bluuebunny/crossref_metadata_2025 huggingface dataset:
How Much Consumption Insurance Beyond Self-Insurance?
Authors: Kaplan Greg , Violante Giovanni L
Published: October 2010

We assess the degree of consumption smoothing implicit in a calibrated life-cycle version of the standard incomplete-markets model, and we compare it to the empirical estimates of Richard Blundell, Luigi Pistaferri, and Ian Preston (2008) (BPP hereafter) on US data. Households in the data have access to more consumption insurance against permanent earnings shocks than in the model. BPP estimate that 36 percent of permanent shocks are insurable, whereas the model's counterpart of the BPP estimator varies between 7 percent and 22 percent, depending on the tightness of debt limits. We also show that the BPP estimator has a downward bias that grows as borrowing limits become tighter. (JEL D31, D91, E21).
Assessment of the seroprevalence of viral hepatitis B, viral hepatitis C and HIV in multitransfused thalassaemia major patients in Karachi, Pakistan
Authors: Riaz Haris , Riaz Talha , Ullah Faizan , Aziz Sina , Khan Muhammad Ubaid , Pervaiz Rida , Ejaz Areeba , Hasan Muhammad , Moiz Fatima , Naqvi Syed Anwar Ahmad
Published: October 2010

This cross-sectional study reveals the seroprevalence of hepatitis B, hepatitis C and HIV in multi-transfused thalassemia major patients. Thirty-four out of 79 (43.0%) patients enrolled in the study serologically tested positive for hepatitis C (mean ± standard deviation age = 12 ± 4.1 years), four (5.1%) for hepatitis B and none for HIV. Some of the measures that should be adapted are: safe blood transfusions; awareness programmes through print and electronic media; and the early screening of such hazardous infections.
Computational approaches for RNA energy parameter estimation
Authors: Andronescu Mirela , Condon Anne , Hoos Holger H. , Mathews David H. , Murphy Kevin P.
Published: October 2010

Methods for efficient and accurate prediction of RNA structure are increasingly valuable, given the current rapid advances in understanding the diverse functions of RNA molecules in the cell. To enhance the accuracy of secondary structure predictions, we developed and refined optimization techniques for the estimation of energy parameters. We build on two previous approaches to RNA free-energy parameter estimation: (1) the Constraint Generation (CG) method, which iteratively generates constraints that enforce known structures to have energies lower than other structures for the same molecule; and (2) the Boltzmann Likelihood (BL) method, which infers a set of RNA free-energy parameters that maximize the conditional likelihood of a set of reference RNA structures. Here, we extend these approaches in two main ways: We propose (1) a max-margin extension of CG, and (2) a novel linear Gaussian Bayesian network that models feature relationships, which effectively makes use of sparse data by sharing statistical strength between parameters. We obtain significant improvements in the accuracy of RNA minimum free-energy pseudoknot-free secondary structure prediction when measured on a comprehensive set of 2518 RNA molecules with reference structures. Our parameters can be used in conjunction with software that predicts RNA secondary structures, RNA hybridization, or ensembles of structures. Our data, software, results, and parameter sets in various formats are freely available at http://www.cs.ubc.ca/labs/beta/Projects/RNA-Params.
Identification of specific inhibitors for a trypanosomatid RNA editing reaction
Authors: Liang Shuang , Connell Gregory J.
Published: October 2010

Several mitochondrial mRNAs of the trypanosomatid protozoa are edited through the post-transcriptional insertion and deletion of uridylates. The reaction has provided insights into basic cellular biology and is also important as a potential therapeutic target for the diseases caused by trypanosomatid pathogens. Despite this importance, the field has been hindered by the lack of specific inhibitors that could be used as probes of the reaction mechanism or developed into novel therapeutics. In this study, an electrochemiluminescent aptamer-switch was utilized in a high-throughput screen for inhibitors of a trypanosomatid RNA editing reaction. The screen identified GW5074, mitoxantrone, NF 023, protoporphyrin IX, and D-sphingosine as inhibitors of insertion editing, with IC50values ranging from 1 to 3 μM. GW5074 and protoporphyrin IX are demonstrated to inhibit at or before the endonuclease cleavage that initiates editing and will be valuable biochemical probes for the early events of the in vitro reaction. Since protoporphyrin IX and sphingosine are both naturally present within the trypanosomatids, their effectiveness as in vitro inhibitors is also suggestive of the potential for in vivo modulatory roles.
Chiral histidine selection by D-ribose RNA
Authors: Illangasekare Mali , Turk Rebecca , Peterson G. Colin , Lladser Manuel , Yarus Michael
Published: October 2010

The invariant choice of L-amino acids and D-ribose RNA for biological translation requires explanation. Here we study this chiral choice using mixed, equimolar D-ribose RNAs having 15, 18, 21, 27, 35, and 45 contiguous randomized nucleotides. These are used for simultaneous affinity selection of the smallest bound and eluted RNAs using equal amounts of L- and D-His immobilized on an achiral glass support, with racemic histidine elution. The experiment as a whole therefore determines whether RNA containing D-ribose binds L-histidine or D-histidine more easily (that is, by using a site that is more abundant/requires fewer nucleotides). The most prevalent/smallest RNA sites are reproducibly and repeatedly selected and there is a four- to sixfold greater abundance of L-histidine sites. RNA's chiral D-ribose therefore yields a more frequent fit to L-histidine. Accordingly, a D-ribose RNA site for L-His is smaller by the equivalent of just over one conserved nucleotide. The most prevalent L-His site also performs better than the most frequent D-His site—but rarer D-ribose RNAs can bind D-His with excellent affinity and discrimination. The prevalent L-His site is one we have selected before under very different conditions. Thus, selection is again reproducible, as is the recurrence of cognate coding triplets in these most probable L-His sites. If our selected RNA population were equilibrated with racemic His, we calculate that L-His would participate in seven of eight His:RNA complexes, or more. Thus, if D-ribose RNA were first chosen biologically, translational L-His usage could have followed.
The Association Between Patient-Reported Drug Taking and Gaps and Overlaps in Antidepressant Drug Dispensing
Authors: Gardarsdottir Helga , Egberts Toine CG , Heerdink Eibert R
Published: October 2010

Background:

In daily practice, treatment adherence and persistence (duration) have mainly been investigated using large administrative databases. However, patients rarely collect a subsequent prescription on the day that the last dose has been consumed from the prior prescription. Therefore, the drug treatment patterns constructed from prescribing or dispensing moments in administrative databases can seem irregular, while patients in the real-world setting continue drug taking without gaps or overlaps in their drug use.

Objective:

To investigate whether patient-reported drug taking concurs with length of gaps and overlaps seen in an antidepressant dispensing database.

Methods:

Questionnaires on drug taking were sent from Dutch pharmacies to patients using second-generation antidepressants during September–December 2008. Gaps and overlaps between subsequently dispensed prescriptions were investigated. Patients with a gap/overlap were divided into 3 subgroups based on gap/overlap magnitude (<5% of total observed treatment time; gap/overlap ≥5% but <20% of total observed time; ≥20% of total observed treatment time) and compared for patient-reported drug taking.

Results:

The study population (N = 205) was predominantly female (62.9%), with a mean ± SD age of 48.0 ± 13.6 years. About 71% of the subjects had a gap, 27% had an overlap, and 2% had no gap/overlap between dispensing moments. Patients with a gap ≥20% reported nonadherent behavior more often (p < 0.01) than patients with shorter gaps. No significant differences in reported adherence were found between patients with different overlap magnitudes. Patients with a gap of ≥20% were the least likely to inform their physician or pharmacist about using their medication differently from label instructions.

Conclusions:

Patients with larger dispensing gaps more frequently report that they have skipped a dose, changed their dose, or used less medication than instructed. Dispensing gaps do not necessarily indicate that the medicine is not used on gap days. More research is needed to investigate the validity of dispensing patterns and their correlation with drug taking in the real-world setting.
Mineralogical, Chemical, and Physical Characterization of Synthetic Al-Substituted Maghemites (γ−Fe2−xAlxO3)
Authors: Batista Marcelo A. , da Costa Antonio C. S. , Bigham Jerry M. , de Santana Henrique , Zaia Dimas A. M. , de Souza junior Ivan G.
Published: October 2010

Maghemite (γ-Fe2O3) is a ferrimagnetic Fe oxide commonly found in tropical and subtropical soils, especially in the topsoil where it is usually a product of burning. Isomorphic substitution (IS) of the Fe in maghemite by different metals (mainly Al3+) can modify its mineralogical and chemical attributes, and these modifications may be important to understanding the formation and properties of this mineral in soils and sediments. The objective of this work was to evaluate the crystallochemical alterations of synthetic, Al-substituted maghemites prepared by the precipitation of magnetites from alkaline aqueous media containing FeSO4·7H2O with increasing amounts of Al2(SO4)3·7H2O to obtain hypothetical Al3+ for Fe3+ substitutions ranging from 0.0 to 40.0 mol %. The Al-substituted magnetites were washed and dried, and then heated to 250ºC for 4 h to form yellowish red maghemites that were characterized by total chemical analysis, X-ray diffraction, specific surface area (SSA), mass-specific magnetic susceptibility, infrared spectroscopy, transmission electronic microscopy, and color. Increasing Al3+ substitution to an experimental maximum of 15.9 mol % decreased both the a0 dimension of the cubic unit cell (a0 = 0.8339 − 396.157 × 10−16 Al, r2 = 0.99) and the mean crystallite dimension (MCD = 76.4–3.15Al, r2 = 0.79) of the maghemites. With the decrease in MCD came a more yellowish color, an increase in SSA, and a decrease in crystallinity as measured through extraction of the samples with acid ammonium oxalate. The mass-specific magnetic susceptibility of the maghemites increased with Al3+ substitution up to 5.3 mol % and then decreased with further replacement of Fe by Al. Solid-phase aluminum in excess of 16 mol % substitution appeared to occur as a separate, poorly crystalline phase that was X-ray amorphous.
FTIR and XRD Investigations of Tetracycline Intercalation in Smectites
Authors: Li Zhaohui , Kolb Vera M. , Jiang Wei-Teh , Hong Hanlie
Published: October 2010

Due to swelling, smectite minerals are capable of intercalating many organic molecules in their interlayer space. Tetracycline (TC) is a group of antibiotics used extensively in human and veterinary medicine. The great aqueous solubility and long environmental half life of TC mean that the study of interactions between swelling clay minerals and TC are of great importance in TC transport and retention in subsurface soils. In the present study, the intercalation of TC molecules at different levels into smectites was investigated using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The shift of the FTIR bands of amide I and II in comparison to crystalline TC suggested a strong interaction between the amide groups and the clay surfaces. The band at 1455 cm−1 remained the same after TC intercalation into SAz-1, SWy-2, and SYn-1, suggesting that complexation was not a dominant mechanism of TC uptake by these minerals. With cation exchange as the major mechanism of TC intercalation into these minerals, simultaneous removal of H+ from solution protonated the TC molecules and provided a positive charge to interact with negatively charged mineral surfaces even in neutral to slightly alkaline conditions. The increase in interlayer distance after intercalation by TC, as revealed by XRD, suggested a tilted orientation of the intercalated TC molecules in both twisted conformation in acidic condition and extended conformation in alkaline condition.
Glycerol-Intercalated Mg-Al Hydrotalcite as a Potential Solid Base Catalyst for Transesterification
Authors: Xi Yuanzhou , Davis Robert J.
Published: October 2010

Glycerol is a byproduct of biodiesel synthesis by transesterification of triglycerides with short-chain alcohols in the presence of solid base catalysts. Because hydrotalcite is a potentially useful basic catalyst for the transesterification reaction, the interaction of glycerol with hydrotalcite is the focus of this work. Glycerol was intercalated into Mg-Al hydrotalcite with a Mg/Al molar ratio of 4 under elevated temperatures of 4432/503 K in the absence and presence of NaOH. The resulting materials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and N2 adsorption. The amount of glycerol incorporated into hydrotalcite increased with increasing temperature of intercalation. However, the brucite-like sheets of hydrotalcite partially decomposed during the intercalation process at the highest temperature. The presence of NaOH stabilized the hydrotalcite layers against decomposition under high temperature (503 K). The intercalated materials exposed large surface areas ranging from 142 to 663 m2 g−1, depending on the preparation conditions. The glycerol-intercalated hydrotalcites were less catalytically active than hydrotalcite with OH− counterions for the transesterification of tributyrin with methanol. The lower reactivity of glycerol-intercalated hydrotalcite was probably the result of a strong interaction between the intercalated glycerolate (HOCH2-CHOH-CH2O−) and the partially decomposed brucite-like sheets.
Colloid Diffusion in Compacted Bentonite: Microstructural Constraints
Authors: Holmboe Michael , Wold Susanna , Jonsson Mats
Published: October 2010

In Sweden and in many other countries, a bentonite barrier will be used in the repository for spent nuclear fuel. In the event of canister failure, colloidal diffusion is a potential, but scarcely studied mechanism of radionuclide migration through the bentonite barrier. Column and in situ experiments are vital in understanding colloid diffusion and in providing information about the micro structure of compacted bentonite and identifying cut-off limits for colloid filtration. This study examined diffusion of negatively charged 2-, 5-, and 15-nm gold colloids in 4-month diffusion experiments using MX-80 Wyoming bentonite compacted to dry densities of 0.6–2.0 g/cm3. Breakthrough of gold colloids was not observed in any of the three diffusion experiments. In a gold-concentration profile analysis, colloid diffusion was only observed for the smallest gold colloids at the lowest dry density used (estimated apparent diffusivity Da ≈ 5 × 10−13 m2/s). The results from a microstructure investigation using low-angle X-ray diffraction suggest that at the lowest dry density used, interlayer transport of the smallest colloids cannot be ruled out as a potential diffusion pathway, in addition to the expected interparticle transport. In all other cases, with either greater dry densities or larger gold colloids, compacted bentonite will effectively prevent diffusion of negatively charged colloids due to filtration.
Bioavailability of Fe(III) In Loess Sediments: An Important Source of Electron Acceptors
Authors: Bishop Michael E. , Jaisi Deb P. , Dong Hailiang , Kukkadapu Ravi K. , Ji Junfeng
Published: October 2010

Fe-reducing micro-organisms can change the oxidation state of structural Fe in clay minerals. The interactions with complex clays and clay minerals in natural materials remain poorly understood, however. The objective of this study was to determine if Fe(III) in loess was available as an electron acceptor and to study subsequent mineralogical changes. The loess samples were collected from St. Louis (Peoria), Missouri, USA, and Huanxia (HX) and Yanchang (YCH), in the Shanxi Province of China. The total Fe concentrations for the three samples was 1.69, 2.76, and 3.29 wt.%, respectively, and Fe(III) content was 0.48, 0.69, and 1.27 wt.%, respectively. All unreduced loess sediments contained Fe (oxyhydr)oxides and phyllosilicates. Bioreduction experiments were performed using Shewanella putrefaciens CN32 with lactate as the sole electron donor and Fe(III) in loess as the sole electron acceptor with and without anthraquinone-2, 6-disulfonate (AQDS) as an electron shuttle. Experiments were performed in non-growth (bicarbonate buffer) and growth (M1) media. The unreduced and bioreduced solids were analyzed by X-ray diffraction, Mössbauer spectroscopy, diffuse reflectance spectroscopy, and scanning electron microscopy/energy dispersive spectroscopy. Despite many similarities among the three loess samples, the extent and rate of Fe(III) reduction varied significantly. In the presence of AQDS the extent of reduction in the non-growth experiment was 25% of total Fe(III) in HX, 34% in Peoria, and 38% in YCH. The extent of reduction in the growth experiment was 72% in HX, 94% in Peoria, and 65% in YCH. The extent of bioreduction was less in the absence of AQDS. Overall, AQDS and the M1 growth medium significantly enhanced the rate and extent of bioreduction. Fe(III) in (oxyhydr)oxides and phyllosilicates was bioreduced. Siderite was absent in control samples, but was identified in bioreduced samples. The present research suggests that Fe(III) in loess sediments is an important potential source of electron acceptors that could support microbial activity under favorable conditions.
Origin and Depositional Environment of Palygorskite and Sepiolite from the Ypresian Phosphatic Series, Southwestern Tunisia
Authors: Tlili A. , Felhi M. , Montacer M.
Published: October 2010

The Ypresian phosphatic series of the Gafsa-Metlaoui basin, southwestern Tunisia, is represented by an alternation of phosphatic levels and interbedded facies, which are composed of marly clay and silica-rich rocks. The present work aimed to clarify the genesis of palygorskite and sepiolite of the interbedded facies and to understand the depositional environment of the phosphatic series. The interbedded facies of the Stah and Jellabia mines were investigated using X-ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-ray microanalysis (EDX) of individual constituents and their aggregates. The data obtained indicate that samples are made up of francolite, calcite, dolomite, quartz, feldspars, and clay minerals; the latter consist of palygorskite-sepiolite minerals associated with smectite. Observations by SEM revealed the occurrence of palygorskite and sepiolite as fine and filamentous fibers with thread-like facies and coating dolomite, calcite, and a marly matrix. Such features can be considered as textural evidence of authigenic palygorskite-sepiolite. At the bottom of the Stah section, SEM observations revealed that the fine fibers are more abundant within silica-rich rocks. Silica is commonly available due to bacterial activity saturating its environment with the silicic acid required for the formation of palygorskite-sepiolite. In the interbedded facies of the Jellabia section, the moderate fibrous clay content and the presence of well crystallized dolomite revealed that the shallow-marine water was characterized by high-Mg and low-Si activities.
A Tandem Mass Spectrometry Triplex Assay for the Detection of Fabry, Pompe, and Mucopolysaccharidosis-I (Hurler)
Authors: Duffey Trisha A , Bellamy Garland , Elliott Susan , Fox Angela C , Glass Michael , Turecek Frantisek , Gelb Michael H , Scott C Ronald
Published: October 2010

BACKGROUND

We sought to develop a tandem mass spectrometry assay in which the enzymatic activities of 3 lysosomal enzymes (α-glucosidase, α-galactosidase A, and α-l-iduronidase) could be quantified in dried blood spots by using a single assay buffer.

METHODS

A 3-mm dried blood spot punch was incubated in a single assay buffer with 3 different substrates and internal standards. The sample was processed by a simple liquid-liquid extraction by using ethyl acetate. The extract was dried down and resuspended in solvent for injection into the tandem mass spectrometer. Products and internal standards were monitored by multiple reaction monitoring.

RESULTS

Assay for the 3 lysosomal enzymes was successfully achieved with acceptable statistics. The assay can be performed by using a minimal quantity of disposable supplies and equipment. The entire procedure fits into a 48-h cycle including data analysis. Data from 5990 anonymous newborn dried blood spots showed an approximate bell-shaped distribution of enzymatic activities (mean values of 19.0, 11.5, and 3.5 μmol · h−1 · (L blood)−1 for α-glucosidase, α-galactosidase A, and α-l-iduronidase, respectively. Blank values obtained in the absence of blood were 0.13, 0.24, and 0.45 μmol · h−1 · (L blood)−1, respectively). By assaying 3 enzymes at once, problematic samples are spotted for reanalysis if enzyme activity values are low for all enzymes (for example, if insufficient blood is present in the assay).

CONCLUSIONS

This method demonstrates that a triplex assay in a single buffer and with minimal supplies and labor can be adapted to a high-throughput newborn screening laboratory for the analysis of Pompe, Fabry, and mucopolysaccharidosis-I (Hurler) diseases.
Brief Psycho-Social Interventions in the Treatment of Specific Childhood Phobias: A Controlled Trial and a 1-Year Follow-Up
Authors: Flatt Natalie , King Neville
Published: October 2010

Forty-three youth aged 7–17 years old who fulfilled DSM-IV criteria for assorted specific phobias, were randomised to a one-session exposure treatment, a psycho-education package or a waitlist control conditions. Participants were assessed using semi-structured interviews, self-report measures and an individualised behavioural avoidance test (BAT). Assessments were completed pre- and posttest. At the 1-year follow-up, self-report measures along with a generalised version of the individualised BAT were re-administered. Results exhibited that both active treatment conditions were superior to the waitlist control on the BAT, self-efficacy ratings; however, no significant differences were found on functioning levels and other self-report measures with the exception of the Fear Survey Schedule — Revised. Additionally, no significant differences were found between the two active conditions at posttest or the 1-year follow-up. Implications and future research strategies are discussed.
Effects of a Brief Behavioural Activation Treatment on Activities of Various Difficulty and Depression
Authors: Bailey Debra L. , Arco Lucius
Published: October 2010

This study examined, first, effectiveness of a brief behavioural activation treatment for depression, in which participants engaged concurrently in activities of various difficulty instead of a standard least-to-most difficult sequence; and second, the relationship between behavioural self-observations of changes in activity levels and depressive symptomatology. Two adults with mild to moderate BDI-II depressive symptoms participated in a with-in participant multiple baseline study that contained 8 weekly conjoint sessions. Results showed that depression decreased to minimal levels at posttreatment and 1-month follow-up as a function of increases in activities of various difficulty. Results suggest early initiation of more difficult activities, and corroborate the relationship between increased activities and decreased depressive symptoms.
Suppressing Sensorimotor Activity Modulates the Discrimination of Auditory Emotions But Not Speaker Identity
Authors: Banissy Michael J. , Sauter Disa Anna , Ward Jamie , Warren Jane E. , Walsh Vincent , Scott Sophie K.
Published: October 2010

Our ability to recognize the emotions of others is a crucial feature of human social cognition. Functional neuroimaging studies indicate that activity in sensorimotor cortices is evoked during the perception of emotion. In the visual domain, right somatosensory cortex activity has been shown to be critical for facial emotion recognition. However, the importance of sensorimotor representations in modalities outside of vision remains unknown. Here we use continuous theta-burst transcranial magnetic stimulation (cTBS) to investigate whether neural activity in the right postcentral gyrus (rPoG) and right lateral premotor cortex (rPM) is involved in nonverbal auditory emotion recognition. Three groups of participants completed same–different tasks on auditory stimuli, discriminating between the emotion expressed and the speakers' identities, before and following cTBS targeted at rPoG, rPM, or the vertex (control site). A task-selective deficit in auditory emotion discrimination was observed. Stimulation to rPoG and rPM resulted in a disruption of participants' abilities to discriminate emotion, but not identity, from vocal signals. These findings suggest that sensorimotor activity may be a modality-independent mechanism which aids emotion discrimination.
RBPJκ-Dependent Signaling Is Essential for Long-Term Maintenance of Neural Stem Cells in the Adult Hippocampus
Authors: Ehm Oliver , Göritz Christian , Covic Marcela , Schäffner Iris , Schwarz Tobias J. , Karaca Esra , Kempkes Bettina , Kremmer Elisabeth , Pfrieger Frank W. , Espinosa Lluis , Bigas Anna , Giachino Claudio , Taylor Verdon , Frisén Jonas , Lie D. Chichung
Published: October 2010

The generation of new neurons from neural stem cells in the adult hippocampal dentate gyrus contributes to learning and mood regulation. To sustain hippocampal neurogenesis throughout life, maintenance of the neural stem cell pool has to be tightly controlled. We found that the Notch/RBPJκ-signaling pathway is highly active in neural stem cells of the adult mouse hippocampus. Conditional inactivation of RBPJκ in neural stem cellsin vivoresulted in increased neuronal differentiation of neural stem cells in the adult hippocampus at an early time point and depletion of the Sox2-positive neural stem cell pool and suppression of hippocampal neurogenesis at a later time point. Moreover, RBPJκ-deficient neural stem cells displayed impaired self-renewalin vitroand loss of expression of the transcription factor Sox2. Interestingly, we found that Notch signaling increases Sox2 promoter activity and Sox2 expression in adult neural stem cells. In addition, activated Notch and RBPJκ were highly enriched on the Sox2 promoter in adult hippocampal neural stem cells, thus identifying Sox2 as a direct target of Notch/RBPJκ signaling. Finally, we found that overexpression of Sox2 can rescue the self-renewal defect in RBPJκ-deficient neural stem cells. These results identify RBPJκ-dependent pathways as essential regulators of adult neural stem cell maintenance and suggest that the actions of RBPJκ are, at least in part, mediated by control of Sox2 expression.
Spontaneous Seizures and Altered Gene Expression in GABA Signaling Pathways in amind bombMutant Zebrafish
Authors: Hortopan Gabriela A. , Dinday Matthew T. , Baraban Scott C.
Published: October 2010

Disruption of E3 ubiquitin ligase activity in immature zebrafishmind bombmutants leads to a failure in Notch signaling, excessive numbers of neurons, and depletion of neural progenitor cells. This neurogenic phenotype is associated with defects in neural patterning and brain development. Because developmental brain abnormalities are recognized as an important feature of childhood neurological disorders such as epilepsy and autism, we determined whether zebrafish mutants with grossly abnormal brain structure exhibit spontaneous electrical activity that resembles the long-duration, high-amplitude multispike discharges reported in immature zebrafish exposed to convulsant drugs. Electrophysiological recordings from agar immobilizedmind bombmutants at 3 d postfertilization confirmed the occurrence of electrographic seizure activity; seizure-like behaviors were also noted during locomotion video tracking of freely behaving mutants. To identify genes differentially expressed in themind bombmutant and provide insight into molecular pathways that may mediate these epileptic phenotypes, a transcriptome analysis was performed using microarray. Interesting candidate genes were further analyzed using conventional reverse transcriptase-PCR and real-time quantitative PCR, as well as whole-mountin situhybridization. Approximately 150 genes, some implicated in development, transcription, cell metabolism, and signal transduction, are differentially regulated, including downregulation of several genes necessary for GABA-mediated signaling. These findings identify a collection of gene transcripts that may be responsible for the abnormal electrical discharge and epileptic activities observed in amind bombzebrafish mutant. This work may have important implications for neurological and neurodevelopmental disorders associated with mutations in ubiquitin ligase activity.
Slow Degradation and AggregationIn Vitroof Mutant GABAAReceptor γ2(Q351X) Subunits Associated with Epilepsy
Authors: Kang Jing-Qiong , Shen Wangzhen , Lee Melissa , Gallagher Martin J. , Macdonald Robert L.
Published: October 2010

The GABAAreceptor γ2 subunit nonsense mutation Q351X has been associated with the genetic epilepsy syndrome generalized epilepsy with febrile seizures plus, which includes a spectrum of seizures types from febrile seizures to Dravet syndrome. Although most genetic epilepsy syndromes are mild and remit with age, Dravet syndrome has a more severe clinical course with refractory seizures associated with developmental delay and cognitive impairment. The basis for the broad spectrum of seizure phenotypes is uncertain. We demonstrated previously that the GABAAreceptor γ2 subunit gene Q351X mutation suppressed biogenesis of wild-type partnering α1 and β2 subunits in addition to its loss of function. Here we show that γ2S(Q351X) subunits have an additional impairment of biogenesis. Mutant γ2(Q351X) subunits were degraded more slowly than wild-type γ2 subunits and formed SDS-resistant, high-molecular-mass complexes or aggregates in multiple cell types, including neurons. The half-life of γ2S(Q351X) subunits was ∼4 h, whereas that of γ2S subunits was ∼2 h. Mutant subunits formed complexes rapidly after synthesis onset. Using multiple truncated subunits, we demonstrated that aggregate formation was a general phenomenon for truncated γ2S subunits and that their Cys-loop cysteines were involved in aggregate formation. Protein aggregation is a hallmark of neurodegenerative diseases, but the effects of the mutant γ2S(Q351X) subunit aggregates on neuronal function and survival are unclear. Additional validation of the mutant subunit aggregationin vivoand determination of the involved signaling pathways will help reveal the pathological effects of these mutant subunit aggregates in the pathogenesis of genetic epilepsy syndromes.
Latent Inputs Improve Estimates of Neural Encoding in Motor Cortex
Authors: Chase Steven M. , Schwartz Andrew B. , Kass Robert E.
Published: October 2010

Typically, tuning curves in motor cortex are constructed by fitting the firing rate of a neuron as a function of some observed action, such as arm direction or movement speed. These tuning curves are then often interpreted causally as representing the firing rate as a function of the desired movement, or intent. This interpretation implicitly assumes that the motor command and the motor act are equivalent. However, any kind of perturbation, be it external, such as a visuomotor rotation, or internal, such as muscle fatigue, can create a difference between the motor intent and the action. How do we estimate the tuning curve under these conditions? Furthermore, it is well known that, during learning or adaptation, the relationship between neural firing and the observed movement can change. Does this change indicate a change in the inputs to the population, or a change in the way those inputs are processed?

In this work, we present a method to infer the latent, unobserved inputs into the population of recorded neurons. Using data from nonhuman primates performing brain–computer interface experiments, we show that tuning curves based on these latent directions fit better than tuning curves based on actual movements. Finally, using data from a brain–computer interface learning experiment in which half of the units were decoded incorrectly, we demonstrate how this method might differentiate various aspects of motor adaptation.
Interdependent Roles for Accessory KChIP2, KChIP3, and KChIP4 Subunits in the Generation of Kv4-EncodedIAChannels in Cortical Pyramidal Neurons
Authors: Norris Aaron J. , Foeger Nicholas C. , Nerbonne Jeanne M.
Published: October 2010

The rapidly activating and inactivating voltage-dependent outward K+(Kv) current,IA, is widely expressed in central and peripheral neurons.IAhas long been recognized to play important roles in determining neuronal firing properties and regulating neuronal excitability. Previous work demonstrated that Kv4.2 and Kv4.3 α-subunits are the primary determinants ofIAin mouse cortical pyramidal neurons. Accumulating evidence indicates that native neuronal Kv4 channels function in macromolecular protein complexes that contain accessory subunits and other regulatory molecules. The K+channel interacting proteins (KChIPs) are among the identified Kv4 channel accessory subunits and are thought to be important for the formation and functioning of neuronal Kv4 channel complexes. Molecular genetic, biochemical, and electrophysiological approaches were exploited in the experiments described here to examine directly the roles of KChIPs in the generation of functional Kv4-encodedIAchannels. These combined experiments revealed that KChIP2, KChIP3, and KChIP4 are robustly expressed in adult mouse posterior (visual) cortex and that all three proteins coimmunoprecipitate with Kv4.2. In addition, in cortical pyramidal neurons from mice lacking KChIP3 (KChIP3−/−), meanIAdensities were reduced modestly, whereas in meanIAdensities in KChIP2−/−and WT neurons were not significantly different. Interestingly, in both KChIP3−/−and KChIP2−/−cortices, the expression levels of the other KChIPs (KChIP2 and 4 or KChIP3 and 4, respectively) were increased. In neurons expressing constructs to mediate simultaneous RNA interference-induced reductions in the expression of KChIP2, 3, and 4,IAdensities were markedly reduced and Kv current remodeling was evident.
Intact Working Memory for Relational Information after Medial Temporal Lobe Damage
Authors: Jeneson Annette , Mauldin Kristin N. , Squire Larry R.
Published: October 2010

Working memory has traditionally been viewed as independent of the hippocampus and related medial temporal lobe structures. Yet memory-impaired patients with medial temporal lobe damage are sometimes impaired at remembering relational information (e.g., an object and its location) across delays as short as a few seconds. This observation has raised the possibility that medial temporal lobe structures are sometimes critical for maintaining relational information, regardless of whether the task depends on working or long-term memory. An alternative possibility is that these structures are critical for maintaining relational information only when the task exceeds working memory capacity and depends instead on long-term memory. To test these ideas, we drew on a method used previously in a classic study of digit span in patient HM that distinguished immediate memory from long-term memory. In two experiments, we assessed the ability of four patients with medial temporal lobe lesions to maintain varying numbers of object–location associations across a 1 s retention interval. In both experiments, the patients exhibited a similar pattern of performance. They performed similarly to controls when only a small number of object–location associations needed to be maintained, and they exhibited an abrupt discontinuity in performance with larger set sizes. This pattern of results supports the idea that maintenance of relational information in working memory is intact after damage to the hippocampus and related medial temporal lobe structures and that damage to these structures impairs performance only when the task depends on long-term memory.
Cued Spatial Attention Drives Functionally Relevant Modulation of the Mu Rhythm in Primary Somatosensory Cortex
Authors: Jones Stephanie R. , Kerr Catherine E. , Wan Qian , Pritchett Dominique L. , Hämäläinen Matti , Moore Christopher I.
Published: October 2010

Cued spatial attention modulates functionally relevant alpha rhythms in visual cortices in humans. Here, we present evidence for analogous phenomena in primary somatosensory neocortex (SI). Using magnetoencephalography, we measured changes in the SI mu rhythm containing mu-alpha (7–14 Hz) and mu-beta (15–29 Hz) components. We found that cued attention impacted mu-alpha in the somatopically localized hand representation in SI, showing decreased power after attention was cued to the hand and increased power after attention was cued to the foot, with significant differences observed 500–1100 ms after cue. Mu-beta showed differences in a time window 800–850 ms after cue. The visual cue also drove an early evoked response beginning ∼70 ms after cue with distinct peaks modulated with cued attention. Distinct components of the tactile stimulus-evoked response were also modulated with cued attention. Analysis of a second dataset showed that, on a trial-by-trial basis, tactile detection probabilities decreased linearly with prestimulus mu-alpha and mu-beta power. These results support the growing consensus that cue-induced alpha modulation is a functionally relevant sensory gating mechanism deployed by attention. Further, while cued attention had a weaker effect on the allocation of mu-beta, oscillations in this band also predicted tactile detection.
Epothilone D Improves Microtubule Density, Axonal Integrity, and Cognition in a Transgenic Mouse Model of Tauopathy
Authors: Brunden Kurt R. , Zhang Bin , Carroll Jenna , Yao Yuemang , Potuzak Justin S. , Hogan Anne-Marie L. , Iba Michiyo , James Michael J. , Xie Sharon X. , Ballatore Carlo , Smith Amos B. , Lee Virginia M.-Y. , Trojanowski John Q.
Published: October 2010

Neurons in the brains of those with Alzheimer's disease (AD) and many frontotemporal dementias (FTDs) contain neurofibrillary tangles comprised of hyperphosphorylated tau protein. Tau normally stabilizes microtubules (MTs), and tau misfolding could lead to a loss of this function with consequent MT destabilization and neuronal dysfunction. Accordingly, a possible therapeutic strategy for AD and related “tauopathies” is treatment with a MT-stabilizing anti-cancer drug such as paclitaxel. However, paclitaxel and related taxanes have poor blood–brain barrier permeability and thus are unsuitable for diseases of the brain. We demonstrate here that the MT-stabilizing agent, epothilone D (EpoD), is brain-penetrant and we subsequently evaluated whether EpoD can compensate for tau loss-of-function in PS19 tau transgenic mice that develop forebrain tau inclusions, axonal degeneration and MT deficits. Treatment of 3-month-old male PS19 mice with low doses of EpoD once weekly for a 3 month period significantly improved CNS MT density and axonal integrity without inducing notable side-effects. Moreover, EpoD treatment reduced cognitive deficits that were observed in the PS19 mice. These results suggest that certain brain-penetrant MT-stabilizing agents might provide a viable therapeutic strategy for the treatment of AD and FTDs.
Analysis of theastray/robo2Zebrafish Mutant Reveals that Degenerating Tracts Do Not Provide Strong Guidance Cues for Regenerating Optic Axons
Authors: Wyatt Cameron , Ebert Anselm , Reimer Michell M. , Rasband Kendall , Hardy Melissa , Chien Chi-Bin , Becker Thomas , Becker Catherina G.
Published: October 2010

During formation of the optic projection inastray/robo2mutant zebrafish, optic axons exhibit rostrocaudal pathfinding errors, ectopic midline crossing and increased terminal arbor size. Here we show that these errors persist into adulthood, even whenrobo2function is conditionally reduced only during initial formation of the optic projection. Adult errors include massive ectopic optic tracts in the telencephalon. During optic nerve regeneration inastray/robo2animals, these tracts are not repopulated and ectopic midline crossing is reduced compared with unlesioned mutants. This is despite a comparable macrophage/microglial response and upregulation ofcontactin1ain oligodendrocytes of entopic and ectopic tracts. However, other errors, such as expanded termination areas and ectopic growth into the tectum, were frequently recommitted by regenerating optic axons. Retinal ganglion cells with regenerating axons reexpressrobo2and expression ofslitligands is maintained in some areas of the adult optic pathway. However,slitexpression is reduced rostral and caudal to the chiasm, compared with development and ubiquitous overexpression of Slit2 did not elicit major pathfinding phenotypes. This shows that (1) there is not an efficient correction mechanism for large-scale pathfinding errors of optic axons during development; (2) degenerating tracts do not provide a strong guidance cue for regenerating optic axons in the adult CNS, unlike the PNS; and (3)robo2is less important for pathfinding of optic axons during regeneration than during development.
Sound-Induced Enhancement of Low-Intensity Vision: Multisensory Influences on Human Sensory-Specific Cortices and Thalamic Bodies Relate to Perceptual Enhancement of Visual Detection Sensitivity
Authors: Noesselt Toemme , Tyll Sascha , Boehler Carsten Nicolas , Budinger Eike , Heinze Hans-Jochen , Driver Jon
Published: October 2010

Combining information across modalities can affect sensory performance. We studied how co-occurring sounds modulate behavioral visual detection sensitivity (d′), and neural responses, for visual stimuli of higher or lower intensity. Co-occurrence of a sound enhanced human detection sensitivity for lower- but not higher-intensity visual targets. Functional magnetic resonance imaging (fMRI) linked this to boosts in activity-levels for sensory-specific visual and auditory cortex, plus multisensory superior temporal sulcus (STS), specifically for a lower-intensity visual event when paired with a sound. Thalamic structures in visual and auditory pathways, the lateral and medial geniculate bodies, respectively (LGB, MGB), showed a similar pattern. Subject-by-subject psychophysical benefits correlated with corresponding fMRI signals in visual, auditory, and multisensory regions. We also analyzed differential “coupling” patterns of LGB and MGB with other regions in the different experimental conditions. Effective-connectivity analyses showed enhanced coupling of sensory-specific thalamic bodies with the affected cortical sites during enhanced detection of lower-intensity visual events paired with sounds. Coupling strength between visual and auditory thalamus with cortical regions, including STS, covaried parametrically with the psychophysical benefit for this specific multisensory context. Our results indicate that multisensory enhancement of detection sensitivity for low-contrast visual stimuli by co-occurring sounds reflects a brain network involving not only established multisensory STS and sensory-specific cortex but also visual and auditory thalamus.
Book Review
Authors: Lees Susan H.
Published: October 2010

Implementing Rural Development Projects: Lessons from AID and World Bank Experiences. Edited by Elliot Morss and David D. Gow Boulder: Westview Press. 1985 243 pp ($27 50)

Rural Development: Putting the Last First. Robert Chambers London: Longman 1983. 246pp.
Increased hepcidin levels three days after gynecological interventions
Authors: Gyarmati Béla , Szabó Eszter , Szalay Balázs , Cseh Áron , Czuczy Noémi , Toldi Gergely , Vásárhelyi Barna , Takáts Zoltán
Published: October 2010

A hepcidin a vasfelszívódást és a plazmavasszintet közvetlenül csökkentő endogén vegyület. Technikai okok miatt meghatározása nem terjedt el, klinikai jelentőségére vonatkozóan korlátozottak az adatok. Munkánk során nő gyógyászati műtétek kapcsán elemeztük a bekövetkező hepcidinszint-változást. Vizsgálatunk során 17 nőgyógyá szati műtéten átesett nő esetében a műtét előtt közvetlenül, majd azt követően 3 nappal vett vérmintában határoztuk meg tömegspektrometriával a hepcidinszintet, valamint ELISA-módszerrel a legfontosabb hepcidininduktor, az interleukin-6 szintjét. A műtét után csökkent a szérumvasszint [medián, interkvartilis (17,85 [15,25–24,9] versus 10,1 [7,6–15,0] μmol/L, p<0,01)] és transzferrinszint [60,3 (55,93–67,18) versus 53,1 (49,7–60,0) μmol/L, p<0,01], míg nőtt a hepcidinszint [2,75 (2,24–3,51) versus 8,01 (6,8–9,67) μg/L, p<0,01) és az interleukin-6-szint (ND – nem detektálható) [ND [ND – 2.2] versus 8,15 (2,31–12,86), p<0,01].
Következtetés:
A műtétet követő vasanyagcsere-változásokkal egyidejűleg a hepcidinszint – hasonlóan más akutfázis-fehérjékhez – gyorsan emelkedik. Eredményeink alapján a hepcidinszint emelkedése és a vasszint csökkenése közötti ok-okozati kapcsolat valószínűsíthető. A hepcidinszint mérésének a mindennapos gyakorlatban a műtétet követő vasanyagcsere-változás monitorozásában, esetleges előrejelzésében lehet szerepe. Elterjedése azonban rutin laboratóriumi tesztek hiányában egyelőre nem valószínű. Orv. Hetil., 2010,
43,
1790–1794.
Data on secondary prevention of coronary artery disease in Hungary and some changes in the last ten years (EUROASPIRE 1995–2005)
Authors: Jánosi András , Östör Erika , Borbás Sarolta , Kazinczy Rita , Káli András , Vámos István , Bradák Anna , Podmaniczky Márta
Published: October 2010

Az Európai Kardiológus Társaság EUROASPIRE I–II–III néven vizsgálatsorozatot kezdeményezett a másodlagos prevenció európai helyzetének felmérésére. Magyarország ugyanazon két kardiológiai centrum bevonásával részt vett ebben a jelentős epidemiológiai vizsgálatsorozatban. A szerzők az elmúlt 10 év hazai adatait elemzik. Összesen 1627 – 70 évesnél fiatalabb – koszorúérbeteg kórházi és utánvizsgálati adatait dolgozták fel standardizált módszerekkel. Az ischaemiás szívbetegség miatt kezelt betegek között csökkent a férfiak, és nőtt a nőbetegek, valamint a 60 évnél idősebbek aránya. A vizsgált rizikófaktorok kórházi dokumentálása jelentősen javult: az utolsó adatfelvétel időpontjában a betegek 89–99%-ában ezen adatok rögzítése a kórlapban megtörtént. A vizsgálati időpontokban csökkent a szisztolés és a diasztolés vérnyomás átlagértéke, valamint a harmadik vizsgálati időpontban 0,4 mmol/L-rel alacsonyabb volt az össz- és az LDL-koleszterin átlagértéke, mint a vizsgálat kezdetén. A HDL-koleszterin átlagértéke nem változott, a triglicerid esetén pedig az átlag növekedését figyelték meg. A tíz év alatt folyamatosan és jelentősen nőtt (23%-ról 49%-ra) a súlyosan elhízottak, valamint a diabetesesek aránya (27%-ról 45%-ra). A hypertoniások száma csak az első és második vizsgálati időpont között csökkent, a harmadik időpontban a megvizsgáltak 44%-ában 140/90 Hgmm feletti vérnyomásértéket mértek. A dohányzó betegek aránya a második és a harmadik adatfelvételi időpont között 8%-kal csökkent, a vizsgálat lezárásakor az aktív dohányosok aránya 18% volt. Jelentősen csökkent (60%-ról 24%-ra) az 5,5 mmol/L feletti összkoleszterin-értékkel bíró betegek aránya, ugyanakkor az összkoleszterin jelenlegi célértékét (4,5 mmo/L) a betegek 57%-a nem érte el. A másodlagos prevenció területén az elmúlt 10 évben kétségtelen javulás igazolható, de még mindig nem sikerült megfelelően csökkenteni a magas vérnyomást, a koleszterinszintet, a dohányzók arányát, és aggasztó az elhízottak és a cukorbetegek számának növekedése. A szerzők – a helyzet javítása érdekében – fontosnak tartják a prevenció fontosságának hangsúlyozását az orvosképzésben és az orvos-továbbképzésben, valamint az együttműködés javítását a kórházi orvosok, a családorvosok és a betegek között. Orv. Hetil., 2010,
43,
1776–1782.