bluuebunny/crossref_metadata_2025 huggingface dataset:
The postnatal development of spinal sensory processing
Authors: Fitzgerald Maria , Jennings Ernest
Published: July 2002

The mechanisms by which infants and children process pain should be
viewed within the context of a developing sensory nervous system. The
study of the neurophysiological properties and connectivity of sensory
neurons in the developing spinal cord dorsal horn of the intact
postnatal rat has shed light on the way in which the newborn central
nervous system analyzes cutaneous innocuous and noxious stimuli. The
receptive field properties and evoked activity of newborn dorsal horn
cells to single repetitive and persistent innocuous and noxious inputs
are developmentally regulated and reflect the maturation of excitatory
transmission within the spinal cord. These changes will have an
important influence on pain processing in the postnatal period.
A human
DAZ
transgene confers partial rescue of the mouse
Dazl
null phenotype
Authors: Slee R. , Grimes B. , Speed R. M. , Taggart M. , Maguire S. M. , Ross A. , McGill N. I. , Saunders P. T. K. , Cooke H. J.
Published: July 2002

In a subset of infertile men, a spectrum of spermatogenic defects ranging from a complete absence of germ cells (sertoli cell only) to oligozoospermia is associated with microdeletions of the
DAZ
(deleted in azoospermia
)
gene cluster on human distal Yq.
DAZ
encodes a testis-specific protein with RNA-binding potential recently derived from a single-copy gene
DAZL1
(DAZ
-
like) on chromosome 3. Y chromosomal
DAZ
homologues are confined to humans and higher primates. It remains unclear which function unique to higher primate spermatogenesis
DAZ
may serve, and the functional status of the gene recently has been questioned. To assess the extent of functional conservation we have tested the capacity of a human
DAZ
gene contained in a 225-kb yeast artificial chromosome to complement the sterile phenotype of the
Dazl
null mouse (
Dazl
−/−
), which is characterized by severe germ-cell depletion and meiotic failure. Although
Dazl
−/−
mice remained infertile when the
DAZ
transgene was introduced, histological examination revealed a partial and variable rescue of the mutant phenotype, manifest as a pronounced increase in the germ cell population of the seminiferous tubules and survival to the pachytene stage of meiosis. As well as constituting definitive proof of the spermatogenic role of the
DAZ
gene product, these findings confirm the high degree of functional conservation between the
DAZ
and
DAZL1
genes, suggesting they may constitute a single target for contraceptive intervention and raising the possibility of therapeutic up-regulation of the
DAZL1
gene in infertile men.
A highly conserved sequence is a novel gene involved inde novovitamin B6 biosynthesis
Authors: Ehrenshaft Marilyn , Bilski Piotr , Li Ming Y. , Chignell Colin F. , Daub Margaret E.
Published: July 2002

TheCercospora nicotianae SOR1(singlet oxygen resistance) gene was identified previously as a gene involved in resistance of this fungus to singlet-oxygen-generating phototoxins. Although homologues toSOR1occur in organisms in four kingdoms and encode one of the most highly conserved proteins yet identified, the precise function of this protein has, until now, remained unknown. We show thatSOR1is essential in pyridoxine (vitamin B6) synthesis inC. nicotianaeandAspergillus flavus,although it shows no homology to previously identified pyridoxine synthesis genes identified inEscherichia coli. Sequence database analysis demonstrated that organisms encode eitherSOR1orE. colipyridoxine biosynthesis genes, but not both, suggesting that there are two divergent pathways forde novopyridoxine biosynthesis in nature. Pathway divergence appears to have occurred during the evolution of the eubacteria. We also present data showing that pyridoxine quenches singlet oxygen at a rate comparable to that of vitamins C and E, two of the most highly efficient biological antioxidants, suggesting a previously unknown role for pyridoxine in active oxygen resistance.
Linear coupling between cerebral blood flow and oxygen consumption in activated human cortex
Authors: Hoge Richard D. , Atkinson Jeff , Gill Brad , Crelier Gérard R. , Marrett Sean , Pike G. Bruce
Published: July 2002

The aim of this study was to test the hypothesis that, within a specific cortical unit, fractional changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen consumption (
CMR

O
2

) are coupled through an invariant relationship during physiological stimulation. This aim was achieved by simultaneously measuring relative changes in these quantities in human primary visual cortex (V1) during graded stimulation with patterns designed to selectively activate different populations of V1 neurons. Primary visual cortex was delineated individually in each subject by using phase-encoded retinotopic mapping. Flow-sensitive alternating inversion recovery MRI, in conjunction with blood oxygenation-sensitive MRI and hypercapnic calibration, was used to monitor CBF and
CMR

O
2

. The stimuli used included (
i
) diffuse isoluminant chromatic displays; (
ii
) high spatial-frequency achromatic luminance gratings; and (
iii
) radial checkerboard patterns containing both color and luminance contrast modulated at different temporal rates. Perfusion responses to each pattern were graded by varying luminance and/or color modulation amplitudes. For all stimulus types, fractional changes in blood flow and oxygen uptake were found to be linearly coupled in a consistent ratio of approximately 2:1. The most potent stimulus produced CBF and
CMR

O
2

increases of 48 ± 5% and 25 ± 4%, respectively, with no evidence of a plateau for oxygen consumption. Estimation of aerobic ATP yields from the observed
CMR

O

2

increases and comparison with the maximum possible anaerobic ATP contribution indicate that elevated energy demands during brain activation are met largely through oxidative metabolism.
Neutral evolution of mutational robustness
Authors: van Nimwegen Erik , Crutchfield James P. , Huynen Martijn
Published: July 2002

We introduce and analyze a general model of a population evolving over a network of selectively neutral genotypes. We show that the population’s limit distribution on the neutral network is solely determined by the network topology and given by the principal eigenvector of the network’s adjacency matrix. Moreover, the average number of neutral mutant neighbors per individual is given by the matrix spectral radius. These results quantify the extent to which populations evolve mutational robustness—the insensitivity of the phenotype to mutations—and thus reduce genetic load. Because the average neutrality is independent of evolutionary parameters—such as mutation rate, population size, and selective advantage—one can infer global statistics of neutral network topology by using simple population data available fromin vitroorin vivoevolution. Populations evolving on neutral networks of RNA secondary structures show excellent agreement with our theoretical predictions.
Copolymer 1 acts against the immunodominant epitope 82–100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking
Authors: Aharoni Rina , Teitelbaum Dvora , Arnon Ruth , Sela Michael
Published: July 2002

The synthetic random amino acid copolymer Copolymer 1 (Cop 1, Copaxone, glatiramer acetate) suppresses experimental autoimmune encephalomyelitis, slows the progression of disability, and reduces relapse rate in multiple sclerosis (MS). Cop 1 binds to various class II major histocompatibility complex (MHC) molecules and inhibits the T cell responses to several myelin antigens. In this study we attempted to find out whether, in addition to MHC blocking, Cop 1, which is immunologically cross-reactive with myelin basic protein (MBP), inhibits the response to this autoantigen by T cell receptor (TCR) antagonism. Two experimental systems, “prepulse assay” and “split APC assay,” were used to discriminate between competition for MHC molecules and TCR antagonism. The results in both systems using T cell lines/clones from mouse and human origin indicated that Cop 1 is a TCR antagonist of the 82–100 epitope of MBP. In contrast to the broad specificity of the MHC blocking induced by Cop 1, its TCR antagonistic activity was restricted to the 82–100 determinant of MBP and could not be demonstrated for proteolipid protein peptide or even for other MBP epitopes. Yet, it was shown for all the MBP 82–100-specific T cell lines/clones tested that were derived from mice as well as from an MS patient. The ability of Cop 1 to act as altered peptide and induce TCR antagonistic effect on the MBP p82–100 immunodominant determinant response elucidates further the mechanism of Cop 1 therapeutic activity in experimental autoimmune encephalomyelitis and MS.
Long-range charge hopping in DNA
Authors: Bixon M. , Giese Bernd , Wessely Stephan , Langenbacher Thomas , Michel-Beyerle Maria E. , Jortner Joshua
Published: July 2002

The fundamental mechanisms of charge migration in DNA are pertinent for current developments in molecular electronics and electrochemistry-based chip technology. The energetic control of hole (positive ion) multistep hopping transport in DNA proceeds via the guanine, the nucleobase with the lowest oxidation potential. Chemical yield data for the relative reactivity of the guanine cations and of charge trapping by a triple guanine unit in one of the strands quantify the hopping, trapping, and chemical kinetic parameters. The hole-hopping rate for superexchange-mediated interactions via two intervening AT base pairs is estimated to be 10
9
s
−1
at 300 K. We infer that the maximal distance for hole hopping in the duplex with the guanine separated by a single AT base pair is 300 ± 70 Å. Although we encounter constraints for hole transport in DNA emerging from the number of the mediating AT base pairs, electron transport is expected to be nearly sequence independent because of the similarity of the reduction potentials of the thymine and of the cytosine.
Purification and characterization of sortase, the transpeptidase that cleaves surface proteins of
Staphylococcus aureus
at the LPXTG motif
Authors: Ton-That Hung , Liu Gwen , Mazmanian Sarkis K. , Faull Kym F. , Schneewind Olaf
Published: July 2002

Surface proteins of
Staphylococcus aureus
are linked to the bacterial cell wall by sortase, an enzyme that cleaves polypeptides at the threonine of the LPXTG motif. Surface proteins can be released from staphylococci by treatment with hydroxylamine, resulting in the formation of threonine hydroxamate. Staphylococcal extracts, as well as purified sortase, catalyze the hydroxylaminolysis of peptides bearing an LPXTG motif, a reaction that can be inhibited with sulfhydryl-modifying reagents. Replacement of the single conserved cysteine at position 184 of sortase with alanine abolishes enzyme activity. Thus, sortase appears to catalyze surface-protein anchoring by means of a transpeptidation reaction that captures cleaved polypeptides as thioester enzyme intermediates.
Genetic ablation of root cap cells inArabidopsis
Authors: Tsugeki Ryuji , Fedoroff Nina V.
Published: July 2002

The root cap is increasingly appreciated as a complex and dynamic plant organ. Root caps sense and transmit environmental signals, synthesize and secrete small molecules and macromolecules, and in some species shed metabolically active cells. However, it is not known whether root caps are essential for normal shoot and root development. We report the identification of a root cap-specific promoter and describe its use to genetically ablate root caps by directing root cap-specific expression of a diphtheria toxin A-chain gene. Transgenic toxin-expressing plants are viable and have normal aerial parts but agravitropic roots, implying loss of root cap function. Several cell layers are missing from the transgenic root caps, and the remaining cells are abnormal. Although the radial organization of the roots is normal in toxin-expressing plants, the root tips have fewer cytoplasmically dense cells than do wild-type root tips, suggesting that root meristematic activity is lower in transgenic than in wild-type plants. The roots of transgenic plants have more lateral roots and these are, in turn, more highly branched than those of wild-type plants. Thus, root cap ablation alters root architecture both by inhibiting root meristematic activity and by stimulating lateral root initiation. These observations imply that the root caps contain essential components of the signaling system that determines root architecture.
Crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus
Authors: Bressanelli Stéphane , Tomei Licia , Roussel Alain , Incitti Ilario , Vitale Rosa Letizia , Mathieu Magali , De Francesco Raffaele , Rey Félix A.
Published: July 2002

We report the crystal structure of the RNA-dependent RNA polymerase of hepatitis C virus, a major human pathogen, to 2.8-Å resolution. This enzyme is a key target for developing specific antiviral therapy. The structure of the catalytic domain contains 531 residues folded in the characteristic fingers, palm, and thumb subdomains. The fingers subdomain contains a region, the “fingertips,” that shares the same fold with reverse transcriptases. Superposition to the available structures of the latter shows that residues from the palm and fingertips are structurally equivalent. In addition, it shows that the hepatitis C virus polymerase was crystallized in a closed fingers conformation, similar to HIV-1 reverse transcriptase in ternary complex with DNA and dTTP [Huang H., Chopra, R., Verdine, G. L. & Harrison, S. C. (1998)
Science
282, 1669–1675]. This superposition reveals the majority of the amino acid residues of the hepatitis C virus enzyme that are likely to be implicated in binding to the replicating RNA molecule and to the incoming NTP. It also suggests a rearrangement of the thumb domain as well as a possible concerted movement of thumb and fingertips during translocation of the RNA template-primer in successive polymerization rounds.
Calcium isotope fractionation between soft and mineralized tissues as a monitor of calcium use in vertebrates
Authors: Skulan Joseph , DePaolo Donald J.
Published: July 2002

Calcium from bone and shell is isotopically lighter than calcium of soft tissue from the same organism and isotopically lighter than source (dietary) calcium. When measured as the
44
Ca/
40
Ca isotopic ratio, the total range of variation observed is 5.5‰, and as much as 4‰ variation is found in a single organism. The observed intraorganismal calcium isotopic variations and the isotopic differences between tissues and diet indicate that isotopic fractionation occurs mainly as a result of mineralization. Soft tissue calcium becomes heavier or lighter than source calcium during periods when there is net gain or loss of mineral mass, respectively. These results suggest that variations of natural calcium isotope ratios in tissues may be useful for assessing the calcium and mineral balance of organisms without introducing isotopic tracers.
Activity-based protein profiling: The serine hydrolases
Authors: Liu Yongsheng , Patricelli Matthew P. , Cravatt Benjamin F.
Published: July 2002

With the postgenome era rapidly approaching, new strategies for the functional analysis of proteins are needed. To date, proteomics efforts have primarily been confined to recording variations in protein level rather than activity. The ability to profile classes of proteins on the basis of changes in their activity would greatly accelerate both the assignment of protein function and the identification of potential pharmaceutical targets. Here, we describe the chemical synthesis and utility of an active-site directed probe for visualizing dynamics in the expression and function of an entire enzyme family, the serine hydrolases. By reacting this probe, a biotinylated fluorophosphonate referred to as FP-biotin, with crude tissue extracts, we quickly and with high sensitivity detect numerous serine hydrolases, many of which display tissue-restricted patterns of expression. Additionally, we show that FP-biotin labels these proteins in an activity-dependent manner that can be followed kinetically, offering a powerful means to monitor dynamics simultaneously in both protein function and expression.
Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase
Authors: Ober Dietrich , Hartmann Thomas
Published: July 2002

Pyrrolizidine alkaloids are preformed plant defense compounds with sporadic phylogenetic distribution. They are thought to have evolved in response to the selective pressure of herbivory. The first pathway-specific intermediate of these alkaloids is the rare polyamine homospermidine, which is synthesized by homospermidine synthase (HSS). The HSS gene from
Senecio vernalis
was cloned and shown to be derived from the deoxyhypusine synthase (DHS) gene, which is highly conserved among all eukaryotes and archaebacteria. DHS catalyzes the first step in the activation of translation initiation factor 5A (eIF5A), which is essential for eukaryotic cell proliferation and which acts as a cofactor of the HIV-1 Rev regulatory protein. Sequence comparison provides direct evidence for the evolutionary recruitment of an essential gene of primary metabolism (DHS) for the origin of the committing step (HSS) in the biosynthesis of pyrrolizidine alkaloids.
Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in
Tetrahymena
Authors: Strahl Brian D. , Ohba Reiko , Cook Richard G. , Allis C. David
Published: July 2002

Studies into posttranslational modifications of histones, notably acetylation, have yielded important insights into the dynamic nature of chromatin structure and its fundamental role in gene expression. The roles of other covalent histone modifications remain poorly understood. To gain further insight into histone methylation, we investigated its occurrence and pattern of site utilization in
Tetrahymena
, yeast, and human HeLa cells. In
Tetrahymena
, transcriptionally active macronuclei, but not transcriptionally inert micronuclei, contain a robust histone methyltransferase activity that is highly selective for H3. Microsequence analyses of H3 from
Tetrahymena,
yeast, and HeLa cells indicate that lysine 4 is a highly conserved site of methylation, which to date, is the major site detected in
Tetrahymena
and yeast. These data document a nonrandom pattern of H3 methylation that does not overlap with known acetylation sites in this histone. In as much as H3 methylation at lysine 4 appears to be specific to macronuclei in
Tetrahymena
, we suggest that this modification pattern plays a facilitatory role in the transcription process in a manner that remains to be determined. Consistent with this possibility, H3 methylation in yeast occurs preferentially in a subpopulation of H3 that is preferentially acetylated.
Contaminant bioavailability in soils, sediments, and aquatic environments
Authors: Traina Samuel J. , Laperche Valérie
Published: July 2002

The aqueous concentrations of heavy metals in soils, sediments, and
aquatic environments frequently are controlled by the dissolution and
precipitation of discrete mineral phases. Contaminant uptake by
organisms as well as contaminant transport in natural systems typically
occurs through the solution phase. Thus, the thermodynamic solubility
of contaminant-containing minerals in these environments can directly
influence the chemical reactivity, transport, and ecotoxicity of their
constituent ions. In many cases, Pb-contaminated soils and sediments
contain the minerals anglesite (PbSO
4
), cerussite
(PbCO
3
), and various lead oxides (e.g., litharge, PbO) as
well as Pb
2+
adsorbed to Fe and Mn (hydr)oxides. Whereas
adsorbed Pb can be comparatively inert, the lead oxides, sulfates, and
carbonates are all highly soluble in acidic to circumneutral
environments, and soil Pb in these forms can pose a significant
environmental risk. In contrast, the lead phosphates [e.g.,
pyromorphite, Pb
5
(PO
4
)
3
Cl] are
much less soluble and geochemically stable over a wide pH range.
Application of soluble or solid-phase phosphates (i.e., apatites) to
contaminated soils and sediments induces the dissolution of the
“native” Pb minerals, the desorption of Pb adsorbed by hydrous
metal oxides, and the subsequent formation of pyromorphites
in
situ
. This process results in decreases in the chemical lability
and bioavailability of the Pb without its removal from the contaminated
media. This and analogous approaches may be useful strategies for
remediating contaminated soils and sediments.
Manganese oxide minerals: Crystal structures and economic and environmental significance
Authors: Post Jeffrey E.
Published: July 2002

Manganese oxide minerals have been used for thousands of years—by
the ancients for pigments and to clarify glass, and today as ores of Mn
metal, catalysts, and battery material. More than 30 Mn oxide minerals
occur in a wide variety of geological settings. They are major
components of Mn nodules that pave huge areas of the ocean floor and
bottoms of many fresh-water lakes. Mn oxide minerals are ubiquitous in
soils and sediments and participate in a variety of chemical reactions
that affect groundwater and bulk soil composition. Their typical
occurrence as fine-grained mixtures makes it difficult to study their
atomic structures and crystal chemistries. In recent years, however,
investigations using transmission electron microscopy and powder x-ray
and neutron diffraction methods have provided important new insights
into the structures and properties of these materials. The crystal
structures for todorokite and birnessite, two of the more common Mn
oxide minerals in terrestrial deposits and ocean nodules, were
determined by using powder x-ray diffraction data and the Rietveld
refinement method. Because of the large tunnels in todorokite and
related structures there is considerable interest in the use of these
materials and synthetic analogues as catalysts and cation exchange
agents. Birnessite-group minerals have layer structures and readily
undergo oxidation reduction and cation-exchange reactions and play a
major role in controlling groundwater chemistry.
Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection
Authors: Detours Vincent , Perelson Alan S.
Published: July 2002

Interactions between αβ T cell receptors and peptides bound to molecules encoded by the MHC genes underly T cell activation. More than 1% of T cells are activated by foreign (allogenic) MHC molecules, a phenomenon called alloreactivity. Reconciling the high frequency of alloreactivity with the fact that only 1 T cell in 10
4
–10
6
responds to a given foreign antigen presented on self MHC has been a long-standing puzzle. We show, by using a quantitative model, that this difference follows from the affinity model of T cell selection. Further, we demonstrate that highly alloreactive pre- and post-selection repertoires can be obtained without assuming germline bias of T cell receptors toward recognition of allele-specific MHC residues. It has been proposed that alloreactivity occurs because self and foreign MHCs bind different subsets of self peptides or alter their conformation differently. We find that such effects decrease rather than increase alloreactivity. Overall, our results show that the affinity model of T cell selection can quantitatively explain both self MHC restriction and high alloreactivity.
Epstein–Barr virus nuclear protein 2 interacts with p300, CBP, and PCAF histone acetyltransferases in activation of the LMP1 promoter
Authors: Wang Lian , Grossman Steven R. , Kieff Elliott
Published: July 2002

The Epstein–Barr virus (EBV) nuclear protein 2 (EBNA2) and herpes simplex virion protein 16 (VP16) acidic domains that mediate transcriptional activation now are found to have affinity for p300, CBP, and PCAF histone acetyltransferases (HATs). Transcriptionally inactive point mutations in these domains lack affinity for p300, CBP, or PCAF. P300 and CBP copurify with the principal HAT activities that bind to EBNA2 or VP16 acidic domains through velocity sedimentation and anion-exchange chromatography. EBNA2 binds to both the N- and C-terminal domains of p300 and coimmune-precipitates from transfected 293T cells with p300. In EBV-infected Akata Burkitt's tumor cells that do not express the EBV encoded oncoproteins EBNA2 or LMP1, p300 expression enhances the ability of EBNA2 to up-regulate LMP1 expression. Through its intrinsic HAT activity, PCAF can further potentiate the p300 effect. In 293 T cells, P300 and CBP (but not PCAF) can also coactivate transcription mediated by the EBNA2 or VP16 acidic domains and HAT-negative mutants of p300 have partial activity. Thus, the EBNA2 and VP16 acidic domains can utilize the intrinsic HAT or scaffolding properties of p300 to activate transcription.
An
in vivo
approach showing the chemotactic activity of leukotriene B
4
in acute renal ischemic-reperfusion injury
Authors: Noiri Eisei , Yokomizo Takehiko , Nakao Akihide , Izumi Takashi , Fujita Toshiro , Kimura Satoshi , Shimizu Takao
Published: July 2002

Neutrophil migration protects the body against foreign invasion. Sequestration and activation of neutrophils, however, require stringent regulation because they may also cause tissue damage by the release of lysosomal enzymes and reactive oxygen species. The activity of various chemoattractants [e.g., leukotriene B
4
(LTB
4
), interleukin-8, and complements] has been documented by
in vitro
assays, whereas
in vivo
data have been limited mostly to histology. To examine in an
in vivo
model the chemotactic activity and subsequent tissue infiltration and the role of a specific chemoattractant, LTB
4
, we used a rat renal ischemia-reperfusion injury model. Fluorescence-labeled Chinese hamster ovary (CHO) cells stably expressing the LTB
4
receptor (CHO-BLT) were able to accumulate along with neutrophils in the postischemic kidney, in contrast to vector control CHO cells. Furthermore, LTB
4
antagonists that protect against the decrease in renal function and diminish the tissue myeloperoxidase activity also led to the marked decrease in the number of CHO-BLT cells and neutrophils. Thus, LTB
4
alone appears sufficient to cause cells to migrate into postischemic tissues, and its dominant role in reperfusion injury has been demonstrated. The utilization of transfectants to pinpoint the role of LTB
4
in these
in vivo
experiments suggests their potential use with other ligands and/or in other pathological conditions.
Changes in mitochondrial genetic codes as phylogenetic characters: Two examples from the flatworms
Authors: Telford Maximilian J. , Herniou Elisabeth A. , Russell Robert B. , Littlewood D. Timothy J.
Published: July 2002

Shared molecular genetic characteristics other than DNA and protein sequences can provide excellent sources of phylogenetic information, particularly if they are complex and rare and are consequently unlikely to have arisen by chance convergence. We have used two such characters, arising from changes in mitochondrial genetic code, to define a clade within the Platyhelminthes (flatworms), the Rhabditophora. We have sampled 10 distinct classes within the Rhabditophora and find that all have the codon AAA coding for the amino acid Asn rather than the usual Lys and AUA for Ile rather than the usual Met. We find no evidence to support claims that the codon UAA codes for Tyr in the Platyhelminthes rather than the standard stop codon. The Rhabditophora are a very diverse group comprising the majority of the free-living turbellarian taxa and the parasitic Neodermata. In contrast, three other classes of turbellarian flatworm, the Acoela, Nemertodermatida, and Catenulida, have the standard invertebrate assignments for these codons and so are convincingly excluded from the rhabditophoran clade. We have developed a rapid computerized method for analyzing genetic codes and demonstrate the wide phylogenetic distribution of the standard invertebrate code as well as confirming already known metazoan deviations from it (ascidian, vertebrate, echinoderm/hemichordate).
Capture of a protein synthesis-dependent component of long-term depression
Authors: Kauderer Beth S. , Kandel Eric R.
Published: July 2002

Hippocampal-based behavioral memories and hippocampal-based forms
of synaptic plasticity, such as long-term potentiation, are divisible
into short- and long-term phases, with the long-term phase requiring
the synthesis of new proteins and mRNA for its persistence. By
contrast, it is less clear whether long-term depression (LTD) can be
divisible into phases. We here describe that in stable hippocampal
organotypic cultures, LTD also is not a unitary event but a multiphase
process. A prolonged stimulus of 900 stimuli spaced at 1 Hz for 15 min
induces a late phase of LTD, which is protein- and mRNA
synthesis-dependent. By contrast, a short train of the same 900 stimuli
massed at 5 Hz for 3 min produces only a short-lasting LTD. This
short-lasting LTD is capable of capturing late-phase LTD. The 5-Hz
stimulus or the prolonged 1-Hz stimulus in the presence of protein
synthesis inhibitors each can be transformed into an enduring late
phase of depression when the prolonged stimulus is applied to another
input in the same population of neurons.
Improved barley broiler feed with transgenic malt containing heat-stable (1,3–1,4)-β-glucanase
Authors: von Wettstein Diter , Mikhaylenko Galina , Froseth John A. , Kannangara C. Gamini
Published: July 2002

The low nutritional value of barley for poultry is because of the
absence of an intestinal enzyme for efficient depolymerization of
(1,3–1,4)-β-glucan, the major polysaccharide of the endosperm cell
walls. This leads to high viscosity in the intestine, limited nutrient
uptake, decreased growth rate, and unhygienic sticky droppings adhering
to chickens and floors of the production cages. Consequently, the 7.5
billion broiler chickens produced annually in the United States are
primarily raised on corn–soybean diets. Here we show that addition to
normal barley of 6.2% transgenic malt containing a thermotolerant
(1,3–1,4)-β-glucanase (4.28 μg⋅g
−1
soluble
protein) provides a weight gain equivalent to corn diets. The number of
birds with adhering sticky droppings is drastically reduced. Intestines
and excrements of chickens fed the barley control diet contained large
amounts of soluble (1,3–1,4)-β-glucan, which was reduced by 75 and
50%, respectively, by adding transgenic malt to the diet. The amount
of active recombinant enzyme in the small intestine corresponded to
that present in the feed, whereas an 11-fold concentration of the
enzyme was observed in the ceca, and a 7.5-fold concentration occurred
in the excrement. Glycosylation of the β-glucanase isolated from the
ceca testified to its origin from the transgenic barley. Analysis of
the data from this trial demonstrates the possibility of introducing
individual recombinant enzymes into various parts of the
gastrointestinal tract of chickens with transgenic malt and thereby the
possibility of evaluating their effect on the metabolism of a given
ingredient targeted by the enzyme.
An alternative, nonapoptotic form of programmed cell death
Authors: Sperandio Sabina , de Belle Ian , Bredesen Dale E.
Published: July 2002

The term apoptosis often has been used interchangeably with
the term programmed cell death. Here we describe a form of programmed
cell death that is distinct from apoptosis by the criteria of
morphology, biochemistry, and response to apoptosis inhibitors.
Morphologically, this alternative form of programmed cell death appears
during development and in some cases of neurodegeneration. Despite its
lack of response to caspase inhibitors and Bcl-x
L
, we show
that this form of cell death is driven by an alternative caspase-9
activity that is Apaf-1-independent. Characterization of this
alternative form of programmed cell death should lead to new insight
into cell death programs and their roles in development and
degeneration.
The sentrin-conjugating enzyme mUbc9 interacts with GLUT4 and GLUT1 glucose transporters and regulates transporter levels in skeletal muscle cells
Authors: Giorgino Francesco , de Robertis Ottilia , Laviola Luigi , Montrone Carmela , Perrini Sebastio , McCowen Karen C. , Smith Robert J.
Published: July 2002

Glucose transport in insulin-regulated tissues is mediated by the
GLUT4 and GLUT1 transporters. Using the yeast two-hybrid system, we
have cloned the sentrin-conjugating enzyme mUbc9 as a protein that
interacts with the GLUT4 COOH-terminal intracellular domain. The mUbc9
enzyme was found to bind directly to GLUT4 and GLUT1 through an 11-aa
sequence common to the two transporters and to modify both transporters
covalently by conjugation with the mUbc9 substrate, sentrin.
Overexpression of mUbc9 in L6 skeletal muscle cells decreased GLUT1
transporter abundance 65%, resulting in decreased basal glucose
transport. By contrast, mUbc9 overexpression increased GLUT4 abundance
8-fold, leading to enhanced transport stimulation by insulin. A
dominant-negative mUbc9 mutant lacking catalytic activity had effects
opposite to those of wild-type mUbc9. The regulation of GLUT4 and GLUT1
was specific, as evidenced by an absence of mUbc9 interaction with or
regulation of the GLUT3 transporter isoform in L6 skeletal muscle
cells. The mUbc9 sentrin-conjugating enzyme represents a novel
regulator of GLUT1 and GLUT4 protein levels with potential importance
as a determinant of basal and insulin-stimulated glucose uptake in
normal and pathophysiological states.
Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates
Authors: Weinberg Joel M. , Venkatachalam Manjeri A. , Roeser Nancy F. , Nissim Itzhak
Published: July 2002

Kidney proximal tubule cells developed severe energy deficits during hypoxia/reoxygenation not attributable to cellular disruption, lack of purine precursors, the mitochondrial permeability transition, or loss of cytochrome
c
. Reoxygenated cells showed decreased respiration with complex I substrates, but minimal or no impairment with electron donors at complexes II and IV. This was accompanied by diminished mitochondrial membrane potential (ΔΨ
m
). The energy deficit, respiratory inhibition, and loss of ΔΨ
m
were strongly ameliorated by provision of α-ketoglutarate plus aspartate (αKG/ASP) supplements during either hypoxia or only during reoxygenation. Measurements of
13
C-labeled metabolites in [3-
13
C]aspartate-treated cells indicated the operation of anaerobic pathways of αKG/ASP metabolism to generate ATP, yielding succinate as end product. Anaerobic metabolism of αKG/ASP also mitigated the loss of ΔΨ
m
that occurred during hypoxia before reoxygenation. Rotenone, but not antimycin or oligomycin, prevented this effect, indicating that electron transport in complex I, rather than F
1
F
0
-ATPase activity, had been responsible for maintenance of ΔΨ
m
by the substrates. Thus, tubule cells subjected to hypoxia/reoxygenation can have persistent energy deficits associated with complex I dysfunction for substantial periods of time before onset of the mitochondrial permeability transition and/or loss of cytochrome
c
. The lesion can be prevented or reversed by citric acid cycle metabolites that anaerobically generate ATP by intramitochondrial substrate-level phosphorylation and maintain ΔΨ
m
via electron transport in complex I. Utilization of these anaerobic pathways of mitochondrial energy metabolism known to be present in other mammalian tissues may provide strategies to limit mitochondrial dysfunction and allow cellular repair before the onset of irreversible injury by ischemia or hypoxia.
Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD8+and CD4+T lymphocytes
Authors: Oxenius Annette , Price David A. , Easterbrook Philippa J. , O'Callaghan Christopher A. , Kelleher Anthony D. , Whelan Joseph A. , Sontag Glenn , Sewell Andrew K. , Phillips Rodney E.
Published: July 2002

Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection without clear understanding of its immunological effects. Here, we demonstrate that early use of HAART during primary infection preserves HIV-specific CD8+T cells physically and functionally while HIV-specific T cell help is sustained. We also show that even transient administration of HAART at seroconversion can preserve HIV-specific immunity. In contrast, delayed initiation of HAART is associated with a progressive loss of HIV-specific CD8+T cells and absent HIV-specific T cell help. These results imply that HIV-specific T help is damaged during primary HIV-1 infection. Early drug treatment, which preserves this immunity, also preserves HIV-specific CD8+T cells. These results have implications for understanding the early pathogenesis of HIV-1 infection and suggest that acute HIV infection should be treated aggressively and as early as possible.
Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety
Authors: Simpson Joseph R. , Drevets Wayne C. , Snyder Abraham Z. , Gusnard Debra A. , Raichle Marcus E.
Published: July 2002

Regional cerebral blood flow (BF) was examined in the human
medial prefrontal cortex (MPFC) with positron emission tomography
during anticipatory anxiety. Transient anxiety was induced in normal
subjects by having them anticipate a painful shock to the fingers of
one hand. BF was decreased during anticipatory anxiety, relative to an
eyes-closed resting condition, in two regions of the MPFC (Brodmann
Areas 10/32 and 24/25). BF decreases in these areas were inversely
correlated with anxiety self rating, such that the
least
anxious subjects exhibited the largest BF reductions, whereas the most
anxious subjects showed no significant BF reduction or a slight
increase. BF changes in MPFC and in the midbrain were correlated with
each other and with anxiety self rating. These results are consistent
with the hypothesis that BF reductions in MPFC, previously observed in
cognitive tasks, reflect a dynamic balance between focused attention
and subject anxiety and may occur from a functionally active baseline
or default state. The characterization of such relationships within the
human brain enables new insights into the integration of cognition and
emotion.
Pre-Global Surveyor evidence for Martian ground water
Authors: Donahue Thomas M.
Published: July 2002

A time-dependent theory for the evolution of water on Mars is presented. Using this theory and invoking a large number of observational constraints, I argue that these constraints require that a large reservoir of water exists in the Martian crust at depths shallow enough to interact strongly with the atmosphere. The constraints include the abundance of atmospheric water vapor, escape fluxes of hydrogen and deuterium, D/H ratios in the atmosphere and in hydrous minerals found in one Martian meteorite, alteration of minerals in other meteorites, and fluvial features on the Martian surface. These results are consonant with visual evidence for recent groundwater seepage obtained by the Mars Global Surveyor satellite.
Thinking styles and teachers' characteristics
Authors: Zhang Li‐fang , Sternberg Robert J.
Published: July 2002

This study had two goals. The first was to validate further Sternberg's theory of mental self‐government in a cross‐cultural setting. The second was to investigate the relationship between thinking styles and teachers' characteristics. Research participants were one hundred ninety‐three (65 male and 128 female) in‐service teachers studying in the Bachelor of Education degree program and the Postgraduate Certificate in Education program at the University of Hong Kong. The participants responded to the Chinese version of the Thinking Styles Questionnaire for Teachers (TSQT) that has its theoretical foundation in Sternberg's theory of mental self‐government. They also provided a range of demographic information such as age, gender, family income, and duration of their teaching experience. Furthermore, they rated themselves on a 5‐point Likert scale about their teaching practices and about their perceptions of their school environment. The results of the study showed that the TSQT is a reliable and valid inventory for assessing the thinking styles of primary and secondary school in‐service teachers in Hong Kong. Cronbach's alphas ranged from .58 to .75, with a mean of .68 and a median of .66. A principal‐axis factor analysis followed by an oblique rotation resulted in two factors that accounted for 73.8% of the variance in the data. Moreover, results from stepwise multiple‐regression procedures indicated that six characteristics of teachers were significantly correlated with the thinking styles specified by the theory of mental self‐government. These teacher characteristics are gender, professional work experience outside school settings, the degree of enjoying adopting new teaching materials, a tendency for using group projects in assessing student achievement, perceived autonomy for determining their teaching contents, and their rating of the quality of their students. We discussed seven possibilities for using the knowledge about thinking styles to facilitate an enhancement of teaching and learning.
Rethinking Russia From Zardob: Hasan Melikov Zardabi and the “Native” Intelligentsia
Authors: Jersild Austin
Published: July 2002

Many non-Russians in the Russian Empire were active members of imperial educated society (obshchestvo), and they often conceived of the colonial advance of Russia as part of the march of the progressive West and “civilization” itself into the backward lands of the East. Reformist empire builders who criticized the brutal wars and population transfers that marked the conquest of the southern borderlands also emphasized the civilizing mission of the empire on its eastern frontier. This article explores the conception of Russia and its empire in the work of the Azerbaijani publicist Hasan Melikov Zardabi. Zardabi was genuinely enthusiastic about Russia and the prospect of an enlightened imperial future for the lands of the former khanates on the frontier of the Iranian and Ottoman empires. The unusual circumstances of his life, however, which included exile to his remote and native village of Zardob, a small fishing village on the Kura River to the west of Baku, compelled him to re-evaluate his estimation of Russia and the benefits of imperial rule. Zardabi learned from his experience in Zardob, and grew to rethink his earlier views about civilization and the Russian Empire.
Workforce Agility: The New Employee Strategy for the Knowledge Economy
Authors: Breu Karin , Hemingway Christopher J. , Strathern Mark , Bridger David
Published: July 2002

The notion of the agile workforce has been discussed as central to creating the agile organization, which achieves superior environmental responsiveness in contexts of turbulence and change. Previous agility research has focused overly on the organization, paying scant attention to the workforce. This paper addresses a significant gap in agility research by reporting on the first empirical study to examine how the pressures of organizational agility impact upon the workforce. Survey evidence from 515 UK organizations is used for eliciting an initial indicator of workforce agility. The data suggest that agile workforces acquire the five capabilities of intelligence, competencies, collaboration, culture and information systems (IS). From an information technology (IT) perspective the determinants of workforce agility are flexible infrastructure platforms that support the rapid introduction of new IS and the enhancement of IT competencies across the entire workforce. The survey also revealed that information and communications technology applications increase workforce agility most when used for collaborative working.
A Role for the Actin Cytoskeleton of Saccharomyces cerevisiae in Bipolar Bud-Site Selection
Authors: Yang Shirley , Ayscough Kathryn R. , Drubin David G.
Published: July 2002

Saccharomyces cerevisiae cells select bud sites according to one of two predetermined patterns. MATa and MATα cells bud in an axial pattern, and MATa/α cells bud in a bipolar pattern. These budding patterns are thought to depend on the placement of spatial cues at specific sites in the cell cortex. Because cytoskeletal elements play a role in organizing the cytoplasm and establishing distinct plasma membrane domains, they are well suited for positioning bud-site selection cues. Indeed, the septin-containing neck filaments are crucial for establishing the axial budding pattern characteristic of MATa and MATα cells. In this study, we determined the budding patterns of cells carrying mutations in the actin gene or in genes encoding actin-associated proteins: MATa/α cells were defective in the bipolar budding pattern, but MATa and MATα cells still exhibit a normal axial budding pattern. We also observed that MATa/α actin cytoskeleton mutant daughter cells correctly position their first bud at the distal pole of the cell, but mother cells position their buds randomly. The actin cytoskeleton therefore functions in generation of the bipolar budding pattern and is required specifically for proper selection of bud sites in mother MATa/α cells. These observations and the results of double mutant studies support the conclusion that different rules govern bud-site selection in mother and daughter MATa/α cells. A defective bipolar budding pattern did not preclude an sla2-6 mutant from undergoing pseudohyphal growth, highlighting the central role of daughter cell bud-site selection cues in the formation of pseudohyphae. Finally, by examining the budding patterns of mad2-1 mitotic checkpoint mutants treated with benomyl to depolymerize their microtubules, we confirmed and extended previous evidence indicating that microtubules do not function in axial or bipolar bud-site selection.
Fibroblast Growth Factor-2 (FGF-2) Induces Vascular Endothelial Growth Factor (VEGF) Expression in the Endothelial Cells of Forming Capillaries: An Autocrine Mechanism Contributing to Angiogenesis
Authors: Seghezzi Graziano , Patel Sundeep , Ren Christine J. , Gualandris Anna , Pintucci Giuseppe , Robbins Edith S. , Shapiro Richard L. , Galloway Aubrey C. , Rifkin Daniel B. , Mignatti Paolo
Published: July 2002

FGF-2 and VEGF are potent angiogenesis inducers in vivo and in vitro. Here we show that FGF-2 induces VEGF expression in vascular endothelial cells through autocrine and paracrine mechanisms. Addition of recombinant FGF-2 to cultured endothelial cells or upregulation of endogenous FGF-2 results in increased VEGF expression. Neutralizing monoclonal antibody to VEGF inhibits FGF-2–induced endothelial cell proliferation. Endogenous 18-kD FGF-2 production upregulates VEGF expression through extracellular interaction with cell membrane receptors; high-Mr FGF-2 (22–24-kD) acts via intracellular mechanism(s). During angiogenesis induced by FGF-2 in the mouse cornea, the endothelial cells of forming capillaries express VEGF mRNA and protein. Systemic administration of neutralizing VEGF antibody dramatically reduces FGF-2-induced angiogenesis. Because occasional fibroblasts or other cell types present in the corneal stroma show no significant expression of VEGF mRNA, these findings demonstrate that endothelial cell-derived VEGF is an important autocrine mediator of FGF-2-induced angiogenesis. Thus, angiogenesis in vivo can be modulated by a novel mechanism that involves the autocrine action of vascular endothelial cell-derived FGF-2 and VEGF.