bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of Multi-Target Agents for Neurological Diseases via Ligand Design
Authors: Bolognesi Maria Laura , Melchiorre Carlo , Van der Schyf Cornelis J. , Youdim Moussa
Published: March 2012

The incidence of neurological disorders in the developed world is rising in concert with an increase in human life expectancy, due in large part to better nutrition and health care. Even as drug discovery efforts are refocused on these disorders, there has been a dearth in the introduction of new disease-modifying therapies to prevent or delay their onset, or reverse their progression. Mounting evidence points to complex and heterogeneous etiopathologies that underlie these diseases. Therefore, it is unlikely that disorders in this class will be mitigated by any single drug that acts exclusively on a single pathway or target. The rational design of novel drug entities with the ability to simultaneously address multiple drug targets of a complex pathophysiology has recently emerged as a new paradigm in drug discovery. Similarly to the concept of multi-target agents within the psychopharmacology field, ligand design has gained an increasing prominence within the medicinal chemistry community. In this chapter we discuss several examples of select chemical scaffolds (polyamines, alkylxanthines, and propargyl carbamates) wherein these concepts were applied to develop novel drug candidates for Alzheimer's disease and Parkinson's disease.
Formulating Nanoparticles to Achieve Oral and Intravenous Delivery of Challenging Drugs
Authors: Vauthier Christine
Published: March 2012

Nanoparticles were found suitable materials to transport drugs in vivo. Their application as drug carrier by intravenous and oral routes of administration generally improves efficiency of treatments with existing molecules. Their use makes possible the development of treatments with challenging new molecules displaying a high therapeutic potential such as nucleic acids, proteins and peptides. Success of drug delivery methods using nanoparticles is greatly influenced by the ability of the drug carrier to cross biological barriers and by the specificity of its biodistribution. The aim of this review was to present few aspects of the formulation of nanoparticles designed for the delivery of drugs by the oral route and by intravenous injections. It focuses on strategies developed to design surface properties of the nanoparticles. The rational behind this choice is that surface properties were identified as a major parameter influencing the in vivo fate of nanoparticles. Specific examples were taken from developments made on poly(alkylcyanoacrylate) nanoparticles. This review shows that formulation strategies are closely linked with biological phenomena governing interactions between nanoparticles and the host. It indicated that nanoparticle surface properties need to be finely tuned to achieve the desired properties and that all surface modifications can be performed by an appropriate chemistry.
Development and In Vitro Evaluations of a Lipid Nanoparticle Formulation Containing Tretinoin
Authors: Das Surajit , Kiong Ng Wai , Tan Reginald B.H.
Published: March 2012

Tretinoin has shown its effectiveness in the treatment of several skin diseases, such as acne vulgaris, photoaging, psoriasis, and epithelial skin cancer. Nevertheless, formulation of effective delivery systems of tretinoin is challenging due to its poor solubility as well as high chemical- and photo-instability. Furthermore, skin irritation cause by tretinoin upon topical application is also a concern. In addition, sustained and prolonged drug release is required at the disease site for effective treatment. Keeping all these in mind, we hypothesized that encapsulation of tretinoin in solid lipid nanoparticles (SLNs) will avoid the above mentioned drawbacks associated with tretinoin. Additionally, SLNs are expected to penetrate into skin due to its nano size and provide sustained and prolonged drug release due to solid matrix of SLNs. Thus, SLNs containing tretinoin were developed by varying different formulation parameters, such as types of lipids, types of surfactants, lipid concentration, surfactant concentration, drug concentration, homogenization time, and sonication time. Emulsification-ultrasonification method was adopted to prepare SLNs. Particle size, polydispersity index (PI), and zeta potential (ZP) were measured by photon correlation spectroscopy. Surface morphology and shape of SLNs were checked by cryogenic scanning electron microscopy (cryo-SEM). Encapsulation efficiency (EE) of the SLNs was determined by HPLC. Drug release study was performed in 10 mM phosphate buffer containing 2% Tween® 80 (pH 7.4). Further, short-term stability study was also performed to check the stability of SLNs. Formulation parameters exhibited significant impact on the size, PI, ZP, and EE. The developed SLNs demonstrated 113.50±0.89 nm particle size, 0.182±0.007 PI, -38.70±0.56 mV ZP, and 78.18±4.26% EE. Cryo-SEM image revealed smooth and spherical SLNs. SLNs were stable during storage at 4°C. In vitro drug release study showed sustained and prolonged drug release from SLNs. Hence, the developed tretinoin-loaded SLNs can be incorporated into a gel formulation for topical application.
Nanocomposites Prepared by Ultrasonic Spray Pyrolysis and Their Applications
Authors: Zheng Rongbo
Published: March 2012

We have developed ultrasonic spray pyrolysis, a one-step, continuous, scalable and rapid route, to synthesize nanocomposites with different morphology. The morphology can be tuned via selecting different carbon source. Rattle-type Carbon hollow spheres, high-density magnetite nanoparticles located in carbon hollow microspheres, carbon-iron oxide black pigments with tunable density, and silver porous hollow spheres can be obtained when sodium citrate, citrate acid and glucose were used as carbon source, respectively. Due to the presence of OH, CC and CH groups in aforementioned nanocomposites, they exhibit good dispersibility in both polar and nonpolar solvents. Finally, their applications in Li-ion battery and electrophoretic displays were investigated.
Sintering Studies on the Various Properties of Barium Titanate Nanoparticles Synthesized by a Novel Technique
Authors: Sundararajan T. , Karthik T. , Balasivanandha Prabu S.
Published: March 2012

Barium Titanate nanoparticles were synthesized by a novel dry milling process. The powders were characterized by XRD, Laser Raman Spectroscopy, SEM and EDX techniques. The Laser Raman spectral data corroborated well with the inferences from XRD patterns. The effects of microwave and conventional sintering at 10000C on the various properties of Barium Titanate nanoparticles were compared. The average size of microwave sintered sample was about 50 nm lesser than sample sintered by conventional technique. LCZ meter was used to study the dielectric properties. Microwave sintered Barium Titanate showed a 16 % increase in the relative dielectric constant value at the lowest applied frequency of 100 kHz which was attributed to the enhanced tetragonality of the microwave sintered nanoparticles. Microwave sintered compacts showed relatively lower hysteresis loss, higher polarization maximum values which were attributed to the minimized grain growth during microwave sintering. The microwave processing consumed 1/6th of the energy consumed during the conventional processing, thus proving its higher energy efficiency without compromising the dielectric properties of Barium Titanate nanoparticles.
Dry Powder Nanoparticulate Formulations for Mucosal Vaccination
Authors: Scherließ Regina , Buske Simon
Published: March 2012

Intranasal administration of nanoparticulate dry powder vaccine formulations seems to be an advantageous option due to the fact that particles smaller than 250 nm can be taken up by specialized cells (M-cells) in the mucosa resulting in both local and systemic immune response. Among other reactions this causes the secretion of dimeric IgA (sIgA) into the mucus promoting entrapment of pathogens directly in the mucus1.

In this study non-water soluble nanoparticles of chitosan and sodium deoxycholate were prepared via ionic coacervation. The particle size distribution of the products was determined via photon correlation spectroscopy (PCS). The obtained particles showed a monomodal distribution with an average size of about 250 nm (size distribution by volume). These particles seem to be ideal carriers for model antigens such as bovine serum albumin (BSA), which can be incorporated during the particle forming process. In order to obtain a dry powder the nanosuspension can be spray dried or freeze dried using mannitol as matrix. Spray-dried products are known for having a particle size of less than 10 µm. The product can be re-dispersed rapidly resulting in a nanoparticulate dispersion.. For nasal application, the spray dried formulation can be used directly as dry powder vaccine or may be further processed in order to obtain a suitable formulation by immobilisation onto bigger carrier particles to allow preferential nasal deposition. Such formulations might represent a promising vaccine delivery system in the near future.
Functionalization of SiO2 Nanoparticles and Their Superhydrophobic Surface Coating
Authors: Sehlleier Y. H. , Abdali A. , Hülser T. , Wiggers H. , Schulz C.
Published: March 2012

Silica (SiO2) nanoparticles synthesized from the gas phase in a microwave plasma reactor were dispersed in organic solvents and subsequently chemically modified with silane coupling agents (SCAs) to reduce agglomeration. A transparent and stable dispersion of silica nanoparticles in toluene could be achieved after functionalization with octyltriethoxysilane (OTES). FTIR measurements indicated that the concentration of free hydroxyl groups on the nanoparticle surface was notably decreased. Nanodispersions of functionalized silica particles with several SCAs were prepared and coated onto glass substrates. The resulting highly hydrophilic/hydrophobic glass substrates were investigated by water contact angle measurements. As a result, the hydrophobically OTES-functionalized silica nanoparticles in toluene showed an average diameter of 28 nm and remained for more than eight weeks.
Morphological Studies of Polyaniline/TiO2 Polymer Composite
Authors: Narsimlu N. , Kavitha B. , Srinivasu D. , Sivakumar K.
Published: March 2012

Small angle x-ray scattering (SAXS) and spectroscopic (IR, UV/VIS) techniques are used to investigate the interaction between titanium dioxide (TiO2) and semiconductor-polymer poly(N-(4-sulfophenyl)aniline (PSA), in poly(N-(4-sulfophenyl) aniline/TiO2 composite (TPSA). Spectroscopic studies indicated the composite formation of TiO2 and PSA. The optical band gap reduction of TiO2 is taking place due to composite formation. Small angle x-ray scattering (SAXS) is used to determine the radius of gyration of cross section (Rc), radius (R) and length (L) of rode-like particle, persistence length (a*), surface fractal dimension (Ds) and PSA layer thickness (E) on TiO2 in aqueous solution and powder form. The results indicate that the aggregation of TiO2 particles upon drying was reduced by formation composite with semiconductor-polymer. Only the particle length of TPSA particle (rod-like shape) increases on drying, probably due to increasing the void sizes as well as formation of aggregation. Persistence length of the TPSA particles decreases with respect to the increase of contact area between solvent and solute, weight of the particles and surface roughness, compared to its individual components. The PSA layer thickness on TiO2 is 3.6 nm and decreases (to 2.6 nm) on dehydration due to the expulsions of water molecules from TiO2/PSA composite.
Bound Water Investigations on Disaccharide Based Glycolipids
Authors: Mohammad Seyed , Hosseini Mirzadeh , Hashim Rauzah , Heidelberg Thorsten , Timimi Bakir A.
Published: March 2012

The bound water content for isomeric disaccharide based glycolipids is determined by deuterium NMR spectroscopy and DSC. The NMR investigation faced obstacles due to pseudo-isotropic spectra for β-glycoside based on β-1,4-linked disaccharides, i.e. dodecyl β lactoside and dodecyl β-cellobioside. Only at temperatures significantly exceeding 100 °C typical powder spectra could be observed. The determined bound water content for the lactoside is with only two molecules water per surfactant surprisingly small. A slightly higher value was determined for a branched β-maltoside. While this investigation did not require high temperature, the spectra were poorly resolved and quadrupole splittings had to be estimated based on the half-peak width of a single broad signal. The low bound water contents rise questions on the reliability of the D-NMR method for these compounds, or more generically in case of high temperature requirements and poorly resolved powder spectra. In order to evaluate the data, a DSC investigation based on the freezing and melting of water was targeted. A model study on dodecyl β-maltoside indicates a reasonable agreement with previous D-NMR spectroscopic investigations on the same compound. This result indicates that DSC may be used to evaluate the low bound water contents determined by D-NMR.
Nano-sized Delivery for Agricultural Chemicals
Authors: Zhao Min , Liu Lei , Her Robert , Kalantar Tom , Schmidt Dale , Mathieson Todd , Tolley Mike , Yau Kerrm , Wensing Steven , Zhang Qiang , Zettler Mark , Li Ze-Sheng , Zweifel Dan
Published: March 2012

In today's ever-increasing competition and regulatory restriction environment, it is critical for Ag-Chemical companies to have a sustained effort to explore and leverage novel and innovative technologies for more effective and efficient formulation and delivery systems. In recent years, nano-technology has been a particularly active area, and has shown the potential in enhancing bio-efficacy, bio-availability, and better penetration or uptake, especially for poorly soluble active ingredients. Our cellular uptake study demonstrated the penetration, uptake, and mobility of NPs in model cell systems. The subsequent hydroponic delivery study proved that NPs can transport through root and move upward through xylem. Several types of pesticide active ingredients were incorporated into nano-capsules. When compared to conventional micron-sized formulations, the nano-capsule formulations demonstrated significantly higher levels of activity. These studies indicate the potential for improving the effectiveness of agricultural active ingredients using nano-sized particles, including functionalized nano-capsules.
Characterization of transcriptional profiling of Kupffer cells during liver regeneration in rats
Authors: Xu Cunshuan , Chen Xiaoguang , Chang Cuifang , Wang Gaiping , Wang Wenbo , Zhang Lianxing , Zhu Qiushi , Wang Lei
Published: March 2012

KCs (Kupffer cells), as an important hepatic immunoregulatory cells, play a key role in LR (liver regeneration). Uncovering the transcriptional profiling of KCs after PH (partial hepatectomy) would likely clarify its implication in LR. Here, we isolated KCs by methods of Percoll density gradient centrifugation and immunomagnetic beads. Transcriptional profiles of KCs were monitored up to 168 h post‐PH using microarray. By comparing the expression profile of KCs at 2–168 h post‐PH with that of the control and applying the statistical and bioinformatics criteria, we found 1407 known and 927 unknown genes related to LR. K‐means clustering analysis grouped these 1407 genes into robust 14 time‐course clusters representing distinct patterns of regulation. Based on gene‐set enrichment analysis, genes encoding products involved in cytokine signalling, inflammatory response and cell chaemotaxis were highly enriched in the cluster characterized by gradual up‐regulation and then return; genes in defence response and immune response were enriched in clusters ‘the general down‐regulation during LR’; genes in fatty acid synthesis and sterol metabolism were preferentially distributed in the cluster ‘gradual increase’; whereas genes in the categories ‘lipid catabolism’ and ‘glycolysis’ were enriched in cluster ‘decrease at two intervals’. According to the above analysis, KCs were seemingly sensitive to operative stimulus; immune defence and detoxification function of KCs obviously dropped post‐operatively; fatty acid synthesis were enhanced, whereas lipid catabolism and glycolysis were reduced after PH. This study provides a detailed in vivo gene expression profile of KCs, providing a framework to better understand the molecular mechanisms underlying the regeneration process at cellular level.
Les erreurs de mesure en céphalométrie 2D
Authors: Bourriau Jérôme , Bidange Guillaume , Foucart Jean-Michel
Published: March 2012

L’utilisation de la téléradiographie de profil (norma latéralis) à des fins cliniques est
très étroitement liée à la précision d’identification et de localisation des différents
« points » requis lors de l’élaboration des différentes analyses céphalométriques. L’objet
de cette étude est d’analyser l’influence de deux paramètres que sont la distance
foyer-objet et le type de récepteur, sur la précision de localisation des 19 points
céphalométriques les plus usités puis d’analyser la répercussion des erreurs de
localisation sur les mesures céphalométriques. Un groupe de 53 orthodontistes a été
aléatoirement sélectionné ; tous ont identifié 19 points céphalométriques sur des clichés
radiographiques argentiques ou numériques, réalisés à 1 m 50 ou à 4 m. Les résultats
montrent qu’il n’existe pas de différence statistiquement significative liée à la distance
foyer-sujet ou au type de récepteur. Indépendamment du mode d’acquisition radiologique,
chaque point céphalométrique présente un nuage de dispersion caractéristique, les points
les plus fiables étant généralement situés dans le plan sagittal médian. Les mesures
céphalométriques qui présentent la plus forte variabilité sont liées à la position des
apex incisifs, ce qui conduit à relativiser leur importance lors de l’établissement du
plan de traitement et du suivi thérapeutique. De manière analogue, l’utilisation du plan
de Francfort est sujette à controverse au regard de la plus grande fiabilité des autres
plans de référence du crâne et plus particulièrement S-Na.
Techniques radiographiques utiles en
orthodontie
Authors: Felizardo Rufino , Thomas Alexis , Foucart Jean-Michel
Published: March 2012

En orthopédie dento-faciale, le praticien dispose d’un large éventail de techniques
d’imagerie médicale pour l’aider dans ses différentes phases de diagnostic ou de suivi
thérapeutique. Les clichés rétro-alvéolaires, rétro-coronaires, panoramiques ou la
téléradiographie sont des techniques bidimensionnelles que l’on pourra compléter, si
nécessaire, par des techniques volumiques ou sectionnelles (scanner à rayons X,
tomographie volumique à faisceau conique ou cone beam). À chaque type de
clichés correspondent des critères de qualité qu’il faut respecter afin de tirer le
meilleur de chaque image, éviter les artéfacts ou les images construites susceptibles de
diminuer l’apport diagnostique et donc le service rendu au patient. Il faut savoir perdre
alors quelques instants pour parfaire le positionnement du patient dans l’appareil
radiologique plutôt que de multiplier les prises de vues par manque d’optimisation des
protocoles de radiologie.
Les erreurs de mesure en céphalométrie 3D :
à propos de l’analyse cranio-faciale vestibulaire
Authors: Papé Romain de , Pizelle Christophe , Foucart Jean-Miche
Published: March 2012

Le développement des techniques d’imagerie tridimensionnelle
générant une faible irradiation (tomodensitométrie et tomographie
volumique à faisceau conique ou cone beam) rend
désormais possible la réalisation d’une céphalométrie 3D pour certains
cas cliniques complexes en substitution de la céphalométrie 2D conventionnelle.
Néanmoins, le développement de telles analyses implique l’identification
des points anatomiques les plus fiables. Un groupe de 15 orthodontistes
a été aléatoirement sélectionné ; tous ont identifié 33 points sur
un examen volumique tomodensitométrique, les points ayant été choisis
à partir de l’analyse cranio-faciale vestibulaire, historiquement
connue pour sa reproductibilité. Les résultats confirment la grande
fiabilité des points de référence liés aux canaux semi-circulaires (vestibion).
Ils montrent, comme en céphalométrie 2D conventionnelle, que chaque
point présente un nuage de dispersion caractéristique et que les
points les plus fiables sont liés à des structures anatomiques facilement
identifiables (foramen, pointes osseuses…).
Imagerie des désordres temporo-mandibulaires
Authors: Felizardo Rufino , Foucart Jean-Michel , Pizelle Christophe
Published: March 2012

Longtemps dominée par les clichés standard (les tomographies réalisées bouche ouverte et
bouche fermée et l’IRM), l’imagerie des articulations temporo-mandibulaires a
progressivement perdu ses indications face à un examen clinique bien codifié, suffisant
dans la majorité des cas. Son apport diagnostique, et la modification de prise en charge
thérapeutique des dysfonctions temporo-mandibulaires qui en découle, est en effet très
faible au regard du coût en termes d’économie de santé (IRM) et d’irradiation
(tomographies, CBCT, scanner). Nous aborderons dans cet article les différentes
pathologies que le praticien est susceptible de rencontrer, et les situations dans
lesquelles les examens restent indiqués.
Equilibrium magnetization of a nanogranular magnetic film with perpendicular anisotropy in a tilted magnetic field
Authors: Kalita V. M. , Ryabchenko S. M.
Published: March 2012

An influence of demagnetizing field on a process of equilibrium magnetization of nanogranular films with perpendicular anisotropy in a tilted magnetic field is studied theoretically. An effect of the canting and flipping of granules magnetic moments on magnetization curves is described. It is shown that in a tilted field the transition from an inhomogeneous state to the state with a uniform orientation of magnetic moments takes place in a critical way.
Magnetic phase segregation and glass nature of Pr0.4Bi0.3Ca0.3MnO3 manganite
Authors: Desnenko V. A. , Rykova A. I. , Sirenko V. A. , Fedorchenko A. V. , Cherny A. S. , Khatsko E. N. , Eremenko A. V.
Published: March 2012

The results of detailed investigations of magnetic properties of Pr0.4Bi0.3Ca0.3MnO3 manganites at low temperatures are presented. The performed investigations of temperature, field and frequency dependences of magnetization and susceptibility as well as the magnetization relaxation processes indicate that below TC = 44 K the manganite Pr0.4Bi0.3Ca0.3MnO3 is in the magnetic phase-segregated state with ferromagnetic inclusions forming a cluster glass.
Micromechanical properties of C70 single crystals in the temperature range 77–350 K
Authors: Lubenets S. V. , Natsik V. D. , Fomenko L. S. , Rusakova A. V. , Osipyan Yu. A. , Orlov V. I. , Sidorov N. S. , Izotov A. N.
Published: March 2012

Hexagonal single crystals of C70 down to 1–2 mm in size were grown, which allowed the investigation of their low-temperature mechanical properties for the first time. Morphology, microplasticity anisotropy, and the temperature dependence of Vickers microhardness HV (T) of the C70 crystals involving all known phase transitions were studied with the aid of optical microscopy and microindentation in the temperature range 77–350 K. The association of the features of HV (T) dependence with orientation phase transformations was analyzed. It is suggested that microplasticity anisotropy of the C70 crystals correlates with the active slip systems.
Evolution of the electrical resistance of YBa2Cu3O7−δ with δd ≈ 0.45 under high hydrostatic pressures
Authors: Vovk R. V. , Khadzhai G. Ya. , Obolenskii M. A.
Published: March 2012

The temperature dependence of the electrical resistance of YBa2Cu3O7−δ in the plane of the layers is studied at hydrostatic pressures of up to 10 kbar. The dependences obtained above the superconducting transition temperature can be approximated to high accuracy by a model of (s-d)-scattering of electrons on phonons. Applying a high pressure causes a reduction in the resistance that is substantially greater at high than at low temperatures. This may be related to a weakening of the electron-phonon interaction with increasing pressure.
Lower soil moisture threshold for transpiration decline under water deficit correlates with lower canopy conductance and higher transpiration efficiency in drought-tolerant cowpea
Authors: Belko Nouhoun , Zaman-Allah Mainassara , Cisse Ndiaga , Diop Ndeye Ndack , Zombre Gerard , Ehlers Jeffrey D. , Vadez Vincent
Published: March 2012

As water availability is critical for reproduction, terminal drought tolerance may involve water-saving traits. Experiments were undertaken under different vapour pressure deficit (VPD) and water regimes (water stress (WS) and well watered (WW)) to test genotypic differences and trait relationships in the fraction of transpirable soil water (FTSW) at which transpiration declines, canopy conductance (proxied by transpiration rate (TR, g H2O cm–2 h–1)), canopy temperature depression (CTD, °C), transpiration efficiency (TE, g kg–1) and growth parameters, using 15 contrasting cowpea (Vigna unguiculata (L.) Walp.) genotypes. Under WW conditions at the vegetative and early podding stages, plant mass and leaf area were larger under low VPD, and was generally lower in tolerant than in sensitive genotypes. Several tolerant lines had lower TR under WW conditions and restricted TR more than sensitive lines under high VPD. Under WS conditions, transpiration declined at a lower FTSW in tolerant than in sensitive lines. Tolerant lines also maintained higher TR and CTD under severe stress. TE was higher in tolerant genotypes under WS conditions. Significant relationships were found between TR, and TE, CTD and FTSW under different water regimes. In summary, traits that condition how genotypes manage limited water resources discriminated between tolerant and sensitive lines. Arguably, a lower canopy conductance limits plant growth and plant water use, and allows tolerant lines to behave like unstressed plants until the soil is drier and to maintain a higher TR under severe stress, as lower TR at high VPD leads to higher TE.
Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity
Authors: Kim Jiyoung , Villadsen René , Sørlie Therese , Fogh Louise , Grønlund Signe Z. , Fridriksdottir Agla J. , Kuhn Irene , Rank Fritz , Wielenga Vera Timmermans , Solvang Hiroko , Edwards Paul A. W. , Børresen-Dale Anne-Lise , Rønnov-Jessen Lone , Bissell Mina J. , Petersen Ole William
Published: March 2012

The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors. We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than their basal-like counterparts. The tumorigenicity and invasive potential of the luminal-like cancer cells relied strongly on the expression of the gene
GCNT1
, which encodes a key glycosyltransferase controlling O-glycan branching. These findings demonstrate that basal-like cells, as defined currently, are not a
requirement
for breast tumor aggressiveness, and that within a single tumor there are multiple “stem-like” cells with tumorigenic potential casting some doubt on the hypothesis of hierarchical or differentiative loss of tumorigenicity.
Analyses of Genetic Variation in Populations of Oregon Chub, a Threatened Floodplain Minnow in a Highly Altered Environment
Authors: DeHaan Patrick W. , Scheerer Paul D. , Rhew Ron , Ardren William R.
Published: March 2012

The Oregon chub Oregonichthys crameri is a small floodplain minnow endemic to the Willamette River basin of western Oregon. Historically the species was widely abundant and probably relied on periodic floods for dispersal and genetic exchange among populations. The species has declined substantially in the past 100 years due to habitat alterations and the introduction of nonnative species and is currently listed as threatened under the U.S. Endangered Species Act. Information on the level of genetic variation within and among populations did not exist when the species was listed or when a recovery plan was being developed. In this study, we used a suite of nine microsatellite loci to characterize genetic variation within and among 16 sampling locations and provide information to help guide future recovery efforts. Even though many locations are presently isolated from one another, we observed relatively high levels of genetic variation within collections. Temporal samples revealed that the levels of genetic variation were stable over time despite fluctuations in abundance. Estimates of effective population size (Ne) for three sampling locations ranged from approximately 120 to 220 and suggest that there is no immediate threat from inbreeding or genetic drift. We observed a significant level of genetic variation among sampling locations (global FST = 0.078) and significant differences in allele frequencies among all sampling locations. Our results suggest that the different locations represent distinct populations of Oregon chub and that greater levels of gene flow occur among populations within the Santiam and Middle Fork Willamette River subbasins. The information presented in this study will help guide Oregon chub recovery efforts, including the refinement of recovery areas and future population introduction efforts, and will help address the challenge of managing populations largely in isolation from one another in order to minimize threats from nonnative species.
Differential Interactions of Two Introduced Piscivorous Salmonids with a Native Cyprinid in Lentic Systems: Implications for Conservation of Roundtail Chub
Authors: Laske Sarah M. , Rahel Frank J. , Hubert Wayne A.
Published: March 2012

The effects of multiple nonnative piscivore species on native prey species in lentic systems are poorly understood. We studied the relative predation risks posed by two piscivorous salmonids (brown trout Salmo trutta and lake trout Salvelinus namaycush) to endemic roundtail chub Gila robusta in two lakes within the upper Colorado River basin. Gill nets were set in various habitat types to study habitat use by the three species before and after the onset of summer stratification. Roundtail chub and brown trout were mainly associated with shallow‐water habitats, and this association did not change with thermal period. By contrast, lake trout habitat use changed with thermal period as fish moved from shallow areas in the spring to deepwater habitat after stratification. These habitat use patterns indicate that roundtail chub are more susceptible to predation by brown trout than by lake trout because both roundtail chub and brown trout occupy the littoral zone for a prolonged period. Diet data indicated that brown trout consumed littoral fish species (i.e., cyprinids), whereas lake trout primarily consumed opossum shrimp Mysis spp. and dipterans (true flies). Brown trout consumed proportionally more fish than did lake trout, began feeding on fish at smaller total lengths, and increased fish consumption during the period of thermal stratification. An important consideration for efforts to conserve lentic roundtail chub populations is the prevention of future introductions of littoral predators.
Towards quantum simulations of biological information flow
Authors: Dorner Ross , Goold John , Vedral Vlatko
Published: March 2012

Recent advances in the spectroscopy of biomolecules have highlighted the possibility of quantum coherence playing an active role in biological energy transport. The revelation that quantum coherence can survive in the hot and wet environment of biology has generated a lively debate across both the physics and biology communities. In particular, it remains unclear to what extent non-trivial quantum effects are used in biology and what advantage, if any, they afford. We propose an analogue quantum simulator, based on currently available techniques in ultra-cold atom physics, to study a model of energy and electron transport based on the Holstein Hamiltonian. By simulating the salient aspects of a biological system in a tunable laboratory set-up, we hope to gain insight into the validity of several theoretical models of biological quantum transport in a variety of relevant parameter regimes.
Patterns of periodic holes created by increased cell motility
Authors: Chen Ting-Hsuan , Guo Chunyan , Zhao Xin , Yao Yucheng , Boström Kristina I. , Wong Margaret N. , Tintut Yin , Demer Linda L. , Ho Chih-Ming , Garfinkel Alan
Published: March 2012

The reaction and diffusion of morphogens is a mechanism widely used to explain many spatial patterns in physics, chemistry and developmental biology. However, because experimental control is limited in most biological systems, it is often unclear what mechanisms account for the biological patterns that arise. Here, we study a biological model of cultured vascular mesenchymal cells (VMCs), which normally self-organize into aggregates that form into labyrinthine configurations. We use an experimental control and a mathematical model that includes reacting and diffusing morphogens and a third variable reflecting local cell density. With direct measurements showing that cell motility was increased ninefold and threefold by inhibiting either Rho kinase or non-muscle myosin-II, respectively, our experimental results and mathematical modelling demonstrate that increased motility alters the multicellular pattern of the VMC cultures, from labyrinthine to a pattern of periodic holes. These results suggest implications for the tissue engineering of functional replacements for trabecular or spongy tissue such as endocardium and bone.
Direct influence of residual stress on the bending stiffness of cantilever beams
Authors: Shi M. X. , Liu B. , Zhang Z. Q. , Zhang Y. W. , Gao H. J.
Published: March 2012

Although the cantilever beam has been widely used as a sensor to measure various physical quantities, important issues such as how residual stress affects its bending stiffness and what are the underlying physical origins have not been fully understood. We perform both theoretical analyses and finite-element simulations to demonstrate for the first time that without changing the material tangent stiffness, residual stress within the beam can directly influence the bending stiffness of the beam. This direct influence arises from two origins: geometry nonlinearity and Poisson’s ratio effect. For a cantilever beam with adsorbed macromolecules on its surfaces, we find that longer macromolecular chains have lower normal stiffness and larger intermolecular forces, which makes the effect of the residual stress more pronounced. The excellent agreement between our theoretical predictions and finite-element calculation results validate our analysis. The present work provides an important framework for improving the sensitivity of a cantilever beam as a sensor.
Species richness matters for the quality of ecosystem services: a test using seed dispersal by frugivorous birds
Authors: García Daniel , Martínez Daniel
Published: March 2012

The positive link between biodiversity and ecosystem functioning is a current paradigm in ecological science. However, little is known of how different attributes of species assemblages condition the quality of many services in real ecosystems affected by human impact. We explore the links between the attributes of a frugivore assemblage and the quantitative and qualitative components of its derived ecosystem service, seed dispersal, along a landscape-scale gradient of anthropogenic forest loss. Both the number and the richness of seeds being dispersed were positively related to frugivore abundance and richness. Seed dispersal quality, determined by the fine-scale spatial patterns of seed deposition, mostly depended on frugivore richness. In fact, richness was the only attribute of the frugivore assemblage affecting the probability of seed dispersal into deforested areas of the landscape. The positive relationships between frugivore richnessper se(i.e. independent of frugivore abundance and composition) and all components of seed dispersal suggest the existence of functional complementarity and/or facilitation between frugivores. These links also point to the whole assemblage of frugivores as a conservation target, if we aim to preserve a complete seed dispersal service and, hence, the potential for vegetation regeneration and recovery, in human-impacted landscapes.
Dental functional traits of mammals resolve productivity in terrestrial ecosystems past and present
Authors: Liu Liping , Puolamäki Kai , Eronen Jussi T. , Ataabadi Majid M. , Hernesniemi Elina , Fortelius Mikael
Published: March 2012

We have recently shown that rainfall, one of the main climatic determinants of terrestrial net primary productivity (NPP), can be robustly estimated from mean molar tooth crown height (hypsodonty) of mammalian herbivores. Here, we show that another functional trait of herbivore molar surfaces, longitudinal loph count, can be similarly used to extract reasonable estimates of rainfall but also of temperature, the other main climatic determinant of terrestrial NPP. Together, molar height and the number of longitudinal lophs explain 73 per cent of the global variation in terrestrial NPP today and resolve the main terrestrial biomes in bivariate space. We explain the functional interpretation of the relationships between dental function and climate variables in terms of long- and short-term demands. We also show how the spatially and temporally dense fossil record of terrestrial mammals can be used to investigate the relationship between biodiversity and productivity under changing climates in geological time. The placement of the fossil chronofaunas in biome space suggests that they most probably represent multiple palaeobiomes, at least some of which do not correspond directly to any biomes of today's world.
Tradeoffs limit the evolution of male traits that are attractive to females
Authors: Wagner William E. , Beckers Oliver M. , Tolle Amanda E. , Basolo Alexandra L.
Published: March 2012

Tradeoffs occur between a variety of traits in a diversity of organisms, and these tradeoffs can have major effects on ecological and evolutionary processes. Far less is known, however, about tradeoffs between male traits that affect mate attraction than about tradeoffs between other types of traits. Previous results indicate that females of the variable field cricket,
Gryllus lineaticeps
, prefer male songs with higher chirp rates and longer chirp durations. In the current study, we tested the hypothesis that a tradeoff between these traits affects the evolution of male song. The two traits were negatively correlated among full-sibling families, consistent with a genetically based tradeoff, and the tradeoff was stronger when nutrients were limiting. In addition, for males from 12 populations reared in a common environment, the traits were negatively correlated within populations, the strength of the tradeoff was largely invariant across populations, and the within-population tradeoff predicted how the traits have evolved among populations. A widespread tradeoff thus affects male trait evolution. Finally, for males from four populations assayed in the field, the traits were negatively correlated within and among populations. The tradeoff is thus robust to the presence of environmental factors that might mask its effects. Together, our results indicate there is a fundamental tradeoff between male traits that: (i) limits the ability of males to produce multiple attractive traits; (ii) limits how male traits evolve; and (iii) might favour plasticity in female mating preferences.
Coprolites as a source of information on the genome and diet of the cave hyena
Authors: Bon Céline , Berthonaud Véronique , Maksud Frédéric , Labadie Karine , Poulain Julie , Artiguenave François , Wincker Patrick , Aury Jean-Marc , Elalouf Jean-Marc
Published: March 2012

We performed high-throughput sequencing of DNA from fossilized faeces to evaluate this material as a source of information on the genome and diet of Pleistocene carnivores. We analysed coprolites derived from the extinct cave hyena (
Crocuta crocuta spelaea
), and sequenced 90 million DNA fragments from two specimens. The DNA reads enabled a reconstruction of the cave hyena mitochondrial genome with up to a 158-fold coverage. This genome, and those sequenced from extant spotted (
Crocuta crocuta
) and striped (
Hyaena hyaena
) hyena specimens, allows for the establishment of a robust phylogeny that supports a close relationship between the cave and the spotted hyena. We also demonstrate that high-throughput sequencing yields data for cave hyena multi-copy and single-copy nuclear genes, and that about 50 per cent of the coprolite DNA can be ascribed to this species. Analysing the data for additional species to indicate the cave hyena diet, we retrieved abundant sequences for the red deer (
Cervus elaphus
), and characterized its mitochondrial genome with up to a 3.8-fold coverage. In conclusion, we have demonstrated the presence of abundant ancient DNA in the coprolites surveyed. Shotgun sequencing of this material yielded a wealth of DNA sequences for a Pleistocene carnivore and allowed unbiased identification of diet.
A quantitative atlas of polyadenylation in five mammals
Authors: Derti Adnan , Garrett-Engele Philip , MacIsaac Kenzie D. , Stevens Richard C. , Sriram Shreedharan , Chen Ronghua , Rohl Carol A. , Johnson Jason M. , Babak Tomas
Published: March 2012

We developed PolyA-seq, a strand-specific and quantitative method for high-throughput sequencing of 3′ ends of polyadenylated transcripts, and used it to globally map polyadenylation (polyA) sites in 24 matched tissues in human, rhesus, dog, mouse, and rat. We show that PolyA-seq is as accurate as existing RNA sequencing (RNA-seq) approaches for digital gene expression (DGE), enabling simultaneous mapping of polyA sites and quantitative measurement of their usage. In human, we confirmed 158,533 known sites and discovered 280,857 novel sites (FDR < 2.5%). On average 10% of novel human sites were also detected in matched tissues in other species. Most novel sites represent uncharacterized alternative polyA events and extensions of known transcripts in human and mouse, but primarily delineate novel transcripts in the other three species. A total of 69.1% of known human genes that we detected have multiple polyA sites in their 3′UTRs, with 49.3% having three or more. We also detected polyadenylation of noncoding and antisense transcripts, including constitutive and tissue-specific primary microRNAs. The canonical polyA signal was strongly enriched and positionally conserved in all species. In general, usage of polyA sites is more similar within the same tissues across different species than within a species. These quantitative maps of polyA usage in evolutionarily and functionally related samples constitute a resource for understanding the regulatory mechanisms underlying alternative polyadenylation.
RIP-chip-SRM—a new combinatorial large-scale approach identifies a set of translationally regulated bantam/miR-58 targets in C. elegans
Authors: Jovanovic Marko , Reiter Lukas , Clark Alejandra , Weiss Manuel , Picotti Paola , Rehrauer Hubert , Frei Andreas , Neukomm Lukas J. , Kaufman Ethan , Wollscheid Bernd , Simard Martin J. , Miska Eric A. , Aebersold Ruedi , Gerber André P. , Hengartner Michael O.
Published: March 2012

MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression. As miRNAs are involved in a wide range of biological processes and diseases, much effort has been invested in identifying their mRNA targets. Here, we present a novel combinatorial approach, RIP-chip-SRM (RNA-binding protein immunopurification + microarray + targeted protein quantification via selected reaction monitoring), to identify de novo high-confidence miRNA targets in the nematode Caenorhabditis elegans. We used differential RIP-chip analysis of miRNA-induced silencing complexes from wild-type and miRNA mutant animals, followed by quantitative targeted proteomics via selected reaction monitoring to identify and validate mRNA targets of the C. elegans bantam homolog miR-58. Comparison of total mRNA and protein abundance changes in mir-58 mutant and wild-type animals indicated that the direct bantam/miR-58 targets identified here are mainly regulated at the level of protein abundance, not mRNA stability.
Up‐regulation of Anxa2 gene promotes proliferation and invasion of breast cancer MCF‐7 cells
Authors: Wu B. , Zhang F. , Yu M. , Zhao P. , Ji W. , Zhang H. , Han J. , Niu R.
Published: March 2012

Objective

The metastatic ability of breast cancer cells with chemoresistant properties is higher when compared to that of their parental wild‐type cells. Expression of AnnexinA2 (Anxa2), a 36‐kDa calcium‐dependent phospholipid binding protein, is increased in metastatic tumours and has been found to be associated with the phenotype of drug resistance and metastasis.

Materials and Methods and Results

In the present study, we found that up‐regulation of Anxa2 correlates with enhanced migration and invasion ability of MCF‐7 breast cancer cells both in vitro and in vivo. Western blot analysis revealed that exposure to chemotherapeutic drugs may induce elevated expression of Anxa2. In addition, our data have shown that Anxa2 might influence proliferation, migration and invasion of MCF‐7 cells by increasing expression of c‐myc and cyclin D1 via activation of Erk1/2 signalling pathways.

Conclusion

Our findings suggest that up‐regulation of Anxa2 may play an important role in modulating proliferation and invasion of breast cancer MCF‐7 cells through regulation of many relevant downstream target genes.
Studies into primary and secondary infection processes by Plasmodiophora brassicae on canola
Authors: Feng J. , Hwang S.‐F. , Strelkov S. E.
Published: March 2012

The early stages of infection of canola roots by the clubroot pathogen Plasmodiophora brassicae were investigated. Inoculation with 1 × 105 resting spores mL−1 resulted in primary (root hair) infection at 12 h after inoculation (hai). Secondary (cortical) infection began to be observed at 72 hai. When inoculated onto plants at a concentration of 1 × 104 mL−1, secondary zoospores produced primary infections similar to those obtained with resting spores at a concentration of 1 × 105 mL−1. Secondary zoospores caused secondary infections earlier than resting spores. When the plants were inoculated with 1 × 107 resting spores mL−1, 2 days after being challenged with 1 × 104 or 1 × 105 resting spores mL−1, secondary infections were observed on the very next day, which was earlier than the secondary infections resulting from inoculation with 1 × 107 resting spores mL−1 alone and more severe than those produced by inoculation with 1 × 104 or 1 × 105 resting spores mL−1 alone. Compared with the single inoculations, secondary infections on plants that had received both inoculations remained at higher levels throughout a 7‐day time course. These data indicate that primary zoospores can directly cause secondary infection when the host is under primary infection, helping to understand the relationship and relative importance of the two infection stages of P. brassicae.