bluuebunny/crossref_metadata_2025 huggingface dataset:
The evolution of protein domain families
Authors: Buljan Marija , Bateman Alex
Published: July 2009

Protein domains are the common currency of protein structure and function. Over 10000 such protein families have now been collected in the Pfam database. Using these data along with animal gene phylogenies from TreeFam allowed us to investigate the gain and loss of protein domains. Most gains and losses of domains occur at protein termini. We show that the nature of changes is similar after speciation or duplication events. However, changes in domain architecture happen at a higher frequency after gene duplication. We suggest that the bias towards protein termini is largely because insertion and deletion of domains at most positions in a protein are likely to disrupt the structure of existing domains. We can also use Pfam to trace the evolution of specific families. For example, the immunoglobulin superfamily can be traced over 500 million years during its expansion into one of the largest families in the human genome. It can be shown that this protein family has its origins in basic animals such as the poriferan sponges where it is found in cell-surface-receptor proteins. We can trace how the structure and sequence of this family diverged during vertebrate evolution into constant and variable domains that are found in the antibodies of our immune system as well as in neural and muscle proteins.
Why there is more to protein evolution than protein function: splicing, nucleosomes and dual-coding sequence
Authors: Warnecke Tobias , Weber Claudia C. , Hurst Laurence D.
Published: July 2009

There is considerable variation in the rate at which different proteins evolve. Why is this? Classically, it has been considered that the density of functionally important sites must predict rates of protein evolution. Likewise, amino acid choice is usually assumed to reflect optimal protein function. In the present article, we briefly review evidence suggesting that this protein function-centred view is too simplistic. In particular, we concentrate on how selection acting during the protein's production history can also affect protein evolutionary rates and amino acid choice. Exploring the role of selection at the DNA and RNA level, we specifically address how the need (i) to specify exonic splice enhancer motifs in pre-mRNA, and (ii) to ensure nucleosome positioning on DNA have an impact on amino acid choice and rates of evolution. For both, we review evidence that sequence affected by more than one coding demand is particularly constrained. Strikingly, in mammals, splicing-related constraints are quantitatively as important as expression parameters in predicting rates of protein evolution. These results indicate that there is substantially more to protein evolution than protein functional constraints.
Evidence for an episodic model of protein sequence evolution
Authors: Studer Romain A. , Robinson-Rechavi Marc
Published: July 2009

The evolution of protein function appears to involve alternating periods of conservative evolution and of relatively rapid change. Evidence for such episodic evolution, consistent with some theoretical expectations, comes from the application of increasingly sophisticated models of evolution to large sequence datasets. We present here some of the recent methods to detect functional shifts, using amino acid or codon models. Both provide evidence for punctual shifts in patterns of amino acid conservation, including the fixation of key changes by positive selection. Although a link to gene duplication, a presumed source of functional changes, has been difficult to establish, this episodic model appears to apply to a wide variety of proteins and organisms.
Usingin vivozebrafish models to understand the biochemical basis of neutrophilic respiratory disease
Authors: Martin Jane S. , Renshaw Stephen A.
Published: July 2009

Neutrophilic inflammation in the lung protects against infectious disease, and usually resolves spontaneously after removal of the inflammatory stimulus. However, much lung disease is caused by a failure of resolution of neutrophilic inflammation. Our laboratory is seeking an understanding of the biochemical basis of inflammation resolution, using the zebrafish model system. Zebrafish larvae are transparent, allowing visualization of GFP (green fluorescent protein)-labelled leucocytes during inflammation in vivo, and they can be readily manipulated by a range of forward and reverse genetic techniques. This combination of advantages makes zebrafish a powerful tool for the study of in vivo inflammatory processes. Using this model, we have visualized the process of inflammation resolution in vivo, and identified a role for apoptosis in this process. In addition, we have performed a forward genetic screen for mutants with defective resolution of inflammation, and reverse genetic experiments examining the influence of candidate genes on inflammation resolution. We have established a platform for screening for compounds with anti-inflammatory activity, which has yielded a number of interesting leads. Looking forward to succeed in the future, we are working at combining mutants, transgenes and pharmacological agents to dissect the biochemical basis of inflammation resolution, and to identify compounds that might be used to treat patients with respiratory disease.
ENU mutagenesis as a tool for understanding lung development and disease
Authors: Yates Laura , McMurray Fiona , Zhang Youming , Greenfield Andy , Moffatt Miriam , Cookson William , Dean Charlotte
Published: July 2009

ENU (N-ethyl-N-nitrosourea) is a chemical mutagen that randomly induces point mutations in DNA. Since the 1990s ENU has been successfully used as a means to obtain mouse mutants using both gene-driven (reverse genetics) and phenotype-driven (forward genetics) approaches. A high-efficiency ENU approach results in approx. 25 functional mutations per genome; most of these will result in hypomorphic alleles. Our group has recently begun using ENU mutagenesis as a tool for understanding lung development and disease. In collaboration with other groups at MRC Harwell, we have undertaken a screen for recessive mutations affecting mouse lung development. We are currently pursuing two lines identified from this screen, Hel (head, eye and lung) and RecBA17. Both these lines exhibit lung defects and we believe that by studying the phenotypes and identifying the causative mutations, we may also shed light on lung disease pathogenesis. In collaboration with Bill Cookson and Miriam Moffatt, we are also taking a gene-driven approach for understanding asthma. Using the Harwell ENU sperm archive, we have recovered mouse lines harbouring mutations in the asthma-susceptibility genes Phf11 (PHD finger protein 11) and Dpp10 (dipeptidylpeptidase 10). Functional analyses of these alleles are currently under way.
Role of CFTR,Pseudomonas aeruginosaand Toll-like receptors in cystic fibrosis lung inflammation
Authors: Buchanan Paul J. , Ernst Robert K. , Elborn J. Stuart , Schock Bettina
Published: July 2009

CF (cystic fibrosis) is a severe autosomal recessive disease most common in Northwest European populations. Underlying mutations in the CFTR (CF transmembrane conductance regulator) gene cause deregulation of ion transport and subsequent dehydration of the airway surface liquid, producing a viscous mucus layer on the airway surface of CF patients. This layer is readily colonized by bacteria such as Pseudomonas aeruginosa. Owing to the resulting environment and treatment strategies, the bacteria acquire genetic modifications such as antibiotic resistance, biofilm formation, antimicrobial peptide resistance and pro-inflammatory lipid A structures. Lipid A is a component of the lipopolysaccharide cell wall present on bacteria and is recognized by TLR4 (Toll-like receptor 4). Its detection elicits a pro-inflammatory response that is heightened over time due to the addition of fatty acids to the lipid A structure. Eradication of bacteria from the lungs of CF patients becomes increasingly difficult and eventually leads to mortality. In the present review, we describe the role of lipid A as a virulent factor of Ps. aeruginosa; however, it appears that further work is needed to investigate the role of CFTR in the innate immune response and in modifying the pathogen–host interaction.
Regulation of Cdc45 in the cell cycle and after DNA damage
Authors: Broderick Ronan , Nasheuer Heinz-Peter
Published: July 2009

The Cdc (cell division cycle) 45 protein has a central role in the regulation of the initiation and elongation stages of eukaryotic chromosomal DNA replication. In addition, it is the main target for a Chk1 (checkpoint kinase 1)-dependent Cdc25/CDK2 (cyclin-dependent kinase 2)-independent DNA damage checkpoint signal transduction pathway following low doses of BPDE (benzo[a]pyrene dihydrodiol epoxide) treatment, which causes DNA damage similar to UV-induced adducts. Cdc45 interacts physically and functionally with the putative eukaryotic replicative DNA helicase, the MCM (mini-chromosome maintenance) complex, and forms a helicase active ‘supercomplex’, the CMG [Cdc45–MCM2–7–GINS (go-ichi-ni-san)] complex. These known protein–protein interactions, as well as unknown interactions and post-translational modifications, may be important for the regulation of Cdc45 and the initiation of DNA replication following DNA damage. Future studies will help to elucidate the molecular basis of this newly identified S-phase checkpoint pathway which has Cdc45 as a target.
Electronic effects on melting: Comparison of aluminum cluster anions and cations
Authors: Starace Anne K. , Neal Colleen M. , Cao Baopeng , Jarrold Martin F. , Aguado Andrés , López José M.
Published: July 2009

Heat capacities have been measured as a function of temperature for aluminum cluster anions with 35–70 atoms. Melting temperatures and latent heats are determined from peaks in the heat capacities; cohesive energies are obtained for solid clusters from the latent heats and dissociation energies determined for liquid clusters. The melting temperatures, latent heats, and cohesive energies for the aluminum cluster anions are compared to previous measurements for the corresponding cations. Density functional theory calculations have been performed to identify the global minimum energy geometries for the cluster anions. The lowest energy geometries fall into four main families: distorted decahedral fragments, fcc fragments, fcc fragments with stacking faults, and “disordered” roughly spherical structures. The comparison of the cohesive energies for the lowest energy geometries with the measured values allows us to interpret the size variation in the latent heats. Both geometric and electronic shell closings contribute to the variations in the cohesive energies (and latent heats), but structural changes appear to be mainly responsible for the large variations in the melting temperatures with cluster size. The significant charge dependence of the latent heats found for some cluster sizes indicates that the electronic structure can change substantially when the cluster melts.
Modification of the valence band structures of polar and nonpolar plane wurtzite-GaN by anisotropic strain
Authors: Fu Deyi , Zhang Rong , Wang Baigeng , Zhang Zeng , Liu Bin , Xie Zili , Xiu Xiangqian , Lu Hai , Zheng Youdou , Edwards Gerard
Published: July 2009

The influence of anisotropic strain on the valence band structure and related properties, including excitonic transition energies, transition polarization selection rules, band-edge hole effective masses, and exciton reduced effective masses, of polar and nonpolar plane GaN are systematically investigated using the well-known k⋅p Hamiltonian approach. We re-examine the band deformation potentials D3 and D4, and interband hydrostatic deformation potentials a1 and a2, and find that they take the values 9.4, −4.7, −3.0, and −12.4 eV, respectively. In order to correctly interpret the optical properties of GaN, the spin-orbit coupling effect cannot be neglected. Our numerical calculations show that pure linear polarization light emissions and absorptions can be obtained. In addition, the two topmost valence subbands can be effectively separated to reduce the band-edge density of state by manipulating the strain states in GaN epilayers, which is favorable for laser diode design. Furthermore, the band-edge hole effective masses exhibit significant in-plane anisotropy and are sensitive to the residual strain, while the influence of the residual strain on the exciton reduced effective masses is relatively weak.
Thermal diffusivity measurements of thin plates and filaments using lock-in thermography
Authors: Mendioroz Arantza , Fuente-Dacal Raquel , Apiñaniz Estibaliz , Salazar Agustín
Published: July 2009

Photothermal radiometry has been widely used to measure the thermal diffusivity of bulk materials. In the case of thin plates and filaments, a one-dimensional heat propagation model including heat losses has been developed, predicting that the thermal diffusivity can be obtained by recording both the surface temperature amplitude and phase profile slopes (“slope method”). However, this method has given highly overestimated values of the thermal diffusivity of poor-conducting films and filaments. In this paper we analyze the effect of the experimental factors affecting the thermal diffusivity measurements of thin plates and filaments using infrared thermography, in order to establish the experimental conditions needed to obtain accurate and reliable values of the diffusivity of any kind of material using the slope method. We present the calculations of the surface temperature of thin isotropic and anisotropic plates heated by a modulated and tightly focused laser beam, showing that the slope method is also valid for this kind of pointlike heating. Special attention is paid to the effect of surface heat losses (convective and radiative) on the diffusivity measurements of small-dimension and poor-conducting materials. Lock-in thermography measurements performed in the best experimental conditions on a wide set of samples of different thermal properties (thin isotropic and anisotropic plates and filaments) confirm the validity of the slope method to measure accurately the thermal diffusivity of samples of these shapes.
Study of polarization properties of light emitted from a-plane InGaN/GaN quantum well-based light emitting diodes
Authors: Huang Hung-Hsun , Wu Yuh-Renn
Published: July 2009

This paper discusses the optical characteristics of a nonpolar a-plane InGaN/GaN quantum well with different indium compositions, quantum well widths, and injection carrier densities. The self-consistent Poisson and 6×6 k⋅p Schrödinger solver has been applied to study the band structures in nonpolar a-plane InGaN-based quantum well light emitting diodes (LEDs). We find that the larger indium composition and smaller well width make the energy separation of |Y⟩-like state to |Z⟩-like state larger, and as a result enhance the polarization ratio of light. However, the polarization ratio decreases as the carrier injection increases, which might be a drawback for high power applications. We have studied the optimization condition for designing the a-plane InGaN quantum well LED for applications, such as liquid crystal display backlight modules and lasers, which would be useful information for device designs.
Directional spherical multipole wavelets
Authors: Hayn Michael , Holschneider Matthias
Published: July 2009

We construct a family of admissible analysis reconstruction pairs of wavelet families on the sphere. The construction is an extension of the isotropic Poisson wavelets. Similar to those, the directional wavelets allow a finite expansion in terms of off-center multipoles. Unlike the isotropic case, the directional wavelets are not a tight frame. However, at small scales, they almost behave like a tight frame. We give an explicit formula for the pseudodifferential operator given by the combination analysis-synthesis with respect to these wavelets. The Euclidean limit is shown to exist and an explicit formula is given. This allows us to quantify the asymptotic angular resolution of the wavelets.
Photocurrent transients in all-polymer solar cells: Trapping and detrapping effects
Authors: McNeill Christopher R. , Hwang Inchan , Greenham Neil C.
Published: July 2009

We have studied photocurrent transients in all-polymer bulk-heterojunction solar cells based on poly(3-hexylthiophene) and poly((9,9-dioctylfluorene)-2,7-diyl-alt-[4,7-bis(3-hexylthien-5-yl)-2,1,3-benzothiadiazole]-2′,2″-diyl). By illuminating devices with square pulses of light of varying intensity, we reveal nonlinear photocurrent transients on the timescale of tens of microseconds. These microsecond photocurrent transients are attributed to the effects of trapping and detrapping of charges on this timescale, in particular, electrons. The buildup of trapped electrons results in the appearance of a peak in the photocurrent at high intensities at ∼10 μs after turn on. This trapped charge produces a local reduction in the strength of the internal electric field near the anode resulting in a net decrease in charge separation efficiency and an increase in the likelihood of bimolecular recombination due to increased and overlapping electron and hole densities. After turn off, a long photocurrent tail is observed with charge still being extracted after 0.5 ms consistent with the detrapping of deeply trapped charges. We are able to reproduce the observed transient photocurrent features using a time-dependent drift-diffusion model incorporating the trapping and detrapping of electrons.
Hybrid polymer-porous silicon photonic crystals for optical sensing
Authors: De Stefano L. , Rotiroti L. , De Tommasi E. , Rea I. , Rendina I. , Canciello M. , Maglio G. , Palumbo R.
Published: July 2009

Porous silicon based one-dimensional photonic crystals, such as Bragg mirror and optical microcavity, has been modified by infiltration of a new biocompatible polymer, an amino functionalized poly(ε-caprolactone) (PCL-NH2), and characterized as optical biochemical sensors. The entrapped polymer adds strong chemical stability to the nanocrystalline matrix on exposure to alkaline solutions preserving the device sensing abilities in monitoring volatile substances and chemical compounds. On the basis of these results, these hybrid structures can be proposed as a high performance platform for biochemical applications.
The Sp(1)-Kepler problems
Authors: Meng Guowu
Published: July 2009

Let n≥2 be a positive integer. To each irreducible representation σ of Sp(1), an Sp(1)-Kepler problem in dimension (4n−3) is constructed and analyzed. This system is superintegrable, and when n=2 it is equivalent to a generalized MICZ-Kepler problem in dimension of 5. The dynamical symmetry group of this system is Õ∗(4n) with the Hilbert space of bound states H(σ) being the unitary highest weight representation of O∗˜(4n) with highest weight, (−1,⋯,−1,−(1+σ¯)), which occurs at the rightmost nontrivial reduction point in the Enright–Howe–Wallach classification diagram for the unitary highest weight modules. Here σ¯ is the highest weight of σ. Furthermore, it is shown that the correspondence σ↔H(σ) is the theta-correspondence for dual pair (Sp(1),O∗(4n))⊆Sp(8n,R).
Half-metallic properties of perovskite BaCrO3 and BaCr0.5Ti0.5O3 superlattice: LSDA+U calculations
Authors: Zhu Z. H. , Yan X. H.
Published: July 2009

Under the local-spin density approximation method plus on-site coulomb interaction U correction (LSDA+U), the BaCrO3 in the perovskite structure is found to be half-metallic ferromagnet with an integral magnet moment of 2.000 Bohr magnetons (μB) per unit. The feasibility of constructing the BaCr0.5Ti0.5O3 superlattice to stabilize the perovskite phase for the BaCrO3 is theoretically explored. Additionally, the influence of screened parameters U on the electronic structures and magnet moments of the perovskite BaCrO3 and BaCr0.5Ti0.5O3 superlattice is expounded.
Molecular beam epitaxy of SrTiO3 with a growth window
Authors: Jalan Bharat , Moetakef Pouya , Stemmer Susanne
Published: July 2009

Many complex oxides with only nonvolatile constituents do not have a wide growth window in conventional molecular beam epitaxy (MBE) approaches, which makes it difficult to obtain stoichiometric films. Here it is shown that a growth window in which the stoichiometry is self-regulating can be achieved for SrTiO3 films by using a hybrid MBE approach that uses a volatile metal-organic source for Ti, titanium tetra isopropoxide (TTIP). The growth window widens and shifts to higher TTIP/Sr flux ratios with increasing temperature, showing that it is related to the desorption of the volatile TTIP. We demonstrate stoichiometric, highly perfect, insulating SrTiO3 films. The approach can be adapted for the growth of other complex oxides that previously were believed to have no wide MBE growth window.
In-plane thermal conductivity of nanoscale polyaniline thin films
Authors: Jin Jiezhu , Manoharan Mohan P. , Wang Qing , Haque M. A.
Published: July 2009

Thermal characterization of conducting polymers is important in understanding transport phenomena in energy conversion and flexible electronics devices. We present an experimental technique to determine the in-plane thermal conductivity and the thermal contact resistance of thin films on substrates simultaneously. For 20 nm thick polyaniline films on SiO2 substrate, the respective values were measured to be 0.0406 W/m K and 0.806 K m2/W. We also observed thickness dependence of in-plane thermal conductivity, which suggests that heat transfer is governed by phonon-boundary scattering when the film thickness is close to the mean free path.
Polarization of one-dimensional periodic systems in a static electric field: Sawtooth potential treatment revisited
Authors: Kirtman Bernard , Ferrero Mauro , Rérat Michel , Springborg Michael
Published: July 2009

Various periodic piecewise linear potentials for extracting the electronic response of an infinite periodic system to a uniform electrostatic field are examined. It is shown that discontinuous potentials, such as the sawtooth, cannot be used for this purpose. Continuous triangular potentials can be successfully employed to determine both even- and odd-order (hyper)polarizabilities, as demonstrated here for the first time, although the permanent dipole moment of the corresponding long finite chain remains out of reach. Moreover, for typical highly polarizable organic systems, the size of the repeated unit has to be much larger than that of the finite system in order to obtain convergence with respect to system size. All results are illustrated both through extensive model calculations and through ab initio calculations on poly- and oligoacetylenes.
Solvation dynamics in ionic fluids: An extended Debye–Hückel dielectric continuum model
Authors: Song Xueyu
Published: July 2009

Motivated by our recent proposition on the possibility of using dielectric continuum models to interpret experimental measurements of solvation dynamics in room temperature ionic liquids [J. Phys. Chem. A 110, 8623 (2006)], some detailed simulation studies are performed to test the validity of our proposition. From these simulation studies, it seems to be justified that an extended Debye–Hückel continuum model can be used to understand the solvation dynamics of ionic fluids. The theoretical underpinning of such an extended Debye–Hückel model is presented from the general dispersion relation in electrodynamics. The connection with the static extension from the dressed ion theory of electrolyte solutions is also discussed. Such a connection between the Debye–Hückel theory and the dispersion relation may be exploited to enhance our understanding of the electric double layer problem not only for the static case but also for dynamic situations.
Drawing the Line: How People with Autism Copy Line Drawings of Three-Dimensional Objects
Authors: Sheppard Elizabeth , Ropar Danielle , Mitchell Peter
Published: July 2009

It is purported that the local perceptual style characteristic of those with autism results in them reproducing line drawings in a more localised manner than comparison individuals. Here we report an exception to this: the drawing strategies of those with autism were more global. When reproducing line drawings depicting three-dimensional objects, a sample of fifty-six participants with autism showed a greater tendency to begin by copying the two-dimensional outline of the figure than fifty-seven matched comparison participants (39.3% versus 8.8% of group; χ21 = 14.46, p < 0.0005). We argue that this is consistent with the perception of those with autism being less conceptually driven, but not necessarily less global.
Seasonal changes in optically assessed epidermal phenolic compounds and chlorophyll contents in leaves of sessile oak (Quercus petraea): towards signatures of phenological stage
Authors: Louis Juliette , Meyer Sylvie , Maunoury-Danger Florence , Fresneau Chantal , Meudec Emmanuelle , Cerovic Zoran G.
Published: July 2009

Seasonal patterns of dry mass invested in chlorophyll and epidermal phenolic compounds (EPhen) were investigated in vivo using optical methods, in leaves of 2-year-old oaks (Quercus petraea Matt. (Liebl.)) grown under semi-controlled conditions. The plasticity of the seasonal pattern was investigated by applying stem girdling treatment. In control young expanding leaves, leaf dry mass per area, dry mass investment in chlorophyll and abaxial EPhen content increased. In late May, at leaf maturity, these variables reached a plateau, and adaxial and abaxial EPhen contents became similar. Thereafter, as leaves aged, dry mass investment in chlorophyll gradually decreased, whereas it remained steady for EPhen. Girdling treatment impacted this seasonal pattern differently depending on the phenological stage. Treatment effects and their reversion revealed in vivo EPhen turnover. Finally, optical signatures of immature and mature leaf phenological stages with contrasting nitrogen and carbon economy were proposed, based on the relationship between the chlorophyll to EPhen ratio and the leaf nitrogen to carbon ratio.
Hydraulic redistribution by Protea 'Sylvia' (Proteaceae) facilitates soil water replenishment and water acquisition by an understorey grass and shrub
Authors: Hawkins Heidi-J. , Hettasch Hans , West Adam G. , Cramer Michael D.
Published: July 2009

Proteaceae of the Cape Floristic Region, South Africa, transpire throughout the summer drought, implying access to deep water. Hydraulic redistribution by Protea ‘Sylvia’ [P. susannae E. Phillips × P. exima (Salisb. Ex Knight) Fource; Proteaceae] was investigated in overnight pot and field experiments, where it was hypothesised that (1) Proteaceae replenish water in upper soil layers, (2) hydraulic redistribution facilitates nutrient uptake and (3) shallow-rooted understorey plants ‘parasitise’ water from proteas. Potted Sylvias redistributed ~17% of the tritiated water supplied, equating to 34 ± 1.2 mL plant−1. Shallow-rooted Cyanodon dactylon (L.) Pers. (Poaceae), plants growing in the same pots as Sylvia contained amounts of labelled water similar to those found in Sylvia, indicting water parasitism. In the field, Sylvia plants growing in aeolian sands took up the deuterated water applied at 1.2 m depth as indicated by increased δ2H of plant xylem water from –38 ± 0.8 to 334 ± 157‰. This deuterated water was then redistributed to the upper soil layer (0.2 and 0.4 m), as indicated by increased δ2H of soil water from –24.5 ± 0.7 to –8.0 ± 3.0‰ and soil moisture from 0.48 to 0.89%. Lithium, as a K-analogue, was taken up equally by plants watered with deep water and those not watered, probably since both had access to naturally-occurring deep water. Water in stems of the shallow-rooted understorey shrub, Leysera gnaphalodes (L.) L. (Asteraceae) had similar δ2H values to stems of Sylvia (P = 0.939), again indicating water parasitism was tightly coupled to the protea. We conclude that hydraulic redistribution by Proteaceae plays an important role in soil water replenishment, water supply to shallow-rooted plants, and, thus, ecosystem structure and function during the summer drought of the Cape Floristic Region.
Genetic technologies for the identification of plant genes controlling environmental stress responses
Authors: Papdi Csaba , Joseph Mary Prathiba , Salamó Imma Pérez , Vidal Sabina , Szabados László
Published: July 2009

Abiotic conditions such as light, temperature, water availability and soil parameters determine plant growth and development. The adaptation of plants to extreme environments or to sudden changes in their growth conditions is controlled by a well balanced, genetically determined signalling system, which is still far from being understood. The identification and characterisation of plant genes which control responses to environmental stresses is an essential step to elucidate the complex regulatory network, which determines stress tolerance. Here, we review the genetic approaches, which have been used with success to identify plant genes which control responses to different abiotic stress factors. We describe strategies and concepts for forward and reverse genetic screens, conventional and insertion mutagenesis, TILLING, gene tagging, promoter trapping, activation mutagenesis and cDNA library transfer. The utility of the various genetic approaches in plant stress research we review is illustrated by several published examples.
Flooding tolerance: suites of plant traits in variable environments
Authors: Colmer T. D. , Voesenek L. A. C. J.
Published: July 2009

Flooding regimes of different depths and durations impose selection pressures for various traits in terrestrial wetland plants. Suites of adaptive traits for different flooding stresses, such as soil waterlogging (short or long duration) and full submergence (short or long duration – shallow or deep), are reviewed. Synergies occur amongst traits for improved internal aeration, and those for anoxia tolerance and recovery, both for roots during soil waterlogging and shoots during submergence. Submergence tolerance of terrestrial species has recently been classified as either the Low Oxygen Quiescence Syndrome (LOQS) or the Low Oxygen Escape Syndrome (LOES), with advantages, respectively, in short duration or long duration (shallow) flood-prone environments. A major feature of species with the LOQS is that shoots do not elongate upon submergence, whereas those with the LOES show rapid shoot extension. In addition, plants faced with long duration deep submergence can demonstrate aspects of both syndromes; shoots do not elongate, but these are not quiescent, as new aquatic-type leaves are formed. Enhanced entries of O2 and CO2 from floodwaters into acclimated leaves, minimises O2 deprivation and improves underwater photosynthesis, respectively. Evolution of ‘suites of traits’ are evident in wild wetland species and in rice, adapted to particular flooding regimes.
Presynaptic peptidergic modulation of olfactory receptor neurons in Drosophila
Authors: Ignell Rickard , Root Cory M. , Birse Ryan T. , Wang Jing W. , Nässel Dick R. , Winther Åsa M. E.
Published: July 2009

The role of classical neurotransmitters in the transfer and processing of olfactory information is well established in many organisms. Neuropeptide action, however, is largely unexplored in any peripheral olfactory system. A subpopulation of local interneurons (LNs) in the
Drosophila
antannal lobe is peptidergic, expressing
Drosophila
tachykinins (DTKs). We show here that olfactory receptor neurons (ORNs) express the DTK receptor (DTKR). Using two-photon microscopy, we found that DTK applied to the antennal lobe suppresses presynaptic calcium and synaptic transmission in the ORNs. Furthermore, reduction of DTKR expression in ORNs by targeted RNA interference eliminates presynaptic suppression and alters olfactory behaviors. We detect opposite behavioral phenotypes after reduction and over expression of DTKR in ORNs. Our findings suggest a presynaptic inhibitory feedback to ORNs from peptidergic LNs in the antennal lobe.
Preerythrocytic, live-attenuated
Plasmodium falciparum
vaccine candidates by design
Authors: VanBuskirk Kelley M. , O'Neill Matthew T. , De La Vega Patricia , Maier Alexander G. , Krzych Urszula , Williams Jack , Dowler Megan G. , Sacci John B. , Kangwanrangsan Niwat , Tsuboi Takafumi , Kneteman Norman M. , Heppner Donald G. , Murdock Brant A. , Mikolajczak Sebastian A. , Aly Ahmed S. I. , Cowman Alan F. , Kappe Stefan H. I.
Published: July 2009

Falciparum malaria is initiated when
Anopheles
mosquitoes transmit the
Plasmodium
sporozoite stage during a blood meal. Irradiated sporozoites confer sterile protection against subsequent malaria infection in animal models and humans. This level of protection is unmatched by current recombinant malaria vaccines. However, the live-attenuated vaccine approach faces formidable obstacles, including development of accurate, reproducible attenuation techniques. We tested whether
Plasmodium falciparum
could be attenuated at the early liver stage by genetic engineering. The
P. falciparum
genetically attenuated parasites (GAPs) harbor individual deletions or simultaneous deletions of the sporozoite-expressed genes
P52
and
P36
. Gene deletions were done by double-cross-over recombination to avoid genetic reversion of the knockout parasites. The gene deletions did not affect parasite replication throughout the erythrocytic cycle, gametocyte production, mosquito infections, and sporozoite production rates. However, the deletions caused parasite developmental arrest during hepatocyte infection. The double-gene deletion line exhibited a more severe intrahepatocytic growth defect compared with the single-gene deletion lines, and it did not persist. This defect was assessed in an in vitro liver-stage growth assay and in a chimeric mouse model harboring human hepatocytes. The strong phenotype of the double knockout GAP justifies its human testing as a whole-organism vaccine candidate using the established sporozoite challenge model. GAPs might provide a safe and reproducible platform to develop an efficacious whole-cell malaria vaccine that prevents infection at the preerythrocytic stage.
The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis
Authors: Guo Deliang , Hildebrandt Isabel J. , Prins Robert M. , Soto Horacio , Mazzotta Mary M. , Dang Julie , Czernin Johannes , Shyy John Y.-J. , Watson Andrew D. , Phelps Michael , Radu Caius G. , Cloughesy Timothy F. , Mischel Paul S.
Published: July 2009

The EGFR/PI3K/Akt/mTOR signaling pathway is activated in many cancers including glioblastoma, yet mTOR inhibitors have largely failed to show efficacy in the clinic. Rapamycin promotes feedback activation of Akt in some patients, potentially underlying clinical resistance and raising the need for alternative approaches to block mTOR signaling. AMPK is a metabolic checkpoint that integrates growth factor signaling with cellular metabolism, in part by negatively regulating mTOR. We used pharmacological and genetic approaches to determine whether AMPK activation could block glioblastoma growth and cellular metabolism, and we examined the contribution of EGFR signaling in determining response in vitro and in vivo. The AMPK-agonist AICAR, and activated AMPK adenovirus, inhibited mTOR signaling and blocked the growth of glioblastoma cells expressing the activated EGFR mutant, EGFRvIII. Across a spectrum of EGFR-activated cancer cell lines, AICAR was more effective than rapamycin at blocking tumor cell proliferation, despite less efficient inhibition of mTORC1 signaling. Unexpectedly, addition of the metabolic products of cholesterol and fatty acid synthesis rescued the growth inhibitory effect of AICAR, whereas inhibition of these lipogenic enzymes mimicked AMPK activation, thus demonstrating that AMPK blocked tumor cell proliferation primarily through inhibition of cholesterol and fatty acid synthesis. Most importantly, AICAR treatment in mice significantly inhibited the growth and glycolysis (as measured by
18
fluoro-2-deoxyglucose microPET) of glioblastoma xenografts engineered to express EGFRvIII, but not their parental counterparts. These results suggest a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers.
Edge pedestal control in quiescent H-mode discharges in DIII-D using co-plus counter-neutral beam injection
Authors: Burrell K.H. , Osborne T.H. , Snyder P.B. , West W.P. , Fenstermacher M.E. , Groebner R.J. , Gohil P. , Leonard A.W. , Solomon W.M.
Published: July 2009

We have made two significant discoveries in our recent studies of quiescent H-mode (QH-mode) plasmas in DIII-D. First, we have found that we can control the edge pedestal density and pressure by altering the edge particle transport through changes in the edge toroidal rotation. This allows us to adjust the edge operating point to be close to, but below the ELM stability boundary, maintaining the ELM-free state while allowing up to a factor of two increase in edge pressure. The ELM boundary is significantly higher in more strongly shaped plasmas, which broadens the operating space available for QH-mode and leads to improved core performance. Second, for the first time on any tokamak, we have created QH-mode plasmas with strong edge co-rotation; previous QH-modes in all tokamaks had edge counter-rotation. This result demonstrates that counter-NBI and edge-counter rotation are not essential conditions for QH-mode. Both these investigations benefited from the edge stability predictions based on peeling–ballooning mode theory. The broadening of the ELM-stable region with plasma shaping is predicted by that theory. The theory has also been extended to provide a model for the edge harmonic oscillation that enhances edge transport in the QH-mode. Many of the features of that theory agree with the experimental results reported either previously or in this paper. One notable example is the prediction that co-rotating QH-mode is possible provided sufficient shear in the edge rotation can be created.
Two distinct regimes of turbulence in HL-2A tokamak plasmas
Authors: Zhao K.J. , Dong J.Q. , Yan L.W. , Hong W.Y. , Li Q. , Qian J. , Cheng J. , Liu A.D. , Zhao H.L. , Kong D.F. , Liu Yi , Huang Y. , Song X.M. , Ding X.T. , Yang Q.W. , Duan X.R. , Liu Yong
Published: July 2009

Two distinct regimes of turbulence are identified with Langmuir probe arrays in the edge plasmas of the HuanLiuqi (HL)-2A tokamak for the first time. The spatial and temporal coherent characteristics of the low frequency fluctuations (LFFs) of 20–100 kHz are found in significant contrast to the high frequency ambient turbulence (HFAT) of 100 kHz or higher. In the LFF regime, the deviations from the regular linear dispersion relations of the HFAT are observed. The poloidal and toroidal correlation lengths of the former are measured one order of magnitude longer than that of the latter. The ratio of the temporal scales of the fluctuations in the LFF and HFAT regimes is estimated to be of the same order as that for the spatial scales. The LFF may coexist with and differentiate from the geodesic acoustic modes. The bispectrum analysis of the data indicates that nonlinear three wave coupling between the LFF and HFAT is a possible creation mechanism for the former. The possible correlation of the results with the theory and simulation predictions on quasimodes is discussed.
CENP-H–containing Complex Facilitates Centromere Deposition of CENP-A in Cooperation with FACT and CHD1
Authors: Okada Masahiro , Okawa Katsuya , Isobe Toshiaki , Fukagawa Tatsuo
Published: July 2009

Centromere identity is thought to be determined by epigenetic mechanisms. The centromere-specific histone H3 variant CENP-A plays a central role in specifying the locus where the centromere is constructed. However, the precise mechanisms that target CENP-A to centromeric chromatin are poorly understood. Here, we show that facilitates chromatin transcription (FACT) localizes to centromeres in a CENP-H–containing complex-dependent manner. In conditional mutant cell lines for SSRP1, a subunit of FACT, centromere targeting of newly synthesized CENP-A is severely inhibited. The chromatin remodeling factor CHD1 binds to SSRP1 both in vivo and in vitro and associates with centromeres. The centromeric localization of CHD1 is lost in SSRP1-depleted cells. RNA interference knockdown of CHD1 leads to a decrease in the amount of centromere localized CENP-A. These findings indicate that the CENP-H–containing complex facilitates deposition of newly synthesized CENP-A into centromeric chromatin in cooperation with FACT and CHD1.
Integrating bioclimate with population models to improve forecasts of species extinctions under climate change
Authors: Brook Barry W. , Akçakaya H. Resit , Keith David A. , Mace Georgina M. , Pearson Richard G. , Araújo Miguel B.
Published: July 2009

Climate change is already affecting species worldwide, yet existing methods of risk assessment have not considered interactions between demography and climate and their simultaneous effect on habitat distribution and population viability. To address this issue, an international workshop was held at the University of Adelaide in Australia, 25–29 May 2009, bringing leading species distribution and population modellers together with plant ecologists. Building on two previous workshops in the UK and Spain, the participants aimed to develop methodological standards and case studies for integrating bioclimatic and metapopulation models, to provide more realistic forecasts of population change, habitat fragmentation and extinction risk under climate change. The discussions and case studies focused on several challenges, including spatial and temporal scale contingencies, choice of predictive climate, land use, soil type and topographic variables, procedures for ensemble forecasting of both global climate and bioclimate models and developing demographic structures that are realistic and species-specific and yet allow generalizations of traits that make species vulnerable to climate change. The goal is to provide general guidelines for assessing the Red-List status of large numbers of species potentially at risk, owing to the interactions of climate change with other threats such as habitat destruction, overexploitation and invasive species.
Systems-level cancer gene identification from protein interaction network topology applied to melanogenesis-related functional genomics data
Authors: Milenković Tijana , Memišević Vesna , Ganesan Anand K. , Pržulj Nataša
Published: July 2009

Many real-world phenomena have been described in terms of large networks. Networks have been invaluable models for the understanding of biological systems. Since proteins carry out most biological processes, we focus on analysing protein–protein interaction (PPI) networks. Proteins interact to perform a function. Thus, PPI networks reflect the interconnected nature of biological processes and analysing their structural properties could provide insights into biological function and disease. We have already demonstrated, by using a sensitive graph theoretic method for comparing topologies of node neighbourhoods called ‘graphlet degree signatures’, that proteins with similar surroundings in PPI networks tend to perform the same functions. Here, we explore whether the involvement of genes in cancer suggests the similarity of their topological ‘signatures’ as well. By applying a series of clustering methods to proteins' topological signature similarities, we demonstrate that the obtained clusters are significantly enriched with cancer genes. We apply this methodology to identify novel cancer gene candidates, validating 80 per cent of our predictions in the literature. We also validate predictions biologically by identifying cancer-related negative regulators of melanogenesis identified in our siRNA screen. This is encouraging, since we have done this solely from PPI network topology. We provide clear evidence that PPI network structure around cancer genes is different from the structure around non-cancer genes. Understanding the underlying principles of this phenomenon is an open question, with a potential for increasing our understanding of complex diseases.
Invasion, persistence and control in epidemic models for plant pathogens: the effect of host demography
Authors: Cunniffe Nik J. , Gilligan Christopher A.
Published: July 2009

Many epidemiological models for plant disease include host demography to describe changes in the availability of susceptible tissue for infection. We compare the effects of using two commonly used formulations for host growth, one linear and the other nonlinear, upon the outcomes for invasion, persistence and control of pathogens in a widely used, generic model for botanical epidemics. The criterion for invasion, reflected in the basic reproductive number,R0, is unaffected by host demography:R0is simply a function of epidemiological parameters alone. When, however, host growth is intrinsically nonlinear, unexpected results arise for persistence and the control of disease. The endemic level of infection (I∞) also depends uponR0. We show, however, that the sensitivity ofI∞to changes inR0> 1 depends upon which underlying epidemiological parameter is changed. IncreasingR0by shortening the infectious period results in a monotonic increase inI∞. If, however, an increase inR0is driven by increases in transmission rates or by decreases in the decay of free-living inoculum,I∞first increases (R0< 2), but then decreases (R0> 2). This counterintuitive result means that increasing the intensity of control can result in more endemic infection.
Taxonomic homogenization of woodland plant communities over 70 years
Authors: Keith Sally A. , Newton Adrian C. , Morecroft Michael D. , Bealey Clive E. , Bullock James M.
Published: July 2009

Taxonomic homogenization (TH) is the increasing similarity of the species composition of ecological communities over time. Such homogenization represents a form of biodiversity loss and can result from local species turnover. Evidence for TH is limited, reflecting a lack of suitable historical datasets, and previous analyses have generated contrasting conclusions. We present an analysis of woodland patches across a southern English county (Dorset) in which we quantified 70 years of change in the composition of vascular plant communities. We tested the hypotheses that over this time patches decreased in species richness, homogenized, or shifted towards novel communities. Although mean species richness at the patch scale did not change, we found increased similarity in species composition among woodlands over time. We concluded that the woodlands have undergone TH without experiencing declines in local diversity or shifts towards novel communities. Analysis of species characteristics suggested that these changes were not driven by non-native species invasions or climate change, but instead reflected reorganization of the native plant communities in response to eutrophication and increasingly shaded conditions. These analyses provide, to our knowledge, the first direct evidence of TH in the UK and highlight the potential importance of this phenomenon as a contributor to biodiversity loss.