bluuebunny/crossref_metadata_2025 huggingface dataset:
Hessian eigenmaps: Locally linear embedding techniques for high-dimensional data
Authors: Donoho David L. , Grimes Carrie
Published: May 2003

We describe a method for recovering the underlying parametrization of scattered data (

m
i

) lying on a manifold
M
embedded in high-dimensional Euclidean space. The method, Hessian-based locally linear embedding, derives from a conceptual framework of local isometry in which the manifold
M
, viewed as a Riemannian submanifold of the ambient Euclidean space ℝ

n

, is locally isometric to an open, connected subset Θ of Euclidean space ℝ

d

. Because Θ does not have to be convex, this framework is able to handle a significantly wider class of situations than the original ISOMAP algorithm. The theoretical framework revolves around a quadratic form ℋ(
f
) = ∫

M

 ∥

H
f

(
m
)∥

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dm
defined on functions
f
:
M
↦ ℝ. Here
Hf
denotes the Hessian of
f
, and ℋ(
f
) averages the Frobenius norm of the Hessian over
M
. To define the Hessian, we use orthogonal coordinates on the tangent planes of
M
. The key observation is that, if
M
truly is locally isometric to an open, connected subset of ℝ

d

, then ℋ(
f
) has a (
d
+ 1)-dimensional null space consisting of the constant functions and a
d
-dimensional space of functions spanned by the original isometric coordinates. Hence, the isometric coordinates can be recovered up to a linear isometry. Our method may be viewed as a modification of locally linear embedding and our theoretical framework as a modification of the Laplacian eigenmaps framework, where we substitute a quadratic form based on the Hessian in place of one based on the Laplacian.
Modulation of mitochondrial function by endogenous Zn
2+
pools
Authors: Sensi Stefano L. , Ton-That Dien , Sullivan Patrick G. , Jonas Elizabeth A. , Gee Kyle R. , Kaczmarek Leonard K. , Weiss John H.
Published: May 2003

Recent evidence suggests that intracellular Zn
2+
accumulation contributes to the neuronal injury that occurs in epilepsy or ischemia in certain brain regions, including hippocampus, amygdala, and cortex. Although most attention has been given to the vesicular Zn
2+
that is released into the synaptic space and may gain entry to postsynaptic neurons, recent studies have highlighted pools of intracellular Zn
2+
that are mobilized in response to stimulation. One such Zn
2+
pool is likely bound to cytosolic proteins, like metallothioneins. Applying imaging techniques to cultured cortical neurons, this study provides novel evidence for the presence of a mitochondrial pool distinct from the cytosolic protein or ligand-bound pool. These pools can be pharmacologically mobilized largely independently of each other, with Zn
2+
release from one resulting in apparent net Zn
2+
transfer to the other. Further studies found evidence for complex and potent effects of Zn
2+
on isolated brain mitochondria. Submicromolar levels, comparable to those that might occur on strong mobilization of intracellular compartments, induced membrane depolarization (loss of Δψ
m
), increases in currents across the mitochondrial inner membrane as detected by direct patch clamp recording of mitoplasts, increased O
2
consumption and decreased reactive oxygen species (ROS) generation, whereas higher levels decreased O
2
consumption and increased ROS generation. Finally, strong mobilization of protein-bound Zn
2+
appeared to induce partial loss of Δψ
m
, suggesting that movement of Zn
2+
between cytosolic and mitochondrial pools might be of functional significance in intact neurons.
Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility
Authors: Smirnova Irina , Mann Navjiwan , Dols Annemiek , Derkx H. H. , Hibberd Martin L. , Levin Michael , Beutler Bruce
Published: May 2003

As the central component of the human endotoxin sensor, Toll-like receptor 4 (TLR4) functions in the early detection and response to Gram-negative infection. We therefore examined a large collection of patients with meningococcal sepsis, comparing the frequency of rare TLR4 coding changes to those in an ethnically matched control population. TLR2 sequences were also acquired and compared. Total nucleotide variation at TLR4 and TLR2 loci was assayed by using a novel computational method. A total of 3.01 megabases of coding sequence was captured at these loci from white subjects with or without meningococcal disease. Authentic mutations were found and high-quality, bidirectional coverage was measured across the coding region by usingmutationseeker, a program specifically designed to assay locus-specific genetic load. Using a method that obviates the confounding effect of linkage disequilibrium, we observed that rare heterozygous missense mutations of TLR4 contribute to the development of systemic meningococcal disease among white populations of the southern United Kingdom (P= 0.02; odds ratio 8.2). When results from all white populations were pooled, an overwhelmingly significant excess of such mutations was observed among individuals with disease (P= 2 × 10−6; odds ratio 27.0). The common white TLR4 variant (TLR4B), synonymous TLR4 substitutions, and variant TLR2 alleles were not significantly over-represented among patients with systemic meningococcal infections. No single variant of TLR4 was significantly over-represented in the meningococcal population. Collectively, however, rare TLR4 coding variants were markedly over-represented. Sensing via TLR4 probably contributes to the early containment of meningococcal infection, and sensing defects create increased risk of disease.
Genomewide transcriptional changes associated with genetic alterations and nutritional supplementation affecting tryptophan metabolism in
Bacillus subtilis
Authors: Berka Randy M. , Cui Xianju , Yanofsky Charles
Published: May 2003

DNA microarrays comprising ≈95% of the
Bacillus subtilis
annotated protein coding ORFs were deployed to generate a series of snapshots of genomewide transcriptional changes that occur when cells are grown under various conditions that are expected to increase or decrease transcription of the
trp
operon segment of the aromatic supraoperon. Comparisons of global expression patterns were made between cells grown in the presence of indole acrylic acid, a specific inhibitor of tRNA
Trp
charging; cells deficient in expression of the
mtrB
gene, which encodes the tryptophan-activated negative regulatory protein, TRAP; WT cells grown in the presence or absence of two or three of the aromatic amino acids; and cells harboring a tryptophanyl tRNA synthetase mutation conferring temperature-sensitive tryptophan-dependent growth. Our findings validate expected responses of the tryptophan biosynthetic genes and presumed regulatory interrelationships between genes in the different aromatic amino acid pathways and the histidine biosynthetic pathway. Using a combination of supervised and unsupervised statistical methods we identified ≈100 genes whose expression profiles were closely correlated with those of the genes in the
trp
operon. This finding suggests that expression of these genes is influenced directly or indirectly by regulatory events that affect or are a consequence of altered tryptophan metabolism.
A molecular approach to comparative phylogeography of extant Malagasy lemurs
Authors: Pastorini Jennifer , Thalmann Urs , Martin Robert D.
Published: May 2003

The lemurs of Madagascar provide an excellent model for exploring evolutionary diversification. This study investigates genetic divergence among most extant lemur taxa in relation to potential geographical boundaries to gene flow. For this purpose, ≈2,400 bp of mitochondrial DNA (part of the
COIII
gene;
ND3
,
ND4L
, and
ND4
genes; and five tRNAs) were sequenced in a total of 131 lemurs from 5 families, 12 genera, 25 species, and 18 subspecies to reconstruct phylogenetic relationships among them. The comprehensive range of taxa makes this a particularly suitable molecular data set to examine lemur evolution. Those data clearly reveal that the Betsiboka River acts as an isolating barrier between populations of lemurs in north-western Madagascar. The Tsiribihina River similarly serves as a barrier to gene flow between northern and southern populations of lemurs in central western Madagascar, whereas the Mahavavy River does not seem to lead to genetic isolation of lemur populations. Several discrepancies among molecular data, current taxonomy, and geographic distribution along the western coast emerged. Examination of geographical distribution of the taxa concerned in comparison with distribution boundaries of other lemur taxa in that region yielded explanations for these inconsistencies.
Eulemur fulvus
and
Eulemur mongoz
are the only lemur taxa that also occur outside Madagascar, on the Comoro Islands. Genetic data show no significant differentiation between Malagasy and Comorian populations of these species, supporting the interpretation that both were introduced only recently to the Comoro Islands.
Functional conservation of light, oxygen, or voltage domains in light sensing
Authors: Cheng Ping , He Qiyang , Yang Yuhong , Wang Lixin , Liu Yi
Published: May 2003

In
Neurospora
, the flavin adenine dinucleotide-containing protein WHITE COLLAR-1 is the blue-light photoreceptor for the circadian clock and other light responses. The putative chromophore-binding domain of WC-1, its light, oxygen, or voltage (LOV) domain, is similar to the LOV domains found in the plant phototropins, the
Neurospora
VIVID (VVD) protein, and the
Arabidopsis
FKF1 and its related proteins. Studies of the plant phototropins have identified 11 flavin-contacting residues that are also conserved in the LOV domains of WC-1, VVD, and FKF1. In this study, by mutating the putative WC-1 flavin-binding sites, we show that these sites are important for the light function of the protein, suggesting that the WC-1 LOV domain adapts a structure similar to that of the phototropin LOV domains. By creating a
Neurospora
strain in which the LOV domain of WC-1 is swapped with that of VVD, we show that the LOV domain of VVD partially replaces the function of the WC-1 LOV domain, suggesting that VVD is a
wc
-dependent photoreceptor in
Neurospora
. Furthermore, we show that the
Neurospora
strains containing a chimeric WC-1 protein with the LOV domain from FKF1 or phot1 can also sense light, suggesting that FKF1 and its related proteins are light sensors in
Arabidopsis
. Taken together, our data suggest that these LOV domains are structurally similar protein modules involved in blue-light sensing.
Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake
Authors: Anson R. Michael , Guo Zhihong , de Cabo Rafael , Iyun Titilola , Rios Michelle , Hagepanos Adrienne , Ingram Donald K. , Lane Mark A. , Mattson Mark P.
Published: May 2003

Dietary restriction has been shown to have several health benefits including increased insulin sensitivity, stress resistance, reduced morbidity, and increased life span. The mechanism remains unknown, but the need for a long-term reduction in caloric intake to achieve these benefits has been assumed. We report that when C57BL/6 mice are maintained on an intermittent fasting (alternate-day fasting) dietary-restriction regimen their overall food intake is not decreased and their body weight is maintained. Nevertheless, intermittent fasting resulted in beneficial effects that met or exceeded those of caloric restriction including reduced serum glucose and insulin levels and increased resistance of neurons in the brain to excitotoxic stress. Intermittent fasting therefore has beneficial effects on glucose regulation and neuronal resistance to injury in these mice that are independent of caloric intake.
IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist
Authors: Nakae Susumu , Saijo Shinobu , Horai Reiko , Sudo Katsuko , Mori Shigeo , Iwakura Yoichiro
Published: May 2003

IL-17 is a T cell-derived, proinflammatory cytokine that is suspected to be involved in the development of various inflammatory diseases. Although there are elevated levels of IL-17 in synovial fluid of patients with rheumatoid arthritis, the pathogenic role of IL-17 in the development of rheumatoid arthritis remains to be elucidated. In this report, the effects of IL-17 deficiency were examined in IL-1 receptor antagonist-deficient (IL-1Ra
−/−
) mice that spontaneously develop an inflammatory and destructive arthritis due to unopposed excess IL-1 signaling. IL-17 expression is greatly enhanced in IL-1Ra
−/−
mice, suggesting that IL-17 activity is involved in the pathogenesis of arthritis in these mice. Indeed, the spontaneous development of arthritis did not occur in IL-1Ra
−/−
mice also deficient in IL-17. The proliferative response of ovalbumin-specific T cells from DO11.10 mice against ovalbumin cocultured with antigen-presenting cells from either IL-1Ra
−/−
mice or wild-type mice was reduced by IL-17 deficiency, indicating insufficient T cell activation. Cross-linking OX40, a cosignaling molecule on CD4
+
T cells that plays an important role in T cell antigen-presenting cell interaction, with anti-OX40 Ab accelerated the production of IL-17 induced by CD3 stimulation. Because OX40 is induced by IL-1 signaling, IL-17 induction is likely to be downstream of IL-1 through activation of OX40. These observations suggest that IL-17 plays a crucial role in T cell activation, downstream of IL-1, causing the development of autoimmune arthritis.
Ever shorter telomere 1 (
EST1
)-dependent reverse transcription by
Candida
telomerase
in vitro
: Evidence in support of an activating function
Authors: Singh Sunitha M. , Lue Neal F.
Published: May 2003

Telomerase is an RNA–protein complex responsible for the extension of one strand of the telomere terminal repeats. Analysis of the telomerase complex in the budding yeast
Saccharomyces cerevisiae
has revealed the presence of one catalytic protein subunit (Est2p/TERT) and at least two noncatalytic components (Est1p and Est3p). The TERT subunit is essential for telomerase function, both
in vitro
and
in vivo
. In contrast, the Est1p and Est3p subunits, although required for telomere extension
in vivo
, have not been shown to affect enzyme activity
in vitro
. We recently identified orthologues of the
Saccharomyces
telomerase subunits in
Candida albicans
(named CaTERT, CaEst1p, and CaEst3p). Analysis of telomerase from the
Candida Caest1
-Δ strains revealed a primer-specific defect in its activity
in vitro
: The mutant enzyme was impaired in its ability to extend some, but not all, telomeric primers. The CaEst1p-responsive primers have 3′ ends that are clustered in two loci within the 23-bp
Candida
telomere repeat. The degree of CaEst1p-dependence was modulated by the length and sequence of the 5′ ends. For CaEst1p-dependent primers, the wild-type enzyme consistently exhibited a greater
V
max
than the mutant enzyme in kinetic studies. These results suggest that CaEst1p augments the ability of telomerase to reverse-transcribe through selected barriers in the telomere repeat by acting as an allosteric activator and provide the basis for a functional
in vitro
assay for a noncatalytic protein component of the telomerase complex.
Agonist unbinding from receptor dictates the nature of deactivation kinetics of G protein-gated K
+
channels
Authors: Benians Amy , Leaney Joanne L. , Tinker Andrew
Published: May 2003

G protein-gated inwardly rectifying K
+
(Kir) channels are found in neurones, atrial myocytes, and endocrine cells and are involved in generating late inhibitory postsynaptic potentials, slowing the heart rate and inhibiting hormone release. They are activated by G protein-coupled receptors (GPCRs) via the inhibitory family of G protein, G
i/o
, in a membrane-delimited fashion by the direct binding of Gβγ dimers to the channel complex. In this study we are concerned with the kinetics of deactivation of the cloned neuronal G protein-gated K
+
channel, Kir3.1 + 3.2A, after stimulation of a number of GPCRs. Termination of the channel activity on agonist removal is thought to solely depend on the intrinsic hydrolysis rate of the G protein α subunit. In this study we present data that illustrate a more complex behavior. We hypothesize that there are two processes that account for channel deactivation: agonist unbinding from the GPCR and GTP hydrolysis by the G protein α subunit. With some combinations of agonist/GPCR, the rate of agonist unbinding is slow and rate-limiting, and deactivation kinetics are not modulated by regulators of G protein-signaling proteins. In another group, channel deactivation is generally faster and limited by the hydrolysis rate of the G protein α subunit. G protein isoform and interaction with G protein-signaling proteins play a significant role with this group of GPCRs.
Substoichiometric shifting in the plant mitochondrial genome is influenced by a gene homologous to MutS
Authors: Abdelnoor Ricardo V. , Yule Ryan , Elo Annakaisa , Christensen Alan C. , Meyer-Gauen Gilbert , Mackenzie Sally A.
Published: May 2003

The plant mitochondrial genome is retained in a multipartite structure that arises by a process of repeat-mediated homologous recombination. Low-frequency ectopic recombination also occurs, often producing sequence chimeras, aberrant ORFs, and novel subgenomic DNA molecules. This genomic plasticity may distinguish the plant mitochondrion from mammalian and fungal types. In plants, relative copy number of recombination-derived subgenomic DNA molecules within mitochondria is controlled by nuclear genes, and a genomic shifting process can result in their differential copy number suppression to nearly undetectable levels. We have cloned a nuclear gene that regulates mitochondrial substoichiometric shifting in
Arabidopsis
. The
CHM
gene was shown to encode a protein related to the MutS protein of
Escherichia coli
that is involved in mismatch repair and DNA recombination. We postulate that the process of substoichiometric shifting in plants may be a consequence of ectopic recombination suppression or replication stalling at ectopic recombination sites to effect molecule-specific copy number modulation.
Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins
Authors: Irie Yasuyuki , Saeki Makio , Kamisaki Yoshinori , Martin Emil , Murad Ferid
Published: May 2003

Several reports have described an activity that modifies nitrotyrosine-containing proteins and their immunoreactivity to nitrotyrosine Abs. Without knowing the product of the reaction, this new activity has been called a “denitrase.” In those studies, some nonspecific proteins, which have multiple tyrosine residues, e.g., albumin, were used as a substrate. Therefore, the studies were based on an unknown mechanism of reaction and potentially a high background. To solve these problems, one of the most important things is to find a more suitable substrate for assay of the enzyme. We developed an assay strategy for determining the substrate for denitrase combining 2D-gel electrophoresis and an on-blot enzyme assay. The resulting substrate from RAW 264.7 cells was Histone H1.2, an isoform protein of linker histone. Histone H1.2 has only one tyrosine residue in the entire molecule, which ensures the exact position of the substrate to be involved. It has been reported that Histones are the most prominent nitrated proteins in cancer tissues. It was also demonstrated that tyrosine nitration of Histone H1 occurs
in vivo
. These findings lead us to the idea that Histone H1.2 might be an intrinsic substrate for denitrase. We nitrated recombinant and purified Histone H1.2 chemically and subjected it to an on-blot enzyme assay to characterize the activity. Denitrase activity behaved as an enzymatic activity because the reaction was time dependent and was destroyed by heat or trypsin treatment. The activity was shown to be specific for Histone H1.2, to differ from proteasome activity, and to require no additional cofactors.
Comparative Genome Organization of Human, Murine, and Feline MHC Class II Region
Authors: Yuhki Naoya , Beck Thomas , Stephens Robert M. , Nishigaki Yoko , Newmann Kymberly , O'Brien Stephen J.
Published: May 2003

To study comparative molecular dynamics in the genesis of the major histocompatibility complex (MHC), we determined a complete nucleotide sequence spanning 758,291 bp of the domestic cat (Felis catus) extended and classical class II region. The feline class II MHC includes 44 genes (31 predicted to be expressed) which display DNA sequence homology and ordered gene synteny with humanHLAand mouseH2,in extended class II and centromere proximal regions (DMtoDO) of the classical class II region. However, remarkable genomic alterations including gene gain and loss plus size differentials of 250 kb are evident in comparisons of the cat class II with those of human and mouse. The cat MHC lacks the entireDQregion and retains only relict pseudogene homologs ofDPgenes, compensated by expansion and reorganization of seven modernDRgenes. Repetitive gene families within the feline MHC comprise 35% of the feline MHC with very different density and abundance of GC levels,SINES, LINES,STRs, and retro-elements from the same repeats in human and mouse MHC. Comparison of the feline MHC with the murine and human MHC offers a detailed view of the consequences of genome organization in three mammalian lineages.
Isolation and Characterization of the Neutral Leucine Aminopeptidase (LapN) of Tomato
Authors: Tu Chao-Jung , Park Sang-Youl , Walling Linda L.
Published: May 2003

Tomatoes (Lycopersicon esculentum) express two forms of leucine aminopeptidase (LAP-A and LAP-N) and two LAP-like proteins. The relatedness of LAP-N and LAP-A was determined using affinity-purified antibodies to four LAP-A protein domains. Antibodies to epitopes in the most N-terminal region were able to discriminate between LAP-A and LAP-N, whereas antibodies recognizing central and COOH-terminal regions recognized both LAP polypeptides. Two-dimensional immunoblots showed that LAP-N and the LAP-like proteins were detected in all vegetative (leaves, stems, roots, and cotyledons) and reproductive (pistils, sepals, petals, stamens, and floral buds) organs examined, whereas LAP-A exhibited a distinct expression program.LapN was a single-copy gene encoding a rare-class transcript. A full-length LapN cDNA clone was isolated, and the deduced sequence had 77% peptide sequence identity with the wound-induced LAP-A. Comparison of LAP-N with other plant LAPs identified 28 signature residues that classified LAP proteins as LAP-N or LAP-A like. Overexpression of a His6-LAP-N fusion protein in Escherichia coli demonstrated distinct differences in His6-LAP-N and His6-LAP-A activities. Similar to LapA, the LapN RNA encoded a precursor protein with a molecular mass of 60 kD. The 5-kD presequence had features similar to plastid transit peptides, and processing of the LAP-N presequence could generate the mature 55-kD LAP-N. Unlike LapA, the LapN transcript contained a second in-frame ATG, and utilization of this potential initiation codon would yield a 55-kD LAP-N protein. The localization of LAP-N could be controlled by the balance of translational initiation site utilization and LAP-N preprotein processing.
Enhancement of Plant-Microbe Interactions Using a Rhizosphere Metabolomics-Driven Approach and Its Application in the Removal of Polychlorinated Biphenyls,
Authors: Narasimhan Kothandaraman , Basheer Chanbasha , Bajic Vladimir B. , Swarup Sanjay
Published: May 2003

Persistent organic pollutants, such as polychlorinated biphenyls (PCBs), are a global problem. We demonstrate enhanced depletion of PCBs using root-associated microbes, which can use plant secondary metabolites, such as phenylpropanoids. Using a “rhizosphere metabolomics” approach, we show that phenylpropanoids constitute 84% of the secondary metabolites exuded from Arabidopsis roots. Phenylpropanoid-utilizing microbes are more competitive and are able to grow at least 100-fold better than their auxotrophic mutants on roots of plants that are able to synthesize or overproduce phenylpropanoids, such as flavonoids. Better colonization of the phenylpropanoid-utilizing strain in a gnotobiotic system on the roots of flavonoid-producing plants leads to almost 90% removal of PCBs in a 28-d period. Our work complements previous approaches to engineer soil microbial populations based on opines produced by transgenic plants and used by microbes carrying opine metabolism genes. The current approach based on plant natural products can be applied to contaminated soils with pre-existing vegetation. This strategy is also likely to be applicable to improving the competitive abilities of biocontrol and biofertilization strains.
Nod Factor and Elicitors Activate Different Phospholipid Signaling Pathways in Suspension-Cultured Alfalfa Cells
Authors: den Hartog Martine , Verhoef Nathalie , Munnik Teun
Published: May 2003

Lipo-chitooligosaccharides (Nod factors) are produced by symbiotic Rhizobium sp. bacteria to elicit Nod responses on their legume hosts. One of the earliest responses is the formation of phosphatidic acid (PA), a novel second messenger in plant cells. Remarkably, pathogens have also been reported to trigger the formation of PA in nonlegume plants. To investigate how host plants can distinguish between symbionts and pathogens, the effects of Nod factor and elicitors (chitotetraose and xylanase) on the formation of PA were investigated in suspension-cultured alfalfa (Medicago sativa) cells. Theoretically, PA can be synthesized via two signaling pathways, i.e. via phospholipase D (PLD) and via phospholipase C in combination with diacylglycerol (DAG) kinase. Therefore, a strategy involving differential radiolabeling with [32P]orthophosphate was used to determine the contribution of each pathway to PA formation. In support, PLD activity was specifically measured by using the ability of the enzyme to transfer the phosphatidyl group of its substrate to a primary alcohol. In practice, Nod factor, chitotetraose, and xylanase induced the formation of PA and its phosphorylated product DAG pyrophosphate within 2 min of treatment. However, whereas phospholipase C and DAG kinase were activated during treatment with all three different compounds, PLD was only activated by Nod factor. No evidence was obtained for the activation of phospholipase A2.
Growth Ring Formation in the Starch Granules of Potato Tubers
Authors: Pilling Emma , Smith Alison M.
Published: May 2003

Starch granules from higher plants contain alternating zones of semicrystalline and amorphous material known as growth rings. The regulation of growth ring formation is not understood. We provide several independent lines of evidence that growth ring formation in the starch granules of potato (Solanum tuberosum) tubers is not under diurnal control. Ring formation is not abolished by growth in constant conditions, and ring periodicity and appearance are relatively unaffected by a change from a 24-h to a 40-h photoperiod, and by alterations in substrate supply to the tuber that are known to affect the diurnal pattern of tuber starch synthesis. Some, but not all, of the features of ring formation are consistent with the involvement of a circadian rhythm. Such a rhythm might operate by changing the relative activities of starch-synthesizing enzymes: Growth ring formation is disrupted in tubers with reduced activity of a major isoform of starch synthase. We suggest that physical as well as biological mechanisms may contribute to the control of ring formation, and that a complex interplay of several factors may by involved.
Solubilization of an Arabinan Arabinosyltransferase Activity from Mung Bean Hypocotyls
Authors: Nunan Kylie Joy , Scheller Henrik Vibe
Published: May 2003

The biosynthesis of polysaccharides destined for the plant cell wall and the subsequent assembly of the cell wall are poorly understood processes that are currently the focus of much research. Arabinan, a component of the pectic polysaccharide rhamnogalacturonan I, is composed of arabinosyl residues connected via various glycosidic linkages, and therefore, the biosynthesis of arabinan is likely to involve more than one arabinosyltransferase. We have studied the transfer of [14C]arabinose (Ara) from UDP-l-arabinopyranose onto polysaccharides using microsomal membranes isolated from mung bean (Vigna radiata) hypocotyls. [14C]arabinosyl and [14C]xylosyl residues were incorporated into endogenous products due to the presence of UDP-Xyl-4-epimerase activity. Enzymatic digestion of endogenous products with endo-arabinanase released very little radiolabeled sugars, whereas digestion with arabinofuranosidase released some [14C]Ara. Microsomal membranes solubilized with the detergent octyl glucoside were able to add a single [14C]Ara residue onto (1→5)-linked α-l-arabino-oligosaccharide acceptors. The reaction had a pH optimum of 6.5 and a requirement for manganese ions. However, enzymatic digestion of the radiolabeled oligosaccharides with endo-arabinanase and arabinofuranosidases could not fully release the radiolabeled Ara residue, indicating that the [14C]Ara residue was not a (1→2)-, (1→3)-, or (1→5)-linked α-l-arabinofuranosyl residue. Rather, mild acid treatment of the product suggested that the radiolabeled Ara residue was in a pyranose conformation, and this result was confirmed by thin-layer chromatography of radiolabeled partially methylated sugars. Using microsomal membranes separated on a discontinuous sucrose gradient, the arabinosyltransferase activity appears to be mainly localized to Golgi membranes.
Molecular Cloning and Functional Characterization of Three Distinct N-Methyltransferases Involved in the Caffeine Biosynthetic Pathway in Coffee Plants
Authors: Uefuji Hirotaka , Ogita Shinjiro , Yamaguchi Yube , Koizumi Nozomu , Sano Hiroshi
Published: May 2003

Caffeine is synthesized from xanthosine throughN-methylation and ribose removal steps. In the present study, three types of cDNAs encodingN-methyltransferases were isolated from immature fruits of coffee (Coffea arabica) plants, and designated asCaXMT1, CaMXMT2, andCaDXMT1, respectively. The bacterially expressed encoded proteins were characterized for their catalytic properties. CaXMT1 catalyzed formation of 7-methylxanthosine from xanthosine with aK  m value of 78 μm, CaMXMT2 catalyzed formation of 3,7-dimethylxanthine (theobromine) from 7-methylxanthine with a K  m of 251 μm, and CaDXMT1 catalyzed formation of 1,3,7-trimethylxanthine (caffeine) from 3,7-dimethylxanthine with aK  m of 1,222 μm. The crude extract of Escherichia coli was found to catalyze removal of the ribose moiety from 7-methylxanthosine, leading to the production of 7-methylxanthine. As a consequence, when all three recombinant proteins and E. coli extract were combined, xanthosine was successfully converted into caffeine in vitro. Transcripts for CaDXMT1 were predominantly found to accumulate in immature fruits, whereas those for CaXMT1and CaMXMT2 were more broadly detected in sites encompassing the leaves, floral buds, and immature fruits. These results suggest that the presently identified threeN-methyltransferases participate in caffeine biosynthesis in coffee plants and substantiate the proposed caffeine biosynthetic pathway: xanthosine → 7-methylxanthosine → 7-methylxanthine → theobromine → caffeine.
The ILRI Graduate Fellows Programme: a case study of impact (1978‐1997)
Authors: Eley R. , Ibrahim H. , Hambly H. , Demeke Mulat , Smalley M.
Published: May 2003

The paper explores the extent to which degree‐based postgraduate training programmes contribute to the development of individual skills and careers in agricultural science as well as towards institutional capacity for national agricultural research in Africa. In the case of the International Livestock Research Institute’s Graduate Fellowship Programme it was concluded that advanced agricultural science training in Africa provides a vital process of human and institutional development. The results of this study indicate the success of degree‐based training in terms of achieving improved gender equity, rapid employment, and a high rate of return to the country of origin. These results stand out against the “brain drain” commonly associated with capacity building in national agricultural research systems (NARS). The paper recommends strategies to be adopted by ILRI and its partners for future degree training and capacity building in sub‐Saharan Africa.
Seeking a facilities management philosophy for the changing workplace
Authors: Cairns George
Published: May 2003

Promotes the notion that the emergent field of facility/facilities management (FM) requires a philosophical basis, where philosophy refers not to esoteric, academic abstraction, but to the basic theory and general principles of knowledge that underpin everyday activity. Argues specifically for generation of a philosophy of “the workplace”; the separate but related social, physical, technological and organizational contexts of work; the centre stage of FM activity, in order to: first, provide a knowledge base that critically engages with the complexities and ambiguities of these diverse but interconnected contexts of work; second, engage with some of the failings of FM knowledge to date, where idealistic best practice is presented as if it were theory, and simplistic research presents universal solutions based upon limited engagement with a single context; and third, provide a knowledge base that can stand up to critical analysis from other fields of knowledge, some of which overlap with that of FM.
Organisational career management in Israel
Authors: Tzabbar Daniel , Vardi Yoav , Baruch Yehuda
Published: May 2003

This study explores some important aspects of organisational career management (OCM) in Israel. Overall, our data, obtained from 136 large firms, represented by their human resource managers (HRMs), reflect a fairly paternalistic approach to career management; careers are mostly managed by the organisation. Specifically, we also found that: 1. For making promotion decisions HRMs tend to rely on particularistic criteria and evaluations programs; 2. For managing promotion HRMs rely on internal HR development programs; and 3. Because upward mobility opportunities are limited, many opt for external labour markets to acquire managerial talent. Implications of these findings and directions for future research are discussed.
Determinants and impacts of environmental performance in SMEs
Authors: Lefebvre Élisabeth , Lefebvre Louis A. , Talbot Stéphane
Published: May 2003

The paper analyzes empirical evidence from 368 environmentally responsive small and medium‐sized enterprises (SMEs) operating in four industries. The results demonstrate that firms' environmental performance cannot be viewed as a one‐dimensional concept and that determinants of firms' environmental performance depend on the dimension retained. The impacts of firms' environmental performance on their innovativeness and competitiveness vary according to the industry within which they operate. However, impacts on product and process innovations as well as on managerial innovations are positive and significant in all four industries.
Improvement reviews in new product development
Authors: Lilly Bryan , Porter Thomas
Published: May 2003

This research examines how organizations can use improvement reviews to enhance learning from product development experiences. We review learning related literature and highlight learning barriers that firms should attempt to minimize when conducting reviews. We then discuss two studies aimed at better understanding the effectiveness of improvement reviews. The first study suggests that improvement reviews can facilitate learning by leading to a reduction in the recurrence of people‐related problems, though reviews had no impact on reducing market or product related problems. The second study involved depth interviews with new product developers. Interview comments provide insights into improvement review best practices and shed light on why improvement reviews are sometimes ineffective. A set of managerial recommendations is provided.
Technology transfer as technological learning: a source of competitive advantage for firms with limited R&D resources
Authors: Lin Bou‐Wen
Published: May 2003

The objective of this article is to answer why and how firms in developing countries with limited R&D resources can gain sustainable competitive advantage through technology transfer (TT). Successful firms are those that can accumulate competence through internal technological learning after transferring technologies from external technology sources. Organizational intelligence, firm specificity of technology, and causal ambiguity are identified as three mediators between technological learning performance and several antecedents previously discussed in the literature. A survey of Taiwanese manufacturers is conducted to explore the technological learning phenomenon as an integral part of TT, which is important but often neglected. This article also provides an interesting research setting for the evaluation of technological learning theories.
Manipulation of CD98 Expression Affects both Trophoblast Cell Fusion and Amino Acid Transport Activity during Syncytialization of Human Placental BeWo Cells
Authors: Kudo Yoshiki , Boyd C. A. R. , Millo J. , Sargent I. L. , Redman C. W. G.
Published: May 2003

The physiological importance of CD98 surface antigen in regulating placental trophoblast cell fusion and amino acid transport activity has been studied in parallel in a cell model of syncytialization (the cytotrophoblast cell line BeWo following increased intracellular cAMP by forskolin treatment) using antisense oligonucleotides. CD98 protein abundance (determined by Western blot) was decreased by 50 % following antisense oligonucleotide transfection. Transfection with antisense oligonucleotide altered the responses of BeWo to forskolin. Cell fusion (determined by a quantitative flow cytometry assay) was inhibited by 57 %, and both human chorionic gonadotropin secretion and L‐leucine influx through system L were suppressed. These findings show that CD98 is involved in the process of cell fusion necessary for syncytiotrophoblast formation and that during this physiologically important event, amino acid transport activity is also regulated through expression of this membrane protein.
NANOELECTRONICS: SOME CURRENT ASPECTS AND PROSPECTS
Authors: HULL ROBERT , MARTEL RICHARD , XU J. M.
Published: May 2003

A brief summary is provided of selected current activities in the field of nanoelectronics, which is taken here to mean the fabrication and integration of active microelectronic components with feature dimensions of tens of nanometers or less. Particular emphasis is placed upon the classes of nanoelectronic devices that were discussed at the 2002 WOFE Conference.
RECENT PROGRESS OF FERROELECTRIC MEMORIES
Authors: ISHIWARA HIROSHI
Published: May 2003

Recent progress of ferroelectric random access memories (FeRAMs) is reviewed. First, novel ferroelectric materials, which are suitable for both low temperature crystallization and low voltage operation are introduced. Then, various cell structures in FeRAMs are discussed, in which particular attention is paid to non-destructive-readout-type cells such as a 1T-type cell composed of a single ferroelectric-gate field effect transistor. Finally, a novel 1T2C-type non-destructive-readout cell with good data retention characteristic is introduced and its basic operation is presented.
SEMICONDUCTOR THIN FILMS AND THIN FILM DEVICES FOR ELECTROTEXTILES
Authors: SHUR MICHAEL S. , RUMYANTSEV SERGEY L. , GASKA REMIS
Published: May 2003

We discuss the evolution from wearable electronics and conductive textiles to electrotextiles with embedded semiconducting films and semiconductor devices and review different semiconductor technologies competing for applications in electrotextiles. We also report on fabrication, characterization, and properties of nanocrystalline semiconductor and metal films and thin-film device structures chemically deposited on fibers, cloth, and large area flexible substrates at low temperatures (close to room temperature). Our approach is based on a new process of depositing polycrystalline CdSe (1.75 eV), CdS (2.4 eV), PbS (0.4 eV), PbSe (0.24 eV) and CuxS (semiconductor/metal) films on flexible substrates from the water solutions of complex-salt compounds. We have covered areas up to 8 × 10 inches but the process can be scaled up. The film properties are strongly affected by processing.

We fabricated a lateral solar cell with alternating Cu2-xS and nickel contact stripes deposited on top of a view foil. These sets of contacts represented "ohmic" and "non-ohmic" contacts, respectively. Then CdS films of approximately 0.5 μm thick were deposited on top. We also fabricated a "sandwich" type photovoltaic cell, where the CdS film was sandwiched between an In2O3 layer deposited on a view foil and a Cu2-xS layer deposited on top. Both structures exhibited transient response under light, with the characteristic response time decreasing with the illumination wavelength. This is consistent with having deeper localized states in the energy gap determining the transients for shorter wavelength radiation. (Slow transients related to trapping effects are typical for polycrystalline CdS materials.)

We also report on the photovoltaic effect in CdS/CuS films deposited on trylene threads and on a field effect in these films deposited on a flexible copper wire. CdS films deposited on viewfoils exhibit unique behavior under stress and UV radiation exposure with reproducible resistance changes of several orders of magnitude with bending up to 10 mm curvature.

Our results clearly demonstrate the feasibility of using this technology for photovoltaic and microelectronics applications for electrotextiles and wearable electronics applications.
LOW FREQUENCY NOISE IN GALLIUM NITRIDE FIELD EFFECT TRANSISTORS
Authors: RUMYANTSEV SERGEY L. , SHUR MICHAEL S. , GASKA REMIS , LEVINSHTEIN MICHAEL. E. , KHAN M. ASIF , SIMIN GRIGORY , YANG J. W.
Published: May 2003

We report on experimental study of the low frequency noise in GaN-based Field Effect Transistors. In both GaN Metal Semiconductor Field Effect Transistors (MESFETs) and AlGaN/GaN Heterostructure Field Effect Transistors (HFETs), the main noise sources are located in the channel. Gate voltage dependence of noise in MESFETs complies with the Hooge formula and indicates the bulk origin of noise. The dependencies of the Hooge parameter, α, on sheet electron concentration ns in HFETs are extracted from measured drain current fluctuations taking into account the contact resistance, and the resistance of the ungated regions of the transistors. At low channel concentrations α is inversely proportional to ns (α ~ 1/ns). This dependence as well as the temperature dependence of noise might be explained by electron tunneling from the 2D gas into the traps in the bulk GaN or AlGaN.
HOT-PHONON LIMITED ELECTRON ENERGY RELAXATION IN AlN/GaN
Authors: MATULIONIS A. , LIBERIS J. , ARDARAVIČIUS L. , SMART J. , PAVLIDIS D. , HUBBARD S. , EASTMAN L. F.
Published: May 2003

Microwave noise technique is applied to study energy dissipation in an AlN/GaN heterostructure containing a two-dimensional electron gas channel. Measurements of the dissipated power and the noise temperature are performed at 80 K lattice temperature in the electric field range up to 40 kV/cm. The energy relaxation time is found to decrease from 40 ps to 0.55 ps when the bias is increased. The experimental data are discussed in the electron temperature approximation assuming electron energy dissipation on optical phonons and hot-phonon effects. Dependencies of the hot-phonon number and the hot-phonon temperature on the hot-electron temperature are deduced. The frequency cutoff imposed by the limited energy dissipation through optical phonons is estimated.
Regulation and Mechanisms of ATP-Binding Cassette Transporter A1-Mediated Cellular Cholesterol Efflux
Authors: Wang Nan , Tall Alan R.
Published: May 2003

ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and HDL metabolism. ABCA1 mediates cellular cholesterol and phospholipid efflux to lipid-poor apolipoproteins, and upregulation of ABCA1 activity is antiatherogenic. ApoA-I, the major apolipoprotein component of HDL, promotes ABCA1-mediated cholesterol and phospholipid efflux, probably by directly binding to ABCA1. ABCA1 gene expression is markedly increased in cholesterol-loaded cells as a result of activation of LXR/RXR. ABCA1 protein turnover is rapid. ABCA1 contains a PEST—proline (P), glutamate (E), serine (S), and threonine (T)—sequence in the intracellular segment that mediates ABCA1 degradation by a thiol protease, calpain. ApoA-I and apoE stabilize ABCA1 in a novel mode of regulation by decreasing PEST sequence-mediated calpain proteolysis. ABCA1-mediated cholesterol and phospholipid efflux are distinctly regulated and affected by the activity of other gene products. Stearyol CoA desaturase decreases ABCA1-mediated cholesterol efflux but not phospholipid efflux, likely by decreasing the cholesterol pool available to ABCA1. This and other evidence suggest that ABCA1 promotes cholesterol and phospholipid efflux, probably by directly transporting both lipids as substrates.
Critical Role of
l
-Arginine in Endothelial Cell Survival During Oxidative Stress
Authors: Suschek Christoph V. , Schnorr Oliver , Hemmrich Karsten , Aust Olivier , Klotz Lars-Oliver , Sies Helmut , Kolb-Bachofen Victoria
Published: May 2003

Background—

Oxidative damage of vascular endothelium represents an important initiation step in the development of atherosclerosis. Recently, we reported about protection of inducible nitric oxide synthase (iNOS)-derived high-output NO in endothelial cells. Because iNOS activity critically depends on the availability of its substrate
l
-arginine, the present study aims at elucidating iNOS-mediated effects on H
2
O
2
-induced apoptosis of cytokine-activated rat aortic endothelial cells (AECs) subject to medium
l
-arginine concentrations.

Methods and Results—

In cytokine-activated AECs, iNOS activity was found to be half-maximal at 60 μmol/L arginine, which represents the medium serum level in rats but also in humans. Maximal activity is seen at and above 200 μmol/L arginine. Activated cells grown in the absence of arginine with minimal iNOS activity are highly sensitive toward H
2
O
2
-induced apoptosis, and increases in medium arginine concentrations result in increased cell survival. Moreover, competition experiments show that iNOS activity is completely dependent on cationic amino acid transporter-mediated arginine uptake. We also find that the arginine-dependent protection includes inhibition of endothelial lipid peroxidation and increases in the expression of vasoprotective stress response genes.

Conclusions—

Our data demonstrate that arginine concentrations corresponding to physiological serum levels do not allow for optimal endothelial iNOS activity. Thus, decreases in systemic arginine concentrations, or locally within atherosclerotic plaques, will impair the endothelial iNOS-mediated stress response and will significantly increase the risk of endothelial dysfunction.