bluuebunny/crossref_metadata_2025 huggingface dataset:
Sagace: A web-based search engine for biomedical databases in Japan
Authors: Morita Mizuki , Igarashi Yoshinobu , Ito Maori , Chen Yi-An , Nagao Chioko , Sakaguchi Yuki , Sakate Ryuichi , Masui Tohru , Mizuguchi Kenji
Published: October 2012

Background

In the big data era, biomedical research continues to generate a large amount of data, and the generated information is often stored in a database and made publicly available. Although combining data from multiple databases should accelerate further studies, the current number of life sciences databases is too large to grasp features and contents of each database.

Findings

We have developed Sagace, a web-based search engine that enables users to retrieve information from a range of biological databases (such as gene expression profiles and proteomics data) and biological resource banks (such as mouse models of disease and cell lines). With Sagace, users can search more than 300 databases in Japan. Sagace offers features tailored to biomedical research, including manually tuned ranking, a faceted navigation to refine search results, and rich snippets constructed with retrieved metadata for each database entry.

Conclusions

Sagace will be valuable for experts who are involved in biomedical research and drug development in both academia and industry. Sagace is freely available athttp://sagace.nibio.go.jp/en/.
Diversity of heterotrimeric G-protein γ subunits in plants
Authors: Trusov Yuri , Chakravorty David , Botella José Ramón
Published: October 2012

Background

Heterotrimeric G-proteins, consisting of three subunits Gα, Gβ and Gγ are present in most eukaryotes and mediate signaling in numerous biological processes. In plants, Gγ subunits were shown to provide functional selectivity to G-proteins. Three unconventional Gγ subunits were recently reported in Arabidopsis, rice and soybean but no structural analysis has been reported so far. Their relationship with conventional Gγ subunits and taxonomical distribution has not been yet demonstrated.

Results

After an extensive similarity search through plant genomes, transcriptomes and proteomes we assembled over 200 non-redundant proteins related to the known Gγ subunits. Structural analysis of these sequences revealed that most of them lack the obligatory C-terminal prenylation motif (CaaX). According to their C-terminal structures we classified the plant Gγ subunits into three distinct types. Type A consists of Gγ subunits with a putative prenylation motif. Type B subunits lack a prenylation motif and do not have any cysteine residues in the C-terminal region, while type C subunits contain an extended C-terminal domain highly enriched with cysteines. Comparative analysis of C-terminal domains of the proteins, intron-exon arrangement of the corresponding genes and phylogenetic studies suggested a common origin of all plant Gγ subunits.

Conclusion

Phylogenetic analyses suggest that types C and B most probably originated independently from type A ancestors. We speculate on a potential mechanism used by those Gγ subunits lacking isoprenylation motifs to anchor the Gβγ dimer to the plasma membrane and propose a new flexible nomenclature for plant Gγ subunits. Finally, in the light of our new classification, we give a word of caution about the interpretation of Gγ research in Arabidopsis and its generalization to other plant species.
A rule-based algorithm for automatic bond type perception
Authors: Zhang Qian , Zhang Wei , Li Youyong , Wang Junmei , Zhang Liling , Hou Tingjun
Published: October 2012

Assigning bond orders is a necessary and essential step for characterizing a chemical structure correctly in force field based simulations. Several methods have been developed to do this. They all have advantages but with limitations too. Here, an automatic algorithm for assigning chemical connectivity and bond order regardless of hydrogen for organic molecules is provided, and only three dimensional coordinates and element identities are needed for our algorithm. The algorithm uses hard rules, length rules and conjugation rules to fix the structures. The hard rules determine bond orders based on the basic chemical rules; the length rules determine bond order by the length between two atoms based on a set of predefined values for different bond types; the conjugation rules determine bond orders by using the length information derived from the previous rule, the bond angles and some small structural patterns. The algorithm is extensively evaluated in three datasets, and achieves good accuracy of predictions for all the datasets. Finally, the limitation and future improvement of the algorithm are discussed.
National inventory of emergency departments in Singapore
Authors: Wen Leana S , Venkataraman Anantharaman , Sullivan Ashley F , Camargo Carlos A
Published: October 2012

Background

Emergency departments (EDs) are the basic units of emergency care. We performed a national inventory of all Singapore EDs and describe their characteristics and capabilities.

Methods

Singapore EDs accessible to the general public 24/7 were surveyed using the National ED Inventories instrument (
http://www.emnet-nedi.org). ED staff members were asked about ED characteristics with reference to calendar year 2007.

Results

Fourteen EDs participated (100% response). All EDs were located in hospitals, and most (92%) were independent departments. One was a psychiatric ED; the rest were general EDs. Among general EDs, all had a contiguous layout, with medical and surgical care provided in one area. All but two EDs saw both adults and children; one ED was adult-only, and the other saw only children. Six were in the public sector and seven in private health-care institutions, with public EDs seeing the majority (78%) of ED patients. Each private ED had an annual patient census of <30,000. These EDs received 2% of ambulances and had an inpatient admission rate of 7%. Each public ED had an annual census of >60,000. They received 98% of ambulances and had an inpatient admission rate of 30%. Two public EDs reported being overcapacity; no private EDs did. For both public and private EDs, availability of consultant resources in EDs was high, while technological resources varied.

Conclusion

Characteristics and capabilities of Singapore EDs varied and were largely dependent on whether they are in public or private hospitals. This initial inventory establishes a benchmark to further monitor the development of emergency care in Singapore.
Fabrication of docetaxel surfaced Fe3O4 magnetite nanoparticles and their cytotoxicity on 4 T1 breast cancer cells
Authors: Yazdi MH , Najafi Z Niazzadeh , Khorramizadeh MR , Amini M , Shahverdi AR
Published: October 2012

Background

In the recent years, there is an increasing attention to the using of Fe3O4 magnetite nanoparticles (MNPs) as drug delivery systems. Application of this nanoparticles could profit advantages of nanomedicine to enhance biological activity of pharmaceutical ingredients.

Methods

Fe3O4 MNPs were synthesised by a chemical method and characterized by transmission electron microscopy and energy-dispersive spectroscopy techniques. In the next step, docetaxel-coated Fe3O4 MNPs were prepared, using percipitation method. The surface chemistry of docetaxel-coated Fe3O4 MNPs as well as their thermal decomposition characteristics were examined using fourier transform infrared spectroscopy and thermogravimetric analyzer equipment, respectively. The cytotoxicity assay was conducted on 4 T1 breast cancer carsinoma by MTT assay to evaluate the possible in vitro antiproliferative effects of docetaxel-coated Fe3O4 MNPs.

Results

During precipitation process, docetaxel molecules were precipitated on the surface of Fe3O4 MNPs by the ratio of 3:100 w/w which indicates that each milligram of coated Fe3O4 MNPs averagely contained 30 μg pure docetaxel compound. Docetaxel showed aniproliferative effects against mentioned cell line. The higestest concentartion of docetaxel (80 μg/ml) caused about 80% cell death. However, the results demostarted that much lower amounts of docetaxel will be needed in combination of Fe3O4 MNPs to produce the potent antiproliferative effect compared to docetaxel alone. Dose response cytotoxicity assay of docetaxel-coated Fe3O4 MNPs against 4 T1 breast cancer cells showed that lower amount of docetaxel (0.6 μg/ml) can exhibit higher cytotoxic effect against this cancer cell line (90% cell death).
Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells
Authors: Khaghanzadeh Narges , Mojtahedi Zahra , Ramezani Mohammad , Erfani Nasrollah , Ghaderi Abbas
Published: October 2012

Background

Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer.

Methods

The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT) assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells), and propidium iodide (for necrotic cells) dyes were employed.

Results

Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed.

Conclusions

We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.
Radiation effect on Marangoni convection boundary layer flow of a nanofluid
Authors: Mat Nor Azian Aini , Arifin Norihan M , Nazar Roslinda , Ismail Fudziah
Published: October 2012

Purpose

In this paper, we present a mathematical model for Marangoni convection boundary layer flow with radiation and different types of nanoparticles, namely, Cu, Al2O3, and TiO2 in a water-based fluid.

Method

The governing equations in the form of partial differential equations have been reduced to a set of ordinary differential equations by applying suitable similarity transformations, which is then solved numerically using the shooting method.

Results

Numerical results are obtained for the surface-temperature gradient or the heat transfer rate as well as the temperature profiles for some values of the governing parameters, namely, the nanoparticle volume fraction φ, the constant exponent β, and thermal radiation parameter N
r.

Conclusion

The results indicate that the heat transfer rate at the surface decreases as the thermal radiation parameter N
r increases.

MSC: 76N20, fluid mechanics.
Long-term time-lapse microgravity and geotechnical monitoring of relict salt mines, Marston, Cheshire, U. K.
Authors: Pringle Jamie K. , Styles Peter , Howell Claire P. , Branston Michael W. , Furner Rebecca , Toon Sam M.
Published: October 2012

The area around the town of Northwich in Cheshire, U. K., has a long history of catastrophic ground subsidence caused by a combination of natural dissolution and collapsing abandoned mine workings within the underlying Triassic halite bedrock geology. In the village of Marston, the Trent and Mersey Canal crosses several abandoned salt mine workings and previously subsiding areas, the canal being breached by a catastrophic subsidence event in 1953. This canal section is the focus of a long-term monitoring study by conventional geotechnical topographic and microgravity surveys. Results of 20 years of topographic time-lapse surveys indicate specific areas of local subsidence that could not be predicted by available site and mine abandonment plan and shaft data. Subsidence has subsequently necessitated four phases of temporary canal bank remediation. Ten years of microgravity time-lapse data have recorded major deepening negative anomalies in specific sections that correlate with topographic data. Gravity 2D modeling using available site data found upwardly propagating voids, and associated collapse material produced a good match with observed microgravity data. Intrusive investigations have confirmed a void at the major anomaly. The advantages of undertaking such long-term studies for near-surface geophysicists, geotechnical engineers, and researchers working in other application areas are discussed.
Zebrafish models flex their muscles to shed light on muscular dystrophies
Authors: Berger Joachim , Currie Peter D.
Published: October 2012

Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.
Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis
Authors: Moscarello Mario A. , Lei Helena , Mastronardi Fabrizio G. , Winer Shawn , Tsui Hubert , Li Zhen , Ackerley Cameron , Zhang Li , Raijmakers Reinout , Wood D. Denise
Published: November 2012

Multiple sclerosis (MS) is the most common CNS-demyelinating disease of humans, showing clinical and pathological heterogeneity and a general resistance to therapy. We first discovered that abnormal myelin hypercitrullination, even in normal appearing white matter, by peptidylarginine deiminases (PADs) correlates strongly with disease severity and might have an important role in MS progression. Hypercitrullination is known to promote focal demyelination through reduced myelin compaction. Here we report that 2-chloroacetamidine (2CA) a small-molecule, PAD active-site inhibitor, dramatically attenuates disease at any stage in independent neurodegenerative as well as autoimmune MS mouse models. 2CA reduced PAD activity and protein citrullination to pre-disease status. In the autoimmune models, disease induction uniformly induced spontaneous hypercitrullination with citrulline+ epitopes targeted frequently. 2CA rapidly suppressed T cell autoreactivity, clearing brain and spinal cord infiltrates, through selective removal of newly activated T cells. 2CA essentially prevented disease when administered before disease onset or before autoimmune induction, making hypercitrullination and specifically PAD enzymes a therapeutic target in MS models and thus possibly MS.
Asymmetric Bis(alkoxycarbonylation) Reaction of Cyclic Olefins Catalyzed by Palladium in the Presence of Copper(I) Triflate
Authors: Aratani Takahiro , Tahara Kenji , Takeuchi Susumu , Kitamura Satoko , Murai Moemi , Fujinami Shuhei , Inomata Katsuhiko , Ukaji Yutaka
Published: October 2012

A palladium-catalyzed asymmetric bis(alkoxycarbonylation) reaction of 1,2-dihydronaphthalenes and related cyclic olefins in the presence of copper(I) triflate was achieved by using a chiral bioxazoline ligand under normal pressure of carbon monoxide and oxygen to give the corresponding optically active cis-dicarboxylates with enantioselectivities up to 94% ee. An asymmetric intra- and intermolecular bis(alkoxycarbonylation) reaction of a prochiral diol possessing dihydronaphthalene skeleton also proceeded enantioselectively by an appropriate selection of the substituent of bioxazoline ligand. The carbonylation product derived from 8-methoxy-1,2-dihydronaphthalene was applied to the synthesis of a biologically active hexahydrobenz[e]isoindole derivative.
Fluorescent Tin(IV) Complexes with Schiff Base Ligands: Synthesis, Structures, and Fluorescence Lifetime
Authors: Takano Kentaro , Takahashi Masayuki , Fukushima Takaaki , Takezaki Makoto , Tominaga Toshihiro , Akashi Haruo , Takagi Hideaki , Shibahara Takashi
Published: October 2012

Eleven Schiff base tin(IV) complexes of the type [SnCl3(L)] (HL: Schiff base) were synthesized and structurally characterized by X-ray crystallography and 1H NMR spectroscopy, and their properties were investigated. The Schiff bases are prepared from aldehydes with a benzene or a naphthalene ring and 8-aminoquinoline or its derivatives. The complexes adopt geometries close to octahedral, with three chloride ions coordinated meridionally. Eight of the eleven tin complexes show fluorescence in DMSO, and the emission range from bluish green to orange (λmax: 492–545 nm). Two solid tin complexes are fluorescent, although they are not in DMSO, and one tin complex is not fluorescent even in the solid state. The fluorescence quantum yields (Φf) of the complexes depend very much on the ligands (Φf = 0.21–0.022). The fluorescence lifetimes (τ = 0.49–1.76 ns) were measured and the results will be discussed. DFT calculation (B3LYP/Sn, LanL2DZ; others, 6-31G**) shows that the order of the magnitudes of HOMO–LUMO gaps is consonant with that of the emission wavelengths (λmax) of the complexes. All the cyclic voltammograms of the Schiff base ligands and the complexes exhibited irreversible waves and these results suggest that the reduction products of the ligands and the complexes were unstable under the time scale in CV measurements (0.1 V s−1). Relatively good correlation was observed between reduction potentials in DMSO and the energies of LUMO.
Pd0-Mediated Rapid C-[18F]Fluoromethylation by the Cross-Coupling Reaction of a [18F]Fluoromethyl Halide with an Arylboronic Acid Ester: Novel Method for the Synthesis of a 18F-Labeled Molecular Probe for Positron Emission Tomography
Authors: Doi Hisashi , Goto Miki , Suzuki Masaaki
Published: November 2012

Pd0-Mediated C-[18F]fluoromethylation of pinacolborane-substituted benzoate 1 and [18F]FCH2X (X = Br or I) has been carried out with a focus on the rapid incorporation of a [18F]fluoromethyl group into an aryl carbon framework. The reaction of 1 and [18F]FCH2I under the conditions of [Pd2(dba)3]/P(o-CH3C6H5)3 (1:6) and K2CO3 in DMF at 65 °C for 5 min afforded the [18F]fluoromethylated benzoate [18F]-2 in 23% HPLC analytical yield. The coupling efficiency was significantly enhanced by the reaction of 1 and [18F]FCH2Br under the conditions of [Pd2(dba)3]/P(o-tolyl)3 (1:6) and K2CO3 in DMPU:H2O (9:1) at 120 °C within 15 min to afford [18F]-2 in 64% HPLC analytical yield (up to 86% HPLC analytical yield when strictly controlling the reaction temperature with ±3 °C accuracy) and 66% decay-corrected isolated yield based on [18F]FCH2Br. The total synthesis time starting from the production of 18F− in the cyclotron was 88 min. The reaction was extended to various aryl compounds.
N,N-Di- and N,N,C-Trialkylation of α-Sulfoximino Esters
Authors: Hata Shingo , Maeda Tatsuya , Shimizu Makoto
Published: October 2012

N,N-Dialkylation of α-sulfoximino esters with Grignard reagents proceeds to give α-N,N-dialkylamino esters. N,N,C-Trialkylated product is also obtained via the oxidation and nucleophilic addition reaction of the intermediary enolate.
Application of dynamic susceptibility contrast-enhanced perfusion in temporal lobe epilepsy
Authors: Xing Wu , Wang Xiaoyi , Xie Fangfang , Liao Weihua
Published: November 2012

Background

Accurately locating the epileptogenic focus in temporal lobe epilepsy (TLE) is important in clinical practice. Single-photon emission computed tomography (SPECT) and positron-emission tomography (PET) have been widely used in the lateralization of TLE, but both have limitations. Magnetic resonance perfusion imaging can accurately and reliably reflect differences in cerebral blood flow and volume.

Purpose

To investigate the diagnostic value of dynamic susceptibility contrast-enhanced (DSC) perfusion magnetic resonance imaging (MRI) in the lateralization of the epileptogenic focus in TLE.

Material and Methods

Conventional MRI and DSC-MRI scanning was performed in 20 interictal cases of TLE and 20 healthy volunteers. The relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) of the bilateral mesial temporal lobes of the TLE cases and healthy control groups were calculated. The differences in the perfusion asymmetry indices (AIs), derived from the rCBV and rCBF of the bilateral mesial temporal lobes, were compared between the two groups.

Results

In the control group, there were no statistically significant differences between the left and right sides in terms of rCBV (left 1.55±0.32, right 1.57±0.28) or rCBF (left 99.00±24.61, right 100.38±23.46) of the bilateral mesial temporal lobes. However, in the case group the ipsilateral rCBV and rCBF values (1.75±0.64 and 96.35±22.63, respectively) were markedly lower than those of the contralateral side (2.01± 0.79 and 108.56±26.92; P < 0.05). Both the AI of the rCBV (AIrCBV; 13.03±10.33) and the AI of the rCBF (AIrCBF; 11.24±8.70) of the case group were significantly higher than that of the control group (AIrCBV 5.55± 3.74, AIrCBF 5.12±3.48; P < 0.05). The epileptogenic foci of nine patients were correctly lateralized using the 95th percentile of the AIrCBV and AIrCBF of the control group as the normal upper limits.

Conclusion

In patients with TLE interictal, both rCBV and rCBF of the ipsilateral mesial temporal lobe were markedly lower than that of healthy control subjects. DSC-MRI can provide lateralization for TLE.
The use of a novel method of endovenous steam ablation in treatment of great saphenous vein insufficiency: own experiences
Authors: Mlosek R K , Woźniak W , Gruszecki L , Stapa R Z
Published: November 2012

Objective

Endovascular procedures are gaining more and more popularity as treatment of great saphenous vein (GSV) incompetence. The purpose of the present study was to assess the efficacy of steam GSV ablation.

Methods

Steam ablation using the steam vein sclerosis system (CERMA, France) was performed in 20 patients with GSV incompetence. The efficacy of the procedure was evaluated using ultrasound and the following parameters were assessed: changes in lumen diameter, GSV wall thickness, reflux and presence/absence of blood flow.

Results

The GSV steam ablation resulted in the obliteration of the vein lumen in all patients – reflux or blood flow were not observed in any subject. A significant decrease of GSV lumen diameter and an increase of GSV wall thickness were also observed in all subjects following the procedure. No postoperative complications were noted. The steam ablation technique was also positively assessed by the patients.

Conclusions

Steam ablation is an endovascular surgical technique, which can become popular and widely used due to its efficacy and safety. It is also easy to use and patient-friendly. The research on its use should be continued.
The Aerodynamic Characterization of Generic Tail Fin Shapes
Authors: Singh K. , Hemmati A. , Wood D.H.
Published: November 2012

This paper describes the experimental characterization of the yaw response of a range of generic tail fin shapes: delta wings, right triangles, rectangles, and ellipses. The fins were tested in a wind tunnel without the complication of blades and nacelle. They were released from an initial angle, usually 45°, and the subsequent response recorded using an accurate potentiometer. Unsteady tail fin performance can be analysed using unsteady slender body theory and the quasi-steady analysis originally developed for wind vanes. Both predict a linear, second order response so the measured responses are quantified in terms of the natural frequency and damping ratio. It is shown that unsteady slender body theory is slightly more accurate, but both fail to describe the full complexity of the response.
Effects of Leading-Edge Protection Tape on Wind Turbine Blade Performance
Authors: Sareen Agrim , Sapre Chinmay A. , Selig Michael S.
Published: November 2012

This paper presents results of a study to investigate the impact of using wind protection tape (WPT) to protect the leading edge of wind turbine airfoils from erosion. The tests were conducted on the DU 96-W-180 wind turbine airfoil at three Reynolds numbers between 1 and 1.85 million and angles of attack spanning the low drag range of the airfoil. Tests were run by varying the chordwise extent of the wind protection tape on the upper and lower surface in order to determine the relative impact of each configuration on the aerodynamics of the airfoil. The objective was to assess the performance losses due to the wind protection tape and compare them with losses due to leading-edge erosion in order to determine the potential benefits of using such tape to protect wind turbine blades. Results showed that the application of wind protection tape caused a drag increase of 5–15% for the various configurations tested and was significantly less detrimental to airfoil performance than leading edge erosion that could otherwise occur.
CFD Sensitivity Analysis of a Straight-Blade Vertical Axis Wind Turbine
Authors: Almohammadi Khaled M , Ingham D B , Ma L , Pourkashanian M
Published: November 2012

This paper investigates the flow field features and the predicted power coefficient of a straight blade vertical axis wind turbine (SB-VAWT) using computational fluid dynamics modeling using 2D simulations. The Unsteady Navier-Stokes equations are solved with the concept of Reynolds averaging using the commercial software FLUENT and the sliding mesh technique is applied. In the mesh phase, three parameters have been investigated, namely the cell type, the cell aspect ratio on the airfoil surface, and the total number of cells in the computational domain. In the simulation phase, two parameters have been investigated, namely the time step/Courant number, and the turbulence intensity. Significant differences have been observed in the flow field features and on the predicted power coefficient for some of these parameters which if not considered in details could lead to unreliable predictions. The sensitivity of the parameters is not equally significant and this paper suggests which parameters should be focused on in the modeling process. The convergence behavior of the quadrilateral based mesh is found to be more consistent compared to the triangular based mesh. In the mesh phase, the cell aspect ratio on the airfoil surface was found to be a significant factor, whereas the turbulence intensity was found to be a significant fac-tor in the simulation phase.
E. coli 6S RNA release from RNA polymerase requires σ70 ejection by scrunching and is orchestrated by a conserved RNA hairpin
Authors: Panchapakesan Shanker Shyam S. , Unrau Peter J.
Published: November 2012

The 6S RNA in Escherichia coli suppresses housekeeping transcription by binding to RNA polymerase holoenzyme (core polymerase + σ70) under low nutrient conditions and rescues σ70-dependent transcription in high nutrient conditions by the synthesis of a short product RNA (pRNA) using itself as a template. Here we characterize a kinetic intermediate that arises during 6S RNA release. This state, consisting of 6S RNA and core polymerase, is related to the formation of a top-strand “release” hairpin that is conserved across the γ-proteobacteria. Deliberately slowing the intrinsic 6S RNA release rate by nucleotide feeding experiments reveals that σ70 ejection occurs abruptly once a pRNA length of 9 nucleotides (nt) is reached. After σ70 ejection, an additional 4 nt of pRNA synthesis is required before the 6S:pRNA complex is finally released from core polymerase. Changing the E. coli 6S RNA sequence to preclude formation of the release hairpin dramatically slows the speed of 6S RNA release but, surprisingly, does not alter the abruptness of σ70 ejection. Rather, the pRNA size required to trigger σ70 release increases from 9 nt to 14 nt. That a precise pRNA length is required to trigger σ70 release either with or without a hairpin implicates an intrinsic “scrunching”-type release mechanism. We speculate that the release hairpin serves two primary functions in the γ-proteobacteria: First, its formation strips single-stranded “−10” 6S RNA interactions away from σ70. Second, the formation of the hairpin accumulates RNA into a region of the polymerase complex previously associated with DNA scrunching, further destabilizing the 6S:pRNA:polymerase complex.
Tackling urban poverty in China: the Minimum Living Standard Scheme and its limitations
Authors: Peng Zhaiwen , Ding Yi
Published: October 2012

As a cash transfer programme aiming to guarantee a minimum income for registered urban residents, the urban Minimum Living Standard Scheme (MLSS) has played a vital role in tackling the new poverty This article explains the driving force behind the expansion of the urban MLSS, describes how it works, and analyses its key limitations. It stresses that the decentralised programme administration without practical accountability means that the localities provide protection based on their capacity to finance it and the political will to do so. And urban dwellers living in poverty cannot therefore in practice receive assistance based on their social rights and needs.
A child-sensitive approach to social protection: serving practical and strategic needs
Authors: Roelen Keetie , Sabates-Wheeler Rachel
Published: October 2012

Social protection is increasingly considered a development success story. At the same time, it still does too little to account for social differentiation and to address vulnerability, as opposed to poverty. Child sensitive social protection has gained considerable momentum, particularly in a developing country context, raising questions about its concept and practical implications. We argue that three types of vulnerabilities call for more tailored thinking about social protection for children and discuss implications for social protection interventions on the basis of case studies. Child sensitive social protection requires a critical perspective and for context to guide its design and delivery.
All in it together? Disabled people, the Coalition and welfare to work
Authors: Patrick Ruth
Published: October 2012

This paper critically explores the Westminster coalition government’s efforts to assist disabled people off benefits and into paid employment, focusing on the ongoing migration of Incapacity Benefit claimants onto Employment and Support Allowance. Drawing on the social model of disability, it is argued that the current reform agenda individualises the problem of disability; placing too much emphasis on disabled people’s employability while neglecting broader societal barriers to their full and equal labour market participation. Given these shortcomings, it seems unlikely that the Coalition’s approach will help disabled people to make the transition from welfare-to-work.
Thalamus-Derived Molecules Promote Survival and Dendritic Growth of Developing Cortical Neurons
Authors: Sato Haruka , Fukutani Yuma , Yamamoto Yuji , Tatara Eiichi , Takemoto Makoto , Shimamura Kenji , Yamamoto Nobuhiko
Published: October 2012

The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening byin situhybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.
The Dynamic Nature of Top-Down Signals Originating from Prefrontal Cortex: A Combined fMRI–TMS Study
Authors: Lee Taraz G. , D'Esposito Mark
Published: October 2012

The prefrontal cortex (PFC) is proposed to be the source of top-down signals that can modulate extrastriate visual processing in accordance with behavioral goals, yet little direct causal evidence for this hypothesis exists. Using theta burst transcranial magnetic stimulation, we disrupted PFC function in human participants before performing a working memory task during fMRI scanning. PFC disruption decreased the tuning of extrastriate cortex responses, coinciding with decrements in working memory performance. We also found that activity in the homologous PFC region in the nonstimulated hemisphere predicted performance following disruption. Specifically, those participants with greater homologous PFC activity and greater connectivity between this region and extrastriate cortex were the most resistant to PFC disruption. These findings provide evidence for a compensatory mechanism following insults to the brain, and insight into the dynamic nature of top-down signals originating from the PFC.
A Novel BACHD Transgenic Rat Exhibits Characteristic Neuropathological Features of Huntington Disease
Authors: Yu-Taeger Libo , Petrasch-Parwez Elisabeth , Osmand Alexander P. , Redensek Adriana , Metzger Silke , Clemens Laura E. , Park Larry , Howland David , Calaminus Carsten , Gu Xiaofeng , Pichler Bernd , Yang X. William , Riess Olaf , Nguyen Huu Phuc
Published: October 2012

Huntington disease (HD) is an inherited progressive neurodegenerative disorder, characterized by motor, cognitive, and psychiatric deficits as well as neurodegeneration and brain atrophy beginning in the striatum and the cortex and extending to other subcortical brain regions. The genetic cause is an expansion of the CAG repeat stretch in theHTTgene encoding huntingtin protein (htt). Here, we generated an HD transgenic rat model using a human bacterial artificial chromosome (BAC), which contains the full-lengthHTTgenomic sequence with 97 CAG/CAA repeats and all regulatory elements. BACHD transgenic rats display a robust, early onset and progressive HD-like phenotype including motor deficits and anxiety-related symptoms. In contrast to BAC and yeast artificial chromosome HD mouse models that express full-length mutant huntingtin, BACHD rats do not exhibit an increased body weight. Neuropathologically, the distribution of neuropil aggregates and nuclear accumulation of N-terminal mutant huntingtin in BACHD rats is similar to the observations in human HD brains. Aggregates occur more frequently in the cortex than in the striatum and neuropil aggregates appear earlier than mutant htt accumulation in the nucleus. Furthermore, we found an imbalance in the striatal striosome and matrix compartments in early stages of the disease. In addition, reduced dopamine receptor binding was detectable byin vivoimaging. Our data demonstrate that this transgenic BACHD rat line may be a valuable model for further understanding the disease mechanisms and for preclinical pharmacological studies.
A Longitudinal Study of the Long-Term Consequences of Drinking during Pregnancy: HeavyIn UteroAlcohol Exposure Disrupts the Normal Processes of Brain Development
Authors: Lebel Catherine , Mattson Sarah N. , Riley Edward P. , Jones Kenneth L. , Adnams Colleen M. , May Philip A. , Bookheimer Susan Y. , O'Connor Mary J. , Narr Katherine L. , Kan Eric , Abaryan Zvart , Sowell Elizabeth R.
Published: October 2012

Exposure to alcoholin uterocan cause birth defects, including face and brain abnormalities, and is the most common preventable cause of intellectual disabilities. Here we use structural magnetic resonance imaging to measure cortical volume change longitudinally in a cohort of human children and youth with prenatal alcohol exposure (PAE) and a group of unexposed control subjects, demonstrating that the normal processes of brain maturation are disrupted in individuals whose mothers drank heavily during pregnancy. Trajectories of cortical volume change within children and youth with PAE differed from those of unexposed control subjects in posterior brain regions, particularly in the parietal cortex. In these areas, control children appear to show a particularly plastic cortex with a prolonged pattern of cortical volume increases followed by equally vigorous volume loss during adolescence, while the alcohol-exposed participants showed primarily volume loss, demonstrating decreased plasticity. Furthermore, smaller volume changes between scans were associated with lower intelligence and worse facial morphology in both groups, and were related to the amount of PAE during each trimester of pregnancy in the exposed group. This demonstrates that measures of IQ and facial dysmorphology predict, to some degree, the structural brain development that occurs in subsequent years. These results are encouraging in that interventions aimed at altering “experience” over time may improve brain trajectories in individuals with heavy PAE and possibly other neurodevelopmental disorders.
On the Anticipatory Precue Activity in Motor Cortex
Authors: Confais Joachim , Kilavik Bjørg Elisabeth , Ponce-Alvarez Adrián , Riehle Alexa
Published: October 2012

Motor cortical neurons are activated during movement preparation and execution, and in response to task-relevant visual cues. A few studies also report activation before the expected presentation of cues. Here, we study specifically this anticipatory activity preceding visual cues in motor cortical areas. We recorded the activity of 1215 neurons in the motor cortex of two macaque monkeys while they performed a center-out reaching task, including two consecutive delays of equal duration, known in advance. During the first delay (D1), they had to await the spatial cue and only reach to the cued target after the second delay (D2). Forty-two percent of the neurons displayed anticipatory activity during D1. Among these anticipatory neurons, 59% increased (D1up) their activity and the remaining decreased (D1down) their activity. By classifying the neurons according to these firing rate profiles during D1, we found that the activity during D2 differed in a systematic way. The D1up neurons were more likely to discharge phasically soon after the spatial cue and were less active during movement execution, whereas the D1down neurons showed the opposite pattern. But, regardless of their temporal activity profiles, the two categories seemed equally involved in early and late motor preparation, as reflected in their directional selectivity. This precue activity in motor cortex may reflect two complementary, coexisting processes: the facilitation of incoming spatial information in parallel with the downregulation of corticospinal excitability to prevent a premature response.
Multisensory Representation of Frequency across Audition and Touch: High Density Electrical Mapping Reveals Early Sensory-Perceptual Coupling
Authors: Butler John S. , Foxe John J. , Fiebelkorn Ian C. , Mercier Manuel R. , Molholm Sophie
Published: October 2012

The frequency of environmental vibrations is sampled by two of the major sensory systems, audition and touch, notwithstanding that these signals are transduced through very different physical media and entirely separate sensory epithelia. Psychophysical studies have shown that manipulating frequency in audition or touch can have a significant cross-sensory impact on perceived frequency in the other sensory system, pointing to intimate links between these senses during computation of frequency. In this regard, the frequency of a vibratory event can be thought of as a multisensory perceptual construct. In turn, electrophysiological studies point to temporally early multisensory interactions that occur in hierarchically early sensory regions where convergent inputs from the auditory and somatosensory systems are to be found. A key question pertains to the level of processing at which the multisensory integration of featural information, such as frequency, occurs. Do the sensory systems calculate frequency independently before this information is combined, or is this feature calculated in an integrated fashion during preattentive sensory processing? The well characterized mismatch negativity, an electrophysiological response that indexes preattentive detection of a change within the context of a regular pattern of stimulation, served as our dependent measure. High-density electrophysiological recordings were made in humans while they were presented with separate blocks of somatosensory, auditory, and audio-somatosensory “standards” and “deviants,” where the deviant differed in frequency. Multisensory effects were identified beginning at ∼200 ms, with the multisensory mismatch negativity (MMN) significantly different from the sum of the unisensory MMNs. This provides compelling evidence for preattentive coupling between the somatosensory and auditory channels in the cortical representation of frequency.
Not Lost in Translation: Neural Responses Shared Across Languages
Authors: Honey Christopher J. , Thompson Christopher R. , Lerner Yulia , Hasson Uri
Published: October 2012

How similar are the brains of listeners who hear the same content expressed in different languages? We directly compared the fMRI response time courses of English speakers and Russian speakers who listened to a real-life Russian narrative and its English translation. In the translation, we tried to preserve the content of the narrative while reducing the structural similarities across languages. The story evoked similar brain responses, invariant to the structural changes across languages, beginning just outside early auditory areas and extending through temporal, parietal, and frontal cerebral cortices. The similarity of responses across languages was nearly equal to the similarity of responses within each language group. The present results demonstrate that the human brain processes real-life information in a manner that is largely insensitive to the language in which that information is conveyed. The methods introduced here can potentially be used to quantify the transmission of meaning across cultural and linguistic boundaries.
Adaptation of Spike Timing Precision Controls the Sensitivity to Interaural Time Difference in the Avian Auditory Brainstem
Authors: Higgs Matthew H. , Kuznetsova Marina S. , Spain William J.
Published: October 2012

While adaptation is widely thought to facilitate neural coding, the form of adaptation should depend on how the signals are encoded. Monaural neurons early in the interaural time difference (ITD) pathway encode the phase of sound input using spike timing rather than firing rate. Such neurons in chicken nucleus magnocellularis (NM) adapt to ongoing stimuli by increasing firing rate and decreasing spike timing precision. We measured NM neuron responses while adapting them to simulated physiological input, and used these responses to construct inputs to binaural coincidence detector neurons in nucleus laminaris (NL). Adaptation of spike timing in NM reduced ITD sensitivity in NL, demonstrating the dominant role of timing in the short-term plasticity as well as the immediate response of this sound localization circuit.
Reduction of Synaptojanin 1 Ameliorates Synaptic and Behavioral Impairments in a Mouse Model of Alzheimer's Disease
Authors: McIntire Laura Beth J. , Berman Diego E. , Myaeng Jennifer , Staniszewski Agnieszka , Arancio Ottavio , Di Paolo Gilbert , Kim Tae-Wan
Published: October 2012

Decades of research have correlated increased levels of amyloid-β peptide (Aβ) with neuropathological progression in Alzheimer's disease (AD) patients and transgenic models. Aβ precipitates synaptic and neuronal anomalies by perturbing intracellular signaling, which, in turn, may underlie cognitive impairment. Aβ also alters lipid metabolism, notably causing a deficiency of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a phospholipid that regulates critical neuronal functions. Haploinsufficiency of the gene encoding synaptojanin 1 (Synj1), a major PI(4,5)P2phosphatase in the brain, provided protection against PI(4,5)P2breakdown and electrophysiological deficits attributable to Aβ. Based on these data, we tested whether reduction of Synj1 could rescue cognitive deficits and Aβ-induced morphological alterations of synapses. We found that hemizygous deletion ofSynj1in the context of a mouse model expressing the Swedish mutant of amyloid precursor protein rescues deficits in learning and memory without affecting amyloid load.Synj1heterozygosity also rescued PI(4,5)P2deficiency in a synaptosome-enriched fraction from the brain of Tg2576 mice. Genetic disruption ofSynj1attenuated Aβ oligomer-induced changes in dendritic spines of cultured hippocampal neurons, sparing mature spine classes, which corroborates the protective role for Synj1 reduction against Aβ insult at the synapse. These results indicate that Synj1 reduction ameliorates AD-associated behavioral and synaptic deficits, providing evidence that Synj1 and, more generally, phosphoinositide metabolism may be promising therapeutic targets. Our work expands on recent studies identifying lipid metabolism and lipid-modifying enzymes as targets of AD-associated synaptic and behavioral impairment.