bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Symptoms of Depression With Weight Loss: Results of a Randomized Trial
Authors: Faulconbridge Lucy F. , Wadden Thomas A. , Berkowitz Robert I. , Sarwer David B. , Womble Leslie G. , Hesson Louise A. , Stunkard Albert J. , Fabricatore Anthony N.
Published: February 2009

Recent studies of rimonabant have re‐awakened interest in the possible adverse psychiatric effects of weight loss, as well as of weight loss medications. This study examined changes in symptoms of depression in 194 obese participants (age = 43.7 ± 10.2 years; BMI = 37.6 ± 4.1 kg/m2) in a 1‐year randomized trial of lifestyle modification and medication. Participants were assigned to (i) sibutramine alone; (ii) lifestyle modification alone; (iii) sibutramine plus lifestyle modification (i.e., combined therapy); or (iv) sibutramine plus brief therapy. Participants completed the Beck Depression Inventory‐II (BDI‐II) at baseline and weeks 6, 10, 18, 26, 40, and 52. At 1 year, participants in combined therapy lost the most weight and those in sibutramine alone the least (12.1 ± 8.8% vs. 5.5 ± 6.5%; P < 0.01). Mean BDI‐II scores across all participants declined from 8.1 ± 6.9 to 6.2 ± 7.7 at 1 year (P < 0.001), with no significant differences among groups. Despite this favorable change, 13.9% of participants (across the four groups) reported potentially discernible increases (≥ 5 points on the BDI‐II) in symptoms of depression at week 52. They lost significantly less weight than participants in the rest of the sample (5.4 ± 7.8% vs. 9.0 ± 7.8%, respectively; P < 0.03). The baseline prevalence of suicidal ideation was 3.6%. Seven new cases of suicidal ideation were observed during the year, with three in lifestyle modification alone. Further research is needed to identify characteristics of obese patients at risk of negative mood changes (and suicidal ideation) in response to behavioral and pharmacologic therapies.
Obesity and Sugar‐sweetened Beverages in African‐American Preschool Children: A Longitudinal Study
Authors: Lim Sungwoo , Zoellner Jamie M. , Lee Joyce M. , Burt Brian A. , Sandretto Anita M. , Sohn Woosung , Ismail Amid I. , Lepkowski James M.
Published: February 2009

A representative sample of 365 low‐income African‐American preschool children aged 3–5 years was studied to determine the association between sugar‐sweetened beverage consumption (soda, fruit drinks, and both combined) and overweight and obesity. Children were examined at a dental clinic in 2002–2003 and again after 2 years. Dietary information was collected using the Block Kids Food Frequency Questionnaire. A BMI score was computed from recorded height and weight. Overweight and obesity were defined by national reference age‐sex specific BMI: those with an age‐sex specific BMI ≥85th, but <95th percentile as overweight and those with BMI ≥95th age‐sex specific percentile as obese. The prevalence of overweight was 12.9% in baseline, and increased to 18.7% after 2 years. The prevalence of obesity increased from 10.3 to 20.4% during the same period. Baseline intake of soda and all sugar‐sweetened beverages were positively associated with baseline BMI z‐scores. After adjusting for covariates, additional intake of fruit drinks and all sugar‐sweetened beverages at baseline showed significantly higher odds of incidence of overweight over 2 years. Among a longitudinal cohort of African‐American preschool children, high consumption of sugar‐sweetened beverages was significantly associated with an increased risk for obesity.
Histone deacetylases: salesmen and customers in the post‐translational modification market
Authors: Brandl André , Heinzel Thorsten , Krämer Oliver H.
Published: February 2009

HDACs (histone deacetylases) are enzymes that remove the acetyl moiety from N‐∍‐acetylated lysine residues in histones and non‐histone proteins. In recent years, it has turned out that HDACs themselves are also subject to post‐translational modification. Such structural alterations can determine the stability, localization, activity and protein—protein interactions of HDACs. This subsequently affects the modification of their substrates and the co‐ordination of cellular signalling networks. Intriguingly, physiologically relevant non‐histone proteins are increasingly found to be deacetylated by HDACs, and aberrant deacetylase activity contributes to several severe human diseases. Targeting the catalytic activity of these enzymes and their post‐translational modifications are therefore attractive targets for therapeutical intervention strategies. To achieve this ambitious goal, details on the molecular mechanisms regulating post‐translational modifications of HDACs are required. This review summarizes aspects of the current knowledge on the biological role and enzymology of the phosphorylation, acetylation, ubiquitylation and sumoylation of HDACs.
The second green revolution? Production of plant-based biodegradable plastics
Authors: Mooney Brian P.
Published: February 2009

Biodegradable plastics are those that can be completely degraded in landfills, composters or sewage treatment plants by the action of naturally occurring micro-organisms. Truly biodegradable plastics leave no toxic, visible or distinguishable residues following degradation. Their biodegradability contrasts sharply with most petroleum-based plastics, which are essentially indestructible in a biological context. Because of the ubiquitous use of petroleum-based plastics, their persistence in the environment and their fossil-fuel derivation, alternatives to these traditional plastics are being explored. Issues surrounding waste management of traditional and biodegradable polymers are discussed in the context of reducing environmental pressures and carbon footprints. The main thrust of the present review addresses the development of plant-based biodegradable polymers. Plants naturally produce numerous polymers, including rubber, starch, cellulose and storage proteins, all of which have been exploited for biodegradable plastic production. Bacterial bioreactors fed with renewable resources from plants – so-called ‘white biotechnology’ – have also been successful in producing biodegradable polymers. In addition to these methods of exploiting plant materials for biodegradable polymer production, the present review also addresses the advances in synthesizing novel polymers within transgenic plants, especially those in the polyhydroxyalkanoate class. Although there is a stigma associated with transgenic plants, especially food crops, plant-based biodegradable polymers, produced as value-added co-products, or, from marginal land (non-food), crops such as switchgrass (Panicum virgatum L.), have the potential to become viable alternatives to petroleum-based plastics and an environmentally benign and carbon-neutral source of polymers.
Out, in and back again: PtdIns(4,5)P2 regulates cadherin trafficking in epithelial morphogenesis
Authors: Schill Nicholas J. , Anderson Richard A.
Published: February 2009

The morphogenesis of epithelial cells in the tissue microenvironment depends on the regulation of the forces and structures that keep cells in contact with their neighbours. The formation of cell–cell contacts is integral to the establishment and maintenance of epithelial morphogenesis. In epithelial tissues, the misregulation of the signalling pathways that control epithelial polarization induces migratory and invasive cellular phenotypes. Many cellular processes influence cadherin targeting and function, including exocytosis, endocytosis and recycling. However, the localized generation of the lipid messenger PtdIns(4,5)P2 is emerging as a fundamental signal controlling all of these processes. The PtdIns(4,5)P2-generating enzymes, PIPKs (phosphatidylinositol phosphate kinases) are therefore integral to these pathways. By the spatial and temporal targeting of PIPKs via the actions of its functional protein associates, PtdIns(4,5)P2 is generated at discrete cellular locales to provide the cadherin-trafficking machinery with its required lipid messenger. In the present review, we discuss the involvement of PtdIns(4,5)P2 and the PIPKs in the regulation of the E-cadherin (epithelial cadherin) exocytic and endocytic machinery, the modulation of actin structures at sites of adhesion, and the direction of cellular pathways which determine the fate of E-cadherin and cell–cell junctions. Recent work is also described that has defined phosphoinositide-mediated E-cadherin regulatory pathways by the use of organismal models.
Structure of human porphobilinogen deaminase at 2.8 Å: the molecular basis of acute intermittent porphyria
Authors: Gill Raj , Kolstoe Simon E. , Mohammed Fiyaz , Al d-Bass Abeer , Mosely Julie E. , Sarwar Mohammed , Cooper Jonathan B. , Wood Stephen P. , Shoolingin-Jordan Peter M.
Published: February 2009

Mutations in the human PBGD (porphobilinogen deaminase) gene cause the inherited defect AIP (acute intermittent porphyria). In the present study we report the structure of the human uPBGD (ubiquitous PBGD) mutant, R167Q, that has been determined by X-ray crystallography and refined to 2.8 Å (1 Å=0.1 nm) resolution (Rfactor=0.26, Rfree=0.29). The protein crystallized in space group P21212 with two molecules in the asymmetric unit (a=81.0 Å, b=104.4 Å and c=109.7 Å). Phases were obtained by molecular replacement using the Escherichia coli PBGD structure as a search model. The human enzyme is composed of three domains each of approx. 110 amino acids and possesses a dipyrromethane cofactor at the active site, which is located between domains 1 and 2. An ordered sulfate ion is hydrogen-bonded to Arg26 and Ser28 at the proposed substrate-binding site in domain 1. An insert of 29 amino acid residues, present only in mammalian PBGD enzymes, has been modelled into domain 3 where it extends helix α23 and forms a β-hairpin structure that contributes to a continuous hydrogen-bonding network spanning domains 1 and 3. The structural and functional implications of the R167Q mutation and other mutations that result in AIP are discussed.
Manifestation of single macromolecule quantum dynamics in photon distribution function of blinking fluorescence
Authors: Osad’ko I. S. , Fedyanin V. V.
Published: February 2009

Distribution function wN(T) for photons created by three-level nanoparticle in time interval T under cw laser excitation is calculated for various methods of photon counting. It is found that each exponential process exp(−λit) in quantum dynamics of three-level nanoparticle manifests itself via Poissonian function PN(λit)=(λit)N exp(−λit)/N! in the photon distribution function wN(T). The distribution function wN(T) is expressed via two or three integrals of two or three Poissonian functions PN(λit). The simple mathematical expression for wN(T) enables one to calculate photon distribution in blinking fluorescence with on and off intervals. A scaling between photon distribution function wN(T) and photoelectric pulse distribution function wn(T) is found. Comparison of the theoretical distribution wn(T) and the distribution measured in blinking fluorescence of single polymer molecule dPPV-PPyV and complex organic molecule 1,1′-didodecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) is carried out. The theoretical distributions are able to describe those found in an experiment.
Distinguished trajectories in time dependent vector fields
Authors: Madrid J. A. Jiménez , Mancho A. M.
Published: February 2009

We introduce a new definition of distinguished trajectory that generalizes the concepts of fixed point and periodic orbit to aperiodic dynamical systems. This new definition is valid for identifying distinguished trajectories with hyperbolic and nonhyperbolic types of stability. The definition is implemented numerically and the procedure consists of determining a path of limit coordinates. It has been successfully applied to known examples of distinguished trajectories. In the context of highly aperiodic realistic flows our definition characterizes distinguished trajectories in finite time intervals, and states that outside these intervals trajectories are no longer distinguished.
Two-dimensional electron systems in HgTe quantum wells
Authors: Kvon Z. D. , Olshanetsky E. B. , Mikhailov N. N. , Kozlov D. A.
Published: February 2009

A brief review is given on the results of research on the properties of two-dimensional (2D) electron systems in quantum wells based on CdHgTe∕HgTe∕CdHgTe double heterojunctions with surface orientations of (100) and (013). The main features of the energy spectrum are described. The results of experiments yielding information about the parameters of the energy spectrum are presented. From cyclotron resonance measurements the effective mass of the 2D electrons in HgTe quantum wells with inverted band structure is obtained as a function of the density of such electrons, Ns, in the range 2.2×1011cm−2⩽Ns⩽9.6×1011cm−2. This density dependence indicates an appreciable nonparabolicity of the spectrum: the mass increases with increasing Ns in that range from a value (0.026±0.005)m0 to (0.0335±0.005)m0. The giant spin splitting observed in asymmetric HgTe quantum wells is discussed, and the results of experimental research on the transition from a quantum Hall liquid to an insulator and the plateau-plateau transition in 2D electron systems in HgTe quantum wells are recounted. The 2D electron-hole system observed recently in the quantum wells under study, which is the first realization of a 2D semimetal, is described. It is found that it arises in lightly doped quantum wells with an inverted band structure and surface orientation (013). The magnetotransport is found to exhibit a number of features (positive magnetoresistance, variable-sign Hall effect, anomalous behavior in the quantum Hall effect regime) due to the simultaneous existence of 2D electrons and holes.
Convective instability of flow in a symmetric channel with spatially periodic structures
Authors: Takaoka Masanori , Sano Taro , Yamamoto Hisakazu , Mizushima Jiro
Published: February 2009

Convective instability of flow in a two-dimensional symmetric channel with periodic suddenly expanded sections is investigated numerically under given inlet and outlet boundary conditions as a finite-length flow. A localized disturbance is added at the inlet of the channel and the subsequent spatiotemporal development of the disturbance is observed. The localized disturbance forms a similarly evolving wave packet while traveling downstream, which enables us to study the nature of convective instability. It is found that the wave packet consists of two intrinsic waves propagating with distinct phase velocities. The spatial structure and the phase velocity of these intrinsic waves are compared with the eigenmode of stability under two different periodic boundary conditions, one of which imposes the flow to have the same periodic length with that of the channel geometry and the other twice the periodic length together with a shift-and-reflect symmetry. It is clarified that the two kinds of waves are well approximated by these two eigenmodes. Our results link a closed flow under periodic boundary conditions to an open flow in a finite-length channel with periodic structures, which enables us to estimate the critical Reynolds number of convective instability and the traveling velocity of the wave packet.
Magnetic microsphere-based mixers for microdroplets
Authors: Roy Tamal , Sinha Ashok , Chakraborty Sayan , Ganguly Ranjan , Puri Ishwar K.
Published: February 2009

While droplet-based microfluidic systems have several advantages over traditional flow-through devices, achieving adequate mixing between reagents inside droplet-based reactors remains challenging. We describe an active mixing approach based on the magnetic stirring of self-assembled chains of magnetic microspheres within the droplet as these stirrers experience a rotating magnetic field. We measure the mixing of a water-soluble dye in the droplet in terms of a dimensional mixing parameter as the field-rpm, fluid viscosity, and microsphere loading are parametrically varied. These show that the mixing rate has a maximum value at a critical Mason number that depends upon the operating conditions.
Magnetic order of Cr thin films in Nb/Cr/Fe-nanoisland hybrid: A comparative study between magnetic and superconducting properties
Authors: Navarro E. , Vélez M. , Huttel Y. , Junquera A. Pérez , Martín J. I. , de Lima O. F. , Cebollada A. , Alameda J. M. , Vicent J. L.
Published: February 2009

Shifted hysteresis loops characteristic of the exchange bias effect between a ferromagnet and an antiferromagnet are demonstrated in structures formed by a 2.5 nm Cr layer deposited on top of an array of Fe nanoislands (Cr/Fe-nanoislands). This effect evidences the persistence of antiferromagnetic (AF) order for Cr layers much thinner than the thickness reported in the literature. The field shift measured is found to increase for the smallest island sizes, which can be related with the enhancement of the Fe-nanoisland surface to volume ratio. The comparative study between superconducting proximity effects in Nb/Cr/Fe-nanoislands and Nb/normal metal/Fe-nanoisland hybrids (where the normal metals used are Al and Pt) confirms the presence of AF order in the 2.5 nm Cr spacer layer. A much shorter penetration depth of the Cooper pairs into the AF Cr layers than in the normal metal Pt and Al spacer layers is deduced.
Boundary effects on the dynamics of exciton polaritons in semiconductor microcavities
Authors: Zhang Yongyou , Jin Guojun , Ma Yu-Qiang
Published: February 2009

Using the coupled Gross–Pitaevskii equations, we investigate the boundary effects on the dynamics of exciton polaritons in semiconductor microcavities excited by an applied vertical pump field. As the radius of the Gaussian pump field is far larger than a critical value, the boundaries of semiconductor microcavities will strongly enhance the anisotropy of the polariton-polariton scattering, and thus the polarization dependence of the polariton-polariton scattering can be neglected. Moreover, the pump threshold behavior of the anisotropy in the polariton-polariton scattering can be avoided by introducing fixed boundary conditions. In the low excitation regime, such an enhancement of anisotropy can be used to generate a pair of nearly intensity-symmetric correlated polaritons, and this efficacy can be more easily achieved by using square microcavities with small area.
Enhanced dielectric response of GeO2-doped CaCu3Ti4O12 ceramics
Authors: Amaral F. , Rubinger C. P. L. , Valente M. A. , Costa L. C. , Moreira R. L.
Published: February 2009

CaCu 3 Ti 4 O 12 ceramic samples were prepared by solid state conventional route using stoichiometric amounts of CuO, TiO2, and CaCO3. Afterward the material was doped with GeO2 with concentrations up to 6% by weight and sintered at 1050 °C for 12 h. The influence of doping on the microstructure, vibrational modes, and dielectric properties of the material was investigated by x-ray diffraction, scanning electron microscopy coupled with an energy dispersive spectrometer, and infrared and dielectric measurements between 100 Hz and 30 MHz. The materials presented huge dielectric response, which increases with doping level relative to undoped CaCu3Ti4O12. The main effect of doping on the microstructure is the segregation of Cu-rich phase in the ceramic grain boundaries. Cole–Cole modeling correlates well the effects of this segregation with the relaxation parameters obtained. The intrinsic phonon contributions for the dielectric response were obtained and discussed together with the structural evolution of the system.
Scanning probe charge reading of ferroelectric domains
Authors: Kim Byong M. , Adams Donald E. , Tran Quan , Ma Qing , Rao Valluri
Published: February 2009

A scanning probe charge-detection technique based on direct piezoelectric effect is demonstrated to read alternating bit polarizations in a ferroelectric media The bit signal is generated by spatially modulating charges interacting with a probe tip scanning in contact with the media. A periodicity of the bits is used with an appropriate scan speed to modulate the signal frequency. A signal-to-noise ratio of 10 dB has been achieved for a contact force of 100 nN. The modulation of the bit signal frequency into the 2 kHz data rate is achieved by coupling 0.4 μm spacing between alternating polarizations with scanning speed of 1.6 mm/s.
Nuclear magnetic resonance implementation of universal quantum gate with constant Hamiltonian evolution
Authors: Liu Wenzhang , Zhang Jingfu , Cao Ye , Huo Wen Yi , Hao Liang , Long Gui Lu , Deng Zhiwei
Published: February 2009

In this letter, we report an experimental demonstration of single-step realization of universal quantum gate in a nuclear magnetic resonance quantum information processor. The scheme uses a constant Hamiltonian evolution and is robust against decoherence. Our work focuses on the implementation of the controlled-NOT gate. Several sets of parameters are obtained and they provide flexibility to suppress decoherence for quantum computation.
Point defects in sputtered NiO films
Authors: Jang Wei-Luen , Lu Yang-Ming , Hwang Weng-Sing , Hsiung Tung-Li , Wang H. Paul
Published: February 2009

The dominant point defects in p-type NiO films were determined by analyzing the coordination number (CN) change with various annealing temperatures and the composition profile of double-layer films deposited individually in oxygen and in argon atmospheres. The results show that the nonstoichiometry of sputtered NiO film is determined by the number of nickel atoms rather than by the number of oxygen atoms. It is concluded that nickel vacancies are the dominant point defects that result in the electrical conductivity of NiO films.
InGaN/GaN multiple quantum well solar cells with long operating wavelengths
Authors: Dahal R. , Pantha B. , Li J. , Lin J. Y. , Jiang H. X.
Published: February 2009

We report on the fabrication and photovoltaic characteristics of InGaN solar cells by exploiting InGaN/GaN multiple quantum wells (MQWs) with In contents exceeding 0.3, attempting to alleviate to a certain degree the phase separation issue and demonstrate solar cell operation at wavelengths longer than previous attainments (>420 nm). The fabricated solar cells based on In0.3Ga0.7N/GaN MQWs exhibit an open circuit voltage of about 2 V, fill factor of about 60%, and an external efficiency of 40% (10%) at 420 nm (450 nm).
Impact of salinity on early reproductive physiology of tomato (Solanum lycopersicum) in relation to a heterogeneous distribution of toxic ions in flower organs
Authors: Ghanem Michel Edmond , van Elteren Johannes , Albacete Alfonso , Quinet Muriel , Martínez-Andújar Cristina , Kinet Jean-Marie , Pérez-Alfocea Francisco , Lutts Stanley
Published: February 2009

The effect of short-term treatments (10 days) by a high salt level (150 mm NaCl) on vegetative and reproductive development was investigated in tomato plants (Solanum lycopersicum L. cv. Ailsa Craig) at two developmental stages. Salinity applied during flowering transition reduced shoot biomass and delayed the appearance of the first inflorescence. Both shoot and root biomasses were reduced when salt was applied during the development of the first inflorescence. At both stages, areas of young leaves decreased and time to first anthesis increased, while total number of flowers in the first inflorescence was not affected. Flower abortion, reduction of pollen number and viability were higher when salinity was applied during inflorescence development. Na+ accumulated in all organs while K+ decreased. Laser ablation inductively coupled plasma mass spectrometry microanalysis revealed that Na+ accumulated in style, ovaries and anther intermediate layers but not in the tapetum nor in the pollen grains when salinity was applied during inflorescence development. K+ was not significantly affected in these structures. Soluble carbohydrates dramatically increased in leaves and decreased in the inflorescence under salt stress conditions. The failure of inflorescence to develop normally under salt stress can be better explained in terms of altered source–sink relationships rather than accumulation of toxic ions.
Inflammation and mitochondrial fatty acid β-oxidation link obesity to early tumor promotion
Authors: Khasawneh J. , Schulz M. D. , Walch A. , Rozman J. , de Angelis M. Hrabe , Klingenspor M. , Buck A. , Schwaiger M. , Saur D. , Schmid R. M. , Klöppel G. , Sipos B. , Greten F. R. , Arkan M. C.
Published: February 2009

Obesity is associated with increased risk for developing pancreatic cancer, and it is suggested that insulin resistance provides the missing link. Here we demonstrate that under the context of genetic susceptibility, a high fat diet (HFD) predisposes mice with oncogenic
K-ras
activation to accelerated pancreatic intraepithelial neoplasm (PanIN) development. Tumor promotion is closely associated with increased inflammation and abrogation of TNFR1 signaling significantly blocks this process underlining a central role for TNFα in obesity-mediated enhancement of PanIN lesions. Interestingly, however, despite increased TNFα levels, mice remain insulin sensitive. We show that, while aggravating tumor promotion, a HFD exerts dramatic changes in energy metabolism through enhancement of pancreatic exocrine insufficiency, metabolic rates, and expression of genes involved in mitochondrial fatty acid (FA) β-oxidation that collectively contribute to improved glucose tolerance in these mice. While on one hand these findings provide significant evidence that obesity is linked to tumor promotion in the pancreas, on the other it suggests alterations in inflammatory responses and bioenergetic pathways as the potential underlying cause.
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
Authors: Tropea Daniela , Giacometti Emanuela , Wilson Nathan R. , Beard Caroline , McCurry Cortina , Fu Dong Dong , Flannery Ruth , Jaenisch Rudolf , Sur Mriganka
Published: February 2009

Rett Syndrome (RTT) is a severe form of X-linked mental retardation caused by mutations in the gene coding for methyl CpG-binding protein 2 (MECP2). Mice deficient in MeCP2 have a range of physiological and neurological abnormalities that mimic the human syndrome. Here we show that systemic treatment of MeCP2 mutant mice with an active peptide fragment of Insulin-like Growth Factor 1 (IGF-1) extends the life span of the mice, improves locomotor function, ameliorates breathing patterns, and reduces irregularity in heart rate. In addition, treatment with IGF-1 peptide increases brain weight of the mutant mice. Multiple measurements support the hypothesis that RTT results from a deficit in synaptic maturation in the brain: MeCP2 mutant mice have sparse dendritic spines and reduced PSD-95 in motor cortex pyramidal neurons, reduced synaptic amplitude in the same neurons, and protracted cortical plasticity in vivo. Treatment with IGF-1 peptide partially restores spine density and synaptic amplitude, increases PSD-95, and stabilizes cortical plasticity to wild-type levels. Our results thus strongly suggest IGF-1 as a candidate for pharmacological treatment of RTT and potentially of other CNS disorders caused by delayed synapse maturation.
Ab initio construction of a eukaryotic transcriptome by massively parallel mRNA sequencing
Authors: Yassour Moran , Kaplan Tommy , Fraser Hunter B. , Levin Joshua Z. , Pfiffner Jenna , Adiconis Xian , Schroth Gary , Luo Shujun , Khrebtukova Irina , Gnirke Andreas , Nusbaum Chad , Thompson Dawn-Anne , Friedman Nir , Regev Aviv
Published: February 2009

Defining the transcriptome, the repertoire of transcribed regions encoded in the genome, is a challenging experimental task. Current approaches, relying on sequencing of ESTs or cDNA libraries, are expensive and labor-intensive. Here, we present a general approach for ab initio discovery of the complete transcriptome of the budding yeast, based only on the unannotated genome sequence and millions of short reads from a single massively parallel sequencing run. Using novel algorithms, we automatically construct a highly accurate transcript catalog. Our approach automatically and fully defines 86% of the genes expressed under the given conditions, and discovers 160 previously undescribed transcription units of 250 bp or longer. It correctly demarcates the 5′ and 3′ UTR boundaries of 86 and 77% of expressed genes, respectively. The method further identifies 83% of known splice junctions in expressed genes, and discovers 25 previously uncharacterized introns, including 2 cases of condition-dependent intron retention. Our framework is applicable to poorly understood organisms, and can lead to greater understanding of the transcribed elements in an explored genome.
A systems biology understanding of the synergistic effects of arsenic sulfide and Imatinib in BCR/ABL-associated leukemia
Authors: Zhang Qun-Ye , Mao Jian-Hua , Liu Ping , Huang Qiu-Hua , Lu Jing , Xie Yin-Yin , Weng Lin , Zhang Yan , Chen Quan , Chen Sai-Juan , Chen Zhu
Published: February 2009

In this study, we show that combined use of Imatinib (IM) and arsenic sulfide [As
4
S
4
(AS)] exerts more profound therapeutic effects in a
BCR
/
ABL
-positive mouse model of chronic myeloid leukemia (CML) than either drug as a single agent. A systematic analysis of dynamic changes of the proteome, phosphoproteome, and transcriptome in K562 cells after AS and/or IM treatment was performed to address the mechanisms underlying this synergy. Our data indicate that AS promotes the activities of the unfolded protein reaction (UPR) and ubiquitination pathway, which could form the biochemical basis for the pharmacological effects of this compound. In this CML model, AS targets BCR/ABL through the ubiquitination of key lysine residues, leading to its proteasomal degradation, whereas IM inhibits the PI3K/AKT/mTOR pathway. Combination of the 2 agents synergistically arrests the cell cycle, decreases activity of BCR/ABL, and leads to activation of intrinsic and extrinsic apoptosis pathways through complex modifications to both transcription and protein levels. Thus, these results suggest potential clinical benefits of IM/AS combination therapy for human CML.
Generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interest
Authors: Emonet Sebastien F. , Garidou Lucile , McGavern Dorian B. , de la Torre Juan C.
Published: February 2009

Several arenaviruses cause hemorrhagic fever disease in humans for which no licensed vaccines are available and current therapeutic intervention is limited to the off-label use of the wide-spectrum antiviral ribavirin. However, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has proven to be a Rosetta stone for the investigation of virus–host interactions. Arenaviruses have a bisegmented negative-strand RNA genome. The S segment encodes for the virus nucleoprotein and glycoprotein, whereas the L segment encodes for the virus polymerase (L) and Z protein. The ability to generate recombinant LCMV (rLCMV) expressing additional foreign genes of interest would open novel avenues for the study of virus–host interactions and the development of novel vaccine strategies and high-throughput screens to identify antiarenaviral molecules. To this end, we have developed a trisegmented (1L + 2S) rLCMV-based approach (r3LCMV). Each of the two S segments in r3LCMV was altered to replace one of the viral genes by a gene of interest. All r3LCMVs examined expressing different reported genes were stable both genetically and phenotypically and exhibited wild-type growth properties in cultured cells. Reporter gene expression in r3LCMV-infected cells provided an accurate surrogate of levels of virus multiplication. Notably, some r3LCMVs displayed highly attenuated virulence in mice but induced protective immunity against a subsequent lethal challenge with wild-type LCMV, supporting the potential development of r3LCMV-based vaccines.
EphA2 Engages Git1 to Suppress Arf6 Activity Modulating Epithelial Cell–Cell Contacts
Authors: Miura Koichi , Nam Jin-Min , Kojima Chie , Mochizuki Naoki , Sabe Hisataka
Published: February 2009

ADP-ribosylation factor (Arf) 6 activity is crucially involved in the regulation of E-cadherin–based cell–cell adhesions. Erythropoietin-producing hepatocellular carcinoma (Eph)-family receptors recognize ligands, namely, ephrins, anchored to the membrane of apposing cells, and they mediate cell–cell contact-dependent events. Here, we found that Arf6 activity is down-regulated in Madin-Darby canine kidney cells, which is dependent on cell density and calcium ion concentration, and we provide evidence of a novel signaling pathway by which ligand-activated EphA2 suppresses Arf6 activity. This EphA2-mediated suppression of Arf6 activity was linked to the induction of cell compaction and polarization, but it was independent of the down-regulation of extracellular signal-regulated kinase 1/2 kinase activity. We show that G protein-coupled receptor kinase-interacting protein (Git) 1 and noncatalytic region of tyrosine kinase (Nck) 1 are involved in this pathway, in which ligand-activated EphA2, via its phosphorylated Tyr594, binds to the Src homology 2 domain of Nck1, and then via its Src homology 3 domain binds to the synaptic localizing domain of Git1 to suppress Arf6 activity. We propose a positive feedback loop in which E-cadherin–based cell–cell contacts enhance EphA-ephrinA signaling, which in turn down-regulates Arf6 activity to enhance E-cadherin–based cell–cell contacts as well as the apical-basal polarization of epithelial cells.
Vps41 Phosphorylation and the Rab Ypt7 Control the Targeting of the HOPS Complex to Endosome–Vacuole Fusion Sites
Authors: Cabrera Margarita , Ostrowicz Clemens W. , Mari Muriel , LaGrassa Tracy J. , Reggiori Fulvio , Ungermann Christian
Published: February 2009

Membrane fusion depends on multisubunit tethering factors such as the vacuolar HOPS complex. We previously showed that the vacuolar casein kinase Yck3 regulates vacuole biogenesis via phosphorylation of the HOPS subunit Vps41. Here, we link the identified Vps41 phosphorylation site to HOPS function at the endosome–vacuole fusion site. The nonphosphorylated Vps41 mutant (Vps41 S-A) accumulates together with other HOPS subunits on punctate structures proximal to the vacuole that expand in a class E mutant background and that correspond to in vivo fusion sites. Ultrastructural analysis of this mutant confirmed the presence of tubular endosomal structures close to the vacuole. In contrast, Vps41 with a phosphomimetic mutation (Vps41 S-D) is mislocalized and leads to multilobed vacuoles, indicative of a fusion defect. These two phenotypes can be rescued by overproduction of the vacuolar Rab Ypt7, revealing that both Ypt7 and Yck3-mediated phosphorylation modulate the Vps41 localization to the endosome–vacuole junction. Our data suggest that Vps41 phosphorylation fine-tunes the organization of vacuole fusion sites and provide evidence for a fusion “hot spot” on the vacuole limiting membrane.
Right Atrial Tumor
Authors: Bakir Ihsan , Van Vaerenbergh Geert , Deshpande Ranjit , Coddens Jose , Vanermen Hugo
Published: February 2009

Cardiac tumors are rarely observed. The incidence of primary cardiac tumors in autopsy series ranges from 0.0017% to 0.19%.1,2 Surgical resection is the main therapy for the majority of the cardiac tumors. Surgical treatment of these tumors carries an operative mortality rate of 3% or less.4 In this article, we present our experience with a female patient, who had a right sided atrial tumor mimicking a myxoma. Port access surgery was performed through a small right sided “key-hole” working port in the fourth intercostal space. Extracorporeal circulation was conducted by femoro-femoral bypass and a kinetic assisted venous drainage system. Although, the safety and efficacy of port access approach have been well documented for resection of left atrial tumors in some series,14,17 use of this technique for right atrial tumor resection can be detrimental.
Intra–aortic Filtration in Cardiac Surgery
Authors: Schmitz Christoph , Binder Konrad , Bonatti Johannes O. , van Boven Wim Jan , Glauber Mattia , Mestres Carlos A. , Wimmer-Greinecker Gerhard
Published: February 2009

Cardiac surgery is associated with a significant risk of adverse outcomes, particularly neurologic and renal. Embolic events are the primary source of these deleterious consequences. Intraaortic filtration is the only current technology shown to effectively capture particulates released during cardiac procedures and decrease morbidity and mortality. Although most surgical candidates may potentially benefit from intraaortic filtration, some patients are more likely to experience improved outcomes. Based on the evidence reported in the literature and the extensive experience of the authors, the following opinion details the authors’ rationale and recommendations for patient selection for intraaortic filtration during cardiac surgery.
Tendril-lessRegulates Tendril Formation in Pea Leaves
Authors: Hofer Julie , Turner Lynda , Moreau Carol , Ambrose Mike , Isaac Peter , Butcher Susan , Weller James , Dupin Adeline , Dalmais Marion , Le Signor Christine , Bendahmane Abdelhafid , Ellis Noel
Published: February 2009

Tendrils are contact-sensitive, filamentous organs that permit climbing plants to tether to their taller neighbors. Tendrilled legume species are grown as field crops, where the tendrils contribute to the physical support of the crop prior to harvest. The homeotic tendril-less (tl) mutation in garden pea (Pisum sativum), identified almost a century ago, transforms tendrils into leaflets. In this study, we used a systematic marker screen of fast neutron–generated tl deletion mutants to identify Tl as a Class I homeodomain leucine zipper (HDZIP) transcription factor. We confirmed the tendril-less phenotype as loss of function by targeting induced local lesions in genomes (TILLING) in garden pea and by analysis of the tendril-less phenotype of the t mutant in sweet pea (Lathyrus odoratus). The conversion of tendrils into leaflets in both mutants demonstrates that the pea tendril is a modified leaflet, inhibited from completing laminar development by Tl. We provide evidence to show that lamina inhibition requires Unifoliata/LEAFY-mediated Tl expression in organs emerging in the distal region of the leaf primordium. Phylogenetic analyses show that Tl is an unusual Class I HDZIP protein and that tendrils evolved either once or twice in Papilionoid legumes. We suggest that tendrils arose in the Fabeae clade of Papilionoid legumes through acquisition of the Tl gene.
A note on medieval microfabrication: the visualization of a prayer nut by synchrotron-based computer X-ray tomography
Authors: Reischig Peter , Blaas Jorik , Botha Charl , Bravin Alberto , Porra Liisa , Nemoz Christian , Wallert Arie , Dik Joris
Published: February 2009

One of the most fascinating objects in the Rijksmuseum (Amsterdam, The Netherlands) is an early 16th century prayer nut. This spherical wooden object measures 4 cm in diameter and consists of two hemispheres connected with a small hinge so that it can be opened. The interior of the nut holds wood carvings with scenes from the life of Christ. These miniature reliefs show an incredible degree of finish with carving details well beyond the millimetre scale. In the present paper it is shown how synchrotron-based computer X-ray tomography revealed the structure and fabrication method of the bead. The central part of the relief was cut from a single piece of wood, rather than assembled from multiple components, underlining the extraordinary manual dexterity of its maker. In addition, a piece of fibrous material contained in the inner structure of the bead is revealed. This may have served as a carrier for an odorous compound, which would be in line with the religious function of the prayer nut.
The effect of esmolol on the QTc interval during induction of anaesthesia in patients with coronary artery disease
Authors: Erdil F. , Demirbilek S. , Begec Z. , Ozturk E. , But A. , Ozcan Ersoy M.
Published: February 2009

The aim of this study was to evaluate whether esmolol has an effect on QT interval during induction of anaesthesia using etomidate and fentanyl in patients with known coronary artery disease. Sixty patients were prospectively randomised to either a control group or the esmolol group. Esmolol was administered as a bolus 1 mg.kg−1, followed by a continuous infusion at 250 μg.kg−1min−1. All patients received etomidate 0.3 mg.kg−1 and fentanyl 15 μg.kg−1. The ECG was recorded prior to induction of anaesthesia (T0), 5 min following the start of drug infusions (T1), 1 min following etomidate (T2), 3 min following vecuronium (T3), 30 s (T4), 2 min (T5) and 4 min (T6) after intubation. In the esmolol group, QTc interval was significantly shorter at T1, T2 and T4 compared to the control group (p < 0.05). In conclusion, QTc interval increased following tracheal intubation during induction of anaesthesia using etomidate and fentanyl. An infusion of Esmolol attenuated the QTc interval prolongation associated with tracheal intubation.
Optimising tracheal intubation success rate using the Airtraq laryngoscope
Authors: Dhonneur G. , Abdi W. , Amathieu R. , Ndoko S. , Tual L.
Published: February 2009

In this study we have used a video‐recording, retrospective analysis technique to evaluate the influence of the Airtraq™ laryngoscope manipulations and the resulting changes in position of the glottic opening and inter‐arytenoids cleft, on the success rate of tracheal intubation. The video recordings of the internal views of 109 tracheal intubation attempts, in 50 anaesthetised patients were analysed. We demonstrated that successful tracheal intubation using the Airtraq laryngoscope require the glottic opening to be centred in the view, and positioning the inter‐arytenoid cleft medially below the horizontal line in the centre of the view. We also demonstrated that repositioning of the Airtraq laryngoscope following a failed tracheal intubation attempt required the performance of a standard series of manoeuvres.
Assessing the performance of a consultant anaesthetist by control chart methodology*
Authors: Runcie C. J.
Published: February 2009

The performance of trainee anaesthetists has been assessed by control chart methodology, but while assessment of consultants’ performance has been suggested, published reports are rare. In order to test the value of control charts, I monitored my insertion of arterial and central venous cannulae over 3 years, documenting success or failure both for the first pass of the needle and for the intended site of cannulation. The resultant control charts clearly show episodes of changed performance. It was necessary to modify the technique used to assess trainees, specifically with relation to definitions of success, failure and ‘acceptable’ failure rates. The information obtained from these charts is well suited to inform an appraisal or revalidation discussion with both reflective and assessment elements.
Advances in the understanding of dyskeratosis congenita
Authors: Walne Amanda J. , Dokal Inderjeet
Published: February 2009

Dyskeratosis congenita (DC) is a rare inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is characterised by mucocutaneous abnormalities, bone marrow failure and a predisposition to cancer. Bone marrow failure is the principal cause of premature mortality. Studies over the last 10 years have demonstrated that DC is principally a disease of defective telomere maintenance. All DC patients have very short telomeres and the genetically characterised cases of DC have mutations in six genes which either encode components of the telomerase complex (DKC1, TERC, TERT, NOP10, NHP2) or shelterin (TINF2); these are important in the elongation and protection of the telomeric end, respectively. These advances have led to the recognition of cryptic forms of DC, such as presentations with aplastic anaemia and myelodysplasia. They have also increased our understanding of normal haematopoiesis and provided new insights to the aetiology of some cases of aplastic anaemia and related haematological disorders.
The effect of proteasome inhibitor MG132 on experimental inflammatory bowel disease
Authors: Inoue S , Nakase H , Matsuura M , Mikami S , Ueno S , Uza N , Chiba T
Published: February 2009

Immunoproteasome up-regulation enhances the processing of nuclear factor-κB (NF-κB) and degradation of IκBα, which correlates with increased amounts of NF-κB in the various cells. Aberrant activation of NF-κB is involved in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to elucidate the effect of proteasome inhibitor MG132 on experimental IBD. We investigated the effects of MG132 on intestinal inflammation and epithelial regeneration in both interleukin-10-deficient (IL-10−/−) mice and mice with dextran sulphate sodium (DSS)-induced colitis. Body weight, histological findings and tumour necrosis factor (TNF)-α mRNA expression, epithelial cell proliferation and NF-κB p65 activity in colonic tissues were examined. The effects of MG132 on cell proliferation, migration and multiple drug resistance 1 (MDR1) gene expression were determined in vitro. MG132 ameliorated intestinal inflammation of IL-10−/− mice by decreasing TNF-α mRNA expression in the colonic tissues, which was associated with suppression of NF-κB activation, and reduced significantly the number of Ki-67-positive intestinal epithelial cells. On the other hand, MG132 did not reduce intestinal inflammation in mice with DSS-induced colitis, and delayed significantly the recovery of body weight and epithelial regeneration. MG132 also suppressed significantly epithelial cell proliferation, cell migration and MDR1 gene expression in vitro. Proteasome inhibition reduces T cell-mediated intestinal inflammation, but may interrupt both epithelial regeneration and barrier function of colonic mucosa. Optimal use of proteasome inhibitor should be kept in mind when we consider its clinical application for patients with IBD.
Antioxidants in soil organic matter and in associated plant materials
Authors: Rimmer D. L. , Smith A. M.
Published: February 2009

The presence of antioxidants in soil could have a significant effect on the dynamics of soil organic matter. In this paper we report some preliminary experiments, which demonstrate that antioxidants can be extracted from soils and that the quantities vary from soil to soil. Extraction with 1.0 m NaOH was effective, and this was then used on a range of mineral and organic soils, and the antioxidant capacity of the resulting extracts was measured. The antioxidant capacities obtained were positively correlated with soil carbon contents and with the dissolved organic carbon contents of the extracts. Expressing the data per mass of soil carbon showed that the antioxidants generally decreased with depth in the soil profile, suggesting that they were subject to degradation during humification. In a follow‐up study, soil, litter and fresh plant samples were collected from 15 sites with a wide variety of vegetation types and analysed for their antioxidant capacities. The aim was to show that the antioxidant capacities in the soils were related to the antioxidant capacities of the fresh plant material and/or litter above. The antioxidant capacities of the soil samples were less than those in either fresh material or litter. While there was a significant positive relationship between the antioxidant capacities of fresh material and litter, no relationship existed between the antioxidant capacities of the soils and those of either fresh material or litter.