bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotropic-nematic spinodals of rigid long thin rodlike colloids by event-driven Brownian dynamics simulations
Authors: Tao Yu-Guo , den Otter W. K. , Dhont J. K. G. , Briels W. J.
Published: April 2006

The isotropic-nematic spinodals of solutions of rigid spherocylindrical colloids with various shape anisotropies L∕D in a wide range from 10 to 60 are investigated by means of Brownian dynamics simulations. To make these simulations feasible, we developed a new event-driven algorithm that takes the excluded volume interactions between particles into account as instantaneous collisions, but neglects the hydrodynamic interactions. This algorithm is applied to dense systems of highly elongated rods and proves to be efficient. The calculated isotropic-nematic spinodals lie between the previously established binodals in the phase diagram and extrapolate for infinitely long rods to Onsager’s [Ann. N. Y. Acad. Sci. 51, 627 (1949)] theoretical predictions. Moreover, we investigate the shear induced shifts of the spinodals, qualitatively confirming the theoretical prediction of the critical shear rate at which the two spinodals merge and the isotropic-nematic phase transition ceases to exist.
Patterned regions of porous silicon through trapped hydrogen bubbles
Authors: Ou Fung Suong , Saraf Laxmikant V. , Baer Donald. R.
Published: April 2006

Hydrogen (H2) bubbles trapped around lithographically formed etch pits on silicon single crystal surfaces were used to guide the formation of patterned regions of porous silicon (PSi). Lithography and (electro) chemical etching were utilized to form PSi and guide this growth. It was observed that the pits were surrounded by round regions of PSi suggesting that H2 bubbles defined the areas of PSi formation. PSi porosity seemed to form primarily at the bubble edges, lowering overall etch rate near the bubble center. This is consistent with a variable rate of bubble expansion and an ability of the H2 to mask or slow the reaction in the bubble center. Contrary to our initial expectations, the surface profile suggested that the region away from the bubbles was also etched, but very uniformly.
Multi-island single-electron devices from self-assembled colloidal nanocrystal chains
Authors: Weiss Dirk N. , Brokmann Xavier , Calvet Laurie E. , Kastner Marc A. , Bawendi Moungi G.
Published: April 2006

We report the fabrication of multi-island single-electron devices made by lithographic contacting of self-assembled alkanethiol-coated gold nanocrystals. The advantages of this method, which bridges the dimensional gap between lithographic and NC sizes, are (1) the fact that all tunnel junctions are defined by self-assembly rather than lithography and (2) the high ratio of gate capacitance to total capacitance. The rich electronic behavior of a double-island device, measured at 4.2K, is predicted by combining finite element and Monte Carlo simulations, and it can be fully explained by the standard theory of Coulomb blockade with very few adjustable parameters.
Search for ferromagnetism in undoped and cobalt-doped HfO2−δ
Authors: Ramachandra Rao M. S. , Kundaliya Darshan C. , Ogale S. B. , Fu L. F. , Welz S. J. , Browning N. D. , Zaitsev V. , Varughese B. , Cardoso C. A. , Curtin A. , Dhar S. , Shinde S. R. , Venkatesan T. , Lofland S. E. , Schwarz S. A.
Published: April 2006

We report on the search for ferromagnetism in undoped and cobalt-doped high-k dielectric HfO2 films. Over a broad range of growth conditions, we do not observe ferromagnetism in undoped HfO2 films. On the other hand, we do observe room temperature ferromagnetism in dilutely Co-doped HfO2 films, but the origin of the same appears extrinsic (a Co rich surface layer) at least for the regime of growth conditions explored.
Collector current map of gain and stimulated recombination on the base quantum well transitions of a transistor laser
Authors: Chan R. , Feng M. , Holonyak N. , James A. , Walter G.
Published: April 2006

Data are presented showing significant structure in the collector I-V characteristics of a transistor laser, a decrease (“compression”) in the common-emitter gain (β≡ΔIC∕ΔIB), that can be mapped in some detail and related to quantum well (QW) carrier recombination. The change in gain (β) and laser wavelength corresponding to stimulated recombination (stimulated emission) on QW transitions, which is compared with operation in spontaneous recombination (cavity Q spoiled), is used with conventional transistor charge analysis to reveal the dynamic properties of the transistor laser.
Strained Pt Schottky diodes on n-type Si and Ge
Authors: Liao M. H. , Kuo P.-S. , Jan S.-R. , Chang S. T. , Liu C. W.
Published: April 2006

The variation of electron barrier height and built-in voltage of Pt Schottky diodes on the mechanically strained n-type Si and Ge is investigated experimentally and theoretically. The mechanical strain is measured by Raman spectroscopy and analyzed by the finite element method. The built-in voltage and barrier height measured by capacitance-voltage and current-voltage methods, respectively, decrease with increasing external tensile strain. The reduction of the built-in voltage and barrier height originates mainly from the conduction band lowering with strain. The extracted value of conduction band lowering is consistent with the theoretical calculations using the “stress-free” boundary condition.
Correlation between optical properties and interface morphology of GaAs∕AlGaAs quantum wells
Authors: Moret N. , Oberli D. Y. , Pelucchi E. , Gogneau N. , Rudra A. , Kapon E.
Published: April 2006

We investigate the embedded interfaces of GaAs∕AlGaAs quantum wells grown by metal organic vapor phase epitaxy on slightly (<1°)-misoriented (001) substrates using selective etching and atomic force microscopy. Depending on the substrate misorientation, we observe different growth modes at the embedded interfaces, which are directly correlated to the photoluminescence linewidth. We show that the narrowest linewidth is obtained on 0.2°-off (001) substrates for which the heterointerfaces consist of atomically smooth narrow terraces.
Effect of size in nanowires grown by the vapor-liquid-solid mechanism
Authors: Chen Zhuo , Cao Chuanbao
Published: April 2006

The effects of size on the growth kinetics of nanowires by the vapor-liquid-solid mechanism are presented. The dependences of the growth rate and the activation energy of crystallization on size are given quantitatively. The obtained theoretical results show that the smaller the nanowire radius, the slower the growth rate, and the activation energy of crystallization will increase with decreasing radius of the nanowire. These theoretical predictions are in agreement with the experimental cases.
External magnetic field influence on Hα line in abnormal glow discharge
Authors: Obradović B. M. , Dojčinović I. P. , Kuraica M. M. , Purić J.
Published: April 2006

Influence of the external axial magnetic field on the hydrogen Hα line profiles in an abnormal glow discharge has been studied. It has been found that the applied magnetic field predominantly increases the intensity of central component of the characteristic excessively broadened Hα profile. Magnetic filed causes helical motion of electrons along the electric field lines and prolongs their trajectories increasing the number of collisions with matrix gas. This explains the increase of the central component of Hα profile and can be regarded as an experimental proof for the main contribution of electron excitation to that part of the profile.
Prismatic stacking faults in epitaxially laterally overgrown GaN
Authors: Mei J. , Srinivasan S. , Liu R. , Ponce F. A. , Narukawa Y. , Mukai T.
Published: April 2006

We report on the presence of optically active stacking faults on basal and prismatic planes in epitaxially laterally overgrown GaN (ELOG) on {112¯2} facets. The structure of the faults has been analyzed using diffraction contrast electron microscopy. We show that stacking faults on {112¯0} prismatic planes involve a lattice displacement of 12⟨11¯01⟩, parallel to the fault plane. They appear as jogs connecting basal-plane stacking faults, the latter with a lattice displacement of 16⟨202¯3⟩. These faults are observed only in the laterally overgrown regions that grow on {112¯2} planes, which indicates that the stacking fault formation is closely related to the orientation of the growth surface. Possible formation mechanisms of these faults are discussed. Direct correlation between TEM and cathodoluminescence shows that these prismatic-plane and basal-plane stacking faults are optically active with light emission at 3.30 and 3.41eV, respectively.
Electrical conductivity of a single electrospun fiber of poly(methyl methacrylate) and multiwalled carbon nanotube nanocomposite
Authors: Sundaray Bibekananda , Subramanian V. , Natarajan T. S. , Krishnamurthy K.
Published: April 2006

Electrospinning produces polymeric fibers with diameters in the range of 10μm–10nm by accelerating a charged polymer jet under a high electric field. We report the preparation of conducting nanocomposite fibers of poly(methyl methacrylate) (PMMA) and multiwalled carbon nanotubes (MWCNTs) by electrospinning. The fibers obtained are long and well aligned. The carbon nanotubes are found to be oriented along the fiber axis. The room temperature dc electrical conductivity of a single fiber with MWCNT (0.05% w/w) shows about a ten orders of magnitude improvement from the pure PMMA. The conductivity increases with MWCNT concentration.
Strain rate sensitivity of a nanocrystalline Cu synthesized by electric brush plating
Authors: Jiang Zhonghao , Liu Xianli , Li Guangyu , Jiang Qing , Lian Jianshe
Published: April 2006

A method for synthesizing bulk nanocrystalline Cu by an electric brush-plating technique is reported. This brush-plated nanocrystalline Cu has a fine (26nm) and quite uniform grain structure and predominant high-angle grain boundaries. A pronounced strain rate sensitivity of the stress with an m of 0.104 and the Coble creep and a subsequent transition to the power-law creep were observed in room temperature tensile and creep tests. The dominant grain boundary deformation due to the truly nanocrystalline structure of this nanocrystalline Cu is responsible for the observed strain rate sensitivity.
InGaAs dual channel transistors with negative differential resistance
Authors: Sugaya Takeyoshi , Komori Kazuhiro , Yamane Takashi , Hori Souichirou , Yonei Kenji
Published: April 2006

We demonstrate InGaAs dual channel transistors (DCTs) with negative differential resistance (NDR) fabricated on an InP (001) substrate. The dual channel structure consists of high and low mobility InGaAs quantum wells combined with an InAlAs barrier layer. NDR characteristics of the DCTs depend on the thicknesses of the low mobility and barrier layers and the indium content of the high mobility channel. The NDR mechanism is thought to be the carrier transfer from the high mobility channel to the low mobility channel.
Quantitative mobility spectrum analysis of AlGaN∕GaN heterostructures using variable-field hall measurements
Authors: Biyikli N. , Xie J. , Moon Y.-T. , Yun F. , Stefanita C.-G. , Bandyopadhyay S. , Morkoç H. , Vurgaftman I. , Meyer J. R.
Published: April 2006

Carrier transport properties of AlGaN∕GaN heterostructures have been analyzed with the quantitative mobility spectrum analysis (QMSA) technique. The nominally undoped Al0.08Ga0.92N∕GaN sample was grown by plasma-assisted molecular beam epitaxy on a GaN/sapphire template prepared with hydride vapor phase epitaxy. Variable-magnetic-field Hall measurements were carried out in the temperature range of 5–300K and magnetic field range of 0.01–7T. QMSA was applied to the experimental variable-field data to extract the concentrations and mobilities associated with the high-mobility two-dimensional electron gas and the relatively low-mobility bulk electrons for the temperature range investigated. The mobilities at T=80K are found to be 7100 and 880cm2∕Vs, respectively, while the corresponding carrier densities are 7.0×1011 and 8×1014cm−3. Any conclusions drawn from conventional Hall measurements at a single magnetic field would have been highly misleading.
Effect of exogenous gonadotrophins on ovarian morphology and oocyte maturation in the southern hairy nosed wombat Lasiohinus latifrons during the breeding season
Authors: McDonald C. H. , Taggart D. A. , Breed W. G. , Druery G. V. , Shimmin G. A. , Finlayson G. R. , Paris M. C. J.
Published: April 2006

The effect of the exogenous administration of porcine follicle-stimulating hormone (pFSH) and pregnant mare serum gonadotrophin (PMSG) on ovarian follicular development and oocyte maturation in the southern hairy nosed wombat Lasiorhinus latifrons was investigated. Three experimental groups were administered pFSH at various doses and for different treatment lengths, followed by 25 mg porcine luteinising hormone (pLH) 12 h after the last dose of pFSH. Another group was given PMSG followed 72 h later by 25 mg pLH. Animals were killed 24 h after pLH. The left ovary was fixed for histology and the morphology of the antral follicles was determined, whereas follicular oocytes in the right ovary were aspirated, fixed, stained with 4′,6′-diamidino-2-phenylindole, and viewed for nuclear maturation. There was no significant difference in the mean number of ovarian follicles >1 mm, or in the size class of follicles assessed between control and experimental groups. However, a trend was observed suggesting a possible increase in follicles >3.0 mm in experimental groups compared with control animals. In all females administered exogenous porcine gonadotrophins, but not controls, some of the mural granulosa cells of large tertiary antral follicles had markedly enlarged nuclei (approximately 14 µm in diameter). All oocytes from the control group remained at the germinal vesicle stage, whereas approximately 40% of oocytes retrieved from the pFSH groups and 82.4% retrieved from the PMSG-primed animals had undergone germinal vesicle break down, with a small number reaching meiosis II. The present study shows that exogenous administration of either pFSH or PMSG to hairy nosed wombats can induce follicular growth and oocyte maturation. Such findings could be useful in the development of reproductive technology in this species.
Meat and Livestock Association Plenary Lecture 2005. Oocyte signalling molecules and their effects on reproduction in ruminants
Authors: McNatty Kenneth P. , Lawrence Stephen , Groome Nigel P. , Meerasahib Mohammed F. , Hudson Norma L. , Whiting Lynda , Heath Derek A. , Juengel Jennifer L.
Published: April 2006

Sheep (Ovis aries) are a highly diverse species, with more than 900 different breeds that vary significantly in their physiological characteristics, including ovulation rate and fecundity. From examination of inherited patterns of ovulation rate, several breeds have been identified with point mutations in two growth factor genes that are expressed in oocytes. Currently, five different point mutations have been identified in the BMP15 (GDF9b) gene and one in GDF9. Animals heterozygous for the GDF9 and/or the BMP15 mutations have higher ovulation rates than their wild-type counterparts. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile owing to arrested follicular development. In bovine and ovine ovaries, GDF9 was expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 was expressed exclusively in oocytes from the primary stage: no data for the ontogeny of BMP15 expression are currently available for cattle. In vitro, ovine growth differentiation factor 9 (oGDF9) has no effect on 3H-thymidine incorporation by either bovine or ovine granulosa cells, whereas ovine bone morphogenetic protein 15 (oBMP15) has modest (1.2- to 1.6-fold; P < 0.05) stimulatory effects. Ovine GDF9 or oBMP15 alone inhibited progesterone production by bovine granulosa cells, whereas in ovine cells only oGDF9 was inhibitory. The effects of oGDF9 and oBMP15 together were often cooperative and not always the same as those observed for each factor alone. Active immunisation of ewes with BMP15 and/or GDF9 peptides affected ovarian follicular development and ovulation rate. Depending on the GDF9 and/or BMP15 vaccine formulation, ovulation rate was either increased or suppressed. A primary and single booster immunisation of ewes with a BMP15 peptide in a water-based adjuvant has led to 19–40% increases in lambs born per ewe lambing. Collectively, the evidence suggests that oocyte signalling molecules have profound effects on reproduction in mammals, including rodents, humans and ruminants. Moreover, in vivo manipulation of these oocyte signalling molecules provides new opportunities for the management of the fertility of ruminants.
Leptin modulates nitric oxide production and lipid metabolism in human placenta
Authors: White Verónica , González Elida , Capobianco Evangelina , Pustovrh Carolina , Martínez Nora , Higa Romina , Baier Mario , Jawerbaum Alicia
Published: April 2006

Leptin has significant effects on appetite, energy expenditure, lipid mobilisation and reproduction. During pregnancy, leptin is produced in the placenta, a tissue in which leptin receptors are highly expressed, suggesting autocrine/paracrine functions for this hormone. In the present study, a putative role of leptin as a regulator of nitric oxide (NO) production and lipid metabolism was evaluated in term human placenta. We demonstrated that leptin enhanced NO production in human placental explants (P < 0.01). Although leptin did not modify the placental levels of cholesteryl esters and phospholipids, leptin decreased levels of triglycerides (P < 0.01) and cholesterol (P < 0.001) in term human placenta. The effect of leptin on lipid mass seems to be independent of the modulation of de novo lipid synthesis because leptin did not modify the incorporation of 14C-acetate into any of the lipids evaluated. We investigated the effects of leptin on placental lipid catabolism and found that in both term human placental explants and primary cultures of trophoblastic cells, leptin increased glycerol release, an index of the hydrolysis of esterified lipids, in a dose-dependent manner. In conclusion, we have shown that leptin affects NO production and lipid catabolism in human placenta, providing supportive evidence for a role of leptin in placental functions that would determine the transfer of nutrients to the developing fetus.
Effects of postnatal steroids on Na+/K+-ATPase activity and α1- and β1-subunit protein expression in the cerebral cortex and renal cortex of newborn lambs
Authors: Kim Chang-Ryul , Sadowska Grazyna B. , Petersson Katherine H. , Merino Maricruz , Sysyn Gregory D. , Padbury James F. , Stonestreet Barbara S.
Published: April 2006

Na+/K+-ATPase is a membrane-bound enzyme responsible for Na+/K+ translocation across cell membranes. It is essential for the generation of electrochemical gradients, which control the ionic environment necessary for electrical activity and water and electrolyte balance. Newborn infants who are at risk of developing bronchopulmonary dysplasia (BPD) are frequently treated with corticosteroids. Although these infants are at risk for neurological, water and electrolyte abnormalities, there is little information regarding the effects of clinically relevant doses of corticosteroids on Na+/K+-ATPase activity and protein isoform expression in the brain and kidney of newborns. In the present study, we examined the effects of dexamethasone on cerebral cortical and renal cortical Na+/K+-ATPase activity and α1- and β1-protein isoform expression in newborn lambs. Lambs were given four injections of a placebo (n = 11) or one of three different doses of dexamethasone (0.01 mg kg−1, n = 9; 0.25 mg kg−1, n = 11; or 0.50 mg kg−1, n = 9) 12 h apart on Postnatal Days 3 and 4 up to 18 h before harvest of the cerebral cortex and renal cortex. We selected doses in a range to approximate those used to treat infants with BPD. Na+/K+-ATPase activity was measured in membrane preparations as ouabain-sensitive inorganic phosphate liberation from ATP and α1- and β1-subunit abundance by Western immunoblot. Postnatal treatment of lambs with dexamethasone resulted in a 21.4% increase in Na+/K+-ATPase activity and a 30.4% increase in catalytic α1-protein expression in the cerebral cortex at a dose of 0.50 mg kg−1 dexamethasone, but not at the lower doses. Dexamethasone treatment was not associated with changes in β1-isoform expression in the cerebral cortex. In the kidney, dexamethasone treatment was not associated with significant changes in Na+/K+-ATPase activity or α1- or β1-isoform expression for the doses we examined. Therefore, clinically relevant corticosteroid treatment exerts dose-related, differential organ-specific effects on Na+/K+-ATPase activity and protein isoform expression in newborn lambs.
Carrying the FecB (Booroola) mutation is associated with lower birth weight and slower post-weaning growth rate for lambs, as well as a lighter mature bodyweight for ewes
Authors: Gootwine E. , Rozov A. , Bor A. , Reicher S.
Published: April 2006

The present study was conducted in an Assaf flock in which the FecB (Booroola) mutation was segregated to determine whether the FecB mutation affects birthweight and the pre- and post-weaning growth rate of ewe lambs, as well as the mature bodyweight of ewes. Significant differences (P = 0.01) in birthweight (mean ± s.e.m.) were found between BB ewe lambs (4.03 ± 0.08 kg) and B+ and ++ ewe lambs (4.16 ± 0.04 and 4.32 ± 0.07 kg, respectively), which themselves did not differ significantly (P > 0.05). An FecB-associated maternal effect on the birthweight of ewe lambs was also detected, with the birthweight of lambs born to BB mothers (3.93 ± 0.08 kg) being significantly (P < 0.0001) different from the birthweight of lambs born to B+ and ++ mothers (4.26 ± 0.04 and 4.33 ± 0.07 kg, respectively), which did not differ significantly. The genotypes of the lambs did not affect their preweaning growth rate. However, the post-weaning growth rate of ewe BB lambs (274 ± 5 g day−1) was significantly (P = 0.05) different from the similar (P > 0.05) post-weaning growth rates of B+ and ++ lambs (284 ± 3 and 290 ± 4 g day−1, respectively). The genotype at the FecB locus also affected the mature bodyweight of ewes, with that of BB ewes (67.3 ± 1.4 kg) being significantly (P < 0.001) different from the similar mature bodyweight of B+ and ++ ewes (70.8 ± 1.1 and 70.1 ± 1.7 kg, respectively).
Effect of undernutrition on uterine progesterone and oestrogen receptors and on endocrine profiles during the ovine oestrous cycle
Authors: Sosa C. , Abecia J. A. , Forcada F. , Viñoles C. , Tasende C. , Valares J. A. , Palacín I. , Martin G. B. , Meikle A.
Published: April 2006

In the present study, it was investigated whether undernutrition affected the binding capacity, immunoreactivity and mRNA expression for uterine oestrogen and progesterone receptors (ER and PR, respectively) in sheep, as well as whether the responses were associated with changes in plasma concentrations of progesterone (P4), oestradiol (E2), glucose, fatty acids, insulin, leptin and insulin-like growth factor (IGF)-I during the oestrous cycle. Twenty ewes were fed either 1.5 (C) or 0.5 (L) times their maintenance requirements and were killed on Day 5 or 14 of the cycle (Day 0 = oestrus). Compared with Group C, Group L had higher concentrations of non-esterified fatty acids and lower concentrations of insulin, leptin and IGF-I. Group L also had higher plasma concentrations of P4 during the final days of the luteal phase. At oestrus in both treatment groups, there were peaks in the concentrations of glucose, insulin and IGF-I. For ER and PR, transcript expression, binding capacity and immunoreactivity were higher on Day 5 than on Day 14 of the cycle. The binding capacities for ER and PR were lower in Group L than in Group C on Day 5. Group C showed more immunoreactive staining for ER than did Group L in two of five cell types, whereas no effect of treatment was observed for PR immunoreactivity. There was more PR mRNA in the uterine horn contralateral to the corpus luteum in Group C than in Group L ewes. We conclude that undernutrition impairs steroid receptor expression and binding capacity. This may alter the uterine environment and help explain the reductions in embryo survival.
Ultrastructure, osmotic tolerance, glycerol toxicity and cryopreservation of caput and cauda epididymidal kangaroo spermatozoa
Authors: McClean Rhett , MacCallum Catriona , Blyde David , Holt William V. , Johnston Stephen D.
Published: April 2006

The aim of the present study was to compare cryopreservation, osmotic tolerance and glycerol toxicity between mature and immature epididymal kangaroo spermatozoa to investigate whether the lack of cryopreservation success of cauda epididymidal spermatozoa may be related to the increased complexity of the sperm ultrastructure acquired during epididymal transit. Caput and cauda epididymidal spermatozoa were recovered from red-necked wallabies (RNW; Macropus rufogriseus) and eastern grey kangaroos (EGK; M. giganteus). In Experiment 1, caput and cauda epididymidal spermatozoa were frozen and thawed using a standard cryopreservation procedure in Tris-citrate buffer with or without 20% glycerol. Although cryopreservation of caput epididymidal spermatozoa resulted in a significant increase in sperm plasma membrane damage, they were more tolerant of the procedure than spermatozoa recovered from the cauda epididymidis (P < 0.05). In Experiment 2, caput and cauda epididymidal EGK spermatozoa were diluted into phosphate-buffered saline media of varying osmolarity and their osmotic tolerance determined. Plasma membranes of caput epididymidal spermatozoa were more tolerant of hypo-osmotic media than were cauda epididymidal spermatozoa (P < 0.05). In Experiment 3, caput and cauda epididymidal RNW spermatozoa were incubated in Tris-citrate buffer with and without 20% glycerol at 35 and 4°C to examine the cytotoxic effects of glycerol. At both temperatures, caput epididymidal spermatozoa showed less plasma membrane damage compared with cauda epididymidal spermatozoa when exposed to 20% glycerol (P < 0.05). These experiments clearly indicate that epididymal maturation of kangaroo spermatozoa results in a decreased ability to withstand the physiological stresses associated with cryopreservation.
Differential effects of Hsc70 and Hsp70 on the intracellular trafficking and functional expression of epithelial sodium channels
Authors: Goldfarb Samuel B. , Kashlan Ossama B. , Watkins Jeffrey N. , Suaud Laurence , Yan Wusheng , Kleyman Thomas R. , Rubenstein Ronald C.
Published: April 2006

The members of the cytoplasmic 70-kDa heat shock protein family are involved in appropriate folding and trafficking of newly synthesized proteins in the cell. Hsc70, which is expressed constitutively, and Hsp70, the expression of which is stress- and heat shock-induced, are often considered to have similar cellular functions in this regard, but there are suggestions that the intracellular functions of these homologous but not identical proteins may differ. We tested the hypothesis that Hsc70 and Hsp70 would have differential effects on the expression of the epithelial sodium channel (ENaC). In
Xenopus
oocytes, overexpression of human Hsc70 decreased the functional (defined as amiloride-sensitive whole-oocyte current) and surface expression of murine ENaC (mENaC) in a concentration-dependent fashion. In contrast, coinjection of a moderate amount of Hsp70 cRNA (10 ng) increased the functional and surface expression of mENaC, whereas a higher amount of coinjected Hsp70 cRNA (30 ng) decreased mENaC functional and surface expression. The increase in mENaC functional expression with coinjection of 10 ng of Hsp70 cRNA was antagonized by the additional coinjection of Hsc70 cRNA in a concentration-dependent fashion. These data are consistent with Hsc70 and Hsp70 having differential and antagonistic effects with regard to the intracellular trafficking of mENaC in oocytes, which may have an impact on our understanding and potential treatment of diseases of aberrant ion channel trafficking.
Self-organized similarity, the evolutionary emergence of groups of similar species
Authors: Scheffer Marten , van Nes Egbert H.
Published: April 2006

Ecologists have long been puzzled by the fact that there are so many similar species in nature. Here we show that self-organized clusters of look-a-likes may emerge spontaneously from coevolution of competitors. The explanation is that there are two alternative ways to survive together: being sufficiently different or being sufficiently similar. Using a model based on classical competition theory, we demonstrate a tendency for evolutionary emergence of regularly spaced lumps of similar species along a niche axis. Indeed, such lumpy patterns are commonly observed in size distributions of organisms ranging from algae, zooplankton, and beetles to birds and mammals, and could not be well explained by earlier theory. Our results suggest that these patterns may represent self-constructed niches emerging from competitive interactions. A corollary of our findings is that, whereas in species-poor communities sympatric speciation and invasion of open niches is possible, species-saturated communities may be characterized by convergent evolution and invasion by look-a-likes.
Immunological synapse arrays: Patterned protein surfaces that modulate immunological synapse structure formation in T cells
Authors: Doh Junsang , Irvine Darrell J.
Published: April 2006

T cells are activated by recognition of foreign peptides displayed on the surface of antigen presenting cells (APCs), an event that triggers assembly of a complex microscale structure at the T cell–APC interface known as the immunological synapse (IS). It remains unresolved whether the unique physical structure of the synapse itself impacts the functional response of T cells, independent of the quantity and quality of ligands encountered by the T cell. As a first step toward addressing this question, we created multicomponent protein surfaces presenting lithographically defined patterns of tethered T cell receptor (TCR) ligands (anti-CD3 “activation sites”) surrounded by a field of tethered intercellular adhesion molecule-1 (ICAM-1), as a model substrate on which T cells could be seeded to mimic T cell–APC interactions. CD4+T cells seeded on these surfaces polarized and migrated; on contact with activation sites, T cells assembled an IS with a structure modulated by the physical pattern of ligand encountered. On surfaces patterned with focal spots of TCR ligand, T cells stably interacted with activation sites, proliferated, and secreted cytokines. In contrast, T cells interacting with activation sites patterned to preclude centralized clustering of TCR ligand failed to form stable contacts with activation sites, exhibited aberrant PKC-θ clustering in a fraction of cells, and had significantly reduced production of IFN-γ. These results suggest that focal clustering of TCR ligand characteristic of the “mature” IS may be required under some conditions for full T cell activation.
Quorum-sensing regulation governs bacterial adhesion, biofilm development, and host colonization in
Pantoea stewartii
subspecies
stewartii
Authors: Koutsoudis Maria D. , Tsaltas Dimitrios , Minogue Timothy D. , von Bodman Susanne B.
Published: April 2006

The phytopathogenic bacterium
Pantoea stewartii
subsp.
stewartii
synthesizes stewartan exo/capsular polysaccharide (EPS) in a cell density-dependent manner governed by the EsaI/EsaR quorum-sensing (QS) system. This study analyzes biofilm development and host colonization of the WT and QS regulatory mutant strains of
P. stewartii
. First, we show that the cell density-dependent synthesis of stewartan EPS, governed by the EsaI/EsaR QS system, is required for proper bacterial adhesion and development of spatially defined, 3D biofilms. Second, a nonvirulent mutant lacking the
esaI
gene adheres strongly to surfaces and develops densely packed, less structurally defined biofilms
in vitro
. This strain appears to be arrested in a low cell density developmental mode. Exposure of this strain to exogenous
N
-acyl-homoserine lactone counteracts this adhesion phenotype. Third, QS mutants lacking the EsaR repressor attach poorly to surfaces and form amorphous biofilms heavily enmeshed in excess EPS. Fourth, the WT strain disseminates efficiently within the xylem, primarily in a basipetal direction. In contrast, the two QS mutant strains remain largely localized at the site of infection. Fifth, and most significantly, epifluorescence microscopic imaging of infected leaf tissue and excised xylem vessels reveals that the bacteria colonize the xylem with unexpected specificity, particularly toward the annular rings and spiral secondary wall thickenings of protoxylem, as opposed to indiscriminate growth to fill the xylem lumen. These observations are significant to bacterial plant pathogenesis in general and may reveal targets for disease control.
Crystal structure of the
Anopheles gambiae
3-hydroxykynurenine transaminase
Authors: Rossi Franca , Garavaglia Silvia , Giovenzana Giovanni Battista , Arcà Bruno , Li Jianyong , Rizzi Menico
Published: April 2006

In
Anopheles gambiae
, the vector for the most deadly malaria parasite
Plasmodium falciparum
, xanthurenic acid (XA) plays a key role in parasite gametogenesis and fertility. In mosquitoes, XA is produced by transamination of 3-hydroxykynurenine (3-HK), a reaction that represents the main route to prevent the accumulation of the potentially toxic 3-HK excess. Interfering with XA metabolism in
A. gambiae
therefore appears an attractive avenue for the development of malaria transmission-blocking drugs and insecticides. We have determined the crystal structure of
A. gambiae
3-HK transaminase in its pyridoxal 5′-phosphate form and in complex with a newly synthesized competitive enzyme inhibitor. Structural inspection of the enzyme active site reveals the key molecular determinants for ligand recognition and catalysis. Major contributions toward inhibitor binding are provided by a salt bridge between the inhibitor carboxylate and Arg-356 and by a remarkable hydrogen bond network involving the anthranilic moiety of the inhibitor and backbone atoms of residues Gly-25 and Asn-44. This study may be useful for the structure-based design of specific enzyme inhibitors of potential interest as antimalarial agents.
Dominant-negative inhibition of the Axl receptor tyrosine kinase suppresses brain tumor cell growth and invasion and prolongs survival
Authors: Vajkoczy Peter , Knyazev Pjotr , Kunkel Andrea , Capelle Hans-Holger , Behrndt Sandra , von Tengg-Kobligk Hendrik , Kiessling Fabian , Eichelsbacher Uta , Essig Marco , Read Tracy-Ann , Erber Ralf , Ullrich Axel
Published: April 2006

Malignant gliomas remain incurable brain tumors because of their diffuse-invasive growth. So far, the genetic and molecular events underlying gliomagenesis are poorly understood. In this study, we have identified the receptor tyrosine kinase Axl as a mediator of glioma growth and invasion. We demonstrate that Axl and its ligand Gas6 are overexpressed in human glioma cell lines and that Axl is activated under baseline conditions. Furthermore, Axl is expressed at high levels in human malignant glioma. Inhibition of Axl signaling by overexpression of a dominant-negative receptor mutant (AXL-DN) suppressed experimental gliomagenesis (growth inhibition >85%,
P
< 0.05) and resulted in long-term survival of mice after intracerebral glioma cell implantation when compared with Axl wild-type (AXL-WT) transfected tumor cells (survival times: AXL-WT, 10 days; AXL-DN, >72 days). A detailed analysis of the distinct hallmarks of glioma pathology, such as cell proliferation, migration, and invasion and tumor angiogenesis, revealed that inhibition of Axl signaling interfered with cell proliferation (inhibition 30% versus AXL-WT), glioma cell migration (inhibition 90% versus mock and AXL-WT,
P
< 0.05), and invasion (inhibition 62% and 79% versus mock and AXL-WT, respectively;
P
< 0.05). This study describes the identification, functional manipulation,
in vitro
and
in vivo
validation, and preclinical therapeutic inhibition of a target receptor tyrosine kinase mediating glioma growth and invasion. Our findings implicate Axl in gliomagenesis and validate it as a promising target for the development of approaches toward a therapy of these highly aggressive but, as yet, therapy-refractory, tumors.
Senescence marker protein 30 functions as gluconolactonase in
l
-ascorbic acid biosynthesis, and its knockout mice are prone to scurvy
Authors: Kondo Yoshitaka , Inai Yoko , Sato Yasunori , Handa Setsuko , Kubo Sachiho , Shimokado Kentaro , Goto Sataro , Nishikimi Morimitsu , Maruyama Naoki , Ishigami Akihito
Published: April 2006

We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgen-independent manner with aging. Here, we report its sequence homology found in two kinds of bacterial gluconolactonases (GNLs) by using the
blast
search. Then, through a biochemical study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species. SMP30 purified from the rat liver had lactonase activity toward various aldonolactones, such as
d
- and
l
-glucono-δ-lactone,
d
- and
l
-gulono-γ-lactone, and
d
- and
l
-galactono-γ-lactone, with a requirement for Zn
2+
or Mn
2+
as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the liver. The lactonase reaction with
l
-gulono-γ-lactone is the penultimate step in
l
-ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this synthetic process was verified here by a nutritional study using SMP30 knockout mice. These knockout mice (
n
= 6), fed a vitamin C-deficient diet, did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary and then died by 135 days after the start of receiving the deficient diet. The AA levels in their livers and kidneys at the time of death were <1.6% of those in WT control mice. In addition, by using the SMP30 knockout mouse, we demonstrate that the alternative pathway of AA synthesis involving
d
-glucurono-γ-lactone operates
in vivo
, although its flux is fairly small.
The
Arabidopsis
homolog of trithorax, ATX1, binds phosphatidylinositol 5-phosphate, and the two regulate a common set of target genes
Authors: Alvarez-Venegas Raul , Sadder Monther , Hlavacka Andrej , Baluška František , Xia Yuannan , Lu Guoqing , Firsov Alexey , Sarath Gautam , Moriyama Hideaki , Dubrovsky Joseph G. , Avramova Zoya
Published: April 2006

The
Arabidopsis
homolog of trithorax, ATX1, regulates numerous functions in
Arabidopsis
beyond the homeotic genes. Here, we identified genome-wide targets of ATX1 and showed that ATX1 is a receptor for a lipid messenger, phosphatidylinositol 5-phosphate, PI5P. PI5P negatively affects ATX1 activity, suggesting a regulatory pathway connecting lipid-signaling with nuclear functions. We propose a model to illustrate how plants may respond to stimuli (external or internal) that elevate cellular PI5P levels by altering expression of ATX1-controlled genes.
Ligand-induced and nonfusogenic dissolution of a viral membrane
Authors: Law Mansun , Carter Gemma C. , Roberts Kim L. , Hollinshead Michael , Smith Geoffrey L.
Published: April 2006

Hitherto, all enveloped viruses were thought to shed their lipid membrane during entry into cells by membrane fusion. The extracellular form of
Vaccinia virus
has two lipid envelopes surrounding the virus core, and consequently a single fusion event will not deliver a naked core into the cell. Here we report a previously underscribed mechanism in which the outer viral membrane is disrupted by a ligand-induced nonfusogenic reaction, followed by the fusion of the inner viral membrane with the plasma membrane and penetration of the virus core into the cytoplasm. The dissolution of the outer envelope depends on interactions with cellular polyanionic molecules and requires the virus glycoproteins A34 and B5. This discovery represents a remarkable example of how viruses manipulate biological membranes, solves the topological problem of how a double-enveloped virus enters cells, reveals a new effect of polyanions on viruses, and provides a therapeutic approach for treatment of poxvirus infections, such as smallpox.
Water dynamics and salt-activation of enzymes in organic media: Mechanistic implications revealed by NMR spectroscopy
Authors: Eppler Ross K. , Komor Russell S. , Huynh Joyce , Dordick Jonathan S. , Reimer Jeffrey A. , Clark Douglas S.
Published: April 2006

Deuterium spin relaxation was used to examine the motion of enzyme-bound water on subtilisin Carlsberg colyophilized with inorganic salts for activation in different organic solvents. Spectral editing was used to ensure that the relaxation times were associated with relatively mobile deuterons, which were contributed almost entirely by D
2
O rather than hydrogen–deuteron exchange on the protein. The results indicate that the timescale of motion for residual water molecules on the biocatalyst, (τ
c
)

D
2
O

, in hexane decreased from 65 ns (salt-free) to 0.58 ns (98% CsF) as (
k
cat
/
K
M
)
app
of the biocatalyst preparation increased from 0.092 s
−1
·M
−1
(salt-free) to 1,140 s
−1
·M
−1
(98% CsF). A similar effect was apparent in acetone; the timescale decreased from 24 ns (salt-free) to 2.87 ns (98% KF), with a corresponding increase in (
k
cat
/
K
M
)
app
of 0.140 s
−1
·M
−1
(salt-free) to 12.8 s
−1
·M
−1
(98% KF). Although a global correlation between water mobility and enzyme activity was not evident, linear correlations between ln[(
k
cat
/
K
M
)
app
] and (τ
c
)

D
2
O

were obtained for salt-activated enzyme preparations in both hexane and acetone. Furthermore, a direct correlation was evident between (
k
cat
/
K
M
)
app
and the total amount of mobile water per mass of enzyme. These results suggest that increases in enzyme-bound water mobility mediated by the presence of salt act as a molecular lubricant and enhance enzyme flexibility in a manner functionally similar to temperature. Greater flexibility may permit a larger degree of local transition-state mobility, reflected by a more positive entropy of activation, for the salt-activated enzyme compared with the salt-free enzyme. This increased mobility may contribute to the dramatic increases in biocatalyst activity.
Thousands of samples are needed to generate a robust gene list for predicting outcome in cancer
Authors: Ein-Dor Liat , Zuk Or , Domany Eytan
Published: April 2006

Predicting at the time of discovery the prognosis and metastatic potential of cancer is a major challenge in current clinical research. Numerous recent studies searched for gene expression signatures that outperform traditionally used clinical parameters in outcome prediction. Finding such a signature will free many patients of the suffering and toxicity associated with adjuvant chemotherapy given to them under current protocols, even though they do not need such treatment. A reliable set of predictive genes also will contribute to a better understanding of the biological mechanism of metastasis. Several groups have published lists of predictive genes and reported good predictive performance based on them. However, the gene lists obtained for the same clinical types of patients by different groups differed widely and had only very few genes in common. This lack of agreement raised doubts about the reliability and robustness of the reported predictive gene lists, and the main source of the problem was shown to be the small number of samples that were used to generate the gene lists. Here, we introduce a previously undescribed mathematical method, probably approximately correct (PAC) sorting, for evaluating the robustness of such lists. We calculate for several published data sets the number of samples that are needed to achieve any desired level of reproducibility. For example, to achieve a typical overlap of 50% between two predictive lists of genes, breast cancer studies would need the expression profiles of several thousand early discovery patients.
Human vitamin B
12
absorption measurement by accelerator mass spectrometry using specifically labeled
14
C-cobalamin
Authors: Carkeet Colleen , Dueker Stephen R. , Lango Jozsef , Buchholz Bruce A. , Miller Joshua W. , Green Ralph , Hammock Bruce D. , Roth John R. , Anderson Peter J.
Published: April 2006

There is a need for an improved test of human ability to assimilate dietary vitamin B
12
. Assaying and understanding absorption and uptake of B
12
is important because defects can lead to hematological and neurological complications. Accelerator mass spectrometry is uniquely suited for assessing absorption and kinetics of carbon-14 (
14
C)-labeled substances after oral ingestion because it is more sensitive than decay counting and can measure levels of
14
C in microliter volumes of biological samples with negligible exposure of subjects to radioactivity. The test we describe employs amounts of B
12
in the range of normal dietary intake. The B
12
used was quantitatively labeled with
14
C at one particular atom of the dimethylbenzimidazole (DMB) moiety by exploiting idiosyncrasies of
Salmonella
metabolism. To grow aerobically on ethanolamine,
Salmonella enterica
must be provided with either preformed B
12
or two of its precursors, cobinamide and DMB. When provided with
14
C-DMB specifically labeled in the C2 position, cells produced
14
C-B
12
of high specific activity (2.1 GBq/mmol, 58 mCi/mmol) (1 Ci = 37 GBq) and no detectable dilution of label from endogenous DMB synthesis. In a human kinetic study, a physiological dose (1.5 μg, 2.2 kBq/59 nCi) of purified
14
C-B
12
was administered and showed plasma appearance and clearance curves consistent with the predicted behavior of the pure vitamin. This method opens new avenues for study of B
12
assimilation.
Mitigation strategies for pandemic influenza in the United States
Authors: Germann Timothy C. , Kadau Kai , Longini Ira M. , Macken Catherine A.
Published: April 2006

Recent human deaths due to infection by highly pathogenic (H5N1) avian influenza A virus have raised the specter of a devastating pandemic like that of 1917–1918, should this avian virus evolve to become readily transmissible among humans. We introduce and use a large-scale stochastic simulation model to investigate the spread of a pandemic strain of influenza virus through the U.S. population of 281 million individuals forR0(the basic reproductive number) from 1.6 to 2.4. We model the impact that a variety of levels and combinations of influenza antiviral agents, vaccines, and modified social mobility (including school closure and travel restrictions) have on the timing and magnitude of this spread. Our simulations demonstrate that, in a highly mobile population, restricting travel after an outbreak is detected is likely to delay slightly the time course of the outbreak without impacting the eventual number ill. ForR0< 1.9, our model suggests that the rapid production and distribution of vaccines, even if poorly matched to circulating strains, could significantly slow disease spread and limit the number ill to <10% of the population, particularly if children are preferentially vaccinated. Alternatively, the aggressive deployment of several million courses of influenza antiviral agents in a targeted prophylaxis strategy may contain a nascent outbreak with lowR0, provided adequate contact tracing and distribution capacities exist. For higherR0, we predict that multiple strategies in combination (involving both social and medical interventions) will be required to achieve similar limits on illness rates.