
Progressive Postnatal Motoneuron Loss in Mice Lacking GDF-15
Authors: Strelau Jens , Strzelczyk Adam , Rusu Patricia , Bendner Gerald , Wiese Stefan , Diella Francesca , Altick Amy L. , von Bartheld Christopher S. , Klein Rüdiger , Sendtner Michael , Unsicker Klaus
Published: October 2009

Growth/differentiation factor-15 (GDF-15) is a widely expressed distant member of the TGF-β superfamily with prominent neurotrophic effects on midbrain dopaminergic neurons. We show here that GDF-15-deficient mice exhibit progressive postnatal losses of spinal, facial, and trigeminal motoneurons. This deficit reaches a ∼20% maximum at 6 months and is accompanied by losses of motor axons and significant impairment of rotarod skills. Similarly, sensory neurons in dorsal root ganglia (L4, L5) are reduced by 20%, whereas sympathetic neurons are not affected. GDF-15 is expressed and secreted by Schwann cells, retrogradely transported along adult sciatic nerve axons, and promotes survival of axotomized facial neurons as well as cultured motor, sensory, and sympathetic neurons. Despite striking similarities in the GDF-15 and CNTF knock-out phenotypes, expression levels of CNTF and other neurotrophic factors in the sciatic nerve were unaltered suggesting that GDF-15 is a genuine novel trophic factor for motor and sensory neurons.
Brain Hemispheres Selectively Track the Expected Value of Contralateral Options
Authors: Palminteri Stefano , Boraud Thomas , Lafargue Gilles , Dubois Bruno , Pessiglione Mathias
Published: October 2009

A main focus in economics is on binary choice situations, in which human agents have to choose between two alternative options. The classical view is that decision making consists of valuating each option, comparing the two expected values, and selecting the higher one. Some neural correlates of option values have been described in animals, but little is known about how they are represented in the human brain: are they integrated into a single center or distributed over different areas? To address this issue, we examined whether the expected values of two options, which were cued by visual symbols and chosen with either the left or right hand, could be distinguished using functional magnetic resonance imaging. The two options were linked to monetary rewards through probabilistic contingencies that subjects had to learn so as to maximize payoff. Learning curves were fitted with a standard computational model that updates, on a trial-by-trial basis, the value of the chosen option in proportion to a reward prediction error. Results show that during learning, left and right option values were specifically expressed in the contralateral ventral prefrontal cortex, regardless of the upcoming choice. We therefore suggest that expected values are represented in a distributed manner that respects the topography of the brain systems elicited by the available options.
Broadband Shifts in Local Field Potential Power Spectra Are Correlated with Single-Neuron Spiking in Humans
Authors: Manning Jeremy R. , Jacobs Joshua , Fried Itzhak , Kahana Michael J.
Published: October 2009

A fundamental question in neuroscience concerns the relation between the spiking of individual neurons and the aggregate electrical activity of neuronal ensembles as seen in local field potentials (LFPs). Because LFPs reflect both spiking activity and subthreshold events, this question is not simply one of data aggregation. Recording from 20 neurosurgical patients, we directly examined the relation between LFPs and neuronal spiking. Examining 2030 neurons in widespread brain regions, we found that firing rates were positively correlated with broadband (2–150 Hz) shifts in the LFP power spectrum. In contrast, narrowband oscillations correlated both positively and negatively with firing rates at different recording sites. Broadband power shifts were a more reliable predictor of neuronal spiking than narrowband power shifts. These findings suggest that broadband LFP power provides valuable information concerning neuronal activity beyond that contained in narrowband oscillations.
Molecular Reconstruction of mGluR5a-Mediated Endocannabinoid Signaling Cascade in Single Rat Sympathetic Neurons
Authors: Won Yu-Jin , Puhl Henry L. , Ikeda Stephen R.
Published: October 2009

Endocannabinoids (eCB) such as 2-arachidonylglycerol (2-AG) are lipid metabolites that are synthesized in a postsynaptic neurons and act upon CB1cannabinoid receptors (CB1R) in presynaptic nerve terminals. This retrograde transmission underlies several forms of short and long term synaptic plasticity within the CNS. Here, we constructed a model system based on isolated rat sympathetic neurons, in which an eCB signaling cascade could be studied in a reduced, spatially compact, and genetically malleable system. We constructed a complete eCB production/mobilization pathway by sequential addition of molecular components. Heterologous expression of four components was required for eCB production and detection: metabotropic glutamate receptor 5a (mGluR5a), Homer 2b, diacylglycerol lipase α, and CB1R. In these neurons, application ofl-glutamate produced voltage-dependent modulation of N-type Ca2+channels mediated by activation of CB1R. Using both molecular dissection and pharmacological agents, we provide evidence that activation of mGluR5a results in rapid enzymatic production of 2-AG followed by activation of CB1R. These experiments define the critical elements required to recapitulate retrograde eCB production and signaling in a single peripheral neuron. Moreover, production/mobilization of eCB can be detected on a physiologically relevant time scale using electrophysiological techniques. The system provides a platform for testing candidate molecules underlying facilitation of eCB transport across the plasma membrane.
Human Reinforcement Learning Subdivides Structured Action Spaces by Learning Effector-Specific Values
Authors: Gershman Samuel J. , Pesaran Bijan , Daw Nathaniel D.
Published: October 2009

Humans and animals are endowed with a large number of effectors. Although this enables great behavioral flexibility, it presents an equally formidable reinforcement learning problem of discovering which actions are most valuable because of the high dimensionality of the action space. An unresolved question is how neural systems for reinforcement learning—such as prediction error signals for action valuation associated with dopamine and the striatum—can cope with this “curse of dimensionality.” We propose a reinforcement learning framework that allows for learned action valuations to be decomposed into effector-specific components when appropriate to a task, and test it by studying to what extent human behavior and blood oxygen level-dependent (BOLD) activity can exploit such a decomposition in a multieffector choice task. Subjects made simultaneous decisions with their left and right hands and received separate reward feedback for each hand movement. We found that choice behavior was better described by a learning model that decomposed the values of bimanual movements into separate values for each effector, rather than a traditional model that treated the bimanual actions as unitary with a single value. A decomposition of value into effector-specific components was also observed in value-related BOLD signaling, in the form of lateralized biases in striatal correlates of prediction error and anticipatory value correlates in the intraparietal sulcus. These results suggest that the human brain can use decomposed value representations to “divide and conquer” reinforcement learning over high-dimensional action spaces.
Perceptual Learning of Object Shape
Authors: Gölcü Doruk , Gilbert Charles D.
Published: October 2009

Recognition of objects is accomplished through the use of cues that depend on internal representations of familiar shapes. We used a paradigm of perceptual learning during visual search to explore what features human observers use to identify objects. Human subjects were trained to search for a target object embedded in an array of distractors, until their performance improved from near-chance levels to over 80% of trials in an object-specific manner. We determined the role of specific object components in the recognition of the object as a whole by measuring the transfer of learning from the trained object to other objects sharing components with it. Depending on the geometric relationship of the trained object with untrained objects, transfer to untrained objects was observed. Novel objects that shared a component with the trained object were identified at much higher levels than those that did not, and this could be used as an indicator of which features of the object were important for recognition. Training on an object also transferred to the components of the object when these components were embedded in an array of distractors of similar complexity. These results suggest that objects are not represented in a holistic manner during learning but that their individual components are encoded. Transfer between objects was not complete and occurred for more than one component, regardless of how well they distinguish the object from distractors. This suggests that a joint involvement of multiple components was necessary for full performance.
Dendritic Compartment and Neuronal Output Mode Determine Pathway-Specific Long-Term Potentiation in the Piriform Cortex
Authors: Johenning Friedrich W. , Beed Prateep S. , Trimbuch Thorsten , Bendels Michael H. K. , Winterer Jochen , Schmitz Dietmar
Published: October 2009

The apical dendrite of layer 2/3 pyramidal cells in the piriform cortex receives two spatially distinct inputs: one projecting onto the distal apical dendrite in sensory layer 1a, the other targeting the proximal apical dendrite in layer 1b. We observe an expression gradient of A-type K+channels that weakens the backpropagating action potential-mediated depolarization in layer 1a compared with layer 1b. We find that the pairing of presynaptic and postsynaptic firing leads to significantly smaller Ca2+signals in the distal dendritic spines in layer 1a compared with the proximal spines in layer 1b. The consequence is a selective failure to induce long-term potentiation (LTP) in layer 1a, which can be rescued by pharmacological enhancement of action potential backpropagation. In contrast, LTP induction by pairing presynaptic and postsynaptic firing is possible in layer 1b but requires bursting of the postsynaptic cell. This output mode strongly depends on the balance of excitation and inhibition in the piriform cortex. We show, on the single-spine level, how the plasticity of functionally distinct synapses is gated by the intrinsic electrical properties of piriform cortex layer 2 pyramidal cell dendrites and the cellular output mode.
Cytoplasmic Polyadenylation Element-Binding Protein Regulates Neurotrophin-3-Dependent β-Catenin mRNA Translation in Developing Hippocampal Neurons
Authors: Kundel Mitchell , Jones Kendrick J. , Shin Chan Y. , Wells David G.
Published: October 2009

Neuronal morphogenesis, the growth and arborization of neuronal processes, is an essential component of brain development. Two important but seemingly disparate components regulating neuronal morphology have previously been described. In the hippocampus, neurotrophins, particularly brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3), act to enhance cell growth and branching, while activity-induced branching was shown to be dependent upon intracellular β-catenin. We now describe a molecular link between NT3 stimulation and β-catenin increase in developing neurons and demonstrate that this process is required for the NT3-mediated increase in process branching. Here, we show that β-catenin is rapidly increased specifically in growth cones following NT3 stimulation. This increase in β-catenin is protein synthesis dependent and requires the activity of cytoplasmic polyadenylation element-binding protein-1 (CPEB1), an mRNA-binding protein that regulates mRNA translation. We find that CPEB1 protein binds β-catenin mRNA in a CPE-dependent manner and that both localize to growth cones of developing hippocampal neurons. Both the NT3-mediated rapid increase in β-catenin and process branching are abolished when CPEB1 function is inhibited. In addition, the NT3-mediated increase in β-catenin in growth cones is dependent upon internal calcium and the activity of CaMKII (calcium/calmodulin-dependent kinase II). Together, these results suggest that CPEB1 regulates β-catenin synthesis in neurons and may contribute to neuronal morphogenesis.
Dual Neural Routing of Visual Facilitation in Speech Processing
Authors: Arnal Luc H. , Morillon Benjamin , Kell Christian A. , Giraud Anne-Lise
Published: October 2009

Viewing our interlocutor facilitates speech perception, unlike for instance when we telephone. Several neural routes and mechanisms could account for this phenomenon. Using magnetoencephalography, we show that when seeing the interlocutor, latencies of auditory responses (M100) are the shorter the more predictable speech is from visual input, whether the auditory signal was congruent or not. Incongruence of auditory and visual input affected auditory responses ∼20 ms after latency shortening was detected, indicating that initial content-dependent auditory facilitation by vision is followed by a feedback signal that reflects the error between expected and received auditory input (prediction error). We then used functional magnetic resonance imaging and confirmed that distinct routes of visual information to auditory processing underlie these two functional mechanisms. Functional connectivity between visual motion and auditory areas depended on the degree of visual predictability, whereas connectivity between the superior temporal sulcus and both auditory and visual motion areas was driven by audiovisual (AV) incongruence. These results establish two distinct mechanisms by which the brain uses potentially predictive visual information to improve auditory perception. A fast direct corticocortical pathway conveys visual motion parameters to auditory cortex, and a slower and indirect feedback pathway signals the error between visual prediction and auditory input.
Spinal Interneurons Differentiate Sequentially from Those Driving the Fastest Swimming Movements in Larval Zebrafish to Those Driving the Slowest Ones
Authors: McLean David L. , Fetcho Joseph R.
Published: October 2009

Studies of neuronal networks have revealed few general principles that link patterns of development with later functional roles. While investigating the neural control of movements, we recently discovered a topographic map in the spinal cord of larval zebrafish that relates the position of motoneurons and interneurons to their order of recruitment during swimming. Here, we show that the map reflects an orderly pattern of differentiation of neurons driving different movements. First, we use high-speed filming to show that large-amplitude swimming movements with bending along much of the body appear first, with smaller, regional swimming movements emerging later. Next, using whole-cell patch recordings, we demonstrate that the excitatory circuits that drive large-amplitude, fast swimming movements at larval stages are present and functional early on in embryos. Finally, we systematically assess the orderly emergence of spinal circuits according to swimming speed using transgenic fish expressing the photoconvertible protein Kaede to track neuronal differentiationin vivo. We conclude that a simple principle governs the development of spinal networks in which the neurons driving the fastest, most powerful swimming in larvae develop first with ones that drive increasingly weaker and slower larval movements layered on over time. Because the neurons are arranged by time of differentiation in the spinal cord, the result is a topographic map that represents the speed/strength of movements at which neurons are recruited and the temporal emergence of networks. This pattern may represent a general feature of neuronal network development throughout the brain and spinal cord.
Adult-Born Hippocampal Dentate Granule Cells Undergoing Maturation Modulate Learning and Memory in the Brain
Authors: Deng Wei , Saxe Michael D. , Gallina Iryna S. , Gage Fred H.
Published: October 2009

Adult-born dentate granule cells (DGCs) contribute to learning and memory, yet it remains unknown when adult-born DGCs become involved in the cognitive processes. During neurogenesis, immature DGCs display distinctive physiological characteristics while undergoing morphological maturation before final integration into the neural circuits. The survival and activity of the adult-born DGCs can be influenced by the experience of the animal during a critical period when newborn DGCs are still immature. To assess the temporal importance of adult neurogenesis, we developed a transgenic mouse model that allowed us to transiently reduce the numbers of adult-born DGCs in a temporally regulatable manner. We found that mice with a reduced population of adult-born DGCs at the immature stage were deficient in forming robust, long-term spatial memory and displayed impaired performance in extinction tasks. These results suggest that immature DGCs that undergo maturation make important contributions to learning and memory.
Permanent Functional Reorganization of Retinal Circuits Induced by Early Long-Term Visual Deprivation
Authors: Di Marco Stefano , Nguyen Vincent A. , Bisti Silvia , Protti Dario A.
Published: October 2009

Early sensory experience shapes the functional and anatomical connectivity of neuronal networks. Light deprivation alters synaptic transmission and modifies light response properties in the visual system, from retinal circuits to higher visual centers. These effects are more pronounced during a critical period in juvenile life and are mostly reversed by restoring normal light conditions. Here we show that complete light deprivation, from birth to periods beyond the critical period, permanently modifies the receptive field properties of retinal ganglion cells. Visual deprivation reduced both the strength of light responses in ganglion cells and their receptive field size. Light deprivation produced an imbalance in the ratio of inhibitory to excitatory inputs, with a shift toward larger inhibitory conductances. Ganglion cell receptive fields in visually deprived animals showed a spatial mismatch of inhibitory and excitatory inputs and inhibitory inputs were highly scattered over the receptive field. These results indicate that visual experience early in life is critical for the refinement of retinal circuits and for appropriate signaling of the spatiotemporal properties of visual stimuli, thus influencing the response properties of neurons in higher visual centers and their processing of visual information.
Effects of the Antipsychotic Risperidone on Dopamine Synthesis in Human Brain Measured by Positron Emission Tomography with l-[β-11C]DOPA: A Stabilizing Effect for Dopaminergic Neurotransmission?
Authors: Ito Hiroshi , Takano Harumasa , Takahashi Hidehiko , Arakawa Ryosuke , Miyoshi Michie , Kodaka Fumitoshi , Okumura Masaki , Otsuka Tatsui , Suhara Tetsuya
Published: October 2009

Effects of antipsychotic drugs have widely been considered to be mediated by blockade of postsynaptic dopamine D2receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. To investigate the effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission in relation with occupancy of dopamine D2receptors, changes in dopamine synthesis capacity by antipsychotics and occupancy of dopamine D2receptors were measured by positron emission tomography (PET) in healthy men. PET studies using [11C]raclopride andl-[β-11C]DOPA were performed under resting condition and oral administration of single dose of the antipsychotic drug risperidone on separate days. Although occupancy of dopamine D2receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D2receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.
Intrabody Gene Therapy Ameliorates Motor, Cognitive, and Neuropathological Symptoms in Multiple Mouse Models of Huntington's Disease
Authors: Southwell Amber L. , Ko Jan , Patterson Paul H.
Published: October 2009

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease resulting from the expansion of a glutamine repeat in the huntingtin (Htt) protein. Current therapies are directed at managing symptoms such as chorea and psychiatric disturbances. In an effort to develop a therapy directed at disease prevention we investigated the utility of highly specific, anti-Htt intracellular antibodies (intrabodies). We previously showed that VL12.3, an intrabody recognizing the N terminus of Htt, and Happ1, an intrabody recognizing the proline-rich domain of Htt, both reduce mHtt-induced toxicity and aggregation in cell culture and brain slice models of HD. Due to the different mechanisms of action of these two intrabodies, we then tested both in the brains of five mouse models of HD using a chimeric adeno-associated virus 2/1 (AAV2/1) vector with a modified CMV enhancer/chicken β-actin promoter. VL12.3 treatment, while beneficial in a lentiviral model of HD, has no effect on the YAC128 HD model and actually increases severity of phenotype and mortality in the R6/2 HD model. In contrast, Happ1 treatment confers significant beneficial effects in a variety of assays of motor and cognitive deficits. Happ1 also strongly ameliorates the neuropathology found in the lentiviral, R6/2, N171-82Q, YAC128, and BACHD models of HD. Moreover, Happ1 significantly prolongs the life span of N171-82Q mice. These results indicate that increasing the turnover of mHtt using AAV-Happ1 gene therapy represents a highly specific and effective treatment in diverse mouse models of HD.
Beclin 1 Gene Transfer Activates Autophagy and Ameliorates the Neurodegenerative Pathology in α-Synuclein Models of Parkinson's and Lewy Body Diseases
Authors: Spencer Brian , Potkar Rewati , Trejo Margarita , Rockenstein Edward , Patrick Christina , Gindi Ryan , Adame Anthony , Wyss-Coray Tony , Masliah Eliezer
Published: October 2009

Accumulation of the synaptic protein α-synuclein (α-syn) is a hallmark of Parkinson's disease (PD) and Lewy body disease (LBD), a heterogeneous group of disorders with dementia and parkinsonism, where Alzheimer's disease and PD interact. Accumulation of α-syn in these patients might be associated with alterations in the autophagy pathway. Therefore, we postulate that delivery of beclin 1, a regulator of the autophagy pathway, might constitute a strategy toward developing a therapy for LBD/PD. Overexpression of α-syn from lentivirus transduction in a neuronal cell line resulted in lysosomal accumulation and alterations in autophagy. Coexpression of beclin 1 activated autophagy, reduced accumulation of α-syn, and ameliorated associated neuritic alterations. The effects of beclin 1 overexpression on LC3 and α-syn accumulation were partially blocked by 3-MA and completely blocked by bafilomycin A1. In contrast, rapamycin enhanced the effects of beclin 1. To evaluate the potential effects of activating autophagyin vivo, a lentivirus expressing beclin 1 was delivered to the brain of a α-syn transgenic mouse. Neuropathological analysis demonstrated that beclin 1 injections ameliorated the synaptic and dendritic pathology in the tg mice and reduced the accumulation of α-syn in the limbic system without any significant deleterious effects. This was accompanied by enhanced lysosomal activation and reduced alterations in the autophagy pathway. Thus, beclin 1 plays an important role in the intracellular degradation of α-syn either directly or indirectly through the autophagy pathway and may present a novel therapeutic target for LBD/PD.
Functional reconstruction of NANOS3 expression in the germ cell lineage by a novel transgenic reporter reveals distinct subcellular localizations of NANOS3
Authors: Yamaji Masashi , Tanaka Takashi , Shigeta Mayo , Chuma Shinichiro , Saga Yumiko , Saitou Mitinori
Published: October 2009

Mutations of RNA-binding proteins such as NANOS3, TIAL1, and DND1 in mice have been known to result in the failure of survival and/or proliferation of primordial germ cells (PGCs) soon after their fate is specified (around embryonic day (E) 8.0), leading to the infertility of these animals. However, the mechanisms of actions of these RNA-binding proteins remain largely unresolved. As a foundation to explore the role of these RNA-binding proteins in germ cells, we established a novel transgenic reporter strain that expresses NANOS3 fused with EGFP under the control ofNanos3regulatory elements. NANOS3–EGFP exhibited exclusive expression in PGCs as early as E7.25, and continued to be expressed in female germ cells until around E14.5 and in male germ cells throughout the fetal period with declining expression levels after E16.5. NANOS3–EGFP resumed strong expression in postnatal spermatogonia and continued to be expressed in undifferentiated spermatogonial cells in adults. Importantly, theNanos3–EGFPtransgene rescued the sterile phenotype ofNanos3homozygous mutants, demonstrating the functional equivalency of NANOS3–EGFP with endogenous NANOS3. We found that throughout germ cell development, a predominant amount of  NANOS3–EGFP co-localized with TIAL1 (also known as TIAR) and phosphorylated eukaryotic initiation factor 2α, markers for the stress granules, whereas a fraction of it showed co-localization with DCP1A, a marker for the processing bodies. On the other hand, NANOS3–EGFP did not co-localize with Tudor domain-containing protein 1, a marker for the intermitochondrial cements, in spermatogenic cells. These findings unveil the presence of distinct posttranscriptional regulations in PGCs soon after their specification, for which RNA-binding proteins such as NANOS3 and TIAL1 would play critical functions.
Nutritional status and nutritional rehabilitation of elderly living in long-term care
Authors: Lelovics Zsuzsanna
Published: October 2009

A dolgozat témája a tartós bentlakásos intézményekben élők táplálásához és táplálkozásához kapcsolódó legfontosabb tényezők feltérképezése, a szociális otthonokban élő időskorúak tápláltsági állapotának felmérése, és az eredmények alapján a táplálkozási rehabilitációra javaslattétel.
Célkitűzések:
A tartós bentlakásos intézményekben élő hatvanévesek és idősebbek (időskorúak) tápláltsági állapotának meghatározása. A tartós bentlakásos intézményekben élő időskorúak testtömegindexének (BMI) változása. Az elmúlt fél évtized során a tartós bentlakásos intézményekben élő időskorúak tápláltságiállapot-változásának megállapítása. Az akut és krónikus betegségek összefüggésének megállapítása a tápláltsági állapottal. A tartós bentlakásos intézményekben élő időskorúak klinikai tápszerrel való ellátottságának felmérése. Annak megállapítása, hogy milyen a feltárt vélelmezett befolyásoló tényezők és a MUST szerinti tápláltsági állapot közötti összefüggés.
Módszerek:
Összesen 4774 hatvanéves és idősebb (28,9–30,9%-át férfiak, 69,1–71,2%-át nők adták, az összes résztvevő átlagéletkora 77,8±8,9 év volt) tartós bentlakásos intézményben élő, önként jelentkező gondozott tápláltsági állapotát szűrtük 2004-ben és 2006-ban a Malnutrition Universal Screening Tool (MUST) kérdőívvel és az általunk összeállított kérdőívvel, 2008-ban a Nutrition Day 2008 nyomtatványait használtuk.
Eredmények:
Felméréseink eredményei szerint az alultápláltságra veszélyeztetett idős személyek aránya a szociális otthonokban igen nagy (26,8–77,0%). Az ellátottak 29,5%-ánál tápláltságiállapot-felmérés negyedévente vagy annál ritkábban történik. A tápláltsági állapot multifaktoriális, sok tényező határozza meg a tápláltsági állapotot (például mozgáskorlátozottság, láz). Az étvágytalanság és a nyelési nehezítettség 2,5-szer gyakoribb, a mozgáskorlátozottság, a dementia, valamint a hiányos fogazat a nagy rizikójú idősek csoportjában közel kétszer (1,6–1,7-szer) gyakoribb, mint az idős, szociális otthonban élők körében. Az idegrendszeri kórképek szignifikánsan függnek össze a tápláltsági állapottal. Az idegrendszeri betegségek előfordulási gyakorisága az elmúlt években szignifikánsan nőtt.
Következtetések:
A táplálkozási rehabilitáció nem ér véget a tápláltsági állapot szűrésével, ellenkezőleg, azzal kezdődik. Annak eredményei alapján elengedhetetlen a táplálkozási irányelvek és szükség esetén a személyre szabott étrend meghatározása.
Link between diabetes and diastolic dysfunction and the diagnostic role of echocardiography
Authors: Nagy András , Cserép Zsuzsanna
Published: October 2009

Diabetes mellitus, a disease that has been reaching epidemic proportions, is an important risk factor to the development of cardiovascular complication. The left ventricular diastolic dysfunction represents the earliest pre-clinical manifestation of diabetic cardiomyopathy, preceding systolic dysfunction and being able to evolve to symptomatic heart failure. In early stages, these changes appear reversible with tight metabolic control, but as pathologic processes become organized, the changes are irreversible and contribute to an excess risk of heart failure among diabetic patients. Doppler echocardiography provides reliable data in the stages of diastolic function, as well as for systolic function. Combination of pulsed tissue Doppler study of mitral annulus with transmitral inflow may be clinically valuable for obtaining information about left ventricular filling pressure and unmasking Doppler inflow pseudonormal pattern, a hinge point for the progression toward advanced heart failure. Subsequently we give an overview about diabetes and its complications, their clinical relevance and the role of echocardiography in detection of diastolic heart failure in diabetes.
Myoanabolic steroids and selective androgen receptor modulators: mechanism of action and perspectives
Authors: Tóth Miklós
Published: October 2009

Interest in anabolic steroids has been renewed in the last decade with the discovery of tissue-selective androgen receptor modulators exhibiting high myotropic and small androgenic activity. An explanation put forward by us in 1982 for the mechanism of the preferential myotropic effect of nandrolone (19-nortestosterone) exploits the fundamental difference between the 5α-reductase concentrations in skeletal muscle and androgenic target tissue. In androgenic tissue, testosterone is converted to the more potent 5α-dihydrotestosterone whereas nandrolone is converted to a less potent derivative. As 5α-reduction is negligible in skeletal muscle, this explains why nandrolone shows a greater myotropic to androgenic ratio when compared with testosterone. Anabolic steroids that do not undergo 5α-reduction exert myotropic-androgenic dissociation because their effect in androgenic tissues is not amplified by 5α-reduction. Tissue selectivity by receptor modulators may be achieved by inducing specific conformational changes of the androgen receptor that affect its interaction with transcriptional coregulators. Anabolic activity is mediated by the stimulation of ribosomal RNA synthesis therefore regulation of this synthesis by anabolic steroids would deserve detailed studies.
Geoengineering and Economic Assessment of a Potential Carbon Capture and Storage Site in Southeast Queensland, Australia
Authors: Cinar Y. , Neal P. R. , Allinson W. G. , Sayers J.
Published: October 2009

This paper presents geoengineering and economic sensitivity analyses and assessments of the Wunger Ridge flank carbon capture and storage (CCS) site. Both geoengineering and economics are needed to derive the number of wells required to inject a certain amount of CO2 for a given period.

A numerical reservoir simulation examines injection rates ranging from 0.5 to 1.5 million tonnes of CO2 year for 25 years of injection. Primary factors affecting the ability to inject CO2 include permeability, formation fracture gradient, aquifer strength, and multiphase flow functions. Secondary factors include the solubility of CO2 in the formation brine, injection well location with respect to the flow barriers/low-permeability aquifers, model geometry including faults, grid size and refinement, and injection well type. Less significant factors include hydrodynamic effects.

The economics are assessed using an internally developed tech-noeconomic model. The model optimizes the CO2 injection cost on the basis of geoengineering data and recent equipment costs. The overall costs depend on the initial costs of CO2 separation and source-to-sink distances and their associated pipeline costs. Secondary cost variations are highly dependent on fracture gradient, permeability, and CO2 injection rates. Depending on the injection characteristics, the specific cost of CO2 avoided is between AUS 62 and 80 per tonne.
A New Method for Vertical Leak Detection in Low to Moderate Permeability Flooded Reservoirs
Authors: Walser D. W. , Astakhov D. K. , Stanley G. R.
Published: October 2009

Rising commodity prices have resulted in an increase in secondary recovery projects that are associated with lower permeability reservoirs. These processes often inject fluids above the parting pressure for the duration of the life of the flood, and pressurization takes place as fluids leak off from the exposed surface area of the induced fracture into the surrounding moderate or low-permeability reservoir matrix. The primary difference between these situations and conventional flooding is that matrix fluid migration is initiating off an induced fracturing plane, as opposed to point-source initiation.

During the early history of a flood, mass-balance issues are often ignored, as average reservoir pressures are typically low, and injection rates can dramatically exceed production. As pressures rise, some localized portions of the reservoir not only can exceed virgin static pressures, but volumes near existing induced fractures can approach or equal the pressure in those fractures. When this occurs, vertical fracturing initiates within the reservoir, and can migrate either above or below the reservoir, depending upon the location of the closest lower stress interval.

A new method to detect the location of vertical "leakage" has been developed. This method uses existing surface tiltmeter (STM) technologies and a new surface deformation calculation regime to zero in on volumetric changes that occur above or below the limits of the given reservoir. This method uses measured surface deformation from observed tilt to extrapolate the volumetric change at different specified depths. With a number of constraints and using a linear geophysical model based on poroelastic equations, an inversion routine is used to find the reservoir compaction or expansion at different depths. When volumetric change best fits the measured deformation data (or tilt) at the surface, the depth and aerial location is then correlated to the area near a specific well or wells.
Line-Tension-Based Modification of Young's Equation for Rock/Oil/Brine Systems
Authors: Saini Dayanand , Rao Dandina N.
Published: October 2009

The two-century-old Young's equation has been widely used in petroleum engineering to depict the reservoir wettability in terms of contact angle, which is a function of surface free energies of the system. For solid/liquid/vapor (S/L/V) systems, Young's equation has been modified in the recent literature to include a line-tension term. This modification was sought to accommodate the imbalance of intermolecular forces experienced by the three-phase confluence zone. Also, Young's equation does not account for the vertical component of liquid/vapor surface tension. The present study aims to experimentally investigate the applicability of the line-tension-based modification of Young's equation to solid/liquid/liquid (rock/ oil/brine) (S/L/L) systems of interest to the petroleum industry.

Both the ambient- and reservoir-condition optical cells were used, with stock-tank and live oil, respectively, to determine the drop-size dependence of dynamic contact angle subtended by the oil/brine interface with the rock surface. The experimental data were correlated with the modified Young's equation to determine the magnitude of line tension for different rock/oil/brine systems. To the best of our knowledge, this is the first attempt to apply the modified Young's equation to rock/oil/brine systems and to measure line tension for a rock/live-crude-oil/brine system at reservoir conditions of pressure and temperature.

The measured line tension for S/L/L systems, while being positive and of the same order of magnitude as in S/L/V systems, correlates well with the water-advancing contact angle and the adhesion number, a ratio of adhesion force to capillary force. This experimental study indicates that the extent of deviation from Young's equation exhibited by rock/oil/brine systems may be directly related to the rock/oil adhesion interaction. This study reinforces the need to include the rock/oil adhesion force in our consideration of rock/fluid interactions, wettability, and their impact on enhanced-oil-recovery (EOR)/improved-oil-recovery (IOR) processes.
Injectivity Characteristics of EOR Polymers
Authors: Seright R. S. , Seheult Mac , Talashek Todd
Published: October 2009

For applications in which enhanced-oil-recovery (EOR) polymer solutions are injected, we estimate injectivity losses (relative to water injectivity) if fractures are not open. We also consider the degree of fracture extension that may occur if fractures are open. Three principal EOR polymer properties are examined that affect injectivity: (1) debris in the polymer, (2) polymer rheology in porous media, and (3) polymer mechanical degradation. An improved test was developed to measure the tendency of EOR polymers to plug porous media. The new test demonstrated that plugging tendencies varied considerably among both partially hydrolyzed polyacrylamide (HPAM) and xanthan polymers.

Rheology and mechanical degradation in porous media were quantified for a xanthan and an HPAM polymer. Consistent with previous work, we confirmed that xanthan solutions show pseudoplastic behavior in porous rock that closely parallels that in a viscometer. Xanthan was remarkably resistant to mechanical degradation, with a 0.1% xanthan solution (in seawater) experiencing only a 19% viscosity loss after flow through 102-md Berea sandstone at a pressure gradient of 24,600 psi/ft.

For 0.1% HPAM in both 0.3% NaCl brine and seawater in 573-md Berea sandstone, Newtonian behavior was observed at low to moderate fluid fluxes, while pseudodilatant behavior was seen at moderate to high fluxes. No evidence of pseudoplastic behavior was seen in the porous rock, even though one solution exhibited a power-law index of 0.64 in a viscometer. For this HPAM in both brines, the onset of mechanical degradation occurred at a flux of 14 ft/d in 573-md Berea.

Considering the polymer solutions investigated, satisfactory injection of more than 0.1 pore volume (PV) in field applications could only be expected for the cleanest polymers (i.e., that do not plug before 1,000 cm3/cm2 throughput), without inducing fractures (or formation parts for unconsolidated sands). Even in the absence of face plugging, the viscous nature of the solutions investigated requires that injectivity must be less than one-fifth that of water if formation parting is to be avoided (unless the injectant reduces the residual oil saturation and substantially increases the relative permeability to water). Since injectivity reductions of this magnitude are often economically unacceptable, fractures or fracture-like features are expected to open and extend significantly during the course of most polymer floods. Thus, an understanding of the orientation and growth of fractures may be crucial for EOR projects in which polymer solutions are injected.