bluuebunny/crossref_metadata_2025 huggingface dataset:
No Association Between Leptin Levels and Sleep Duration or Quality in Obese Adults
Authors: Knutson Kristen L. , Galli Giulia , Zhao Xiongce , Mattingly Megan , Cizza Giovanni ,   ; for the NIDDK Sleep Extension Study
Published: July 2011

Previous research in lean subjects has found lower leptin levels associated with shorter sleep duration. Since leptin levels are higher and some of the actions of leptin are impaired in obese individuals, one cannot assume that sleep will be similarly associated with leptin in obese individuals. The aim of this paper was to examine the cross‐sectional association between habitual sleep duration and quality and plasma leptin levels in a sample of 80 obese men and premenopausal women aged 18–50 years. Leptin levels (ng/ml) were assayed on a fasting blood sample taken in the morning. We calculated a relative leptin level by dividing leptin by body fat percentage. Sleep duration and sleep efficiency were measured by 2 weeks of wrist actigraphy and respiratory disturbance index (RDI), a measure of sleep disordered breathing, was assessed by a portable screening device on a single night. Mean leptin levels and body fat percentage were higher in women than men (P < 0.001), however, mean RDI was higher in men (P = 0.01). There were no significant associations between relative leptin level and any of the sleep measures, including sleep duration, sleep efficiency, and sleep disordered breathing. There was also no difference between men and women in the association between sleep and leptin. In conclusion, contrary to what has been reported in other studies, measures of sleep duration and quality were not associated with leptin levels in our sample of obese adults.
The Central Cannabinoid CB1 Receptor Is Required for Diet‐Induced Obesity and Rimonabant's Antiobesity Effects in Mice
Authors: Pang Zhen , Wu Nancy N. , Zhao Weiguang , Chain David C. , Schaffer Erica , Zhang Xin , Yamdagni Preeti , Palejwala Vaseem A. , Fan Chunpeng , Favara Sarah G. , Dressler Holly M. , Economides Kyriakos D. , Weinstock Daniel , Cavallo Jean S. , Naimi Souad , Galzin Anne‐Marie , Guillot Etienne , Pruniaux Marie‐Pierre , Tocci Michael J. , Polites H. Greg
Published: July 2011

Cannabinoid receptor CB1 is expressed abundantly in the brain and presumably in the peripheral tissues responsible for energy metabolism. It is unclear if the antiobesity effects of rimonabant, a CB1 antagonist, are mediated through the central or the peripheral CB1 receptors. To address this question, we generated transgenic mice with central nervous system (CNS)–specific knockdown (KD) of CB1, by expressing an artificial microRNA (AMIR) under the control of the neuronal Thy1.2 promoter. In the mutant mice, CB1 expression was reduced in the brain and spinal cord, whereas no change was observed in the superior cervical ganglia (SCG), sympathetic trunk, enteric nervous system, and pancreatic ganglia. In contrast to the neuronal tissues, CB1 was undetectable in the brown adipose tissue (BAT) or the liver. Consistent with the selective loss of central CB1, agonist‐induced hypothermia was attenuated in the mutant mice, but the agonist‐induced delay of gastrointestinal transit (GIT), a primarily peripheral nervous system‐mediated effect, was not. Compared to wild‐type (WT) littermates, the mutant mice displayed reduced body weight (BW), adiposity, and feeding efficiency, and when fed a high‐fat diet (HFD), showed decreased plasma insulin, leptin, cholesterol, and triglyceride levels, and elevated adiponectin levels. Furthermore, the therapeutic effects of rimonabant on food intake (FI), BW, and serum parameters were markedly reduced and correlated with the degree of CB1 KD. Thus, KD of CB1 in the CNS recapitulates the metabolic phenotype of CB1 knockout (KO) mice and diminishes rimonabant's efficacy, indicating that blockade of central CB1 is required for rimonabant's antiobesity actions.
Performance analysis of W-shaped rib roughened solar air heater
Authors: Lanjewar Atul Manikrao , Bhagoria Jiwan Lal , Sarviya Rishindra Mohan
Published: July 2011

Artificial rib roughness is a convenient method for enhancing thermal performance of solar air heater. An experimental investigation has been carried out to study the thermo-hydraulic performance of solar air heater using W-shaped ribs on absorber plate, the roughened wall being heated while the remaining three walls being insulated. W-shaped ribs have been tested both pointing downstream (W-down) and upstream (W-up) to the flow. The roughened wall has relative roughness height (e/Dh) of 0.03375, relative roughness pitch (p/e) of 10 and duct aspect ratio (B/H) of 8. The airflow rate corresponds to Reynolds number between 2300 and 14 000. The heat transfer results have been compared with those for smooth duct under similar flow and thermal boundary condition. Thermo-hydraulic performance ratio of roughened absorber plate by providing W-shape roughness is in the range of 1.46–1.95 for W-down and 1.21–1.73 for W-up ribs. Friction factor and heat transfer coefficient correlations have been developed based on the law of wall similarity and heat-momentum transfer analogy.
A comparative study of single and double pulse of laser induced breakdown spectroscopy of silver
Authors: Rashid Babar , Ahmed Rizwan , Ali Raheel , Baig M. A.
Published: July 2011

We present a comparative study of the collinear and orthogonal pre-ablation dual pulse configurations of laser induced breakdown spectroscopy (LIBS) of silver using Nd:YAG lasers. The effect of the inter-pulse delay and the ratio of the laser pulse energies on the signal intensity enhancement for both the dual pulse configurations have been investigated. Using the first laser at 532 nm and second laser at 1064 nm delayed by 5 μs, we achieved nearly 2 times signal enhancement in the collinear double-pulsed configuration and nearly 12 times in the pre-ablation orthogonal configuration as compared to SP LIBS. It is ascertained that at the optimized value of the inter-pulse delay between the two lasers, the intensity ratio of the neutral silver lines follows the local thermo dynamical equilibrium (LTE) condition and it is also in excellent agreement with that of the relative transitions probabilities ratio listed in the NIST data base.
Intrinsic rotation generation in ELM-free H-mode plasmas in the DIII-D tokamak—Experimental observations
Authors: Müller S. H. , Boedo J. A. , Burrell K. H. , deGrassie J. S. , Moyer R. A. , Rudakov D. L. , Solomon W. M. , Tynan G. R.
Published: July 2011

A detailed description is presented of the experiment reported in [S. H. Müller et al., Phys. Rev. Lett. 106, 115001 (2011)], which reported the first measurements of fluid turbulent stresses in a tokamak H-mode pedestal. Mach probe measurements disclosed a narrow co-current rotation layer at the separatrix, which is also seen in some L-modes [J. A. Boedo et al., Phys. Plasmas 18, 032510 (2011)]. Independent evidence for the existence of the edge co-rotation layer is presented from main-ion rotation measurements by charge-exchange-recombination spectroscopy in comparable helium plasmas. The probe measurements are validated against density and electron temperature profiles from Thomson scattering and in terms of the measured turbulent particle transport, which is consistent with the global density rise. Non-diffusive non-convective angular momentum transport is required by two independent experimental observations: (1) A persistent dip in the rotation profile separates the edge layer from the evolving core region during intrinsic rotation development. (2) The rotation profiles with co- and counter-current neutral beam injection appear well described as the simple sum of a constant intrinsic part and the beam-driven part, also demonstrating the profile-independence of the intrinsic torque. Characteristics of the turbulent fluctuations composing the fluid turbulent stresses are discussed: Up to 0.5 cm inside the separatrix, the low amplitude of the Reynolds stress (<0.05 Nm of torque) is due to both a reduction of the fluctuation amplitudes at the peak of the edge co-rotation layer and weak correlations between the toroidal and radial velocity fluctuations. Further into the core, the correlations increase significantly up to a value of +0.75, resulting in an almost unidirectional character of the turbulent Reynolds stress, generating substantial counter-current torques up to −2 Nm. Additional mechanisms must be present to balance these torques and explain the co-current core-plasma spin-up at a rate of +0.3 Nm.
Coalescence collision of liquid drops I: Off-center collisions of equal-size drops
Authors: Acevedo-Malavé Alejandro , García-Sucre Máximo
Published: July 2011

The Smoothed Particle Hydrodynamics method (SPH) is used here to model off-center collisions of equal-size liquid drops in a three-dimensional space. In this study the Weber number is calculated for several conditions of the droplets dynamics and the velocity vector fields formed inside the drops during the collision process are shown. For the permanent coalescence the evolution of the kinetic and internal energy is shown and also the approaching to equilibrium of the resulting drop. Depending of the Weber number three possible outcomes for the collision of droplets is obtained: permanent coalescence, flocculation and fragmentation. The fragmentation phenomena are modeled and the formation of small satellite drops can be seen. The ligament that is formed follows the “end pinching” mechanism and it is transformed into a flat structure.
Seedling recruitment of native perennial grasses within existing swards
Authors: Thapa R. , Kemp D. R. , Michalk D. L. , Badgery W. B. , Simmons A. T.
Published: July 2011

Two field experiments, one each on Austrodanthonia spp. and Bothriochloa macra, investigated the effects of biomass manipulation, seed level modification, site preparation and pasture composition on the recruitment of native perennial grass seedlings. The experiments coincided with drier than average years and although successful emergence of seedlings occurred, survival was extremely low. In the Austrodanthonia experiment, control treatments resulted in the emergence of only 1 seedling/m2, whereas there were 130/m2 in the best treatment which had biomass cut with plant material removed, seed added, and the soil surface scarified. Insecticide treatments increased emergence as seed-harvesting ants are common in these systems, but the benefits were small. Similarly, B. macra had no emergence in the control treatment compared with 73 seedlings/m2 in the best treatment, which was pasture cropped, and had seed added and herbicide applied. Availability of microsites may be a major constraint to B. macra emergence, as soil disturbance through pasture cropping substantially increased seedling numbers (279/m2). The effects of herbicide on emergence were small with the largest being related to bare ground and litter biomass. Austrodanthonia seedling numbers at emergence were related to bare ground, litter and green biomass. Survival of young Austrodanthonia plants 24 weeks after emergence was negatively related to plant cover, but only in treatments where plant material was cut and removed. The success of survival was determined at 52 weeks after emergence and the number of young plants that survived in both experiments seemed to have been influenced by the presence of competitive biomass of existing plants.
Seasonal distribution of loline alkaloid concentration in meadow fescue infected with Neotyphodium uncinatum
Authors: Patchett Brian , Gooneratne Ravi , Fletcher Lester , Chapman Bruce
Published: July 2011

Loline alkaloids are present in meadow fescue containing the endophyte (Neotyphodium uncinatum Gams, Petrini and Schmidt) (Clavicipitacae). Root, crown and shoot loline alkaloid concentrations in 10 selected lines from meadow fescue ecotypes are reported for the first time, from a Canterbury farm during 2004–05. The concentrations of four loline alkaloid derivatives, N-formyl loline (NFL), N-acetyl loline (NAL), N-acetyl norloline (NANL) and N-methyl loline (NML), in these lines (each line represented by one genotype) were determined at four harvest dates during late spring, late summer, and early and late autumn. There were marked differences in loline alkaloid concentration between lines and seasons. Maximum shoot loline concentration was recorded in summer (up to 2860 µg/g in Fp408). Root loline alkaloid concentration was substantially higher in late autumn (up to 790 µg/g in Fp408) and the shoot concentration correspondingly lower than in spring, summer and early autumn suggesting loline alkaloid transportation from shoots to roots. In the lines tested at each of the four harvest dates in spring, summer, and autumn, the root, crown, and shoot alkaloid concentration with minor exceptions was NFL > NAL > NANL > NML.
Genetic gain in yield and associated changes in phenotype, trait plasticity and competitive ability of South Australian wheat varieties released between 1958 and 2007
Authors: Sadras Victor O. , Lawson Chris
Published: July 2011

To quantify the genetic gain in yield and associated changes in phenotype, we compared 13 South Australian wheat varieties released between 1958 and 2007. Crops were grown in three environments with a range of yield between 4.1 and 6.1 t/ha. Yield increased linearly with year of cultivar release at a rate of 25 ± 3.4 kg/ha per year. Yield improvement was associated with a linear increase in harvest index over the whole period 1958–2007 and increased shoot biomass for varieties released after the early 1980s. A non-linear model with an inflection point at 1982 ± 1.6 emphasised two phases in the time trend of grain size: it decreased between 1957 and 1982 and increased afterwards. The plasticity of grain size increased 2-fold after 1982. Grain number increased until the early 1980s and stabilised afterwards. Grain number was associated with crop growth rate between stem elongation and anthesis, and grain size was associated with crop growth rate per grain. Crop growth rate between stem elongation and anthesis increased after the early 1980s in parallel with increased radiation-use efficiency and independently of changes in capture of radiation. Candidate traits to explain the improvement in radiation-use efficiency include increased stomatal conductance and greener leaves. The concentration of water-soluble carbohydrates in shoots at anthesis increased with year of cultivar release at 0.12 ± 0.018% per year. In two out of three environments, yield response to competition declined with year of cultivar release, which was consistent with the communal plant ideotype.
Spatial and temporal second messenger codes for growth cone turning
Authors: Nicol Xavier , Hong Kwan Pyo , Spitzer Nicholas C.
Published: July 2011

Cyclic AMP (cAMP) and calcium are ubiquitous, interdependent second messengers that regulate a wide range of cellular processes. During development of neuronal networks they are critical for the first step of circuit formation, transducing signals required for axon pathfinding. Surprisingly, the spatial and temporal cAMP and calcium codes used by axon guidance molecules are unknown. Here, we identify characteristics of cAMP and calcium transients generated in growth cones during Netrin-1–dependent axon guidance. In filopodia, Netrin-1–dependent Deleted in Colorectal Cancer (DCC) receptor activation induces a transient increase in cAMP that causes a brief increase in calcium transient frequency. In contrast, activation of DCC in growth cone centers leads to a transient calcium-dependent cAMP increase and a sustained increase in frequency of calcium transients. We show that filopodial cAMP transients regulate spinal axon guidance in vitro and commissural axon pathfinding in vivo. These growth cone codes provide a basis for selective activation of specific downstream effectors.
Comparing the role of absolute sea-level rise and vertical tectonic motions in coastal flooding, Torres Islands (Vanuatu)
Authors: Ballu Valérie , Bouin Marie-Noëlle , Siméoni Patricia , Crawford Wayne C. , Calmant Stephane , Boré Jean-Michel , Kanas Tony , Pelletier Bernard
Published: July 2011

Since the late 1990s, rising sea levels around the Torres Islands (north Vanuatu, southwest Pacific) have caused strong local and international concern. In 2002–2004, a village was displaced due to increasing sea incursions, and in 2005 a United Nations Environment Programme press release referred to the displaced village as perhaps the world’s first climate change “refugees.” We show here that vertical motions of the Torres Islands themselves dominate the apparent sea-level rise observed on the islands. From 1997 to 2009, the absolute sea level rose by 150 + /-20 mm. But GPS data reveal that the islands subsided by 117 + /-30 mm over the same time period, almost doubling the apparent gradual sea-level rise. Moreover, large earthquakes that occurred just before and after this period caused several hundreds of mm of sudden vertical motion, generating larger apparent sea-level changes than those observed during the entire intervening period. Our results show that vertical ground motions must be accounted for when evaluating sea-level change hazards in active tectonic regions. These data are needed to help communities and governments understand environmental changes and make the best decisions for their future.
Protein–protein interface-binding peptides inhibit the cancer therapy target human thymidylate synthase
Authors: Cardinale Daniela , Guaitoli Giambattista , Tondi Donatella , Luciani Rosaria , Henrich Stefan , Salo-Ahen Outi M. H. , Ferrari Stefania , Marverti Gaetano , Guerrieri Davide , Ligabue Alessio , Frassineti Chiara , Pozzi Cecilia , Mangani Stefano , Fessas Dimitrios , Guerrini Remo , Ponterini Glauco , Wade Rebecca C. , Costi M. Paola
Published: July 2011

Human thymidylate synthase is a homodimeric enzyme that plays a key role in DNA synthesis and is a target for several clinically important anticancer drugs that bind to its active site. We have designed peptides to specifically target its dimer interface. Here we show through X-ray diffraction, spectroscopic, kinetic, and calorimetric evidence that the peptides do indeed bind at the interface of the dimeric protein and stabilize its di-inactive form. The “LR” peptide binds at a previously unknown binding site and shows a previously undescribed mechanism for the allosteric inhibition of a homodimeric enzyme. It inhibits the intracellular enzyme in ovarian cancer cells and reduces cellular growth at low micromolar concentrations in both cisplatin-sensitive and -resistant cells without causing protein overexpression. This peptide demonstrates the potential of allosteric inhibition of hTS for overcoming platinum drug resistance in ovarian cancer.
The Ataxin-2 protein is required for microRNA function and synapse-specific long-term olfactory habituation
Authors: McCann Cathal , Holohan Eimear E. , Das Sudeshna , Dervan Adrian , Larkin Aoife , Lee John Anthony , Rodrigues Veronica , Parker Roy , Ramaswami Mani
Published: July 2011

Local control of mRNA translation has been proposed as a mechanism for regulating synapse-specific plasticity associated with long-term memory. We show here that glomerulus-selective plasticity of
Drosophila
multiglomerular local interneurons observed during long-term olfactory habituation (LTH) requires the Ataxin-2 protein (Atx2) to function in uniglomerular projection neurons (PNs) postsynaptic to local interneurons (LNs). PN-selective knockdown of Atx2 selectively blocks LTH to odorants to which the PN responds and in addition selectively blocks LTH-associated structural and functional plasticity in odorant-responsive glomeruli. Atx2 has been shown previously to bind DEAD box helicases of the Me31B family, proteins associated with Argonaute (Ago) and microRNA (miRNA) function. Robust transdominant interactions of
atx2
with
me31B
and
ago1
indicate that Atx2 functions with miRNA-pathway components for LTH and associated synaptic plasticity. Further direct experiments show that Atx2 is required for miRNA-mediated repression of several translational reporters in vivo. Together, these observations (
i
) show that Atx2 and miRNA components regulate synapse-specific long-term plasticity in vivo; (
ii
) identify Atx2 as a component of the miRNA pathway; and (
iii
) provide insight into the biological function of Atx2 that is of potential relevance to spinocerebellar ataxia and neurodegenerative disease.
Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer
Authors: Chang Kai-Hsiung , Li Rui , Papari-Zareei Mahboubeh , Watumull Lori , Zhao Yan Daniel , Auchus Richard J. , Sharifi Nima
Published: July 2011

In the majority of cases, advanced prostate cancer responds initially to androgen deprivation therapy by depletion of gonadal testosterone. The response is usually transient, and metastatic tumors almost invariably eventually progress as castration-resistant prostate cancer (CRPC). The development of CRPC is dependent upon the intratumoral generation of the potent androgen, dihydrotestosterone (DHT), from adrenal precursor steroids. Progression to CRPC is accompanied by increased expression of steroid-5α-reductase isoenzyme-1 (SRD5A1) over SRD5A2, which is otherwise the dominant isoenzyme expressed in the prostate. DHT synthesis in CRPC is widely assumed to require 5α-reduction of testosterone as the obligate precursor, and the increased expression of SRD5A1 is thought to reflect its role in converting testosterone to DHT. Here, we show that the dominant route of DHT synthesis in CRPC bypasses testosterone, and instead requires 5α-reduction of androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT. This alternative pathway is operational and dominant in both human CRPC cell lines and fresh tissue obtained from human tumor metastases. Moreover, CRPC growth in mouse xenograft models is dependent upon this pathway, as well as expression of SRD5A1. These findings reframe the fundamental metabolic pathway that drives CRPC progression, and shed light on the development of new therapeutic strategies.
Crossed ratchet effects on magnetic domain walls: geometry and transverse field effects
Authors: Alija A , Hierro-Rodríguez A , Pérez-Junquera A , Alameda J M , Martín J I , Vélez M
Published: July 2011

Domain wall propagation across a 2D array of asymmetric holes is strongly dependent on the domain wall configuration: i.e. on whether the wall is flat or kinked. This results in interesting crossed ratchet and asymmetric accommodation effects that have been studied as a function of geometry and transverse field. Micromagnetic simulations have shown that the observation of crossed ratchet effects is easier for arrow than for triangular holes due to a larger field range in which kink propagation is the preferred mode for domain wall motion. Also, it has been found that dc transverse fields can produce a significant enhancement of the easy axis asymmetric accommodation and, also, that ac transverse fields can be rectified by the crossed ratchet potential.
Polarization-independent plasmon-induced transparency for plasmonic sensing
Authors: Chen Zhihong , Dai Lei , Jiang Chun
Published: July 2011

We design a three-dimensional structure consisting of cross-slit metallic photonic crystals and dielectric photonic crystals embedded in a background material to achieve electromagnetically induced transparency for TE/TM polarization modes. Numerical simulation demonstrates that the mechanism of this phenomenon is based on the coupling effect between the excited surface plasmonic mode and waveguide mode supported by metallic and dielectric photonic crystals, respectively. In particular, one of the transmission dips of the system is very sensitive to the background material, where the sensitivity (nm/RIU) of the system is more than 700 nm/RIU. Meanwhile, polarization-independent transparency of the structure makes our system possess great potential for achieving high-performance sensors.
Electronic structure at the interfaces of vertically aligned zinc oxide nanowires and sensitizing layers in photochemical solar cells
Authors: Chen Z H , Liu C P , Wang H E , Tang Y B , Liu Z T , Zhang W J , Lee S T , Zapien J A , Bello I
Published: July 2011

Vertically aligned zinc oxide (ZnO) nanowires (NWs) coated with cadmium telluride (CdTe) shell layers via simple evaporation have been used to fabricate photochemical solar cells. The narrow bandgap of CdTe (∼1.45 eV) enhances the optical absorption in the range of visible light. The detailed electronic structures of ZnO/CdTe and ZnO/Dye were investigated and compared with the aid of ultraviolet photoemission spectroscopy. The analysis shows electric dipole at the ZnO/dye interface due to Zn2+/carboxy bonding while no significant bonding existed at the ZnO/CdTe interface. The ZnO/CdTe interface is a characteristic of a small heterojunction barrier where the excited electrons can be transferred to the conduction band of ZnO NWs through defect levels. The average stable short circuit current density taken at the fifth minute of light illumination for the photochemical solar cell reaches 4.69 mA cm−2, while it is only 3.90 mA cm−2 for in situ dye sensitized solar cells.
Two-dimensional electron transport in MgZnO/ZnO heterostructures: role of interface roughness
Authors: Thongnum A , Sa-yakanit V , Pinsook U
Published: July 2011

Mobility of two-dimensional electron gases in MgZnO/ZnO heterostructures with interface roughness effects was investigated theoretically using path-integral framework. We modelled the roughness-induced fluctuation by including two major effects, i.e. the electron and polarization-induced positive charge concentrations. We showed that both effects cause the scattering potential in the in-plane direction and hence affect the 2D mobility. In this work, we treated both electron and polarization-induced positive charge concentrations as equally important factors and then calculated the electron mobility and compared with the experimental result of Mg0.2Zn0.8O/ZnO heterostructure at high-electron concentrations. We found that the fitting parameters Δ = 0.26 nm, Λ = 2.5 nm gave good description to the mobility data. We also showed that neglecting the polarization-induced positive charge concentration led to overestimating the 2D mobility.
Enhanced contrast ratio of homogeneously aligned liquid crystal displays by controlling the surface-anchoring strength
Authors: Lim Young Jin , Woo Chang Woo , Oh Sang Hoon , Mukherjee Amrita , Lee Seung Hee , Baek Ji Ho , Kim Kyeong Jin , Yang Myung Su
Published: July 2011

The dark state of homogeneously aligned liquid crystal displays (LCDs) associated with the in-plane switching of a LC director depends on their molecular ordering. We propose a new approach to reduce the light leakage in the dark state of homogeneously aligned LCDs. A very small amount of reactive mesogen (RM) is mixed with the LC material and polymerized at room temperature and also at a low temperature (−20 °C) to strengthen the surface-anchoring energy. The contrast ratio of the low-temperature cured cell is improved by about 50% over that of the pure LC cell and the room temperature cured RM-mixed LC cell due to an enhanced order parameter.
Validation of 3D multimodality roadmapping in interventional neuroradiology
Authors: Ruijters Daniel , Homan Robert , Mielekamp Peter , van de Haar Peter , Babic Drazenko
Published: July 2011

Three-dimensional multimodality roadmapping is entering clinical routine utilization for neuro-vascular treatment. Its purpose is to navigate intra-arterial and intra-venous endovascular devices through complex vascular anatomy by fusing pre-operative computed tomography (CT) or magnetic resonance (MR) with the live fluoroscopy image. The fused image presents the real-time position of the intra-vascular devices together with the patient's 3D vascular morphology and its soft-tissue context. This paper investigates the effectiveness, accuracy, robustness and computation times of the described methods in order to assess their suitability for the intended clinical purpose: accurate interventional navigation. The mutual information-based 3D–3D registration proved to be of sub-voxel accuracy and yielded an average registration error of 0.515 mm and the live machine-based 2D–3D registration delivered an average error of less than 0.2 mm. The capture range of the image-based 3D–3D registration was investigated to characterize its robustness, and yielded an extent of 35 mm and 25° for >80% of the datasets for registration of 3D rotational angiography (3DRA) with CT, and 15 mm and 20° for >80% of the datasets for registration of 3DRA with MR data. The image-based 3D–3D registration could be computed within 8 s, while applying the machine-based 2D–3D registration only took 1.5 µs, which makes them very suitable for interventional use.
S100A4-induced cell motility and metastasis is restricted by the Wnt/β-catenin pathway inhibitor calcimycin in colon cancer cells
Authors: Sack Ulrike , Walther Wolfgang , Scudiero Dominic , Selby Mike , Aumann Jutta , Lemos Clara , Fichtner Iduna , Schlag Peter M. , Shoemaker Robert H. , Stein Ulrike
Published: July 2011

The calcium-binding protein S100A4 is a central mediator of metastasis formation in colon cancer. S100A4 is a target gene of the Wnt/β-catenin pathway, which is constitutively active in the majority of colon cancers. In this study a high-throughput screen was performed to identify small-molecule compounds targeting the S100A4-promoter activity. In this screen calcimycin was identified as a transcriptional inhibitor of S100A4. In colon cancer cells calcimycin treatment reduced S100A4 mRNA and protein expression in a dose- and time-dependent manner. S100A4-induced cellular processes associated with metastasis formation, such as cell migration and invasion, were inhibited by calcimycin in an S100A4-specific manner. Calcimycin reduced β-catenin mRNA and protein levels despite the expression of Δ45-mutated β-catenin. Consequently, calcimycin inhibited Wnt/β-catenin pathway activity and the expression of prominent β-catenin target genes such as S100A4, cyclin D1, c-myc, and dickkopf-1. Finally, calcimycin treatment of human colon cancer cells inhibited metastasis formation in xenografted immunodeficient mice. Our results demonstrate that targeting the expression of S100A4 with calcimycin provides a functional strategy to restrict cell motility in colon cancer cells. Therefore calcimycin may be useful for studying S100A4 biology, and these studies may serve as a lead for the development of treatments for colon cancer metastasis.
Genetic interaction betweenCaenorhabditis elegansteneurinten-1and prolyl 4-hydroxylasephy-1and their function in collagen IV–mediated basement membrane integrity during late elongation of the embryo
Authors: Topf Ulrike , Chiquet-Ehrismann Ruth
Published: July 2011

Teneurins are a family of phylogenetically conserved proteins implicated in pattern formation and morphogenesis. The sole orthologue in Caenorhabditis elegans, ten-1, is important for hypodermal cell migration, neuronal migration, path finding and fasciculation, gonad development, and basement membrane integrity of some tissues. However, the mechanisms of TEN-1 action remain to be elucidated. Using a genome-wide RNA interference approach, we identified phy-1 as a novel interaction partner of ten-1. phy-1 codes for the catalytic domain of collagen prolyl 4-hydroxylase. Loss of phy-1 significantly enhanced the embryonic lethality of ten-1 null mutants. Double-mutant embryos arrested during late elongation with epidermal defects, disruption of basement membranes, and detachment of body wall muscles. We found that deletion of phy-1 caused aggregation of collagen IV in body wall muscles in elongated embryos and triggered the loss of tissue integrity in ten-1 mutants. In addition, phy-1 and ten-1 each genetically interact with genes encoding collagen IV. These findings support a functional mechanism in which loss of ten-1, together with a reduction of assembled and secreted basement membrane collagen IV protein, leads to detachment of the epidermis from muscle cells during late elongation of the embryo when mechanical stress is generated by muscle contractions.
An active kinase domain is required for retention of PKCθ at the T cell immunological synapse
Authors: Cartwright Natalia G. , Kashyap Anuj K. , Schaefer Brian C.
Published: July 2011

Protein kinase Cθ (PKCθ) is a serine/threonine kinase that plays an essential role in antigen-regulated responses of T lymphocytes. Upon antigen stimulation, PKCθ is rapidly recruited to the immunological synapse (IS), the region of contact between the T cell and antigen-presenting cell. This behavior is unique among T cell PKC isoforms. To define domains of PKCθ required for retention at the IS, we generated deletion and point mutants of PKCθ. We used quantitative imaging analysis to assess IS retention of PKCθ mutants in antigen-stimulated T cell clones. Deletion of the kinase domain or site-directed mutation of a subset of known PKCθ phosphorylation sites abrogated or significantly reduced IS retention, respectively. IS retention did not correlate with phosphorylation of specific PKCθ residues but rather with kinase function. Thus PKCθ catalytic competence is essential for stable IS retention.
MICAL-like1 mediates epidermal growth factor receptor endocytosis
Authors: Abou-Zeid Nancy , Pandjaitan Rudy , Sengmanivong Lucie , David Violaine , Le Pavec Gwenaelle , Salamero Jean , Zahraoui Ahmed
Published: July 2011

Small GTPase Rabs are required for membrane protein sorting/delivery to precise membrane domains. Rab13 regulates epithelial tight junction assembly and polarized membrane transport. Here we report that Molecule Interacting with CasL (MICAL)-like1 (MICAL-L1) interacts with GTP-Rab13 and shares a similar domain organization with MICAL. MICAL-L1 has a calponin homology (CH), LIM, proline rich and coiled-coil domains. It is associated with late endosomes. Time-lapse video microscopy shows that green fluorescent protein–Rab7 and mcherry-MICAL-L1 are present within vesicles that move rapidly in the cytoplasm. Depletion of MICAL-L1 by short hairpin RNA does not alter the distribution of a late endosome/lysosome-associated protein but affects the trafficking of epidermal growth factor receptor (EGFR). Overexpression of MICAL-L1 leads to the accumulation of EGFR in the late endosomal compartment. In contrast, knocking down MICAL-L1 results in the distribution of internalized EGFR in vesicles spread throughout the cytoplasm and promotes its degradation. Our data suggest that the N-terminal CH domain associates with the C-terminal Rab13 binding domain (RBD) of MICAL-L1. The binding of Rab13 to RBD disrupts the CH/RBD interaction, and may induce a conformational change in MICAL-L1, promoting its activation. Our results provide novel insights into the MICAL-L1/Rab protein complex that can regulate EGFR trafficking at late endocytic pathways.
The period of the somite segmentation clock is sensitive to Notch activity
Authors: Kim Woong , Matsui Takaaki , Yamao Masataka , Ishibashi Makoto , Tamada Kota , Takumi Toru , Kohno Kenji , Oba Shigeyuki , Ishii Shin , Sakumura Yuichi , Bessho Yasumasa
Published: July 2011

The number of vertebrae is defined strictly for a given species and depends on the number of somites, which are the earliest metameric structures that form in development. Somites are formed by sequential segmentation. The periodicity of somite segmentation is orchestrated by the synchronous oscillation of gene expression in the presomitic mesoderm (PSM), termed the “somite segmentation clock,” in which Notch signaling plays a crucial role. Here we show that the clock period is sensitive to Notch activity, which is fine-tuned by its feedback regulator, Notch-regulated ankyrin repeat protein (Nrarp), and that Nrarp is essential for forming the proper number and morphology of axial skeleton components. Null-mutant mice for Nrarp have fewer vertebrae and have defective morphologies. Notch activity is enhanced in the PSM of the Nrarp−/– embryo, where the ∼2-h segmentation period is extended by 5 min, thereby forming fewer somites and their resultant vertebrae. Reduced Notch activity partially rescues the Nrarp−/– phenotype in the number of somites, but not in morphology. Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs.
Baculovirus IAP1 induces caspase-dependent apoptosis in insect cells
Authors: Ikeda Motoko , Yamada Hayato , Ito Hiroyuki , Kobayashi Michihiro
Published: July 2011

Baculoviruses encode inhibitors of apoptosis (IAPs), which are classified into five groups, IAP1–5, based on their sequence homology. Most of the baculovirus IAPs with anti-apoptotic functions belong to the IAP3 group, with certain exceptions. The functional roles of IAPs from other groups during virus infection have not been well established. We have previously shown that Hyphantria cunea multiple nucleopolyhedrovirus (HycuMNPV) encodes three iap genes, hycu-iap1, hycu-iap2 and hycu-iap3, and that only Hycu-IAP3 has anti-apoptotic activity against actinomycin D-induced apoptosis of Spodoptera frugiperda
Sf9 cells. In the present study, we demonstrate that transient expression of Hycu-IAP1 is capable of inducing apoptosis and/or stimulating caspase-3-like protease activity in various lepidopteran and dipteran cell lines. Transient-expression assay analysis also demonstrates that not only Hycu-IAP1 but also IAP1s from Autographa californica MNPV, Bombyx mori NPV and Orgyia pseudotsugata MNPV (OpMNPV) are capable of inducing apoptosis, and that apoptosis induced by Hycu-IAP1 is precluded by the functional anti-apoptotic baculovirus protein Hycu-IAP3. In HycuMNPV-infected Spilosoma imparilis (SpIm) cells and OpMNPV-infected Ld652Y cells, caspase-3-like protease activity is markedly stimulated during the late stages of infection, and the caspase-3-like protease activity stimulated in HycuMNPV-infected SpIm cells is repressed by RNA interference-mediated silencing of hycu-iap1. In addition, initiator caspase Bm-Dronc, the B. mori homologue of Dronc, is cleaved upon transfection of BM-N cells with a plasmid expressing Hycu-IAP1. These results provide the first evidence that baculovirus IAP1s act to induce caspase-dependent apoptosis, possibly by replacing the cellular IAP1 that prevents Dronc activation.
High rate of viral evolution in the capsid protein of porcine parvovirus
Authors: Streck André Felipe , Bonatto Sandro Luis , Homeier Timo , Souza Carine Kunzler , Gonçalves Karla Rathje , Gava Danielle , Canal Cláudio Wageck , Truyen Uwe
Published: July 2011

In recent years, it has been shown that some parvoviruses exhibit high substitution rates, close to those of RNA viruses. In order to monitor and determine new mutations in porcine parvovirus (PPV), recent PPV field isolates from Austria, Brazil, Germany and Switzerland were sequenced and analysed. These samples, together with sequences retrieved from GenBank, were included in three datasets, consisting of the complete NS1 and VP1 genes and a partial VP1 gene. For each dataset, the nucleotide substitution rate and the molecular clock were determined. Analysis of the PPV field isolates revealed that a recently described amino acid substitution, S436T, appeared to be common in the VP2 protein in the Austrian, Brazilian and German virus populations. Furthermore, new amino acid substitutions were identified, located mainly in the viral capsid loops. By inferring the evolutionary dynamics of the PPV sequences, nucleotide substitution rates of approximately 10−5 substitutions per site per year for the non-structural protein gene and 10−4 substitutions per site per year for the capsid protein gene (for both viral protein datasets) were found. The latter rate is similar to those commonly found in RNA viruses. An association of the phylogenetic tree with the molecular clock analysis revealed that the mutations on which the divergence for both capsid proteins was based occurred in the past 30 years. Based on these findings, it was concluded that PPV variants are continuously evolving and that vaccines, which are based mainly on strains isolated about 30 years ago, should perhaps be updated.
A proteogenomic analysis of Anopheles gambiae using high-resolution Fourier transform mass spectrometry
Authors: Chaerkady Raghothama , Kelkar Dhanashree S. , Muthusamy Babylakshmi , Kandasamy Kumaran , Dwivedi Sutopa B. , Sahasrabuddhe Nandini A. , Kim Min-Sik , Renuse Santosh , Pinto Sneha M. , Sharma Rakesh , Pawar Harsh , Sekhar Nirujogi Raja , Mohanty Ajeet Kumar , Getnet Derese , Yang Yi , Zhong Jun , Dash Aditya P. , MacCallum Robert M. , Delanghe Bernard , Mlambo Godfree , Kumar Ashwani , Keshava Prasad T.S. , Okulate Mobolaji , Kumar Nirbhay , Pandey Akhilesh
Published: July 2011

Anopheles gambiae is a major mosquito vector responsible for malaria transmission, whose genome sequence was reported in 2002. Genome annotation is a continuing effort, and many of the approximately 13,000 genes listed in VectorBase for Anopheles gambiae are predictions that have still not been validated by any other method. To identify protein-coding genes of An. gambiae based on its genomic sequence, we carried out a deep proteomic analysis using high-resolution Fourier transform mass spectrometry for both precursor and fragment ions. Based on peptide evidence, we were able to support or correct more than 6000 gene annotations including 80 novel gene structures and about 500 translational start sites. An additional validation by RT-PCR and cDNA sequencing was successfully performed for 105 selected genes. Our proteogenomic analysis led to the identification of 2682 genome search–specific peptides. Numerous cases of encoded proteins were documented in regions annotated as intergenic, introns, or untranslated regions. Using a database created to contain potential splice sites, we also identified 35 novel splice junctions. This is a first report to annotate the An. gambiae genome using high-accuracy mass spectrometry data as a complementary technology for genome annotation.
Systems Biology of Tomato Fruit Development: Combined Transcript, Protein, and Metabolite Analysis of Tomato Transcription Factor (nor, rin) and Ethylene Receptor (Nr) Mutants Reveals Novel Regulatory Interactions
Authors: Osorio Sonia , Alba Rob , Damasceno Cynthia M.B. , Lopez-Casado Gloria , Lohse Marc , Zanor Maria Inés , Tohge Takayuki , Usadel Björn , Rose Jocelyn K.C. , Fei Zhangjun , Giovannoni James J. , Fernie Alisdair R.
Published: July 2011

Tomato (Solanum lycopersicum) is an established model to study fleshy fruit development and ripening. Tomato ripening is regulated independently and cooperatively by ethylene and transcription factors, including nonripening (NOR) and ripening-inhibitor (RIN). Mutations of NOR, RIN, and the ethylene receptor Never-ripe (Nr), which block ethylene perception and inhibit ripening, have proven to be great tools for advancing our understanding of the developmental programs regulating ripening. In this study, we present systems analysis of nor, rin, and Nr at the transcriptomic, proteomic, and metabolomic levels during development and ripening. Metabolic profiling marked shifts in the abundance of metabolites of primary metabolism, which lead to decreases in metabolic activity during ripening. When combined with transcriptomic and proteomic data, several aspects of the regulation of metabolism during ripening were revealed. First, correlations between the expression levels of a transcript and the abundance of its corresponding protein were infrequently observed during early ripening, suggesting that posttranscriptional regulatory mechanisms play an important role in these stages; however, this correlation was much greater in later stages. Second, we observed very strong correlation between ripening-associated transcripts and specific metabolite groups, such as organic acids, sugars, and cell wall-related metabolites, underlining the importance of these metabolic pathways during fruit ripening. These results further revealed multiple ethylene-associated events during tomato ripening, providing new insights into the molecular biology of ethylene-mediated ripening regulatory networks.
A Common Genetic Determinism for Sensitivities to Soil Water Deficit and Evaporative Demand: Meta-Analysis of Quantitative Trait Loci and Introgression Lines of Maize
Authors: Welcker Claude , Sadok Walid , Dignat Grégoire , Renault Morgan , Salvi Silvio , Charcosset Alain , Tardieu François
Published: July 2011

Evaporative demand and soil water deficit equally contribute to water stress and to its effect on plant growth. We have compared the genetic architectures of the sensitivities of maize (Zea mays) leaf elongation rate with evaporative demand and soil water deficit. The former was measured via the response to leaf-to-air vapor pressure deficit in well-watered plants, the latter via the response to soil water potential in the absence of evaporative demand. Genetic analyses of each sensitivity were performed over 21 independent experiments with (1) three mapping populations, with temperate or tropical materials, (2) one population resulting from the introgression of a tropical drought-tolerant line in a temperate line, and (3) two introgression libraries genetically independent from mapping populations. A very large genetic variability was observed for both sensitivities. Some lines maintained leaf elongation at very high evaporative demand or water deficit, while others stopped elongation in mild conditions. A complex architecture arose from analyses of mapping populations, with 19 major meta-quantitative trait loci involving strong effects and/or more than one mapping population. A total of 68% of those quantitative trait loci affected sensitivities to both evaporative demand and soil water deficit. In introgressed lines, 73% of the tested genomic regions affected both sensitivities. To our knowledge, this study is the first genetic demonstration that hydraulic processes, which drive the response to evaporative demand, also have a large contribution to the genetic variability of plant growth under water deficit in a large range of genetic material.
Supporting Care Leavers to Fulfil their Educational Aspirations: Resilience, Relationships and Resistance to Help
Authors: Driscoll Jenny
Published: July 2011

Most children in state care do not do as well in school as their peers, but the period of leaving care and transition to adulthood may offer a ‘turning point’ for positive change. Based on a small study of care leavers in England, this article employs the concept of resilience to explore the significance of supportive relationships in enabling this group of young people to make decisions about their future and encouraging them to overcome setbacks in educational attainment.
Adolescents’ Views on Families as Metaphors in Hong Kong: Implications for Pre‐counselling Assessment
Authors: Chan Zenobia C. Y.
Published: July 2011

This interpretative study aims to offer metaphors that describe family meanings from the adolescent’s perspective by encouraging them to give a metaphor with their own explanation on a self‐administering essay form. This study has three objectives: to explore the family meanings as a metaphor from the Hong Kong adolescent’s perspective; to reveal any common and unique features of these metaphors; and to search for the possibilities of collecting metaphors from adolescents as a pre‐counselling assessment tool. The 12 participants for this study were referred to me for family counselling because of poor self‐esteem, loss of life goals or ineffective relationships with their parents. Based on the 12 metaphors, the following five themes can be discerned: (i) gender role in a family, (ii) Chinese culture in a family, (iii) heat in a family, (iv) security in a family and (v) the family as honey and a loan company. Based on the above five themes, there are some common metaphors (e.g. a warm place, honey, a shelter, a boat shelter, a chick and a hen, a volcano, a fire, an oven and a loan company), trans‐cultural and unique metaphors (e.g. a wet market and ‘Kung Fu’ experts), and those that are culturally specified. Both strengths and limitations of collecting and analysing metaphors were discussed.