bluuebunny/crossref_metadata_2025 huggingface dataset:
Thioredoxin-linked mitigation of allergic responses to wheat
Authors: Buchanan B. B. , Adamidi C. , Lozano R. M. , Yee B. C. , Momma M. , Kobrehel K. , Ermel R. , Frick O. L.
Published: July 2002

Thioredoxin, a ubiquitous 12-kDa regulatory disulfide protein, was found to reduce disulfide bonds of allergens (convert S—S to 2 SH) and thereby mitigate the allergenicity of commercial wheat preparations. Allergenic strength was determined by skin tests with a canine model for food allergy. Statistically significant mitigation was observed with 15 of 16 wheat-sensitive animals. The allergenicity of the protein fractions extracted from wheat flour with the indicated solvent was also assessed: the gliadins (ethanol) were the strongest allergens, followed by glutenins (acetic acid), albumins (water), and globulins (salt water). Of the gliadins, the α and β fractions were most potent, followed by the γ and ω types. Thioredoxin mitigated the allergenicity associated with the major protein fractions—i.e, the gliadins (including the α, β, and γ types) and the glutenins—but gave less consistent results with the minor fractions, the albumins and globulins. In all cases, mitigation was specific to thioredoxin that had been reduced either enzymically by NADPH and NADP–thioredoxin reductase or chemically by dithiothreitol; reduced glutathione was without significant effect. As in previous studies, thioredoxin was particularly effective in the reduction of intramolecular (intrachain) disulfide bonds. The present results demonstrate that the reduction of these disulfide bonds is accompanied by a statistically significant decrease in allergenicity of the active proteins. This decrease occurs alongside the changes identified previously—i.e., increased susceptibility to proteolysis and heat, and altered biochemical activity. The findings open the door to the testing of the thioredoxin system in the production of hypoallergenic, more-digestible foods.
In the absence of the invariant chain, HLA-DR molecules display a distinct array of peptides which is influenced by the presence or absence of HLA-DM
Authors: Lightstone Liz , Hargreaves Roseanna , Bobek Gabriele , Peterson Mary , Aichinger Gerald , Lombardi Giovanna , Lechler Robert
Published: July 2002

The independent influences of invariant chain (Ii) and HLA-DM molecules on the array of naturally processed peptides displayed by HLA-DR molecules were studied using transfected cell lines. The absence of Ii led to an altered set of HLA-DR-bound peptides as judged by the discriminating responses of alloreactive T cell clones. While most T cell clones raised against DR+Ii+DM+peripheral blood mononuclear cells (PBMC) failed to respond to DR+Ii−DM−cells, T cell clones raised against DR+Ii−DM−transfectants were not stimulated by DR+Ii+DM+cells. Furthermore, coexpression of HLA-DM with HLA-DR1 in the absence of Ii augmented responses of anti-PBMC T cell clones but inhibited allorecognition by T cell clones raised against DR+Ii−DM−transfectants. The conformational integrity of the class II molecules, as judged by serology, suggests that the patterns of reactivity of the T cell clones reflect specificity for different alloantigen-bound peptides. Hence, discordant regulation of expression of major histocompatibility complex class II, Ii, and HLA-DM moleculesin vivomay lead to the display of novel self-peptides and possible interruption of self-tolerance.
Phosphorylation and subunit organization of axonal neurofilaments determined by scanning transmission electron microscopy
Authors: Leapman R. D. , Gallant P. E. , Reese T. S. , Andrews S. B.
Published: July 2002

Phosphorylation plays a critical role in controlling the function of cytoskeletal assemblies but no direct method yet exists to measure the phosphorylation state of proteins at the level of individual molecules and assemblies. Herein, we apply scanning transmission electron microscopy in combination with electron energy loss spectroscopy to measure the distributions of mass and phosphorus in neurofilaments (NFs) isolated from the squid giant axon. We find that native squid NFs, in contrast to typical reconstituted intermediate filaments, are a relatively homogeneous population containing only eight coiled-coil dimers per cross section. The measured stoichiometry of ∼1:1 for light/heavy peptides strongly suggests that squid NFs are composed of heterodimers. Furthermore, each heavy chain of the dimers carries at least 100 phosphate groups and is, therefore, near-maximally phosphorylated. These results also demonstrate that scanning transmission electron microscopy combined with electron energy loss spectroscopy at the nanometer scale is capable of characterizing the level and distribution of phosphorylation in individual mass-mapped protein assemblies.
Structural flexibility in transcription complex formation revealed by protein–DNA photocrosslinking
Authors: Cleary Michele A. , Pendergrast P. Shannon , Herr Winship
Published: July 2002

The Oct-1 POU domain binds diverse DNA-sequence elements and forms a higher-order regulatory complex with the herpes simplex virus coregulator VP16. The POU domain contains two separate DNA-binding domains joined by a flexible linker. By protein–DNA photocrosslinking we show that the relative positioning of the two POU DNA-binding domains on DNA varies depending on the nature of the DNA target. On a single VP16-responsive element, the POU domain adopts multiple conformations. To determine the structure of the Oct-1 POU domain in a multiprotein complex with VP16, we allowed VP16 to interact with previously crosslinked POU-domain–DNA complexes and found that VP16 can associate with multiple POU-domain conformations. These results reveal the dynamic potential of a DNA-binding domain in directing transcriptional regulatory complex formation.
Versatile 5′ phosphoryl coupling of small and large molecules to an RNA
Authors: Huang Faqing , Yarus Michael
Published: July 2002

A Ca
2+
-requiring catalytic RNA is shown to create 5′ phosphate–phosphate linkages with all nucleotides and coenzymes including CoA, nicotinamide adenine dinucleotide phosphate, thiamine phosphate, thiamine pyrophosphate, and flavin mononucleotide. In addition to these small molecules, macromolecules such as RNAs with 5′-diphosphates, and nonnucleotide molecules like Nɛ-phosphate arginine and 6-phosphate gluconic acid also react. That is, the self-capping RNA isolate 6 is an apparently universal 5′ phosphate-linker, reacting with any nucleophile containing an unblocked phosphate. These RNA reactions demonstrate a unique RNA catalytic capability and imply versatile and specific posttranscriptional RNA modification by RNA catalysis.
Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy
Authors: Kopin Alan S. , McBride Edward W. , Gordon Michelle C. , Quinn Suzanne M. , Beinborn Martin
Published: July 2002

The brain cholecystokinin-B/gastrin receptor (CCK-BR) is a major target for drug development because of its postulated role in modulating anxiety, memory, and the perception of pain. Drug discovery efforts have resulted in the identification of small synthetic molecules that can selectively activate this receptor subtype. These drugs include the peptide-derived compound PD135,158 as well as the nonpeptide benzodiazepine-based ligand, L-740,093 (S enantiomer). We now report that the maximal level of receptor-mediated second messenger signaling that can be achieved by these compounds (drug efficacy) markedly differs among species homologs of the CCK-BR. Further analysis reveals that the observed differences in drug efficacy are in large part explained by single or double aliphatic amino acid substitutions between respective species homologs. This interspecies variability in ligand efficacy introduces the possibility of species differences in receptor-mediated function, an important consideration when selecting animal models for preclinical drug testing. The finding that even single amino acid substitutions can significantly affect drug efficacy prompted us to examine ligand-induced signaling by a known naturally occurring human CCK-BR variant (glutamic acid replaced by lysine in position 288;288E → K). When examined using the288E → K receptor, the efficacies of both PD135,158 and L-740,093 (S) were markedly increased compared with values obtained with the wild-type human protein. These observations suggest that functional variability resulting from human receptor polymorphisms may contribute to interindividual differences in drug effects.
Human TAF
II
28 interacts with the human T cell leukemia virus type I Tax transactivator and promotes its transcriptional activity
Authors: Caron Cécile , Mengus Gabrielle , Dubrowskaya Veronica , Roisin Armelle , Davidson Irwin , Jalinot Pierre
Published: July 2002

The Tax protein encoded by human T cell leukemia virus type I transactivates the viral promoter by forming a complex with several cellular factors bound to three repeats of a specific upstream regulatory sequence. We have shown that transactivation by Tax was correlated with its ability to interact with the C-terminal moiety of the TATA box-binding protein (TBP). In the present study, the ability of Tax to interact with several human TBP-associated factors (TAF
II
s) was analyzed. We show that Tax interacts selectively with hTAF
II
28 in transfected HeLa cells. A direct interaction between Tax and hTAF
II
28 was also observed
in vitro
with purified proteins. In transient expression studies we show that overexpression of hTAF
II
28 significantly increased transactivation by Tax, both in the absence and in the presence of overexpressed TBP. The ability of hTAF
II
28 to potentiate transactivation correlated with the ability of Tax to interact with hTAF
II
28 and also with the ability of hTAF
II
28 to interact with TBP. Coexpression of TBP and hTAF
II
28 resulted in an additive increase in transactivation by Tax. From these observations we propose that transcriptional activation by Tax involves multiple interactions with TFIID via its TBP and hTAF
II
28 subunits.
Malignant transformation of early lymphoid progenitors in mice expressing an activated Blk tyrosine kinase
Authors: Malek Sami N. , Dordai Dominic I. , Reim Johannes , Dintzis Howard , Desiderio Stephen
Published: July 2002

The intracellular signals governing cellular proliferation and developmental progression during lymphocyte development are incompletely understood. The tyrosine kinase Blk is expressed preferentially in the B lineage, but its function in B cell development has been largely unexplored. We have generated transgenic mice expressing constitutively active Blk [Blk(Y495F)] in the B and T lymphoid compartments. Expression of Blk(Y495F) in the B lineage at levels similar to that of endogenous Blk induced B lymphoid tumors of limited clonality, whose phenotypes are characteristic of B cell progenitors at the proB/preB-I to preB-II transition. Expression of constitutively active Blk in the T lineage resulted in the appearance of clonal, thymic lymphomas composed of intermediate single positive cells. Taken together, these results indicate that specific B and T cell progenitor subsets are preferentially susceptible to transformation by Blk(Y495F) and suggest a role for Blk in the control of proliferation during B cell development.
Underlying assumptions of developmental models
Authors: Britten Roy J.
Published: July 2002

These 10 obvious propositions make a model of the specification of form, intended to expose underlying assumptions of developmental biology for examination and future experimentation. (I) The control of development is by means of local interactions, rather than global control mechanisms. (II) A macromolecule near a specific site will bind by mass action. (III) Starting with a precursor cell, all cells are assembled automatically by specifically binding macromolecules. (IV) At the surface of cells are specific adhesion sites that determine how all cells bind to each other. (V) An organism will assemble automatically from parts (macromolecules, structures, and cells) specified by nuclear control factors. (VI) The nuclear control factors in each cell are from precursor cells and factors derived by signaling from other cells. (VII)The macromolecules that determine specific binding, cell adhesion, and signaling are controlled by nuclear control factors, and in a grand feedback the cell adhesion and signaling systems determine the nuclear factor patterns. (VIII) The embryonic precursor cells for organs, termed “precursor groups,” are linked by adhesion and signaling relationships. (IX)The precursor groups include precursors for regions of an organ and boundary cells between regions having few cell types, growing without additional specific cell-to-cell relationships. (X)Organs are held together by cell adhesion in functional relationships. Thus the form and function of the organism is specified entirely by local control mechanisms. Without global control systems, information for form is in the genes for structural proteins, adhesion molecules, control factors, signaling molecules, and their control regions.
Resected RNA pseudoknots and their recognition by histidyl-tRNA synthetase
Authors: Felden Brice , Giegé Richard
Published: July 2002

Duplexes constituted by closed or open RNA circles paired to single-stranded oligonucleotides terminating with 3′-CCA
OH
form resected pseudoknots that are substrates of yeast histidyl-tRNA synthetase. Design of this RNA fold is linked to the mimicry of the pseudoknotted amino acid accepting branch of the tRNA-like domain from brome mosaic virus, known to be charged by tyrosyl-tRNA synthetases, with RNA minihelices recapitulating accepting branches of canonical tRNAs. Prediction of the histidylation function of the new family of minimalist tRNA-like structures relates to the geometry of resected pseudoknots that allows proper presentation to histidyl-tRNA synthetase of analogues of the histidine identity determinants N-1 and N73 present in tRNAs. This geometry is such that the analogue of the major N-1 histidine determinant in the RNA circles faces the analogue of the discriminator N73 nucleotide in the accepting oligonucleotides. The combination of identity elements found in tRNA
His
species from archaea, eubacteria, and organelles (G-1/C73) is the most efficient for determining histidylation of the duplexes. The inverse combination (C-1/G73) leads to the worst histidine acceptors with charging efficiencies reduced by 2–3 orders of magnitude. Altogether, these findings open new perspectives for understanding evolution of tRNA identity and serendipitous RNA functions.
Construction and validation of yeast artificial chromosome contig maps by RecA-assisted restriction endonuclease cleavage
Authors: Lauer Peter , Schneider Sandra S. , Gnirke Andreas
Published: July 2002

RecA-assisted restriction endonuclease (RARE) cleavage is an “Achilles’ heel” approach to restriction mapping whereby a RecA-protein–oligodeoxynucleotide complex protects an individual restriction site from methylation, thus limiting subsequent digestion to a single, predetermined site. We have used RARE cleavage to cut yeast artificial chromosomes (YACs) at specific
Eco
RI sites located within or adjacent to sequence-tagged sites (STSs). Each cleavage reaction produces two YAC fragments whose sizes are a direct measure of the position of the STS in the YAC. In this fashion, we have positioned 45 STSs within a contig of 19 independent YACs and constructed a detailed RARE-cleavage map that represents 8.4 Mbp of human chromosome 6p21.3–22. By comparing maps of overlapping YACs, we were able to detect seven internal deletions that ranged from ≈75 kbp to ≈1 Mbp in size. Thirteen pairs of
Eco
RI sites were targeted for double RARE cleavage in uncloned total human DNA. The excised fragments, up to 2 Mbp in size, were resolved by pulsed-field gel electrophoresis and were detected by hybridization. In general, the genomic RARE-cleavage results support the YAC-based map. In one case, the distance in uncloned DNA between the two terminal
Eco
RI sites of a YAC insert was ≈1 Mbp larger than the YAC itself, indicating a major deletion. The general concept of RARE-cleavage mapping as well as its applications and limitations are discussed.
Regular and stochastic dynamics in the real quadratic family
Authors: Lyubich Mikhail
Published: July 2002

We prove the Regulat or Stochastic Conjecture for the real quadratic family which asserts that almost every real quadratic map

P
c
, c ∈

[−2, 1/4], has either an attracting cycle or an absolutely continuous invariant measure.
Compression, gain, and nonlinear distortion in an active cochlear model with subpartitions
Authors: Chadwick R. S.
Published: July 2002

The propagation of inhomogeneous, weakly nonlinear waves is considered in a cochlear model having two degrees of freedom that represent the transverse motions of the tectorial and basilar membranes within the organ of Corti. It is assumed that nonlinearity arises from the saturation of outer hair cell active force generation. I use multiple scale asymptotics and treat nonlinearity as a correction to a linear hydroelastic wave. The resulting theory is used to explain experimentally observed features of the response of the cochlear partition to a pure tone, including: the amplification of the response in a healthy cochlea vs a dead one; the less than linear growth rate of the response to increasing sound pressure level; and the amount of distortion to be expected at high and low frequencies at basal and apical locations, respectively. I also show that the outer hair cell nonlinearity generates retrograde waves.
Evidence for specific nucleocytoplasmic transport pathways used by leucine-rich nuclear export signals
Authors: Elfgang Claudia , Rosorius Olaf , Hofer Lotte , Jaksche Herbert , Hauber Joachim , Bevec Dorian
Published: July 2002

Various proteins with different biological activities have been observed to be translocated from the nucleus to the cytoplasm in an energy- and signal-dependent manner in eukaryotic cells. This nuclear export is directed by nuclear export signals (NESs), typically characterized by hydrophobic, primarily leucine, amino acid residues. Moreover, it has been shown that CRM1/exportin 1 is an export receptor for leucine-rich NESs. However, additional NES-interacting proteins have been described. In particular, eukaryotic initiation factor 5A (eIF-5A) has been shown to be a critical cellular cofactor for the nuclear export of the HIV type 1 (HIV-1) Rev trans-activator protein. In this study we compared the nuclear export activity of NESs of different origin. Microinjection of export substrates into the nucleus of somatic cells in combination with specific inhibitors indicated that specific nuclear export pathways exist for different NES-containing proteins. In particular, inhibition of eIF-5A blocked the nuclear export of NESs derived from the HIV-1 Rev and human T cell leukemia virus type I Rex trans-activators, whereas nucleocytoplasmic translocation of the protein kinase inhibitor-NES was unaffected. In contrast, however, inhibition of CRM1/exportin 1 blocked the nuclear export of all NES-containing proteins investigated. Our data confirm that CRM1/exportin 1 is a general export receptor for leucine-rich NESs and suggest that eIF-5A acts either upstream of CRM1/exportin 1 or forms a complex with the NES and CRM1/exportin 1 in the nucleocytoplasmic translocation of the HIV-1 Rev and human T cell leukemia virus type I Rex RNA export factors.
A chimeric prokaryotic ancestry of mitochondria and primitive eukaryotes
Authors: Karlin Samuel , Brocchieri Luciano , Mrázek Jan , Campbell Allan M. , Spormann Alfred M.
Published: July 2002

We provide data and analysis to support the hypothesis that the ancestor of animal mitochondria (Mt) and many primitive amitochondrial (a-Mt) eukaryotes was a fusion microbe composed of aClostridium-like eubacterium and aSulfolobus-like archaebacterium. The analysis is based on several observations: (i) The genome signatures (dinucleotide relative abundance values) ofClostridiumandSulfolobusare compatible (sufficiently similar) and each has significantly more similarity in genome signatures with animal Mt sequences than do all other available prokaryotes. That stable fusions may require compatibility in genome signatures is suggested by the compatibility of plasmids and hosts. (ii) The expanded energy metabolism of the fusion organism was strongly selective for cementing such a fusion. (iii) The molecular apparatus of endospore formation inClostridiumserves as raw material for the development of the nucleus and cytoplasm of the eukaryotic cell.
Phenotypic reversal of the
btn1
defects in yeast by chloroquine: A yeast model for Batten disease
Authors: Pearce David A. , Carr Carrie J. , Das Biswadip , Sherman Fred
Published: July 2002

BTN1
of
Saccharomyces cerevisiae
encodes an ortholog of
CLN3
, the human Batten disease gene. We have reported previously that deletion of
BTN1
,
btn1-
Δ, resulted in a pH-dependent resistance to
d
-(−)-threo-2-amino-1-[p-nitrophenyl]-1,3-propanediol (ANP). This phenotype was caused by
btn1-
Δ strains having an elevated ability to acidify growth medium through an elevated activity of the plasma membrane H
+
-ATPase, resulting from a decreased vacuolar pH during early growth. We have determined that growing
btn1-
Δ strains in the presence of chloroquine reverses the resistance to ANP, decreases the rate of medium acidification, decreases the activity of plasma membrane H
+
-ATPase, and elevates vacuolar pH. However, an additional effect of this phenotypic reversal is that activity of plasma membrane H
+
-ATPase is decreased further and vacuolar pH is increased further as
btn1-
Δ strains continue to grow. This phenotypic reversal of
btn1-
Δ can be considered for developing a therapy for Batten disease.
In vitro
synthesis of the nucleotide loop of cobalamin by
Salmonella typhimurium
enzymes
Authors: Maggio-Hall Lori A. , Escalante-Semerena Jorge C.
Published: July 2002

In
Salmonella typhimurium
, the CobU, CobS, CobT, and CobC proteins have been proposed to catalyze the late steps in adenosylcobalamin biosynthesis, which define the nucleotide loop assembly pathway. This paper reports the
in vitro
assembly of the nucleotide loop of adenosylcobalamin from its precursors adenosylcobinamide, 5,6-dimethylbenzimidazole, nicotinate mononucleotide, and GTP. Incubation of these precursors with the CobU, CobS, and CobT proteins resulted in the synthesis of adenosylcobalamin−5′-phosphate. This cobamide was isolated by HPLC, identified by UV-visible spectroscopy and mass spectrometry, and shown to support growth of a cobalamin auxotroph. Adenosylcobalamin−5′-phosphate was also isolated from reaction mixtures containing adenosylcobinamide-GDP (the product of the CobU reaction) and α-ribazole-5′-phosphate (the product of the CobT reaction) as substrates and CobS. These results allowed us to conclude that CobS is the cobalamin(-5′-phosphate) synthase enzyme in
S. typhimurium
. The CobC enzyme, previously shown to dephosphorylate α-ribazole-5′-phosphate to α-ribazole, was shown to dephosphorylate adenosylcobalamin−5′-phosphate to adenosylcobalamin. Adenosylcobinamide was converted to adenosylcobalamin in reactions where all four enzymes were present in the reaction mixture. This
in vitro
system offers a unique opportunity for the rapid synthesis and isolation of cobamides with structurally different lower-ligand bases that can be used to investigate the contributions of the lower-ligand base to cobalamin-dependent reactions.
Opening of a monomer-monomer interface of the trimeric bacteriophage T4-coded GP45 sliding clamp is required for clamp loading onto DNA
Authors: Latham Gary J. , Dong Feng , Pietroni Paola , Dozono Jody M. , Bacheller Daniel J. , von Hippel Peter H.
Published: July 2002

The replication system of bacteriophage T4 uses a trimeric ring-shaped processivity clamp (gp45) to tether the replication polymerase (gp43) to the template-primer DNA. This ring is placed onto the DNA by an ATPase-driven clamp-loading complex (gp44/62) where it then transfers, in closed form, to the polymerase. It generally has been assumed that one of the functions of the loading machinery is to open the clamp to place it around the DNA. However, the mechanism by which this occurs has not been fully defined. In this study we design and characterize a double-mutant gp45 protein that contains pairs of cysteine residues located at each monomer-monomer interface of the trimeric clamp. This mutant protein is functionally equivalent to wild-type gp45. However, when all three monomer-monomer interfaces are tethered by covalent crosslinks formed (reversibly or irreversibly) between the cysteine pairs these closed clamps can no longer be loaded onto the DNA nor onto the polymerase, effectively eliminating processive strand-displacement DNA synthesis. Analysis of the individual steps of the clamp-loading process shows that the ATPase-dependent interactions between the clamp and the clamp loader that precede DNA binding are hyperstimulated by the covalently crosslinked ring, suggesting that binding of the closed ring induces a futile, ATP-driven, ring-opening cycle. These findings and others permit further characterization and ordering of the steps involved in the T4 clamp-loading process.
Chromosome regions between centromeres and proximal crossovers are the physical sites of major effect loci for yield in potato: Genetic analysis employing meiotic mutants
Authors: Buso J. A. , Boiteux L. S. , Tai G. C. C. , Peloquin S. J.
Published: July 2002

Meiotic mutant (2n) gametes formed by first-division restitution without crossover (FDR-NCO) are expected to be superior to FDR with crossover (FDR-CO) because they transmit to the progeny, without disruption by recombination, almost 100% of the parental genotype. FDR-CO transfers ≈80% of the parental heterozygosity and a large fraction of the epistatic interactions. Another genetic expectation associated with both FDR gametes is their equivalence for the phenotypic expression of traits controlled by genes residing between centromeres and proximal crossover sites. This set of unique cytogenetic features of FDR mutants was employed here as a tool to infer physical location of quantitative trait loci controlling total tuber yield (TTY) in potato. Two assays were conducted to verify the superiority of FDR-NCO over FDR-CO gametes for TTY by using progenies from 4x–2x factorial crosses. Male clones were 2n-pollen producers by either FDR-CO or FDR-NCO mechanisms. Compared with the 4x parents, TTY of the progenies ranged from 41% to 175% (i.e., high-parent heterosis). However, no significant TTY differences were observed between FDR-CO and FDR-NCO families. In addition, the size of variance components of males was smaller than females and near zero. Our results reinforce the hypothesis that genes controlling yielding ability have a predominant physical location between centromeres and proximal chiasmata. Quantitative trait loci in chromosome regions with reduced levels of recombination may provide a partial explanation for the slow progress in increasing TTY through conventional 4x–4x crosses and for the often high degree of heterosis obtained by introgressing genetic diversity via 4x–2x crosses in potato.
HIV-1 Gag shares a signature motif with annexin (Anx7), which is required for virus replication
Authors: Srivastava M. , Cartas M. , Rizvi T. A. , Singh S. P. , Serio D. , Kalyanaraman V. S. , Pollard H. B. , Srinivasan A.
Published: July 2002

Genetic and biochemical analyses of the Gag protein of HIV-1 indicate a crucial role for this protein in several functions related to viral replication, including viral assembly. It has been suggested that Gag may fulfill some of the functions by recruiting host cellular protein(s). In our effort to identify structural and functional homologies between Gag and cellular cytoskeletal and secretory proteins involved in transport, we observed that HIV-1 Gag contains a unique PGQM motif in the capsid region. This motif was initially noted in the regulatory domain of synexin the membrane fusion protein of
Xenopus laevis
. To evaluate the functional significance of the highly conserved PGQM motif, we introduced alanine (A) in place of individual residues of the PGQM and deleted the motif altogether in a Gag expression plasmid and in an HIV-1 proviral DNA. The proviral DNA containing mutations in the PGQM motif showed altered expression, assembly, and release of viral particles in comparison to parental (NL4-3) DNA. When tested in multiple- and single-round replication assays, the mutant viruses exhibited distinct replication phenotypes; the viruses containing the A for the G and Q residues failed to replicate, whereas A in place of the P and M residues did not inhibit viral replication. Deletion of the tetrapeptide also resulted in the inhibition of replication. These results suggest that the PGQM motif may play an important role in the infection process of HIV-1 by facilitating protein–protein interactions between viral and/or viral and cellular proteins.
Phenomenological theory of mortality evolution: Its singularities, universality, and superuniversality
Authors: Azbel’ Mark Ya.
Published: July 2002

The probability to survive to the agexuniversally increases with the mean lifespanx̄. For species as remote as humans and flies, for a givenxthe rate of its evolution withx̄is constant, except for the narrow vicinity of a certainx̄=x* (which equals 75 years for humans and 32 days for flies and which is independent of age, population, and living conditions). Atx̄≅x* the evolution rate jumps to a different value. Its next jump is predicted atx̄≅ 87 years for humans and ≅ 59 days for flies. Such singularities are well known in physics and mathematics as phase transitions. In the considered case different population “phases” have significantly different survival evolution rates. The evolution is rapid—life expectancy may double within a lifespan of a single generation. Survival probability depends on agexand mean longevityx̄only (for instance, survival curves of 1896 Swedes and 1947 Japanese with approximately equalx̄are very close, although they are related to different races in different countries at different periods in their different history.) With no adjustable parameters, its presented universal law quantitatively agrees with all lifetable data. According to this law, the impact of all factors but age reduces to the mean lifespan only. In advanced and old age, this law is superuniversal—it is approximately the same for species as remote as humans and flies. It yields survival probability that linearly depends on the mean lifespanx̄. As a result, when humanx̄almost doubles (from 35.5 to 69.3 years), life expectancy at 70 years increases from 8 to 9.5 years only. Other implications of the universal law are also considered.
Observing the epoch of galaxy formation
Authors: Steidel Charles C.
Published: July 2002

Significant observational progress
in addressing the question of the origin and early evolution of
galaxies has been made in the past few years, allowing for direct
comparison of the epoch when most of the stars in the universe were
forming to prevailing theoretical models. There is currently broad
consistency between theoretical expectations and the observations, but
rapid improvement in the data will provide much more critical tests of
theory in the coming years.
Molecular cytogenetic dissection of human chromosomes 3 and 21 evolution
Authors: Müller S. , Stanyon R. , Finelli P. , Archidiacono N. , Wienberg J.
Published: July 2002

Chromosome painting in placental mammalians illustrates that genome evolution is marked by chromosomal synteny conservation and that the association of chromosomes 3 and 21 may be the largest widely conserved syntenic block known for mammals. We studied intrachromosomal rearrangements of the syntenic block 3/21 by using probes derived from chromosomal subregions with a resolution of up to 10–15 Mbp. We demonstrate that the rearrangements visualized by chromosome painting, mostly translocations, are only a fraction of the actual chromosomal changes that have occurred during evolution. The ancestral segment order for both primates and carnivores is still found in some species in both orders. From the ancestral primate/carnivore condition an inversion is needed to derive the pig homolog, and a fission of chromosome 21 and a pericentric inversion is needed to derive the Bornean orangutan condition. Two overlapping inversions in the chromosome 3 homolog then would lead to the chromosome form found in humans and African apes. This reconstruction of the origin of human chromosome 3 contrasts with the generally accepted scenario derived from chromosome banding in which it was proposed that only one pericentric inversion was needed. From the ancestral form for Old World primates (now found in the Bornean orangutan) a pericentric inversion and centromere shift leads to the chromosome ancestral for all Old World monkeys. Intrachromosomal rearrangements, as shown here, make up a set of potentially plentiful and informative markers that can be used for phylogenetic reconstruction and a more refined comparative mapping of the genome.
Amblyopes see true alignment where normal observers see illusory tilt
Authors: Popple Ariella V. , Levi Dennis M.
Published: July 2002

Amblyopia (“lazy eye”) is an impairment in visual
acuity resulting from abnormal neural development in the visual cortex.
We tested the responses of ten amblyopic and six normal observers to
illusions of perceived orientation in textures of Gabor patches: the
“Fraser illusion,” the “phase illusion,” and a “tilted
chain” illusion. The illusory tilt of the stimulus rows was matched
by actual tilt in the opposite direction by using the method of
constant stimuli. Amblyopes showed a significant increase in the Fraser
illusion, a decrease in the phase illusion, and a reversal of the
tilted chain illusion. Amblyopic performance could be simulated in
normal observers by reducing the length of the rows. These results can
be modeled by a theory which places the neural abnormality in amblyopia
at the level of second stage grouping processes. Additionally, the
illusions might be useful in the early diagnosis of amblyopia without
the need for prior refractive correction.
Role of microtubules in the intracellular distribution of tobacco mosaic virus movement protein
Authors: Más Paloma , Beachy Roger N.
Published: July 2002

Despite its central role in virus infection, little is known
about the mechanisms of intracellular trafficking of virus components
within infected cells. In this study, we followed the dynamics of
tobacco mosaic virus movement protein (MP) distribution in living
protoplasts after disruption of microtubules (MTs) by cold treatment
and subsequent rewarming to 29°C. At early stages of infection, cold
treatment (4°C) caused the accumulation of MP fused to green
fluorescent protein (GFP) in large virus replication bodies that
localized in perinuclear positions, whereas at midstages of infection,
the association of MP:GFP with MTs was disrupted. Rewarming the
protoplasts to 29°C reestablished the association of MTs with the
replication bodies that subsequently spread throughout the cytoplasm
and to the periphery of the cell. The role of MTs in the intracellular
distribution of the MP also was analyzed by examining the distribution
pattern of a nonfunctional mutant of MP (TAD5). Like MP:GFP, TAD5:GFP
interacted with the endoplasmic reticulum membranes and colocalized
with its viral RNA but did not colocalize with MTs. The involvement of
MTs in the intracellular distribution of tobacco mosaic virus MP is
discussed.
Task Specificity in the Use of Words in Mathematics: Evidence from Bilingual Problem Solvers
Authors: Bernardo Allan B.I.
Published: July 2002

Mathematics is often said to be a different language in itself. Three experiments were conducted to show some evidence for this common notion. It was hypothesized that in math word problem solving, people interpret words like “more” and “less” in specialized ways that are specific to the task of math word problem solving. Subjects were given texts with quantitative information, but the texts were framed either as math problems or as stories, and were written either in English or Filipino. Subjects were then asked to verify statements that describe quantitative relations given in the text; these relations either stated an exact or an inexact quantitative difference. The verification responses and verification times in three experiments show that subjects more often accepted the inexact difference as true when the text was framed as a story compared to when framed as a problem. These results support the hypothesis that the use of the specialized meaning is specific to the task of solving word problems in math. The data were equivocal about the role of the language used in the operation of this knowledge. The results were discussed in terms of the implications of specificity of knowledge, context sensitivity, and the possible role of language use in the process of learning and developing mathematical knowledge.
Short‐term Memory in Time Interval Production
Authors: Fortin Claudette
Published: July 2002

This article summarizes results from several studies on the effect of nontemporal processing on concurrent time estimation. These studies use an experimental paradigm that was developed to interpolate various nontemporal tasks in time interval production. Produced intervals were specifically lengthened by increasing the amount of short‐term memory processing performed in a concurrent search task. The interference was shown with many short‐term memory tasks, using various durations and methods in the temporal task. The effect on temporal production seems to be positively related to the level of difficulty of the short‐term memory task. Finally, processing item or order information affects simultaneous time production, whereas its maintenance has no effect. An interference analysis of these phenomena suggests that interruption in time estimation is caused by both temporal and nontemporal tasks simultaneously requiring processing in short‐term memory.
Within‐class Ability Grouping: Placement of pupils in groups and self‐concept
Authors: MacIntyre Helen , Ireson Judith
Published: July 2002

Abstract With the introduction of the literacy and numeracy hours, children are being grouped by ability within the primary classroom. Within‐class ability grouping is seen as a means of raising attainment that avoids the social and emotional disadvantages of streaming. This research examined within‐class grouping for mathematics in six classes in one primary school. The aim of the research was to examine whether pupils' placement in ability groups was consistent with their ability, as indicated by a standardised test, and to explore the relationships between pupils' self‐concepts, their mathematical ability and their placement in groups. The sample consisted of 145 children in years 3 to 5. Standardised mathematics test scores and a measure of self‐concept were collected for each child. Teachers provided information about the ability groups in their classes. Seven children were selected for interview on the basis of their mathematics self‐concept scores. The analysis revealed considerable overlap between the standardised test scores of children in the high‐, middle‐ and low‐ability groups. There was a significant but weak correlation between mathematics ability and mathematics self‐concept. The interviews revealed that children whose self‐concept scores were consonant with their ability group thought they had been correctly placed, but those with discrepant scores were less happy. The implications of the findings are discussed in relation the salience of ability grouping within the classroom.
The Anatomy of an International Cartel: Cyanide, 1897-1927
Authors: Lougheed Alan
Published: July 2002

The development of a new product or a new process, if adopted by the market, may generate a number of economic processes including secondary innovations to promote the exploitation of the new discovery. Such technological advances may also promote new industrial ventures which may exist over many decades, enhancing economic development. The history of the adoption of the cyanide process for the extraction of gold from its ores exemplifies such developments. One outcome was the formation of an international cyanide cartel.
How does syringe distribution in prison affect consumption of illegal drugs by prisoners?
Authors: NELLES JOACHIM , FUHRER ANDREAS , HIRSBRUNNER HANS PETER
Published: July 2002

Drug injection and syringe sharing is common among IDUs in prison. As a consequence, the prevalence of blood‐borne viral infections is several‐fold higher in prison than in the corresponding communities. Prisoners have been denied access to syringe exchange programmes, even though they have been proven to be highly effective in community settings. A 12‐month harm reduction programme which included syringe exchange was introduced into the only female prison (Hindelbank) in Switzerland. The programme was studied for 12 months (pilot phase). After the programme was completed, there was follow‐up 12 months later (follow‐up phase). Baseline data were collected on 137 of 161 prisoners. Follow up‐data were collected on 57 of 64 prisoners. Participants were interviewed several times about their use and injection of drugs and their shared use of syringes. Additional data on the number of syringes exchanged were also collected. Reports of drug use and injection in prison did not increase. The exchange of syringes was related to drug availability. Frequency of drug use increased in relation to duration of incarceration. Frequency of drug use decreased the longer the project had been implemented. None of the main arguments raised against the introduction of syringe distribution into prison, such as assault or an increase in drug injecting, was evident in this study. The results, although limited by the nature and the size of the prison, suggest that syringe exchange has a role in the prison setting.
New laboratory tests in acute pancreatitis
Authors: Kylänpää‐Bäck MARJA‐LEENA , REPO HEIKKI , KEMPPAINEN ESKO
Published: July 2002

Abstract Acute pancreatitis (AP) is a common disease with wide variation of severity. The diagnosis of AP is usually based on high serum amylase or lipase values but the accuracy of these methods is considered unsatisfactory. One in five of the patients develops a severe disease and carries a considerable risk of development of organ failure and high mortality. Early detection of patients with severe AP and especially those with increased risk of organ failure is importance since such patients seem to benefit from treatment in an intensive care unit started as soon as possible after presentation. In addition to enzymological methods, increasing interest has been focused on laboratory markers reflecting the level of inflammatory response in AP. At present, in routine clinical work the most commonly used severity marker is serum C‐reactive protein, the concentration of which rises too slowly to be used for early prediction of severity. New therapies aiming at modifying the course of systemic inflammation in AP are being developed and therefore monitoring the patient's immune inflammatory status is needed. In this review article we present the current knowledge of laboratory tests, which has been evaluated for diagnostic and prognostic purposes in AP.
Involvement of CNS cholinergic systems in alcohol drinking of P rats
Authors: KATNER S. N. , McBRIDE W. J. , LUMENG L. , LI T.‐K. , MURPHY J. M.
Published: July 2002

Abstract Experiments were undertaken to determine if CNS muscarinic‐ and nicotinic‐cholinergic receptors are involved in regulating alcohol drinking of rats from the selectively‐bred alcohol‐preferring P line. Intracerebroventricular (i.c.v.) drug infusions were administered into the lateral ventricle of female P rats 15 minutes before ethanol access. The muscarinic antagonists pirenzepine and scopolamine were tested on limited access (4 hours/day) to a 10% (v/v) ethanol solution. Food and water were available ad libitum. Nicotine and the nicotinic antagonist mecamylamine were tested on limited access (4 hours/day) to 10% (v/v) ethanol and 0.0125% saccharin solutions. Food was available ad libitum and water was available during the remaining 20 hours. The baseline ethanol intakes ranged between an average of 3.0 ± 0.3 g/kg/4 hours and 3.4 ± 0.3 g/kg/4 hours. Administration of 40‐100 m g pirenzepine (M1‐selective antagonist) had no effect on ethanol, food or water consumption. However, 20‐80 m g scopolamine, a non‐selective muscarinic antagonist, dosedependently decreased ethanol intake as much as 60% (p < 0.05) without altering food or water consumption. The nicotinic antagonist mecamylamine (20‐120 m g) did not alter ethanol intake, but nicotine (40‐80 m g) dose‐dependently decreased ethanol drinking as much as 60% within the first 30 minutes (p < 0.05) without an effect on saccharin intake. The results suggest that: (a), muscarinic receptors, with the possible exception of the M1 subtype, are involved in regulating alcohol drinking and (b), activation of nicotinic receptors can reduce alcohol drinking of the P line of rats.
Mutations in the Essential Spindle Checkpoint Gene bub1 Cause Chromosome Missegregation and Fail to Block Apoptosis in Drosophila
Authors: Basu Joydeep , Bousbaa Hassan , Logarinho Elsa , Li ZeXiao , Williams Byron C. , Lopes Carla , Sunkel Claudio E. , Goldberg Michael L.
Published: July 2002

We have characterized the Drosophila mitotic checkpoint control protein Bub1 and obtained mutations in the bub1 gene. Drosophila Bub1 localizes strongly to the centromere/kinetochore of mitotic and meiotic chromosomes that have not yet reached the metaphase plate. Animals homozygous for P-element–induced, near-null mutations of bub1 die during late larval/pupal stages due to severe mitotic abnormalities indicative of a bypass of checkpoint function. These abnormalities include accelerated exit from metaphase and chromosome missegregation and fragmentation. Chromosome fragmentation possibly leads to the significantly elevated levels of apoptosis seen in mutants.

We have also investigated the relationship between Bub1 and other kinetochore components. We show that Bub1 kinase activity is not required for phosphorylation of 3F3/2 epitopes at prophase/prometaphase, but is needed for 3F3/2 dephosphorylation at metaphase. Neither 3F3/2 dephosphorylation nor loss of Bub1 from the kinetochore is a prerequisite for anaphase entry. Bub1's localization to the kinetochore does not depend on the products of the genes zw10, rod, polo, or fizzy, indicating that the kinetochore is constructed from several independent subassemblies.