bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of acetohydroxyacid synthase from Mycobacterium tuberculosis and the identification of its new inhibitor from the screening of a chemical library
Authors: Choi Kyoung-Jae , Yu Yeon Gyu , Hahn Hoh Gyu , Choi Jung-Do , Yoon Moon-Young
Published: August 2005

Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate‐ (ThDP‐) and FAD‐dependent enzyme that catalyzes the first common step in the biosynthetic pathway of the branched‐amino acids such as leucine, isoleucine, and valine. The genes of AHAS from Mycobacterium tuberculosis were cloned, and overexpressed in E. coli and purified to homogeneity. The purified AHAS from M. tuberculosis is effectively inhibited by pyrazosulfuron ethyl (PSE), an inhibitor of plant AHAS enzyme, with the IC50 (inhibitory concentration 50%) of 0.87 μM. The kinetic parameters of M. tuberculosis AHAS were determined, and an enzyme activity assay system using 96‐well microplate was designed. After screening of a chemical library composed of 5600 compounds using the assay system, a new class of AHAS inhibitor was identified with the IC50 in the range of 1.8–2.6 μM. One of the identified compounds (KHG20612) further showed growth inhibition activity against various strains of M. tuberculosis. The correlation of the inhibitory activity of the identified compound against AHAS to the cell growth inhibition activity suggested that AHAS might be served as a target protein for the development of novel anti‐tuberculosis therapeutics.
Modulating furin activity with designed mini‐PDX peptides: Synthesis and in vitro kinetic evaluation
Authors: Basak Ajoy , Lotfipour Farzaneh
Published: August 2005

A peptide was designed from reactive site loop structure of α1 Antitrypsin Portland known as α1 PDX as a novel mini‐PDX inhibitor of furin. The sequence was derived from (367–394) that contains the crucial furin cleavage motif RIPR
382. A P3 mutant replacing Ile380 by Leu was prepared as a first model peptide. A Cys residue was inserted at each terminal of the peptide for purpose of cyclisation which was accomplished by air or iodine‐induced oxidation. This mini‐PDX peptide both cyclic and acyclic form inhibited in vitro furin activity (IC50 in nM) when measured against either substrates Boc‐RVRR⇓MCA or QVEGF‐C [Abz‐QVHSIIRR⇓SLP‐Y(NO2)‐A‐CONH2, Abz = 2‐amino benzoic acid and Y(NO2) = 3‐nitro tyrosine], latter being derived from vascular endothelial growth factor‐C (VEGF‐C) processing site. The geometrically constrained structure mimicking PDX reactive loop is crucial for enzyme inhibition. Our study further revealed that both mini‐PDX peptides inactivate furin in a slow tight binding manner, with disulfide‐bridged cyclic form being slightly more potent. Unlike PDX, these peptides inhibit furin via a different mechanistic pathway. The study provides an alternate strategy for development of efficient peptide‐based inhibitors of Proprotein Convertases including furin.
Free uptake of cell‐penetrating peptides by fission yeast
Authors: Parenteau Julie , Klinck Roscoe , Good Liam , Langel Ülo , Wellinger Raymund J. , Elela Sherif Abou
Published: August 2005

An increasing number of peptides translocate the plasma membrane of mammalian cells promising new avenues for drug delivery. However, only a few examples are known to penetrate the fungal cell wall. We compared the capacity of different fluorophore‐labelled peptides to translocate into fission yeast and human cells and determined their intracellular distribution. Most of the 20 peptides tested were able to enter human cells, but only one, transportan 10 (TP10), efficiently penetrated fission yeast and was distributed uniformly inside the cells. The results show that the fungal cell wall may reduce, but does not block peptide uptake.
Wnt‐3a regulates chondrocyte differentiation via c‐Jun/AP‐1 pathway
Authors: Hwang Sang-Gu , Yu Sung-Sook , Lee Soo-Woong , Chun Jang-Soo
Published: August 2005

Our previous study indicated that interleukin (IL)‐1β induces expression of several Wnt proteins in chondrocytes and causes chondrocyte dedifferentiation via the c‐Jun/activator protein‐1 (AP‐1) pathway. This study examined whether Wnt‐3a causes chondrocyte dedifferentiation via the c‐Jun/AP‐1 pathway. Wnt‐3a inhibited chondrogenesis of mesenchymal cells by stabilizing cell–cell adhesion in a manner independent of β‐catenin transcriptional activity. Wnt‐3a also induced dedifferentiation of articular chondrocytes by stimulating the transcriptional activity of β‐catenin‐T cell‐factor/lymphoid‐enhancer‐factor (Tcf/Lef) complex. In chondrocytes, Wnt‐3a caused the expression of c‐Jun and its phosphorylation by c‐Jun N‐terminal kinase (JNK), resulting in activation of AP‐1. AP‐1 activation suppressed the expression of Sox‐9, a major transcription factor regulating type II collagen expression. Collectively, our results suggest that Wnt‐3a inhibits chondrogenesis by stabilizing cell–cell adhesion and that it causes dedifferentiation of chondrocytes by activating of β‐catenin‐Tcf/Lef transcriptional complex and the c‐Jun/AP‐1 pathway.
Surface energy balance errors in AGCMs: Implications for ocean‐atmosphere model coupling
Authors: Gleckler P. J.
Published: August 2005

The oceanic poleward heat transport (TO) implied by an atmospheric General Circulation Model (GCM) can help evaluate a model's readiness for coupling with an ocean GCM. A well known problem is that the sub‐tropical Southern Hemisphere TO implied by many models is equatorward, contrary to most observationally‐based estimates. By correcting the TO of a diversity of models with satellite‐derived observations, an earlier study demonstrated that the dominant TO problems could be explained by model errors in cloud radiative effects. Such errors were argued to be primarily responsible for the erroneous Southern Hemisphere TO. However, systematic evaluation of one model in a later study suggested that the equatorward Southern Hemisphere TO might also be attributable to biases in the ocean surface latent heat flux. In this study we revisit the problem with a more recent suite of simulations, and demonstrate that collectively models have improved, but only slightly. We then use ocean surface fluxes estimates to examine the problem from a surface point of view. Our results clarify that common model errors in the surface latent heat flux can afflict TO as dramatically as errors in cloud radiative effects. To illustrate the relative importance of the two errors, diagnostic tests are introduced that should become increasingly useful as estimates of ocean surface fluxes are improved.
Organic carbon yields from small, mountainous rivers, New Zealand
Authors: Carey Anne E. , Gardner Christopher B. , Goldsmith Steven T. , Lyons W. Berry , Hicks D. Murray
Published: August 2005

Small mountainous rivers (SMR) have recently been recognized as important contributors of organic carbon to the marine environment. We present dissolved and particulate organic carbon fluxes from previously unexamined rivers of the southwestern region of New Zealand's North Island and additional flux data from the Southern Alps, South Island, New Zealand. The dissolved fluxes are relatively low and show little variation. The particulate fluxes are less than our previous estimates but still high compared to other non‐SMR watersheds.
Effective stress in double porous media with two immiscible fluids
Authors: Khalili N. , Witt R. , Laloui L. , Vulliet L. , Koliji A.
Published: August 2005

A rigorous evaluation of effective stress in double porous media with two immiscible fluids is presented. The effective stress parameters are derived and their quantification in terms of physically measurable parameters is discussed.
Vibrational energy relaxation of azulene studied by the transient grating method. I. Supercritical fluids
Authors: Kimura Y. , Yamamoto Y. , Fujiwara H. , Terazima M.
Published: August 2005

The vibrational energy dissipation process of the ground-state azulene in supercritical xenon, carbon dioxide, and ethane has been studied by the transient grating spectroscopy. In this method, azulene in these fluids was photoexcited by two counterpropagating subpicosecond laser pulses at 570nm, which created a sinusoidal pattern of vibrationally hot ground-state azulene inside the fluids. The photoacoustic signal produced by the temperature rise of the solvent due to the vibrational energy relaxation of azulene was monitored by the diffraction of a probe pulse. The temperature-rise time constants of the solvents were determined at 383 and 298K from 0.7 to 2.4 in ρr, where ρr is the reduced density by the critical density of the fluids, by the fitting of the acoustic signal based on a theoretical model equation. In xenon, the temperature-rise time constant was almost similar to the vibrational energy-relaxation time constant of the photoexcited solute determined by the transient absorption measurement [D. Schwarzer, J. Troe, M. Votsmeier, and M. Zerezke, J. Chem. Phys. 105, 3121 (1996)] at the same reduced density irrespective of the solvent temperature. On the other hand, the temperature-rise time constants in ethane were larger than the vibrational energy-relaxation time constants by a factor of about 2. In carbon dioxide, the difference was small. From these results, the larger time constants of the solvent temperature rise than those of the vibrational energy relaxation in ethane and carbon dioxide were interpreted in terms of the vibrational-vibrational (V-V) energy transfer between azulene and solvent molecules and the vibrational-translational (V-T) energy transfer between solvent molecules. The contribution of the V-V energy transfer process against the V-T energy transfer process has been discussed.
Improvement of current-control induced by oxide notch in very short field-effect transistor
Authors: Cavassilas Nicolas , Bescond Marc , Autran Jean-Luc
Published: August 2005

A two-dimensional quantum ballistic transport model based on the nonequilibrium Green’s function formalism has been used to theoretically investigate the effects induced by an oxide notch in a very short (7 nm) thin-film metal-oxide-semiconductor field-effect transistor. Our investigation shows that a well adjusted notch permits an improvement of on-off current ratio Ion∕Ioff of about 244% with no detrimental change in the drive current Ion. This remarkable result is explained by a nontrivial influence of notch on conduction-band structure in thin film. Therefore, a well optimized notch seems to be a good solution to have a much better control of short channel effects in transistor where the transport has a strong quantum behavior.
Diffusion and microstructural properties of solutions of charged nanosized proteins: Experiment versus theory
Authors: Gapinski J. , Wilk A. , Patkowski A. , Häußler W. , Banchio A. J. , Pecora R. , Nägele G.
Published: August 2005

We have reanalyzed our former static small-angle x-ray scattering and photon correlation spectroscopy results on dense solutions of charged spherical apoferritin proteins using theories recently developed for studies of colloids. The static structure factors S(q), and the small-wave-number collective diffusion coefficient Dc determined from those experiments are interpreted now in terms of a theoretical scheme based on a Derjaguin-Landau-Verwey-Overbeek-type continuum model of charged colloidal spheres. This scheme accounts, in an approximate way, for many-body hydrodynamic interactions. Stokesian dynamics computer simulations of the hydrodynamic function have been performed for the first time for dense charge-stabilized dispersions to assess the accuracy of the theoretical scheme. We show that the continuum model allows for a consistent description of all experimental results, and that the effective particle charge is dependent upon the protein concentration relative to the added salt concentration. In addition, we discuss the consequences of small ions dynamics for the collective protein diffusion within the framework of the coupled-mode theory.
NMR shielding constants for hydrogen guest molecules in structure II clathrates
Authors: Alavi Saman , Ripmeester J. A. , Klug D. D.
Published: August 2005

Proton NMR shielding constants and chemical shifts for hydrogen guests in small and large cages of structure II clathrates are calculated using density-functional theory and the gauge-invariant atomic-orbital method. Shielding constants are calculated at the B3LYP level with the 6-311++G(d,p) basis set. The calculated chemical shifts are corrected with a linear regression to reproduce the experimental chemical shifts of a set of standard molecules. The calculated chemical shifts of single hydrogen molecules in the small and large structure II cages are 4.94 and 4.84 ppm, respectively, which show that within the error range of the method the H2 guest molecules in the small and large cages cannot be distinguished. Chemical shifts are also calculated for double occupancy of the hydrogen guests in small cages, and double, triple, and quadruple occupancy in large cages. Multiple occupancy changes the chemical shift of the hydrogen guests by approximately 0.2 ppm. The relative effects of other guest molecules and the cage on the chemical shift are studied for the cages with multiple occupancies.
Ultrafast electron dynamics and enhanced optical nonlinearities of CdS-capped Au∕BaTiO3 composite film
Authors: Yang Yong , Nogami Masayuki , Shi Jianlin , Chen Hangrong , Liu Ye , Qian Shixiong
Published: August 2005

The third-order nonlinear optical responses of gold nanoparticles capped by CdS shells of different thicknesses embedded in BaTiO3 films were investigated by off-resonance femtosecond optical Kerr effect technology at 800nm. The nonlinearities of the Au–CdS core-shell composite nanoparticles exhibit a significant enhancement, compared with their single components, and the χ(3) value apparently increases with the increase in the CdS shell thickness. The electric-field distribution in the composite nanoparticles was calculated using Neeve’s theory [A. E. Neeves and M. H. Birnboim, J. Opt. Soc. Am. B 6, 787 (1989)] to explain the nonlinear enhancement mechanism, which was mainly attributed to the enhancement of the localized electric field in the CdS shell. The electron relaxation dynamics in the Au–CdS nanoparticles with a core-shell structure were found to be the same as that in pure gold nanoparticle systems using the time-resolved pump-probe technique measured at 800nm.
Bismuth replacement by samarium in strontium bismuth niobate and its multiferroic nature
Authors: Srinivas A. , Sritharan T. , Boey F. Y. C.
Published: August 2005

Strontium bismuth niobate (SBN) is a ferroelectric material. This research reports the effects of the total replacement of bismuth in SBN by the rare-earth element, samarium. X-ray-diffraction measurement with Rietveld analysis shows that the tetragonal crystal structure of SBN is essentially retained but is distorted to an orthorhombic form. The new phase shows a ferromagnetic response in addition to its inherent ferroelectric property at room temperature.
Neutron irradiation effects on electrical properties and deep-level spectra in undoped n-AlGaN∕GaN heterostructures
Authors: Polyakov A. Y. , Smirnov N. B. , Govorkov A. V. , Markov A. V. , Pearton S. J. , Kolin N. G. , Merkurisov D. I. , Boiko V. M.
Published: August 2005

The effect of neutron irradiation on the electrical properties of undoped n-AlGaN∕GaN heterostructures is reported. The two-dimensional electron-gas (2DEG) mobility starts to decrease at neutron doses above 1014cm−2, while the 2DEG concentration slightly increases at low doses and decreases dramatically for doses higher than 2.5×1016cm−2. The result is that the mobility/concentration product (a figure of merit for transistors) starts to decrease appreciably after the dose of 1015cm−2. Capacitance-voltage and admittance spectroscopies, indicate that tunneling of electrons into the states near Ec−0.21eV in AlGaN is a serious factor when cooling down the virgin or lightly irradiated samples. For heavily irradiated samples the states in AlGaN are close to 0.3 and 0.45eV, respectively, from the bottom of the conduction band. Deep-level spectroscopy measurements reveal the presence of hole traps with apparent activation energies of 0.18 and 0.21eV for lightly irradiated samples and deeper hole traps with activation energies of 0.6 and 1eV in heavily irradiated samples.
Nanoscale dislocation patterning by ultralow load indentation
Authors: Taylor Curtis R. , Stach Eric A. , Salamo Gregory , Malshe Ajay P.
Published: August 2005

The use of nanoindentation as a dislocation patterning technique for self-assembled nanostructures is investigated. In this context we have studied the behavior of GaAs under ultralow load indentation conditions. It is shown that periodic dislocation arrays are formed and can be well controlled by nanoindentation. Transmission electron microscopy (TEM) reveals that the crystal deforms solely by dislocation activity with no evidence of stacking faults, twinning, fracture, or phase transformation. The resulting strain field is highly localized, indicating that ultralow load nanoindentation may provide an excellent means to mechanically bias nanostructure nucleation and patterning during subsequent crystal growth.
Pseudo-epitaxial lead zirconate titanate thin film on silicon substrate with enhanced ferroelectric polarization
Authors: Goh Wei Chuan , Yao Kui , Ong C. K.
Published: August 2005

A pseudo-epitaxial Pb(Zr0.52Ti0.48)O3 (PZT) thin film was fabricated on a silicon substrate using a La0.7Sr0.3MnO3∕YBa2Cu3O7−δ∕yttria-stabilized zirconia heterostructure template by a pulsed-laser deposition process. The pseudo-epitaxial PZT thin film was characterized with broad x-ray diffraction peaks and granular morphology with nanometer-sized pores distributed across the film. Despite the imperfect epitaxial quality, the pseudo-epitaxial PZT thin film exhibited a substantially larger ferroelectric polarization than those “ideal” epitaxial films deposited on silicon substrates. The possible mechanisms underlying this phenomenon were analyzed, and the results indicated that only improving the epitaxial quality without considering the tensile stress relief is not sufficient in achieving the optimal ferroelectric polarization for a ferroelectric film on silicon substrate.
GaN resistive hydrogen gas sensors
Authors: Yun Feng , Chevtchenko Serguei , Moon Yong-Tae , Morkoç Hadis , Fawcett Timothy J. , Wolan John T.
Published: August 2005

GaN epilayers grown by organometallic vapor phase epitaxy have been used to fabricate resistive gas sensors with a pair of planar ohmic contacts. Detectible sensitivity to H2 gas for a wide range of gas mixtures in an Ar ambient has been realized; the lowest concentration tested is ∼0.1% H2 (in Ar), well below the lower combustion limit in air. No saturation of the signal is observed up to 100% H2 flow. Real-time response to H2 shows a clear and sharp response with no memory effects during the ramping cycles of H2 concentration. The change in current at a fixed voltage to hydrogen was found to change with sensor geometry. This appears to be consistent with a surface-adsorption-induced change of conductivity; a detailed picture of the gas sensing mechanism requires further systematic studies.
Dual-gate organic thin-film transistors
Authors: Gelinck G. H. , van Veenendaal E. , Coehoorn R.
Published: August 2005

A dual-gate organic thin-film transistor is realized using solution-processed organic semiconductor and insulator layers. Electrodes are made from gold. Compared to conventional single-gate transistors, this device type has a higher on current and steeper subthreshold slope. We show that the improved performance is the result of a nonconstant threshold voltage rather than formation of a second accumulation channel. Formation of a second accumulation channel does occur but the field-effect mobility associated with this channel is a factor 104 lower than the primary channel due to the relatively rough insulator-semiconductor interface.
Self-assembled multiferroic nanostructures in the CoFe2O4-PbTiO3 system
Authors: Li Jianhua , Levin Igor , Slutsker Julia , Provenzano Virgil , Schenck Peter K. , Ramesh R. , Ouyang Jun , Roytburd Alexander L.
Published: August 2005

The effect of substrate orientation on the morphologies of epitaxial self-assembled nanostructures was demonstrated using multiferroic 0.67PbTiO3-0.33CoFe2O4 thin films. The two-phase composite films were grown by pulsed laser deposition on single crystal SrTiO3 substrates having (001) and (110) orientations. The nanostructures of both orientations consisted of vertical rod- or platelet-like columns of CoFe2O4 dispersed in a PbTiO3 matrix. For the (001) orientation the platelet habits were parallel to the {110} planes, whereas for the (110) orientation the platelets were parallel to the {111} planes. The differences were explained using a thermodynamic theory of heterophase structures.
The effect of raised beds on soil structure, waterlogging, and productivity on duplex soils in Western Australia
Authors: Bakker D. M. , Hamilton G. J. , Houlbrooke D. J. , Spann C.
Published: August 2005

Waterlogging and poor soil structure in the root-zone of duplex soils in Western Australia has long been recognised as a major constraint to the production of agricultural crops and pastures. The effect of raised beds on waterlogging, soil structure, and productivity of duplex soils was investigated. Five experimental sites were established, monitored, and operated over 5 years as well as 3 larger scale demonstration sites which were operated over 4 or 3 years. Treatments consisted of raised beds and a normal no-till seed bed as the control. The beds were made with a bed former after the soil had been deep cultivated. Bulk density and steady-state infiltration rate observations indicated significant and lasting improvements in soil structure in the beds. The incidence of waterlogging in raised beds was reduced and this was accompanied by an increase in runoff from the raised beds. The average grain yield increase from the beds was 18% for a variety of crops across a range of climatic conditions and duplex soils. Seven years after the introduction of raised beds for broad-acre farming in Western Australia, more than an estimated 30 000 ha of crops is now grown on raised beds.
In situ dynamics of recently allocated 14C in pasture soil and soil solution collected with Rhizon Soil Moisture Samplers
Authors: Bhupinderpal-Singh  , Hedley M. J. , Saggar S.
Published: August 2005

Information on the dynamics of recently photo-assimilated carbon (C) allocated to roots and root-derived exudates in soils is scarce and experimentally difficult to obtain. We used Rhizon Soil Moisture SamplersTM (RSMS) placed at different depths in soil (20, 40, 80, 120 mm) to monitor short-term dynamics of root and root-derived C at the root–soil interface after 14CO2 pulse-labelling of pasture cores. At the 20 mm depth, 14C activity in soil solution peaked within 2 h of 14CO2 application. The peak of 14C activity took longer to appear and slower to disappear with increased depth. Negligible amounts of 14C as soluble exudates were found in the soil solution. The pattern of initial 14C activity in soil solution, allocation of recently assimilated 14C in roots, and root mass distribution with depth were closely related to each other. This suggested that the rapid appearance of 14CO2 in soil solution is more closely linked to root respiration of recent 14C-assimilates (transferred via shoots to roots) and/or to microbial decomposition of root-released 14C-assimilates than to transfer by diffusion of atmospheric 14CO2 through open soil surface to different depths in soil. The use of RSMS was an effective, simple, and non-destructive method to monitor the dynamics of root-derived 14C by in situ sampling of soil solution.
Classification issues for the Hydrosol and Organosol Soil Orders to better encompass surface acidity and deep sulfidic horizons in acid sulfate soils
Authors: Wilson B. P.
Published: August 2005

The Australian Soil Classification (ASC) suggests that, owing to a lack of data available at the time of publication, modifications may be required for those soils containing sulfidic or sulfuric materials. The soil survey since undertaken for the acid sulfate soil risk maps of coastal NSW has provided sufficient data to suggest changes to the ASC, specifically with reference to horizons overlying sulfidic and sulfuric materials, and deep sulfidic materials. During the risk map survey a database of 308 sulfidic or sulfuric profiles was produced that contains descriptions, classifications, and laboratory data. It is this database that is examined in this paper. While the ASC successfully encompasses most characteristics which are important for land use, many of the risk map profiles contained an acidic, non acid sulfate, near surface layer that is not encompassed by the ASC. Hence, it is suggested here that a Supra acidic subgroup be included in the Hydrosol and Organosol Soil Orders to signify a near surface horizon with a pH <5.5 which is not sulfuric and which does not qualify as a Melacic horizon. The inclusion of an additional class to encompass deep sulfidic materials is also suggested for Hydrosols but, due to lack of data, not for other soil orders.
Increased risk of zinc deficiency in wheat on soils limed to correct soil acidity
Authors: Brennan R. F. , Bolland M. D. A. , Bell R. W.
Published: August 2005

Addition of lime to ameliorate soil acidity has been observed to induce zinc (Zn) deficiency for wheat in sandy soils of south-western Australia, reducing grain yields. The implications of widespread use of lime to treat acid soils for the residual value of Zn in these soils are not known. In a glasshouse experiment, using a Zn-deficient sand from south-western Australia, 3 levels of finely powdered calcium carbonate were added and incubated in moist soil for 6 weeks at 22°C to produce three different pH values (1 : 5 soil : 0.01 m CaCl2): 4.9 (original soil not treated with calcium carbonate), 5.8, and 7.4. Five amounts of Zn, as solutions of Zn sulfate, were then incubated in moist soil for 0, 30, 60, 120, and 180 days before sowing spring wheat (Triticum aestivum L.). The residual value of the applied Zn was determined using yield of dried shoots, Zn content in dried shoots, and soil test Zn (DTPA extraction). This was done by calculating the effectiveness of the incubated Zn for all 3 soils relative to the effectiveness of Zn applied just before sowing wheat (0 day incubation, freshly applied Zn) for the soil not treated with calcium carbonate. As measured using yield of dried shoots, Zn content of dried shoots, or soil test Zn, the residual value of the incubated Zn decreased with increasing soil pH and with increasing period of incubation of Zn with moist soil before sowing wheat. The critical Zn concentration, associated with 90% of the total yield of dried wheat shoots, was (mg Zn/kg) 13 in the youngest mature growth (apex and youngest emerged leaf), and 20 for rest of dried shoots. These values were similar to current critical values for unlimed soils. The relationship between yield of dried shoots and DTPA soil test Zn was similar for unlimed and limed soils, so similar critical soil test Zn was applicable on the sandy soil regardless of soil pH. Critical DTPA soil test Zn, the soil test Zn that was related to 90% of the maximum yield of dried shoots, was 0.14 mg Zn/mg soil. To combat the increased risk of Zn deficiency on soils limed to ameliorate soil acidity, fertiliser Zn needs to be re-applied to the soil when soil and plant tests indicate a high likelihood of deficiency.
Landscapes without boundaries: wildlife and their environments in northern Australia
Authors: Woinarski J. C. Z. , Williams R. J. , Price O. , Rankmore B.
Published: August 2005

This paper provides an introduction to the ecological fabric of northern Australia, described here as being a land characterised by extreme climatic seasonality and largely devoid of marked topographic features. Largely as a result of the latter trait, many species have extensive geographic ranges, and the spatial turnover in species composition is extremely limited. Somewhat counter-intuitively, these two traits can be accommodated by organisms only through reliance on critical, but often subtle, landscape variation. We present some preliminary models for Gouldian finch (Erythrura gouldiae) and black-footed tree-rat (Mesembriomys gouldii) to illustrate patterns of variation in their resource availability, and the consequences of such variation. We discuss briefly some studies that have attempted to integrate, or at least consider, these elements.
Sustainable development in the indigenous-owned savanna: innovative institutional design for cooperative wildlife management
Authors: Altman Jon , Cochrane Michelle
Published: August 2005

This study examines a particular form of cooperative wildlife management on Aboriginal land in the tropical savanna of the Northern Territory of Australia, in the context of broader questions about governance. It asks how governance at the local or community level can be designed to ensure sustainable development and real economic benefit for the region’s long-term indigenous residents. It is argued here that sustainable development will require hybrid institutions that accommodate and value the principles and practices of indigenous resource management, while also recognising the benefits of broader regional resource governance. Emerging best practice in wildlife harvesting that is founded on careful scientific assessments of sustainability is identified, and an approach to northern development based on sustainability and locally controlled commercialisation is canvassed. Future challenges to the proposed approach include convincing governments and state agencies of its national as well as regional benefits. Reform of governance to facilitate its rapid implementation is desirable, in the context of the relative poverty currently experienced by many indigenous people in tropical north Australia.
Myc interacts genetically with Tip48/Reptin and Tip49/Pontin to control growth and proliferation during
Drosophila
development
Authors: Bellosta Paola , Hulf Toby , Diop Soda Balla , Usseglio Fabrice , Pradel Jacques , Aragnol Denise , Gallant Peter
Published: August 2005

The transcription factor dMyc is the sole
Drosophila
ortholog of the vertebrate c-
myc
protooncogenes and a central regulator of growth and cell-cycle progression during normal development. We have investigated the molecular basis of dMyc function by analyzing its interaction with the putative transcriptional cofactors Tip48/Reptin (Rept) and Tip49/Pontin (Pont). We demonstrate that Rept and Pont have conserved their ability to bind to Myc during evolution. All three proteins are required for tissue growth
in vivo
, because mitotic clones mutant for either
dmyc, pont
,or
rept
suffer from cell competition. Most importantly,
pont
shows a strong dominant genetic interaction with
dmyc
that is manifested in the duration of development, rates of survival and size of the adult animal and, in particular, of the eye. The molecular basis for these effects may be found in the repression of certain target genes, such as
mfas
, by dMyc:Pont complexes. These findings indicate that dMyc:Pont complexes play an essential role in the control of cellular growth and proliferation during normal development.
Clioquinol down-regulates mutant huntingtin expressionin vitroand mitigates pathology in a Huntington's disease mouse model
Authors: Nguyen Trent , Hamby Aaron , Massa Stephen M.
Published: August 2005

In investigating the role of metal ions in the pathogenesis of Huntington's disease, we examined the effects of clioquinol, a metal-binding compound currently in clinical trials for Alzheimer's disease treatment, on mutant huntingtin-expressing cells. We found that PC12 cells expressing polyglutamine-expandedhuntingtinexon 1 accumulated less mutant protein and showed decreased cell death when treated with clioquinol. This effect was polyglutamine-length-specific and did not alter mRNA levels or protein degradation rates. Clioquinol treatment of transgenic Huntington's mice (R6/2) improved behavioral and pathologic phenotypes, including decreased huntingtin aggregate accumulation, decreased striatal atrophy, improved rotarod performance, reduction of weight loss, normalization of blood glucose and insulin levels, and extension of lifespan. Our results suggest that clioquinol is a candidate therapy for Huntington's disease and other polyglutamine-expansion diseases.
Targeted disruption of
Mig-6
in the mouse genome leads to early onset degenerative joint disease
Authors: Zhang Yu-Wen , Su Yanli , Lanning Nathan , Swiatek Pamela J. , Bronson Roderick T. , Sigler Robert , Martin Richard W. , Vande Woude George F.
Published: August 2005

Degenerative joint disease, also known as osteoarthritis, is the most common joint disorder in human beings. The molecular mechanism underlying this disease is not fully understood. Here, we report that disruption of
mitogen-inducible gene 6
(
Mig-6
) in mice by homologous recombination leads to early onset degenerative joint disease, which is revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage, and the development of bony outgrowths or osteophyte formation within joint space. The osteophyte formation appears to be derived from proliferation of mesenchymal progenitor cells followed by differentiation into chondrocytes. Absence of the
Rag2
gene does not rescue the joint phenotype, excluding a role for the acquired immune system in the development of this disease. Our results provide insight into the mechanism of osteoarthritis by showing that loss of
Mig-6
leads to early onset of this disease, implying that this gene or its pathway is important in normal joint maintenance. Because of the striking similarity of osteoarthritis in humans and mice, the
Mig-6
mutant mouse should provide a useful animal model for studying the mechanism of this disease and for testing drugs or therapies for treating osteoarthritis.
Additional remains ofWadilemur elegans, a primitive stem galagid from the late Eocene of Egypt
Authors: Seiffert Erik R. , Simons Elwyn L. , Ryan Timothy M. , Attia Yousry
Published: August 2005

The late Eocene prosimianWadilemur elegansfrom the Jebel Qatrani Formation, northern Egypt, was originally interpreted as an anchomomyin adapiform primate based on limited information from the lower molars and distal premolars. Recently recovered fossils attributable to this species, including a proximal femur, the fourth upper premolar and first and second upper molars, and a mandible preserving the lower second premolar and lower canine and incisor alveoli, reveal a number of derived morphological similarities shared with crown strepsirrhines and, in particular, Miocene-to-Recent stem and crown galagids, to the exclusion of known adapiforms. Phylogenetic analysis of 359 morphological features scored across 95 living and extinct crown primate taxa supports a stem galagid placement forWadilemurand olderSaharagalago, and a close relationship between crown strepsirrhines and the Eocene African taxa “Anchomomys”milleri,Djebelemur, andPlesiopithecus(none of which appear to be closely related to European anchomomyins). This scheme of relationships supports the hypothesis that crown Strepsirrhini is of Afro-Arabian origin and that lemuriforms likely colonized Madagascar by crossing the Mozambique Channel.Wadilemur's known dental and postcranial morphology provides additional support for the hypothesis that galagids and lorisids had diverged by the close of the middle Eocene, and, by bolstering the ≈37 million-year-old calibration point for crown lorisiform origins provided bySaharagalago, indirect support for the hypothesis of an ancient origin of crown Strepsirrhini and crown Primates.
IL-10-dependent infectious tolerance after the treatment of experimental allergic encephalomyelitis with redirected CD4+CD25+T lymphocytes
Authors: Mekala Divya J. , Alli Rajshekhar S. , Geiger Terrence L.
Published: August 2005

How small numbers of CD4+CD25+regulatory T cells suppress autoimmune responsesin vivois unclear. In this report we analyze the immunomodulatory activity of CD4+CD25+T cells that are antigen-specifically redirected against myelin basic protein (MBP)89-101-specific autoreactive T cells by a MBP89-101-IAs-ζ chimeric receptor. We have previously shown that these redirected regulatory T cells are highly potent in treating a model autoimmune disease, experimental allergic encephalomyelitis. We show here that they have only limited effectin vivoon autoreactive T cell proliferation and therefore do not act by deleting or suppressing the expansion of pathologic effector cells. Rather, the redirected CD4+CD25+T cells divert the pathologic T helper 1 self-specific T cell response to one characterized by high IL-10 and lower IL-4 production. Significantly, when isolated from the inducing CD4+CD25+regulatory T cells, these self-specific T cells can independently suppress the autoreactive T cell response and experimental allergic encephalomyelitis development in an IL-10-dependent manner. These results provide evidence that CD4+CD25+regulatory T cells can manipulate the adaptive immune responsein vivothrough the infectious induction of tolerance, specifically by promoting the formation of antigen-specific, IL-10-secreting regulatory T cells.
Complex regulation of somatic hypermutation by cis-acting sequences in the endogenous IgH gene in hybridoma cells
Authors: Ronai Diana , Iglesias-Ussel Maria Dolores , Fan Manxia , Shulman Marc J. , Scharff Matthew D.
Published: August 2005

To create high-affinity antibodies, B cells target a high rate of somatic hypermutation (SHM) to the Ig variable-region genes that encode the antigen-binding site. This mutational process requires transcription and is triggered by activation-induced cytidine deaminase (AID), which converts deoxycytidine to deoxyuridine. Mistargeting of AID to non-Ig genes is thought to result in the malignant transformation of B cells, but the mechanism responsible for targeting SHM to certain DNA regions and not to others is largely unknown. Cis-acting elements have been proposed to play a role in directing the hypermutation machinery, but the motifs required for targeting SHM have been difficult to identify because many of the candidate elements, such as promoters or enhancers, are also required for transcription of Ig genes. Here we describe a system in cultured hybridoma cells in which transcription of the endogenous heavy-chain Ig gene continues in the absence of the core intronic enhancer (Eμ) and its flanking matrix attachment regions (MARs). When AID is expressed in these cells, SHM occurred at the WT frequency even when Eμ and the MARs were absent together. Interestingly, SHM occurred at less than the WT frequency when Eμ or the MARs were individually absent. Our results suggest that these intronic regulatory elements can exert a complex influence on SHM that is separable from their role in regulating transcription.
Multiple-Target Tracking: A Role for Working Memory?
Authors: Allen Roy , Mcgeorge Peter , Pearson David G. , Milne Alan
Published: August 2005

In order to identify the cognitive processes associated with target tracking, a dual-task experiment was carried out in which participants undertook a dynamic multiple-object tracking task first alone and then again, concurrently with one of several secondary tasks, in order to investigate the cognitive processes involved. The research suggests that after designated targets within the visual field have attracted preattentive indexes that point to their locations in space, conscious processes, vulnerable to secondary visual and spatial task interference, form deliberate strategies beneficial to the tracking task, before tracking commences. Target tracking itself is realized by central executive processes, which are sensitive to any other cognitive demands. The findings are discussed in the context of integrating dynamic spatial cognition within a working memory framework.
An AP-1/clathrin coat plays a novel and essential role in forming the Weibel-Palade bodies of endothelial cells
Authors: Lui-Roberts Winnie W.Y. , Collinson Lucy M. , Hewlett Lindsay J. , Michaux Grégoire , Cutler Daniel F.
Published: August 2005

Clathrin provides an external scaffold to form small 50–100-nm transport vesicles. In contrast, formation of much larger dense-cored secretory granules is driven by selective aggregation of internal cargo at the trans-Golgi network; the only known role of clathrin in dense-cored secretory granules formation is to remove missorted proteins by small, coated vesicles during maturation of these spherical organelles. The formation of Weibel-Palade bodies (WPBs) is also cargo driven, but these are cigar-shaped organelles up to 5 μm long. We hypothesized that a cytoplasmic coat might be required to make these very different structures, and we found that new and forming WPBs are extensively, sometimes completely, coated. Overexpression of an AP-180 truncation mutant that prevents clathrin coat formation or reduced AP-1 expression by small interfering RNA both block WPB formation. We propose that, in contrast to other secretory granules, cargo aggregation alone is not sufficient to form immature WPBs and that an external scaffold that contains AP-1 and clathrin is essential.
IL-4 receptor expression on CD8+ T cells is required for the development of protective memory responses against liver stages of malaria parasites
Authors: Morrot Alexandre , Hafalla Julius C.R. , Cockburn Ian A. , Carvalho Luzia H. , Zavala Fidel
Published: August 2005

IL-4 receptor (IL-4R)-deficient CD8+ T cells specific for the circumsporozoite protein of Plasmodium yoelii develop a severely impaired memory response after priming with parasites. Memory CD8+ T cells lacking the IL-4R are unable to establish a stable population residing in nonlymphoid organs, although they develop normally in lymphoid organs. Because memory cells from nonlymphoid organs disappear shortly after immunization, the protective antiparasitic activity of this T cell response also is lost. These results demonstrate that IL-4/IL-4R interactions on CD8+ T cells play a critical role in modulating the development and tissue distribution of memory cells induced by parasite immunization. They also indicate that memory cells residing in nonlymphoid tissues are critical for protective immunity against malaria parasites.
Microsomal triglyceride transfer protein lipidation and control of CD1d on antigen-presenting cells
Authors: Dougan Stephanie K. , Salas Azucena , Rava Paul , Agyemang Amma , Kaser Arthur , Morrison Jamin , Khurana Archana , Kronenberg Mitchell , Johnson Caroline , Exley Mark , Hussain M. Mahmood , Blumberg Richard S.
Published: August 2005

Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum (ER) chaperone that loads lipids onto apolipoprotein B, also regulates CD1d presentation of glycolipid antigens in the liver and intestine. We show MTP RNA and protein in antigen-presenting cells (APCs) by reverse transcription–polymerase chain reaction and by immunoblotting of mouse liver mononuclear cells and mouse and human B cell lines. Functional MTP, demonstrated by specific triglyceride transfer activity, is present in both mouse splenocytes and a CD1d-positive mouse NKT hybridoma. In a novel in vitro transfer assay, purified MTP directly transfers phospholipids, but not triglycerides, to recombinant CD1d. Chemical inhibition of MTP lipid transfer does not affect major histocompatibility complex class II presentation of ovalbumin, but considerably reduces CD1d-mediated presentation of α-galactosylceramide (α-galcer) and endogenous antigens in mouse splenic and bone marrow–derived dendritic cells (DCs), as well as in human APC lines and monocyte-derived DCs. Silencing MTP expression in the human monocyte line U937 affects CD1d function, as shown by diminished presentation of α-galcer. We propose that MTP acts upstream of the saposins and functions as an ER chaperone by loading endogenous lipids onto nascent CD1d. Furthermore, our studies suggest that a small molecule inhibitor could be used to modulate the activity of NKT cells.
Surgical Treatment of the Painful Motion Segment
Authors: Burkus J Kenneth
Published: August 2005

Study Design.

Literature review of current bone graft technology and bone graft substitutes used in spinal fusion applications.

Objective.

We reviewed current bone graft technologies and identified the range of bioactive properties that each possesses, such as osteoconductivity, osteoinductivity, and structural, load-bearing capabilities that can be used to either augment or replace autogenous bone graft in spinal fusions.

Summary of Background Data.

Bioactive materials are used in spinal fusion applications to encourage bone formation across an intervertebral motion segment. To be an effective replacement for autogenous bone grafts, a bioactive material must possess the properties of osteoinduction and osteoconduction.

Methods.

Literature review.

Results.

Platelet gel concentrates deliver nonspecific cytokines that influence local cells at the implantation site. Demineralized bone matrix acts as a bone graft enhancer that excludes fibrous tissue of muscle interposition in a fusion mass and is a mildly osteoinductive material. Bone morphogenetic proteins are an integral part of natural bone formation response. They function as differentiation factors that act on mesenchymal stem cells to induce bone formation.

Conclusions.

Patient-derived therapies such as platelet gel concentrates contain cytokines that play a role in bone formation; however, none of them is capable of inducing the entire bone formation cascade. Clinical use of these concentrates could possibly interfere with new bone formation. The use of bone marrow aspiration and concentration techniques has not been convincingly studied in spinal fusions in lower order animal or human clinical studies. Demineralized bone matrix contains small and variable amounts of naturally occurring bone morphogenetic proteins. These products can only function as bone graft extenders. Recombinant bone morphogenetic protein products contain much more highly concentrated and focused amounts of bone morphogenetic proteins, and some have been shown to be clinically effective bone graft replacements.
The effect of disease life history on the evolutionary emergence of novel pathogens
Authors: André Jean-Baptiste , Day Troy
Published: August 2005

We present a general analytical result for the probability that a newly introduced pathogen will evolve adaptations that allow it to maintain itself within any novel host population, as a function of disease life-history parameters. We demonstrate that this probability of ‘evolutionary emergence’ depends on two key properties of the disease life history: (i) the basic reproduction number and (ii) the expected duration of an infection. These parameters encapsulate all of the relevant information and can be combined in a very simple expression, with estimates for the rates of adaptive mutation, to predict the probability of emergence for any novel pathogen. In general, diseases that initially have a large reproductive number and/or that cause relatively long infections are the most prone to evolutionary adaptation.