bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferromagnetic Mn-doped GaN nanowires
Authors: Han Doo Suk , Park Jeunghee , Rhie Kung Won , Kim Soonkyu , Chang Joonyeon
Published: January 2005

We report Mn-doped GaN nanowires exhibiting ferromagnetism even at room temperature. The growth of single-crystalline wurtzite-structured GaN nanowires doped homogeneously with about 5 at. % Mn was achieved by chemical vapor deposition using the reaction of Ga∕GaN∕MnCl2 with NH3. The ferromagnetic hysteresis at 5 and 300 K and the temperature-dependent magnetization curves suggest the Curie temperature around 300 K. Negative magnetoresistance of individual nanowires was observed at the temperatures below 150 K.
Bismuth ion-implanted solid-phase epitaxially grown shallow junction for metal–oxide–semiconductor field-effect transistors
Authors: Tavakoli Shahram Ghanad , Baek Sungkweon , Chang Hyo Sik , Moon Dae Won , Hwang Hyunsang
Published: January 2005

A shallow, low-resistive solid phase epitaxially regrown n+∕p junction was investigated for sub-70 nm metal–oxide–semiconductor field-effect transistors (MOSFETs), using bismuth (Bi) ion-implantation and low temperature rapid thermal annealing. Bi-doped specimens showed a shallow junction depth of ∼15nm (at a background concentration of 5×1018cm−3), low sheet resistance, and leakage current at low temperature processing (700°C). The results indicated that Bi could be a proper dopant for low temperature activated source and drain extensions that are fabricated at low temperatures with the implementation of high-κ dielectric and metal–electrode gate stacks in next generation MOSFETs.
Emission properties of 6.7μm continuous-wave PbSe-based vertical-emitting microcavity lasers operating up to 100K
Authors: Schwarzl T. , Springholz G. , Böberl M. , Kaufmann E. , Roither J. , Heiss W. , Fürst J. , Pascher H.
Published: January 2005

A detailed analysis of midinfrared cw lasing of IV–VI vertical-cavity surface-emitting devices is presented. The structures, based on high-finesse microcavities containing PbSe as active medium, show optically pumped cw laser emission up to temperatures of 100K at a long wavelength of 6.7μm. Stimulated emission with a very narrow beam divergence below 1° and a large temperature tuning range of 70nm is found. The measured linewidth of the laser emission is only 0.6nm, limited by the spectrometer resolution with a strong narrowing with respect to the linewidth of the subthreshold signal. The observed cw output power amounts up to 1.2mW at 85K.
Electromagnetically induced transparency in alkali atoms integrated on a semiconductor chip
Authors: Schmidt H. , Hawkins A. R.
Published: January 2005

We analyze the integration of electromagnetically induced transparency in alkali atoms on a semiconductor chip. We propose the use of antiresonant reflecting optical waveguides with hollow cores to realize the necessary waveguiding capability and optical mode areas of a few square micrometers. We derive the scaling laws and limitations for the reduction in group velocity and single-photon phase shifts as a function of waveguide dimension. We show that miniaturization leads to a large enhancement of single-photon cross-phase modulation, despite the presence of additional limitations due to coherence dephasing and waveguide loss.
Temperature dependence of the dielectric tunability of pyrochlore bismuth zinc niobate thin films
Authors: Tagantsev Alexander K. , Lu Jiwei , Stemmer Susanne
Published: January 2005

The change in permittivity of bismuth zinc niobate (BZN) films with the cubic pyrochlore structure under an applied electric field was measured as a function of temperature. Dielectric measurements were performed using parallel-plate capacitor structures with Pt electrodes on sapphire substrates. The electric field tunability of the permittivity was weakly temperature dependent and increased with decreasing temperature up to the onset of dielectric relaxation. At temperatures below the onset of the dielectric relaxation (∼150K at 1MHz), larger electric fields were required to achieve the highest tunabilities. A simple model of hopping, noninteracting dipoles was not suited to describe the dielectric tunability of BZN thin films. A better description of the experimentally observed behavior at temperatures above the onset of the dielectric relaxation was obtained using a simple random-field model with hopping dipoles in a uniform distribution of random fields.
Highly linear and efficient phase modulators based on GaInAsP-InP three-step quantum wells
Authors: Mohseni H. , An H. , Shellenbarger Z. A. , Kwakernaak M. H. , Abeles J. H.
Published: January 2005

Highly linear and efficient phase modulators based on three-step quantum wells are reported. The spatial separation of electron and hole wave functions in the three-step quantum well leads to enhancement of the linear electro-optic component. In parallel, the quadratic electro-optic component is suppressed using a method based on tailored doping profile. Measured modulation efficiency is 48°∕mm V, and the ratio of linear to quadratic components of the phase modulation is 640 at λ=1560nm. The efficiency is similar to the best reported values for semiconductor modulators at this wavelength, while the linearity is more than one order of magnitude higher.
Elicitation of allergic asthma by immunoglobulin free light chains
Authors: Kraneveld Aletta D. , Kool Mirjam , van Houwelingen Anneke H. , Roholl Paul , Solomon Alan , Postma Dirkje S. , Nijkamp Frans P. , Redegeld Frank A.
Published: January 2005

The observation that only 50% of patients with adult asthma manifest atopy indicates that other inflammatory mechanisms are likely involved in producing the characteristic features of this disorder; namely reversible airway obstruction, hyperresponsiveness, and pulmonary inflammation. Our recent discovery that antigen-specific Ig free light chains (LCs) mediate hypersensitivity-like responses suggests that these molecules may be of import in the pathophysiology of asthma. Using a murine experimental model of nonatopic asthma, we now have shown that an LC antagonist, the 9-mer peptide F991, can abrogate the development of airway obstruction, hyperresponsiveness, and pulmonary inflammation. Further, passive immunization with antigen-specific LCs and subsequent airway challenge can elicit a mast cell-dependent reaction leading to acute bronchoconstriction. These findings, and the demonstration that the concentration of free κ LCs in the sera of patients with adult asthma were significantly increased (as compared with age-matched nonasthmatic individuals), provide previously undescribed insight into the pathogenesis of asthma. In addition, the ability to inhibit pharmacologically LC-induced mast cell activation provides a therapeutic means to prevent or ameliorate the adverse bronchopulmonary manifestations of this incapacitating disorder.
The protein structure prediction problem could be solved using the current PDB library
Authors: Zhang Yang , Skolnick Jeffrey
Published: January 2005

For single-domain proteins, we examine the completeness of the structures in the current Protein Data Bank (PDB) library for use in full-length model construction of unknown sequences. To address this issue, we employ a comprehensive benchmark set of 1,489 medium-size proteins that cover the PDB at the level of 35% sequence identity and identify templates by structure alignment. With homologous proteins excluded, we can always find similar folds to native with an average rms deviation (RMSD) from native of 2.5 Å with ≈82% alignment coverage. These template structures often contain a significant number of insertions/deletions. The
tasser
algorithm was applied to build full-length models, where continuous fragments are excised from the top-scoring templates and reassembled under the guide of an optimized force field, which includes consensus restraints taken from the templates and knowledge-based statistical potentials. For almost all targets (except for 2/1,489), the resultant full-length models have an RMSD to native below 6 Å (97% of them below 4 Å). On average, the RMSD of full-length models is 2.25 Å, with aligned regions improved from 2.5 Å to 1.88 Å, comparable with the accuracy of low-resolution experimental structures. Furthermore, starting from state-of-the-art structural alignments, we demonstrate a methodology that can consistently bring template-based alignments closer to native. These results are highly suggestive that the protein-folding problem can in principle be solved based on the current PDB library by developing efficient fold recognition algorithms that can recover such initial alignments.
Imaging bacterial infections with radiolabeled 1-(2′-deoxy-2′-fluoro-β-D-arabinofuranosyl)-5-iodouracil
Authors: Bettegowda Chetan , Foss Catherine A. , Cheong Ian , Wang Yuchuan , Diaz Luis , Agrawal Nishant , Fox James , Dick James , Dang Long H. , Zhou Shibin , Kinzler Kenneth W. , Vogelstein Bert , Pomper Martin G.
Published: January 2005

Bacterial infections provide diagnostic dilemmas that could be enlightened by modern imaging technologies. We have developed a simple method for imaging bacterial infections in mice that relies on the phosphorylation and trapping of the thymidine kinase (TK) substrate 1-(2′-deoxy-2′-fluoro-β-
d
-arabinofuranosyl)-5-[
125
I] iodouracil ([
125
I]FIAU) within bacteria. FIAU was found to inhibit the growth of WT
Escherichia coli
but not a TK
–
strain, indicating that WT
E. coli
could metabolize this compound.
In silico
analyses demonstrated that all pathogenic strains of bacteria whose genomes have been sequenced contain a TK gene highly homologous to the
E. coli
TK. Accordingly, we demonstrated that localized infections caused by representatives of five genera of bacteria could be readily imaged with [
125
I]FIAU. Such imaging provides a general method for the diagnosis of localized bacterial infections that could be translatable to the clinic.
Directing cell migration with asymmetric micropatterns
Authors: Jiang Xingyu , Bruzewicz Derek A. , Wong Amy P. , Piel Matthieu , Whitesides George M.
Published: January 2005

This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move. Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward their blunt ends.
Seasonal epidemics of cholera inversely correlate with the prevalence of environmental cholera phages
Authors: Faruque Shah M. , Naser Iftekhar Bin , Islam M. Johirul , Faruque A. S. G. , Ghosh A. N. , Nair G. Balakrish , Sack David A. , Mekalanos John J.
Published: January 2005

The relationship among (
i
) the local incidence of cholera, (
ii
) the prevalence in the aquatic environment of
Vibrio cholerae
, and (
iii
) bacterial viruses that attack potentially virulent O1 and O139 serogroup strains of this organism (cholera phages) was studied in Dhaka, Bangladesh. Over nearly a 3-year period, we found that significantly more environmental water samples contained either a phage or a phage-susceptible
V. cholerae
strain than both (
P
< 0.00001). The number of cholera patients varied seasonally during this period and frequently coincided with the presence of pathogenic
V. cholerae
strains in water samples that otherwise lacked detectable cholera phages. Interepidemic periods were characterized by water samples containing cholera phages but no viable bacteria. Our data support the conclusion that cholera phages can influence cholera seasonality and may also play a role in emergence of new
V. cholerae
pandemic serogroups or clones.
Characterization of potential selenium-binding proteins in the selenophosphate synthetase system
Authors: Ogasawara Yuki , Lacourciere Gerard M. , Ishii Kazuyuki , Stadtman Thressa C.
Published: January 2005

Selenophosphate, an activated form of selenium that can serve as a selenium donor, is generated by the
selD
gene product, selenophosphate synthetase (SPS). Selenophosphate is required by several bacteria and by mammals for the specific synthesis of Secys-tRNA, the precursor of selenocysteine in selenoenzymes. Although free selenide can be used
in vitro
for synthesis of selenophosphate, the physiological system that donates selenium to SPS is incompletely characterized. To detect potential selenium-delivery proteins, two known sulfurtransferases and glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) were analyzed for ability to bind and transfer selenium. Rhodanese (EC 2.8.1.1) was shown to bind selenium tightly, with only part of the selenium being available as substrate for SPS in the presence of added reductant. 3-Mercaptopyruvate sulfurtransferase (3-MST; EC 2.8.1.2) and GAPDH also bound selenium supplied as selenodiglutathione formed from

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and glutathione. Selenium bound to 3-MST and GAPDH was released more readily than that from rhodanese and also was more available as a substrate for SPS. Although rhodanese retained tightly bound selenium under aerobic conditions, the protein gradually became insoluble, whereas GAPDH containing bound selenium was stable at neutral pH for a long period. These results indicate that 3-MST and GAPDH have more suitable potentials as a physiological selenium-delivery protein than rhodanese. In the presence of a selenium-binding protein, a low level of selenodiglutathione formed from

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and glutathione could effectively replace the high concentrations of selenide routinely used as substrate in the SPS
in vitro
assays.
Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin
Authors: Isoldi Mauro Cesar , Rollag Mark D. , de Lauro Castrucci Ana Maria , Provencio Ignacio
Published: January 2005

Melanopsin is the photopigment that confers light sensitivity on intrinsically photosensitive retinal ganglion cells. Mammalian intrinsically photosensitive retinal ganglion cells are involved in the photic synchronization of circadian rhythms to the day–night cycle. Here, we report molecular components of melanopsin signaling using the cultured
Xenopus
dermal melanophore system. Photo-activated melanopsin is shown to initiate a phosphoinositide signaling pathway similar to that found in invertebrate photo-transduction. In melanophores, light increases the intracellular level of inositol trisphosphate and causes the dispersion of melanosomes. Inhibition of phospholipase C and protein kinase C and chelation of intracellular calcium block the effect of light on melanophores. At least four proteins, 43, 74, 90, and 134 kDa, are phosphorylated by protein kinase C upon light stimulation. This provides evidence of an invertebrate-like light-activated signaling cascade within vertebrate cells.
Magnetic resonance imaging and angiography for the prerupture diagnosis of rudimentary uterine horn pregnancy
Authors: Ozeren S. , Caliskan E. , Corakci A. , Ozkan S. , Demirci A.
Published: January 2005

Magnetic resonance (MR) imaging and MR angiography were used for the differential diagnosis and preoperative planning of a 17 weeks of age rudimentary horn pregnancy. A 26-year-old primigravida was referred to our hospital with a preliminary diagnosis of abdominal pregnancy. After an inconclusive ultrasound evaluation we were able to identify a rudimentary horn pregnancy, extent of the placental invasion, and the vascular supply via MR imaging and time of flight sequence MR angiography. The obtained data were also used for preoperative planning, which resulted in an uncomplicated, prerupture laparotomy for pregnancy termination and a healthy female.
Making connections between novel transcription factors and their DNA motifs
Authors: Tan Kai , McCue Lee Ann , Stormo Gary D.
Published: January 2005

The key components of a transcriptional regulatory network are the connections between trans-acting transcription factors and cis-acting DNA-binding sites. In spite of several decades of intense research, only a fraction of the estimated ∼300 transcription factors in Escherichia coli have been linked to some of their binding sites in the genome. In this paper, we present a computational method to connect novel transcription factors and DNA motifs in E. coli. Our method uses three types of mutually independent information, two of which are gleaned by comparative analysis of multiple genomes and the third one derived from similarities of transcription-factor-DNA-binding-site interactions. The different types of information are combined to calculate the probability of a given transcription-factor-DNA-motif pair being a true pair. Tested on a study set of transcription factors and their DNA motifs, our method has a prediction accuracy of 59% for the top predictions and 85% for the top three predictions. When applied to 99 novel transcription factors and 70 novel DNA motifs, our method predicted 64 transcription-factor-DNA-motif pairs. Supporting evidence for some of the predicted pairs is presented. Functional annotations are made for 23 novel transcription factors based on the predicted transcription-factor-DNA-motif connections.
Interchromosomal segmental duplications of the pericentromeric region on the human Y chromosome
Authors: Kirsch Stefan , Weiß Birgit , Miner Tracie L. , Waterston Robert H. , Clark Royden A. , Eichler Evan E. , Münch Claudia , Schempp Werner , Rappold Gudrun
Published: January 2005

Basic medical research critically depends on the finished human genome sequence. Two types of gaps are known to exist in the human genome: those associated with heterochromatic sequences and those embedded within euchromatin. We identified and analyzed a euchromatic island within the pericentromeric repeats of the human Y chromosome. This 450-kb island, although not recalcitrant to subcloning and present in 100 tested males from different ethnic origins, was not detected and is not contained within the published Y chromosomal sequence. The entire 450-kb interval is almost completely duplicated and consists predominantly of interchromosomal rather than intrachromosomal duplication events that are usually prevalent on the Y chromosome. We defined the modular structure of this interval and detected a total of 128 underlying pairwise alignments (≥90% and ≥1 kb in length) to various autosomal pericentromeric and ancestral pericentromeric regions. We also analyzed the putative gene content of this region by a combination of in silico gene prediction and paralogy analysis. We can show that even in this exceptionally duplicated region of the Y chromosome, eight putative genes with open reading frames reside, including fusion transcripts formed by the splicing of exons from two different duplication modules as well as members of the homeobox gene family DUX.
Evolution of the Isoprene Biosynthetic Pathway in Kudzu
Authors: Sharkey Thomas D. , Yeh Sansun , Wiberley Amy E. , Falbel Tanya G. , Gong Deming , Fernandez Donna E.
Published: January 2005

Isoprene synthase converts dimethylallyl diphosphate, derived from the methylerythritol 4-phosphate (MEP) pathway, to isoprene. Isoprene is made by some plants in substantial amounts, which affects atmospheric chemistry, while other plants make no isoprene. As part of our long-term study of isoprene synthesis, the genetics of the isoprene biosynthetic pathway of the isoprene emitter, kudzu (Pueraria montana), was compared with similar genes in Arabidopsis (Arabidopsis thaliana), which does not make isoprene. The MEP pathway genes in kudzu were similar to the corresponding Arabidopsis genes. Isoprene synthase genes of kudzu and aspen (Populus tremuloides) were cloned to compare their divergence with the divergence seen in MEP pathway genes. Phylogenetic analysis of the terpene synthase gene family indicated that isoprene synthases are either within the monoterpene synthase clade or sister to it. In Arabidopsis, the gene most similar to isoprene synthase is a myrcene/ocimene (acyclic monoterpenes) synthase. Two phenylalanine residues found exclusively in isoprene synthases make the active site smaller than other terpene synthase enzymes, possibly conferring specificity for the five-carbon substrate rather than precursors of the larger isoprenoids. Expression of the kudzu isoprene synthase gene in Arabidopsis caused Arabidopsis to emit isoprene, indicating that whether or not a plant emits isoprene depends on whether or not it has a terpene synthase capable of using dimethylallyl diphosphate.
Functional Genomics of Eukaryotic Photosynthesis Using Insertional Mutagenesis of Chlamydomonas reinhardtii
Authors: Dent Rachel M. , Haglund Cat M. , Chin Brian L. , Kobayashi Marilyn C. , Niyogi Krishna K.
Published: January 2005

The unicellular green alga Chlamydomonas reinhardtii is a widely used model organism for studies of oxygenic photosynthesis in eukaryotes. Here we describe the development of a resource for functional genomics of photosynthesis using insertional mutagenesis of the Chlamydomonas nuclear genome. Chlamydomonas cells were transformed with either of two plasmids conferring zeocin resistance, and insertional mutants were selected in the dark on acetate-containing medium to recover light-sensitive and nonphotosynthetic mutants. The population of insertional mutants was subjected to a battery of primary and secondary phenotypic screens to identify photosynthesis-related mutants that were pigment deficient, light sensitive, nonphotosynthetic, or hypersensitive to reactive oxygen species. Approximately 9% of the insertional mutants exhibited 1 or more of these phenotypes. Molecular analysis showed that each mutant line contains an average of 1.4 insertions, and genetic analysis indicated that approximately 50% of the mutations are tagged by the transforming DNA. Flanking DNA was isolated from the mutants, and sequence data for the insertion sites in 50 mutants are presented and discussed.
Kallikrein–kinin in stroke, cardiovascular and renal disease
Authors: Chao Julie , Chao Lee
Published: January 2005

Tissue kallikrein, a serine proteinase, produces the potent vasodilator kinin peptide from kininogen substrate. The levels of tissue kallikrein are reduced in humans and animal models with hypertension, cardiovascular and renal disease. Using transgenic and somatic gene transfer approaches, we investigated the role of the tissue kallikrein–kinin system in cardiovascular, renal and central nervous systems. A single injection of the human tissue kallikrein gene in plasmid DNA or an adenoviral vector resulted in a prolonged reduction of blood pressure and attenuation of hypertrophy and fibrosis in the heart and kidney of several hypertensive animal models. Furthermore, enhanced kallikrein–kinin levels after gene transfer exerted beneficial effects, with protection against cardiac remodelling, renal injuries, restenosis, cerebral infarction and neurological deficits in normotensive animal models without haemodynamic effects, indicating direct actions of kallikrein independent of its ability to lower blood pressure. The effects of kallikrein were mediated by the kinin B2 receptor, as the specific B2 receptor antagonist icatibant abolished the actions of kallikrein. Moreover, kallikrein–kinin exhibited pleiotropic effects by inhibiting apoptosis, inflammation, hypertrophy and fibrosis, and promoting angiogenesis and neurogenesis in the heart, kidney, brain and blood vessel. Exogenous administration of kallikrein also led to increased nitric oxide (NO)/cGMP and cAMP levels, and reduced NAD(P)H oxidase activities, superoxide formation and pro‐inflammatory cytokine levels. These results indicate a novel role of kallikrein–kinin through the kinin B2 receptor as an antioxidant and anti‐inflammatory agent in protection against stroke, cardiovascular and renal disease, and may uncover new drug targets for the prevention and treatment of heart failure, vascular injury, end‐stage renal disease and stroke in humans.
Laser Doppler flowmetry is valid for measurement of cerebral blood flow autoregulation lower limit in rats
Authors: Tonnesen Jan , Pryds Anders , Larsen Erik H. , Paulson Olaf B. , Hauerberg John , Knudsen Gitte M.
Published: January 2005

Laser Doppler flowmetry (LDF) is a recent technique that is increasingly being used to monitor relative changes in cerebral blood flow whereas the intra‐arterial 133xenon injection technique is a well‐established method for repeated absolute measurements of cerebral blood flow. The aim of this study was to validate LDF for assessment of cerebral autoregulation and CO2 reactivity with the 133xenon injection technique as the gold standard. Simultaneous measurements of cerebral blood flow (CBF) were collected by LDF (CBFLDF) and the 133xenon method (CBFXe) while (1) cerebral autoregulation was challenged by controlled systemic haemorrhage, or (2) cerebral blood flow was varied by manipulating the arterial partial pressure of CO2 (Pa,CO2). LDF slightly overestimated CBF under conditions of haemorrhagic shock and haemodilution caused by controlled haemorrhage (paired t test, P < 0.05). However for pooled data, the autoregulation lower limit was similar when determined with the 133xenon and the LDF techniques: 65 ± 3.9 mmHg and 60 ± 5.6 mmHg, respectively. Linear regression analysis yielded CBFXe= (1.02 × CBFLDF) + 9.1 and r= 0.90. Even for substantial changes in Pa,CO2, the two methods resulted in similar results. We conclude that even though LDF overestimated CBF during haemorrhagic shock caused by controlled haemorrhage, the lower limit autoregulation was correctly identified. The laser Doppler technique provides a reliable method for detection of a wide range of cerebral blood flow changes under CO2 challenge. Haemodilution influences the two methods differently causing relative overestimation of blood flow by the laser Doppler technique compared to the 133xenon method.
EFFECT OF IONIC AND NONIONIC SUBSTITUENTS ON THE ELECTRORHEOLOGICAL CHARACTERISTICS OF POLYANILINE DERIVATIVES
Authors: CHOI H. J. , CHO M. S. , KIM J. W. , WEBBER R. M. , JHON M. S.
Published: January 2005

We report our experimental results on the electrorheological (ER) characteristics of ER fluids consisting of suspensions of semiconducting polyaniline and copolyaniline particles in silicone oil. Ionic sodium diphenylamine sulfonate and nonionic o-ethoxyaniline were introduced to synthesize copolyanilines, i.e. N-substituted copolyaniline and poly (aniline-co-o-ethoxyaniline), respectively. ER fluids using these particles were compared. ER fluids, which contain the ionic copolymer, showed the highest ER performance among polyaniline and its copolymer systems. This result was interpreted in terms of the conductivities of the particles and their dielectric spectra.
A TECHNIQUE IN THE TOPOLOGY OF CONNECTED SELF-SIMILAR TILES
Authors: NGAI SZE-MAN , TANG TAI-MAN
Published: January 2005

Not much is known about the topological structure of a connected self-similar tile whose interior is disconnected, and even less is understood if the interior consists of infinitely many components. We introduce a technique to show that for a large class of self-similar tiles in ℝ2, the closure of each component of the interior is homeomorphic to a disk. This allows us to prove such a result for the Eisenstein set, the fundamental domain of a well-known quadratic canonical number system, and some other well-known fractal tiles.
ENDOCYTOTIC CYCLING OF PM PROTEINS
Authors: Murphy Angus S. , Bandyopadhyay Anindita , Holstein Susanne E. , Peer Wendy A.
Published: January 2005

Plasma membrane protein internalization and recycling mechanisms in plants share many features with other eukaryotic organisms. However, functional and structural differences at the cellular and organismal level mandate specialized mechanisms for uptake, sorting, trafficking, and recycling in plants. Recent evidence of plasma membrane cycling of members of the PIN auxin efflux facilitator family and the KAT1 inwardly rectifying potassium channel demonstrates that endocytotic cycling of some form occurs in plants. However, the mechanisms underlying protein internalization and the signals that stimulate endocytosis of proteins from the cell-environment interface are poorly understood. Here we summarize what is known of endocytotic cycling in animals and compare those mechanisms with what is known in plants. We discuss plant orthologs of mammalian-trafficking proteins involved in endocytotic cycling. The use of the styryl dye FM4-64 to define the course of endocytotic uptake and the fungal toxin brefeldin A to dissect the internalization pathways are particularly emphasized. Additionally, we discuss progress in identifying distinct endosomal populations marked by the small GTPases Ara6 and Ara7 as well as recently described examples of apparent cycling of plasma membrane proteins.
MOLECULAR PHYSIOLOGY OF LEGUME SEED DEVELOPMENT
Authors: Weber Hans , Borisjuk Ljudmilla , Wobus Ulrich
Published: January 2005

Legume seed development is characterized by progressive differentiation of organs and tissues resulting in developmental gradients A developmental gradient results from the gradual differentiation of different organs or within a single-seed organ and is reflected by heterogeneous populations of cells of different physiological age accumulating different amounts of substances, e.g., mRNAs, proteins, and starch. . The whole process is prone to metabolic control, and distinct metabolite profiles specify the differentiation state. Whereas early embryo growth is mainly maternally controlled, the transition into maturation implies a switch to filial control. A signaling network involving sugars, ABA abscisic acid , and SnRK1 kinases governs maturation. Processes of maturation are activated by changing oxygen/energy levels and/or a changing nutrient state, which trigger responses at the level of transcription and protein phosphorylation. This way seed metabolism becomes adapted to altering conditions. In maturing cotyledons photoheterotrophic metabolism Photoheterotrophic metabolism occurs in green seeds in which specific photoheterotrophic plastids import sugars, are photosynthetically active, and produce oxygen, thereby supporting respiration and overall metabolic activity. improves internal oxygen supply and biosynthetic fluxes and influences assimilate partitioning. Transgenic legumes with changed metabolic pathways and seed composition provide suitable models to study pathway regulation and metabolic control. At the same time, desirable improvements of seed quality and yield may be achieved.
SOLUTE TRANSPORTERS OF THE PLASTID ENVELOPE MEMBRANE
Authors: Weber Andreas P.M. , Schwacke Rainer , Flügge Ulf-Ingo
Published: January 2005

Plastids semi-autonomous, membrane-bound organelles of plant cells that carry out a large number of biosynthetic and other functions such as photosynthesis (chloroplasts), ammonia and sulfur assimilation, and starch storage (amyloplasts) are metabolically extraordinarily active and versatile organelles that are found in all plant cells with the exception of angiosperm pollen grains. Many of the plastid-localized biochemical pathways depend on precursors from the cytosol and, in turn, many cytosolic pathways depend on the supply of precursor molecules from the plastid stroma. Hence, a massive traffic of metabolites occurs across the permeability barrier between plastids and cytosol that is called the plastid envelope membrane. Many of the known plastid envelope solute transporters integral membrane proteins that catalyze the transport of solutes across biological lipid-bilayer membranes have been identified by biochemical purification and peptide sequencing. This approach is of limited use for less abundant proteins and for proteins of plastid subtypes that are difficult to isolate in preparative amounts. Hence, the majority of plastid envelope membrane transporters are not yet identified at the molecular level. The availability of fully sequenced plant genomes, the progress in bioinformatics research, development, or application of computational tools and approaches to explore biological data such as genome sequences or proteomics data to predict membrane transporters localized in plastids, and the development of highly sensitive proteomics systematic, comprehensive analysis of the full set of proteins (the proteome) in an organism, a specific cell or tissue, or a cellular fraction such as internal membrane systems techniques open new avenues toward identifying additional, to date unknown, plastid envelope membrane transporters.
GENETICS OF BRAIN STRUCTURE AND INTELLIGENCE
Authors: Toga Arthur W. , Thompson Paul M.
Published: January 2005

Genetic influences on brain morphology and IQ are well studied. A variety of sophisticated brain-mapping approaches relating genetic influences on brain structure and intelligence establishes a regional distribution for this relationship that is consistent with behavioral studies. We highlight those studies that illustrate the complex cortical patterns associated with measures of cognitive ability. A measure of cognitive ability, known as g, has been shown highly heritable across many studies. We argue that these genetic links are partly mediated by brain structure that is likewise under strong genetic control. Other factors, such as the environment, obviously play a role, but the predominant determinant appears to genetic.
Antiatherogenic potential of red wine: clinician update
Authors: Szmitko Paul E. , Verma Subodh
Published: January 2005

Complications of atherosclerosis remain the leading cause of morbidity and mortality in industrialized countries. Epidemiological studies have repeatedly demonstrated that moderate alcohol intake has a beneficial effect on cardiovascular disease. The purpose of this review is to examine the epidemiological and biological evidence supporting the intake of red wine as a means of reducing atherosclerosis. On the basis of epidemiological studies, moderate intake of alcoholic beverages, including red wine, reduces the risk of cardiovascular, cerebrovascular, and peripheral vascular disease in populations. In addition to the favorable biological effects of alcohol on the lipid profile, on hemostatic factors, and in reducing insulin resistance, the phenolic compounds in red wine appear to interfere with the molecular processes underlying the initiation, progression, and rupture of atherosclerotic plaques. Whether red wine is more beneficial than other types of alcohol remains unclear. Definitive data from a large-scale, randomized clinical end-point trial of red wine intake would be required before physicians can advise patients to use wine as part of preventative or medical therapies.
Involvement of p38-mitogen-activated protein kinase in adenosine receptor-mediated relaxation of coronary artery
Authors: Teng Bunyen , Qin Weixi , Ansari Habib R. , Mustafa S. Jamal
Published: January 2005

The purpose of this study was to explore the involvement of adenosine receptor(s) in porcine coronary artery (PCA) relaxation and to define the role of MAPK signaling pathways. Isometric tensions were recorded in denuded PCA rings. 5′-( N-ethylcarboxamido)adenosine (NECA), a nonselective adenosine receptor agonist, induced a concentration-dependent relaxation (EC50 = 16.8 nM) of PGF2α (10 μM)-preconstricted arterial rings. NECA-induced relaxation was completely blocked by 0.1 μM SCH-58261 (A2A antagonist) at lower doses (1–40 nM) but not at higher doses (80–1,000 nM). MRS-1706 (1 μM, A2B antagonist) was able to shift the NECA concentration-response curve to the right. CGS-21680 (selective A2A agonist) induced responses similarly to NECA, whereas N6-cyclopentyladenosine (A1 agonist) and Cl-IB-MECA (A3 agonist) did not. Furthermore, the effect of NECA was attenuated by the addition of SB-203580 (10 μM, p38 MAPK inhibitor) but not by PD-98059 (10 μM, MEK inhibitor). Interestingly, SB-203580 had no effect on CGS-21680-induced relaxation. Western blot analysis demonstrated that PGF2α and adenosine agonists stimulated p38 MAPK at a concentration of 40 nM in PCA smooth muscle cells. MRS-1706 (1 μM) significantly reduced NECA-induced p38 MAPK phosphorylation. Addition of NECA and SB-203580 alone or in combination inhibited PGF2α-induced p38 MAPK. Western blot data were further confirmed by p38 MAPK activity measurement using activating transcription factor-2 assay. Our results suggest that the adenosine receptor subtype involved in causing relaxation of porcine coronary smooth muscle is mainly A2A subtype, although A2B also may play a role, possibly through p38 MAPK pathway.
Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors
Authors: Zhang Cuihua , Knudson Jarrod D. , Setty Srinath , Araiza Alberto , Dincer Ü. Deniz , Kuo Lih , Tune Johnathan D.
Published: January 2005

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to ANG II is altered under this condition is unknown. Experiments were conducted in control and chronically high-fat-fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60–110 μm) and in vivo (anesthetized and conscious). We found that plasma renin activity and ANG II levels are elevated in high-fat-fed dogs and that this increase in ANG II is associated with a significant increase in ANG II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open-chest dogs. The vasoconstriction to ANG II is abolished by ANG II type 1 (AT1) receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high-fat-fed dogs but not in normal control dogs, i.e., the relationship between coronary venous Po2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT1 and ANG II type 2 (AT2) receptor mRNA levels by real-time PCR revealed no significant difference between normal control and high-fat-fed dogs; however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor-mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating ANG II and/or coronary arteriolar AT1 receptor density.
Analysis of nitric oxide donor effectiveness in resistance vessels
Authors: Hyduke Daniel R. , Liao James C.
Published: January 2005

Decreased nitric oxide (NO) bioavailability is associated with a number of pathological conditions. Administration of a supplemental source of NO can counter the pathological effects arising from decreased NO bioavailability. A class of NO-nucleophile adducts that spontaneously release NO (NONOates) has been developed, and its members show promise as therapeutic sources of NO. Because the NONOates release NO spontaneously, a significant portion of the NO may be consumed by the myriad of NO reactive species present in the body. Here we develop a model to analyze the efficacy of NO delivery, by membrane-impermeable NONOates, in the resistance arterioles. Our model identifies three features of blood vessels that will enhance NONOate efficacy: 1) the amount of NO delivered to the abluminal region increases with lumen radius; 2) the presence of a flow-induced red blood cell-free zone will augment NO delivery; and 3) extravasation of the NONOate into the interstitial space will increase abluminal NO delivery. These results suggest that NONOates may be more effective in larger vessels and that NONOate efficacy can be altered by modifying permeability to the interstitial space.
In vivo adenosine receptor preconditioning reduces myocardial infarct size via subcellular ERK signaling
Authors: Reid Easton A. , Kristo Gentian , Yoshimura Yukihiro , Ballard-Croft Cherry , Keith Byron J. , Mentzer Robert M. , Lasley Robert D.
Published: January 2005

The protective effects of adenosine receptor acute preconditioning (PC) are well known; however, the signaling mechanism mediating this effect has not been determined in in vivo models. The purpose of this study was to determine the role of the extracellular signal-regulated kinase (ERK) pathway in mediating adenosine PC in in vivo rat myocardium. Open-chest rats were submitted to 25 min of coronary artery occlusion and 2 h of reperfusion. ERK activation was assessed by measuring total and dually phosphorylated p44/42 ERK isoforms in nuclear and/or myofilament, mitochondrial, cytosolic, and membrane fractions. Adenosine receptor PC with the A1/A2a agonist 1 S-[1a,2b,3b,4a( S*)]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-3H-imidazo[4,5-b]pyridyl-3-yl]cyclopentane carboxamide (AMP-579) reduced infarct size from 49 ± 3% to 29 ± 3%, an effect that was blocked by the mitogen-activated protein kinase-ERK inhibitor U-0126. ERK isoforms were present in all fractions, with the greatest expression in the cytosolic fraction and the least in the mitochondrial fraction. AMP-579 treatment increased preischemic p44/42 ERK phosphorylation in all fractions 2.7- to 6.9-fold. Reperfusion increased ERK isoform activation in all fractions, but there were no differences between control and AMP-579 hearts. Preischemic increases in phospo-p44/p42 ERK with AMP-579 were blunted by U-0126, although only in mitochondrial and membrane compartments. The PC effects of AMP-579 on infarct size and ERK were blunted by both the A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine and, surprisingly, the A2a antagonist ZM-241385. These results indicate that the unique adenosine receptor agonist AMP-579 exerts its beneficial effects in vivo via both A1 and A2a receptor modulation of subcellular ERK isoform signaling.
Low-pressure reperfusion alters mitochondrial permeability transition
Authors: Bopassa J. C. , Michel P. , Gateau-Roesch O. , Ovize M. , Ferrera R.
Published: January 2005

We hypothesized that low-pressure reperfusion may limit myocardial necrosis and attenuate postischemic contractile dysfunction by inhibiting mitochondrial permeability transition pore (mPTP) opening. Male Wistar rat hearts ( n = 36) were perfused according to the Langendorff technique, exposed to 40 min of ischemia, and assigned to one of the following groups: 1) reperfusion with normal pressure (NP = 100 cmH2O) or 2) reperfusion with low pressure (LP = 70 cmH2O). Creatine kinase release and tetraphenyltetrazolium chloride staining were used to evaluate infarct size. Modifications of cardiac function were assessed by changes in coronary flow, heart rate (HR), left ventricular developed pressure (LVDP), the first derivate of the pressure curve (dP/d t), and the rate-pressure product (RPP = LVDP × HR). Mitochondria were isolated from the reperfused myocardium, and the Ca2+-induced mPTP opening was measured using a potentiometric approach. Lipid peroxidation was assessed by measuring malondialdehyde production. Infarct size was significantly reduced in the LP group, averaging 17 ± 3 vs. 33 ± 3% of the left ventricular weight in NP hearts. At the end of reperfusion, functional recovery was significantly improved in LP hearts, with RPP averaging 10,392 ± 876 vs. 3,969 ± 534 mmHg/min in NP hearts ( P < 0.001). The Ca2+load required to induce mPTP opening averaged 232 ± 10 and 128 ± 16 μM in LP and NP hearts, respectively ( P < 0.001). Myocardial malondialdehyde was significantly lower in LP than in NP hearts ( P < 0.05). These results suggest that the protection afforded by low-pressure reperfusion involves an inhibition of the opening of the mPTP, possibly via reduction of reactive oxygen species production.
Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries
Authors: LaDisa John F. , Olson Lars. E. , Molthen Robert C. , Hettrick Douglas A. , Pratt Phillip F. , Hardel Michael D. , Kersten Judy R. , Warltier David C. , Pagel Paul S.
Published: January 2005

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.
Differential effects of 17β-estradiol, conjugated equine estrogen, and raloxifene on mRNA expression, aggregation, and secretion in platelets
Authors: Jayachandran Muthuvel , Mukherjee Rajarshi , Steinkamp Thomas , LaBreche Peter , Bracamonte Margarita P. , Okano Hiroya , Owen Whyte G. , Miller Virginia M.
Published: January 2005

Changes in platelet functions could contribute to thrombotic risk associated with estrogen treatments. This study was designed to test the hypothesis that three clinically relevant estrogenic treatments affect platelet function comparably. Adult female pigs were ovariectomized and randomized to either no treatment or treatment with oral 17β-estradiol (2 mg/day), conjugated equine estrogen (0.625 mg/day), or raloxifene (60 mg/day) for 4 wk. Platelet turnover, aggregation, and secretion were assessed before and after treatment. Platelet turnover and mRNA increased significantly only in pigs treated with 17β-estradiol. Expression of estrogen receptors increased with ovariectomy and decreased with all treatments. Platelet aggregation and secretion of ATP, platelet-derived growth factor, and matrix metalloproteinase-2 increased with ovariectomy. All treatments reduced both aggregation and secretion. Expression of mRNA for constitutive endothelial nitric oxide synthase (eNOS), but not eNOS protein, increased with ovariectomy. Only eNOS mRNA decreased with all treatments, but only treatment with 17β-estradiol increased secretion of nitric oxide from intact platelets. Platelets from 17β-estradiol-treated animals caused relaxation of coronary arteries, which was sensitive to inhibition of nitric oxide. Although three different estrogenic treatments reversed increases in platelet aggregation caused by ovariectomy, only 17β-estradiol increased platelet RNA and release of platelet-derived nitric oxide. These differences reflect transcriptional and posttranscriptional regulation of protein synthesis in bone marrow megakaryocytes and circulating platelets.