bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering a neural code for vision
Authors: Passaglia Christopher , Dodge Frederick , Herzog Erik , Jackson Scott , Barlow Robert
Published: July 2002

Deciphering the information that eyes, ears, and other sensory organs transmit to the brain is important for understanding the neural basis of behavior. Recordings from single sensory nerve cells have yielded useful insights, but single neurons generally do not mediate behavior; networks of neurons do. Monitoring the activity of all cells in a neural network of a behaving animal, however, is not yet possible. Taking an alternative approach, we used a realistic cell-based model to compute the ensemble of neural activity generated by one sensory organ, the lateral eye of the horseshoe crab,
Limulus polyphemus
. We studied how the neural network of this eye encodes natural scenes by presenting to the model movies recorded with a video camera mounted above the eye of an animal that was exploring its underwater habitat. Model predictions were confirmed by simultaneously recording responses from single optic nerve fibers of the same animal. We report here that the eye transmits to the brain robust “neural images” of objects having the size, contrast, and motion of potential mates. The neural code for such objects is not found in ambiguous messages of individual optic nerve fibers but rather in patterns of coherent activity that extend over small ensembles of nerve fibers and are bound together by stimulus motion. Integrative properties of neurons in the first synaptic layer of the brain appear well suited to detecting the patterns of coherent activity. Neural coding by this relatively simple eye helps explain how horseshoe crabs find mates and may lead to a better understanding of how more complex sensory organs process information.
Twist grain boundaries in three-dimensional lamellar Turing structures
Authors: De Wit A. , Borckmans P. , Dewel G.
Published: July 2002

Steady spatial self-organization of three-dimensional chemical reaction-diffusion systems is discussed with the emphasis put on the possible defects that may alter the Turing patterns. It is shown that one of the stable defects of a three-dimensional lamellar Turing structure is a twist grain boundary embedding a Scherk minimal surface.
Molecular characterization of four induced alleles at the
Ednrb
locus
Authors: Shin Myung K. , Russell Liane B. , Tilghman Shirley M.
Published: July 2002

The
piebald
locus on mouse chromosome 14 encodes the endothelin-B receptor (EDNRB), a G protein-coupled, seven-transmembrane domain protein, which is required for neural crest-derived melanocyte and enteric neuron development. A spontaneous null allele of
Ednrb
results in homozygous mice that are predominantly white and die as juveniles from megacolon. To identify the important domains for EDNRB function, four recessive juvenile lethal alleles created by either radiation or chemical mutagens (
Ednrb
27Pub
,
Ednrb
17FrS
,
Ednrb
1Chlc
, and
Ednrb
3Chlo
) were examined at the molecular level.
Ednrb
27Pub
mice harbor a mutation at a critical proline residue in the fifth transmembrane domain of the EDNRB protein. A gross genomic alteration within the
Ednrb
gene in
Ednrb
3Chlo
results in the production of aberrantly sized transcripts and no authentic
Ednrb
mRNA.
Ednrb
17FrS
mice exhibited a decreased level of
Ednrb
mRNA, supporting previous observations that the degree of spotting in
piebald
mice is dependent on the amount of EDNRB expressed. Finally, no molecular defect was detected in
Ednrb
1Chlc
mice, which produce normal levels of
Ednrb
mRNA in adult brain, suggesting that the mutation affects important regulatory elements that mediate the expression of the gene during development.
Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats
Authors: Chen Zheng-Wang , Ahren Bo , Östenson Claes-Göran , Cintra Antonio , Bergman Tomas , Möller Christer , Fuxe Kjell , Mutt Viktor , Jörnvall Hans , Efendic Suad
Published: July 2002

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern –KR–KK–GKR– has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion
in vivo
at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.
In vitro
selection for altered divalent metal specificity in the RNase P RNA
Authors: Frank Daniel N. , Pace Norman R.
Published: July 2002

The ribozyme RNase P absolutely requires divalent metal ions for catalytic function. Multiple Mg
2+
ions contribute to the optimal catalytic efficiency of RNase P, and it is likely that the tertiary structure of the ribozyme forms a specific metal-binding pocket for these ions within the active-site. To identify base moieties that contribute to catalytic metal-binding sites, we have used
in vitro
selection to isolate variants of the
Escherichia coli
RNase P RNA with altered specificities for divalent metal. RNase P RNA variants with increased activity in Ca
2+
were enriched over 18 generations of selection for catalysis in the presence of Ca
2+
, which is normally disfavored relative to Mg
2+
. Although a wide spectrum of mutations was found in the generation-18 clones, only a single point mutation was common to all clones: a cytosine-to-uracil transition at position 70 (
E. coli
numbering) of RNase P. Analysis of the C70U point mutant in a wild-type background confirmed that the identity of the base at position 70 is the sole determinant of Ca
2+
selectivity. It is noteworthy that C70 lies within the phylogenetically well conserved J3/4-P4-J2/4 region, previously implicated in Mg
2+
binding. Our finding that a single base change is sufficient to alter the metal preference of RNase P is further evidence that the J3/4-P4-J2/4 domain forms a portion of the ribozyme’s active site.
The structure and function of a soybean β-glucan-elicitor-binding protein
Authors: Umemoto Naoyuki , Kakitani Makoto , Iwamatsu Akihiro , Yoshikawa Masaaki , Yamaoka Naoto , Ishida Isao
Published: July 2002

β-Glucan elicitor (GE), released from the cell wall of the phytopathogenic fungusPhytophthora megaspermaby soybean glucanases, causes defense reactions in soybean. A GE-binding protein (GEBP) was purified from the membrane fraction of soybean root cells, and its cDNA was isolated. Expression of the cDNA clone in tobacco suspension cultured cells and inEscherichia coliconferred GE-binding activity to both. An antibody against the recombinant protein was found to inhibit the GE binding with the soybean cotyledon membrane fraction as well as the resulting accumulation of phytoalexin. Immunolocalization assays indicated that the GEBPs are located in the plasma membrane of root cells. These results suggest that the cDNA encodes a GE receptor and may mediate the signaling of the elicitor.
Targeting E2F1–DNA complexes with microgonotropen DNA binding agents
Authors: Chiang Shu-Yuan , Bruice Thomas C. , Azizkhan Jane C. , Gawron Loretta , Beerman Terry A.
Published: July 2002

Microgonotropen (MGT) DNA binding drugs, which consist of an A+T-selective DNA minor groove binding tripyrrole peptide and polyamine chains attached to a central pyrrole that extend drug contact into the DNA major groove, were found to be extraordinarily effective inhibitors of E2 factor 1 (E2F1) association with its DNA promoter element (5′-TTTCGCGCCAAA). The most active of these drugs, MGT-6a, was three orders of magnitude more effective than distamycin and inhibited complexes between E2F1 and the dihydrofolate reductase promoter by 50% at 0.00085 μM. A relationship was found between the measured equilibrium constants for binding of MGTs to the A+T region of d(GGCGA
3
T
3
GGC)/d(CCGCT
3
A
3
CCG) and their inhibition of complex formation between E2F1 and the DNA promoter element. A representative of the potent MGT inhibitors was significantly more active on inhibition of E2F1–DNA complex formation compared with disruption of a preexisting complex.
Galaxies and large scale structure at high redshifts
Authors: Steidel Charles C.
Published: July 2002

It is now straightforward to assemble large samples of very high
redshift (
z
∼ 3) field galaxies selected by their
pronounced spectral discontinuity at the rest frame Lyman limit of
hydrogen (at 912 Å). This makes possible both statistical analyses of
the properties of the galaxies and the first direct glimpse of the
progression of the growth of their large-scale distribution at such an
early epoch. Here I present a summary of the progress made in these
areas to date and some preliminary results of and future plans for a
targeted redshift survey at
z
= 2.7–3.4. Also
discussed is how the same discovery method may be used to obtain a
“census” of star formation in the high redshift Universe, and the
current implications for the history of galaxy formation as a function
of cosmic epoch.
Globular clusters, Hipparcos, and the age of the galaxy
Authors: Reid Neill
Published: July 2002

We discuss the impact of the results from the recent Hipparcos
astrometric satellite on distance estimates of galactic globular
clusters. Recalibrating the clusters not only implies a relatively
small change in the distance to the Large Magellanic Cloud, and hence a
rescaling of several estimates of the Hubble constant, but also leads
to significantly younger cluster ages. Although the data are not yet
conclusive, the results so far point to a likely resolution of the
apparent paradox of a universe younger than its constituents, without
requiring significant modifications to simple cosmological models.
A novel yeast protein influencing the response of RNA polymerase II to transcriptional activators
Authors: Emili Andrew , Kobayashi Ryuji , Ingles C. James
Published: July 2002

A sensitive
in vitro
crosslinking technique using a photoactive derivative of the chimeric activator LexA-E2F-1 was used to identify yeast proteins that might influence the response of RNA polymerase II to transcriptional activators. We found that a novel yeast protein, Xtc1p, could be covalently crosslinked to the activation domain of LexA-E2F-1 when this derivatized activator was bound to DNA upstream of an activator-responsive RNA polymerase II promoter. Because affinity chromatography experiments showed that Xtc1p also bound directly and specifically to the activation domains of E2F-1, the viral activator VP16, and the yeast activator Gal4p and copurified with the RNA polymerase II holoenzyme complex, Xtc1p may modulate the response of RNA polymerase II to multiple activators. Consistent with this notion, yeast strains deleted for the
XTC1
gene exhibited pleiotropic growth defects, including temperature sensitivity, galactose auxotrophy, and a heightened sensitivity to activator overexpression, as well as an altered response to transcriptional activators
in vivo
.
GIPC, a PDZ domain containing protein, interacts specifically with the C terminus of RGS-GAIP
Authors: De Vries Luc , Lou Xiaojing , Zhao Grace , Zheng Bin , Farquhar Marilyn Gist
Published: July 2002

We have identified a mammalian protein called GIPC (for GAIP interacting protein, C terminus), which has a central PDZ domain and a C-terminal acyl carrier protein (ACP) domain. The PDZ domain of GIPC specifically interacts with RGS-GAIP, a GTPase-activating protein (GAP) for Gα
i
subunits recently localized on clathrin-coated vesicles. Analysis of deletion mutants indicated that the PDZ domain of GIPC specifically interacts with the C terminus of GAIP (11 amino acids) in the yeast two-hybrid system and glutathione
S
-transferase (GST)-GIPC pull-down assays, but GIPC does not interact with other members of the RGS (regulators of G protein signaling) family tested. This finding is in keeping with the fact that the C terminus of GAIP is unique and possesses a modified C-terminal PDZ-binding motif (SEA). By immunoblotting of membrane fractions prepared from HeLa cells, we found that there are two pools of GIPC–a soluble or cytosolic pool (70%) and a membrane-associated pool (30%). By immunofluorescence, endogenous and GFP-tagged GIPC show both a diffuse and punctate cytoplasmic distribution in HeLa cells reflecting, respectively, the existence of soluble and membrane-associated pools. By immunoelectron microscopy the membrane pool of GIPC is associated with clusters of vesicles located near the plasma membrane. These data provide direct evidence that the C terminus of a RGS protein is involved in interactions specific for a given RGS protein and implicates GAIP in regulation of additional functions besides its GAP activity. The location of GIPC together with its binding to GAIP suggest that GAIP and GIPC may be components of a G protein-coupled signaling complex involved in the regulation of vesicular trafficking. The presence of an ACP domain suggests a putative function for GIPC in the acylation of vesicle-bound proteins.
Clonal heterogeneity at allelic methylation sites diagnostic for Prader–Willi and Angelman syndromes
Authors: LaSalle Janine M. , Ritchie Rachael J. , Glatt Heather , Lalande Marc
Published: July 2002

Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are developmental disorders resulting from the absence of the paternal or maternal contribution to the 15q11–13 region, respectively. Allele-specific methylation at D15S63 (PW71) has routinely been used as a diagnostic indicator of PWS and AS in DNA samples derived from peripheral blood. Extensive variation in allele-specific methylation patterns, however, has been observed at this site in different tissues, but the frequency or mechanism of this variation has remained uncharacterized. Herein, we have investigated the cellular basis of variation in methylation patterns at four sites of allelic methylation near
SNRPN
by using DNA samples derived from a panel of primary T lymphocyte clones. Interclonal variability was observed at three of these sites, including the diagnostic PW71 site. Changes in allele-specific methylation patterns occurred at a frequency of about one change in 50% of the cells every 22–25 doublings. In contrast, stable allele-specific methylation was observed in these clonal populations at exon 1 of
SNRPN
and the androgen receptor locus on the inactive X chromosome, suggesting that methylation at some CpG sites is more faithfully maintained than others. Clonal heterogeneity at PW71 was not an artifact of cell culture because the absence of allelic methylation was also observed in about 20% of the alleles in unstimulated peripheral blood. These results demonstrate that variation in allele-specific methylation at PW71 and other sites in the PWS/AS region appear to depend on the clonal complexity of the particular tissue and on the lack of strict maintenance of methylation within clones.
GTP bound to chloroplast thylakoid membranes is required for light-induced, multienzyme degradation of the photosystem II D1 protein
Authors: Spetea Cornelia , Hundal Torill , Lohmann Felix , Andersson Bertil
Published: July 2002

Even though light is the driving force in photosynthesis, it also can be harmful to plants. The water-splitting photosystem II is the main target for this light stress, leading to inactivation of photosynthetic electron transport and photooxidative damage to its reaction center. The plant survives through an intricate repair mechanism involving proteolytic degradation and replacement of the photodamaged reaction center D1 protein. Based on experiments with isolated chloroplast thylakoid membranes and photosystem II core complexes, we report several aspects concerning the rapid turnover of the D1 protein. (
i
) The primary cleavage step is a GTP-dependent process, leading to accumulation of a 23-kDa N-terminal fragment. (
ii
) Proteolysis of the D1 protein is inhibited below basal levels by nonhydrolyzable GTP analogues and apyrase treatment, indicating the existence of endogenous GTP tightly bound to the thylakoid membrane. This possibility was corroborated by binding studies. (
iii
) The proteolysis of the 23-kDa primary degradation fragment (but not of the D1 protein) is an ATP- and zinc-dependent process. (
iv
) D1 protein degradation is a multienzyme event involving a strategic (primary) protease and a cleaning-up (secondary) protease. (
v
) The chloroplast FtsH protease is likely to be involved in the secondary degradation steps. Apart from its significance for understanding the repair of photoinhibition, the discovery of tightly bound GTP should have general implications for other regulatory reactions and signal transduction pathways associated with the photosynthetic membrane.
Calexcitin transformation of GABAergic synapses: From excitation filter to amplifier
Authors: Sun Miao-Kun , Nelson Thomas J. , Xu Hui , Alkon Daniel L.
Published: July 2002

Encoding an experience into a lasting memory is thought to involve an altered operation of relevant synapses and a variety of other subcellular processes, including changed activity of specific proteins. Here, we report direct evidence that co-applying (associating) membrane depolarization of rat hippocampal CA1 pyramidal cells with intracellular microinjections of calexcitin (CE), a memory-related signaling protein, induces a long-term transformation of inhibitory postsynaptic potentials from basket interneurons (BAS) into excitatory postsynaptic potentials. This synaptic transformation changes the function of the synaptic inputs from excitation filter to amplifier, is accompanied by a shift of the reversal potential of BAS–CA1 postsynaptic potentials, and is blocked by inhibiting carbonic anhydrase or antagonizing ryanodine receptors. Effects in the opposite direction are produced when anti-CE antibody is introduced into the cells, whereas heat-inactivated CE and antibodies are ineffective. These data suggest that CE is actively involved in shaping BAS–CA1 synaptic plasticity and controlling information processing through the hippocampal networks.
The past and the future fate of the universe and the formation of structure in it
Authors: Rix Hans-Walter
Published: July 2002

The history and the ultimate future fate of the universe as
a whole depend on how much the expansion of the universe is decelerated
by its own mass. In particular, whether the expansion of the universe
will ever come to a halt can be determined from the past expansion.
However, the mass density in the universe does not only govern the
expansion history and the curvature of space, but in parallel also
regulates the growth of hierarchical structure, including the collapse
of material into the dense, virialized regions that we identify with
galaxies. Hence, the formation of galaxies and their clustered
distribution in space depend not only on the detailed physics of how
stars are formed but also on the overall structure of the universe.
Recent observational efforts, fueled by new large, ground-based
telescopes and the Hubble Space Telescope, combined with theoretical
progress, have brought us to the verge of determining the expansion
history of the universe and space curvature from direct observation and
to linking this to the formation history of galaxies.
Composite fermions and bosons: An invitation to electron masquerade in Quantum Hall
Authors: Iye Yasuhiro
Published: July 2002

The two-dimensional electron gas formed at the semiconductor
heterointerface is a theater for many intriguing plays of physics. The
fractional quantum Hall effect (FQHE), which occurs in strong magnetic
fields and low temperatures, is the most fascinating of them. The
concept of composite fermions and bosons not only is beautiful by
itself but also has proved highly successful in providing pictorial
interpretation of the phenomena associated with the FQHE.
Electrochemical preparation of tris(
tert-
butyldimethylsilyl)cyclopropene and its hydride abstraction to tris(
tert-
butyldimethylsilyl)cyclopropenium tetrafluoroborate
Authors: Buchholz Herwig A. , Prakash G. K. Surya , Deffieux Denis , Olah George A.
Published: July 2002

Electrochemical reductive
tert-
butyldimethylsilylation of tetrachlorocyclopropene to 1,2,3-tris(
tert
-butyldimethylsilyl)cyclopropene, a potential strained precursor for Diels–Alder and related cycloaddition reactions, is described. By hydride abstraction with nitrosonium tetrafluoroborate, 1,2,3-tris(
tert
-butyldimethylsilyl)cyclopropene is ionized quantitatively to Hückeloid 2π aromatic tris(
tert-
butyldimethylsilyl)cyclopropenium tetrafluoroborate.
Synergistic activities of multiple phosphotyrosine residues mediate full signaling from the
Drosophila
Torso receptor tyrosine kinase
Authors: Gayko Urte , Cleghon Vaughn , Copeland Terry , Morrison Deborah K. , Perrimon Norbert
Published: July 2002

Here, we identify four tyrosine residues (Y644, Y698, Y767, and Y772) that become phosphorylated after activation of the Torso (Tor) receptor tyrosine kinase. Previously, we characterized phosphotyrosine sites (P-Y630 and P-Y918). Of the six P-Y sites identified, three (Y630, Y644, and Y698) are located in the kinase domain insert region, one (Y918) is located in the C-terminal tail region, and two (Y767 and Y772) are located in the activation loop of the kinase domain. To investigate the function of each P-Y residue in Tor signaling, we have generated transgenic Drosophila embryos expressing mutant Tor receptors containing either single or multiple tyrosine to phenylalanine substitutions. Single P-Y mutations were found to have either positive, negative, or no effect on the signaling activity of the receptor. Elimination of all P-Y sites within the kinase insert region resulted in the complete loss of receptor function, indicating that some combination of these sites is necessary for Tor signaling. Mutation of the C-terminal P-Y918 site revealed that this site is responsible for negative signaling or down-regulation of receptor activity. Mutation of the P-Y sites in the kinase domain activation loop demonstrated that these sites are essential for enzymatic activity. Our analysis provides a detailed
in vivo
example of the extent of cooperativity between P-Y residues in transducing the signal received by a receptor tyrosine kinase and
in vivo
data demonstrating the function of P-Y residues in the activation loop of the kinase domain.
Development of the arbitrarily primed-representational difference analysis method and chromosomal mapping of isolated high throughput rat genetic markers
Authors: Yoshida Yukinari , Ushijima Toshikazu , Yamashita Satoshi , Imai Kohzoh , Sugimura Takashi , Nagao Minako
Published: July 2002

Linkage mapping of quantitative trait loci requires analysis of a large number of animals. Although genetic markers isolated by representational difference analysis (RDA) and its modifications meet the needs, the number of these markers has been limited. In the present study, we established the arbitrarily primed (AP)–RDA method to isolate virtually an unlimited number of the high throughput genetic markers. A representation of the genome, an AP-amplicon, was prepared by AP-PCR with a single primer or with a combination of primers using genomic DNA of the ACI/N (ACI) or BUF/Nac (BUF) rat as a template. By subtracting the AP-amplicon of ACI from that of BUF, a total of 40 polymorphic and independent markers were isolated in seven series of AP-RDA using a single primer. Two series of AP-RDA with primer combination yielded seven additional independent markers. All of the markers gave clear positive/negative signals by hybridization of a filter where AP-amplicons from F
2
rats of ACI and BUF were dot-blotted at a high density without any concentration or purification. All of the 47 independent markers were mapped to unique chromosomal positions by linkage analysis, even though some arbitrary primers had very similar sequences. The markers were also informative between other strains of rats. Simultaneous hybridization of multiple filters made it possible to genotype a large number of rats simultaneously for multiple genetic loci. The AP-RDA method promises isolation of a large number of high throughput genetic markers in any species and is expected to facilitate linkage mapping of subtle quantitative trait loci.
The simultaneous estimation of the number of signals and frequencies of multiple sinusoids when some observations are missing: I. Asymptotics
Authors: Bai Zhidong , Rao Calyampudi R. , Wu Yuehua , Zen Mei-Mei , Zhao Lincheng
Published: July 2002

The problem of simultaneous estimation of the number of signals and frequencies of multiple sinusoids is considered in the case when some observations are missing. The number of signals is estimated with an information theoretic criterion, and the frequencies are estimated with eigenvariation linear prediction. The strong consistency of the estimates of the number of signals and the frequencies is established and the rate of convergence of these estimates is provided. Besides, the limiting distributions of various estimates are given.
Genomic context influences the activity of maize mitochondrial
cox2
promoters
Authors: Lupold D. Shelley , Caoile Angelina G. F. S. , Stern David B.
Published: July 2002

Plant mitochondrial genomes are highly recombinogenic, with a variety of species-specific direct and inverted repeats leading to
in vivo
accumulation of multiple DNA forms. In maize, the
cox2
gene, which encodes subunit II of cytochrome
c
oxidase, lies immediately downstream of a 0.7-kilobase direct repeat, which is present in two copies in the 570-kilobase master chromosome. Promoters for
cox2
exist upstream of both of these copies, in regions we have termed A and B. Three region B promoters are active for
cox2
transcription in the master chromosome, whereas two region A promoters are active for
cox2
transcription after recombination across the direct repeats. We have measured the proportion of genomes carrying region A or B upstream of
cox2
in maize seedlings and found a ratio of approximately 1:6. Promoter strength, based on run-on transcription assays, shows a ratio of 1:4 for region A to region B promoters. These data allowed us to predict the relative contributions of region A and B to mitochondrial transcript accumulation, based on a simple product of genome-form abundance and promoter strength. When promoter use was determined by using quantitative reverse transcriptase–PCR, however, we found that region A promoters were used at an unexpectedly high rate when upstream of
cox2
and used less than expected when not upstream of
cox2
. Thus, the use of this set of promoters seems to respond to genomic context. These results suggest a role for intragenomic and intergenomic recombination in regulating plant mitochondrial gene expression.
Is redshift-dependent evolution of galaxies a theoretical artifact?
Authors: Segal I. E.
Published: July 2002

The physical validity of the hypothesis of (redshift-dependent) luminosity evolution in galaxies is tested by statistical analysis of an intensively studied complete high-redshift sample of normal galaxies. The necessity of the evolution hypothesis in the frame of big-bang cosmology is confirmed at a high level of statistical significance; however, this evolution is quantitatively just as predicted by chronometric cosmology, in which there is no such evolution. Since there is no direct observational means to establish the evolution postulated in big-bang studies of higher-redshift galaxies, and the chronometric predictions involve no adjustable parameters (in contrast to the two in big-bang cosmology), the hypothesized evolution appears from the standpoint of conservative scientific methodology as a possible theoretical artifact.
Two gonadotropin-releasing hormone receptor subtypes with distinct ligand selectivity and differential distribution in brain and pituitary in the goldfish (
Carassius auratus
)
Authors: Illing Nicola , Troskie Brigitte E. , Nahorniak Carol S. , Hapgood Janet P. , Peter Richard E. , Millar Robert P.
Published: July 2002

In the goldfish (
Carassius auratus
) the two endogenous forms of gonadotropin-releasing hormone (GnRH), namely chicken GnRH II ([His
5
,Trp
7
,Tyr
8
]GnRH) and salmon GnRH ([Trp
7
,Leu
8
]GnRH), stimulate the release of both gonadotropins and growth hormone from the pituitary. This control is thought to occur by means of the stimulation of distinct GnRH receptors. These receptors can be distinguished on the basis of differential gonadotropin and growth hormone releasing activities of naturally occurring GnRHs and GnRHs with variant amino acids in position 8. We have cloned the cDNAs of two GnRH receptors, GfA and GfB, from goldfish brain and pituitary. Although the receptors share 71% identity, there are marked differences in their ligand selectivity. Both receptors are expressed in the pituitary but are differentially expressed in the brain, ovary, and liver. Thus we have found and cloned two full-length cDNAs that appear to correspond to different forms of GnRH receptor, with distinct pharmacological characteristics and tissue distribution, in a single species.
Helionitronium trication (NO
2
He
3+
) and helionitrosonium trication (HeNO
3+
)
Authors: Olah George A. , Prakash G. K. Surya , Rasul Golam
Published: July 2002

The structures and stabilities of helionitronium trication NO
2
He
3+
and helionitrosonium trication HeNO
3+
were calculated at the
ab initio
MP2/6–31G** level. The C
s
symmetry structure was found to be a minimum for the NO
2
He
3+
trication, which is isoelectronic and isostructural with the previously studied NO
2
H
2+
. Dissociation of the C
s
symmetry structure into NO
+
and OHe
2+
is thermodynamically preferred by 183.1 kcal/mol (1 cal = 4.18 J), although a kinetic barrier of 12.4 kcal/mol has to be overcome. The C
∞v
symmetry structure was also found to be a minimum for the HeNO
3+
trication.
Screw rotations and glide mirrors: Crystallography in Fourier space
Authors: König Anja , Mermin N. David
Published: July 2002

The traditional crystallographic symmetry elements of screw axes and glide planes are subdivided into those that are removable and those that are essential. A simple real-space criterion, depending only on Bravais class, determines which types can be present in any space group. This terminological refinement is useful in expressing the complementary relation between the real-space and Fourier-space formulations of crystal symmetry, particularly in the case of the two nonsymmorphic space groups that have no systematic extinctions (
I
2
1
2
1
2
1
and
I
2
1
3). A simple analysis in Fourier space demonstrates the nonsymmorphicity of these two space groups, which finds its physical expression not in a characteristic absence of Bragg peaks, but in a characteristic presence of electronic level degeneracies.
On the kinetics of distamycin binding to its target sites on duplex DNA
Authors: Baliga Ramesh , Crothers Donald M.
Published: July 2002

Distamycin A is a well known polyamide antibiotic that can bind in the minor groove of duplex DNA primarily at AT-rich sequences both as a monomer or as a side-by-side antiparallel dimer. The association phase of the distamycin binding reaction has not been studied in either of its binding modes, because of the lack of an adequate UV or CD signal at the low concentrations needed to monitor the fast bimolecular reaction. We report a significant increase in fluorescence amplitude, accompanied by a small red shift, on binding distamycin to its specific target sites. This signal can be used to monitor drug binding in steady-state and time-resolved processes. Distamycin shows extremely fast association with the 1:1 binding site, with a bimolecular rate of 7 × 10
7
M
−1
⋅s
−1
and also fairly rapid dissociation (≈3 s
−1
). When DNA is in excess, there is a slow component in the association reaction whose rate decreases strongly with increasing DNA concentration. Binding of the drug to the 2:1 site occurs in two distinct steps: fast, sequential binding of each drug molecule to the DNA with a bimolecular rate comparable to that at the 1:1 site, followed by a slow (≈4 s
−1
) equilibration to the final population. Dissociation from the 2:1 site is ≈40-fold slower than from the 1:1 site. This study provides the groundwork for analysis of the binding kinetics of longer polyamides and covalently linked polyamides that have recently been shown to inhibit transcription
in vivo
.
Novel polymers: Molecular to nanoscale order in three dimensions
Authors: Wooley Karen L. , Moore Jeffrey S. , Wu Chi , Yang Yulian
Published: July 2002

The assembly of polymer chains in solution is a powerful method
that is leading to the preparation of interesting and unique
macromolecular-based synthetic nanostructures. Specific control over
the intramolecular and intermolecular physical interactions dictates
either the folding of single chains or the aggregation and ordering of
multiple chains. This control is provided through the selective
placement of functional groups along the polymer backbone and the
relative strengths of their attractive and repulsive interactions.
Efficiency of the u,v method of estimation
Authors: Robbins Herbert , Zhang Cun-Hui
Published: July 2002

Given a pool of motorists, how do we estimate the total intensity
of those who had a prespecified number of traffic accidents in the past
year? We previously have proposed the u,v method as a solution to
estimation problems of this type. In this paper, we prove that the u,v
method provides asymptotically efficient estimators in an important
special case.
Constant mean curvature surfaces with three ends
Authors: Grosse-Brauckmann Karsten , Kusner Robert B. , Sullivan John M.
Published: July 2002

We announce the classification of complete almost embedded surfaces
of constant mean curvature, with three ends and genus zero. They are
classified by triples of points on the sphere whose distances are the
asymptotic necksizes of the three ends.
A note on statistical analysis of shape through triangulation of landmarks
Authors: Rao C. Radhakrishna
Published: July 2002

In an earlier paper, the author jointly with S. Suryawanshi proposed statistical analysis of shape through triangulation of landmarks on objects. It was observed that the angles of the triangles are invariant to scaling, location, and rotation of objects. No distinction was made between an object and its reflection. The present paper provides the methodology of shape discrimination when reflection is also taken into account and makes suggestions for modifications to be made when some of the landmarks are collinear.
Should Cancer Survivors Fear Radiation‐Induced Sarcomas?
Authors: Feigen Malcolm
Published: July 2002

Purpose/Results. Ionizing radiation is carcinogenic and the induction of a second malignancy is a serious potential
long‐term complication of radiotherapy. The incidence of radiation‐induced sarcomas was evaluated from many large
epidemiological surveys of long‐term cancer survivors reported in the literature over the past 30 years and only one case
was found for every 1000 patients irradiated.

Discussion. Although greater numbers of cancer patients are receiving radical radiotherapy and surviving free of disease
for longer intervals, cases of radiation‐induced sarcomas are rare and should not deter patients from accepting radiotherapy
as treatment for curable cancers. With improvements in the administration of radiotherapy over the past two decades
which are resulting in less damage to bone and soft tissues, it is likely that fewer cases of this condition will be seen in
the future. If these sarcomas are diagnosed early, long‐term survival can be achieved with surgical excision and possibly
re‐irradiation, as occurs in other types of sarcomas.
Prostatic Leiomyosarcoma: The Case for Combined Modality Therapy
Authors: El-Sharkawi Salah , Vaughton Keith
Published: July 2002

Patient. A 65‐year old man who had previously undergone surgery for benign prostatic hyperplasia presented with
symptoms of recurrent bladder outflow obstruction. Cystoscopy revealed the presence of recurrent tissue.

Results. Histology identified a leiomyosarcoma. Several years after further surgery and radiotherapy, the patient presented
with secondaries in the lungs and brain, but there was no evidence of local recurrence.

Discussion. It is suggested that combined modality therapy (conservative surgical resection followed by adjuvant radical
radiotherapy) be the initial treatment for prostatic leiomyosarcoma.
Microtubule-associated Protein 2c Reorganizes Both Microtubules and Microfilaments into Distinct Cytological Structures in an Actin-binding Protein-280–deficient Melanoma Cell Line
Authors: Cunningham C. Casey , Leclerc Nicole , Flanagan Lisa A. , Lu Mei , Janmey Paul A. , Kosik Kenneth S.
Published: July 2002

The emergence of processes from cells often involves interactions between microtubules and microfilaments. Interactions between these two cytoskeletal systems are particularly apparent in neuronal growth cones. The juvenile isoform of the neuronal microtubule-associated protein 2 (MAP2c) is present in growth cones, where we hypothesize it mediates interactions between microfilaments and microtubules. To approach this problem in vivo, we used the human melanoma cell, M2, which lacks actin-binding protein-280 (ABP-280) and forms membrane blebs, which are not seen in wild-type or ABP-transfected cells. The microinjection of tau or mature MAP2 rescued the blebbing phenotype; MAP2c not only caused cessation of blebbing but also induced the formation of two distinct cellular structures. These were actin-rich lamellae, which often included membrane ruffles, and microtubule-bearing processes. The lamellae collapsed after treatment with cytochalasin D, and the processes retracted after treatment with colchicine. MAP2c was immunocytochemically visualized in zones of the cell that were devoid of tubulin, such as regions within the lamellae and in association with membrane ruffles. In vitro rheometry confirmed that MAP2c is an efficient actin gelation protein capable of organizing actin filaments into an isotropic array at very low concentrations; tau and mature MAP2 do not share this rheologic property. These results suggest that MAP2c engages in functionally specific interactions not only with microtubules but also with microfilaments.
Apical Enrichment of Human EGF Precursor in Madin-Darby Canine Kidney Cells Involves Preferential Basolateral Ectodomain Cleavage Sensitive to a Metalloprotease Inhibitor
Authors: Dempsey Peter J. , Meise Katherine S. , Yoshitake Yoshino , Nishikawa Katsuzo , Coffey Robert J.
Published: July 2002

EGF precursor (proEGF) is a member of the family of membrane-anchored EGF-like growth factors that bind with high affinity to the epidermal growth factor receptor (EGFR). In contrast to human transforming growth factor-α precursor (proTGFα), which is sorted basolaterally in Madin-Darby canine kidney (MDCK) cells (Dempsey, P., and R. Coffey, 1994. J. Biol. Chem. 269:16878–16889), we now demonstrate that human proEGF overexpressed in MDCK cells is found predominantly at the apical membrane domain under steady-state conditions. Nascent proEGF (185 kD) is not sorted but is delivered equally to the apical and basolateral membranes, where it is proteolytically cleaved within its ectodomain to release a soluble 170-kD EGF form into the medium. Unlike the fate of TGFα in MDCK cells, the soluble 170-kD EGF species accumulates in the medium, does not interact with the EGFR, and is not processed to the mature 6-kD peptide. We show that the rate of ectodomain cleavage of 185-kD proEGF is fourfold greater at the basolateral surface than at the apical surface and is sensitive to a metalloprotease inhibitor, batimastat. Batimastat dramatically inhibited the release of soluble 170-kD EGF into the apical and basal medium by 7 and 60%, respectively, and caused a concordant increase in the expression of 185-kD proEGF at the apical and basolateral cell surfaces of 150 and 280%, respectively. We propose that preferential ectodomain cleavage at the basolateral surface contributes to apical domain localization of 185-kD proEGF in MDCK cells, and this provides a novel mechanism to achieve a polarized distribution of cell surface membrane proteins under steady-state conditions. In addition, differences in disposition of EGF and TGFα in polarized epithelial cells offer a new conceptual framework to consider the actions of these polypeptide growth factors.
Vertebrate Isoforms of Actin Capping Protein β Have Distinct Functions in Vivo
Authors: Hart Marilyn C. , Cooper John A.
Published: July 2002

Actin capping protein (CP) binds barbed ends of actin filaments to regulate actin assembly. CP is an α/β heterodimer. Vertebrates have conserved isoforms of each subunit. Muscle cells contain two β isoforms. β1 is at the Z-line; β2 is at the intercalated disc and cell periphery in general. To investigate the functions of the isoforms, we replaced one isoform with another using expression in hearts of transgenic mice.

Mice expressing β2 had a severe phenotype with juvenile lethality. Myofibril architecture was severely disrupted. The β2 did not localize to the Z-line. Therefore, β1 has a distinct function that includes interactions at the Z-line. Mice expressing β1 showed altered morphology of the intercalated disc, without the lethality or myofibril disruption of the β2-expressing mice.

The in vivo function of CP is presumed to involve binding barbed ends of actin filaments. To test this hypothesis, we expressed a β1 mutant that poorly binds actin. These mice showed both myofibril disruption and intercalated disc remodeling, as predicted.

Therefore, CPβ1 and CPβ2 each have a distinct function that cannot be provided by the other isoform. CPβ1 attaches actin filaments to the Z-line, and CPβ2 organizes the actin at the intercalated discs.
Recognition of the Major Histocompatibility Complex Restriction Element Modulates CD8+ T Cell Specificity and Compensates for Loss of  T Cell Receptor Contacts with the Specific Peptide
Authors: Sandberg Johan K. , Kärre Klas , Glas Rickard
Published: July 2002

Triggering of a T cell requires interaction between its specific receptor (TCR) and a peptide antigen presented by a self–major histocompatibility complex (MHC) molecule. TCR recognition of self-MHC by itself falls below the threshold of detection in most systems due to low affinity. To study this interaction, we have used a read-out system in which antigen-specific effector T cells are confronted with targets expressing high levels of MHC compared with the selecting and priming environment. More specifically, the system is based on CD8+ T cells selected in an environment with subnormal levels of MHC class I in the absence of β2-microglobulin. We observe that the MHC restriction element can trigger viral peptide-specific T cells independently of the peptide ligand, provided there is an increase in self-MHC density. Peptide-independent triggering required at least four times the natural in vivo level of MHC expression. Furthermore, recognition of the restriction element at expression levels below this threshold was still enough to compensate for lack of affinity to peptides carrying alanine substitutions in major TCR contact residues. Thus, the specificity in TCR recognition and T cell activation is fine tuned by the avidity for self-MHC, and TCR avidities for peptide and MHC may substitute for each other. These results demonstrate a functional role for TCR avidity for self-MHC in tuning of T cell specificity, and support a role for cross-reactivity on “self” during T cell selection and activation.
Regulation of c-Jun NH2-terminal Kinase ( Jnk) Gene Expression during T Cell Activation
Authors: Weiss Linda , Whitmarsh Alan J. , Yang Derek D. , Rincón Mercedes , Davis Roger J. , Flavell Richard A.
Published: July 2002

The c-Jun NH2-terminal kinases (JNKs) are a group of mitogen-activated protein (MAP) kinases that participate in signal transduction events mediating specific cellular functions. Activation of JNK is regulated by phosphorylation in response to cellular stress and inflammatory cytokines. Here, we demonstrate that JNK is regulated by a second, novel mechanism. Induction of Jnk gene expression is required in specific tissues before activation of this signaling pathway. The in vivo and in vitro ligation of the T cell receptor (TCR) leads to induction of JNK gene and protein expression. TCR signals are sufficient to induce JNK expression, whereas JNK phosphorylation also requires CD28-mediated costimulatory signals. Therefore, both expression and activation contribute to the regulation of the JNK pathway to ensure proper control during the course of an immune response.
Qa-2–Dependent Selection of Cd8α/α T Cell Receptor α/β+ Cells in Murine Intestinal Intraepithelial Lymphocytes
Authors: Das Gobardhan , Gould Dina S. , Augustine Mathew M. , Fragoso Gladis , Scitto Edda , Stroynowski Iwona , Van Kaer Luc , Schust Danny J. , Ploegh Hidde , Janeway Charles A.
Published: July 2002

Murine intestinal intraepithelial lymphocytes (iIELs) are made up of a heterogeneous mix of T cells with unique phenotypes. Whereas CD8+ T cells in peripheral lymphoid organs use CD8α/β and are selected on MHC class Ia molecules, a majority of iIELs use CD8α/α. Here, we report that the presence of CD8α/α TCR-α/β cells in iIELs is independent of classical MHC class I molecules Kb and Db, as illustrated by their presence in Kb/Db double-knockout mice and in mice lacking a nonclassical MHC class I molecule, CD1d. Most strikingly, their presence is decreased by ∼70% in mice lacking transporter associated with antigen processing (TAP). The TAP-dependent nonclassical MHC class I molecule Qa-2 is strongly implicated in the presence of these cells, as inferred from the low numbers of CD8α/α TCR-α/β T cells in mice deficient in Qa-2 genes. Second, a Qa-2–transgenic mouse made in a Qa-2− strain showed an increase in the numbers of CD8α/α cells among its iIELs. Thus, the presence of CD8α/α TCR-α/β cells in iIELs is mainly dependent on the nonclassical MHC class I molecule Qa-2.
Spectral methods in polar coordinates for the Stokes problem. Application to computation in unbounded domains
Authors: Halpern Laurence
Published: July 2002

We present spectral methods for solving the Stokes problem in a circular domain. Their main feature is the uniform inf-sup condition, which allows for optimal error estimates. We apply them to the resolution of exterior problems by coupling with the transparent boundary condition.